2,6-Dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-isopropyl ester 5-(2-methoxy-ethyl) ester

ID: ALA1428

Max Phase: Approved

First Approval: 1988

Molecular Formula: C21H26N2O7

Molecular Weight: 418.45

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Admon | Nemotan | Nimodipine | Nimodipine ap | Periplum | BAY E 9736 | BAY-E-9736 | NSC-758476

Trade Names(3): Nimodipine | Nimotop | Nymalize

Canonical SMILES:  COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1c1cccc([N+](=O)[O-])c1

Standard InChI:  InChI=1S/C21H26N2O7/c1-12(2)30-21(25)18-14(4)22-13(3)17(20(24)29-10-9-28-5)19(18)15-7-6-8-16(11-15)23(26)27/h6-8,11-12,19,22H,9-10H2,1-5H3

Standard InChI Key:  UIAGMCDKSXEBJQ-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 30 31  0  0  0  0  0  0  0  0999 V2000
    3.8625   -6.0792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0792   -6.0792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4667   -5.7167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8625   -6.7875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0792   -6.7875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2417   -5.7292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4667   -7.1375    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.7250   -3.6000    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.4667   -5.0042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6875   -5.7417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0917   -3.9667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0917   -4.6542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6292   -6.0917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.3417   -4.0042    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.7250   -2.8917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.2417   -5.0167    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.6875   -5.0542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.3042   -6.1125    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.2250   -7.1167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.7000   -7.1375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8542   -4.6542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0042   -5.7292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4667   -3.5917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8542   -3.9500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1375   -5.7500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.9125   -5.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5292   -6.1125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7417   -6.0917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4000   -6.0792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0042   -5.0167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  3  1  0
  3  1  1  0
  4  1  2  0
  5  7  1  0
  6  1  1  0
  7  4  1  0
  8 11  1  0
  9  3  1  0
 10  2  1  0
 11 12  1  0
 12  9  2  0
 13  6  1  0
 14  8  1  0
 15  8  2  0
 16  6  2  0
 17 10  2  0
 18 10  1  0
 19  4  1  0
 20  5  1  0
 21  9  1  0
 22 13  1  0
 23 24  1  0
 24 21  2  0
 25 27  1  0
 26 18  1  0
 27 26  1  0
 28 25  1  0
 29 22  1  0
 30 22  1  0
  5  2  2  0
 23 11  2  0
M  CHG  2   8   1  14  -1
M  END

Alternative Forms

1. Parent:

   

   ALA1428

   NIMODIPINE

Molecule Features

Natural Product: No

Oral: Yes

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: Yes

Chirality: No

Availability: Yes

Prodrug: No

Calculated Properties

Molecular Weight: 418.45

Molecular Weight (Monoisotopic): 418.1740

AlogP: 2.97

#Rotatable Bonds: 8

Polar Surface Area: 117.00

Molecular Species: NEUTRAL

HBA: 8

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 2.54

CX LogD: 2.54

Aromatic Rings: 1

Heavy Atoms: 30

QED Weighted: 0.30

Np Likeness Score: -1.02

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88. Zindo FT, Malan SF, Omoruyi SI, Enogieru AB, Ekpo OE, Joubert J..  (2019)  Design, synthesis and evaluation of pentacycloundecane and hexacycloundecane propargylamine derivatives as multifunctional neuroprotective agents.,  163  [PMID:30503945] [10.1016/j.ejmech.2018.11.051]

89. Daniels BJ, Li FF, Furkert DP, Brimble MA..  (2019)  Naturally Occurring Lumazines.,  82  (7): [PMID:31317731] [10.1021/acs.jnatprod.9b00351]

90. Bisi A, Arribas RL, Micucci M, Budriesi R, Feoli A, Castellano S, Belluti F, Gobbi S, de Los Rios C, Rampa A..  (2019)  Polycyclic maleimide-based derivatives as first dual modulators of neuronal calcium channels and GSK-3β for Alzheimer's disease treatment.,  163  [PMID:30530190] [10.1016/j.ejmech.2018.12.003]

