Protonation site and hydrogen bonding in anhydrous and hydrated crystalline forms of doxazosin mesylate from powder data

Abstract

The three-dimensional solid-state structures of two modifications of doxazosin mesylate (C23H26N5O5)+.(CH3SO3)-, 4-amino-2-[4-[(2,3-dihydro-1,4-benzodioxin-2-yl)carbonyl]piperazin-1-yl]-6,7-dimethoxyquinazoline methanesulfonate, a commonly used antihypertensive agent, have been determined by synchrotron X-ray powder diffraction. An anhydrous form (A) and a dihydrate form (dG) crystallize in monoclinic space groups. In both forms the doxazosin molecule is protonated at the N1 atom of the quinazoline bicycle. The N1 atom, and the amino H atoms and O atoms of the mesylate moieties are involved in three-dimensional hydrogen-bonding networks, while solvent water molecules and carboxamide O atoms are also incorporated in a hydrogen-bonding network in dG.

Structural characterization of prazosin hydrochloride and prazosin free base

“…The initial geometrical models of prazosin were taken from the literature 15,16. In the final bond‐restrained Rietveld refinement, all patterns were fitted with the program MRIA28 in the same way as it was done in the structure refinement of doxazosin mesylate 29. Therefore, the different configurations of the piperazine and furan moieties were revealed only at the stage of structural refinement.…”

Powder X-ray study of racemic (2RS,3RS)-5-amino-3-(4-phenylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-ol

“…Since no single crystal of sufficient size and quality was obtained, a structure determination by powder X-ray diffraction was undertaken. In recent years the crystal structures of a number of compounds of pharmaceutical interest have been solved ab initio from powder X-ray diffraction data in the absence of single crystals of sufficient quality (Chan et al, 1999;Shankland et al, 2001;Chernyshev et al, 2003;Kiang et al, 2003;Rukiah et al, 2004;van der Lee et al, 2005;Rukiah & Assaad, 2010;Al-Ktaifani & Rukiah, 2010;Rukiah & Al-Ktaifani, 2011). We used in-house powder X-ray diffraction data to solve and refine the crystal structure of (2RS,3RS)-(I).…”

Powder X-ray study of racemic (2RS,3RS)-5-amino-3-[4-(3-methoxyphenyl)piperazin-1-yl]-1,2,3,4-tetrahydronaphthalen-2-ol

“…This involves a 26-atom (non-H) problem, which requires careful measurement and interpretation of the data in order to optimize the quality of the results. In recent years, the crystal structures of a number of compounds of pharmaceutical interest have been determined by powder X-ray diffraction data as a last resort in the absence of single crystals of sufficient quality (Chan et al, 1999;Shankland et al, 2004;Chernyshev et al, 2003;Kiang et al, 2003;Rukiah et al, 2004;Van der Lee et al, 2005;Rukiah & Assaad, 2010…”