167484-18-6Relevant articles and documents
NOVEL COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Paragraph 0237; 0238, (2019/05/16)
Provided are 2-(piperidin-1-yl)pyrimidin-4(3H)-ones or pharmaceutically acceptable salts thereof, each characterized by having a 1,8-diazaspiro[4.5]deca-3-ene, 1-oxa-8-azaspiro[4.5]deca-3-ene, 2,8-diazaspiro[4.5]deca-3-ene, 2-oxa-8-azaspiro[4.5]deca-3-ene, 2,9-diazaspiro[5.5]undeca-3-ene, 1-oxa-9-azaspiro[5.5]undeca-3-ene, 1,9-diazaspiro[5.5]undeca-4-ene, or 3,9-diazaspiro[5.5]undeca-1-ene structure represented by the following general formula (1):
Conformationally constrained ortho- Anilino diaryl ureas: Discovery of 1-(2-(1′-Neopentylspiro[indoline-3,4′-piperidine]-1-yl)phenyl) -3-(4-(trifluoromethoxy)phenyl)urea, a potent, selective, and bioavailable P2Y1 antagonist
Qiao, Jennifer X.,Wang, Tammy C.,Ruel, Réjean,Thibeault, Carl,L'Heureux, Alexandre,Schumacher, William A.,Spronk, Steven A.,Hiebert, Sheldon,Bouthillier, Gilles,Lloyd, John,Pi, Zulan,Schnur, Dora M.,Abell, Lynn M.,Hua, Ji,Price, Laura A.,Liu, Eddie,Wu, Qimin,Steinbacher, Thomas E.,Bostwick, Jeffrey S.,Chang, Ming,Zheng, Joanna,Gao, Qi,Ma, Baoqing,McDonnell, Patricia A.,Huang, Christine S.,Rehfuss, Robert,Wexler, Ruth R.,Lam, Patrick Y. S.
supporting information, p. 9275 - 9295 (2014/01/06)
Preclinical antithrombotic efficacy and bleeding models have demonstrated that P2Y1 antagonists are efficacious as antiplatelet agents and may offer a safety advantage over P2Y12 antagonists in terms of reduced bleeding liabilities. In this article, we describe the structural modification of the tert-butyl phenoxy portion of lead compound 1 and the subsequent discovery of a novel series of conformationally constrained ortho-anilino diaryl ureas. In particular, spiropiperidine indoline-substituted diaryl ureas are described as potent, orally bioavailable small-molecule P2Y1 antagonists with improved activity in functional assays and improved oral bioavailability in rats. Homology modeling and rat PK/PD studies on benchmark compound 3l will also be presented. Compound 3l was our first P2Y1 antagonist to demonstrate a robust oral antithrombotic effect with mild bleeding liability in the rat thrombosis and hemostasis models.
A facile synthesis of the spiroindoline-based growth hormone secretagogue, MK-677
Qi, Xian Liang,Yang, Er Qun,Zhang, Jun Tao,Wang, Tao,Cao, Xiao Ping
, p. 661 - 664 (2012/07/03)
A facile and improved route for the synthesis of the orally active spiroindoline-based growth hormone secretagogue, MK-677 was described. The key step adopted the Fischer indole/reduction strategy. The preparation of the key intermediates N-protected piperidine carboxaldehyde 5 and the N-Boc-O-benzyl-d-serine (2) are also optimized.