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A 72517

(CAS: 138742-43-5)

Suppliers of A 72517

Company Name Email Tel Country
Shanghai Haoyuan Chemexpress Co., Ltd. [email protected] +86 (21) 5187-0955 / +86 (21) 5895-5995 China

Fax: +86 (21) 5895-5996Purity: >98% Brand:

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Background Information of A 72517

Renin Inhibitor

Solubility of A 72517

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Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase
A 72517 - No Development Reported

Chemical Information

M.Wt Formula CAS No. Synonyms
705.97 C35H55N5O6S2 138742-43-5 Zankiren; 2-benzyl-N'-((2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl)-3-((4-methylpiperazin-1-yl)sulfonyl)-N'-(3-(thiazol-4-yl)propanoyl)propanehydrazide

Structure Information of A 72517

Smiles O=C(N(NC(C(CS(=O)(N1CCN(C)CC1)=O)CC2=CC=CC=C2)=O)[[email protected]@H](CC3CCCCC3)[[email protected]@H](O)[[email protected]@H](O)CC(C)C)CCC4=CSC=N4
InChI InChI=1S/C35H55N5O6S2/c1-26(2)20-32(41)34(43)31(22-28-12-8-5-9-13-28)40(33(42)15-14-30-23-47-25-36-30)37-35(44)29(21-27-10-6-4-7-11-27)24-48(45,46)39-18-16-38(3)17-19-39/h4,6-7,10-11,23,25-26,28-29,31-32,34,41,43H,5,8-9,12-22,24H2,1-3H3,(H,37,44)/t29?,31-,32-,34+/m0/s1

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Chemical and Physical Properties

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Reference

[1].Wessale JL, Kleinert HD, Calzadilla SV, Kovar PJ, Rosenberg SH.Effects of renin inhibitor A-72517 on hemodynamics and cardiac function in sodium-depleted dogs.Am J Hypertens. 1993 Jun;6(6 Pt 1):514-21.
A-72517 is a potent inhibitor of human renin (IC50 = 1.0 nmol/L, pH 7.4 in plasma) and, aside from displaying modest activity against canine plasma renin (IC50 = 110 nmol/L), has been shown to be orally active in the dog and other animals. Renin inhibitors, in general, are presumed to exert their hypotensive effect through a reduction in total peripheral resistance. To elucidate the hemodynamic mechanism of action of this new dipeptidic renin inhibitor, the cardiac and systemic hemodynamic effects of A-72517 were studied in sodium-depleted, pentobarbital-anesthetized dogs. Each dog received either vehicle (n = 8) or a single dose (n = 8/dose) of A-72517 administered intravenously as a priming bolus followed by a 30 min constant infusion; infusion doses were 0.01, 0.05, and 0.1 mg/kg/min. A-72517 elicited significant (P < .05) dose-related reductions in mean arterial pressure (MAP) and systemic vascular resistance (SVR) compared to baseline values and the vehicle-treated group, and the recoveries of MAP and SVR were also dose-related. Plasma renin activity, measured by radioimmunoassay, was nearly completely suppressed during drug infusion at all doses. The hypotensive responses did not alter cardiac output nor did they induce reflex tachycardia at any dose. Left ventricular dP/dtmax did not change during infusion of A-72517, but, when corrected for changes in afterload, showed dose-related increases with drug treatment. Moreover, left ventricular end-diastolic pressure and pulmonary arterial wedge pressure were significantly reduced at the high dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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