Proteins > cAMP-specific 3',5'-cyclic phosphodiesterase 4C
Page last updated: 2024-08-07 17:02:49
cAMP-specific 3',5'-cyclic phosphodiesterase 4C
A 3,5-cyclic-AMP phosphodiesterase 4C that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q08493]
Synonyms
EC 3.1.4.53;
DPDE1;
PDE21
Research
Bioassay Publications (95)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 7 (7.37) | 18.7374 |
| 1990's | 26 (27.37) | 18.2507 |
| 2000's | 38 (40.00) | 29.6817 |
| 2010's | 18 (18.95) | 24.3611 |
| 2020's | 6 (6.32) | 2.80 |
Compounds (61)
Drugs with Inhibition Measurements
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|
| theophylline | Homo sapiens (human) | IC50 | 637.0000 | 3 | 3 |
| theophylline | Homo sapiens (human) | Ki | 530.0000 | 1 | 1 |
| denbufylline | Homo sapiens (human) | IC50 | 0.0851 | 2 | 2 |
| dipyridamole | Homo sapiens (human) | IC50 | 0.5000 | 1 | 1 |
| ibudilast | Homo sapiens (human) | IC50 | 0.2390 | 2 | 2 |
| amrinone | Homo sapiens (human) | IC50 | 113.6000 | 4 | 5 |
| losartan | Homo sapiens (human) | IC50 | 26.0000 | 1 | 1 |
| milrinone | Homo sapiens (human) | IC50 | 6.0000 | 1 | 1 |
| 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone | Homo sapiens (human) | IC50 | 18.9333 | 2 | 3 |
| rolipram | Homo sapiens (human) | IC50 | 2.7812 | 48 | 49 |
| rolipram | Homo sapiens (human) | Ki | 0.2264 | 9 | 9 |
| streptonigrin | Homo sapiens (human) | IC50 | 1.8700 | 1 | 1 |
| thalidomide | Homo sapiens (human) | IC50 | 500.0000 | 1 | 1 |
| trequinsin | Homo sapiens (human) | IC50 | 0.4000 | 1 | 1 |
| zardaverine | Homo sapiens (human) | IC50 | 0.4723 | 3 | 3 |
| 9-benzyladenine | Homo sapiens (human) | IC50 | 160.0000 | 1 | 1 |
| 8-bromo cyclic adenosine monophosphate | Homo sapiens (human) | IC50 | 18.4667 | 2 | 3 |
| enoximone | Homo sapiens (human) | IC50 | 52.6333 | 3 | 3 |
| imazodan | Homo sapiens (human) | IC50 | 6.0000 | 1 | 1 |
| nitraquazone | Homo sapiens (human) | IC50 | 0.0500 | 1 | 1 |
| cipamfylline | Homo sapiens (human) | IC50 | 1.9000 | 1 | 1 |
| cipamfylline | Homo sapiens (human) | Ki | 21.0000 | 1 | 1 |
| 8-((4-chlorophenyl)thio)cyclic-3',5'-amp | Homo sapiens (human) | IC50 | 81.3333 | 2 | 3 |
| 8-thio-benzyl cyclic amp | Homo sapiens (human) | IC50 | 29.0000 | 2 | 3 |
| 8-chloro-cyclic adenosine monophosphate | Homo sapiens (human) | IC50 | 34.3333 | 2 | 3 |
| tadalafil | Homo sapiens (human) | IC50 | 9.8000 | 4 | 4 |
| 4-phenylpyrrolidone-2 | Homo sapiens (human) | IC50 | 1,000.0000 | 1 | 2 |
| cdp 840 | Homo sapiens (human) | IC50 | 0.1032 | 7 | 7 |
| 7-benzylamino-6-chloro-2-piperazino-4-pyrrolidinopteridine | Homo sapiens (human) | IC50 | 0.0160 | 1 | 1 |
| 9-(2-hydroxy-3-nonyl)adenine | Homo sapiens (human) | Ki | 200.0000 | 1 | 1 |
| 9-(2-hydroxy-3-nonyl)adenine | Homo sapiens (human) | IC50 | 16.0000 | 1 | 1 |
| cilomilast | Homo sapiens (human) | IC50 | 0.8180 | 18 | 21 |
| cilomilast | Homo sapiens (human) | Ki | 0.0380 | 2 | 2 |
| rp 73401 | Homo sapiens (human) | IC50 | 0.0035 | 15 | 17 |
| rp 73401 | Homo sapiens (human) | Ki | 0.0011 | 6 | 6 |
| (+)-rolipram | Homo sapiens (human) | IC50 | 1.3500 | 2 | 2 |
| n(6)-benzyl-cyclic adenosine 5'-monophosphate | Homo sapiens (human) | IC50 | 68.0000 | 2 | 3 |
| rolipram | Homo sapiens (human) | IC50 | 1.0980 | 5 | 5 |
| roflumilast | Homo sapiens (human) | IC50 | 0.0008 | 5 | 5 |
| tetomilast | Homo sapiens (human) | IC50 | 0.0740 | 1 | 1 |
| indolidan | Homo sapiens (human) | IC50 | 0.1500 | 1 | 1 |
| fosbretabulin | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| sch 351591 | Homo sapiens (human) | IC50 | 0.0600 | 2 | 2 |
| rs 14203 | Homo sapiens (human) | IC50 | 0.0050 | 2 | 2 |
| gsk 256066 | Homo sapiens (human) | IC50 | 0.0000 | 2 | 2 |
| ci 1044 | Homo sapiens (human) | IC50 | 0.2700 | 1 | 1 |
| l-454,560 | Homo sapiens (human) | IC50 | 0.0037 | 6 | 6 |
| t 1032 | Homo sapiens (human) | IC50 | 3.3000 | 1 | 1 |
| 4-n-butyl-1-(4-(2-methylphenyl)-4-oxo-1-butyl)-piperidine hydrogen chloride | Homo sapiens (human) | Ki | 1.0000 | 1 | 1 |
