(1S,2R,6R,8S,11S,12S,15S,16S)-5,15-dihydroxy-2,16-dimethyl-7-oxapentacyclo[9.7.0.0^{2,8}.0^{6,8}.0^{12,16}]octadec-4-ene-4-carbonitrile

• ChemBase ID: 979
• Molecular Formular: C20H27NO3
• Molecular Mass: 329.43328
• Monoisotopic Mass: 329.19909373
• SMILES: O1[C@@]23[C@@]([C@@H]4[C@H]([C@H]5[C@](CC4)([C@@H](O)CC5)C)CC3)(CC(=C(O)[C@@H]12)C#N)C
• Canonical SMILES: N#CC1=C(O)[C@@H]2[C@]3([C@@](C1)(C)[C@H]1CC[C@]4([C@H]([C@@H]1CC3)CC[C@@H]4O)C)O2
• InChI: InChI=1S/C20H27NO3/c1-18-7-6-14-12(13(18)3-4-15(18)22)5-8-20-17(24-20)16(23)11(10-21)9-19(14,20)2/h12-15,17,22-23H,3-9H2,1-2H3/t12-,13-,14-,15-,17+,18-,19+,20+/m0/s1
• InChIKey: KVJXBPDAXMEYOA-CXANFOAXSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1S,2R,6R,8S,11S,12S,15S,16S)-5,15-dihydroxy-2,16-dimethyl-7-oxapentacyclo[9.7.0.0^{2,8}.0^{6,8}.0^{12,16}]octadec-4-ene-4-carbonitrile; (1S,2R,6R,8S,11S,12S,15S,16S)-5,15-dihydroxy-2,16-dimethyl-7-oxapentacyclo[9.7.0.0^2,^8.0^6,^8.0^1^2,^1^6]octadec-4-ene-4-carbonitrile
• IUPAC Traditional name: trilostane
• Brand Name: Desopan; Modrastane; Modrenal
• Synonyms: Trilostane; trilostane; (1S,2R,6R,8S,11S,12S,15S,16S)-5,15-dihydroxy-2,16-dimethyl-7-oxapentacyclo[9.7.0.0^{2,8}.0^{6,8}.0^{12,16}]octadec-4-ene-4-carbonitrile; Win-24540, Desopan, Modrastane, Modrenal; (4α,5α,17β)-3,17-dihydroxy-4,5-epoxyandrost-2-ene-2-carbonitrile; Trilostane; Vetoryl

Database IDs

• CAS Number: 13647-35-3
• MDL Number: MFCD00199295
• PubChem SID: 160964442; 46507062
• PubChem CID: 656583

CALCULATED PROPERTIES

JChem

• Acid pKa: 5.2311697
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): 1.8450996
• LogD (pH = 7.4): 0.14754808
• Log P: 2.3007839
• Molar Refractivity: 90.1746 cm^3
• Polarizability: 35.464157 Å^3
• Polar Surface Area: 73.48 Å^2
• Rotatable Bonds: 0
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.41
• LOG S: -3.75
• Solubility (Water): 5.93e-02 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; DMSO: ≥17 mg/mL; Pyridine
• Apperance: Off-White Solid; white to tan powder
• Melting Point: 247-257°C (dec.)
• Hydrophobicity(logP): 2.335; 3

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: hydroxysteroid dehydrogenase

Product Information

• Purity: ≥98% (HPLC); 95%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C20H27NO3

DETAILS

DrugBank - DB01108

• Drug Groups: approved; withdrawn; investigational
• Description: Trilostane is an inhibitor of 3 beta-hydroxysteroid dehydrogenase used in the treatment of Cushing's syndrome. It was withdrawn from the United States market in April 1994. [Wikipedia]
• Indication: Used in the treatment of Cushing's syndrome. It is normally used in short-term treatment until permanent therapy is possible.
• Pharmacology: Trilostane blocks an enzyme involved in the production of several steroids including cortisol. Inhibiting this enzyme inhibits the production of cortisol. In Cushing's syndrome, the adrenal gland overproduces steroids. Although steroids are important for various functions of the body, too much can cause problems. Trilostane reduces the amount of steroids produced by the adrenal gland. This product was withdrawn from the U.S. market in April 1994.
• Toxicity: Symptoms of overdose include darkening of skin, drowsiness or tiredness, loss of appetite, mental depression, skin rash, and/or vomiting.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic.
• Half Life: 8 hours.
• References: Komanicky P, Spark RF, Melby JC: Treatment of Cushing's syndrome with trilostane (WIN 24,540), an inhibitor of adrenal steroid biosynthesis. J Clin Endocrinol Metab. 1978 Nov;47(5):1042-51. [Pubmed]
• External Links: Wikipedia

Selleck Chemicals - S1404

Research Area: Endocrinology
Biological Activity:
Trilostane is an inhibitor of 3 β-hydroxysteroid dehydrogenase used in the treatment of Cushing’s syndrome. It is also the first drug approved to treat both pituitary- and adrenal-dependent Cushing’s in dogs. This prescription drug works by stopping the production of cortisol in the adrenal glands. [1]

Sigma Aldrich - SML0141

Biochem/physiol Actions
Trilostane is an inhibitor of 3 β-hydroxysteroid dehydrogenase (3-β-HSD or delta 5-delta 4-isomerase), an essential enzyme for the biosynthesis of all classes of hormonal steroids. It has been used in the treatment of Cushing′s syndrome for stopping the production of cortisol, and is currently approved for dogs in the US, but is still a human drug in the UK and other countries. It is being investigated as a possible treatment for both breast cancer and prostate cancer to prevent the synthesis of estrogens and androgens from endogenous precursors. It has also been used to inhibit endogenous production of progesterone in research studies.

Toronto Research Chemicals - T795600

An inhibitor of steroid biosynthesis. Used as an adrenocortical suppressant. Used in the treatment of breast cancer.

REFERENCES

• Komanicky P, Spark RF, Melby JC: Treatment of Cushing's syndrome with trilostane (WIN 24,540), an inhibitor of adrenal steroid biosynthesis. J Clin Endocrinol Metab. 1978 Nov;47(5):1042-51. Pubmed
• http://en.wikipedia.org/wiki/Trilostane
• Komanicky, P., et al.: J. Clin. Endocrinol. Metab., 47, 1042 (1978)
• Mori, Y., et al., Chem. Pharm. Bull., 29, 2646 (1978)
• Williams, C.J., et al.: Cancer Treat. Rep., 71, 1197 (1987)