Xanomeline is a selective, high-affinity agonist of the M1 muscarinic acetylcholine receptor. It is being investigated as a potential treatment for cognitive impairment in Alzheimer's disease. Xanomeline is synthesized in a multi-step process involving several chemical reactions. Studies have shown that xanomeline can improve cognitive function, particularly in areas of attention, memory, and executive function. It is being studied because of its potential to improve the cognitive symptoms of Alzheimer's disease. Preclinical studies suggest that xanomeline may have neuroprotective effects in addition to its cognitive enhancing properties. However, xanomeline has also been associated with side effects such as nausea, vomiting, and diarrhea. Further research is needed to determine the safety and efficacy of xanomeline in humans.'
xanomeline: a cholinergic agonist; used in the treatment of Alzheimer's disease; structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 60809 |
| CHEMBL ID | 21536 |
| CHEBI ID | 10056 |
| SCHEMBL ID | 121046 |
| MeSH ID | M0202814 |
| Synonym |
|---|
| 3-(4-hexoxy-1,2,5-thiadiazol-3-yl)-1-methyl-5,6-dihydro-2h-pyridine |
| gtpl57 |
| lumeron |
| ly-246708 |
| nnc-11-0232 |
| memcor |
| hexyloxy-tztp |
| pyridine, 3-(4-(hexyloxy)-1,2,5-thiadiazol-3-yl)-1,2,5,6-tetrahydro-1-methyl- |
| ly246708 |
| xanomeline [usan:inn] |
| c14h23n3os |
| 3-(4-(hexyloxy)-1,2,5-thiadiazol-3-yl)-1,2,5,6-tetrahydro-1-methylpyridine |
| D06330 |
| xanomeline (usan) |
| 131986-45-3 |
| xanomeline |
| ly 246708 |
| CHEBI:10056 , |
| 5-[4-(hexyloxy)-1,2,5-thiadiazol-3-yl]-1-methyl-1,2,3,6-tetrahydropyridine |
| ly-246708 free base |
| CHEMBL21536 , |
| 3-hexoxy-4-(1-methyl-3,6-dihydro-2h-pyridin-5-yl)-1,2,5-thiadiazole |
| L000694 |
| 5-(4-hexyloxy-[1,2,5]thiadiazol-3-yl)-1-methyl-1,2,3,6-tetrahydro-pyridine; oxalic acid |
| bdbm50003359 |
| unii-9ori6l73cj |
| 9ori6l73cj , |
| 3-(hexyloxy)-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazole |
| AKOS016007489 |
| FT-0602214 |
| xanomeline [usan] |
| xanomeline [mart.] |
| xanomeline [mi] |
| xanomeline [inn] |
| xanomeline [who-dd] |
| JOLJIIDDOBNFHW-UHFFFAOYSA-N |
| SCHEMBL121046 |
| DTXSID60157286 |
| 5-[4-(hexyloxy)-1,2,5-thiadiazol-3-yl]-1-methyl-1,2,3,6-tetrahydropyridine, aldrichcpr |
| 3-(4-hexyloxy-1 ,2,5-thiadiazol-3-yl)-1 ,2,5,6-tetrahydro-1-methyl-pyridine |
| mfcd00867179 |
| DB15357 |
| DS-15663 |
| 1018845-70-9 |
| Q8042940 |
| SB18821 |
| BCP31492 |
| ly-246708; ly246708; ly 246708 |
| pyridine, 3-[4-(hexyloxy)-1,2,5-thiadiazol-3-yl]-1,2,5,6-tetrahydro-1-methyl- |
| A888347 |
| C72296 |
| HY-105182 |
| 3-(hexyloxy)-4-(1-methyl-1,2,5,6-tetrahydro-3-pyridyl)-1,2,5-thiadiazole |
| SY111357 |
| CS-0025224 |
| EX-A6592 |
| (5m)-5-[4-(hexyloxy)-1,2,5-thiadiazol-3-yl]-1-methyl-1,2,3,6-tetrahydropyridine |
| XNO , |
Xanomeline is a muscarinic receptor agonist currently in phase II clinical trials for the treatment of Alzheimer's disease. Xanomeline binds with high affinity to all five subtypes of musCarinic receptors.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Xanomeline has been shown to bind in a unique manner at M1 and M3 muscarinic receptors, with interactions at both the orthosteric site and an allosteric site. " | ( Mechanisms of M3 muscarinic receptor regulation by wash-resistant xanomeline binding. El-Fakahany, EE; Grant, MK; Noetzel, MJ, 2009) | 2.03 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "Xanomeline did produce reallocation of behavior from cocaine to food with a robust increase in food reinforcers earned at some cocaine/xanomeline dose combinations." | ( Acute and chronic effects of the M1/M4-preferring muscarinic agonist xanomeline on cocaine vs. food choice in rats. Caine, SB; Fulton, BS; Thomsen, M, 2014) | 1.36 |
Xanomeline pretreatment shifted the dose-effect curve for cocaine rightward (up to 5.6-fold increase in A 50), with reallocation of behavior to the food-reinforced lever. Pretreatment followed by extensive washing resulted in a significant wash-resistant reduction in receptor affinity with no significant change in maximal cell surface receptor density.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Xanomeline pretreatment dose-dependently (1.8-10 mg/kg/day) shifted the dose-effect curve for cocaine rightward (up to 5.6-fold increase in A 50), with reallocation of behavior to the food-reinforced lever. " | ( Acute and chronic effects of the M1/M4-preferring muscarinic agonist xanomeline on cocaine vs. food choice in rats. Caine, SB; Fulton, BS; Thomsen, M, 2014) | 2.08 |
| "Pretreatment with xanomeline followed by extensive washing resulted in a significant wash-resistant reduction in receptor affinity with no significant change in maximal cell surface receptor density." | ( Persistent binding and functional antagonism by xanomeline at the muscarinic M5 receptor. El-Fakahany, EE; Grant, MK, 2005) | 0.91 |
| "Pretreatment with xanomeline for 1 min resulted in a concentration-dependent wash-resistant inhibition of [3H]N-methylscopolamine (NMS) binding, with a lower potency than that observed in the continuous presence of xanomeline in the binding assay medium." | ( Long-term changes in the muscarinic M1 receptor induced by instantaneous formation of wash-resistant xanomeline-receptor complex. De Lorme, KC; El-Fakahany, EE; Grant, MK; Noetzel, MJ; Polson, SB, 2007) | 0.88 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " With the discontinuation of two patients because of severe intolerable adverse events, a minimum intolerated dose was reached at 115 mg three times a day, and 100 mg three times a day was defined as the MTD." | ( The safety and tolerance of xanomeline tartrate in patients with Alzheimer's disease. Cutler, NR; Dies, F; Hourani, J; Hurley, DJ; Satterwhite, JH; Sramek, JJ; Wardle, TS, 1995) | 0.59 |
| "The standards of care for Alzheimer's disease, acetylcholinesterase inhibitors such as donepezil (Aricept®), are dose-limited due to adverse side-effects." | ( Improved cognition without adverse effects: novel M1 muscarinic potentiator compares favorably to donepezil and xanomeline in rhesus monkey. Cannon, CE; Dancho, M; Koser, A; Kuduk, SD; Puri, V; Renger, JJ; Uslaner, JM; Vardigan, JD; Wittmann, M, 2015) | 0.63 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " Bioavailability studies in rats indicated an oral bioavailability of about 20-30%, with the N-oxide as the only detected metabolite." | ( 1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes as new potent muscarinic M1 agonists: structure-activity relationship for 3-aryl-2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives. Bymaster, FP; Calligaro, DO; Christensen, MS; Delapp, NW; Felder, CC; Hansen, L; Jensen, AF; Jeppesen, L; Olesen, PH; Rasmussen, T; Rimvall, K; Sauerberg, P; Shannon, HE; Sheardown, MJ; Thomsen, C; Ward, JS; Whitesitt, C, 1999) | 0.3 |
Dosing as compared with oral dosing may be due to differences in the affinity of various FMO family members for xanomeline. Different exposure to these enzymes receive under different dosing regimens.