91. Johannes Zuegg, Alysha Elliott, Maite Amado, Emma Cowie, Ali Hinton, Geraldine Kaeslin, Angela Kavanagh, Anne Kunert, Gabriell Lowe, Soumya Ramu, Janet Reid, Robin Trauer, Mathilde Desselle, Ruth Neale, Karl Hansford, Mark Blascovich, Matthew Cooper. CO-ADD screening of NIH (USA) - Clinical Collection,  [10.6019/CHEMBL4513141]

92. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]

93. Wang Y,Ma H,Huang J,Yao Z,Yu J,Zhang W,Zhang L,Wang Z,Zhuang C.  (2021)  Discovery of bardoxolone derivatives as novel orally active necroptosis inhibitors.,  212  [PMID:33248849] [10.1016/j.ejmech.2020.113030]

94. Egunlusi AO,Malan SF,Omoruyi SI,Ekpo OE,Palchykov VA,Joubert J.  (2020)  Open and rearranged norbornane derived polycyclic cage molecules as potential neuroprotective agents through attenuation of MPP- and calcium overload-induced excitotoxicity in neuroblastoma SH-SY5Y cells.,  204  [PMID:32717484] [10.1016/j.ejmech.2020.112617]

95. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

96. Chen H, Chen X, Sun P, Wu D, Yue H, Pan J, Li X, Zhang C, Wu X, Hua L, Hu W, Yang Z..  (2021)  Discovery of dronedarone and its analogues as NLRP3 inflammasome inhibitors with potent anti-inflammation activity.,  46  [PMID:34062252] [10.1016/j.bmcl.2021.128160]

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101. Bell, Ian M IM and 30 more authors.  2002-06-06  3-Aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency.  [PMID:12036349]

102. de Dios, Alfonso A and 23 more authors.  2005-04-07  Design of potent and selective 2-aminobenzimidazole-based p38alpha MAP kinase inhibitors with excellent in vivo efficacy.  [PMID:15801819]

103. Voets, Marieke M and 7 more authors.  2005-10-20  Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis.  [PMID:16220979]

104. Voets, Marieke M and 6 more authors.  2006-04-06  Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis.  [PMID:16570918]

105. Feng, Yangbo Y and 7 more authors.  2007-04-15  Structure-activity relationships, and drug metabolism and pharmacokinetic properties for indazole piperazine and indazole piperidine inhibitors of ROCK-II.  [PMID:17368019]

106. Feng, Jun J and 13 more authors.  2007-05-17  Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV.  [PMID:17441705]

107. Reck, Folkert F and 8 more authors.  2007-10-04  Novel substituted (pyridin-3-yl)phenyloxazolidinones: antibacterial agents with reduced activity against monoamine oxidase A and increased solubility.  [PMID:17722903]

108. Jiang, Wanlong W and 13 more authors.  2007-10-15  Pyrrolidinones as potent functional antagonists of the human melanocortin-4 receptor.  [PMID:17822895]

109. McBriar, Mark D MD and 12 more authors.  2008-01-01  Discovery of amide and heteroaryl isosteres as carbamate replacements in a series of orally active gamma-secretase inhibitors.  [PMID:17988864]

110. Cai, Zhen-Wei ZW and 13 more authors.  2008-02-15  Synthesis, SAR, and Evaluation of 4-[2,4-Difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1-f][1,2,4]triazine-based VEGFR-2 kinase inhibitors.  [PMID:18221875]

111. Wang, Wei W and 24 more authors.  2008-03-15  Discovery of azetidinone acids as conformationally-constrained dual PPARalpha/gamma agonists.  [PMID:18291645]

112. Frotscher, Martin M and 10 more authors.  2008-04-10  Design, synthesis, and biological evaluation of (hydroxyphenyl)naphthalene and -quinoline derivatives: potent and selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) for the treatment of estrogen-dependent diseases.  [PMID:18324762]

113. Degnan, Andrew P AP and 18 more authors.  2008-08-28  Discovery of (R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide (BMS-694153): a potent antagonist of the human calcitonin gene-related peptide receptor for migraine with rapid and efficient intranasal exposure.  [PMID:18665579]

114. Heim, Ralf R and 8 more authors.  2008-08-28  Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization on potency and selectivity.  [PMID:18672861]

