- TETRAHYDROPYRAZOLO-PYRAZINYL-DIHYDROIMIDAZOLONE OR TETRAHYDROPYRAZOLO-PYRIDINYL-DIHYDROIMIDAZOLONE COMPOUNDS AND METHODS OF USING SAME
-
The application relates to a compound of Formula (I) : or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which modulates the activity of GLP-1 receptor, a pharmaceutical composition comprising a compound of Formula (I), and a method of treating or preventing a disease in which GLP-1 receptor plays a role.
- -
-
Paragraph 00637
(2022/02/05)
-
- Development of the large-scale synthesis of tetrahydropyran glycine, a precursor to the HCV NS5A inhibitor BMS-986097
-
An efficient large-scale synthesis of acid 1, a penultimate precursor to the HCV NS5A inhibitor BMS-986097, along with the final API step are described. Three routes were devised for the synthesis of 1 at the various stages of the program. The third generation route, the one that proved scalable and is the main subject of this paper, features a one-step Michael addition of t-butyl 2-((diphenylmethylene)amino)acetate (24) to (E)-benzyl 4-(1-hydroxycyclopropyl)but-2-enoate (28) followed by cyclization and chiral separation to form 27c, the core skeleton of cap piece 1. The epimerization and chiral resolution of 27c followed by further synthetic manipulations involving the carbamate formation, lactone reduction and cyclization, afforded cyclopropyl pyran 1. A detailed study of diphenylmethane deprotection via acid hydrolysis as well as a key lactone to tetrahydropyran conversion, in order to avoid a side reaction that afforded an alternative cyclization product, are discussed. This synthesis was applied to the preparation of more than 100 g of the final API BMS-986097 for toxicology studies.
- Mathur, Arvind,Wang, Bei,Smith, Daniel,Li, Jianqing,Pawluczyk, Joseph,Sun, Jung-Hui,Wong, Michael Kwok,Krishnananthan, Subramaniam,Wu, Dauh-Rurng,Sun, Dawn,Li, Peng,Yip, Shiuhang,Chen, Bang-Chi,Baran, Phil S.,Chen, Qi,Lopez, Omar D.,Yong, Zhong,Bender, John A.,Nguyen, Van N.,Romine, Jeffrey L.,St Laurent, Denis R.,Wang, Gan,Kadow, John F.,Meanwell, Nicholas A.,Belema, Makonen,Zhao, Rulin
-
p. 10376 - 10387
(2018/05/31)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 49; 50
(2014/05/24)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection of following Fomula (I). Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 49
(2012/12/13)
-
- Bronsted acid mediated cyclization of enaminones. Rapid and efficient access to the tetracyclic framework of the strychnos alkaloids
-
The development of an efficient diastereoselective method that permits rapid construction of the tetracyclic core 17 of the Strychnos-Aspidosperma alkaloids is described. Enaminone 16, synthesized in high yield, has been cyclized under the influence of a Bronsted acid to provide the core tetracyclic framework 17 of the Strychnos alkaloids in optically active form or alternatively to the β-ketoester tetrahydro-β-carboline (THBC) unit 18, by varying the equivalents of acid and the molar concentration. Attempts to utilize 18 to form the C(7)-C(16) bond of the akuammiline related alkaloids represented by strictamine (22), using metal-carbenoid chemistry, are also described.
- Edwankar, Rahul V.,Edwankar, Chitra R.,Namjoshi, Ojas A.,Deschamps, Jeffrey R.,Cook, James M.
-
supporting information; experimental part
p. 181 - 188
(2012/05/19)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment o
- -
-
Page/Page column 95-96
(2012/03/09)
-