Literature DB >> 23964740

Optimization of activity, selectivity, and liability profiles in 5-oxopyrrolopyridine DPP4 inhibitors leading to clinical candidate (Sa)-2-(3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778).

Pratik Devasthale1, Ying Wang, Wei Wang, John Fevig, JianXin Feng, Aiying Wang, Tom Harrity, Don Egan, Nathan Morgan, Michael Cap, Aberra Fura, Herbert E Klei, Kevin Kish, Carolyn Weigelt, Lucy Sun, Paul Levesque, Frederic Moulin, Yi-Xin Li, Robert Zahler, Mark S Kirby, Lawrence G Hamann.   

Abstract

Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.

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Year:  2013        PMID： 23964740     DOI： 10.1021/jm4008906

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  6 in total

1.  BET Bromodomain Inhibitors with One-Step Synthesis Discovered from Virtual Screen.

Authors:  Alex M Ayoub; Laura M L Hawk; Ryan J Herzig; Jiewei Jiang; Andrea J Wisniewski; Clifford T Gee; Peiliang Zhao; Jin-Yi Zhu; Norbert Berndt; Nana K Offei-Addo; Thomas G Scott; Jun Qi; James E Bradner; Timothy R Ward; Ernst Schönbrunn; Gunda I Georg; William C K Pomerantz
Journal:  J Med Chem       Date:  2017-06-07       Impact factor: 7.446

2.  Dipeptidyl peptidase IV as a potential target for selective prodrug activation and chemotherapeutic action in cancers.

Authors:  Arik Dahan; Omri Wolk; Peihua Yang; Sachin Mittal; Zhiqian Wu; Christopher P Landowski; Gordon L Amidon
Journal:  Mol Pharm       Date:  2014-11-13       Impact factor: 4.939

3.  Comprehensive analysis of the Co-structures of dipeptidyl peptidase IV and its inhibitor.

Authors:  Hiroyuki Nojima; Kazuhiko Kanou; Genki Terashi; Mayuko Takeda-Shitaka; Gaku Inoue; Koichiro Atsuda; Chihiro Itoh; Chie Iguchi; Hajime Matsubara
Journal:  BMC Struct Biol       Date:  2016-08-05

4.  Synthesis of Tris-Heterocycles via a Cascade IMCR/Aza Diels-Alder + CuAAC Strategy.

Authors:  Manuel A Rentería-Gómez; Alejandro Islas-Jácome; Shrikant G Pharande; David A Vosburg; Rocío Gámez-Montaño
Journal:  Front Chem       Date:  2019-08-06       Impact factor: 5.221

5.  Synthesis of Polyheterocyclic Dimers Containing Restricted and Constrained Peptidomimetics via IMCR-Based Domino/Double CuAAC Click Strategy.

Authors:  Shrikant G Pharande; Manuel A Rentería-Gómez; Rocío Gámez-Montaño
Journal:  Molecules       Date:  2020-11-11       Impact factor: 4.411

6.  One-pot synthesis of substituted pyrrolo[3,4-b]pyridine-4,5-diones based on the reaction of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamide with amines.

Authors:  Valeriya G Melekhina; Andrey N Komogortsev; Boris V Lichitsky; Vitaly S Mityanov; Artem N Fakhrutdinov; Arkady A Dudinov; Vasily A Migulin; Yulia V Nelyubina; Elizaveta K Melnikova; Michail M Krayushkin
Journal:  Beilstein J Org Chem       Date:  2019-11-25       Impact factor: 2.883
  6 in total

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