| Role | Description |
|---|---|
| muscarinic agonist | Any drug that binds to and activates a muscarinic cholinergic receptor. |
| serotonergic agonist | An agent that has an affinity for serotonin receptors and is able to mimic the effects of serotonin by stimulating the physiologic activity at the cell receptors. Serotonin agonists are used as antidepressants, anxiolytics, and in the treatment of migraine disorders. |
| [role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Class | Description |
|---|---|
| thiadiazoles | |
| tetrahydropyridine | |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Muscarinic acetylcholine receptor M2 | Homo sapiens (human) | EC50 (µMol) | 0.2595 | 0.0000 | 0.7378 | 10.0000 | AID1247230; AID142378 |
| Muscarinic acetylcholine receptor M4 | Homo sapiens (human) | EC50 (µMol) | 0.9673 | 0.0057 | 0.8465 | 6.6069 | AID1167255; AID1167261; AID1167265; AID1247234; AID1510619; AID1510620; AID511600 |
| Muscarinic acetylcholine receptor M5 | Homo sapiens (human) | EC50 (µMol) | 3.2343 | 0.0550 | 1.9570 | 10.0000 | AID1247236; AID142270; AID274680; AID274694; AID274696; AID274698; AID511603 |
| Muscarinic acetylcholine receptor M1 | Homo sapiens (human) | EC50 (µMol) | 1.7005 | 0.0016 | 1.3043 | 10.0000 | AID1167233; AID1167241; AID1167249; AID1247228; AID141033; AID141034; AID141300; AID141314; AID141971; AID274676; AID274694; AID274696; AID274698; AID274700; AID274702; AID511592 |
| Muscarinic acetylcholine receptor M1 | Mus musculus (house mouse) | EC50 (µMol) | 5.7000 | 0.2700 | 4.2900 | 6.9000 | AID141319 |
| Muscarinic acetylcholine receptor M3 | Homo sapiens (human) | EC50 (µMol) | 13,270,233,096.4130 | 0.0004 | 0.9935 | 5.9000 | AID141588; AID274678; AID511597 |
| Muscarinic acetylcholine receptor M3 | Mus musculus (house mouse) | EC50 (µMol) | 11.0000 | 9.9000 | 9.9500 | 10.0000 | AID141597 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID274686 | Activity at human M4 receptor assessed as inhibition of forskolin-stimulated cAMP accumulation | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID142270 | Effective concentration was evaluated against Muscarinic acetylcholine receptor M5 expressed in A9 L cells | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID1247235 | Agonist activity at human muscarinic M4 receptor expressed in CHO cells after 30 mins by GTPgamma35S binding assay relative to acetylcholine | 2015 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 25, Issue:19 | Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as selective and potent muscarinic M₁ agonists. |
| AID141748 | Ability to inhibit the formation of cAMP stimulated by forskolin in A9 L cells expressing in Muscarinic acetylcholine receptor M4 | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID1648533 | Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO-K9 cells measured after 60 mins by Hoechst H33342 dye based confocal plate reader assay | 2020 | Journal of medicinal chemistry, 04-23, Volume: 63, Issue:8 | Red-Emitting Dibenzodiazepinone Derivatives as Fluorescent Dualsteric Probes for the Muscarinic Acetylcholine M |
| AID1167232 | Displacement of [3H]NMS from human M5 receptor expressed in CHO cells by microplate scintillation counting based radioligand binding assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID141971 | Effective concentration required for stimulation of phosphoinositol (PI) hydrolysis in the A9 L cell line transfected with the Muscarinic acetylcholine receptor M1. | 1998 | Journal of medicinal chemistry, Jan-29, Volume: 41, Issue:3 | 1,2,5-Thiadiazole analogues of aceclidine as potent m1 muscarinic agonists. |
| AID511603 | Agonist activity at human muscarinic M5 receptor expressed in BHK-21 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID321021 | Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO cells at pH 6 by wash-resistant binding method | 2008 | Bioorganic & medicinal chemistry, Feb-01, Volume: 16, Issue:3 | Synthesis and evaluation of xanomeline analogs--probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor. |
| AID1167256 | Agonist activity at human M4 receptor expressed in HEK293T cells by BRET based Gq protein engagement assay relative to carbachol | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID1247233 | Agonist activity at human muscarinic M3 receptor expressed in CHO cells after 30 mins by GTPgamma35S binding assay relative to acetylcholine | 2015 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 25, Issue:19 | Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as selective and potent muscarinic M₁ agonists. |
| AID141588 | Effective concentration was evaluated against Muscarinic acetylcholine receptor M3 expressed in A9 L cells | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID1167255 | Agonist activity at human M4 receptor expressed in HEK293T cells by BRET based Gq protein engagement assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID1247229 | Agonist activity at human muscarinic M1 receptor expressed in CHO cells after 30 mins by GTPgamma35S binding assay relative to acetylcholine | 2015 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 25, Issue:19 | Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as selective and potent muscarinic M₁ agonists. |
| AID1648530 | Displacement of 4-(2-((1E,3E)-5-((E)-3,3-Dimethyl-1-(6-oxo-6-((2-(4-(4-(1-(2-oxo-2-(11-oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-5-yl)ethyl)piperidin-4-yl)butyl)piperazin-1-yl)ethyl)amino)hexyl)-5-sulfoindolin-2-ylidene)penta-1,3-dien-1-yl)-3,3-dimet | 2020 | Journal of medicinal chemistry, 04-23, Volume: 63, Issue:8 | Red-Emitting Dibenzodiazepinone Derivatives as Fluorescent Dualsteric Probes for the Muscarinic Acetylcholine M |
| AID1510623 | Agonist activity at human Muscarinic acetylcholine receptor M4 expressed in HEK cells co-expressing Glosensor construct assessed as decrease in isoproterenol-induced cAMP accumulation at 10 uM to 0.3 nM incubated for 2 hrs in presence of isoproterenol and | 2019 | ACS medicinal chemistry letters, Jun-13, Volume: 10, Issue:6 | Discovery of Selective M4 Muscarinic Acetylcholine Receptor Agonists with Novel Carbamate Isosteres. |
| AID321020 | Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO cells at pH 8 in continuous presence of radioligand | 2008 | Bioorganic & medicinal chemistry, Feb-01, Volume: 16, Issue:3 | Synthesis and evaluation of xanomeline analogs--probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor. |
