compound 18 [PMID: 24119557]   Click here for help

GtoPdb Ligand ID: 10695

Synonyms: sovesudil (proposed INN)
Compound class: Synthetic organic
Comment: Compound 18 is a Rho-associated, coiled coil containing protein kinase (ROCK) inhibitor from Amakem Therapeutics [1]. It contains a carboxylic ester moiety that is intended to facilitate rapid inactivation by esterases in vivo, as a mechanism to reduce systemic or local ROCK-associated side effects. This approach of exploiting designed metabolic inactivation is used to produce so-called 'soft' drugs. Compound 18's chemical structure matches that submitted to the WHO for INN sovesudil. Compound 18 is intended as an intraocular pressure (IOP)-lowering agent, and is expected to be devoid of the systemic blood pressure lowering side effect that is associated with systemic exposure to fasudil and therefore precludes fasudil's use in non-cardiovascular indications [2]. It is also expected to cause less local hyperemia than older ROCK inhibitor chemotypes. See our entry for compound 8 [PMID: 25898023], which is another soft ROCK inhibitor from Amakem Therapeutics.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 94.31
Molecular weight 407.16
XLogP 3.68
No. Lipinski's rules broken 0
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Canonical SMILES CCCOC(=O)c1cccc(c1)c1cc(ccc1CN)C(=O)Nc1ccncc1F
Isomeric SMILES CCCOC(=O)c1cccc(c1)c1cc(ccc1CN)C(=O)Nc1ccncc1F
InChI InChI=1S/C23H22FN3O3/c1-2-10-30-23(29)17-5-3-4-15(11-17)19-12-16(6-7-18(19)13-25)22(28)27-21-8-9-26-14-20(21)24/h3-9,11-12,14H,2,10,13,25H2,1H3,(H,26,27,28)