78154-49-1Relevant academic research and scientific papers
Biochemical and structural evaluation of highly selective 2-arylbenzoxazole-based transthyretin amyloidogenesis inhibitors
Johnson, Steven M.,Connelly, Stephen,Wilson, Ian A.,Kelly, Jeffery W.
, p. 260 - 270 (2008/09/18)
To develop potent transthyretin (TTR) amyloidogenesis inhibitors that also display high binding selectivity in blood, it proves useful to systematically optimize each of the three substructural elements that comprise a typical inhibitor: the two aryl rings and the linker joining them. In the first study, described herein, structural modifications to one aryl ring were evaluated by screening a library of 2-arylbenzoxazoles bearing thyroid hormone-like aryl substituents on the 2-aryl ring. Several potent and highly selective amyloidogenesis inhibitors were identified that exhibit minimal thyroid hormone nuclear receptor and COX-1 binding. High resolution crystal structures (1.3-1.5 ?) of three inhibitors (2f, 4f, and 4d) in complex with TTR were obtained to characterize their binding orientation. Collectively, the results demonstrate that thyroid hormone-like substitution patterns on one aryl ring lead to potent and highly selective TTR amyloidogenesis inhibitors that lack undesirable thyroid hormone receptor or COX-1 binding.
Synthesis, antimicrobial, and QSAR studies of substituted benzamides
Kumar, Anil,Narasimhan, Balasubramanian,Kumar, Devinder
, p. 4113 - 4124 (2008/03/11)
A series of new substituted benzamides were synthesized and tested in vitro for their antibacterial activity against Gram-positive and Gram-negative bacteria and as well for antifungal activity. The compounds 8i and 9 showed better activity among the different benzamides synthesized. The structural characteristics governing antibacterial activities of substituted benzamides were studied using QSAR methodology. The results showed that the antimicrobial activity could be modeled using the topological descriptors, molecular connectivity indices (2χv and 2χ) and Kiers shape index (κα1). The low residual activity and high cross-validated r2 values (rcv2) observed indicated the predictive ability of the developed QSAR models.
Tertiary Amine-Catalyzed Acyl Group Exchange Reaction of N,O-Diacyl-o-aminophenols. Its Mechanism and Factors Determining the Relative Stability of Acyl Exchanged Isomer Pairs
Sakurai, Tadamitsu,Kojima, Shuichi,Inoue, Hiroyasu
, p. 3141 - 3148 (2007/10/02)
Acyl substituent effects on the equilibrium and rate constants for the acyl group exchange reactions of various N,O-diacyl-o-aminophenols have been investigated in solvents with different polarities.It was found that the relative stability of acyl exchanged isomer pairs is determined solely by the inductive effect of acyl groups, provided that the steric hindrance of acyl substituents bonded to amide nitrogen affects the stability to the same extent.The importance of steric hindrance exerted by a bulky acyl group in determining the relative stability was demonstrated by analyzing the correlation between the standard free energy change (ΔG0) and pKa, which were used as the measure of the relative stability of isomer pairs and of the electron-with drawing ability of acyl groups, respectively.On the other hand, the logarithms of catalytic rate constants for the acyl migration reactions were correlated well to the pKa values.In addition to this finding, a large negative value of activation entropy (ΔS=-160 J K-1 mol-1) and the Broensted coefficient β of 0.65 for the reaction of N,O-(acetyl)-(1-naphthoyl) pair of N,O-diacyl-o-aminophenol provide a definitive evidence for the rate-determining proton transfer from this derivative to amine catalyst in the transition state.
Oxidation of 2,3-Disubstituted Indoles with m-Chloroperbenzoic Acid. Formation of o-Aminophenol Derivatives and a Dimeric Product
Hino, Tohru,Yamaguchi, Hitoshi,Matsuki, Kenji,Nakano, Kumiko,Sodeoka, Mikiko,Nakagawa, Masako
, p. 141 - 146 (2007/10/02)
Oxidation of tetrahydrocarbazole (5) with m-chloroperbenzoic acid in methylene dichloride at -60 deg C gave the N-benzoyl-o-aminophenol (11) togehter with the hydroxy-3H-indole (7) and the indol-3(2H)-one (9).The N-benzoyl-o-aminophenol (11) was found to be derived from the hydroxy-4aH-carbazole (7) via an unstable tertiary amine intermediate (17) by further oxidation.The N-benzoyl-o-aminophenol (11) was also obtained by the oxidation of the other hydroxy-3H-indoles (18), (19), and (24).On the other hand, similar oxidation of N-methyl-tetrahydrocarbazole (6) gave the hydroxyenamine (28) and its dimer (27), and of 2,3-diphenylindole (31) and the N-methyl derivative (30) gave the hydroxy-3H-indole (19) and the ketoamide (33), while the 1,4-benzoxazine derivatives (34) and (35) were obtained in the case of the N-acetyl derivative (32).