| 8-(methylthio)cyclic 3',5'-adenosine monophosphate | Homo sapiens (human) | IC50 | 39.0000 | 2 | 3 |
| apremilast | Homo sapiens (human) | IC50 | 0.0860 | 3 | 3 |
| f-amidine | Homo sapiens (human) | IC50 | 110.8000 | 2 | 2 |
| 8-benzylthio-n(6)-n-butyladenosine cyclic-3,5'-monophosphate | Homo sapiens (human) | IC50 | 40.0000 | 2 | 3 |
| pf 04217903 | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| 3-(2,5-dimethoxyphenyl)-6-(3,4-dimethoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine | Homo sapiens (human) | IC50 | 5.2260 | 2 | 2 |
| n-alpha-benzoyl-n5-(2-chloro-1-iminoethyl)-l-ornithine amide | Homo sapiens (human) | IC50 | 5.9000 | 1 | 1 |
| an2728 | Homo sapiens (human) | IC50 | 0.2862 | 4 | 4 |
| bms-911543 | Homo sapiens (human) | IC50 | 5.6000 | 1 | 1 |
| chf6001 | Homo sapiens (human) | IC50 | 0.0000 | 3 | 3 |
| sildenafil | Homo sapiens (human) | IC50 | 8.2333 | 9 | 9 |
| zaprinast | Homo sapiens (human) | IC50 | 24.3333 | 3 | 3 |
| vardenafil | Homo sapiens (human) | IC50 | 4.1500 | 2 | 2 |
| Imidazosagatriazinone | Homo sapiens (human) | IC50 | 0.5000 | 1 | 1 |
| pelrinone | Homo sapiens (human) | IC50 | 4.0000 | 1 | 1 |
| lixazinone | Homo sapiens (human) | IC50 | 0.0060 | 1 | 1 |
| 6-((3s,4s)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)-1-(tetrahydro-2h-pyran-4-yl)-1,5-dihydro-4h-pyrazolo(3,4-d)pyrimidin-4-one | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
Advances in the Development of Phosphodiesterase-4 Inhibitors.Journal of medicinal chemistry, , 10-08, Volume: 63, Issue:19, 2020
Selective inhibitors of cyclic AMP-specific phosphodiesterase: heterocycle-condensed purines.Journal of medicinal chemistry, , Sep-26, Volume: 40, Issue:20, 1997
2-(beta-Arylethylamino)- and 4-(beta-arylethylamino)quinazolines as phosphodiesterase inhibitors.Journal of medicinal chemistry, , Volume: 28, Issue:1, 1985
Substituted 6,7-dihydroimidazo[1,2-a]purin-9(4H)-ones.Journal of medicinal chemistry, , Volume: 23, Issue:11, 1980
Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers.Journal of medicinal chemistry, , May-23, Volume: 45, Issue:11, 2002
Novel and selective calcitonin-inducing agents.Journal of medicinal chemistry, , Mar-23, Volume: 43, Issue:6, 2000
Advances in the Development of Phosphodiesterase-4 Inhibitors.Journal of medicinal chemistry, , 10-08, Volume: 63, Issue:19, 2020
Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.Journal of medicinal chemistry, , Sep-25, Volume: 51, Issue:18, 2008
Selective inhibitors of cyclic AMP-specific phosphodiesterase: heterocycle-condensed purines.Journal of medicinal chemistry, , Sep-26, Volume: 40, Issue:20, 1997
New 5H-pyridazino[4,5-b]indole derivatives. Synthesis and studies as inhibitors of blood platelet aggregation and inotropics.Journal of medicinal chemistry, , Volume: 34, Issue:10, 1991
Synthesis and cardiotonic activity of novel biimidazoles.Journal of medicinal chemistry, , Volume: 33, Issue:1, 1990
Selective inhibitors of cyclic AMP-specific phosphodiesterase: heterocycle-condensed purines.Journal of medicinal chemistry, , Sep-26, Volume: 40, Issue:20, 1997
Inhibition of cyclic adenosine-3',5'-monophosphate phosphodiesterase from vascular smooth muscle by rolipram analogues.Journal of medicinal chemistry, , Volume: 32, Issue:7, 1989
Discovery of novel trimethoxyphenylbenzo[d]oxazoles as dual tubulin/PDE4 inhibitors capable of inducing apoptosis at G2/M phase arrest in glioma and lung cancer cells.European journal of medicinal chemistry, , Nov-15, Volume: 224, 2021
Discovery of sulfonyl hydrazone derivative as a new selective PDE4A and PDE4D inhibitor by lead-optimization approach on the prototype LASSBio-448: In vitro and in vivo preclinical studies.European journal of medicinal chemistry, , Oct-15, Volume: 204, 2020
Design, synthesis, and biological evaluation of novel catecholopyrimidine based PDE4 inhibitor for the treatment of atopic dermatitis.European journal of medicinal chemistry, , Feb-10, Volume: 145, 2018