115. Pinto-Bazurco Mendieta, Mariano A E MA and 5 more authors.  2008-08-28  Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer.  [PMID:18672868]

116. Bey, Emmanuel E and 9 more authors.  2008-11-13  Design, synthesis, biological evaluation and pharmacokinetics of bis(hydroxyphenyl) substituted azoles, thiophenes, benzenes, and aza-benzenes as potent and selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1).  [PMID:18855374]

117. Zhang, Xiaohu X and 24 more authors.  2008-11-27  Lead optimization of 4-acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A2A adenosine receptor antagonists for the treatment of Parkinson's disease.  [PMID:18947224]

118. Chen, Chen C and 18 more authors.  2008-12-11  Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor.  [PMID:19006286]

119. Hille, Ulrike E UE and 7 more authors.  2009-07  Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls.  [PMID:19211174]

120. Kraus, James M and 5 more authors.  2009-03-26  Rational modification of a candidate cancer drug for use against Chagas disease.  [PMID:19239254]

121. Charrier, Nicolas N and 23 more authors.  2009-07-01  Second generation of BACE-1 inhibitors. Part 1: The need for improved pharmacokinetics.  [PMID:19428244]

122. Gibson, Christoph C and 9 more authors.  2009-07-23  Novel small molecule bradykinin B2 receptor antagonists.  [PMID:19552431]

123. Boezio, Alessandro A AA and 25 more authors.  2009-11-15  Discovery and optimization of potent and selective triazolopyridazine series of c-Met inhibitors.  [PMID:19819693]

124. Bey, Emmanuel E and 10 more authors.  2009-11-12  New insights into the SAR and binding modes of bis(hydroxyphenyl)thiophenes and -benzenes: influence of additional substituents on 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) inhibitory activity and selectivity.  [PMID:19831396]

125. Chen, Austin A and 22 more authors.  2010-04-01  Design and optimization of a substituted amino propanamide series of renin inhibitors for the treatment of hypertension.  [PMID:20206513]

126. Hu, Qingzhong Q, Yin, Lina L, Jagusch, Carsten C, Hille, Ulrike E UE and Hartmann, Rolf W RW.  2010-07-08  Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors.  [PMID:20550118]

127. Clarke, Brian B and 21 more authors.  2010-08-01  BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296.  [PMID:20579874]

128. Brigance, Robert P RP and 7 more authors.  2010-08-01  Synthesis and SAR of azolopyrimidines as potent and selective dipeptidyl peptidase-4 (DPP4) inhibitors for type 2 diabetes.  [PMID:20598534]

129. Adams, Christopher M CM and 15 more authors.  2010-08-01  The discovery of potent inhibitors of aldosterone synthase that exhibit selectivity over 11-beta-hydroxylase.  [PMID:20615692]

130. Arhancet, Graciela B and 14 more authors.  2010-08-26  Discovery of novel cyanodihydropyridines as potent mineralocorticoid receptor antagonists.  [PMID:20672820]

131. Hu, Qingzhong Q, Jagusch, Carsten C, Hille, Ulrike E UE, Haupenthal, Jörg J and Hartmann, Rolf W RW.  2010-08-12  Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer.  [PMID:20684610]

132. Corminboeuf, Olivier O and 11 more authors.  2010-11-01  Design and optimization of new piperidines as renin inhibitors.  [PMID:20843686]

133. Manning, David D DD and 19 more authors.  2011-01-01  Novel serotonin type 3 receptor partial agonists for the potential treatment of irritable bowel syndrome.  [PMID:21146988]

134. Marchais-Oberwinkler, Sandrine S and 7 more authors.  2011-01-27  New drug-like hydroxyphenylnaphthol steroidomimetics as potent and selective 17β-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of estrogen-dependent diseases.  [PMID:21189020]

135. Stock, Nicholas N and 19 more authors.  2011-02-01  Sodium [2'-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-4'-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetate (AM432): a potent, selective prostaglandin D2 receptor antagonist.  [PMID:21211969]

136. Patch, Raymond J RJ and 16 more authors.  2011-02-10  Identification of diaryl ether-based ligands for estrogen-related receptor α as potential antidiabetic agents.  [PMID:21218783]

