Cytokinetics, Inc.

Astellas Pharma Gmbh

Marc Andrew Garard

Bradley Paul Morgan

Pu-Ping Lu

Luke W Ashcraft

Scott E Collibee

Hiroaki Tanaka

Fady Malik

Takashi Kamikubo

Masanori Miura

Jeffrey Warrington

Tomoyuki Saito

Susumu Yamaki

Ippei Sato

Yuji Matsushima

Yasuhiro Shiina

Kayoko Mihara

Munemichi Ohe

Hiroshi Kiyohara

David John Morgans, Jr

Gustave Bergnes

Alex R Muci

William F Browne, Iv

Scott Emile Collibee

Jeffrey Michael Warrington

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.

Tetrahydroisoquinoline derivatives

Provided are certain chemical entities, and methods of use to modulate skeletal myosin, skeletal actin, skeletal tropomyosin, skeletal troponin C, skeletal troponin I, skeletal troponin T, and skeletal muscle, including fragments and isoforms thereof, as well as the skeletal sarcomere, and methods of use in the treatment of muscle weakness and/or cachexia, as part of a rehabilitation or conditioning exercise regimen, or in the treatment of fraility, post-polio syndrome, obesity, sarcopenia, wasting syndrome, muscle spasm, and other indications.

Certain chemical entities, compositions, and methods

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Oakland, CA, United States of America

Marc Andrew Garard