470482-40-7Relevant articles and documents
PYRIDAZINONES AS PARP7 INHIBITORS
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Paragraph 1340, (2019/11/11)
The present invention relates to pyridazinones and related compounds which are inhibitors of PARP7 and are useful in the treatment of cancer.
ARYL, HETEROARY, AND HETEROCYCLIC PHARMACEUTICAL COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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Page/Page column 645; 648, (2018/09/21)
Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, Formula IV, and Formula V, or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade.
Silver-catalysed tandem hydroamination and cyclization of 2-trifluoromethyl-1,3-enynes with primary amines: modular entry to 4-trifluoromethyl-3-pyrrolines
Zhou, Xiaofan,Huang, Chaoqian,Zeng, Yu,Xiong, Jiarui,Xiao, Yuanjing,Zhang, Junliang
, p. 1084 - 1087 (2017/02/05)
A highly efficient tandem hydroamination and cyclization reaction of 2-trifluoromethyl-1,3-enynes with primary amines leading to 4-trifluoromethyl-3-pyrrolines was developed by using AgNO3 as a catalyst under mild reaction conditions. This new method is compatible with alkyl, aryl, and allyl primary amines, representing an atom-economical protocol for the construction of 4-trifluoromethyl-3-pyrrolines for the first time.
Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode
Jurica, Elizabeth A.,Wu, Ximao,Williams, Kristin N.,Hernandez, Andres S.,Nirschl, David S.,Rampulla, Richard A.,Mathur, Arvind,Zhou, Min,Cao, Gary,Xie, Chunshan,Jacob, Biji,Cai, Hong,Wang, Tao,Murphy, Brian J.,Liu, Heng,Xu, Carrie,Kunselman, Lori K.,Hicks, Michael B.,Sun, Qin,Schnur, Dora M.,Sitkoff, Doree F.,Dierks, Elizabeth A.,Apedo, Atsu,Moore, Douglas B.,Foster, Kimberly A.,Cvijic, Mary Ellen,Panemangalore, Reshma,Flynn, Neil A.,Maxwell, Brad D.,Hong, Yang,Tian, Yuan,Wilkes, Jason J.,Zinker, Bradley A.,Whaley, Jean M.,Barrish, Joel C.,Robl, Jeffrey A.,Ewing, William R.,Ellsworth, Bruce A.
, p. 1417 - 1431 (2017/03/08)
A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-cis-CF3 to the pyrrolidine improves the human GPR40 binding Ki and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers (R,R)-68 and (S,S)-68 have differential effects on the radioligand used for the binding assay, with (R,R)-68 potentiating the radioligand and (S,S)-68 displacing the radioligand. Compound (R,R)-68 activates both Gq-coupled intracellular Ca2+ flux and Gs-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound (R,R)-68, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound (R,R)-68 significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series.
Influence of 4- or 5-substituents on the pyrrolidine ring of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives on their inhibitory activities towards caspases-3 and -7 Dedicated to Professor Dr. Ernst-Ulrich Würthwein on the occasion of his 65th birthday
Limpachayaporn, Panupun,Riemann, Burkhard,Kopka, Klaus,Schober, Otmar,Sch?fers, Michael,Haufe, Günter
, p. 562 - 578 (2013/07/11)
A series of new 4- or 5-substituted pyrrolidine derivatives of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin bearing additional n-butyl or 4-fluorobutyl groups at the isatin nitrogen were prepared and their inhibitory activities have been tested against caspases-3 and -7, which are known to participate in the execution of the programmed cell death, called apoptosis. Several analogues fluorinated at the 4-position of the pyrrolidine ring were also synthesized since such inhibitors might be developed as 18F-radiotracers for molecular imaging of activated caspases in vivo by PET. Enantiomerically pure diastereomeric 4-fluoropyrrolidinyl derivatives inhibited the enzymes in the nanomolar scale, i.e.100-1000 times more efficient than the corresponding 4-methoxy analogues. The 4,4-difluorinated compound showed the best result with IC50 = 362 nM and 178 nM for the aforementioned caspases. In contrast, the 4-methoxy and 4-trifluoromethyl analogues exhibited less inhibition potencies for the enzymes in the μM scale, whereas all 4-OPEG4 (PEG4 = tetraethyleneglycol) and 5-methoxymethyl derivatives were inactive.
PYRROLIDINE GPR40 MODULATORS
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Page/Page column 33, (2011/04/24)
The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments.
Stereoselective synthesis of Boc-protected cis and trans-4-trifluoromethylprolines by asymmetric hydrogenation reactions
Del Valle, Juan R.,Goodman, Murray
, p. 1600 - 1602 (2007/10/03)
Stereocontrolled synthesis of cis and trans-substituted prolines by a divergent approach, leads to the preparation of cis-(4S)- and trans-(4R)-trifluoromethyl-Lproline from hydroxyproline. The key pyrroline intermediates were subjected to hydrogenation (s