137. De Savi, Chris C and 13 more authors.  2011-03-01  The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis.  [PMID:21300546]

138. Lucas, Simon S, Negri, Matthias M, Heim, Ralf R, Zimmer, Christina C and Hartmann, Rolf W RW.  2011-04-14  Fine-tuning the selectivity of aldosterone synthase inhibitors: structure-activity and structure-selectivity insights from studies of heteroaryl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1-ij]quinolin-4-one derivatives.  [PMID:21384875]

139. Zehnder, Luke L and 25 more authors.  2011-05-12  Optimization of potent, selective, and orally bioavailable pyrrolodinopyrimidine-containing inhibitors of heat shock protein 90. Identification of development candidate 2-amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl}-N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamide.  [PMID:21438541]

140. Foti, Robert S RS, Rock, Dan A DA, Pearson, Josh T JT, Wahlstrom, Jan L JL and Wienkers, Larry C LC.  2011-07  Mechanism-based inactivation of cytochrome P450 3A4 by mibefradil through heme destruction.  [PMID:21447734]

141. De Savi, Chris C and 11 more authors.  2011-06-01  Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis.  [PMID:21536437]

142. William, Anthony D AD and 18 more authors.  2011-07-14  Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma.  [PMID:21604762]

143. Chen, Austin A and 25 more authors.  2011-07-01  Renin inhibitors for the treatment of hypertension: design and optimization of a novel series of tertiary alcohol-bearing piperidines.  [PMID:21641209]

144. Zhang, Lin L and 31 more authors.  2011-09-15  Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I).  [PMID:21798738]

145. Guagnano, Vito V and 16 more authors.  2011-10-27  Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase.  [PMID:21936542]

146. Illig, Carl R CR and 17 more authors.  2011-11-24  Optimization of a potent class of arylamide colony-stimulating factor-1 receptor inhibitors leading to anti-inflammatory clinical candidate 4-cyano-N-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1H-imidazole-2-carboxamide (JNJ-28312141).  [PMID:22039836]

147. Chen, Austin A and 14 more authors.  2011-12-15  Renin inhibitors for the treatment of hypertension: design and optimization of a novel series of spirocyclic piperidines.  [PMID:22071301]

148. Peng, Chi-Chi CC and 6 more authors.  2012-03  Stereospecific metabolism of itraconazole by CYP3A4: dioxolane ring scission of azole antifungals.  [PMID:22106171]

149. Song, Xinyi and 6 more authors.  2012-02-15  Imidazopyridines as selective CYP3A4 inhibitors.  [PMID:22264486]

150. William, Anthony D AD and 16 more authors.  2012-03-22  Discovery of the macrocycle (9E)-15-(2-(pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a potent inhibitor of janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) for the treatment of rheumatoid arthritis.  [PMID:22339472]

151. Henne, Kirk R KR and 13 more authors.  2012-07  Sequential metabolism of AMG 487, a novel CXCR3 antagonist, results in formation of quinone reactive metabolites that covalently modify CYP3A4 Cys239 and cause time-dependent inhibition of the enzyme.  [PMID:22517972]

152. Dugan, Benjamin J BJ and 18 more authors.  2012-06-14  A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779.  [PMID:22594690]

153. Walsky, Robert L RL and 10 more authors.  2012-09  Selective mechanism-based inactivation of CYP3A4 by CYP3cide (PF-04981517) and its utility as an in vitro tool for delineating the relative roles of CYP3A4 versus CYP3A5 in the metabolism of drugs.  [PMID:22645092]

154. Gomaa, Mohamed S MS and 7 more authors.  2012-07-15  Novel retinoic acid 4-hydroxylase (CYP26) inhibitors based on a 3-(1H-imidazol- and triazol-1-yl)-2,2-dimethyl-3-(4-(phenylamino)phenyl)propyl scaffold.  [PMID:22727372]

155. Han, Xiaojun X and 15 more authors.  2012-07-15  The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates. Part 1.  [PMID:22727645]

