Crystal structures of calcium channel antagonists: 2,6-dimethyl-3,5-dicarbomethoxy-4-[2-nitro-, 3-cyano-, 4-(dimethylamino)-, and 2,3,4,5,6-pentafluorophenyl]-1,4-dihydropyridine

Abstract

The crystal structures of 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-nitrophenyl)-1,4-dihydropyridine (Nifedipine) and the 3-cyano-, 4-(dimethylamino)- and 2,3,4,5,6-pentafluorophenyl derivatives were determined. The 1,4-dihydropyridine ring in all four compounds has a boat-type conformation with varying degrees of puckering at the C4 position. Increasing distortion from planarity at this position shows a limited correlation with decreasing biological activity, determined as the ability to inhibit the Ca2+-dependent muscarinic-induced mechanical responses of guinea pig ileal longitudinal smooth muscle.

Human red‐blood‐cell Ca2+‐antagonist binding sites

“…Bay M 5579, a nearly inactive nitrendipine derivative with a free carboxyl group [2, 201, was inactive but VO 2605, a 7-bromosubstituted PN 200-110 [5], had an IC50 value of 201 nM. The substitution at this position is known to be detrimental for Ca2+-channel blockade [32]. Thus, both the steric as well a s the other structural requirements of the red blood cell ghost binding site clearly differ from the well characterized 1,4-dihydropyridine receptors on voltage-dependent Ca2 Other properties of the [3H]nimodipine-labelled ghost binding site were in striking contrast to the 1,4-dihydropyridine receptors on Ca2+ channels.…”

Control of organic polymorph formation: crystallization pathways in acoustically levitated droplets

“…Different crystallization routes were discovered depending on the solvent (Dichlormethane (DCM), ACN, MeOH, acetone, EtOH) [45]. Nifedipine has three known crystalline modification: α, β, and γ [38][39][40]. The crystallization process follows different pathways including the crystalline structures (see Figure 4).…”

3,5-Dimethoxycarbonyl-2,6-dimethyl-4-(2-nitrosophenyl)pyridine and Dichlorobis[3,5-dimethoxycarbonyl-2,6-dimethyl-4-(2-nitrophenyl)pyridine]copper(II)

“…In nifedipine, the nitro group is rotated away from coplanarity with the phenyl ring by approximately 37 ° (Triggle, Schefter & Triggle, 1980). The spatial arrangements of the methoxycarbonyl groups at C3 and C5 are also different.…”

“…Thus, the carbonyl groups of the ester functions do not point in the same direction. It is thought that only the sp conformation of the ester group permits hydrogen bonding to the carbonyl O atom as an acceptor group (Triggle, Schefter & Triggle, 1980;Langs, Strong & Triggle, 1990).…”

“…When the plane of the phenyl ring is perpendicular to the plane of the base of the boat, i.e. the plane formed by atoms C2, C3, C5 and C6 of the non-aromatic ring, CI7HI6N205 AND [CuC12(ClvH16N206)2] activity increases (Loev, Goodman, Snader, Tedeschi & Macko, 1974;Triggle, Schefter & Triggle, 1980). The majority of the more than 30 crystal structures of members of the nifedipine family show the ester groups to have the C~--~-O group coplanar with the C==C bond of the 1,4-dihydropyridine ring (Triggle, Langs & Janis, 1989).…”