Page last updated: 2024-12-08

l 753037

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

J 104132: structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID Source	ID
PubMed CID	186002
CHEMBL ID	305576
SCHEMBL ID	6439800
MeSH ID	M0305530

Synonyms (26)

Synonym
l 753037
j-104132
2-butyl-7-(2-((2s)-2-carboxypropyl)-4-methoxyphenyl)-5-(4-methylenedioxyphenyl)cyclopenteno(1,2-b)pyridine-6-carboxylic
l-753,037
j 104132
PDSP2_001713
(5s,6r,7r)-5-benzo[1,3]dioxol-5-yl-2-butyl-7-[2-((s)-2-carboxy-propyl)-4-methoxy-phenyl]-6,7-dihydro-5h-[1]pyrindine-6-carboxylic acid
bdbm50143784
CHEMBL305576 ,
224448-58-2
5h-cyclopenta(b)pyridine-6-carboxylic acid, 5-(1,3-benzodioxol-5-yl)-2-butyl-7-(2-((2s)-2-carboxypropyl)-4-methoxyphenyl)-6,7-dihydro-, (5s,6r,7r)-
198279-45-7
unii-n71z6m3t0i
5h-cyclopenta(b)pyridine-6-carboxylic acid, 5-(1,3-benzodioxol-5-yl)-2-butyl-7-(2-(2-carboxypropyl)-4-methoxyphenyl)-6,7-dihydro-, (5s-(5alpha,6beta,7alpha(r*)))-
n71z6m3t0i ,
mk-547 parent
DTXSID9047332
SCHEMBL6439800
l-753037
5h-cyclopenta(b)pyridine-6-carboxylic acid, 5-(1,3-benzodioxol-5-yl)-2-butyl-7-(2-(2-carboxypropyl)-4-methoxyphenyl)-6,7-dihydro-, (5s-(5.alpha.,6.beta.,7.alpha.(r*)))-
AKOS030532233
HY-10383
CS-5666
(5s,6r,7r)-5-(benzo[d][1,3]dioxol-5-yl)-2-butyl-7-(2-((s)-2-carboxypropyl)-4-methoxyphenyl)-6,7-dihydro-5h-cyclopenta[b]pyridine-6-carboxylic acid
(5s,6r,7r)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[2-[(2s)-2-carboxypropyl]-4-methoxyphenyl]-6,7-dihydro-5h-cyclopenta[b]pyridine-6-carboxylic acid
Q27284642

Research Excerpts

Bioavailability

Excerpt	Reference	Relevance
" Oral bioavailability of J-104132 in rats was approximately 40%."	( Pharmacological properties of J-104132 (L-753,037), a potent, orally active, mixed ETA/ETB endothelin receptor antagonist. Clayton, F; Fukuroda, T; Gabel, R; Hara, K; Hayama, T; Ishikawa, K; Kamei, T; Kanoh, T; Kivlighn, S; Krause, S; Lynch, J; Nishikibe, M; Noguchi, K; Nolan, N; O'Brien, J; Ohta, H; Okada, M; Ozaki, S; Pettibone, D; Saito, M; Siegl, P; William, D; Zingaro, G, 1999)	0.3
" Here we report an expansion of this work by substituting a variety of electron-withdrawing groups at the ortho position and evaluating their effects on oral bioavailability as well as structure-activity relationships."	( Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist. Berens, KL; Blok, N; Bourgoyne, AR; Brock, TA; Bui, H; Decker, ER; Dixon, RA; Holland, GW; Knowles, V; Wang, J; Wu, C; You, TJ, 2004)	0.32

Dosage Studied

Excerpt	Relevance	Reference
" In anesthetized dogs, ET-1 was administered directly into the renal artery or brachial artery to generate dose-response (blood flow) curves, and the inhibitory potency of J-104132 (i."	( Pharmacological properties of J-104132 (L-753,037), a potent, orally active, mixed ETA/ETB endothelin receptor antagonist. Clayton, F; Fukuroda, T; Gabel, R; Hara, K; Hayama, T; Ishikawa, K; Kamei, T; Kanoh, T; Kivlighn, S; Krause, S; Lynch, J; Nishikibe, M; Noguchi, K; Nolan, N; O'Brien, J; Ohta, H; Okada, M; Ozaki, S; Pettibone, D; Saito, M; Siegl, P; William, D; Zingaro, G, 1999)	0.3

