25843-69-0Relevant academic research and scientific papers
Structural design, synthesis and substituent effect of hydrazone-N-acylhydrazones reveal potent immunomodulatory agents
Meira, Cássio S.,dos Santos Filho, José Maurício,Sousa, Caroline C.,Anjos, Pamela S.,Cerqueira, Jéssica V.,Dias Neto, Humberto A.,da Silveira, Rafael G.,Russo, Helena M.,Wolfender, Jean-Luc,Queiroz, Emerson F.,Moreira, Diogo R.M.,Soares, Milena B.P.
, p. 1971 - 1985 (2018/03/12)
4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general.
Design, synthesis and biological evaluation of hybrid bioisoster derivatives of N-acylhydrazone and furoxan groups with potential and selective anti-Trypanosoma cruzi activity
Massarico Serafim, Ricardo Augusto,Gon?alves, José Eduardo,De Souza, Felipe Pereira,De Melo Loureiro, Ana Paula,Storpirtis, Silvia,Krogh, Renata,Andricopulo, Adriano Defini,Dias, Luiz Carlos,Ferreira, Elizabeth Igne
, p. 418 - 425 (2014/07/07)
Hybrid bioisoster derivatives from N-acylhydrazones and furoxan groups were designed with the objective of obtaining at least a dual mechanism of action: cruzain inhibition and nitric oxide (NO) releasing activity. Fifteen designed compounds were synthesized varying the substitution in N-acylhydrazone and in furoxan group as well. They had its anti-Trypanosoma cruzi activity in amastigotes forms, NO releasing potential and inhibitory cruzain activity evaluated. The two most active compounds (6, 14) both in the parasite amastigotes and in the enzyme contain the nitro group in para position of the aromatic ring. The permeability screening in Caco-2 cell and cytotoxicity assay in human cells were performed for those most active compounds and both showed to be less cytotoxic than the reference drug, benznidazole. Compound 6 was the most promising, since besides activity it showed good permeability and selectivity index, higher than the reference drug. Thereby the compound 6 was considered as a possible candidate for additional studies.
A diversity oriented synthesis of 2,10-dioxo-10H-1,2,3,4,4a,5-hexahydropyridazino[3,2-b]quinazolines
Schuler, Elisabeth,Juanico, Nacho,Teixidó, Jordi,Michelotti, Enrique L.,Borrell, José I.
, p. 161 - 173 (2007/10/03)
A parallel method for the synthesis of the title compounds is described. Thus, methyl anthranilates (5) are transformed into 2-aminobenzohydrazides (3) which were treated with 4-oxo acids (4) to afford in high yields and acceptable purity of piridazino[3,2-b]quinazolines (1). Compounds (1) present four diversity centers (R1, R2, R3, and R4). The range of chemically acceptable substituents at each center has been evaluated. The isolation of a possible intermediate in the formation of 1, which presents an amino structure (10), has allowed proposing a complete mechanistic rationalization for the formation of structures (1).
COMPOSES SULFURES HETEROCYCLIQUES. XCVI. REACTION DE L'HYDRAZINE SUR LES DIHYDRO-1,2 BENZOTHIAZINE-3,1 THIONES-4
Legrand, Louis,Lozac'H, Noel
, p. 139 - 143 (2007/10/02)
1-Alkyl-1,2-dihydro-3,1-benzothiazine-4-thiones 1, when reacting with hydrazine, give with a good yield a 1-alkyl-3-amino-2,3-dihydro-1H-quinazoline-4-thione-2, often together with a derivative of 1,3,4-thiadiazole-3. With 1-aryl-1,2-dihydro-3,1-benzothiazine-4-thiones, the main product of the reaction with hydrazine appears to be a 1-aryl-4-hydrazono-1,4-dihydro-2H-3,1-benzothiazine 4, sometimes with some amount of 3.On the contrary, when reacting with hydrazine, 1-alkyl (or 1-aryl)-1,2-dihydro-3,1-benzothiazin-4-ones lead to a 2-alkylamino (or arylamino)-benzohydrazide 5. By thermolysis 4 isomerizes into 2 which is accompanied by derivatives (3 and 7) of 1,3,4-thiadiazole.The structures of compounds 2, 4 and 7 have been studied by NMR and UV spectrometry.