156. Huber, John D JD and 19 more authors.  2012-08-23  Identification of a potent sodium hydrogen exchanger isoform 1 (NHE1) inhibitor with a suitable profile for chronic dosing and demonstrated cardioprotective effects in a preclinical model of myocardial infarction in the rat.  [PMID:22803959]

157. Kim, Heung Jae HJ and 10 more authors.  2012-09-01  Dipeptidyl peptidase-4 inhibitor with β-amino amide scaffold: synthesis, SAR and biological evaluation.  [PMID:22850208]

158. Ruf, Sven S and 16 more authors.  2012-09-13  Novel β-amino acid derivatives as inhibitors of cathepsin A.  [PMID:22861813]

159. Su, Xiangdong X and 6 more authors.  2012-11-01  Adamantyl carboxamides and acetamides as potent human 11β-hydroxysteroid dehydrogenase type 1 inhibitors.  [PMID:23040895]

160. Hanan, Emily J EJ and 22 more authors.  2012-11-26  Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors.  [PMID:23061660]

161. Plowright, Alleyn T AT and 14 more authors.  2013-01-10  Discovery of agonists of cannabinoid receptor 1 with restricted central nervous system penetration aimed for treatment of gastroesophageal reflux disease.  [PMID:23227781]

162. Taygerly, Joshua P and 31 more authors.  2013-02-15  Discovery of INT131: a selective PPARγ modulator that enhances insulin sensitivity.  [PMID:23294830]

163. Arico-Muendel, Christopher C CC and 20 more authors.  2013-04  Metabolites of PPI-2458, a selective, irreversible inhibitor of methionine aminopeptidase-2: structure determination and in vivo activity.  [PMID:23355637]

164. Sevrioukova, Irina F IF and Poulos, Thomas L TL.  2013-05-09  Pyridine-substituted desoxyritonavir is a more potent inhibitor of cytochrome P450 3A4 than ritonavir.  [PMID:23586711]

165. Pinto-Bazurco Mendieta, Mariano A E MA, Hu, Qingzhong Q, Engel, Matthias M and Hartmann, Rolf W RW.  2013-08-08  Highly potent and selective nonsteroidal dual inhibitors of CYP17/CYP11B2 for the treatment of prostate cancer to reduce risks of cardiovascular diseases.  [PMID:23859149]

166. Yu, Chao-Wu CW, Chang, Pei-Teh PT, Hsin, Ling-Wei LW and Chern, Ji-Wang JW.  2013-09-12  Quinazolin-4-one derivatives as selective histone deacetylase-6 inhibitors for the treatment of Alzheimer's disease.  [PMID:23905680]

167. Schoenfeld, Ryan C and 18 more authors.  2013-10-24  Discovery of a novel series of potent non-nucleoside inhibitors of hepatitis C virus NS5B.  [PMID:24069953]

168. Felts, Andrew S and 13 more authors.  2013-11-01  Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety.  [PMID:24074843]

169. Kester, Robert F RF and 31 more authors.  2013-10-24  Optimization of benzodiazepinones as selective inhibitors of the X-linked inhibitor of apoptosis protein (XIAP) second baculovirus IAP repeat (BIR2) domain.  [PMID:24093940]

170. Maltais, René R and 6 more authors.  2014-01-09  Discovery of a non-estrogenic irreversible inhibitor of 17β-hydroxysteroid dehydrogenase type 1 from 3-substituted-16β-(m-carbamoylbenzyl)-estradiol derivatives.  [PMID:24328103]

171. Phillips, Dean P DP and 24 more authors.  2014-04-24  Discovery of trifluoromethyl(pyrimidin-2-yl)azetidine-2-carboxamides as potent, orally bioavailable TGR5 (GPBAR1) agonists: structure-activity relationships, lead optimization, and chronic in vivo efficacy.  [PMID:24666203]

172. Manning, David D DD and 12 more authors.  2014-06-01  The discovery of diazepinone-based 5-HT3 receptor partial agonists.  [PMID:24755431]

173. Rafferty, Stephen W SW, Eisner, Joel R JR, Moore, William R WR, Schotzinger, Robert J RJ and Hoekstra, William J WJ.  2014-06-01  Highly-selective 4-(1,2,3-triazole)-based P450c17a 17,20-lyase inhibitors.  [PMID:24775307]

