RESUMO
A series of novel 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives were designed, synthesized, and their acrosin inhibitory activities in vitro were evaluated. The results of the acrosin inhibitory activity showed that all target compounds were more potent than control TLCK. Compounds AQ-A1, AQ-D3, AQ-D4, AQ-E4 and AQ-E5 exhibited stronger acrosin inhibitory activities than control ISO-1. Especially, compound AQ-E5 displayed the most potent acrosin inhibitory activity in all the compounds, with an IC50 of 0.01µmol/mL. This study provided a new structural class for the development of novel acrosin inhibitory agents.
Assuntos
Amidas/química , Inibidores de Proteases/síntese química , Pirazóis/química , Pirazóis/síntese química , Acrosina/antagonistas & inibidores , Acrosina/metabolismo , Amidas/síntese química , Amidas/farmacocinética , Sítios de Ligação , Domínio Catalítico , Cristalografia por Raios X , Meia-Vida , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Inibidores de Proteases/farmacocinética , Pirazóis/farmacocinéticaRESUMO
A series of novel methyl 5-substituted 1H-benzo[d]imidazol-2-ylcarbamates were designed, synthesized, and their acrosin inhibitory activities evaluated in vitro. The results of acrosin inhibitory activity showed that all title compounds were more potent than the control TLCK. Compound 4w displayed the most potent acrosin inhibitory activity among all the compounds, with an IC(50) of 6.3×10(-5)M. The studies provide a new structural class for the development of novel acrosin inhibitory agents.
Assuntos
Acrosina/antagonistas & inibidores , Benzimidazóis/farmacologia , Benzimidazóis/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos MolecularesRESUMO
In the title compound, C(13)H(15)N(3)O(3), the dihedral angle between the benzene and pyrazole rings is 7.7â (1)° and the O-C-C-N torsion angle of the side chain is 74.1â (2)°. In the crystal, mol-ecules are linked by O-Hâ¯O, N-Hâ¯O and N-Hâ¯N hydrogen bonds.
RESUMO
A series of novel ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives were designed and synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds exhibited acrosin inhibitory activities. Among them, three compounds (5l, 5n, and 5v) were more potent than that of the control TLCK. These provide a new structural type for the development of novel contraceptive acrosin inhibitory agents.
Assuntos
Acrosina/antagonistas & inibidores , Ácidos Carboxílicos/síntese química , Anticoncepcionais/síntese química , Pirazóis/síntese química , Inibidores de Serina Proteinase/síntese química , Software , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Anticoncepcionais/química , Anticoncepcionais/farmacologia , Desenho de Fármacos , Fertilização/fisiologia , Humanos , Masculino , Terapia de Alvo Molecular , Pirazóis/química , Pirazóis/farmacologia , Inibidores de Serina Proteinase/química , Inibidores de Serina Proteinase/farmacologia , Relação Estrutura-Atividade , Tosilina Clorometil Cetona/química , Tosilina Clorometil Cetona/metabolismo , Tosilina Clorometil Cetona/farmacologiaRESUMO
A series of new substituted 4-amino-N-(diaminomethylene) benzenesulfonamides were synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds showed potent acrosin inhibitory activities with compounds 4o and 4p being significantly more potent than the control compound N-alpha-tosyl-L-lysyl-chloromethyl-ketone (TLCK). The compounds provide a new scaffold for the development of acrosin inhibitory agents.
Assuntos
Acrosina/antagonistas & inibidores , Acrosina/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Sulfonamidas/química , Sulfonamidas/farmacologia , Inibidores Enzimáticos/síntese química , Humanos , Modelos Moleculares , Ligação Proteica , Relação Estrutura-Atividade , Sulfonamidas/síntese química , BenzenossulfonamidasRESUMO
Human acrosin is an attracting target for the development of novel male contraceptives. Scaffold hopping was used to optimize the isoxazolecarbaldehyde human acrosin inhibitors and extend their structure-activity relationships. Four kinds of scaffolds, namely benzimidazole, benzothiazole, 3H-indazole, and 5-phenyl-1H-pyrazole, were designed and synthesized. Most of the synthesized compounds showed potent human acrosin inhibitory activity and their binding modes were investigated by molecular docking. The scaffold of the compounds was found to be important for the inhibitory activity. Several compounds were more active than the positive control TLCK, suggesting that they can serve as good starting points for the discovery of novel male contraceptive agents.