[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Inhibition Measurements

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Endothelin-1 receptor	Rattus norvegicus (Norway rat)	Ki	0.0000	0.0000	0.0021	0.0065	AID66210
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (3)

Assay ID	Title	Year	Journal	Article
AID66210	Binding affinity towards Endothelin A receptor	2004	Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8	Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
AID66214	Selectivity for endothelin A receptor over endothelin receptor B	2004	Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8	Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
AID12753	Compound was evaluated for oral bioavailability in rats	2004	Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8	Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (18)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	4 (22.22)	18.2507
2000's	13 (72.22)	29.6817
2010's	1 (5.56)	24.3611
2020's	0 (0.00)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 11.34

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 weak demand-to-supply ratio for research on this compound.

Metric	This Compound (vs All)
Research Demand Index	11.34 (24.57)
Research Supply Index	3.00 (2.92)
Research Growth Index	4.34 (4.65)
Search Engine Demand Index	0.00 (26.88)
Search Engine Supply Index	0.00 (0.95)

This Compound (11.34)

All Compounds (24.57)

Study Types

Publication Type	This drug (%)	All Drugs (%)
Trials	1 (5.56%)	5.53%
Reviews	1 (5.56%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	16 (88.89%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
losartan Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.. losartan : A biphenylyltetrazole where a 1,1'-biphenyl group is attached at the 5-position and has an additional trisubstituted imidazol-1-ylmethyl group at the 4'-position	2	1	0	biphenylyltetrazole; imidazoles	angiotensin receptor antagonist; anti-arrhythmia drug; antihypertensive agent; endothelin receptor antagonist
2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first source	2.02	1	0	chromones; morpholines; organochlorine compound	autophagy inhibitor; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; geroprotector
potassium chloride Potassium Chloride: A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.. potassium chloride : A metal chloride salt with a K(+) counterion.	2.03	1	0	inorganic chloride; inorganic potassium salt; potassium salt	fertilizer
sulfobromophthalein Sulfobromophthalein: A phenolphthalein that is used as a diagnostic aid in hepatic function determination.	2.04	1	0	2-benzofurans; organobromine compound; organosulfonic acid; phenols	dye
nitroblue tetrazolium Nitroblue Tetrazolium: Colorless to yellow dye that is reducible to blue or black formazan crystals by certain cells; formerly used to distinguish between nonbacterial and bacterial diseases, the latter causing neutrophils to reduce the dye; used to confirm diagnosis of chronic granulomatous disease.	2.01	1	0	organic cation
bosentan anhydrous Bosentan: A sulfonamide and pyrimidine derivative that acts as a dual endothelin receptor antagonist used to manage PULMONARY HYPERTENSION and SYSTEMIC SCLEROSIS.	4.9	2	1	primary alcohol; pyrimidines; sulfonamide	antihypertensive agent; endothelin receptor antagonist
tak 044 TAK 044: endothelin receptor antagonist	3.4	1	1
tezosentan tezosentan: structure in first source	3.4	1	1
atrasentan Atrasentan: A pyrrolidine and benzodioxole derivative that acts a RECEPTOR, ENDOTHELIN A antagonist. It has therapeutic potential as an antineoplastic agent and for the treatment of DIABETIC NEPHROPATHIES.	3.4	1	1	pyrrolidines
lu 135252 [no description available]	3.4	1	1
enrasentan enrasentan: decreases ischemic brain injury; an endothelin A and B receptor antagonist; structure in first source. enrasentan : A member of the class of indanes that is 2,3-dihydro-1H-indene which is substituted by a 1,3-benzodioxol-5-yl group, carboxy group, 2-(2-hydroxyethoxy)-4-methoxyphenyl group and a propoxy group at positions 1S, 2R, 3S and 5, respectively. It is an orally active mixed endothelin A/B receptor antagonist with a 100-fold greater affinity for the endothelin A receptor. The drug was being developed by GSK for the treatment of congestive heart failure and pulmonary hypertension (clinical trials discontinued).	3.1	1	0	aromatic ether; benzodioxoles; indanes; monocarboxylic acid; monomethoxybenzene; primary alcohol	antihypertensive agent; endothelin receptor antagonist
tbc-11251 sitaxsentan: endothelin A receptor antagonist; structure in first source	3.4	1	1	benzodioxoles
