Publication number: 20230125280
Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.
Type:
Application
Filed:
September 13, 2022
Publication date:
April 27, 2023
Inventors:
Ippei SATO, Takashi KAMIKUBO, Masanori MIURA, Yuji MATSUSHIMA, Hiroaki TANAKA, Yasuhiro SHIINA, Susumu YAMAKI, Tomoyuki SAITO, Hiroshi KIYOHARA, Munemichi OHE, Kayoko MIHARA, Bradley Paul MORGAN, Fady MALIK, Scott Emile COLLIBEE, Luke ASHCRAFT, Pu-Ping LU, Jeffrey Michael WARRINGTON, Marc GARARD
Publication number: 20230083960
Abstract: Provided herein are compounds of formula (I): or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X1, X2, Ry, Rz, R1, R2, R3, and R4 are as defined herein. Also provided herein is a pharmaceutically acceptable composition comprising a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. Also provided herein are methods of using a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, to treat various diseases, disorders, and conditions responsive to the modulation of the contractility of the skeletal sarcomere.
Type:
Application
Filed:
November 5, 2021
Publication date:
March 16, 2023
Inventors:
Bradley P. MORGAN, Chris Evans, Pu-Ping Lu, Makoto Yamasaki, Wenyue Wang, Scott Collibee, Takuya Makino, Kazuyuki Tsuchiya, Toshio Kurosaki, Susumu Yamaki, Eriko Honjo, Yuka Koizumi, Naoto Katoh, Ryuichi Sekioka, Ikumi Kuriwaki, Denise Andersen