13592-84-2

Upstream product

• 853-23-6 prasterone acetate 
• 68-12-2 N,N-dimethyl-formamide 
• 4394-85-8 4-morpholinecarboxaldehyde 

Relevant academic research and scientific papers

Synthesis and evaluation of novel 17-indazole androstene derivatives designed as CYP17 inhibitors

A series of novel 1H- and 2H-indazole derivatives of the commercially available dehydroepiandrosterone acetate have been synthesized and tested for inhibition of human cytochrome 17α-hydroxylase-C17,20-lyase (CYP17), androgen receptor (AR) binding affinity, and cytotoxic potential against three prostate cancer (PC) cell lines.

Synthesis and biological evaluation of esters of 16-formyl-17-methoxy-dehydroepiandrosterone derivatives as inhibitors of 5α-reductase type 2

In this study, we investigated the in vitro effect of 16-formyl-17-methoxy dehydroepiandrosterone derivatives on the activity of 5α-reductase type 2 (5α-R2) obtained from human prostate. The activity of different concentrations of these derivatives was de

Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17α- hydroxylase-C17,20-lyase (P450(17α)): Potential agents for the treatment of prostate cancer

A new synthetic route to a variety of novel Δ16-17-azolyl steroids is described: it involves the nucleophilic vinylic 'addition-elimination' substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene (2) and azolyl nucleophiles. Some of these novel Δ16-17-azolyl steroids, 6, 17, 19, and 27-29, prepared in good overall yields, are very potent inhibitors of human and rat testicular P450(17α). They are shown to be noncompetitive and appear to be slow-binding inhibitors of human P450(17α). The most potent compounds are 3β-hydroxy-17-(1H-imidazol-1-yl)androsta- 5,16-diene (17), 3β-hydroxy-17-(1H-1,2,3-triazol-1-yl)androsta-5,-16-diene (19), and 17-(1H-imidazol-1-yl)androsta-4,16-dien-3-one (28), with K(i) values of 1.2, 1.4, and 1.9 nM, respectively, being 20-32 times more potent than ketoconazole (K(i) = 38 nM). Spectroscopic studies with a modified form of human P450(17α) indicate that the inhibition process involves binding of steroidal azole nitrogen to the heme iron of the enzyme. Furthermore, some of these potent P450(17α) inhibitors (27-29) are also powerful inhibitors of steroid 5α-reductase, and others (17 and 19) appear to exhibit strong antiandrogenic activity in cultures of the LNCaP human prostatic cancer cell line. These novel compounds with impressive dual biological activities make them strong candidates for development as therapeutic agents for treatment of prostate cancer and other disease states which depend on androgens.

The reaction of azoles with 17-chloro-16-formylandrosta-5,16-dien-3β- yl-acetate: Synthesis and structural elucidation of novel 16-azolylmethylene-17- oxoandrostanes

The synthesis and structural elucidation, by 1D and 2D NMR and X-ray diffraction techniques, of novel E/Z 16-azolylmethylene-17-oxoandrostanes 2-9 prepared from the Vilsmeier-Hack reaction product 17-chloro-16-formylandrosta-5, 16-dien-3β-yl acetate 1 is reported. The reaction proceeds with pyrrole and pyrrole-alike nitrogen heterocycles such as 7-azaindole, indole, and 3-methylindole, in DMF, at 80 °C, in the presence of K2CO 3, and allowed the attachment of privileged heterocyclic moieties, through the nitrogen atom to the steroid core at C16 via a methine carbon bridge, which is unprecedented in the literature and of potential synthetic and biological interest. Considerations on the possible reaction mechanism are included. All the synthesized compounds are new and are currently being tested for biological activities.

NOVEL PRODRUGS OF C-17-HETEROARYL STEROIDAL CYP17 INHIBITORS/ANTIANDROGENS: SYNTHESIS, IN VITRO BIOLOGICAL ACTIVITIES, PHARMACOKINETICS AND ANTITUMOR ACTIVITY

Prodrugs of steroidal C-17 benzoazoles, pyrimidinoazoles (azabenzoazoles) and diazines. Methods of synthesis are also described, whereby a prodrug group is substituted for a functional group at A ring portion of the ABC ring structure of the steroid. Suitable prodrug groups include amino acid groups, succinate groups, phosphate groups, or sulfamate groups. The prodrugs of the disclosed compounds allow for improved oral bioavailability of the compounds that are inhibitors of human CYP 17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds and the corresponding prodrugs are useful for the treatment of conditions such as human prostate cancer, breast cancer, and prostate hyperplasia.

NOVEL C-17-HETEROARYL STEROIDAL CYP17 INHIBITORS/ANTIANDROGENS: SYNTHESIS, IN VITRO BIOLOGICAL ACTIVITIES, PHARMACOKINETICS AND ANTITUMOR ACTIVITY

Described are steroidal C-17 benzoazoles, pyrimidinoazoles (azabenzoazoles) and diazines. Methods for their synthesis are also described, which include methods having a step of nucleophilic vinylic "addition-elimination" substitution reaction of 3F-acetoxy-17-chloro-16-formylandrosta-5,16-diene or analogs thereof and benzoazole or pyrimidinoazole nucleophiles and methods having a palladium catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3F-ol or analogs thereof with tributylstannyl diazines. The compounds are potent inhibitors of human CYP 17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds are useful for the treatment of human prostate cancer. "

The preparation and crystal structure of 16-acetylandrosta-4,16-dien-3-one

Dehydroisoandrosterone was formylated at C-16 by a Vilsmeier reaction and by condensation with methyl formate. The product of the latter reaction was converted to 16-acetylandrosta-4,16-dien-3-one and its X-ray crystal structure was determined.