| AID1167261 | Agonist activity at human M4 receptor expressed in HEK293T cells by BRET based Gq protein activation assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID141594 | Compound was tested for binding inhibition of [3H](R)-QNB to Muscarinic acetylcholine receptor M3 expressed in A9 L cells | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID167153 | Efficacy at muscarinic acetylcholine receptor M1 measured by the ability to inhibit the electrically stimulated twitch of the rabbit vas deferens | 1992 | Journal of medicinal chemistry, Oct-30, Volume: 35, Issue:22 | Novel functional M1 selective muscarinic agonists. 2. Synthesis and structure-activity relationships of 3-pyrazinyl-1,2,5,6-tetrahydro-1-methylpyridines. Construction of a molecular model for the M1 pharmacophore. |
| AID142277 | Compound was tested for binding inhibition of [3H](R)-QNB to Muscarinic acetylcholine receptor M5 expressed in A9 L cells | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID274698 | Agonist activity at human M1/M5(o2o3) chimeric receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID274678 | Agonist activity at human M3 receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID141566 | Displacement of [3H]pirenzepine (Pz) from rat hippocampus muscarinic acetylcholine receptor M1 | 1992 | Journal of medicinal chemistry, Oct-30, Volume: 35, Issue:22 | Novel functional M1 selective muscarinic agonists. 2. Synthesis and structure-activity relationships of 3-pyrazinyl-1,2,5,6-tetrahydro-1-methylpyridines. Construction of a molecular model for the M1 pharmacophore. |
| AID1167231 | Displacement of [3H]NMS from human M4 receptor expressed in CHO cells by microplate scintillation counting based radioligand binding assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID274671 | Inhibition of [3H](R)-QNB binding to human M1 receptor expressed in A9 L cells | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID274701 | Agonist activity at human M1 receptor E170K mutant expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis relative to carbachol | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID232384 | Ratio of EC50(CHO-M2) and EC50(A9L-M1) | 1999 | Journal of medicinal chemistry, Jun-03, Volume: 42, Issue:11 | 1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes as new potent muscarinic M1 agonists: structure-activity relationship for 3-aryl-2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives. |
| AID274696 | Agonist activity at human M1/M5(o3) chimeric receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID511593 | Agonist activity at human muscarinic M1 receptor expressed in CHO-K1 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay relative to acetylcholine | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID511597 | Agonist activity at human muscarinic M3 receptor expressed in BHK-21 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID511608 | Displacement of [3H]-4-DAMP from human muscarinic M4 receptor expressed in BHK-21 cells | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID141978 | Maximum stimulation of phosphoinositol (PI) hydrolysis in the A9 L cell line transfected with the muscarinic acetylcholine receptor M1 at 100 uM | 1998 | Journal of medicinal chemistry, Jan-29, Volume: 41, Issue:3 | 1,2,5-Thiadiazole analogues of aceclidine as potent m1 muscarinic agonists. |
| AID141575 | Binding activity against muscarinic acetylcholine receptor M1 in rat brain, using [3H]-Pz as the radioligand. | 1995 | Journal of medicinal chemistry, Sep-01, Volume: 38, Issue:18 | Functionally selective M1 muscarinic agonists. 3. Side chains and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles. |
| AID274699 | Agonist activity at human M1/M5(o2o3) chimeric receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis relative to carbachol | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID1167250 | Agonist activity at human M1 receptor expressed in HEK293T cells by BRET based beta-arrestin engagement assay relative to carbachol | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID321017 | Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO cells in continuous presence of radioligand | 2008 | Bioorganic & medicinal chemistry, Feb-01, Volume: 16, Issue:3 | Synthesis and evaluation of xanomeline analogs--probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor. |
| AID141319 | Tested against Muscarinic acetylcholine receptor M1 expressed in A9 L cell line | 1997 | Journal of medicinal chemistry, Apr-11, Volume: 40, Issue:8 | Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists. |
| AID1247230 | Agonist activity at human muscarinic M2 receptor expressed in CHO cells after 30 mins by GTPgamma35S binding assay | 2015 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 25, Issue:19 | Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as selective and potent muscarinic M₁ agonists. |
| AID141565 | Displacement of [3H]oxotremorine-M (Oxo-M) from rat hippocampus muscarinic acetylcholine receptor M1 | 1992 | Journal of medicinal chemistry, Oct-30, Volume: 35, Issue:22 | Novel functional M1 selective muscarinic agonists. 2. Synthesis and structure-activity relationships of 3-pyrazinyl-1,2,5,6-tetrahydro-1-methylpyridines. Construction of a molecular model for the M1 pharmacophore. |
| AID322942 | Binding affinity to human cloned muscarinic M5 receptor expressed in CHO cells | 2008 | Bioorganic & medicinal chemistry, Mar-15, Volume: 16, Issue:6 | Docking analyses on human muscarinic receptors: unveiling the subtypes peculiarities in agonists binding. |
| AID142543 | Inhibitory activity was evaluated against Muscarinic acetylcholine receptor M2 expressed in A9 L cells | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID141328 | Ability to stimulate biochemical responses in cell lines expressing muscarinic A9 L receptor sub types | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID9450 | Percent inhibition of Forskolin-Induced cAMP production in A9 L cells expressing m2 receptors | 1997 | Journal of medicinal chemistry, Apr-11, Volume: 40, Issue:8 | Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists. |
| AID1167242 | Agonist activity at human M1 receptor expressed in HEK293T cells by BRET based Gq protein activation assay relative to to carbachol | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID1167234 | Agonist activity at human M1 receptor expressed in HEK293T cells by BRET based Gq protein engagement assay relative carbachol | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID274693 | Inhibition of [3H](R)-QNB binding to human M1/M5(o2o3) chimeric receptor expressed in A9 L cells | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID322940 | Binding affinity to human cloned muscarinic M1 receptor expressed in CHO cells | 2008 | Bioorganic & medicinal chemistry, Mar-15, Volume: 16, Issue:6 | Docking analyses on human muscarinic receptors: unveiling the subtypes peculiarities in agonists binding. |
