4515-18-8Relevant articles and documents
Focal adhesion kinase inhibitor and use
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Paragraph 0404; 0409; 0410, (2019/01/08)
The invention belongs to the field of medicines, relates to a focal adhesion kinase inhibitor and use, in particular relates to a novel focal adhesion kinase inhibitor compound, or stereoisomers, geometric isomers, tautomers, oxynitrides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, further relates to the use of the compound and pharmaceutical compositions as medicines, in particular the use of the compound and pharmaceutical compositions in manufacture of medicines for treatment or prevention of cancer, pulmonary hypertension, and pathological angiogenesis-related diseases.
Structure-activity relationship of 6-methylidene penems bearing 6,5 bicyclic heterocycles as broad-spectrum β-lactamase inhibitors: Evidence for 1,4-thiazepine intermediates with C7 R stereochemistry by computational methods
Venkatesan, Aranapakam M.,Agarwal, Atul,Abe, Takao,Ushirogochi, Hideki,Yamamura, Itsuka,Ado, Mihira,Tsuyoshi, Takasaki,Dos Santos, Osvaldo,Gu, Yansong,Sum, Fuk-Wah,Li, Zhong,Francisco, Gerry,Lin, Yang-I.,Petersen, Peter J.,Yang, Youjun,Kumagai, Toshio,Weiss, William J.,Shlaes, David M.,Knox, James R.,Mansour, Tarek S.
, p. 4623 - 4637 (2007/10/03)
The design and synthesis of a series of 6-methylidene penems containing [6,5]-fused bicycles (thiophene, imidazole, or pyrazle-fused system) as novel class A, B, and C β-lactamase inhibitors is described. These penems proved to be potent inhibitors of the TEM-1 (class A) and AmpC (class C) β-lactamases and less so against the class B metallo-β-lactamase CcrA. Their in vitro and in vivo activities in combination with piperacillin are discussed. On the basis of the crystallographic structures of a serine-bound reaction intermediate of 2 with SHV-1 (class A) and GC1 (class C) enzymes, compounds 14a-1 were designed and synthesized. Penems are proposed to form a seven-membered 1,4 thiazepine ring in both class A and C β-lactamases. The interaction energy calculation for the enzyme-bound intermediates favor the formation of the C7 R enantiomer over the S enantiomer of the 1,4-thiazepine in both β-lactamases, which is consistent with those obtained from the crystal structure of 2 with SHV-1 and GC1.
Process for preparing 6-alkylidene penem derivatives
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, (2008/06/13)
The present invention provides a process of making compounds of formula I, which are useful for the treatment of bacterial infection or disease.
