Synthesis and Pharmacological Evaluation of New Progesterone Esters as 5α-Reductase Inhibitors
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概要
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In this study we report the synthesis and pharmacological evaluation of four new progesterone derivatives; 17α-hydroxy-16β-methylpregna-4, 6-diene-3, 20-dione 12, 17α-cyclopropylcarbonyloxy-16β-methylpregna-4, 6-diene-3, 20-dione 13, 17α-cyclobutylcarbonyloxy-16β-methylpregna-4, 6-diene-3, 20-dione 14, 17α-acetoxy-16β-methylpregna-4, 6-diene-3, 20-dione 15 and the pregnatriene compound 17α-cyclobutylcarbonyloxy-16β-methylpregna-1, 4, 6-triene-3, 20-dione 16. The pharmacological effect of these compounds was determined in vivo as well as in vitro. The evaluation in vivo was carried out on gonadectomized male hamsters that were injected subcutaneously daily with testosterone (T) and/or finasteride, or with the novel compounds. At the end of the treatments the animals were sacrificed and the prostates were weighed. It was observed that when testosterone (T) and finasteride or compounds 12-16 were injected together, the weight of the prostate decreased significantly as compared to that of the testosterone-treated animals. The 5α-reductase inhibitory activity was evaluated in vitro using human prostate homogenates. These experiments showed the following IC_<50> values : compound 12 (alcohol at C-17) 1.2×10^<-6>_M, 13 (cyclopropyl substituent at C-17) 7.9×10^<-10>_M, 14 (cyclobutyl substituent) 3.2×10^<-8>_M, 15 (acetoxy substituent) 6.3×10^<-11>_M and 16 (cyclobutyl substituent) 3.9×10^<-6>_M. It is evident from these data that when the size of the substituent at C-17 is decreased, the 5α-reductase inhibitory activity increases. Apparently, in this biological model, the 5α-reductase inhibitory activity depends upon the steric effect of the substituent at C-17. However, the free alcohol 12 showed much lower 5α-reductase inhibitory activity.
- 公益社団法人日本薬学会の論文
- 2005-12-01
著者
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Ramirez Elena
Department Of Pharmacy Faculty Of Chemistry National University Of Mexico City
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BRATOEFF Eugene
Departamento de Farmacia, Facultad de Quimica, UNAM, Ciudad Universitaria
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CABEZA Marisa
Departamento de Farmacia, Facultad de Quimica, UNAM, Ciudad Universitaria
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Valdez David
Department Of Pharmacy Faculty Of Chemistry National University Of Mexico City
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Bratoeff Eugene
Department Of Pharmacy Faculty Of Chemistry National University Of Mexico City
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Cabeza M
Departments Of Biological Systems And Animal Production Metropolitan University-xochimilco
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Cabeza Marisa
Departamento De Farmacia Facultad De Quimica Unam Ciudad Universitaria
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HEUZE Ivonne
Departments of Biological Systems and Animal Production, Metropolitan University-Xochimilco
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PEREZ Victor
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City
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OCHOA Martha
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City
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TERAN Nayeli
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City
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JIMENEZ Geidy
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City
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RAMIREZ Teresa
Institute of Chemistry, National University of Mexico City
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Ramirez Teresa
Institute Of Chemistry National University Of Mexico City
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Jimenez Geidy
Department Of Pharmacy Faculty Of Chemistry National University Of Mexico City
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Perez Victor
Department Of Pharmacy Faculty Of Chemistry National University Of Mexico City
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Heuze Ivonne
Departments Of Biological Systems And Animal Production Metropolitan University-xochimilco
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Teran Nayeli
Department Of Pharmacy Faculty Of Chemistry National University Of Mexico City
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Ramirez Elena
Departamento De Farmacia Facultad De Quimica Unam Ciudad Universitaria
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Ochoa Martha
Department Of Pharmacy Faculty Of Chemistry National University Of Mexico City
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Bratoeff Eugene
Departamento De Farmacia Facultad De Quimica Unam Ciudad Universitaria
関連論文
- Crystal Structure and Synthesis of 17α-(5-Chlorovaleroyloxy)-16β-methylpregna-4,6-diene-3,20-dione
- Crystal Structure and Synthesis of 17α-Acetoxy-4-bromopregn-4-ene-3, 20-dione
- Crystal Structure and Synthesis of 17α-Hexanoyloxy-16β-methylpregna-4,6-diene-3,20-dione
- Crystal Structure and Synthesis of 17α-(5-Bromovalerayloxy)-16β-methylpregna-4,6-diene-3,20-dione
- Crystal Structure of 17-β-Benzoyloxy-16-β-methylpregna-4,6-diene-3,20-dione
- Crystal Stucture of 17α-Acetoxy-6-chloro-16β-methyl-4, 6-pregnadiene-3, 20-dione
- Synthesis and Pharmacological Evaluation of New Progesterone Esters as 5α-Reductase Inhibitors
- Novel 17 Substituted Pregnadiene Derivatives as 5α-Reductase Inhibitors and Their Binding Affinity for the Androgen Receptor
- Molecular Interactions of New Pregnenedione Derivatives
- 5α-Reductase Inhibitory and Antiandrogenic Activities of Novel Steroids in Hamster Seminal Vesicles
- Synthesis and Pharmacological Evaluation of New 16-Methyl Pregnane Derivatives
- New Progesterone Esters as 5α-Reductase Inhibitors
- Evaluation of New Pregnane Derivatives as 5α-Reductase Inhibitor
- Synthesis and Pharmacological Evaluation of 4-Halo Progesterone Derivatives as Antiandrogen
- Antiandrogenic Effect of 16-Substituted, Non-substituted and D-Homopregnane Derivatives