Steroids inhibitor

Spotts, R. A., F. L. Lukezic, and N. L. Lacasse. The effect of benzimidazole, cholesterol, and a steroid inhibitor on leaf sterols and ozone resistance of bean. Phytopathology 65 45-49, 1975. 

The effect of ketoconazole appears to be mediated by inhibition of adrenal 11-P-hydroxylase and 17,20-lyase, and in some unknown way it prevents the expected rise in ACTH secretion in patients with Cushing s disease (SEDA-12, 228) (SEDA-17, 323). It may, however, cause such a rapid reduction in serum cortisol concentrations that a crisis is precipitated, and patients adrenal function should be carefully monitored. While ketoconazole (400-800 mg/ day) may be a good alternative to other adrenal steroid inhibitors, patients should be observed for signs of hepato-toxicity. Acute adrenal crisis occasionally occurs (586). 

Oral 0.1 mg tablets Adrenal Steroid Inhibitors Aminoglutethimide (Cytadren)... 

The prototypical steroidal inhibitor of aromatase (the enzyme required for estrogen synthesis) is testolactone. It is a weak inhibitor of the enzyme, and large quantities need to be administered to achieve clinical effect. 

In the fields of allergy and respiration, examples include 2-oxo-3-aminoazepine derivatives which act as dual neurokinin (tachykinin) NK1/NK2 receptor probes for development of options for treatment of asthsma and other airway diseases <07BMCL890> and benzo[l, 5]diazepine derivatives as new non-steroidal inhibitors of 17-P-hydroxysteroid dehydrogenase, an enzyme associated with hormone-dependent and neuronal diseases <07JEIMC29>. 

In contrast to the other members of the PDE family, PDE1 is unique in its ability to interact with calmodulin. As would be expected therefore, this interaction can also be the target of potential inhibitors. This appears to be so for some natural-product inhibitors of PDE1 isolated from ginseng root. The ginsenosides Rb, Rc, and Re are moderately active (5-15 pM) steroidal inhibitors of CaM PDE isolated... 

The substrate arachidonic aeid, whieh often leads to formation of inflammatory prostaglandins, is stored in tissues as one of a number of phospholipids these compounds, as the name indicates, comprise complex phosphate-containing esters. The antiinflammatory corticosteroids inhibit the action of the enzyme, phospholipase A2, that frees arachidonic acid. The many undesired effects of those steroids has led to the search for non-steroidal inhibitors of that enzyme. A highly substituted indole derivative has shown good activity as a phospholipase A2 inhibitor. Alkylation of the anion from treatment of indole (32) with benzyl chloride affords the corresponding A-benzylated derivative (33). The methyl ether at the 4 position is then cleaved by means of boron tribromide to yield 34. Alkylation of the enolate from reaction of the phenol with sodium hydride with tert-butylbromoacetate affords the corresponding... 

Initial attempts to develop aromatase inhibitors for use in the treatment of oestrogen-dependent breast cancer involved the use of synthetic steroid analogues of the natural substrates androstenedione and testosterone [53]. Such steroidal inhibitors are reviewed in on p. 272. An alternative approach to the design of aromatase inhibitors was suggested by the discovery [54-56]... 

Non-steroidal and steroidal inhibitors of high potency against aromatase have been developed over the past few years. The rational design of compounds, utilizing proposed mechanistic aspects of the enzyme, has resulted in both reversible and irreversible inhibitors capable of inactivating the target enzyme. 

Powerful competitive steroid inhibitors of aromatase have been synthesized by replacing the C-19 methyl with sulfur- or nitrogen-containing functions that can coordinate to the heme iron (e.g.. Figure 7.31) The 19-methyl substituents include the following CHjSCH... 

The 19-suhstituted analog of androst-4-ene-3, 17 dione steroid inhibitors, Org-30958 [19-(ethyldithio)androst-4-ene-3,17-dione], has been assessed in Phase I clinical trials for estrogen-dependent breast cancer chemotherapy . The ethyldithio substitution apparently renders the steroid more stable extracellularly than the free thiol Org-30365 (19-mercapto-androst-4-ene-3,... 

Jarman, M., S.E. Barrie, and J.M. Llera (1998). The 16,17-double bond is needed for irreversible inhibition of human cytochrome P45017alpha by abiraterone (17-(3-pyridyl)androsta-5, 16-dien-3beta-ol) and related steroidal inhibitors. J. Med. Chem. 41, 5375-5381. 

A number of steroidal inhibitors have been studied, primarily with the goal of treating cancers" " . The enantiomer of progesterone (ent-progesterone) is reported to be a competitive inhibitor of P450 17A (A j = 0.2 jlM) . ... 

M.G. Rowlands (1995). Novel steroidal inhibitors of human cytochrome P45017a (17a-hydroxylase-C 7 Potential agents for the... 

A. Palusczak, M. Palzer, V Huch et al. (2000). Synthesis and evaluation of 17-aliphatic hetero-cycle-substituted steroidal inhibitors of 17a-hydroxylase/C 17-20-lyase (P450 17). J. Med. Chem. 43, 4437-4445. 

Einasteride Steroid inhibitor of 5a-reductase inhibits synthesis of dihydrotestosterone. 

Aminoglut et himide (Cytadren) [Adrenal Steroid Inhibitor]... 

Barrie SE, Potter GA, Goddard PM, et al. Pharmacology of novel steroidal inhibitors of cytochrome P45017a (17p-hydroxylase/C17-20 lyase). J Steroid Biochem Mol Biol 1994 50 267-273. 

There were only three examples of natural products that mechanistically are Ras competitive inhibitors of FPTase. These include the pentapeptide pepticinnamins, and the terpenoids cembranolide and clavaric acid. There was no surprise about the Ras competitive activity of pepticinnamins but the Ras competitive activities of cembranolide and clavaric acid were certainly surprising. Clavaric acid led to the discoveries of a number of steroidal inhibitors that were competitive with either of the two substrates. 

Quest for steroidal inhibitors which discriminate between isoenzymes 145... 

QUEST FOR STEROIDAL INHIBITORS WHICH DISCRIMINATE BETWEEN... 

---