bq 123 cyclo(Trp-Asp-Pro-Val-Leu): derived from the modification of a natural lead of BE-18257B, an endothelin A receptor antagonist; has neuroprotective activity; amino acid sequence given in first source	5.19	3	1	cyclic peptide
y 27632 Y 27632: RN given for di-HCl salt; inhibits Rho-associated protein kinase; inhibits calcium sensitization to affect smooth muscle relaxation; structure in first source. Y-27632 : A monocarboxylic acid amide that is trans-[(1R)-1-aminoethyl]cyclohexanecarboxamide in which one of the nitrogens of the aminocarbony group is substituted by a pyridine nucleus. It has been shown to exhibit inhibitory activity against Rho-associated protein kinase (ROCK) enzyme.	2.03	1	0	aromatic amide
thromboxane a2 Thromboxane A2: An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).. thromboxane A2 : A thromboxane which is produced by activated platelets and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation.	2	1	0	epoxy monocarboxylic acid; thromboxanes A	mouse metabolite
15-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic acid 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid: A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)	2	1	0
enalaprilat anhydrous Enalaprilat: The active metabolite of ENALAPRIL and one of the potent, intravenously administered, ANGIOTENSIN-CONVERTING ENZYME INHIBITORS. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion.. enalaprilat dihydrate : The dihydrate form of enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor that is used (often in the form of its prodrug, enalapril) in the treatment of hypertension and heart failure, for reduction of proteinuria and renal disease in patients with nephropathies, and for the prevention of stroke, myocardial infarction, and cardiac death in high-risk patients. Unlike enalapril, enalaprilat is not absorbed by mouth but is administered by intravenous injection.. enalaprilat (anhydrous) : Enalapril in which the ethyl ester group has been hydrolysed to the corresponding carboxylic acid. Enalaprilat is an angiotensin-converting enzyme (ACE) inhibitor and is used (often in the form of its prodrug, enalapril) in the treatment of hypertension and heart failure, for reduction of proteinuria and renal disease in patients with nephropathies, and for the prevention of stroke, myocardial infarction, and cardiac death in high-risk patients. Unlike enalapril, enalaprilat is not absorbed by mouth but is given by intravenous injection, usually as the dihydrate.	2	1	0	dicarboxylic acid; dipeptide	antihypertensive agent; EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor
bms 193884 [no description available]	3.4	1	1
endothelin-1 Endothelin-1: A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)	4.61	8	0
sodium nitrite Sodium Nitrite: Nitrous acid sodium salt. Used in many industrial processes, in meat curing, coloring, and preserving, and as a reagent in ANALYTICAL CHEMISTRY TECHNIQUES. It is used therapeutically as an antidote in cyanide poisoning. The compound is toxic and mutagenic and will react in vivo with secondary or tertiary amines thereby producing highly carcinogenic nitrosamines.. sodium nitrite : An inorganic sodium salt having nitrite as the counterion. Used as a food preservative and antidote to cyanide poisoning.	2	1	0	inorganic sodium salt; nitrite salt	antidote to cyanide poisoning; antihypertensive agent; antimicrobial food preservative; food antioxidant; poison

Condition	Relationship Strength	Studies
Neointima The new and thickened layer of scar tissue that forms on a PROSTHESIS, or as a result of vessel injury especially following ANGIOPLASTY or stent placement.	2.06	1
Coronary Heart Disease [description not available]	2.02	1
Injury, Myocardial Reperfusion [description not available]	2.02	1
Heart Disease, Ischemic [description not available]	2.02	1
Coronary Disease An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels.	2.02	1
Myocardial Ischemia A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).	2.02	1
Alloxan Diabetes [description not available]	2.42	2
Anoxemia [description not available]	2.03	1
Pulmonary Hypertension [description not available]	2.03	1
Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms.	2.03	1
Hypertension, Pulmonary Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.	2.03	1
Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	2	1
Blood Pressure, High [description not available]	2.4	2
Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.	2.4	2
Cardiac Failure [description not available]	3.83	4
Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.	3.83	4
Chronic Illness [description not available]	3.32	2
Chronic Disease Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).	3.32	2
Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position.	2.01	1

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