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1.
Arch Pharm (Weinheim) ; 357(7): e2300651, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38570819

RESUMO

A series of D-ring modified steroids bearing a vinyl ketone pendant were synthesized and evaluated for antiproliferative activity against breast cancer cell line and cytochromes P450. The lead compound, 21-vinyl 20-keto-pregnene (2f) (IC50 = 2.4 µM), was shown to be a promising candidate for future anticancer drug design, particularly against estrogen receptor α (ERα)-positive breast cancer. The lead compound was found to have a significant effect on the signaling pathways in parental and 4-hydroxytamoxifen-resistant cells. Compound 2f modulated the ERK, cyclin D1, and CDK4 pathways and blocked the expression of ERα, the main driver of breast cancer growth. Compound 2f significantly reduced 17ß-estradiol-induced progesterone receptor expression. Accumulation of cleaved poly(ADP-ribose) polymerase in cells treated with compound 2f indicated induction of apoptosis. The selectivity analysis showed that lead compound 2f produces no significant effects on cytochromes P450, CYP19A1, CYP21A2, and CYP7B1.


Assuntos
Antineoplásicos , Neoplasias da Mama , Proliferação de Células , Receptor alfa de Estrogênio , Transdução de Sinais , Humanos , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Pregnenos/farmacologia , Pregnenos/síntese química , Pregnenos/química , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Estrutura Molecular , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos de Vinila/farmacologia , Compostos de Vinila/síntese química , Compostos de Vinila/química
2.
Org Lett ; 23(6): 2248-2252, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33635666

RESUMO

The total synthesis of (+)-03219A, a rare Δ8,9-pregnene isolated from the marine-derived Streptomyces sp. SCSIO 03219, is described that is based on a series of transformations that enable progression from epichlorohydrin to an ent-estrane, then conversion to a nat-androstane, and finally establishment of the natural product target. Key to the success of these studies was implementation of two rearrangement processes to formally invert the quaternary center at C13 and establish the C10 quaternary center.


Assuntos
Androstanos/síntese química , Estranos/química , Pregnenos/síntese química , Streptomyces/química , Androstanos/química , Estrutura Molecular , Pregnenos/química , Streptomyces/isolamento & purificação
3.
Bioorg Chem ; 108: 104690, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33592485

RESUMO

Novel withangulatin A (WA) derivatives were synthesized and evaluated for antiproliferative activity against four human cancer cell lines (U2OS, MDA-MB-231, HepG2, and A549). Among these derivatives, 10 exhibited the most potent antiproliferative activity, with an IC50 value of 74.0 nM against the human breast cancer cell line MDA-MB-231 and potency that was 70-fold that of WA (IC50 = 5.22 µM). Moreover, 10 caused G2-phase cell cycle arrest in a concentration-dependent manner and induced the apoptosis of MDA-MB-231 cells by increasing intracellular reactive oxygen species (ROS). Compound 10 showed a high selectivity index (SI = 267.03) for breast cancer MDA-MB-231 cells. These results suggest that 10 is a promising anticancer agent.


Assuntos
Antineoplásicos/síntese química , Pregnenos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Potencial da Membrana Mitocondrial , Pregnenos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
4.
Mol Divers ; 25(2): 661-671, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32006297

RESUMO

New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 9-11, oxadiazole, pyrazole and sulfinyl analogs 13-15, via the hydrazide analog 5 of methyl ((5-pregnen-3ß,17ß-diol-15α-yl)thio)propanoate (4) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0 µM and 91.8%, and of 79.8% at concentration of 1.0 µM, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity.


