188726-22-9Relevant academic research and scientific papers
Substituted Pyrrolidines and Methods of Use
-
Paragraph 2029, (2018/04/20)
The invention discloses compounds of Formula (I) wherein R1, R2, R2A, R3, R3A, R4, R4A, and R5 are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.
Discovery and stereoselective synthesis of the novel isochroman neurokinin-1 receptor antagonist 'CJ-17,493'
Shishido, Yuji,Wakabayashi, Hiroaki,Koike, Hiroki,Ueno, Naomi,Nukui, Seiji,Yamagishi, Tatsuya,Murata, Yoshinori,Naganeo, Fumiharu,Mizutani, Mayumi,Shimada, Kaoru,Fujiwara, Yoshiko,Sakakibara, Ayano,Suga, Osamu,Kusano, Rinko,Ueda, Satoko,Kanai, Yoshihito,Tsuchiya, Megumi,Satake, Kunio
, p. 7193 - 7205 (2008/12/22)
A novel central nervous system (CNS) selective neurokinin-1 (NK1) receptor antagonist, (2S,3S)-3-[(1R)-6-methoxy-1-methyl-1-trifluoromethylisochroman-7-yl]-methylamino-2-phenylpiperidine 'CJ-17,493' (compound (+)-1), was synthesized stereoselectively using a kinetic resolution by lipase-PS as a key step. Compound (+)-1 displayed high and selective affinity (Ki = 0.2 nM) for the human NK1 receptor in IM-9 cells, potent activity in the [Sar9, Met(O2)11]SP-induced gerbil tapping model (ED50 = 0.04 mg/kg, sc) and in the ferret cisplatin (10 mg/kg, ip)-induced anti-emetic activity model (vomiting: ED90 = 0.07 mg/kg, sc), all levels of activity comparable with those of CP-122,721. In addition, compound (+)-1 exhibited linear pharmacokinetics rather than the super dose-proportionality of CP-122,721 and this result provides a potential solution for the clinical issue observed with CP-122,721.
Substituted benzylaminopiperidine compounds
-
, (2008/06/13)
The invention provides a substituted benzylaminopiperidine compounds that are useful in the treatment of gastrointestinal disorders; central nervous system (CNS) disorders; inflammatory disease; emesis; urinary incontinence; pain; migraine; sunburn; diseases, disorders and adverse conditions caused byHeliobacter pylori;or angiogenesis, especially CNS disorders in a mammalian subject, especially in humans.