174. De Savi, Chris C and 12 more authors.  2014-06-12  Efficacious inhaled PDE4 inhibitors with low emetic potential and long duration of action for the treatment of COPD.  [PMID:24785301]

175. Sampson, Peter B PB and 23 more authors.  2015-01-08  The discovery of Polo-like kinase 4 inhibitors: design and optimization of spiro[cyclopropane-1,3'[3H]indol]-2'(1'H).ones as orally bioavailable antitumor agents.  [PMID:24867403]

176. Kang, Sunhee S and 19 more authors.  2014-06-26  Lead optimization of a novel series of imidazo[1,2-a]pyridine amides leading to a clinical candidate (Q203) as a multi- and extensively-drug-resistant anti-tuberculosis agent.  [PMID:24870926]

177. Toda, Narihiro N and 27 more authors.  2013-08-08  Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for the Treatment of Type 2 Diabetes.  [PMID:24900747]

178. Park, Eun Ju EJ and 12 more authors.  2014-09-01  Discovery of novel pyrimidine and malonamide derivatives as TGR5 agonists.  [PMID:25082126]

179. Voight, Eric A EA and 27 more authors.  2014-09-11  Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): a temperature-neutral transient receptor potential vanilloid-1 (TRPV1) antagonist with analgesic efficacy.  [PMID:25100568]

180. Cumming, John G JG and 10 more authors.  2015-01-08  Discovery and characterization of MAPK-activated protein kinase-2 prevention of activation inhibitors.  [PMID:25255283]

181. Carry, Jean-Christophe JC and 32 more authors.  2015-01-08  SAR156497, an exquisitely selective inhibitor of aurora kinases.  [PMID:25369539]

182. Mukherjee, Paramita and 7 more authors.  2015-02-12  Novel 2,4-disubstituted pyrimidines as potent, selective, and cell-permeable inhibitors of neuronal nitric oxide synthase.  [PMID:25489882]

183. Sampson, Peter B PB and 24 more authors.  2015-01-08  The discovery of Polo-like kinase 4 inhibitors: identification of (1R,2S).2-(3-((E).4-(((cis).2,6-dimethylmorpholino)methyl)styryl). 1H.indazol-6-yl)-5'-methoxyspiro[cyclopropane-1,3'-indolin]-2'-one (CFI-400945) as a potent, orally active antitumor agent.  [PMID:25723005]

184. Lv, Wei; Liu, Jinzhong; Skaar, Todd C; Flockhart, David A and Cushman, Mark.  2015-03-26  Design and synthesis of norendoxifen analogues with dual aromatase inhibitory and estrogen receptor modulatory activities.  [PMID:25751283]

185. Ai, Yong Y and 9 more authors.  2015-06-11  Synthesis and Biological Evaluation of Novel Olean-28,13β-lactams as Potential Antiprostate Cancer Agents.  [PMID:25992974]

186. Sevrioukova, Irina F IF and Poulos, Thomas L TL.  2015  Current Approaches for Investigating and Predicting Cytochrome P450 3A4-Ligand Interactions.  [PMID:26002732]

187. Green, Jeremy J and 11 more authors.  2015-06-25  Design, Synthesis, and Structure-Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors.  [PMID:26039570]

188. Duraiswamy, Athisayamani Jeyaraj AJ and 16 more authors.  2015-08-13  Discovery and Optimization of a Porcupine Inhibitor.  [PMID:26110200]

189. Neitz, R Jeffrey and 10 more authors.  2015-11-01  Tetrafluorophenoxymethyl ketone cruzain inhibitors with improved pharmacokinetic properties as therapeutic leads for Chagas' disease.  [PMID:26144347]

190. Elkamhawy, Ahmed A and 12 more authors.  2015-10-20  Discovery of potent and selective cytotoxic activity of new quinazoline-ureas against TMZ-resistant glioblastoma multiforme (GBM).  [PMID:26355532]

191. Nirogi, Ramakrishna R and 13 more authors.  2015-10-20  Synthesis and SAR of Imidazo[1,5-a]pyridine derivatives as 5-HT4 receptor partial agonists for the treatment of cognitive disorders associated with Alzheimer's disease.  [PMID:26363507]