| AID225548 | Binding affinity against muscarinic receptor in rat brain membranes using oxotremorine-M as ligand | 1998 | Bioorganic & medicinal chemistry letters, Oct-20, Volume: 8, Issue:20 | Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation. |
| AID142807 | In vitro Muscarinic acetylcholine receptor M2 binding was evaluated in rat brain membranes by using [3H]- Oxo-M | 1999 | Journal of medicinal chemistry, Jun-03, Volume: 42, Issue:11 | 1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes as new potent muscarinic M1 agonists: structure-activity relationship for 3-aryl-2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives. |
| AID1648528 | Displacement of 4-(2-((1E,3E)-5-((E)-3,3-Dimethyl-1-(6-oxo-6-((2-(4-(4-(1-(2-oxo-2-(11-oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-5-yl)ethyl)piperidin-4-yl)butyl)piperazin-1-yl)ethyl)amino)hexyl)-5-sulfoindolin-2-ylidene)penta-1,3-dien-1-yl)-3,3-dimet | 2020 | Journal of medicinal chemistry, 04-23, Volume: 63, Issue:8 | Red-Emitting Dibenzodiazepinone Derivatives as Fluorescent Dualsteric Probes for the Muscarinic Acetylcholine M |
| AID1167228 | Displacement of [3H]NMS from human M1 receptor expressed in CHO cells by microplate scintillation counting based radioligand binding assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID141602 | Maximum stimulation at Muscarinic acetylcholine receptor M3 expressed in A9 L cells | 1997 | Journal of medicinal chemistry, Apr-11, Volume: 40, Issue:8 | Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists. |
| AID1167265 | Agonist activity at human M4 receptor expressed in HEK293T cells by BRET based beta-arrestin engagement assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID274674 | Inhibition of [3H](R)-QNB binding to human M4 receptor expressed in A9 L cells | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID119583 | Effect on salivation in mice, after intraperitoneal administration of 10 mg/kg, activity expressed as a score using a scale of 0-2. | 1995 | Journal of medicinal chemistry, Sep-01, Volume: 38, Issue:18 | Functionally selective M1 muscarinic agonists. 3. Side chains and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles. |
| AID511598 | Agonist activity at human muscarinic M3 receptor expressed in BHK-21 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay relative to acetylcholine | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID167809 | Efficacy at muscarinic acetylcholine receptor M1 measured by the ability to inhibit the electrically stimulated twitch of the rabbit vas deferens | 1992 | Journal of medicinal chemistry, Oct-30, Volume: 35, Issue:22 | Novel functional M1 selective muscarinic agonists. 2. Synthesis and structure-activity relationships of 3-pyrazinyl-1,2,5,6-tetrahydro-1-methylpyridines. Construction of a molecular model for the M1 pharmacophore. |
| AID1167241 | Agonist activity at human M1 receptor expressed in HEK293T cells by BRET based Gq protein activation assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID141034 | Agonistic activity against M1 muscarinic receptor expressed in NIH 3T3 cells | 2001 | Journal of medicinal chemistry, Dec-20, Volume: 44, Issue:26 | Design, synthesis, and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists. |
| AID142608 | Efficacy expressed as PI (percentage of carbachol) against human M1 receptor expressed in CHO cells | 1999 | Bioorganic & medicinal chemistry letters, Jul-19, Volume: 9, Issue:14 | Discovery of a highly potent, functionally-selective muscarinic M1 agonist, WAY-132983 using rational drug design and receptor modelling. |
| AID1482283 | Displacement of [3H]UR-AP060 from human muscarinic acetylcholine receptor M2 expressed in CHOK9 cell homogenate after 3 hrs by liquid scintillation counting assay | 2017 | Journal of medicinal chemistry, 04-27, Volume: 60, Issue:8 | Radiolabeled Dibenzodiazepinone-Type Antagonists Give Evidence of Dualsteric Binding at the M |
| AID1482282 | Displacement of [3H]UNSW-MK259 from human muscarinic acetylcholine receptor M2 expressed in CHOK9 cells after 3 hrs by liquid scintillation counting assay | 2017 | Journal of medicinal chemistry, 04-27, Volume: 60, Issue:8 | Radiolabeled Dibenzodiazepinone-Type Antagonists Give Evidence of Dualsteric Binding at the M |
| AID511596 | Agonist activity at human muscarinic M2 receptor expressed in CHO-K1 cells coexpressing Galpha16 subunit assessed as increase of acetylcholine-induced calcium flux at 10 uM by FLIPR assay relative to acetylcholine | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID274679 | Agonist activity at human M3 receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis relative to carbachol | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID1167262 | Agonist activity at human M4 receptor expressed in HEK293T cells by BRET based Gq protein activation assay relative to carbachol | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID141999 | Inhibitory activity was evaluated against Muscarinic acetylcholine receptor M4 expressed in A9 L cells | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID274694 | Agonist activity at human M1/M5(o2) chimeric receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID141190 | Maximal level of stimulation as a percentage above basal levels. | 2001 | Journal of medicinal chemistry, Dec-20, Volume: 44, Issue:26 | Design, synthesis, and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists. |
| AID1648532 | Displacement of 4-(2-((1E,3E)-5-((E)-1-(6-((3,5-Bis((2-(3-(1-(4-(1-(2-oxo-2-(11-oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-5-yl)ethyl)piperidin-4-yl)butyl)-1H-imidazol-4-yl)propanamido)ethyl)carbamoyl)benzyl)amino)-6-oxohexyl)-3,3-dimethyl-5-sulfoindo | 2020 | Journal of medicinal chemistry, 04-23, Volume: 63, Issue:8 | Red-Emitting Dibenzodiazepinone Derivatives as Fluorescent Dualsteric Probes for the Muscarinic Acetylcholine M |