Development of highly potent phosphodiesterase 4 inhibitors with anti-neuroinflammation potential: Design, synthesis, and structure-activity relationship study of catecholamides bearing aromatic rings.European journal of medicinal chemistry, , Nov-29, Volume: 124, 2016
Catecholic amides as potential selective phosphodiesterase 4D inhibitors: Design, synthesis, pharmacological evaluation and structure-activity relationships.Bioorganic & medicinal chemistry, , Nov-15, Volume: 23, Issue:22, 2015
Design, synthesis, and pharmacological evaluation of N-acylhydrazones and novel conformationally constrained compounds as selective and potent orally active phosphodiesterase-4 inhibitors.Journal of medicinal chemistry, , Sep-13, Volume: 55, Issue:17, 2012
Identification of chalcones as potent and selective PDE5A1 inhibitors.Bioorganic & medicinal chemistry letters, , Jun-15, Volume: 22, Issue:12, 2012
New selective phosphodiesterase 4D inhibitors differently acting on long, short, and supershort isoforms.Journal of medicinal chemistry, , Nov-12, Volume: 52, Issue:21, 2009
Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis.Bioorganic & medicinal chemistry letters, , Apr-15, Volume: 19, Issue:8, 2009
Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.Journal of medicinal chemistry, , Sep-25, Volume: 51, Issue:18, 2008
A new chemical tool for exploring the role of the PDE4D isozyme in leukocyte function.Bioorganic & medicinal chemistry letters, , Volume: 16, Issue:3, 2006
The next generation of phosphodiesterase inhibitors: structural clues to ligand and substrate selectivity of phosphodiesterases.Journal of medicinal chemistry, , May-19, Volume: 48, Issue:10, 2005
Synthesis and biological activities of 1-pyridylisoquinoline and 1-pyridyldihydroisoquinoline derivatives as PDE4 inhibitors.Bioorganic & medicinal chemistry letters, , Jul-21, Volume: 13, Issue:14, 2003
7-Methoxyfuro[2,3-c]pyridine-4-carboxamides as PDE4 inhibitors: a potential treatment for asthma.Bioorganic & medicinal chemistry letters, , Feb-11, Volume: 12, Issue:3, 2002
8-Methoxyquinoline-5-carboxamides as PDE4 inhibitors: a potential treatment for asthma.Bioorganic & medicinal chemistry letters, , Jun-17, Volume: 12, Issue:12, 2002
Novel selective phosphodiesterase (PDE4) inhibitors. 4. Resolution, absolute configuration, and PDE4 inhibitory activity of cis-tetra- and cis-hexahydrophthalazinones.Journal of medicinal chemistry, , Jun-06, Volume: 45, Issue:12, 2002
Phthalazine PDE4 inhibitors. Part 3: the synthesis and in vitro evaluation of derivatives with a hydrogen bond acceptor.Bioorganic & medicinal chemistry letters, , Jan-07, Volume: 12, Issue:1, 2002
Phthalazine PDE4 inhibitors. Part 2: the synthesis and biological evaluation of 6-methoxy-1,4-disubstituted derivatives.Bioorganic & medicinal chemistry letters, , Jan-08, Volume: 11, Issue:1, 2001
Synthesis and biological evaluation of 2,5-dihydropyrazol.Bioorganic & medicinal chemistry letters, , Dec-04, Volume: 10, Issue:23, 2000
Palladium-catalyzed cross-coupling reactions for the synthesis of 6, 8-disubstituted 1,7-naphthyridines: a novel class of potent and selective phosphodiesterase type 4D inhibitors.Journal of medicinal chemistry, , Feb-24, Volume: 43, Issue:4, 2000
Synthesis, structure-activity relationships, and pharmacological profile of 9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6, 7,1-hi]indoles: discovery of potent, selective phosphodiesterase type 4 inhibitors.Journal of medicinal chemistry, , Dec-14, Volume: 43, Issue:25, 2000
The synthesis and biological evaluation of a novel series of phthalazine PDE4 inhibitors I.Bioorganic & medicinal chemistry letters, , Oct-02, Volume: 10, Issue:19, 2000
7-Methoxybenzofuran-4-carboxamides as PDE 4 inhibitors: a potential treatment for asthma.Bioorganic & medicinal chemistry letters, , Sep-18, Volume: 10, Issue:18, 2000
Novel, potent, and selective phosphodiesterase-4 inhibitors as antiasthmatic agents: synthesis and biological activities of a series of 1-pyridylnaphthalene derivatives.Journal of medicinal chemistry, , Mar-25, Volume: 42, Issue:6, 1999
The synthesis and biological evaluation of a novel series of indole PDE4 inhibitors I.Bioorganic & medicinal chemistry letters, , Jul-21, Volume: 8, Issue:14, 1998