192. Sun, Bin B and 7 more authors.  2015-10-15  Design, synthesis, and biological evaluation of amide imidazole derivatives as novel metabolic enzyme CYP26A1 inhibitors.  [PMID:26365710]

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194. Raheem, Izzat T IT and 20 more authors.  2016-01-01  Discovery of pyrazolopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia.  [PMID:26602277]

195. Pace, Jennifer R and 8 more authors.  2016-04-28  Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic.  [PMID:27014922]

196. Wilson, Jonathan E JE and 19 more authors.  2016-06-15  Discovery and development of benzo-[1,2,4]-triazolo-[1,4]-oxazepine GPR142 agonists for the treatment of diabetes.  [PMID:27240550]

197. Norcross, Neil R and 29 more authors.  2016-07-14  Trisubstituted Pyrimidines as Efficacious and Fast-Acting Antimalarials.  [PMID:27314305]

198. Lim, Jongwon J and 17 more authors.  2016-07-14  Discovery of 1-(1H-Pyrazolo[4,3-c]pyridin-6-yl)urea Inhibitors of Extracellular Signal-Regulated Kinase (ERK) for the Treatment of Cancers.  [PMID:27329786]

199. Laufer, Radoslaw R and 21 more authors.  2016-08-01  Discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as novel, highly potent and selective, orally bioavailable inhibitors of Tyrosine Threonine Kinase, TTK.  [PMID:27335255]

200. Cheng, Dai D and 15 more authors.  2016-07-14  Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors.  [PMID:27437076]

201. Zak, Mark M and 19 more authors.  2016-09-22  Minimizing CYP2C9 Inhibition of Exposed-Pyridine NAMPT (Nicotinamide Phosphoribosyltransferase) Inhibitors.  [PMID:27541271]

202. Rackelmann, Nils N and 10 more authors.  2016-10-13  Discovery and Optimization of 1-Phenoxy-2-aminoindanes as Potent, Selective, and Orally Bioavailable Inhibitors of the Na+/H+ Exchanger Type 3 (NHE3).  [PMID:27606885]

203. Blass, Benjamin E BE and 18 more authors.  2016-12-01  Design, synthesis, and evaluation of (2S,4R)-Ketoconazole sulfonamide analogs as potential treatments for Metabolic Syndrome.  [PMID:27789139]

204. Wu, Wen-Lian WL and 14 more authors.  2016-12-01  Design and synthesis of water soluble β-aminosulfone analogues of SCH 900229 as γ-secretase inhibitors.  [PMID:27836402]

205. Siegrist, Romain R and 13 more authors.  2016-12-08  Structure-Activity Relationship, Drug Metabolism and Pharmacokinetics Properties Optimization, and in Vivo Studies of New Brain Penetrant Triple T-Type Calcium Channel Blockers.  [PMID:27933950]

206. Wang, Mingliang M and 6 more authors.  2017-05-26  Discovery of novel 1,2,3,4-tetrahydrobenzo[4, 5]thieno[2, 3-c]pyridine derivatives as potent and selective CYP17 inhibitors.  [PMID:28350999]

207. McEneny-King, Alanna A, Osman, Wesseem W, Edginton, Andrea N AN and Rao, Praveen P N PPN.  2017-06-01  Cytochrome P450 binding studies of novel tacrine derivatives: Predicting the risk of hepatotoxicity.  [PMID:28400237]

208. Melancon, Bruce J and 20 more authors.  2017-06-01  Optimization of M4 positive allosteric modulators (PAMs): The discovery of VU0476406, a non-human primate in vivo tool compound for translational pharmacology.  [PMID:28442253]

209. Miller, Eric J EJ and 16 more authors.  2018-02-08  Discovery of Tetrahydroisoquinoline-Containing CXCR4 Antagonists with Improved in Vitro ADMET Properties.  [PMID:29350534]

210. Deaton, David N DN and 7 more authors.  2018-05-01  2,4-Diamino-8-quinazoline carboxamides as novel, potent inhibitors of the NAD hydrolyzing enzyme CD38: Exploration of the 2-position structure-activity relationships.  [PMID:29576271]