| AID1648531 | Displacement of 4-(2-((1E,3E)-5-((E)-3,3-Dimethyl-1-(6-oxo-6-((2-(3-(1-(4-(1-(2-oxo-2-(11-oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-5-yl)ethyl)piperidin-4-yl)butyl)-1H-imidazol-4-yl)propanamido)ethyl)-amino)hexyl)-5-sulfoindolin-2-ylidene)penta-1,3-d | 2020 | Journal of medicinal chemistry, 04-23, Volume: 63, Issue:8 | Red-Emitting Dibenzodiazepinone Derivatives as Fluorescent Dualsteric Probes for the Muscarinic Acetylcholine M |
| AID9454 | Tested for stimulating PI (phosphoinositol) hydrolysis in A9L-m1 cells, activity expressed as EC50 mM. | 1995 | Journal of medicinal chemistry, Sep-01, Volume: 38, Issue:18 | Functionally selective M1 muscarinic agonists. 3. Side chains and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles. |
| AID141451 | Binding affinity for muscarinic acetylcholine receptor M1 using [3H]pirenzepine (Pz) radioligand in rat hippocampus membranes. | 1998 | Journal of medicinal chemistry, Jan-29, Volume: 41, Issue:3 | 1,2,5-Thiadiazole analogues of aceclidine as potent m1 muscarinic agonists. |
| AID9455 | Stimulating PI (phosphoinositol) hydrolysis in A9L-m1 cells. | 1995 | Journal of medicinal chemistry, Sep-01, Volume: 38, Issue:18 | Functionally selective M1 muscarinic agonists. 3. Side chains and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles. |
| AID141597 | Tested against Muscarinic acetylcholine receptor M3 expressed in A9 L cell line | 1997 | Journal of medicinal chemistry, Apr-11, Volume: 40, Issue:8 | Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists. |
| AID1247236 | Agonist activity at human muscarinic M5 receptor expressed in CHO cells after 30 mins by GTPgamma35S binding assay | 2015 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 25, Issue:19 | Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as selective and potent muscarinic M₁ agonists. |
| AID141182 | Percentage stimulation above basal levels at 100 uM expressed relative to the carbachol response. | 2001 | Journal of medicinal chemistry, Dec-20, Volume: 44, Issue:26 | Design, synthesis, and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists. |
| AID141436 | Maximum stimulation at Muscarinic acetylcholine receptor M1 expressed in A9 L cells | 1997 | Journal of medicinal chemistry, Apr-11, Volume: 40, Issue:8 | Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists. |
| AID511606 | Displacement of [3H]-AFDX-384 from human muscarinic M2 receptor expressed in CHO-K1 cells | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID274695 | Agonist activity at human M1/M5(o2) chimeric receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis relative to carbachol | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID511604 | Agonist activity at human muscarinic M5 receptor expressed in BHK-21 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay relative to acetylcholine | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID274706 | Antipsychotic activity in sc dosed Sprague-Dawley rat assessed as ability to reverse apomorphine effect on prepulse inhibition of the startle response | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID142299 | Stimulation of phosphoinositide hydrolysis in BHK cells expressing human m1 receptor | 1998 | Bioorganic & medicinal chemistry letters, Oct-20, Volume: 8, Issue:20 | Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation. |
| AID274673 | Inhibition of [3H](R)-QNB binding to human M3 receptor expressed in A9 L cells | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID274681 | Agonist activity at human M5 receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis relative to carbachol | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID1247231 | Agonist activity at human muscarinic M2 receptor expressed in CHO cells after 30 mins by GTPgamma35S binding assay relative to acetylcholine | 2015 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 25, Issue:19 | Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as selective and potent muscarinic M₁ agonists. |
| AID1648529 | Displacement of 4-(2-((1E,3E)-5-((E)-3,3-Dimethyl-1-(6-oxo-6-((2-(4-(4-(1-(2-oxo-2-(11-oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-5-yl)ethyl)piperidin-4-yl)butyl)piperazin-1-yl)ethyl)amino)hexyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3,3-dimethyl-3H-i | 2020 | Journal of medicinal chemistry, 04-23, Volume: 63, Issue:8 | Red-Emitting Dibenzodiazepinone Derivatives as Fluorescent Dualsteric Probes for the Muscarinic Acetylcholine M |
| AID1247234 | Agonist activity at human muscarinic M4 receptor expressed in CHO cells after 30 mins by GTPgamma35S binding assay | 2015 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 25, Issue:19 | Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as selective and potent muscarinic M₁ agonists. |
| AID1167249 | Agonist activity at human M1 receptor expressed in HEK293T cells by BRET based beta-arrestin engagement assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID141171 | Binding affinity towards M1 muscarinic receptor expressed in A9 L cells by displacing [3H](R)-QNB radioligand. | 2001 | Journal of medicinal chemistry, Dec-20, Volume: 44, Issue:26 | Design, synthesis, and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists. |
| AID321018 | Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO cells by wash-resistant binding method | 2008 | Bioorganic & medicinal chemistry, Feb-01, Volume: 16, Issue:3 | Synthesis and evaluation of xanomeline analogs--probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor. |
| AID274692 | Inhibition of [3H](R)-QNB binding to human M1/M5(o3) chimeric receptor expressed in A9 L cells | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID141574 | Binding activity against muscarinic acetylcholine receptor M1 in rat brain, using [3H]OXO-M as the radioligand. | 1995 | Journal of medicinal chemistry, Sep-01, Volume: 38, Issue:18 | Functionally selective M1 muscarinic agonists. 3. Side chains and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles. |
| AID732893 | Agonist activity at M3 receptor in guinea pig ileum assessed as contraction at 0.3 to 3 uM | 2013 | ACS medicinal chemistry letters, Feb-14, Volume: 4, Issue:2 | Discovery of novel N-substituted oxindoles as selective m1 and m4 muscarinic acetylcholine receptors partial agonists. |
| AID1482286 | Displacement of [3H]NMS from human muscarinic acetylcholine receptor M2 expressed in CHO cells after 60 mins by scintillation counting assay | 2017 | Journal of medicinal chemistry, 04-27, Volume: 60, Issue:8 | Radiolabeled Dibenzodiazepinone-Type Antagonists Give Evidence of Dualsteric Binding at the M |
