Hit to lead account of the discovery of bisbenzamide and related ureidobenzamide inhibitors of Rho kinase.

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Morwick T, Buttner FH, Cywin CL, Dahmann G, Hickey E, Jakes S, Kaplita P, Kashem MA, Kerr S, Kugler S, Mao W, Marshall D, Paw Z, Shih CK, Wu F, Young E

Hit to lead account of the discovery of bisbenzamide and related ureidobenzamide inhibitors of Rho kinase.

J Med Chem. 2010 Jan 28;53(2):759-77. doi: 10.1021/jm9014263.

PubMed ID
20000469 [ View in PubMed
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Abstract

A highly selective series of bisbenzamide inhibitors of Rho-associated coiled-coil forming protein kinase (ROCK) and a related ureidobenzamide series, both identified by high throughput screening (HTS), are described. Details of the hit validation and lead generation process, including structure-activity relationship (SAR) studies, a selectivity assessment, target-independent profiling (TIP) results, and an analysis of functional activity using a rat aortic ring assay are discussed.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
(S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINERho-associated protein kinase 1Ki (nM)6N/AN/ADetails
FasudilRho-associated protein kinase 1Ki (nM)530N/AN/ADetails
FasudilRho-associated protein kinase 1IC 50 (nM)4300N/AN/ADetails
FasudilRho-associated protein kinase 2IC 50 (nM)660N/AN/ADetails
Y-27632Rho-associated protein kinase 1Ki (nM)150N/AN/ADetails
Y-27632Rho-associated protein kinase 2IC 50 (nM)260N/AN/ADetails
Y-27632Rho-associated protein kinase 2Ki (nM)300N/AN/ADetails