154456-97-0Relevant articles and documents
A Novel Entry to Carbenoid Species via β-Ketosulfoxonium Ylides
Baldwin, Jack E.,Adlington, Robert M.,Godfrey, Christopher R. A.,Gollins, David W.,Vaughan, Jason G.
, p. 1434 - 1435 (1993)
In the presence of suitable rhodium(II) catalysts, lactam derived β-ketosulfoxonium ylides can be transformed to β-oxonitrogen heterocycles, e. g. substituted 4-oxopyrrolidine, via intermediates of carbenoid nature.
Tetrahydropyridopyrimidine compound with anti-tumor activity
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Paragraph 0604-0608, (2020/12/30)
The invention provides a tetrahydropyridopyrimidine compound shown as a formula (I) or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the tetrahydropyridopyrimidine compound and the pharmaceutically acceptable salt thereof, and application of the tetrahydropyridopyrimidine compound or the pharmaceutically acceptable salt thereof in the preparation of a drug forpreventing and/or treating KRAS G12C mutant tumors.
Synthesis and Conformational Properties of 3,4-Difluoro- l -prolines
Hofman, Gert-Jan,Ottoy, Emile,Light, Mark E.,Kieffer, Bruno,Martins, Jose C.,Kuprov, Ilya,Sinnaeve, Davy,Linclau, Bruno
, p. 3100 - 3120 (2019/03/11)
Fluorinated proline derivatives have found diverse applications in areas ranging from medicinal chemistry over structural biochemistry to organocatalysis. Depending on the stereochemistry of monofluorination at the proline 3- or 4-position, different effe
FLUOROHYDROXYPROLINE DERIVATIVES USEFUL IN THE PREPARATION OF PROTEOLYSIS TARGETED CHIMERAS
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Page/Page column 46; 72, (2018/04/14)
There is provided novel small molecule E3 ubiquitin ligase protein binding ligand compounds, and to their utility in PROteolysis Targeted Chimeras (PROTACs), as well as processes for their preparation thereof, and use in medicine. There is particularly provided novel small molecule E3 ubiquitin ligase protein binding inhibitorcompounds based on a fluorohydroxyproline scaffold, to their utility as ligands in synthesizing novel PROTACs, and to synthetic methods therefor.
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.
ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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Paragraph 0572, (2017/03/14)
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an aryl, heteroaryl or heterocycle (R32) are provided. The inhibitors of Factor D described herein reduce the excessive activation of complement.
PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
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, (2008/06/13)
The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.
Practical synthesis of Boc-protected cis-4-trifluoromethyl and cis-4-difluoromethyl-L- prolines
Qiu, Xiao-long,Qing, Feng-ling
, p. 7162 - 7164 (2007/10/03)
A short, efficient, and diastereomerically pure synthesis of N-Boc-cis-4-trifluoromethyl-L-proline (7) and N-Boc-cis-4-difluoromethyl-L-proline (9) from N-Boc-4-oxo- L-proline (4) is described. The reaction of 4 with Me3SiCF3 and the conversion of the carbonyl group of 4 into the difluoromethylene group are the key steps for the synthesis of 7 and 9, respectively.
Stereoselective synthesis of novel chimerical amino acids via a photochemical key step
Wessig, Pablo
, p. 1465 - 1467 (2007/10/03)
The synthesis of novel chimerical amino acid derivatives 6-8 bearing the 6-azatricyclo[3.3.1.033,7]nonane (methanotropane) skeleton is described. Starting with one chirality centre in L-4-oxoprolines 2 we succeeded in the fully stereoselective introduction of four new chirality centres. The key step of our synthetic route is a photochemical cyclization of phenyl ketones, whose stereoselectivity has been explained by the different stability of the triplet biradical conformers.
Synthesis of kainoid analogues
Barraclough, Paul,Hudhomme, Pietrick,Spray, Caroline A.,Young, Douglas W.
, p. 4195 - 4212 (2007/10/02)
4-oxoproline has been used as a chiral template in a synthesis of kainoid analogues which are epimeric with the parent compound at C-3.