| AID9449 | Inhibition of Forskolin-Induced cAMP production in A9 L cells expressing m2 receptors | 1997 | Journal of medicinal chemistry, Apr-11, Volume: 40, Issue:8 | Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists. |
| AID274676 | Agonist activity at human M1 receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID274703 | Agonist activity at human M1 receptor Q185E mutant expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis relative to carbachol | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID141317 | Stimulation of phosphoinositol hydrolysis in the mouse fibroblast cell line A9L-M1 expressing Muscarinic acetylcholine receptor M1. | 1999 | Journal of medicinal chemistry, Jun-03, Volume: 42, Issue:11 | 1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes as new potent muscarinic M1 agonists: structure-activity relationship for 3-aryl-2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives. |
| AID274702 | Agonist activity at human M1 receptor Q185E mutant expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID140904 | Ability to stimulate biochemical responses in cell lines expressing muscarinic A9 L receptor sub types | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID274675 | Inhibition of [3H](R)-QNB binding to human M5 receptor expressed in A9 L cells | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID1510624 | Positive allosteric modulatory activity at human Muscarinic acetylcholine receptor M4 expressed in HEK cells co-expressing Glosensor construct assessed as as increase in acteylcholine-induced cAMP accumulation at 10 uM to 0.3 nM incubated for 7 mins in pr | 2019 | ACS medicinal chemistry letters, Jun-13, Volume: 10, Issue:6 | Discovery of Selective M4 Muscarinic Acetylcholine Receptor Agonists with Novel Carbamate Isosteres. |
| AID274691 | Inhibition of [3H](R)-QNB binding to human M1/M5(o2) chimeric receptor expressed in A9 L cells | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID274683 | Activity at human M2 receptor assessed as inhibition of forskolin-stimulated cAMP accumulation | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID274687 | Activity at human M4 receptor assessed as inhibition of forskolin-stimulated cAMP accumulation relative to carbachol | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID511609 | Displacement of [3H]-4-DAMP from human muscarinic M5 receptor expressed in BHK-21 cells | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID1510620 | Positive allosteric modulatory activity at human Muscarinic acetylcholine receptor M4 expressed in HEK cells co-expressing Glosensor construct assessed as as increase in acteylcholine-induced cAMP accumulation incubated for 7 mins in presence of isoproter | 2019 | ACS medicinal chemistry letters, Jun-13, Volume: 10, Issue:6 | Discovery of Selective M4 Muscarinic Acetylcholine Receptor Agonists with Novel Carbamate Isosteres. |
| AID321019 | Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO cells at pH 6 in continuous presence of radioligand | 2008 | Bioorganic & medicinal chemistry, Feb-01, Volume: 16, Issue:3 | Synthesis and evaluation of xanomeline analogs--probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor. |
| AID1510619 | Agonist activity at human Muscarinic acetylcholine receptor M4 expressed in HEK cells co-expressing Glosensor construct assessed as decrease in isoproterenol-induced cAMP accumulation incubated for 7 mins in presence of isoproterenol by Glosensor cAMP rea | 2019 | ACS medicinal chemistry letters, Jun-13, Volume: 10, Issue:6 | Discovery of Selective M4 Muscarinic Acetylcholine Receptor Agonists with Novel Carbamate Isosteres. |
| AID274700 | Agonist activity at human M1 receptor E170K mutant expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID1167230 | Displacement of [3H]NMS from human M3 receptor expressed in CHO cells by microplate scintillation counting based radioligand binding assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID458979 | Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO cells in ternary complex by EATCM analysis | 2010 | Journal of medicinal chemistry, Mar-11, Volume: 53, Issue:5 | Hybrid molecules from xanomeline and tacrine: enhanced tacrine actions on cholinesterases and muscarinic M1 receptors. |
| AID141306 | Inhibition of [3H](R)-QNB to Muscarinic acetylcholine receptor M1 expressed in A9 L cells | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID274684 | Activity at human M2 receptor assessed as inhibition of forskolin-stimulated cAMP accumulation relative to carbachol | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID274677 | Agonist activity at human M1 receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis relative to carbachol | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID511600 | Agonist activity at human muscarinic M4 receptor expressed in BHK-21 cells coexpressing Galpha16 subunit assessed as increase of acetylcholine-induced calcium flux by FLIPR assay | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID274672 | Inhibition of [3H](R)-QNB binding to human M2 receptor expressed in A9 L cells | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID141300 | Effective concentration was evaluated against Muscarinic acetylcholine receptor M1 expressed in A9 L cells | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID141314 | Stimulation of phosphoinositol hydrolysis in the mouse fibroblast cell line A9L-M1 expressing Muscarinic acetylcholine receptor M1. | 1999 | Journal of medicinal chemistry, Jun-03, Volume: 42, Issue:11 | 1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes as new potent muscarinic M1 agonists: structure-activity relationship for 3-aryl-2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives. |
| AID141452 | Binding affinity for muscarinic acetylcholine receptor M1 using [3H]oxotremorine-M (Oxo-M) radioligand in rat hippocampus membranes | 1998 | Journal of medicinal chemistry, Jan-29, Volume: 41, Issue:3 | 1,2,5-Thiadiazole analogues of aceclidine as potent m1 muscarinic agonists. |
| AID1167229 | Displacement of [3H]NMS from human M2 receptor expressed in CHO cells by microplate scintillation counting based radioligand binding assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID142541 | Compound was tested for its potency towards Muscarinic acetylcholine receptor M2 by inhibiting forskolin induced c-AMP formation in CHO-M2 cells expressing human Muscarinic acetylcholine receptor M2 receptor | 1999 | Journal of medicinal chemistry, Jun-03, Volume: 42, Issue:11 | 1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes as new potent muscarinic M1 agonists: structure-activity relationship for 3-aryl-2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives. |
