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1.
J Med Chem ; 17(8): 898-900, 1974 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-4845383

RESUMO

PIP: 14 6-substituted-Delta6-16-methylene-17alpha-hydroxy-4,6-prenadiene-3, 20-dione 17-acetate derivatives were analyzed by multiparameter regression techniques for quantitative structure-activity relationships. The parameters were published values for hydrophobic bonding power (pi), inductive effect (F), resonance effect (R), and molar refraction of the substituent (MR); the activity was progestational activity by Clauberg test. Least squares analysis showed that pi gave the best fit with single parameters. With 2 parameters, pi and F accounted for 69% of the variance. F and pi squared gave the best 3-term results, suggesting that pi values up to .50 permit the maximum progestational activity, but perhaps larger substituents decrease activity. The 6-methyl derivative was an exception, having 4 standard deviations' higher activity than computed by the 3-term equation, pointing to unusual metabolism.^ieng


Assuntos
Pregnadienos/síntese química , Progesterona , Progestinas/síntese química , Cetosteroides/síntese química , Cinética , Análise de Regressão , Relação Estrutura-Atividade
2.
J Med Chem ; 22(10): 1257-60, 1979 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-513073

RESUMO

The preparation of 7 beta-methyl-5 alpha-dihydrotestosterone acetate and its 2-thia-A-nor analogue is described. Biological evaluation shows that a 7 beta-Me largely decreases myotrophic-androgenic activity in both 5 alpha-dihydrotestosterone and the 2-thia-A nor analogue. Testing for antitumor activity shows that the reduction in breast tumor weight was not significant for either compound, but the final tumor size in the animals treated with 7 beta-methyl-2-thia-A nor steroid at 10 (mg/kg)/day was significantly reduced. The effects of 7 beta-Me steroids on the various organ weights are also described. The influence of 7 beta-Me substituent on the biological activities of androgens may be mediated through direct interaction of the substituent with the receptor surface in contact with the third dimension of the steroid molecule.


Assuntos
Esteroides/síntese química , Androgênios/síntese química , Animais , Antineoplásicos/síntese química , Feminino , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Tamanho do Órgão/efeitos dos fármacos , Ratos , Esteroides/farmacologia
3.
J Med Chem ; 22(1): 119-20, 1979 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-423176

RESUMO

The synthesis of N-cyano-2-aza-A-nor-5alpha-androstan-17beta-ol acetate is described. Cyclization of 1,4-dibromo-1,4-seco-2,3bisnor-5alpha-androstan-17beta-ol acetate with benzylamine in the presence of potassium iodide gives the N-benzyl-2-aza-A-nor steroid. Debenzylation with cyanogen bromide (Von Braun reaction) affords the N-cyano-2-aza-A-nor steroid, which has androgenic activity slightly weaker than that of the corresponding thia compound. The results indicate that NCN may be substituted for--S--as well as for =S. This compound is the first hormonally active steroid containing nitrogen as a heteroatom in the perhydrocyclopentanophenanthrene nucleus.


Assuntos
Azasteroides/síntese química , Esteroides Heterocíclicos/síntese química , Congêneres da Testosterona/síntese química , Androstanos/síntese química , Androstanos/farmacologia , Animais , Azasteroides/farmacologia , Masculino , Músculos/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Ratos , Relação Estrutura-Atividade
4.
J Med Chem ; 20(9): 1139-46, 1977 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-926114

RESUMO

Relationships between chemical structure of androst-4-en-3-one derivatives and their affinity for putative progesterone receptors are described. The binding affinity for 55 derivatives can be expressed by the equation log relative binding affinity (rabbit receptor) = 1.79 + 0.18 (+/-0.11) pia + 1.45 (+/-0.21) pib + 0.010 (+/-0.002) (surface area in hydrophobic pockets) - 0.012 (+/-0.003) (surface area out of hydrophobic pockets) - 0.99 (+/-0.21) MK - 0.33 (+/-0.08) (conformational changes). For this equation, r=0.88. The equation successfully predicts the affinities of other compounds in the literature. The importance of the surface area terms is discussed.


Assuntos
Receptores de Progesterona , Esteroides , Androstenos , Animais , Cobaias , Humanos , Hidroxiprogesteronas , Ligação Proteica , Coelhos , Receptores de Progesterona/metabolismo , Ovinos , Esteroides/metabolismo , Relação Estrutura-Atividade
5.
Steroids ; 34(3): 361-4, 1979 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-494372

RESUMO

Using benzyl alcohol as a hydrogen donor in the presence of Pd on charcoal, 7-methyl-6-dehydrotestosterone acetate was selectively reduced to 7 beta-methyltestosterone acetate in 90% yield. The addition of hydrogen atoms to the 6, 7 double bond proceeded from the less hindered alpha-face of the steroid molecule, giving rise to the 7 beta-methyl product. Gas chromatograph analysis indicated small amounts of the 7 alpha-methyl epimer, 7 beta-methyl-5 alpha-dihydrotestosterone acetate and the 5 beta-epimer. The 6,7 double bond was hydrogenated in preference to 4,5 double bond, although both are trisubstituted.


Assuntos
Di-Hidrotestosterona/análogos & derivados , Metiltestosterona/síntese química , Álcoois Benzílicos , Fenômenos Químicos , Química , Métodos , Oxirredução
6.
Steroids ; 34(5): 589-95, 1979 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-516119

RESUMO

The crystal and molecular structure of 1,2-seco-A-bisnor-5 alpha-androstan-17beta-ol acetate has been determined to evaluated the conformational importance of the intact steroid nucleus. The resulting tricyclic compound retains nearly the same steric profile for the remainder of the molecule when compared to the structures of dihydrotestosterone derivatives with intact A-rings. This may help to explain why these types of molecules retain a significant level of androgenic activity.


Assuntos
Androstanóis , Congêneres da Testosterona , Cristalografia , Modelos Químicos , Conformação Molecular
13.
J Med Chem ; 14(2): 164-7, 1971 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-5544406
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