A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-2-[(2E,4E)- hexadienoyl]-7-(2-(5-methyl-2-[( 1E)-5-methylhexen-1-yl]oxazol-4-yl]ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14i) was identified as a potent human peroxisome proliferator-activated receptor gamma (PPAR gamma) selective agonist (EC(50) = 0.03 mu M) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC(50) = 1.18 mu M). C(max) after oral administration of 14i at 10 mg/kg was 2.2 mu g/ml (4.5 mu M) in male SD rats. Repeated administration of 14i and rosiglitazone for 14 days dose-dependently decreased plasma glucose levels, ED(50) = 4.3 and 23 mg/kg/day, respectively, in male KK-A(y) mice. In female SD rats, repeated administration of 14i at 12.5-100 mg/kg/day for 28 days had no effect on the hematocrit value (Ht) and red blood cell count (RBC), while rosiglitazone significantly decreased them from 25 mg/kg/day. In conclusion, 14i showed about a fivefold stronger hypoglycemic effect and fourfold or more weaker hemodilution effect than rosiglitazone, indicating that 14i is 20-fold or more safer than rosiglitazone. Compound 14i is a promising candidate for an efficacious and safe anti-diabetic drug targeting PPAR gamma and PTP-1B. (C) 2011 Elsevier Ltd. All rights reserved.
[EN] PROCESS FOR SYNTHESIS OF INDENES<br/>[FR] PROCÉDÉ DE SYNTHÈSE D'INDÈNES
申请人:SCG CHEMICALS CO LTD
公开号:WO2015189073A1
公开(公告)日:2015-12-17
The present invention relates to a new process for the synthesis of 2,3,4,5,6,7-substiuted indenes, which are useful precursors for the formation of certain ansa-metailocene catalysts.
作者:Kei Kitamura、Naoyuki Shimada、Craig Stewart、Abdurrahman C. Atesin、Tülay A. Ateşin、Marcus A. Tius
DOI:10.1002/anie.201500881
日期:2015.5.18
A Pd0‐catalyzed asymmetric Nazarov‐type cyclization is described. The optimized ligand for the reaction incorporates a weakly coordinating pyridine ring into a TADDOL‐derived phosphoramidite (TADDOL=α,α,α,α‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol). The reaction leads to the formation of cyclopentenones as single diastereoisomers that incorporate two contiguous asymmetric centers, one tertiary and one
Stereospecific Electrophilic Fluorocyclization of α,β-Unsaturated Amides with Selectfluor
作者:Haiyang Fei、Zheyuan Xu、Hongmiao Wu、Lin Zhu、Hitesh B. Jalani、Guigen Li、Yao Fu、Hongjian Lu
DOI:10.1021/acs.orglett.0c00620
日期:2020.4.3
An efficient fluorocyclization of α,β-unsaturated amides through a formal halocyclization process is developed. The reaction proceeds undertransition-metal-freeconditions and leads to the formation of fluorinated oxazolidine-2,4-diones with excellent regio- and diastereoselectivity. The evaluation of the reaction mechanism based on preliminary experiments and density functional theory calculations
Nickel-Catalyzed Direct Alkylation of C–H Bonds in Benzamides and Acrylamides with Functionalized Alkyl Halides via Bidentate-Chelation Assistance
作者:Yoshinori Aihara、Naoto Chatani
DOI:10.1021/ja401344e
日期:2013.4.10
The alkylation of the ortho C-H bonds in benzamides and acrylamides containing an 8-aminoquinoline moiety as a bidentate directing group with unactivated alkylhalides using nickel complexes as catalysts is described. The reaction shows high functional group compatibility. In reactions of meta-substituted aromatic amides, the reaction proceeds in a highly selective manner at the less hindered C-H bond
Nucleophilic halo-Michael addition under Lewis-base activation
作者:Víctor Laina-Martín、Ignacio Pérez、Jose A. Fernández-Salas、José Alemán
DOI:10.1039/c9cc07068k
日期:——
A simple and general conjugate nucleophilic halogenation is presented. The THTO/halosilane combination has shown the ability to act as a nucleophilic halide source in the conjugate addition to a variety of Michael acceptors. In addition, a straightforward diastereoselective halogen installation using α,β-unsaturated acyloxazolidinones as platforms has been developed.