| AID511607 | Displacement of [3H]-4-DAMP from human muscarinic M3 receptor expressed in BHK-21 cells | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID321022 | Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO cells at pH 8 by wash-resistant binding method | 2008 | Bioorganic & medicinal chemistry, Feb-01, Volume: 16, Issue:3 | Synthesis and evaluation of xanomeline analogs--probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor. |
| AID142257 | Ability to inhibit the formation of cAMP stimulated by forskolin in A9 L cells expressing Muscarinic acetylcholine receptor M2 | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID1247237 | Agonist activity at human muscarinic M5 receptor expressed in CHO cells after 30 mins by GTPgamma35S binding assay relative to acetylcholine | 2015 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 25, Issue:19 | Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as selective and potent muscarinic M₁ agonists. |
| AID142027 | Ability to stimulate biochemical responses in A9 L cell lines expressing Muscarinic acetylcholine receptor M5 | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID142003 | Compound was tested for binding inhibition of [3H](R)-QNB to Muscarinic acetylcholine receptor M4 expressed in A9 L cells | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID511592 | Agonist activity at human muscarinic M1 receptor expressed in CHO-K1 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID1247228 | Agonist activity at human muscarinic M1 receptor expressed in CHO cells after 30 mins by GTPgamma35S binding assay | 2015 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 25, Issue:19 | Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as selective and potent muscarinic M₁ agonists. |
| AID511601 | Agonist activity at human muscarinic M4 receptor expressed in BHK-21 cells coexpressing Galpha16 subunit assessed as increase of acetylcholine-induced calcium flux by FLIPR assay relative to acetylcholine | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. |
| AID119568 | Intraperitoneal dose of 10 mg/Kg was tested for salivation in mice expressed as score. | 1998 | Journal of medicinal chemistry, Jan-29, Volume: 41, Issue:3 | 1,2,5-Thiadiazole analogues of aceclidine as potent m1 muscarinic agonists. |
| AID1167233 | Agonist activity at human M1 receptor expressed in HEK293T cells by BRET based Gq protein engagement assay | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID274690 | Inhibition of [3H](R)-QNB binding to human M1 receptor Thr192Ala mutant expressed in A9 L cells | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID142161 | Maximal level of stimulation as a percentage above basal levels. | 2001 | Journal of medicinal chemistry, Dec-20, Volume: 44, Issue:26 | Design, synthesis, and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists. |
| AID322941 | Binding affinity to human cloned muscarinic M2 receptor expressed in CHO cells | 2008 | Bioorganic & medicinal chemistry, Mar-15, Volume: 16, Issue:6 | Docking analyses on human muscarinic receptors: unveiling the subtypes peculiarities in agonists binding. |
| AID274697 | Agonist activity at human M1/M5(o3) chimeric receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis relative to carbachol | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID458980 | Displacement of [3H]NMS from human muscarinic M1 receptor expressed in CHO cells in binary complex by EATCM analysis | 2010 | Journal of medicinal chemistry, Mar-11, Volume: 53, Issue:5 | Hybrid molecules from xanomeline and tacrine: enhanced tacrine actions on cholinesterases and muscarinic M1 receptors. |
| AID274680 | Agonist activity at human M5 receptor expressed in A9 L cells assessed as stimulation of phosphoinositide hydrolysis | 2006 | Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25 | Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the bind |
| AID142378 | Compound was tested for its potency towards Muscarinic acetylcholine receptor M2 by inhibiting forskolin induced c-AMP formation in CHO-M2 cells | 1999 | Journal of medicinal chemistry, Jun-03, Volume: 42, Issue:11 | 1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes as new potent muscarinic M1 agonists: structure-activity relationship for 3-aryl-2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives. |
| AID141033 | Agonistic activity against M1 muscarinic receptor expressed in A9 L cells. | 2001 | Journal of medicinal chemistry, Dec-20, Volume: 44, Issue:26 | Design, synthesis, and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists. |
| AID142605 | Affinity towards human M1 receptor expressed in CHO cells using [3H]QNB as radioligand | 1999 | Bioorganic & medicinal chemistry letters, Jul-19, Volume: 9, Issue:14 | Discovery of a highly potent, functionally-selective muscarinic M1 agonist, WAY-132983 using rational drug design and receptor modelling. |
| AID1167266 | Agonist activity at human M4 receptor expressed in HEK293T cells by BRET based beta-arrestin engagement assay relative to carbachol | 2014 | Journal of medicinal chemistry, Nov-13, Volume: 57, Issue:21 | Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). |
| AID142651 | Compound was tested for binding inhibition of [3H](R)-QNB to Muscarinic acetylcholine receptor M2 expressed in A9 L cells | 2003 | Journal of medicinal chemistry, Sep-25, Volume: 46, Issue:20 | Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders. |
| AID624218 | Antagonists at Human 5-Hydroxytryptamine receptor 5-HT2B | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345343 | Human M3 receptor (Acetylcholine receptors (muscarinic)) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID624210 | Agonists at Human 5-Hydroxytryptamine receptor 5-HT1A | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345286 | Human M1 receptor (Acetylcholine receptors (muscarinic)) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345326 | Human M2 receptor (Acetylcholine receptors (muscarinic)) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345543 | Human M5 receptor (Acetylcholine receptors (muscarinic)) | 2005 | The Journal of pharmacology and experimental therapeutics, Oct, Volume: 315, Issue:1 | Persistent binding and functional antagonism by xanomeline at the muscarinic M5 receptor. |