Orally active indole N-oxide PDE4 inhibitors.Bioorganic & medicinal chemistry letters, , Nov-03, Volume: 8, Issue:21, 1998
7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase.Journal of medicinal chemistry, , Jun-18, Volume: 41, Issue:13, 1998
Quaternary substituted PDE4 inhibitors I: the synthesis and in vitro evaluation of a novel series of oxindoles.Bioorganic & medicinal chemistry letters, , Jan-20, Volume: 8, Issue:2, 1998
Striking effect of hydroxamic acid substitution on the phosphodiesterase type 4 (PDE4) and TNF alpha inhibitory activity of two series of rolipram analogues: implications for a new active site model of PDE4.Journal of medicinal chemistry, , Jan-29, Volume: 41, Issue:3, 1998
Aryl sulfonamides as selective PDE4 inhibitors.Bioorganic & medicinal chemistry letters, , Oct-06, Volume: 8, Issue:19, 1998
Design, synthesis, and biological activities of new thieno[3,2-d] pyrimidines as selective type 4 phosphodiesterase inhibitors.Journal of medicinal chemistry, , Oct-08, Volume: 41, Issue:21, 1998
Thalidomide analogs and PDE4 inhibition.Bioorganic & medicinal chemistry letters, , Oct-06, Volume: 8, Issue:19, 1998
Synthesis and evaluation of a novel series of phosphodiesterase IV inhibitors. A potential treatment for asthma.Bioorganic & medicinal chemistry letters, , Oct-06, Volume: 8, Issue:19, 1998
9-Benzyladenines: potent and selective cAMP phosphodiesterase inhibitors.Journal of medicinal chemistry, , Jun-06, Volume: 40, Issue:12, 1997
Novel heterocyclic-fused pyridazinones as potent and selective phosphodiesterase IV inhibitors.Journal of medicinal chemistry, , May-09, Volume: 40, Issue:10, 1997
Biarylcarboxylic acids and -amides: inhibition of phosphodiesterase type IV versus [3H]rolipram binding activity and their relationship to emetic behavior in the ferret.Journal of medicinal chemistry, , Jan-05, Volume: 39, Issue:1, 1996
Introduction of a conformational switching element on a pyrrolidine ring. Synthesis and evaluation of (R*,R*)-(+/-)-methyl 3-acetyl-4-[3- (cyclopentyloxy)-4-methoxyphenyl]-3-methyl-1-pyrrolidinecarboxylate, a potent and selective inhibitor of cAMP-specifiJournal of medicinal chemistry, , Dec-22, Volume: 38, Issue:26, 1995
Selective type IV phosphodiesterase inhibitors as antiasthmatic agents. The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenzamides and analogues.Journal of medicinal chemistry, , May-27, Volume: 37, Issue:11, 1994
New bronchodilators. 3. Imidazo[4,5-c][1,8]naphthyridin-4(5H)-ones.Journal of medicinal chemistry, , Dec-25, Volume: 35, Issue:26, 1992
Inhibition of cyclic adenosine-3',5'-monophosphate phosphodiesterase from vascular smooth muscle by rolipram analogues.Journal of medicinal chemistry, , Volume: 32, Issue:7, 1989
Advances in the Development of Phosphodiesterase-4 Inhibitors.Journal of medicinal chemistry, , 10-08, Volume: 63, Issue:19, 2020
Synthesis and structure-activity relationships of cis-tetrahydrophthalazinone/pyridazinone hybrids: a novel series of potent dual PDE3/PDE4 inhibitory agents.Journal of medicinal chemistry, , May-08, Volume: 46, Issue:10, 2003
Novel selective PDE4 inhibitors. 1. Synthesis, structure-activity relationships, and molecular modeling of 4-(3,4-dimethoxyphenyl)-2H-phthalazin-1-ones and analogues.Journal of medicinal chemistry, , Aug-02, Volume: 44, Issue:16, 2001
Pharmacokinetics-Driven Optimization of 4(3 H)-Pyrimidinones as Phosphodiesterase Type 5 Inhibitors Leading to TPN171, a Clinical Candidate for the Treatment of Pulmonary Arterial Hypertension.Journal of medicinal chemistry, , 05-23, Volume: 62, Issue:10, 2019
Synthesis of quinoline derivatives: discovery of a potent and selective phosphodiesterase 5 inhibitor for the treatment of Alzheimer's disease.European journal of medicinal chemistry, , Volume: 60, 2013
Optimization of purine based PDE1/PDE5 inhibitors to a potent and selective PDE5 inhibitor for the treatment of male ED.Bioorganic & medicinal chemistry letters, , May-02, Volume: 15, Issue:9, 2005
