Abstract:
:The identification and optimization of the first activators of fast skeletal muscle are reported. Compound 1 was identified from high-throughput screening (HTS) and subsequently found to improve muscle function via interaction with the troponin complex. Optimization of 1 for potency, metabolic stability, and physical properties led to the discovery of tirasemtiv (25), which has been extensively characterized in clinical trials for the treatment of amyotrophic lateral sclerosis.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Collibee SE,Bergnes G,Muci A,Browne WF 4th,Garard M,Hinken AC,Russell AJ,Suehiro I,Hartman J,Kawas R,Lu PP,Lee KH,Marquez D,Tomlinson M,Xu D,Kennedy A,Hwee D,Schaletzky J,Leung K,Malik FI,Morgans DJ Jr,Morgan BPdoi
10.1021/acsmedchemlett.7b00546subject
Has Abstractpub_date
2018-02-13 00:00:00pages
354-358issue
4issn
1948-5875journal_volume
9pub_type
杂志文章abstract::A series of oxyguanidine analogues of the cysteine protease inhibitor WRR-483 were synthesized and evaluated against cruzain, the major cysteine protease of the protozoan parasite Trypanosoma cruzi. Kinetic analyses of these analogues indicated that they have comparable potency to previously prepared vinyl sulfone cru...
journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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