61809-40-3Relevant academic research and scientific papers
Oxadiazole Derivatives as Dual Orexin Receptor Antagonists: Synthesis, Structure–Activity Relationships, and Sleep-Promoting Properties in Rats
Brotschi, Christine,Roch, Catherine,Gatfield, John,Treiber, Alexander,Williams, Jodi T.,Sifferlen, Thierry,Heidmann, Bibia,Jenck, Francois,Bolli, Martin H.,Boss, Christoph
supporting information, p. 1257 - 1270 (2019/06/17)
The orexin system plays an important role in the regulation of wakefulness. Suvorexant, a dual orexin receptor antagonist (DORA) is approved for the treatment of primary insomnia. Herein, we outline our optimization efforts toward a novel DORA. We started our investigation with rac-[3-(5-chloro-benzooxazol-2-ylamino)piperidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-ylphenyl)methanone (3), a structural hybrid of suvorexant and a piperidine-containing DORA. During the optimization, we resolved liabilities such as chemical instability, CYP3A4 inhibition, and low brain penetration potential. Furthermore, structural modification of the piperidine scaffold was essential to improve potency at the orexin 2 receptor. This work led to the identification of (5-methoxy-4-methyl-2-[1,2,3]triazol-2-ylphenyl)-{(S)-2-[5-(2-trifluoromethoxyphenyl)-[1,2,4]oxadiazol-3-yl]pyrrolidin-1-yl}methanone (51), a potent, brain-penetrating DORA with in vivo efficacy similar to that of suvorexant in rats.
ASK1 INHIBITOR COMPOUNDS AND USES THEREOF
-
Paragraph 0453; 0454, (2018/11/02)
Described herein are compounds, including pharmaceutically acceptable salts, solvates, metabolites, prodrugs thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat non
NOVEL BENZYLAMINO SUBSTITUTED QUINAZOLINES AND DERIVATIVES AS SOS1 INHIBITORS
-
Page/Page column 84, (2018/07/29)
The present invention encompasses compounds of formula (I), wherein the groups R1 to R7 have the meanings given in the claims and specification, their use as inhibitors of SOS1, pharmaceutical compositions which contain compounds of this kind and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.
2-(1,2,3-TRIAZOL-2-YL)BENZAMIDE AND 3-(1,2,3-TRIAZOL-2-YL)PICOLINAMIDE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
-
Paragraph 0437, (2015/06/17)
The present invention relates to 2-(1,2,3-triazol-2-yl)benzamide and 3-(1,2,3-triazol-2-yl)picolinamide derivatives of formula (I) wherein Ar1, Q, and R1 to R5 are as described in the description, to their preparation, to
OREXIN RECEPTOR ANTAGONISTS WHICH ARE [ORTHO BI (HETERO )ARYL]-[2-(META BI (HETERO )ARYL)-PYRROLIDIN-1-YL]-METHANONE DERIVATIVES
-
Page/Page column 98; 99, (2014/05/07)
The present invention relates to [ortho bi-(hetero-)aryl]-[2-(meta bi-(hetero-)aryl)-pyrrolidin-1-yl]- methanone derivatives of formula (I) wherein R, and the rings A1 A2 and A3 are as described in the description, to pharmaceutically acceptable salts thereof, to their preparation, to pharmaceutical compositions containing one or more compounds of formula (I), and to their use as pharmaceuticals, especially to their use as orexin receptor antagonists.
AZETIDINE AMIDE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
-
Page/Page column 41, (2014/09/29)
The present invention relates to azetidine amide derivatives derivatives of formula (I) wherein rings A1 A2 and A3 are as described in the description, to pharmaceutically acceptable salts thereof, to their preparation, to
2-(1,2,3-TRIAZOL-2-YL)BENZAMIDE AND 3-(1,2,3-TRIAZOL-2-YL)PICOLINAMIDE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
-
Page/Page column 59, (2013/05/23)
The present invention relates to 2-(1,2,3-triazol-2-yl)benzamide and 3-(1,2,3-triazol-2- yl)picolinamide derivatives of formula (I) Formula (I) wherein Ar1, Q, and R1 to R5 are as described in the description, to their pre
Synthesis of methyl-, fluoro-, and chloro-substituted 6-hydroxyisoindolin-1-ones
Powers, James J.,Favor, David A.,Rankin, Trent,Sharma, Rashmi,Pandit, Chetan,Jeganathan, Azhwarsamy,Maiti, Samarendra N.
supporting information; experimental part, p. 1267 - 1269 (2009/09/05)
The synthesis of a series of methyl-, fluoro-, and chloro-substituted 6-hydroxyisoindolin-1-ones is described.
