94160-25-5Relevant articles and documents
Discovery of an Oxycyclohexyl Acid Lysophosphatidic Acid Receptor 1 (LPA1) Antagonist BMS-986278 for the Treatment of Pulmonary Fibrotic Diseases
Cheng, Peter T. W.,Kaltenbach, Robert F.,Zhang, Hao,Shi, Jun,Tao, Shiwei,Li, Jun,Kennedy, Lawrence J.,Walker, Steven J.,Shi, Yan,Wang, Ying,Dhanusu, Suresh,Reddigunta, Ramesh,Kumaravel, Selvakumar,Jusuf, Sutjano,Smith, Daniel,Krishnananthan, Subramaniam,Li, Jianqing,Wang, Tao,Heiry, Rebekah,Sum, Chi Shing,Kalinowski, Stephen S.,Hung, Chen-Pin,Chu, Ching-Hsuen,Azzara, Anthony V.,Ziegler, Milinda,Burns, Lisa,Zinker, Bradley A.,Boehm, Stephanie,Taylor, Joseph,Sapuppo, Julia,Mosure, Kathy,Everlof, Gerry,Guarino, Victor,Zhang, Lisa,Yang, Yanou,Ruan, Qian,Xu, Carrie,Apedo, Atsu,Traeger, Sarah C.,Cvijic, Mary Ellen,Lentz, Kimberley A.,Tirucherai, Giridhar,Sivaraman, Lakshmi,Robl, Jeffrey,Ellsworth, Bruce A.,Rosen, Glenn,Gordon, David A.,Soars, Matthew G.,Gill, Michael,Murphy, Brian J.
, p. 15549 - 15581 (2021/11/16)
The oxycyclohexyl acid BMS-986278 (33) is a potent lysophosphatidic acid receptor 1 (LPA1) antagonist, with a human LPA1 Kb of 6.9 nM. The structure-activity relationship (SAR) studies starting from the LPA1 antagonist clinical compound BMS-986020 (1), which culminated in the discovery of 33, are discussed. The detailed in vitro and in vivo preclinical pharmacology profiles of 33, as well as its pharmacokinetics/metabolism profile, are described. On the basis of its in vivo efficacy in rodent chronic lung fibrosis models and excellent overall ADME (absorption, distribution, metabolism, excretion) properties in multiple preclinical species, 33 was advanced into clinical trials, including an ongoing Phase 2 clinical trial in patients with lung fibrosis (NCT04308681).
TRICYCLIC COMPOUND SERVING AS IMMUNOMODULATOR
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Paragraph 0589-0590, (2019/01/04)
Provided are compounds of formula I and formula II or pharmaceutically acceptable salts of the compounds and pharmaceutical compositions thereof. The compounds of formula I and formula II or the pharmaceutically acceptable salts of the compounds provide indole 2,3-dioxygenase (IDO) inhibitory activity and are capable of treating IDO-mediated immunosuppressive diseases, such as infectious diseases or cancer.
9H-Carbazole-1-carboxamides as potent and selective JAK2 inhibitors
Zimmermann, Kurt,Sang, Xiaopeng,Mastalerz, Harold A.,Johnson, Walter L.,Zhang, Guifen,Liu, Qingjie,Batt, Douglas,Lombardo, Louis J.,Vyas, Dinesh,Trainor, George L.,Tokarski, John S.,Lorenzi, Matthew V.,You, Dan,Gottardis, Marco M.,Lippy, Jonathan,Khan, Javed,Sack, John S.,Purandare, Ashok V.
, p. 2809 - 2812 (2015/06/08)
The discovery, synthesis, and characterization of 9H-carbazole-1-carboxamides as potent and selective ATP-competitive inhibitors of Janus kinase 2 (JAK2) are discussed. Optimization for JAK family selectivity led to compounds 14 and 21, with greater than 45-fold selectivity for JAK2 over all other members of the JAK kinase family.
