5228-61-5Relevant articles and documents
A preparation method of a dog or CAT
-
Paragraph 0011; 0028; 0033-0034, (2019/03/29)
The invention discloses a dog or CAT a kind of preparation method. Characterized in that (1) in order to inter-bromobenzene as the starting material, nitric acid/sulfuric acid system through the nitration reaction, process for preparing the intermediate 1 (2, 4 - dibromo nitrobenzene); (2) using the intermediate 1 as raw materials, through the ammonia in methanol solution of ammoniation reaction, to prepare the intermediate 2 (5 - bromo - 2 - nitroaniline); (3) using the intermediate 2 and thiophenol sodium solution as raw materials, through the condensation reaction, process for preparing the intermediate 3 (4 - phenylthio - 2 - nitroaniline); (4) intermediate 3 through the palladium catalytic hydrogenation reduction, to produce intermediate 4 (4 - phenylthio - 1, 2 - phenylenediamine); (5) intermediate 4 and melamine-based methyl formate solution, through the cyclization reaction, the profuse benzene reaches zuo generating products. The method clean environment, the production cost is low, with a purity of 99.5% or more, the yield is not lower than 84.0%.
Importance of 5/6-aryl substitution on the pharmacological profile of 4?-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1?-biphenyl]-2-carboxylic acid derived PPARγ agonists
Obermoser, Victoria,Mauersberger, Robert,Schuster, Daniela,Czifersky, Monika,Lipova, Marina,Siegl, Monika,Kintscher, Ulrich,Gust, Ronald
supporting information, p. 590 - 603 (2016/12/09)
In this structure-activity relationship study, the influence of aryl substituents at position 5 or 6 on the pharmacological profile of the partial PPARγ agonist 4‘-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1‘-biphenyl]-2-carboxylic acid was investigated. This lead was previously identified as the essential part of telmisartan to induce PPARγ activation. Para-OCH3-phenyl substitution strongly increased potency and efficacy independent of the position. Both compounds represent full agonists because of strong hydrophobic contacts with the amino acid Phe363 in the ligand binding domain. Partial agonists with higher potency than telmisartan or the lead were obtained with OH or Cl substituents at the phenyl ring. Molecular modeling suggested additional hydrogen or halogen bonds with Phe360 located at helix 7. It is assumed that these interactions fix helix 7, thereby promoting a partial agonist conformation of the receptor. The theoretical considerations correlate very well with the results from the luciferase transactivation assay using hPPARγ-LBD as well as those from a time-resolved fluorescent resonance energy transfer (TR-FRET) assay in which the coactivator (TRAP220, PGC-1α) recruitment and corepressor (NCoR1) release pattern was investigated.
NOVEL TRICYCLIC COMPOUNDS AS INHIBITORS OF MUTANT IDH ENZYMES
-
Page/Page column 65, (2016/06/28)
The present invention is directed to tricyclic compounds of formula (I) which are inhibitors of one or more mutant IDH enzymes: (I). The present invention is also directed to uses of the tricyclic compounds described herein in the potential treatment or prevention of cancers in which one or more mutant IDH enzymes are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such cancers.