Assuntos
Antineoplásicos , Pregnenos , Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , Simulação de Acoplamento Molecular , Pregnenos/síntese química , Pregnenos/química , Pregnenos/farmacologia , Receptores Androgênicos/química
5.
Eur J Med Chem ; 210: 112980, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33176943

RESUMO

To develop novel GLS1 inhibitors as effective therapeutic agents for triple-negative breast cancer (TNBC), 25 derivatives were synthesized from the natural inhibitor withangulatin A (IC50 = 18.2 µM). Bioassay optimization identified a novel and selective GLS1 inhibitor 7 (IC50 = 1.08 µM). In MDA-MB-231 cells, 7 diminished cellular glutamate levels by blocking glutaminolysis pathway, further triggering the generation of reactive oxygen species to induce caspase-dependent apoptosis. Molecular docking indicated that 7 interacted with a new reacting site of allosteric binding pocket by forming various interactions in GLS1. The intraperitoneal administration of 7 at a dose of 50 mg/kg exhibited remarkable therapeutic effects and no apparent toxicity in the MDA-MB-231 xenograft model, indicating its potential as a novel GLS1 inhibitor for treatment of TNBC.


Assuntos
Antineoplásicos/farmacologia , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Glutaminase/antagonistas & inibidores , Pregnenos/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Glutaminase/metabolismo , Humanos , Estrutura Molecular , Pregnenos/síntese química , Pregnenos/química , Relação Estrutura-Atividade , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
6.
Drug Dev Res ; 75(2): 76-87, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24648170

RESUMO

The preparation of novel E-salignone derivatives and their biological evaluation as potential antimetastatic agents is described. The E-salignone amide derivatives were prepared from epiandrosterone and androsterone, and characterized by analytical (1) H NMR, (13) C NMR, and mass spectrometry. The derivatives were evaluated for antimetastatic activity in MDA-MB-231 cells by using a transwell assay. Comparing with the positive control, LY294002, compounds 19b, 19d, and 19e exhibited significant inhibitory effects on the EGF-induced invasion of MB-MDA-231 cells. Moreover, compound 19b also had antimigration effects in wound-healing assay. Compound 19b may represent a novel antimetastatic agent for treating breast cancer.


Assuntos
Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/prevenção & controle , Pregnenos/síntese química , Pregnenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Cromonas/farmacologia , Feminino , Humanos , Estrutura Molecular , Morfolinas/farmacologia , Invasividade Neoplásica , Metástase Neoplásica , Pachysandra/química , Pregnenos/química , Pregnenos/isolamento & purificação , Relação Estrutura-Atividade
7.
J Med Chem ; 54(11): 3926-34, 2011 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-21504158

RESUMO

This study addresses the hypothesis that the lack of anesthetic activity for (3α,5α)-3-hydroxypregn-16-ene-11,20-dione (Δ(16)-alphaxalone) is explained by the steroid Δ(16) double bond constraining the steroid 20-carbonyl group to a position that prevents it from favorably interacting with γ-aminobutyric acid type A (GABA(A)) receptors. A series of Δ(16) and Δ(17(20)) analogues of Δ(16)-alphaxalone was prepared to evaluate this hypothesis in binding, electrophysiological, and tadpole anesthesia experiments. The results obtained failed to support the hypothesis. Instead, the results indicate that it is the presence of the C-21 methyl group in Δ(16)-alphaxalone, not the location of the constrained C-20 carbonyl group, that prevents Δ(16)-alphaxalone from interacting strongly with the GABA(A) receptor and having anesthetic activity. Consistent with this conclusion, a Δ(17(20)) analogue of Δ(16)-alphaxalone without a C-21 methyl group was found to be very similar to the anesthetic steroid (3α,5α)-3-hydroxypregnane-11,20-dione (alphaxalone) with regard to time of onset and rate of recovery from anesthesia when administered to mice by tail vein injection.


Assuntos
Anestésicos/química , Pregnanodionas/química , Pregnenos/síntese química , Receptores de GABA-A/metabolismo , Anestesia Intravenosa , Anestésicos/administração & dosagem , Anestésicos/farmacologia , Animais , Larva/efeitos dos fármacos , Camundongos , Estrutura Molecular , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Técnicas de Patch-Clamp , Pregnanodionas/administração & dosagem , Pregnanodionas/farmacologia , Pregnenos/administração & dosagem , Pregnenos/química , Pregnenos/farmacologia , Ratos , Xenopus laevis
8.
Eur J Med Chem ; 45(7): 3063-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20417993

