Novel, potent, selective, and orally bioavailable human βII-tryptase inhibitors
摘要:
The synthesis of novel [1,2,4]oxadiazoles and their structure-activity relationship (SAR) for the inhibition of tryptase and related serine proteases is presented. Elaboration of the P'-side afforded potent, selective, and orally bioavailable tryptase inhibitors. (c) 2006 Elsevier Ltd. All rights reserved.
Compounds of Formula I or pharmaceutically acceptable salts or solvates thereof, wherein A, B, D, Ar1, Ar2, R2, R3, R4, a, m and n are defined in the specification, methods for the use thereof, processes for making and pharmaceutical compositions containing the same.
Novel, potent, selective, and orally bioavailable human βII-tryptase inhibitors
作者:David Sperandio、Vincent W.-F. Tai、Julia Lohman、Bernie Hirschbein、Rohan Mendonca、Chang-Sun Lee、Jeffrey R. Spencer、James Janc、Margaret Nguyen、Jerlyn Beltman、Paul Sprengeler、Heleen Scheerens、Tong Lin、Liang Liu、Ashwini Gadre、Alisha Kellogg、Michael J. Green、Mary E. McGrath
DOI:10.1016/j.bmcl.2006.04.088
日期:2006.8
The synthesis of novel [1,2,4]oxadiazoles and their structure-activity relationship (SAR) for the inhibition of tryptase and related serine proteases is presented. Elaboration of the P'-side afforded potent, selective, and orally bioavailable tryptase inhibitors. (c) 2006 Elsevier Ltd. All rights reserved.
Synthesis and Aldose Reductase Inhibitory Activities of NovelO-Substituted Hydroxyphenylacetic Acid Derivatives
novel aldosereductase inhibitors, several O‐substituted hydroxyphenylacetic acidderivatives were investigated. The highest inhibitoryactivity was found for compounds 7b and 7c bearing a cyclohexylmethyl substituent. This result demonstrates that within these series, this moiety is a useful surrogate for the 4‐bromo‐2‐fluorobenzyl residue which can be often found in potent aldosereductase inhibitors
为了继续我们旨在制备新型醛糖还原酶抑制剂的工作,研究了几种 O 取代的羟基苯乙酸衍生物。发现带有环己基甲基取代基的化合物 7b 和 7c 的抑制活性最高。该结果表明,在这些系列中,该部分是 4-溴-2-氟苄基残基的有用替代物,该残基通常可在有效的醛糖还原酶抑制剂中找到。