(1S,2R,10R,11S,14R,15S)-14-acetyl-14-hydroxy-2,8,15-trimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-6,8-dien-5-one

• ChemBase ID: 235
• Molecular Formular: C22H30O3
• Molecular Mass: 342.4718
• Monoisotopic Mass: 342.21949482
• SMILES: O[C@]1([C@@]2([C@H]([C@H]3[C@@H]([C@@]4(C(=CC(=O)CC4)C(=C3)C)C)CC2)CC1)C)C(=O)C
• Canonical SMILES: O=C1CC[C@]2(C(=C1)C(=C[C@@H]1[C@@H]2CC[C@]2([C@H]1CC[C@]2(O)C(=O)C)C)C)C
• InChI: InChI=1S/C22H30O3/c1-13-11-16-17(20(3)8-5-15(24)12-19(13)20)6-9-21(4)18(16)7-10-22(21,25)14(2)23/h11-12,16-18,25H,5-10H2,1-4H3/t16-,17+,18+,20-,21+,22+/m1/s1
• InChIKey: VXIMPSPISRVBPZ-NWUMPJBXSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1S,2R,10R,11S,14R,15S)-14-acetyl-14-hydroxy-2,8,15-trimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-6,8-dien-5-one; (1S,2R,10R,11S,14R,15S)-14-acetyl-14-hydroxy-2,8,15-trimethyltetracyclo[8.7.0.0^2,^7.0^1^1,^1^5]heptadeca-6,8-dien-5-one
• IUPAC Traditional name: megestrol
• Brand Name: Magestin; Maygace; Megace; Megeron; Megestat; Megestil; Megestin; Nia; Niagestin; Ovaban; Ovarid; Volidan
• Synonyms: 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione; Megestrol Acetate; Megestrolo [DCIT]; Megestrolum [INN-Latin]; Megestryl acetate; MGA; Megestrol

Database IDs

• CAS Number: 3562-63-8
• PubChem SID: 160963698
• PubChem CID: 1909019090; 19090
• Chemspider ID: 18023
• Wikipedia Title: Megestrol

CALCULATED PROPERTIES

JChem

• Acid pKa: 12.6991005
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 3.2826188
• LogD (pH = 7.4): 3.2826166
• Log P: 3.282619
• Molar Refractivity: 99.5039 cm^3
• Polarizability: 38.614105 Å^3
• Polar Surface Area: 54.37 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.7
• LOG S: -4.52
• Solubility (Water): 1.04e-02 g/l

PROPERTIES

Physical Property

• Solubility: 2 µg/mL (at 37°C for the acetate salt)
• Hydrophobicity(logP): 3.2

DETAILS

DrugBank - DB00351

• Drug Groups: approved
• Description: 17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. [PubChem]
• Indication: For the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). Also used for the palliative management of recurrent, inoperable, or metastatic breast cancer, endometrial cancer, and prostate cancer in Canada and some other countries.
• Pharmacology: Megestrol is a synthetic progestin and has the same physiologic effects as natural progesterone. These effects include induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. Mestrogel has slight glucocorticoid activity and very slight mineralocorticoid activity. This drug has no estrogenic, androgenic, or anabolic activity. The precise mechanism of megestrol’s antianorexic and anticachetic effects is unknown. Initially developed as a contraceptive, it was first evaluated in breast cancer treatment in 1967.
• Toxicity: No serious unexpected side effects have resulted from studies involving megestrol acetate oral suspension administered in dosages as high as 1200 mg/day. Treatment with megestrol acetate, an orexigenic agent, has also resulted in iatrogenic adrenal suppression. The mechanism is presumably related to the glucocorticoid properties of megestrol acetate [PMID: 12872362].
• Affected Organisms: Humans and other mammals
• Biotransformation: Primarily hepatic. Megestrol metabolites which were identified in urine constituted 5% to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces. No active metabolites have been identified.
• Absorption: Variable, but well absorbed orally.
• Half Life: 34 hours
• Elimination: The major route of drug elimination in humans is urine. ; Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces.
• References: Berenstein EG, Ortiz Z: Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004310. [Pubmed] ; Pascual Lopez A, Roque i Figuls M, Urrutia Cuchi G, Berenstein EG, Almenar Pasies B, Balcells Alegre M, Herdman M: Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. J Pain Symptom Manage. 2004 Apr;27(4):360-9. [Pubmed] ; Rao GG, Miller DS: Hormonal therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther. 2006 Jan;6(1):43-7. [Pubmed] ; Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH: Classification and pharmacology of progestins. Maturitas. 2008 Sep-Oct;61(1-2):171-80. [Pubmed] ; Orme LM, Bond JD, Humphrey MS, Zacharin MR, Downie PA, Jamsen KM, Mitchell SL, Robinson JM, Grapsas NA, Ashley DM: Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression. Cancer. 2003 Jul 15;98(2):397-405. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - M208040

Megestrol is an orally active progestogen. Megestrol is used in combinations as oral contraceptive and as antineoplastic agent.

REFERENCES

• Berenstein EG, Ortiz Z: Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004310. Pubmed
• Pascual Lopez A, Roque i Figuls M, Urrutia Cuchi G, Berenstein EG, Almenar Pasies B, Balcells Alegre M, Herdman M: Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. J Pain Symptom Manage. 2004 Apr;27(4):360-9. Pubmed
• Rao GG, Miller DS: Hormonal therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther. 2006 Jan;6(1):43-7. Pubmed
• Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH: Classification and pharmacology of progestins. Maturitas. 2008 Sep-Oct;61(1-2):171-80. Pubmed
• Orme LM, Bond JD, Humphrey MS, Zacharin MR, Downie PA, Jamsen KM, Mitchell SL, Robinson JM, Grapsas NA, Ashley DM: Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression. Cancer. 2003 Jul 15;98(2):397-405. Pubmed
• Dea-Ayuela, M., et al.: Bioorg. Med. Chem., 16, 7770 (2008)
• Santana, L., et al.: J. Med. Chem., 51, 6740 (2008)
• Gonzalez-Diaz, H., et al.: Curr. Pharm. Des., 16, 2737 (2008)