RESUMO

A procedure is described for the preparation of A-homo-5-pregnenes via an acid catalyzed rearrangement of cyclopropylcarbinols assisted by microwave irradiation. 3alpha-Hydroxy and 4alpha-hydroxy-A-homo-5-pregnen-20-one, analogues of the neuroactive steroid allopregnanolone, were obtained by means of a regioselective epoxidation of a double bond in the expanded A-ring, using a fructose-derived chiral ketone as catalyst and oxone as oxidant. Although both these compounds were marginally active in inhibiting TBPS binding to GABA(A) receptors, 3beta-hydroxy-A-homo-5-pregnen-20-one was almost as active as allopregnanolone. Reduction of the double bond of the latter compound resulted in a ten fold loss of activity.


Assuntos
Pregnenos/síntese química , Pregnenos/farmacologia , Receptores de GABA-A/metabolismo , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Hidróxidos/química , Masculino , Micro-Ondas , Modelos Moleculares , Conformação Molecular , Pregnenos/química , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar
9.
Steroids ; 75(12): 801-4, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20206643

RESUMO

A facile synthesis of 21-triazolyl derivatives of pregnenolone and their potential antitumour activity is reported. The scheme involves the transformation of the starting pregnenolone acetate into pregnenolone, conversion of pregnenolone to 21-bromo pregnenolone and finally the one-pot, two-step in situ conversion of the bromo derivative to the 21-triazolyl pregnenolone using the 'click chemistry' approach. These derivatives were screened for their anticancer activity against seven human cancer cell lines. The compounds especially 5a, 5b, 5c, 5e, 5g and 5h exhibited significant anticancer activity with compound 5e as the most active in this study.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Pregnenos/química , Pregnenos/farmacologia , Triazóis/química , Acetileno/química , Antineoplásicos/química , Azidas/química , Catálise , Linhagem Celular Tumoral , Cobre/química , Humanos , Concentração Inibidora 50 , Pregnenos/síntese química , Estereoisomerismo , Especificidade por Substrato
10.
Steroids ; 74(2): 229-32, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19041660

RESUMO

An efficient method to prepare 5, 9-cyclo-1, 11-oxido-pregn-16-ene-3, 20-dione in one pot was reported. Treatment of 9-bromide-11-hydroxypregna-1, 4, 16-trien-3, 20-dione with Raney Ni in absolute ethanol afforded 5, 9-cyclo-1, 11-oxido-pregn-16-ene-3, 20-dione by two annulation reactions in reasonable yield. The absolute configuration was also confirmed by X-ray crystal analysis.


Assuntos
Pregnatrienos/química , Pregnenodionas/química , Pregnenos/síntese química , Cristalografia por Raios X , Halogenação , Pregnenos/química , Estereoisomerismo , Especificidade por Substrato
11.
Bioorg Med Chem Lett ; 18(8): 2558-61, 2008 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-18375119

RESUMO

A series of 7 alpha-aminobisnorsteroids were synthesized and their in vitro antimicrobial activity was evaluated regarding Gram-positive and Gram-negative bacteria. The stereoselective reductive amination of 7-ketosteroid 3 with NH(4)OAc, in the presence of NaBH(3)CN, afforded a high yield of 7 alpha-aminosteroid 4. The 3,7-diaminobisnorsteroids were obtained by the reductive amination of 4 with NH(4)OT(f), Boc-spermidine, and Boc-spermine. 3 alpha,7 alpha-Diaminobisnorsterol dihydrochloride 15 showed the highest antimicrobial activity against Streptococcus pyogenes 308 A with a MIC value of 1.6 microg/mL. Hemolytic activities of the compounds 13-20 were determined. Compound 13 showed MHC value at 100 microg/mL.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Pregnenos/síntese química , Pregnenos/farmacologia , Aminação , Antibacterianos/química , Viabilidade Microbiana/efeitos dos fármacos , Estrutura Molecular , Pregnenos/química , Relação Estrutura-Atividade
12.
Bioorg Khim ; 33(3): 332-6, 2007.
Artigo em Russo | MEDLINE | ID: mdl-17682389

RESUMO

(19R)- and (19S)-tert-Butyldimethylsilyl (TBS) ethers of 19-hydroxy-19-vinyl-16alpha,17alpha-cyclohexanopregn-5-en-20-ones were synthesized. These compounds containing the 1,5-oxydienoic motif were subjected to the anionic oxy-Cope rearrangement to obtain 3beta-TBS ether of 6beta-(3-oxopropyl)-16alpha,17alpha-cyclohexano-19-nor-pregn-5(10)-en-20-one. The structures of the compounds synthesized were confirmed by the analysis of their H and 13C NMR spectra.


