Title of article :
Synthesis, SAR studies, and pharmacological evaluation of 3-anilino-4-(3-indolyl) maleimides with conformationally restricted structure as orally bioavailable PKCβ-selective inhibitors Original Research Article
Author/Authors :
Masahiro Tanaka
، نويسنده , , Shoichi Sagawa، نويسنده , , Jun-ichi Hoshi، نويسنده , , Fumito Shimoma، نويسنده , , Katsutaka Yasue، نويسنده , , Minoru Ubukata، نويسنده , , Tomoyuki Ikemoto، نويسنده , , Yasunori Hase، نويسنده , , Mitsuru Takahashi، نويسنده , , Tomohiko Sasase، نويسنده , , Nobuhisa Ueda، نويسنده , , Mutsuyoshi Matsushita، نويسنده , , Takashi Inaba، نويسنده ,
Abstract :
Conformationally restricted 3-anilino-4-(3-indolyl)maleimide derivatives were designed and synthesized aiming at discovery of novel protein kinase Cβ (PKCβ)-selective inhibitors possessing oral bioavailability. Among them, compounds having a fused five-membered ring at the indole 1,2-position inhibited PKCβ2 with IC50 of nM-order and showed good oral bioavailability. One of the most potent compounds was found to be PKCβ-selective over other 6 isozymes and exhibited ameliorative effects in a rat diabetic retinopathy model via oral route.
Keywords :
PKC? selective inhibitor , 3-Anilino-4-(3-indolyl)maleimide , Orally active compounds , Diabetic complications
