94160-25-5Relevant academic research and scientific papers
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).
9-SUBSTITUTED AMINO TRIAZOLO QUINAZOLINE DERIVATIVES AS ADENOSINE RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITIONS AND THEIR USE
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Page/Page column 54; 77, (2020/06/19)
In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I): (I), and pharmaceutically acceptable salts thereof, wherein, ring A, R1 and R2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
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.
Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177)
De Lucca, George V.,Shi, Qing,Liu, Qingjie,Batt, Douglas G.,Beaudoin Bertrand, Myra,Rampulla, Rick,Mathur, Arvind,Discenza, Lorell,D'Arienzo, Celia,Dai, Jun,Obermeier, Mary,Vickery, Rodney,Zhang, Yingru,Yang, Zheng,Marathe, Punit,Tebben, Andrew J.,Muckelbauer, Jodi K.,Chang, Chiehying J.,Zhang, Huiping,Gillooly, Kathleen,Taylor, Tracy,Pattoli, Mark A.,Skala, Stacey,Kukral, Daniel W.,McIntyre, Kim W.,Salter-Cid, Luisa,Fura, Aberra,Burke, James R.,Barrish, Joel C.,Carter, Percy H.,Tino, Joseph A.
, p. 7915 - 7935 (2016/10/12)
Bruton's tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure-activity relationships (SARs) leading to a novel second generation series of potent and selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide 6 (BMS-935177) was selected to advance into clinical development.
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.
Synthesis of aminoiderivatives of 4,5,6,7-tetrahydro-benzothiazole. II. 4, 5 and 6-aminomethyl derivatives with cardiovascular activity
Maillard,Delaunay,Langlois,et al.
, p. 457 - 460 (2007/10/02)
The ethyl esters of 4,5,6,7-tetrahdyro-benzothiazolyl-4 carboxylic acids were synthesized from corresponding ethyl 1-oxo-2 bromo-cyclohexane-carboxylates. Their reduction to alcohols, which were then transformed into tosylates, leads to the aminomethyl derivatives. These derivatives are practically devoid of antihistaminic H2 and dopaminergic activities but have interesting cardiovascular properties.