Assuntos
Pregnanos/síntese química , Pregnenos/química , Espectroscopia de Ressonância Magnética , Pregnanos/química , Pregnenos/síntese química , Estereoisomerismo
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 27(5): 966-8, 2007 May.
Artigo em Chinês | MEDLINE | ID: mdl-17655115

RESUMO

Three kinds of derivatives, 16alpha, 17alpha-epoxy-6-methylene-pregn-4-ene-3,20-dione(EMPD I), 16alpha, 17alpha-epoxy-6-methyl-pregn-4,6-diene-3,20-dione (EMPD II) and 16alpha, 17alpha-epoxy-6-methyl-pregn-4-ene-3, 20-dione(EMPD III) were synthesized and their FTIR, UV and 1H NMR spectra were described. EMPD II is a novel compound. In the UV spectra, the maximum absorptions peaks of EMPD I, EMPD II and EMPD III are at 259, 287 and 239 nm respectively. Their IR spectra are also obviously different. For EMPD I, there are two absorption peaks, which are respectively at 3084 cm(-1) originated from ==CH2 and 3 030 cm(-1) from C==CH--. For EMPD II and III, there is only one absorption peak at 3054 cm(-1). From 1710-1660 cm(-1), only one absorption peak appears for EMPD III, but two appear for EMPD I and EMPD II. In 1H NMR spectrum, the peaks at 4.92 (s, 1H), 5.06 (s, 1H) and 5.88 (s, 1H) were observed for EMPD I; the peaks at 1.83 (s, 3H), 5.87 (s, 1H) and 5.85 (s, 1H) for EMPD II; while the peaks at 1.06-1.07 (d, 3H), 5.78 ppm (s, 1H, 1 ppm=l nicrog x mL(-1)), for EMPD III.


Assuntos
Compostos de Epóxi/análise , Compostos de Epóxi/síntese química , Espectroscopia de Ressonância Magnética/métodos , Pregnenos/análise , Pregnenos/síntese química , Espectrofotometria/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
14.
Bioorg Med Chem Lett ; 16(13): 3454-8, 2006 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-16644222

RESUMO

Fluoropyridyl derivatives of [3,2-c]pyrazolo-corticosteroids have high affinity for the glucocorticoid receptor (GR) and are highly active glucocorticoids. They are thus considered to be excellent candidates for PET imaging of GR containing tissues when labeled with fluorine-18 (t(1/2)=110 min). Previously reported syntheses of these fluorinated glucocorticoids were accomplished by conventional thermal nucleophilic halogen exchange reactions with chloropyridyl precursors. These reactions were found to proceed at rates too slow for feasible application to radiosynthesis using [(18)F]fluoride. We have applied microwave-heating methods to these reactions and found that significant rate enhancements can be realized. Kinetic experiments showed an average relative rate ratio of 3/1 for microwave versus conventional heating and preparative experiments showed an average relative conversion ratio of 4.5/1 during the initial 120 min, a period approximating one half-life of the isotope. The microwave method described was used to prepare previously unreported 2'-(2-fluoro-4-pyridyl)-11beta,17,21-trihydroxy-16alpha-methyl-20-oxo-pregn-4-eno-[3,2-c]-pyrazole, which was evaluated for biological activity.


