139290-70-3Relevant articles and documents
Heteroaromatic and aniline derivatives of piperidines as potent ligands for vesicular acetylcholine transporter
Li, Junfeng,Zhang, Xiang,Zhang, Zhanbin,Padakanti, Prashanth K.,Jin, Hongjun,Cui, Jinquan,Li, Aixiao,Zeng, Dexing,Rath, Nigam P.,Flores, Hubert,Perlmutter, Joel S.,Parsons, Stanley M.,Tu, Zhude
, p. 6216 - 6233 (2013)
To identify suitable lipophilic compounds having high potency and selectivity for vesicular acetylcholine transporter (VAChT), a heteroaromatic ring or a phenyl group was introduced into the carbonyl-containing scaffold for VAChT ligands. Twenty new compounds with ALogD values between 0.53 and 3.2 were synthesized, and their in vitro binding affinities were assayed. Six of them (19a, 19e, 19g, 19k, and 24a-b) displayed high affinity for VAChT (Ki = 0.93-18 nM for racemates) and moderate to high selectivity for VAChT over σ1 and σ2 receptors (Ki = 44-4400-fold). These compounds have a methyl or a fluoro substitution that provides the position for incorporating PET radioisotopes C-11 or F-18. Compound (-)-[11C]24b (Ki = 0.78 nM for VAChT, 1200-fold over σ receptors) was successfully synthesized and evaluated in vivo in rats and nonhuman primates. The data revealed that (-)-[11C]24b has highest binding in striatum and has favorable pharmacokinetics in the brain.
Discovery of benzimidazole pyrrolidinyl amides as prolylcarboxypeptidase inhibitors
Shen, Hong C.,Ding, Fa-Xiang,Zhou, Changyou,Xiong, Yusheng,Verras, Andreas,Chabin, Renee M.,Xu, Suoyu,Tong, Xinchun,Xie, Dan,Lassman, Michael E.,Bhatt, Urmi R.,Garcia-Calvo, Margarita M.,Geissler, Wayne,Shen, Zhu,Chen, Dunlu,Sinharoy, Ranabir,Hale, Jeffery J.,Tata, James R.,Pinto, Shirly,Shen, Dong-Ming,Colletti, Steven L.
, p. 1299 - 1305 (2011)
A series of benzimidazole pyrrolidinyl amides containing a piperidinyl group were discovered as novel prolylcarboxypeptidase (PrCP) inhibitors. Low-nanomolar IC50's were achieved for several analogs, of which compound 9b displayed modest ex vivo target engagement in eDIO mouse plasma. Compound 9b was also studied in vivo for its effect on weight loss and food intake in an eDIO mouse model and the results will be discussed.
1,2,3,4-Tetrahydroquinoline-containing αVβ 3 integrin antagonists with enhanced oral bioavailability
Ghosh, Shyamali,Santulli, Rosemary J.,Kinney, William A.,DeCorte, Bart L.,Liu, Li,Lewis, Joan M.,Proost, Jef C.,Leo, Gregory C.,Masucci, John,Hageman, William E.,Thompson, Andrew S.,Chen, Ian,Kawahama, Reiko,Tuman, Robert W.,Galemmo Jr., Robert A.,Johnson, Dana L.,Damiano, Bruce P.,Maryanoff, Bruce E.
, p. 5937 - 5941 (2004)
Selective reduction of the quinoline yielded potent α vβ53 antagonists with improved oral bioavailability relative to the corresponding quinoline derivatives. Reduction of the quinoline ring in an αvβ3 antagonist yielded a 1,2,3,4-tetrahydro derivative as two diastereomers, the four isomers of which were separated by sequential chiral HPLC. Two isomers had significant αVβ3 antagonist activity with improved oral bioavailability, relative to the corresponding quinoline derivative.
ALIPHATIC ACID AMIDE DERIVATIVE
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, (2022/03/19)
The present invention relates to a compound represented by formula (1): the compound having antagonist activity against serotonin 5-HT2A receptors and serotonin 5-HT7 receptors; or a pharmaceutically acceptable salt of the compound. (In the formula, Z is a nitrogen atom and the like; Y is carbonyl and the like; m and n are 1 and the like; R1a through R1d, R2a through R2d, and R4a through R4d are a hydrogen atom and the like; R3 is alkyl and the like; and Q is a specific bicyclic group.)
TRPML MODULATORS
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Paragraph 0814, (2021/06/26)
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