The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione analogues.Journal of medicinal chemistry, , Oct-09, Volume: 46, Issue:21, 2003
Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: structure-activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor.Bioorganic & medicinal chemistry letters, , Dec-01, Volume: 15, Issue:23, 2005
Novel selective phosphodiesterase (PDE4) inhibitors. 4. Resolution, absolute configuration, and PDE4 inhibitory activity of cis-tetra- and cis-hexahydrophthalazinones.Journal of medicinal chemistry, , Jun-06, Volume: 45, Issue:12, 2002
Novel selective PDE4 inhibitors. 3. In vivo antiinflammatory activity of a new series of N-substituted cis-tetra- and cis-hexahydrophthalazinones.Journal of medicinal chemistry, , Jun-06, Volume: 45, Issue:12, 2002
Quaternary substituted PDE4 inhibitors I: the synthesis and in vitro evaluation of a novel series of oxindoles.Bioorganic & medicinal chemistry letters, , Jan-20, Volume: 8, Issue:2, 1998
7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase.Journal of medicinal chemistry, , Jun-18, Volume: 41, Issue:13, 1998
Discovery of sulfonyl hydrazone derivative as a new selective PDE4A and PDE4D inhibitor by lead-optimization approach on the prototype LASSBio-448: In vitro and in vivo preclinical studies.European journal of medicinal chemistry, , Oct-15, Volume: 204, 2020
Advances in the Development of Phosphodiesterase-4 Inhibitors.Journal of medicinal chemistry, , 10-08, Volume: 63, Issue:19, 2020
SAR of a series of 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridines as potent inhibitors of human eosinophil phosphodiesterase.Journal of medicinal chemistry, , Jan-25, Volume: 50, Issue:2, 2007
The next generation of phosphodiesterase inhibitors: structural clues to ligand and substrate selectivity of phosphodiesterases.Journal of medicinal chemistry, , May-19, Volume: 48, Issue:10, 2005
Orally active PDE4 inhibitors with therapeutic potential.Bioorganic & medicinal chemistry letters, , Mar-08, Volume: 14, Issue:5, 2004
Synthesis and structure-activity relationships of cis-tetrahydrophthalazinone/pyridazinone hybrids: a novel series of potent dual PDE3/PDE4 inhibitory agents.Journal of medicinal chemistry, , May-08, Volume: 46, Issue:10, 2003
Novel selective phosphodiesterase (PDE4) inhibitors. 4. Resolution, absolute configuration, and PDE4 inhibitory activity of cis-tetra- and cis-hexahydrophthalazinones.Journal of medicinal chemistry, , Jun-06, Volume: 45, Issue:12, 2002
Novel selective PDE4 inhibitors. 3. In vivo antiinflammatory activity of a new series of N-substituted cis-tetra- and cis-hexahydrophthalazinones.Journal of medicinal chemistry, , Jun-06, Volume: 45, Issue:12, 2002
Phthalazine PDE4 inhibitors. Part 3: the synthesis and in vitro evaluation of derivatives with a hydrogen bond acceptor.Bioorganic & medicinal chemistry letters, , Jan-07, Volume: 12, Issue:1, 2002
Synthesis of 4-(8-benzo[1,2,5]oxadiazol-5-yl-[1,7]naphthyridine-6-yl)-benzoic acid: a potent and selective phosphodiesterase type 4D inhibitor.Bioorganic & medicinal chemistry letters, , Jan-21, Volume: 12, Issue:2, 2002
Novel selective PDE4 inhibitors. 2. Synthesis and structure-activity relationships of 4-aryl-substituted cis-tetra- and cis-hexahydrophthalazinones.Journal of medicinal chemistry, , Aug-02, Volume: 44, Issue:16, 2001
Phthalazine PDE4 inhibitors. Part 2: the synthesis and biological evaluation of 6-methoxy-1,4-disubstituted derivatives.Bioorganic & medicinal chemistry letters, , Jan-08, Volume: 11, Issue:1, 2001
Novel selective PDE4 inhibitors. 1. Synthesis, structure-activity relationships, and molecular modeling of 4-(3,4-dimethoxyphenyl)-2H-phthalazin-1-ones and analogues.Journal of medicinal chemistry, , Aug-02, Volume: 44, Issue:16, 2001
Palladium-catalyzed cross-coupling reactions for the synthesis of 6, 8-disubstituted 1,7-naphthyridines: a novel class of potent and selective phosphodiesterase type 4D inhibitors.Journal of medicinal chemistry, , Feb-24, Volume: 43, Issue:4, 2000
