Omaima M. Aboulwafa

Synthesis of some substituted benzimidazoles with potential antimicrobial activity

SummaryThe synthesis andin vitro antimicrobial evaluation of several benzimidazole derivatives with different heterocyclic nuclei at position-2 are described.ZusammenfassungDie Synthese und antimikrobielle Prüfung einiger Benzimidazole mit verschiedenen heterozyklischen Substituenten in 2-Stellung wird beschrieben.

Synthesis, binding affinities and uterotrophic activity of some 2-substituted estradiol and ring-A-fused pyrone derivatives

Abstract A series of estradiol analogs has been synthesized and examined as potential estrogens. Nuclear modifications included a variety of substituents at the 2 position of estradiol, which was previously thought to be inhibitory for activity, and inclusion of the 3-phenolic hydroxyl group in a γ-pyrone and 3′-formylchromone rings fused to ring A of estradiol. The estrogen relative binding affinities and in vivo assays for uterotrophic activity in rats showed that all the tested compounds were capable of displacing [ 3 H]E 2 from the estrogen receptor sites by different degrees. The highest inhibition of [ 3 H]E 2 binding (78%) to the estrogen receptor was displayed by 2-acetylestradiol which was also a potent uterotrophic agent. Omission of the free 3-hydroxyl functionality by inclusion in a γ-pyrone ring produced a chromone derivative that was capable of inhibiting [ 3 H]E 2 binding by 60% and displayed a uterotrophic response of 97%. Further nuclear modification by introduction of thiosemicarbazone moieties decreased the uterotrophic activity, the highest activity being elicited by the p -bromophenyl thiosemicarbazone derivative. The diketone 2-benzoylacetylestradiol 17β-acetate, 2-(3′-benzylideneacetyl)estradiol and 2-[3′-(3-anisylidene)acetyl]estradiol exhibited high inhibition of binding affinity while eliciting ≈ 50% the uterotrophic activity of estradiol.

Synthesis and biological evaluation of novel N3-substituted dihydropyrimidine derivatives as T-type calcium channel blockers and their efficacy as analgesics in mouse models of inflammatory pain

Low-voltage-activated calcium channels are important regulators of neurotransmission and membrane ion conductance. A plethora of intracellular events rely on their modulation. Accordingly, they are implicated in many disorders including epilepsy, Parkinsons disease, pain and other neurological diseases. Among different subfamilies, T-type calcium channels, and in particular the CaV3.2 isoform, were shown to be involved in nociceptive neurotransmission. The role of CaV3.2 in pain modulation was supported by demonstrating selective antisense oligonucleotide-mediated CaV3.2 knockdown, in vivo antinociceptive effects of T-type blockers, and pain attenuation in CaV3.2 knockout formalin-induced pain model. These Emerging investigations have provided new insights into targeting T-type calcium channels for pain management. Within this scope, various T-type calcium channel blockers have been developed such as mibefradil and ethosuximide. Although being active, most of these molecules interact with other receptors as well. This addresses the need for T-selectivity. Few selective T-type channel blockers of diverse chemical classes were developed such as ABT-639 and TTA-P2. Interestingly, R(-) efonidipine which is a dihydropyridine (DHP) showed T-channel selectivity. Systematic modification of 1,4-dihydropyridine scaffold introduced novel derivatives with 40-fold T-type selectivity over L-type calcium channels. Along these lines, substitution of the DHP core with various analogues favored T-selectivity and may serve as novel pharmacophores. Several dihydropyrimidine (DHPM) mimics were introduced by Squibb as potential candidates. As a continuation of this approach, the current study describes the synthesis of Novel N3 substituted DHPMs with structure similarities to the active DHPs. Different functional groups were introduced to the N3 position through a spacer to gain more information about activity and selectivity. Furthermore, the spacer aims at improving the metabolic stability of the molecules. Initial screening data by whole patch clamp technique showed a robust inhibition of Cav3.2 T-type channels by eleven compounds. Interestingly, four compounds of these were efficient selective T-type blockers. Based on selectivity and efficiency, two compounds were selected for in vivo evaluation in mouse models of inflammatory pain. Results showed effective attenuation of nociception and mechanical hypersensitivity.

Ethyl 5-methyl-7-phenyl-1,2,4-triazolo[4,3-a]pyrimidine-6-carboxyl­ate

In the title compound, C15H14N4O2, the triazolopyrimidine ring system is almost planar (r.m.s. deviation = 0.02 Å) and the phenyl ring is inclined to its mean plane by 42.45 (9)°. The carboxyl group is inclined to the triazolopyrimidine ring mean plane by 57.8 (3)°. In the molecule, there is a short C—H⋯O contact involving the carbonyl O atom and an H atom of the adjacent methyl substituent. In the crystal, neighbouring molecules are linked by C—H⋯O hydrogen bonds, forming chains propagating along [010]. There are also weak π–π interactions present involving the pyridine and phenyl rings of neighbouring chains [intercentroid distance = 3.8580 (16) Å].