Dirhodium(II)-Catalyzed Synthesis of N-(Arylsulfonyl)hydrazines by N–H Amination of Aliphatic Amines

This study reports the development of Rh(II)-catalyzed N–N bond-forming reaction of amino acid derivatives or aliphatic amines to provide hydrazine derivatives through the combined use of Rh2(esp)2 and [(3,4-dimethoxyphenyl)sulfonylimino]-2,4,6-trimethylphenyliodinane (3,4-(MeO)2C6H3SO2N=IMes). This is the first report of N–H amination of aliphatic amines with metal–nitrene species.

Synthesis of Novel Thiazolyl Hydrazine Derivatives and Their Antifungal Activity

A series of novel thiazolyl hydrazine derivatives 3a–3o were synthesized and evaluated for their in vitro antifungal activity against six phytopathogenic strains, namely, Botryosphaeria dothidea (B. d.), Gibberella sanbinetti (G. s.), Fusarium oxysporum (F. o.), Thanatephorus cucumeris (T. c.), Sclerotinia sclerotiorum (S. s.), and Verticillium dahliae (V. d.), by the classical mycelial growth rate method. Biological assessment results showed that most of these target compounds showed good antifungal activity toward tested strains. Especially, compound 3l showed excellent antifungal activities against B. d. and G. s. with relatively lower EC50 values of 0.59 and 0.69 µg/mL, respectively, which were extremely superior to those of commercial fungicides fluopyram, boscalid, and hymexazol and were comparable to those of carbendazim. Given the excellent bioactivity of designed compounds, this kind of thiazolyl hydrazine framework can provide a suitable point for exploring highly efficient antifungal agents.

Arylmethylene hydrazine derivatives containing 1,3-dimethylbarbituric moiety as novel urease inhibitors

A new series of arylmethylene hydrazine derivatives bearing 1,3-dimethylbarbituric moiety 7a–o were designed, synthesized, and evaluated for their in vitro urease inhibitory activity. All the title compounds displayed high anti-urease activity, with IC50 values in the range of 0.61 ± 0.06–4.56 ± 0.18 µM as compared to the two standard inhibitors hydroxyurea (IC50 = 100 ± 0.15 μM) and thiourea (IC50 = 23 ± 1.7 μM). Among the synthesized compounds, compound 7h with 2-nitro benzylidene group was found to be the most potent compound. Kinetic study of this compound revealed that it is a mix-mode inhibitor against urease. Evaluation of the interaction modes of the synthesized compounds in urease active site by molecular modeling revealed that that compounds with higher urease inhibitor activity (7h, 7m, 7c, 7l, 7i, and 7o, with IC50 of 0.61, 0.86, 1.2, 1.34, 1.33, 1.94 μM, respectively) could interact with higher number of residues, specially Arg609, Cys592 (as part of urease active site flap) and showed higher computed free energy, while compounds with lower urease activity (7f, 7n, 7g, and 7a with IC50 of 3.56, 4.56, 3.62 and 4.43 μM, respectively) and could not provide the proper interaction with Arg609, and Cys592 as the key interacting residues along with lower free binding energy. MD investigation revealed compound 7h interacted with Arg609 and Cys592 which are of the key residues at the root part of mobile flap covering the active site. Interacting with the mentioned residue for a significant amount of time, affects the flexibility of the mobile flap covering the active site and causes inhibition of the ureolytic activity. Furthermore, in silico physico-chemical study of compounds 7a–o predicted that all these compounds are drug-likeness with considerable orally availability.

The synthesis of N-(4-aryl-thiazol-2-yl)-N1-(4,5,6,7-tetrahydro-3H-azepin-2-yl)-hydrazine hydrobromides and the cardioprotective activity of (41-methoxyphenyl-thiazol-2-yl) derivative

A novel series of N-(4-aryl-thiazol-2-yl)-N1-(4,5,6,7-tetrahydro-3Н-azepin-2-yl)-hydrazine derivatives were synthesized by interaction of equimolar quantities of substituted α-bromacetophenones with thiosemicarbazide and characterized on the basis of their elemental analyses and spectral data. Study of cardioprotective activity of the all new products in comparison to levocarnitine and its synthetic analogue mildronate were carried out. Thus, specified results indicate, N-[(41-methoxyphenyl)-thiazol-2-yl)]-N1-(4,5,6,7-tetrahydro-3Н-azepin-2-yl)-hydrazine hydrobromide was influenced deceleration of contractive response of smooth muscles to hypoxia 13.2% more effective than levocarnitine and 6.85% more effective than mildronate and were shown pronounced cardioprotective properties. Obtained data justifies further study of N-(4-aryl-thiazol-2-yl)-N1-(4,5,6,7-tetrahydro-3Н-azepin-yl)-hydrazine derivatives as new potential cardioprotective drugs for treatment of various cardiac diseases.

Studying of analgesic and anti-inflammatory activity of 2,4-dioxobutanoic acid hydrazine derivatives

Objective. To study the analgesic and anti-inflammatory activity of water-soluble hydrazine derivatives of 2,4-dioxobutanoic acids, as well as to determine the relationship between the structure of substances and their biological effects. Materials and methods. The laboratory synthesis methods were applied to obtain 2-hydrazine derivatives of 2,4-dioxobutanoic acids. The compounds were tested for biological activity using a hot plate test in mice and an acute inflammatory reaction caused by carrageenan-induced paw edema in rats. Results. The analgesic activity of four compounds is comparable to that of nimesulide. One of the substances obtained is found to exhibit higher anti-inflammatory activity than nimesulide during the 1st and 3rd hours of the experiment. Two compounds with a combination of high analgesic and anti-inflammatory activity were identified. The effect of certain radicals in the structure of the substances on the activities studied was discovered. Conclusions. The revealed relationship between the structure of original compounds and their biological activities can be used in the further synthesis and search for new domestic pharmaceutical substances with investigated effects.