Synthesis, structure-activity relationships, and pharmacological profile of 9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6, 7,1-hi]indoles: discovery of potent, selective phosphodiesterase type 4 inhibitors.Journal of medicinal chemistry, , Dec-14, Volume: 43, Issue:25, 2000
7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase.Journal of medicinal chemistry, , Jun-18, Volume: 41, Issue:13, 1998
1,4-Cyclohexanecarboxylates: potent and selective inhibitors of phosophodiesterase 4 for the treatment of asthma.Journal of medicinal chemistry, , Mar-12, Volume: 41, Issue:6, 1998
SAR of a series of 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridines as potent inhibitors of human eosinophil phosphodiesterase.Journal of medicinal chemistry, , Jan-25, Volume: 50, Issue:2, 2007
Synthesis and biological activities of 1-pyridylisoquinoline and 1-pyridyldihydroisoquinoline derivatives as PDE4 inhibitors.Bioorganic & medicinal chemistry letters, , Jul-21, Volume: 13, Issue:14, 2003
Phthalazine PDE4 inhibitors. Part 3: the synthesis and in vitro evaluation of derivatives with a hydrogen bond acceptor.Bioorganic & medicinal chemistry letters, , Jan-07, Volume: 12, Issue:1, 2002
Phthalazine PDE4 inhibitors. Part 2: the synthesis and biological evaluation of 6-methoxy-1,4-disubstituted derivatives.Bioorganic & medicinal chemistry letters, , Jan-08, Volume: 11, Issue:1, 2001
The synthesis and biological evaluation of a novel series of phthalazine PDE4 inhibitors I.Bioorganic & medicinal chemistry letters, , Oct-02, Volume: 10, Issue:19, 2000
Novel cyclic compounds as potent phosphodiesterase 4 inhibitors.Journal of medicinal chemistry, , Oct-22, Volume: 41, Issue:22, 1998
Orally active indole N-oxide PDE4 inhibitors.Bioorganic & medicinal chemistry letters, , Nov-03, Volume: 8, Issue:21, 1998
The synthesis and biological evaluation of a novel series of indole PDE4 inhibitors I.Bioorganic & medicinal chemistry letters, , Jul-21, Volume: 8, Issue:14, 1998
7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase.Journal of medicinal chemistry, , Jun-18, Volume: 41, Issue:13, 1998
Striking effect of hydroxamic acid substitution on the phosphodiesterase type 4 (PDE4) and TNF alpha inhibitory activity of two series of rolipram analogues: implications for a new active site model of PDE4.Journal of medicinal chemistry, , Jan-29, Volume: 41, Issue:3, 1998
2-Substituted-4-methoxybenzimidazole-based PDE4 inhibitors.Bioorganic & medicinal chemistry letters, , Oct-06, Volume: 8, Issue:19, 1998
Selective type IV phosphodiesterase inhibitors as antiasthmatic agents. The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenzamides and analogues.Journal of medicinal chemistry, , May-27, Volume: 37, Issue:11, 1994
1,4-Cyclohexanecarboxylates: potent and selective inhibitors of phosophodiesterase 4 for the treatment of asthma.Journal of medicinal chemistry, , Mar-12, Volume: 41, Issue:6, 1998
The crystal structure, absolute configuration, and phosphodiesterase inhibitory activity of (+)-1-(4-bromobenzyl)-4-(3-(cyclopentyloxy)- 4-methoxyphenyl)-pyrrolidin-2-one.Journal of medicinal chemistry, , Oct-29, Volume: 36, Issue:22, 1993
SAR of a series of 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridines as potent inhibitors of human eosinophil phosphodiesterase.Journal of medicinal chemistry, , Jan-25, Volume: 50, Issue:2, 2007
Novel selective PDE4 inhibitors. 3. In vivo antiinflammatory activity of a new series of N-substituted cis-tetra- and cis-hexahydrophthalazinones.Journal of medicinal chemistry, , Jun-06, Volume: 45, Issue:12, 2002
Novel selective PDE4 inhibitors. 2. Synthesis and structure-activity relationships of 4-aryl-substituted cis-tetra- and cis-hexahydrophthalazinones.Journal of medicinal chemistry, , Aug-02, Volume: 44, Issue:16, 2001
1,4-Cyclohexanecarboxylates: potent and selective inhibitors of phosophodiesterase 4 for the treatment of asthma.Journal of medicinal chemistry, , Mar-12, Volume: 41, Issue:6, 1998
