Evaluation of New Pregnane Derivatives as 5α-Reductase Inhibitor

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概要

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• The objective of this study was to synthesize several new pregnane derivatives and evaluate them as antiandrogens. From the commercially available 16-dehydropregnenolone acetate(7), two new steroidal compounds were synthesized : 17α-hydroxy-17β-methyl-16β-phenyl-D-homoandrosta-1, 4.6-triene-3, 20-dione(18)and 17α-acetoxy-17β-methyl-16β-phenyl-D-homoandrosta-1, 4.6-triene-3, 20-dione(18)and 17α-acetoxy-17β-methyl-16β-phenyl-D-homoandrosta-1, 4.6-triene-3, 20-dione(19). The 5α-reductase inhibitory effect of the new compounds 18 and 19 together with the previously synthesized intermediates 7, 8, 13, 16, and 17 was determined in three different models : gonadectomized hamster flank organs diameter size, incorporation of[1, 2-^14C]sodium acetate into lipids in flank organs and conversion of[^3H]testosterone(T)to[^3H]dihydrotestosterone(DHT)by Penicillium crustosum. The evaluation of these steroids was carried out with three different controls : one group was treated with vehicle, the second with T and the third group with T plus finasteride. The pharmacological results from this work demonstrated that T significantly increase the diameter of the pigmented spot on the flank organs(p<0.05)as well as the incorporation of labeled sodium acetate into lipids in gonadectomized hamster flank organs(from 0.125 to 0.255nmol per gland). In this study we also observed that broth of Penicilium crustosum converted[^3H]T to[^3H]DHT in a manner comparable to that of the flank organs. All experiments indicated that finasteride as well as steroids 7, 8, 13, 16-19 reduced significantly the conversion of T to DHT in P. crustosum. These compounds also decrease the size of the pigmented spot in the flank organs as well as reducing the incorporation of radiolabeled sodium acetate into lipids ; T and the control sample(treated with vehicle only)were used for comparison. Apparently the presence of the 4, 6-diene-3, 20-dione moiety and also the C-17 ester group produce a higher inhibitory effect on the parameters used. PPThe data from this study indicated also that the three models used for the pharmacological evaluation exhibited comparable results.

• 公益社団法人日本薬学会の論文
• 2001-05-01

著者

• Ramirez Elena

  Department Of Pharmacy Faculty Of Chemistry National University Of Mexico City

• CABEZA Marisa

  Departamento de Farmacia, Facultad de Quimica, UNAM, Ciudad Universitaria

• Bratoeff Eugene

  Department Of Pharmacy Faculty Of Chemistry National University Of Mexico City

• Cabeza M

  Departments Of Biological Systems And Animal Production Metropolitan University-xochimilco

• Cabeza Marisa

  Departamento De Farmacia Facultad De Quimica Unam Ciudad Universitaria

• HEUZE Ivonne

  Departments of Biological Systems and Animal Production, Metropolitan University-Xochimilco

• BRATOEFF Eugene

  Faculty of Chemistry, National University of Mexico D.F.

• Heuze Ivonne

  Departments Of Biological Systems And Animal Production Metropolitan University-xochimilco

• Marti^^'nez Rosa

  Faculty Of Chemistry National University Of Mexico D.f.

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

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