211. Łażewska, Dorota and 13 more authors.  2018-05-15  Novel naphthyloxy derivatives - Potent histamine H3 receptor ligands. Synthesis and pharmacological evaluation.  [PMID:29681486]

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213. Blass, Benjamin E BE and 20 more authors.  2018-07-15  Design and synthesis of functionalized piperazin-1yl-(E)-stilbenes as inhibitors of 17α-hydroxylase-C17,20-lyase (Cyp17).  [PMID:29803730]

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215. Pero, Joseph E JE and 27 more authors.  2018-12-27  Design and Optimization of Sulfone Pyrrolidine Sulfonamide Antagonists of Transient Receptor Potential Vanilloid-4 with in Vivo Activity in a Pulmonary Edema Model.  [PMID:30500190]

216. Teske, Kelly A KA and 5 more authors.  2019-02-01  Development of posaconazole-based analogues as hedgehog signaling pathway inhibitors.  [PMID:30529635]

217. Saccoliti, Francesco F and 21 more authors.  2019-02-14  Design, Synthesis, and Biological Evaluation of New 1-(Aryl-1 H-pyrrolyl)(phenyl)methyl-1 H-imidazole Derivatives as Antiprotozoal Agents.  [PMID:30615444]

218. Boy, Kenneth M and 28 more authors.  2019-03-14  Identification and Preclinical Evaluation of the Bicyclic Pyrimidine γ-Secretase Modulator BMS-932481.  [PMID:30891132]

219. Meyers, Marvin J MJ and 13 more authors.  2019-06-13  4-Aryl Pyrrolidines as Novel Orally Efficacious Antimalarial Agents. Part 2: 2-Aryl-N-(4-arylpyrrolidin-3-yl)acetamides.  [PMID:31223456]

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221. Kaiser, Thomas M; Dentmon, Zackery W; Dalloul, Christopher E; Sharma, Savita K and Liotta, Dennis C.  2020-04-09  Accelerated Discovery of Novel Ponatinib Analogs with Improved Properties for the Treatment of Parkinson's Disease.  [PMID:32292555]

222. Kang, Dongwei and 8 more authors.  2020-05-14  Structure-Based Bioisosterism Yields HIV-1 NNRTIs with Improved Drug-Resistance Profiles and Favorable Pharmacokinetic Properties.  [PMID:32293182]

223. Xue, Si-Tu and 7 more authors.  2020-08-15  Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties.  [PMID:32480301]

224. Zhao, Hongyi and 13 more authors.  2020-09-10  Discovery of a Conformationally Constrained Oxazolidinone with Improved Safety and Efficacy Profiles for the Treatment of Multidrug-Resistant Tuberculosis.  [PMID:32666789]

225. Nair, Satheesh and 39 more authors.  2020-07-09  Optimization of Nicotinamides as Potent and Selective IRAK4 Inhibitors with Efficacy in a Murine Model of Psoriasis.  [PMID:32676146]

226. Zhao, Jian and 10 more authors.  2020-09-01  Discovery of nonpeptide 3,4-dihydroquinazoline-4-carboxamides as potent and selective sst2 agonists.  [PMID:32738999]

227. Zhao, Tong and 12 more authors.  2020-10-08  Novel Human Urate Transporter 1 Inhibitors as Hypouricemic Drug Candidates with Favorable Druggability.  [PMID:32897699]

228. Beck, Hartmut and 21 more authors.  2020-10-22  Potent and Selective Human Prostaglandin F (FP) Receptor Antagonist (BAY-6672) for the Treatment of Idiopathic Pulmonary Fibrosis (IPF).  [PMID:32969660]

229. Harcken, Christian and 22 more authors.  2021-01-14  Discovery of a Series of Pyrazinone RORγ Antagonists and Identification of the Clinical Candidate BI 730357.  [PMID:33488976]

Source

Source(14):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book)
• USP Dictionary of USAN and International Drug Names
• DrugMatrix
• TP-search Transporter Database
• AstraZeneca Deposited Data
• CO-ADD antimicrobial screening data
• WHO Anatomical Therapeutic Chemical Classification
• British National Formulary
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data
• Fraunhofer HDAC6