Assuntos
Corticosteroides/síntese química , Flúor/química , Pregnenos/síntese química , Pirazóis/síntese química , Piridinas/química , Receptores de Glucocorticoides/efeitos dos fármacos , Corticosteroides/farmacologia , Corticosteroides/efeitos da radiação , Glucocorticoides/química , Glucocorticoides/metabolismo , Cinética , Micro-Ondas , Estrutura Molecular , Tomografia por Emissão de Pósitrons/métodos , Pregnenos/química , Pregnenos/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/efeitos da radiação , Piridinas/efeitos da radiação , Receptores de Glucocorticoides/metabolismo , Sensibilidade e Especificidade , Estereoisomerismo , Relação Estrutura-Atividade
15.
J Med Chem ; 45(24): 5397-405, 2002 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-12431067

RESUMO

Ligands for the glucocorticoid receptor labeled with high-energy isotopes are highly desired for their potential applications in nuclear medical studies of the brain where the dysregulation of this receptor system is thought to be involved in various neurodegenerative disorders. Analogues of the glucocorticoid cortivazol have previously been prepared as target compounds for labeling with high-energy isotopes. However, the phenyl rings of arylpyrazoles of this type are not sufficiently activated for nucleophilic substitution reactions that are generally required for the synthesis of radiohalogenated analogues. Since suitably substituted aromatic nitrogen heterocyclic groups are amenable to nucleophilic substitution, the goal of this study was the synthesis of pyridylpyrazolo and pyrimidylpyrazolo analogues similar to cortivazol that could be labeled with radiohalogens in the pyridine or pyrimidine rings. We describe the synthesis of several [3,2-c]pyrazolo steroids containing pyridyl, halopyridyl, and pyrimidyl substituents at the 2' position of the pyrazole ring. These compounds were tested for binding to the glucocorticoid receptor and for biological activity in glucocorticoid responsive HeLa cells grown in tissue culture. Of the pyridyl and pyrimidyl derivatives, 2'-(3-pyridyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxopregn-4-eno[3,2-c]pyrazole showed superior activity in both assays and it was used as the basis for the synthesis of several analogues that were halogenated in the pyridine ring. These halogenated compounds were all tested for their binding to the glucocorticoid receptor and for their biological activity. One, a fluorinated compound 2'-(2-fluoro-5-pyridyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxopregn-4-eno[3,2-c]pyrazole had excellent activity, considerably better than the potent glucocorticoid dexamethasone. Most importantly, fluorination was achieved using a nucleophilic exchange reaction, a method that is adaptable to radiolabeling with the positron-emitting isotope fluorine-18. Thus, considering its superior biological activity and adaptability for facile radiosynthesis, this target compound has the potential for imaging of glucocorticoid receptor containing tissues using positron emission tomography.


Assuntos
Glucocorticoides/síntese química , Pregnenos/síntese química , Pirazóis/síntese química , Compostos Radiofarmacêuticos/síntese química , Receptores de Glucocorticoides/metabolismo , Fosfatase Alcalina/biossíntese , Animais , Ligação Competitiva , Indução Enzimática , Radioisótopos de Flúor , Glucocorticoides/química , Glucocorticoides/metabolismo , Células HeLa , Humanos , Técnicas In Vitro , Marcação por Isótopo , Ligantes , Pregnenos/química , Pregnenos/metabolismo , Pirazóis/química , Pirazóis/metabolismo , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Ratos
16.
Bioorg Khim ; 28(3): 258-60, 2002.
Artigo em Russo | MEDLINE | ID: mdl-12077852

RESUMO

6-O-(3-Methoxycarbonylpropyl)- and 6-O-(3-carboxypropyl)oximes of 16 alpha,17 alpha-cyclohexanopregn-4-ene-3,6,20-trione labeled by tritium in position 1,2 were synthesized. When using homogenous catalysts, the molar radioactivity of the resulting preparations was 1.5-1.7 PBq/mol.


