Synthesis, SAR studies, and pharmacological evaluation of 3-anilino-4-(3-indolyl) maleimides with conformationally restricted structure as orally bioavailable PKCbeta-selective inhibitors |
| |
Authors: | Tanaka Masahiro Sagawa Shoichi Hoshi Jun-ichi Shimoma Fumito Yasue Katsutaka Ubukata Minoru Ikemoto Tomoyuki Hase Yasunori Takahashi Mitsuru Sasase Tomohiko Ueda Nobuhisa Matsushita Mutsuyoshi Inaba Takashi |
| |
Affiliation: | Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki Osaka 569-1125, Japan. |
| |
Abstract: | Conformationally restricted 3-anilino-4-(3-indolyl)maleimide derivatives were designed and synthesized aiming at discovery of novel protein kinase Cbeta (PKCbeta)-selective inhibitors possessing oral bioavailability. Among them, compounds having a fused five-membered ring at the indole 1,2-position inhibited PKCbeta2 with IC50 of nM-order and showed good oral bioavailability. One of the most potent compounds was found to be PKCbeta-selective over other 6 isozymes and exhibited ameliorative effects in a rat diabetic retinopathy model via oral route. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |