4195-25-9Relevant academic research and scientific papers
Toward a treatment of diabesity: In vitro and in vivo evaluation of uncharged bromophenol derivatives as a new series of PTP1B inhibitors
Li, Xiangqian,Xu, Qi,Li, Chao,Luo, Jiao,Li, Xiuxue,Wang, Lijun,Jiang, Bo,Shi, Dayong
, p. 178 - 185 (2019/02/05)
Protein tyrosine phosphatase 1B (PTP1B) has been considered as a validated biological target for type 2 diabetes treatment, but past endeavors to develop inhibitors of PTP1B into drugs have been unsuccessful. Two challenging aspects are selective inhibition and cell permeability. A structure-based strategy was employed to develop uncharged bromophenols as a new series of PTP1B inhibitors. The most potent compound 22 (LXQ46) inhibited PTP1B with an IC50 value of 0.190 μM, and showed remarkable selectivity over other protein tyrosine phosphatases (PTPs, 20–200 folds). In the SPR study, increasing concentrations of compound 22 led to concentration-dependent increases in binding responses, indicating that compound 22 could bind to the surface of PTP1B via noncovalent means. By treating insulin-resistant C2C12 myotubes with compound 22, enhanced insulin and leptin signaling pathways were observed. Long-term oral administration of compound 22 reduced the blood glucose level of diabetic BKS db mice. The glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) in BKS db mice showed that oral administration of compound 22 could increase insulin sensitivity. In addition, long-term oral administration of compound 22 could protect mice from obesity, which was not the result of toxicity. Our pharmacokinetics results from the rat-based assays showed that orally administered compound 22 was absorbed rapidly from the gastrointestinal tract, extensively distributed to the tissues, and rapidly eliminated from the body. All these results indicate that compound 22 could serve as a qualified agent to treat type II diabetes.
Total synthesis of a marine alkaloid - Rigidin E
Cao, Banpeng,Ding, Haixin,Yang, Ruchun,Wang, Xiaoji,Xiao, Qiang
, p. 1412 - 1421 (2012/08/14)
In the present paper, we report an efficient total synthesis of a marine alkaloid, rigidin E. The key tetrasubstituted 2-amino-3-carboxamidepyrrole intermediate was synthesized by cascade Michael addition/intramolecular cyclization between N-(2-(4-(benzyloxy)phenyl)-2-oxoethyl)methanesulfonamide and 3-(4-(benzyloxy) phenyl)-2-cyano-N-methylacrylamide. Subsequent carbonylation with triphosgene catalyzed by I2 and deprotection of benzyl groups afforded rigidin E in 21% overall yield. This strategy has the merits of metal-free reactions, low cost, mild reaction protocols, and easy access to diversity-oriented derivatives for potential structure-activity relationship investigation.
Fibrinogen receptor antagonists and their use
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Page/Page column 64, (2010/08/04)
This invention relates to novel fused bicyclic compounds of the general formula (I): wherein the symbols are defined herein, to pharmaceutical compositions containing the compounds, processes for preparing the compounds, and to methods of using the compounds, alone or in combination with other therapeutic agents. The compounds are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex, and are therefore useful for the inhibition of platelet aggregation, and for the treatment of thrombotic diseases and other diseases.
FIBRINOGEN RECEPTOR ANTAGONISTS AND THEIR USE
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Page/Page column 78, (2010/02/11)
This invention relates to novel fused bicyclic compounds of the general formula (I): wherein the symbols are defined herein, to pharmaceutical compositions containing the compounds, processes for preparing the compounds, and to methods of using the compounds, alone or in combination with other therapeutic agents. The compounds are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex, and are therefore useful for the inhibition of platelet aggregation, and for the treatment of thrombotic diseases and other diseases.
Phenoxyacetic acid derivatives, pharmaceutical compositions and methods
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, (2008/06/13)
Novel phenoxyacetic acid derivative of the formula: STR1 wherein R is a substituted or unsubstituted phenyl group, naphthyl group or a sulfur-containing 5-membered hetero-monocyclic group, R1, R2, R3 and R4 are hydrogen atom, a lower alkyl group, a phenyl-lower alkyl group or phenyl group, R5 is hydrogen atom or a lower alkyl group, R6 is carboxyl group, a protected carboxyl group, hydroxy group or a di(lower alkyl)-amino group, Ring A is a substituted or unsubstituted phenylene group, m is 0 or 1 and n is an integer 0 to 5, provided that, when m is 0, (1) at least either one of R1 to R4 is or/are a phenyl-lower alkyl group or phenyl group, (2) at least either one of R1 to R4 is or/are a lower alkyl group, and R6 is hydroxy group, or (3) all of R1 to R4 are hydrogen atom, and Ring A is a substituted phenylene group, or a pharmaceutically acceptable salt thereof are disclosed. Said derivative (I) and a pharmaceutically acceptable salt thereof have a potent platelet aggregation-inhibiting activity.
