Structural characterization of LASSBio-1289: a new vasoactive N-methyl-N-acylhydrazone derivative

Author(s)

Pereira Sato, Juliana Alves ^[1] ; Costa, Fanny Nascimento ^[1] ; da Rocha, Miguel Divino ^{[2, 3]} ; Barreiro, Eliezer J. ^{[2, 3]} ; Manssour Fraga, Carlos Alberto ^{[2, 3]} ; Punzo, Francesco ^[4] ; Ferreira, Fabio Furlan ^[1]

Affiliation

^[1] Fed Univ ABC UFABC, Ctr Nat & Human Sci CCNH, BR-09210580 Santo Andre, SP - Brazil

^[2] Univ Fed Rio de Janeiro, Inst Biomed Sci, LASSBio, BR-21941902 Rio De Janeiro, RJ - Brazil

^[3] Univ Fed Rio de Janeiro, Grad Program Chem, Inst Chem, BR-21941902 Rio De Janeiro, RJ - Brazil

^[4] Univ Catania, Sez Chim, Dipartimento Sci Farm, I-95125 Catania - Italy

• Document type: Journal article
• Source: CrystEngComm; v. 17, n. 1, p. 165-173, 2015.
• Web of Science Citations: 7

Abstract

LASSBio-1289 compound has been found to promote intense vasodilation and antihypertensive activity. It is an innovative compound, without structural similarities to the three main classes of calcium antagonists. (1,4-dihydropyridines, benzothiazepines and phenylalkylamines) commonly used. A complete knowledge of the structure, including stereochemistry, is essential to lead optimization in drug discovery. For this reason, in this work we determined the crystal structure of this novel vasoactive N-methyl-N-acylhydrazone derivative by means of X-ray powder diffraction data and an ab initio simulating annealing approach, allowing us to observe the relative configuration E of the imine double bond and its conformation as well as its most relevant intermolecular interactions. These findings were also checked by a FTIR analysis and confirmed in solution by NMR. The compound crystallized under a monoclinic crystal system with space group P2(1)/c and unit cell parameters a = 14.5118(3) angstrom, b = 12.1374(2) angstrom, c = 7.5498(1) angstrom, beta = 91.113(1)degrees, V = 1329.53(4) angstrom(3), Z = 4, Z' = 1 and rho(calc) = 1.44042(4) g cm(-3). Moreover, a crystal morphology prediction, experimentally compared with SEM inferred images, allowed a direct comparison of the microcrystalline habit and quality, allowing a study of the potential solvent effect on the crystal growth. (AU)

• FAPESP's process: 08/10537-3 - Study of crystalline pharmaceuticals polymorphs by X-ray powder diffraction and the Rietveld method
• Grantee: Fabio Furlan Ferreira
• Support Opportunities: Research Grants - Young Investigators Grants