682804-53-1Relevant academic research and scientific papers
Nanomolar small molecule inhibitors for ανβ6, ανβ5, and ανβ3 integrins
Goodman, Simon L.,H?lzemann, Günter,Sulyok, G?bor A. G.,Kessler, Horst
, p. 1045 - 1051 (2002)
Integrin adhesion receptors frequently recognize a core amino acid sequence, Arg-Gly-Asp, in their target ligands. Inhibitors with the ability to inhibit one or a small subset of such RGD-dependent integrins have been invaluable in defining their biological function. Here, we have characterized low molecular weight inhibitors for their ability to specifically inhibit ανβ6 integrin, a fibronectin/tenascin receptor. As of yet, no nonpeptidic inhibitor of ανβ6 was known. New peptidomimetic and nonpeptidic compounds were examined in isolated integrin binding assays and in cell adhesion assays for their ability to block ανβ6, ανβ3, ανβ5, and αIIbβ3 integrins. The compounds are based on an aromatically substituted β amino acid or glutaric acid derivative as an acidic center and an aminopyridyl or guanidyl residue as a basic mimetic. We found several classes of inhibitors with different selectivities, especially mono- or biselectivity on the αν-integrins ανβ6 and ανβ3, and nanomolar activity. Furthermore, nearly all compounds are inactive on αIIbβ3. Compound 11 is the first specific, peptidomimetic inhibitor of the ανβ6 integrin receptor.
BENZIMIDAZOLE DERIVATIVES USEFUL AS POTASSIUM CHANNEL INHIBITORS
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Page/Page column 102; 103, (2019/03/12)
The present invention relates to compounds of the general formula (I). The compounds of formula I are potassium channel inhibitors useful for treatment of a cardiac disease, disorder or condition in a mammal.
Structure activity relationships of αv integrin antagonists for pulmonary fibrosis by variation in aryl substituents
Adams, James,Anderson, Edward C.,Blackham, Emma E.,Chiu, Yin Wa Ryan,Clarke, Thomas,Eccles, Natasha,Gill, Luke A.,Haye, Joshua J.,Haywood, Harvey T.,Hoenig, Christian R.,Kausas, Marius,Le, Joelle,Russell, Hannah L.,Smedley, Christopher,Tipping, William J.,Tongue, Tom,Wood, Charlotte C.,Yeung, Jason,Rowedder, James E.,Fray, M. Jonathan,McInally, Thomas,Macdonald, Simon J. F.
supporting information, p. 1207 - 1212 (2015/04/27)
Antagonism of αvβ6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an αvβ3 antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved αvβ6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan αv antagonists having ca. 100 nM potency against αvβ3, αvβ5, αvβ6, and αvβ8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for αvβ3 and αvβ5.
