Medicinal Chemistry of N-Acylhydrazones: New Lead-Compounds of Analgesic, Antiinflammatory and Antithrombotic Drugs

Fraga, Carlos A.M.; Barreiro, Eliezer J.

doi:10.2174/092986706775197881

Cited by 103 publications

(48 citation statements)

References 29 publications

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“…In the case of acid hydrazides 1b and 1c, the reactions with benzaldehyde, adamantan-2-one, and cyclohexanone, respectively, in MeOH occurred smoothly at room temperature and yielded the expected hydrazones 8a-8f in high yields. The analogous reactions with 3 ) For some recent articles on synthesis and biological interest of acylhydrazones see [7a][8a] [13]. acetophenone required acid catalysis (AcOH in EtOH, reflux) to give 8e and 8f (Scheme 5), whereas with benzophenone no hydrazone was obtained.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Selected Reactions of Hydrazides Containing an Imidazole Moiety

Mlostoń

Pieczonka

Kowalczyk

et al. 2011

Helvetica Chimica Acta

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The preparation of two types of imidazole derivatives bearing a hydrazide group was achieved by treatment of the corresponding esters with NH2NH2·H2O in MeOH at room temperature. In the case of 4-(ethoxycarbonyl)-1H-imidazole 3-oxides 3, hydrazides of type 1 were formed with retention of the N-oxide structure (Scheme 1). Interestingly, due to a strong H-bonding, no deoxygenation of the N-O function could be achieved even by treatment of 3 with Raney-Ni. The second type, 2-[(1H-imidazol-2-yl)sulfanyl]acetohydrazides 2, was obtained from 1H-imidazole-2(3H)-thiones 4 in two steps via S-alkylation with methyl bromoacetate, followed by treatment with NH2NH2·H2O (Scheme 2). An imidazole 7, containing both types of hydrazide groups, was prepared analogously from ethyl 2,3-dihydro-2-thioxo-1H-imidazole-4-carboxylate 4d (Scheme 4). Both types of hydrazides, 1 and 2, were transformed successfully to the corresponding acylhydrazones 8 and 9, respectively (Scheme 5). Furthermore, it has been shown that hydrazides of type 1 are useful starting materials for the synthesis of 1,2,4-triazole-3-thiones 11 and 1,3,4-thiadiazole-2-amines 12, bearing an imidazole 3-oxide moiety (Scheme 7). The preparation of two types of imidazole derivatives bearing a hydrazide group was achieved by treatment of the corresponding esters with NH 2 NH 2 ·H 2 O in MeOH at room temperature. In the case of 4-(ethoxycarbonyl)imidazole 3-oxides 3, hydrazides of type 1 were formed with retention of the N-oxide structure (Scheme 1). Interestingly, due to a strong hydrogen bonding, no deoxygenation of the N→O function could be achieved even by treatment of 3 with Raney-nickel. The second type, 2-[(imidazol-2-yl)sulfanyl]acetohydrazides 2, was obtained from 1H-imidazole-2(3H)-thiones 4 in two steps via S-alkylation with methyl bromoacetate followed by treatment with NH 2 NH 2 ·H 2 O (Scheme 2). An imidazole 7, containing both types of hydrazide groups, was prepared analogously from ethyl 2,3-dihydro-2-thioxoimidazole-4-carboxylate 4d (Scheme 4). Both types of hydrazides, 1 and 2, were transformed successfully into the corresponding acylhydrazones 8 and 9, respectively (Scheme 5). Furthermore, it has been shown that hydrazides of type 1 are useful starting materials for the synthesis of 1,2,4-triazole-3-thiones 11 and 1,3,4-thiadiazole-2-amines 12, bearing an imidazole 3-oxide residue (Scheme 7).

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Section: Methodsmentioning

confidence: 99%

Synthesis and Selected Reactions of Hydrazides Containing an Imidazole Moiety

Mlostoń

Pieczonka

Kowalczyk

et al. 2011

Helvetica Chimica Acta

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“…Several studies have indicated that the N-acylhydrazone subunit is a pharmacophore group with analgesic, anti-inflammatory, and antiplatelet properties (11). Therefore, we hypothesized that the compound LASSBio-788 may exert beneficial effects on atherosclerosis, which is a disease that closely associates with inflammation in the cardiovascular system.…”

Section: Anti-atherogenic Effects Of a New Thienylacylhydrazone Derivmentioning

confidence: 99%

Anti-atherogenic Effects of a New Thienylacylhydrazone Derivative, LASSBio-788, in Rats Fed a Hypercholesterolemic Diet

et al. 2013

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Abstract. The compound LASSBio-788 (N-Allyl (2-thienylidene) 3,4-methylenedioxybenzoylhydrazine) is a thienylacylhydrazone derivative shown to have antiplatelet, vasodilatory, and antiinflammatory properties in vitro. We hypothesize that LASSBio-788 may exert beneficial effects on atherosclerosis. Male wistar rats were divided into 4 groups: Control group received standard rat chow, hypercholesterolemic group (HC) and HC+788 (compound LASSBio-788 group) received hypercholesterolemic diet for 45 days. HC+788 group received compound LASSBio-788 (100 mmol/kg) once daily in the last 15 days. LASSBio-788 reduced the levels of total cholesterol (109.1 ± 4.3 vs. 361.0 ± 12.8 mg/dl), triglycerides (66.1 ± 1.1 vs. 186.9 ± 17.7 mg/dl), LDLc (63.2 ± 6.1 vs. 330.9 ± 9.7 mg/dl), VLDLc (9.8 ± 1.1 vs. 45.0 ± 4.6 mg/dl) and malondialdehyde (4.8 ± 0.3 vs. 9.4 ± 0.5 nmol/ml) compared to the HC group. LASSBio-788 presented antiplatelet properties and decreased inflammatory markers levels. LASSBio-788 promoted a decrease in contractile response to phenylephrine and an improvement in endothelium-dependent vasorelaxant response by increasing two-fold the expression of nitric oxide synthase (eNOS). Our results suggest that the compound LASSBio-788 represents a new multi-targeted drug candidate for the treatment of atherosclerosis.

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“…The NAH subunit has been described as the pharmacophoric framework of several bioactive substances from different therapeutic classes 12,13 , indicating the privileged status of this moiety, as has been recently reviewed 14 . So, in the scope of a research program aiming to design, synthesize, and perform the pharmacological evaluation of new platelet antiaggregating lead-compound candidates, we developed new functionalized furyl 1,3-benzodioxolyl-N-acylhydrazone derivatives 9 (Figure 2), designed as isosteres of the antiplatelet thienyl-NAH derivatives 7 and 8.…”

Section: Introductionmentioning

confidence: 95%