| AID1345465 | Human M4 receptor (Acetylcholine receptors (muscarinic)) | 1999 | British journal of pharmacology, Apr, Volume: 126, Issue:7 | Functional comparison of muscarinic partial agonists at muscarinic receptor subtypes hM1, hM2, hM3, hM4 and hM5 using microphysiometry. |
| AID1346264 | Human 5-HT1B receptor (5-Hydroxytryptamine receptors) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345286 | Human M1 receptor (Acetylcholine receptors (muscarinic)) | 2006 | Molecular pharmacology, Aug, Volume: 70, Issue:2 | Differences in kinetics of xanomeline binding and selectivity of activation of G proteins at M(1) and M(2) muscarinic acetylcholine receptors. |
| AID1345615 | Human 5-HT1A receptor (5-Hydroxytryptamine receptors) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID624223 | Antagonists at Human 5-Hydroxytryptamine receptor 5-HT2A | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1259419 | Human 5-HT2A receptor (5-Hydroxytryptamine receptors) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345343 | Human M3 receptor (Acetylcholine receptors (muscarinic)) | 1999 | British journal of pharmacology, Apr, Volume: 126, Issue:7 | Functional comparison of muscarinic partial agonists at muscarinic receptor subtypes hM1, hM2, hM3, hM4 and hM5 using microphysiometry. |
| AID1345170 | Human 5-HT6 receptor (5-Hydroxytryptamine receptors) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID624230 | Agonists at Human 5-Hydroxytryptamine receptor 5-ht1e | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1346867 | Human 5-HT2B receptor (5-Hydroxytryptamine receptors) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345465 | Human M4 receptor (Acetylcholine receptors (muscarinic)) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345286 | Human M1 receptor (Acetylcholine receptors (muscarinic)) | 1999 | British journal of pharmacology, Apr, Volume: 126, Issue:7 | Functional comparison of muscarinic partial agonists at muscarinic receptor subtypes hM1, hM2, hM3, hM4 and hM5 using microphysiometry. |
| AID1345291 | Human 5-HT7 receptor (5-Hydroxytryptamine receptors) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345326 | Human M2 receptor (Acetylcholine receptors (muscarinic)) | 1999 | British journal of pharmacology, Apr, Volume: 126, Issue:7 | Functional comparison of muscarinic partial agonists at muscarinic receptor subtypes hM1, hM2, hM3, hM4 and hM5 using microphysiometry. |
| AID1345543 | Human M5 receptor (Acetylcholine receptors (muscarinic)) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345543 | Human M5 receptor (Acetylcholine receptors (muscarinic)) | 1999 | British journal of pharmacology, Apr, Volume: 126, Issue:7 | Functional comparison of muscarinic partial agonists at muscarinic receptor subtypes hM1, hM2, hM3, hM4 and hM5 using microphysiometry. |
| AID624233 | Agonists at Human 5-Hydroxytryptamine receptor 5-HT1F | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1346603 | Human 5-ht1e receptor (5-Hydroxytryptamine receptors) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1346893 | Human 5-HT2C receptor (5-Hydroxytryptamine receptors) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1346528 | Human 5-HT1D receptor (5-Hydroxytryptamine receptors) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1346739 | Human 5-HT1F receptor (5-Hydroxytryptamine receptors) | 1998 | British journal of pharmacology, Dec, Volume: 125, Issue:7 | Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. |
| AID1345286 | Human M1 receptor (Acetylcholine receptors (muscarinic)) | 1998 | Molecular pharmacology, Jun, Volume: 53, Issue:6 | On the unique binding and activating properties of xanomeline at the M1 muscarinic acetylcholine receptor. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 39 (32.23) | 18.2507 |
| 2000's | 35 (28.93) | 29.6817 |
| 2010's | 35 (28.93) | 24.3611 |
| 2020's | 12 (9.92) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.
| This Compound (51.08) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 16 (12.90%) | 5.53% |
| Reviews | 7 (5.65%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 101 (81.45%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| A Phase 2, Randomized, Double-blinded Study to Assess the Safety, Tolerability, and Efficacy of KarXT in Hospitalized Adults With DSM-5 Schizophrenia [NCT03697252] | Phase 2 | 182 participants (Actual) | Interventional | 2018-09-18 | Completed | ||
| An Open-label Extension Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Subjects With DSM-5 Schizophrenia [NCT04659174] | Phase 3 | 156 participants (Actual) | Interventional | 2021-02-01 | Completed | ||
| A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adults With DSM-5 Schizophrenia [NCT04659161] | Phase 3 | 252 participants (Actual) | Interventional | 2020-12-16 | Completed | ||
| A Multi-center, Open-label Study to Assess the Effectiveness, Long-term Safety, Tolerability, and Durability of Effect of KarXT in Patients With DSM-5 Diagnosis of Schizophrenia [NCT05643170] | Phase 3 | 4 participants (Actual) | Interventional | 2022-11-08 | Terminated(stopped due to Company's business decision.) | ||
| A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adults With DSM-5 Schizophrenia [NCT04738123] | Phase 3 | 256 participants (Actual) | Interventional | 2021-04-06 | Completed | ||
| A Phase I, Double-Blind, Randomized, Multiple-Dose, Pilot Study Comparing Xanomeline Administered Alone to Xanomeline Administered in Combination With Trospium Chloride in Normal Healthy Volunteers [NCT02831231] | Phase 1 | 70 participants (Actual) | Interventional | 2016-09-07 | Completed | ||
| An Open-label Extension Study to Assess the Long-term Safety and Tolerability of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia [NCT05304767] | Phase 3 | 280 participants (Anticipated) | Interventional | 2022-03-07 | Enrolling by invitation | ||
| A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia [NCT05145413] | Phase 3 | 400 participants (Anticipated) | Interventional | 2021-11-12 | Recruiting | ||
| An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in De Novo Subjects With DSM-5 Schizophrenia [NCT04820309] | Phase 3 | 568 participants (Actual) | Interventional | 2021-06-02 | Active, not recruiting | ||
| A Phase 3, Multicenter, Two-part Study With a 5-week Double-blind Part (Randomized, Parallel-group, Placebo-controlled) Followed by a 12-week Open-label Extension Part, to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese [NCT05919823] | Phase 3 | 158 participants (Anticipated) | Interventional | 2023-05-29 | Recruiting | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||