Assuntos
Cicloexanos/síntese química , Oximas/síntese química , Pregnenos/síntese química , Catálise , Cicloexanos/química , Marcação por Isótopo , Espectroscopia de Ressonância Magnética , Oximas/química , Pregnenos/química , Trítio
17.
Steroids ; 59(12): 696-701, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7900168

RESUMO

A synthesis of (19E)-3 beta,17-dihydroxy-20-oxopregn-5-en-19-al 19-(O-carboxymethyl)oxime (15), is reported. Hydride reduction of ketone 1 gave the (20R)-hydroxy derivative 2 as the main product. Formylation of 2 followed by cleavage of the epoxide ring and mild Jones oxidation afforded aldehyde 6. Oximation with (O-carboxymethyl)hydroxylamine and subsequent methylation yielded methyl ester 8 which was selectively hydrolyzed to alcohol 9 and oxidized to ketone 10. Enolacetylation, epoxidation, and hydrolysis led to the desired 19-(O-carboxymethyl)oxime derivative of 17-hydroxypregnenolone 15.


Assuntos
17-alfa-Hidroxipregnenolona/análogos & derivados , Pregnenos/síntese química , 17-alfa-Hidroxipregnenolona/análise , 17-alfa-Hidroxipregnenolona/síntese química , Biomarcadores/análise , Haptenos
18.
Steroids ; 47(4-5): 249-59, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3590239

RESUMO

Recently several allylic steroids have been found in gonadal and breast tissues. In order to establish their presence and identity in tissues and determine the possible biological properties, a method for the synthesis of 4-pregnene-3 alpha,20 alpha-diol, 4-pregnene-3 alpha, 20 beta-diol, 4-pregnene-3 beta,20 alpha-diol, and 4-pregnene-3 beta,20 beta-diol was developed using 4-pregnene-3,20-dione (progesterone) as substrate and freshly-prepared aluminum isopropoxide in isopropyl alcohol as reducing agent. The yields were about 19%, 30%, 13%, and 38% for the 3 alpha,20 alpha-, 3 alpha,20 beta-, 3 beta,20 alpha-, and 3 beta,20 beta-diols, respectively. The structures and stereochemistry of these diols were established using proton and carbon NMR spectroscopy and infrared and mass spectrometry.


Assuntos
Pregnenos/síntese química , Fenômenos Químicos , Química , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas , Pregnenos/isolamento & purificação , Estereoisomerismo
19.
J Steroid Biochem ; 16(1): 61-7, 1982 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7062740

RESUMO

A new class of modified progesterones with an additional ring in the 16 alpha , 17 alpha-position (pregna-D'-pentaranes) are described. Compounds containing 4- and 6-membered D'-ring (D'4- and D'6-pentaranes) were synthesized by the cycloaddition of acetylene or 1,3-butadiene, respectively, to the conjugated 16-double bond of 16-dehydro-20-keto steroids. The D'3-pentarane was prepared by the addition of diazomethane to the steroidal olefin followed by decomposition of the intermediate 16 alpha , 17 alpha-pyrazoline. The D'5-pentarane was obtained by conventional contraction of cyclohexane D'-ring of the corresponding D'6-pentarane. Progestational and contraceptive activity has been investigated for these compounds. They were found to exhibit a high progestational activity in the McPhail assay and also to be active in the pregnancy maintenance test in ovariectomized rabbits. Some of the D'-pentaranes displayed a remarkable contraceptive effect in combination with mestranol.


Assuntos
Pregnenos/síntese química , Animais , Feminino , Mestranol/farmacologia , Ovulação/efeitos dos fármacos , Pregnenolona/análogos & derivados , Pregnenolona/metabolismo , Progestinas/síntese química , Ratos
20.
Steroids ; 34(6 Spec no): 683-92, 1979.
Artigo em Inglês | MEDLINE | ID: mdl-538775

RESUMO

The compounds named in the title were prepared by routes which included the reduction of suitable 16 alpha,17-epoxypregnan-20-ones with aluminium amalgam to give 16 alpha-hydroxypregnan-20-ones, and reduction of the 20-oxo function either with sodium borohydride to obtain the 3,16 alpha,20 beta-triols or with lithium-liquid ammonia to obtain the 3,16 alpha,20 alpha-triols.


Assuntos
Pregnanotriol/síntese química , Pregnenos/síntese química , Hidroxiesteroides/síntese química , Hidroxiesteroides/urina , Pregnanotriol/urina , Pregnenos/urina , Padrões de Referência , Estereoisomerismo
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