Metyrapone

Base Information

• Chemical Name: Metyrapone
• CAS No.: 54-36-4
• Deprecated CAS: 37245-80-0
• Molecular Formula: C14H14 N2 O
• Molecular Weight: 226.278
• Hs Code.: 2933399090
• European Community (EC) Number: 200-206-2
• NSC Number: 760076,25265
• UNII: ZS9KD92H6V
• DSSTox Substance ID: DTXSID1023314
• Nikkaji Number: J1.369B
• Wikipedia: Metyrapone
• Wikidata: Q821641
• NCI Thesaurus Code: C47619
• RXCUI: 6923
• Pharos Ligand ID: MCCG1ACQPY4M
• Metabolomics Workbench ID: 43257
• ChEMBL ID: CHEMBL934
• Mol file: 54-36-4.mol

Synonyms:Métopirone;Methbipyranone;Methopyrapone;Metopiron;Metopirone;Metyrapone;SU 4885

Chemical Property of Metyrapone

Chemical Property:

• Vapor Pressure: 4.11E-06mmHg at 25°C
• Melting Point: 52-55 °C(lit.)
• Refractive Index: 1.6419 (estimate)
• Boiling Point: 384.4°Cat760mmHg
• PKA: 4.61±0.10(Predicted)
• Flash Point: 189.3°C
• PSA: 42.85000
• Density: 1.12g/cm³
• LogP: 2.63710
• Storage Temp.: Store at +4°C
• Solubility.: H2O: soluble (sparingly)
• XLogP3: 2
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 226.110613074
• Heavy Atom Count: 17
• Complexity: 275

Purity/Quality:

Metyrapone ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)(C1=CN=CC=C1)C(=O)C2=CN=CC=C2
• Recent ClinicalTrials: Effects of Metyrapone in Patients With Hypercortisolism
• Recent EU Clinical Trials: Investigating cardiometabolic risk factors and changes in chronobiology patterns in patients with autonomous adrenal cortisol secretion
• Description: Metyrapone (54-36-4) inhibits cytochrome P450-mediated prostaglandin omega hydroxylation. Inhibits steroid 11β-hydroxylase thereby inhibiting cortisol biosynthesis.
• Uses: Metyrapone acts as a glucocorticoid synthesis inhibitor, maintaining stress-hormone levels. Diagnostic aid (pituitary function);steroid 11?-hydroxylase inhibitor glucocorticoid synthesis inhibitor
• Therapeutic Function: Diagnostic aid (pituitary function)
• Clinical Use: Metyrapone is used in the differential diagnosis of both adrenocortical insufficiency and Cushing’s syndrome (hypercortisolism). The drug tests the functional competence of the hypothalamic–pituitary axis when the adrenals are able to respond to corticotrophin; that is, when primary adrenal insufficiency has been ruled out. After metyrapone administration, a patient with a disease of pituitary origin cannot achieve a compensatory increase in the urinary excretion of 17-hydroxycorticosteroids or 11-deoxysteroids. Moreover, if pituitary corticotrophin is suppressed by an autonomously secreting adrenal carcinoma, there will be no increase in response to metyrapone. On the other hand, if pituitary corticotrophin secretion is maintained, as occurs in adrenal hyperplasia, the inhibition of corticoid synthesis produced by metyrapone will stimulate corticotrophin secretion and the release of metabolites of precursor urinary steroids, which can be measured as 17-hydroxycorticosteroids. Metyrapone is now used less frequently in the differential diagnosis of Cushing’s syndrome because of the ability to measure plasma corticotrophin directly. The steroid-inhibiting properties of metyrapone have also been used in the treatment of Cushing’s syndrome, and it remains one of the more effective drugs used to treat this syndrome. However, the compensatory rise in corticotrophin levels in response to falling cortisol levels tends to maintain adrenal activity.This requires that glucocorticoids be administered concomitantly to suppress hypothalamic–pituitary activity. Although metyrapone interferes with 11β- and 18- hydroxylation reactions and thereby inhibits aldosterone synthesis, it may not cause mineralocorticoid deficiency because of the compensatory increased production of 11-desoxycorticosterone.

Technology Process of Metyrapone

There total 9 articles about Metyrapone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 38.0%

meso-2,3-di-(3-pyridyl)-2,3-butanediol → metyrapone (54-36-4) + 3,3-di-pyridin-3-yl-butan-2-one (33977-49-0) + 3,3'-(1,2-bis-methylene-ethane-1,2-diyl)-bis-pyridine (96953-46-7) + (Z)-2,3-Di-pyridin-3-yl-4-sulfooxy-but-2-ene-1-sulfonic acid; compound with ammonia

Guidance literature:

With sulfuric acid; for 70h; Further byproducts given;

DOI:10.1016/S0040-4039(02)00243-5

Reference yield:

3-Bromopyridine (626-55-1,163928-56-1) + 2-methyl-1-(pyridin-3-yl)propan-1-one (51227-29-3) → metyrapone (54-36-4)

Guidance literature:

With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In tetrahydrofuran; for 3.5h; Inert atmosphere; Reflux;

Reference yield:

methyl-3-pyridylketone (350-03-8) → metyrapone (54-36-4)

Guidance literature:

Multi-step reaction with 2 steps

1: isopropyl alcohol; acetic acid / Einwirkung von UV-Licht

2: concentrated H₂SO₄

With sulfuric acid; acetic acid; isopropyl alcohol;

DOI:10.1021/ja01524a050

upstream raw materials:

2,3-di-3-pyridyl-2,3-butanediol

methyl-3-pyridylketone

3-Bromopyridine

2-methyl-1-(pyridin-3-yl)propan-1-one

Downstream raw materials:

2-Methyl-1-<3'-(1'-oxopyridyl)>-2-(3''-pyridyl)-propan-1-one

2-Methyl-2-<3''-(1''-oxopyridyl)>-1-(3'-pyridyl)-propan-1-one

2-Methyl-1,2-bis-3-(1-oxopyridyl)propan-1-one

3-(1-methylethenyl)pyridine

Refernces

Deoxy-cytochalasins from a marine-derived fungus Spicaria elegans

10.1139/V09-006

This research aimed to discover new bioactive secondary metabolites from marine fungi, specifically focusing on the marine-derived fungus Spicaria elegans. The study sought to isolate cytochalasins, which are known for their cytotoxic properties against cancer cell lines. To achieve this, the researchers treated Spicaria elegans with the cytochrome P-450 inhibitor metyrapone, leading to the discovery of two new deoxy-cytochalasins, 7-deoxy-cytochalasin Z7 (1) and 7-deoxy-cytochalasin Z9 (2), which were identified as plausible precursors of cytochalasins Z7 and Z9, respectively. The structures of these compounds were elucidated using spectroscopic methods, and the absolute configuration of compound 1 was determined by the conventional Mosher ester method. The cytotoxicities of the compounds were evaluated against two cancer cell lines, A-549 and P-388. Key chemicals used in the process included metyrapone as the P-450 inhibitor, (S)- and (R)-α-methoxy-α-trifluoromethyl-α-phenylacetic acid (MTPA) for the determination of absolute configuration, and the MTT assay for cytotoxicity evaluation. The results indicated that the biosynthetic oxidation at the 7 position of cytochalasins was due to cytochrome P-450, and that the double bond at C-6,7 in compounds 1 and 2 resulted in significantly weaker cytotoxicity compared to cytochalasins Z7 and Z9.