The crystal structure, absolute configuration, and phosphodiesterase inhibitory activity of (+)-1-(4-bromobenzyl)-4-(3-(cyclopentyloxy)- 4-methoxyphenyl)-pyrrolidin-2-one.Journal of medicinal chemistry, , Oct-29, Volume: 36, Issue:22, 1993
Discovery of sulfonyl hydrazone derivative as a new selective PDE4A and PDE4D inhibitor by lead-optimization approach on the prototype LASSBio-448: In vitro and in vivo preclinical studies.European journal of medicinal chemistry, , Oct-15, Volume: 204, 2020
Discovery and Early Clinical Development of Isobutyl 1-[8-Methoxy-5-(1-oxo-3Journal of medicinal chemistry, , 12-10, Volume: 63, Issue:23, 2020
Dual β2-adrenoceptor agonists-PDE4 inhibitors for the treatment of asthma and COPD.Bioorganic & medicinal chemistry letters, , Feb-15, Volume: 22, Issue:4, 2012
Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor.Journal of medicinal chemistry, , Mar-26, Volume: 52, Issue:6, 2009
The next generation of phosphodiesterase inhibitors: structural clues to ligand and substrate selectivity of phosphodiesterases.Journal of medicinal chemistry, , May-19, Volume: 48, Issue:10, 2005
Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.Journal of medicinal chemistry, , Sep-25, Volume: 51, Issue:18, 2008
Novel selective PDE4 inhibitors. 1. Synthesis, structure-activity relationships, and molecular modeling of 4-(3,4-dimethoxyphenyl)-2H-phthalazin-1-ones and analogues.Journal of medicinal chemistry, , Aug-02, Volume: 44, Issue:16, 2001
Synthesis, structure-activity relationships, and pharmacological profile of 9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6, 7,1-hi]indoles: discovery of potent, selective phosphodiesterase type 4 inhibitors.Journal of medicinal chemistry, , Dec-14, Volume: 43, Issue:25, 2000
Discovery of MK-0952, a selective PDE4 inhibitor for the treatment of long-term memory loss and mild cognitive impairment.Bioorganic & medicinal chemistry letters, , Nov-15, Volume: 20, Issue:22, 2010
The discovery and synthesis of highly potent subtype selective phosphodiesterase 4D inhibitors.Bioorganic & medicinal chemistry letters, , Sep-15, Volume: 20, Issue:18, 2010
Alkyl-bridged substituted 8-arylquinolines as highly potent PDE IV inhibitors.Bioorganic & medicinal chemistry letters, , Sep-01, Volume: 19, Issue:17, 2009
Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: structure-activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor.Bioorganic & medicinal chemistry letters, , Dec-01, Volume: 15, Issue:23, 2005
Advances in the Development of Phosphodiesterase-4 Inhibitors.Journal of medicinal chemistry, , 10-08, Volume: 63, Issue:19, 2020
Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent.Journal of medicinal chemistry, , 06-13, Volume: 62, Issue:11, 2019
Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor.Journal of medicinal chemistry, , Mar-26, Volume: 52, Issue:6, 2009
Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors.Bioorganic & medicinal chemistry letters, , Jul-01, Volume: 19, Issue:13, 2009
Identification of a potent new chemotype for the selective inhibition of PDE4.Bioorganic & medicinal chemistry letters, , Feb-15, Volume: 18, Issue:4, 2008
Advances in the Development of Phosphodiesterase-4 Inhibitors.Journal of medicinal chemistry, , 10-08, Volume: 63, Issue:19, 2020
Lead-like Drugs: A Perspective.Journal of medicinal chemistry, , 12-13, Volume: 61, Issue:23, 2018
Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis.Bioorganic & medicinal chemistry letters, , Apr-15, Volume: 19, Issue:8, 2009
Advances in the Development of Phosphodiesterase-4 Inhibitors.Journal of medicinal chemistry, , 10-08, Volume: 63, Issue:19, 2020
Novel class of benzoic acid ester derivatives as potent PDE4 inhibitors for inhaled administration in the treatment of respiratory diseases.Journal of medicinal chemistry, , Feb-13, Volume: 57, Issue:3, 2014
Pharmacokinetics-Driven Optimization of 4(3 H)-Pyrimidinones as Phosphodiesterase Type 5 Inhibitors Leading to TPN171, a Clinical Candidate for the Treatment of Pulmonary Arterial Hypertension.Journal of medicinal chemistry, , 05-23, Volume: 62, Issue:10, 2019
Synthesis of quinoline derivatives: discovery of a potent and selective phosphodiesterase 5 inhibitor for the treatment of Alzheimer's disease.European journal of medicinal chemistry, , Volume: 60, 2013
Identification of chalcones as potent and selective PDE5A1 inhibitors.Bioorganic & medicinal chemistry letters, , Jun-15, Volume: 22, Issue:12, 2012
Optimization of purine based PDE1/PDE5 inhibitors to a potent and selective PDE5 inhibitor for the treatment of male ED.Bioorganic & medicinal chemistry letters, , May-02, Volume: 15, Issue:9, 2005
The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione analogues.Journal of medicinal chemistry, , Oct-09, Volume: 46, Issue:21, 2003
The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 1: 5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione analogues.Journal of medicinal chemistry, , Oct-09, Volume: 46, Issue:21, 2003
1,7- and 2,7-naphthyridine derivatives as potent and highly specific PDE5 inhibitors.Bioorganic & medicinal chemistry letters, , Jul-21, Volume: 13, Issue:14, 2003
Imidazo[5,1-f]triazin-4(3H)-ones, a new class of potent PDE 5 inhibitors.Bioorganic & medicinal chemistry letters, , Mar-25, Volume: 12, Issue:6, 2002
Novel, potent, and selective phosphodiesterase 5 inhibitors: synthesis and biological activities of a series of 4-aryl-1-isoquinolinone derivatives.Journal of medicinal chemistry, , Jun-21, Volume: 44, Issue:13, 2001
Identification of chalcones as potent and selective PDE5A1 inhibitors.Bioorganic & medicinal chemistry letters, , Jun-15, Volume: 22, Issue:12, 2012
The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 1: 5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione analogues.Journal of medicinal chemistry, , Oct-09, Volume: 46, Issue:21, 2003
Inhibition of cyclic nucleotide phosphodiesterase by derivatives of 1,3-bis(cyclopropylmethyl)xanthine.Journal of medicinal chemistry, , Feb-18, Volume: 37, Issue:4, 1994
Enables
This protein enables 3 target(s):
| Target | Category | Definition |
|---|
| 3',5'-cyclic-AMP phosphodiesterase activity | molecular function | Catalysis of the reaction: 3',5'-cyclic AMP + H2O = AMP + H+. [GOC:ai, RHEA:25277] |
| metal ion binding | molecular function | Binding to a metal ion. [GOC:ai] |
| 3',5'-cyclic-GMP phosphodiesterase activity | molecular function | Catalysis of the reaction: 3',5'-cyclic GMP + H2O = GMP + H+. [RHEA:16957] |
Located In
This protein is located in 3 target(s):
| Target | Category | Definition |
|---|
| extracellular space | cellular component | That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid. [ISBN:0198547684] |
| cytosol | cellular component | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. [GOC:hjd, GOC:jl] |
| cilium | cellular component | A specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface and of some cytoplasmic parts. Each cilium is largely bounded by an extrusion of the cytoplasmic (plasma) membrane, and contains a regular longitudinal array of microtubules, anchored to a basal body. [GOC:cilia, GOC:curators, GOC:kmv, GOC:vw, ISBN:0198547684, PMID:16824949, PMID:17009929, PMID:20144998] |
Active In
This protein is active in 3 target(s):
| Target | Category | Definition |
|---|
| cytosol | cellular component | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. [GOC:hjd, GOC:jl] |
| nucleus | cellular component | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. [GOC:go_curators] |
| perinuclear region of cytoplasm | cellular component | Cytoplasm situated near, or occurring around, the nucleus. [GOC:jid] |
Involved In
This protein is involved in 2 target(s):
| Target | Category | Definition |
|---|
| cAMP catabolic process | biological process | The chemical reactions and pathways resulting in the breakdown of the nucleotide cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate). [ISBN:0198506732] |
| cAMP-mediated signaling | biological process | An intracellular signaling cassette that starts with production of cyclic AMP (cAMP), and ends with activation of downstream effectors that further transmit the signal within the cell. [GOC:signaling] |