(1R,2S,7S,10S,11R)-7,11-dimethyl-6-oxatetracyclo[8.8.0.0^{2,7}.0^{11,16}]octadeca-12,15-diene-5,14-dione

• ChemBase编号: 770
• 分子式: C19H24O3
• 平均质量: 300.39206
• 单一同位素质量: 300.17254463
• SMILES: O1[C@@]2([C@H]([C@H]3[C@@H]([C@@]4(C(=CC(=O)C=C4)CC3)C)CC2)CCC1=O)C
• Canonical SMILES: O=C1C=C[C@]2(C(=C1)CC[C@@H]1[C@@H]2CC[C@]2([C@H]1CCC(=O)O2)C)C
• InChI: InChI=1S/C19H24O3/c1-18-9-7-13(20)11-12(18)3-4-14-15(18)8-10-19(2)16(14)5-6-17(21)22-19/h7,9,11,14-16H,3-6,8,10H2,1-2H3/t14-,15+,16+,18+,19+/m1/s1
• InChIKey: BPEWUONYVDABNZ-DZBHQSCQSA-N

名称和登记号

名称

• IUPAC标准名: (1R,2S,7S,10S,11R)-7,11-dimethyl-6-oxatetracyclo[8.8.0.0^{2,7}.0^{11,16}]octadeca-12,15-diene-5,14-dione; (1R,2S,7S,10S,11R)-7,11-dimethyl-6-oxatetracyclo[8.8.0.0^2,^7.0^1^1,^1^6]octadeca-12,15-diene-5,14-dione
• IUPAC传统名: testolactone
• 商标名: Fludestrin; Teolit; Teslac; Teslak; Testolacton
• 别名: Testolactona [INN-Spanish]; Testolactonum [INN-Latin]; Testolattone [Dcit]; Testolactone; (4aS,4bR,10aR,10bS,12aS)-3,4,4a,5,6,10a,10b,11,12,12a-decahydro-10a,12a-dimethyl-2H-phenanthro[2,1-b]pyran-2,8(4bH)-dione; Δ1-Testolactone; Δ1-Testololactone; 13-Hydroxy-3-oxo-13,17-secoandrosta-1,4-dien-17-oic Acid δ-Lactone; D-Homo-17a-oxaandrosta-1,4-diene-3,17-dione; 1,2-Dehydrotestololactone; 1,2-Didehydrotestololactone; 1-Dehydrotestololactone; Δ1-Dehydrotestololactone; 17a-Oxa-D-homo-1,4-androstadiene-3,17-dione; Fludestrin; NSC 23759; SQ 9538; Teolit; Teslac; Teslak; Testolacton; Δ1-Testolactone

登记号

• CAS号: 968-93-4
• PubChem SID: 160964233; 46508076
• PubChem CID: 13769

理论计算性质

JChem

• Acid pKa: 18.836205
• 质子受体: 2
• 质子供体: 0
• LogD (pH = 5.5): 3.2313275
• LogD (pH = 7.4): 3.2313275
• Log P: 3.2313275
• 摩尔折射率: 85.791 cm^3
• 极化性: 33.16237 Å^3
• 极化表面积: 43.37 Å^2
• 可自由旋转的化学键: 0
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.33
• LOG S: -4.12
• 溶解度: 2.30e-02 g/l

分子性质

理化性质

• 溶解度: Chloroform; Slightly soluble (27.4 mg/L)
• 外观: White Solid
• 熔点: 221-223°C
• 疏水性(logP): 3.7

详细说明

DrugBank - DB00894

• Drug Groups: approved
• Description: An antineoplastic agent that is a derivative of progesterone and used to treat advanced breast cancer. [PubChem]
• Indication: For palliative treatment of advanced breast cancer in postmenopausal women.
• Pharmacology: Testolactone is a synthetic anti-neoplastic agent that is structurally distinct from the androgen steroid nucleus in possessing a six-membered lactone ring in place of the usual five-membered carbocyclic D-ring. Despite some similarity to testosterone, testolactone has no in vivo androgenic effect. No other hormonal effects have been reported in clinical studies in patients receiving testolactone.
• Toxicity: Oral LD₅₀s in mouse and dog are 1630 mg/kg and 593-926 mg/kg, respectively.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Metabolized to several derivatives in the liver, all of which preserve the lactone D-ring.
• Absorption: Testolactone is well absorbed from the gastrointestinal tract.
• Protein Binding: ~85%
• Elimination: No clinical effects in humans of testolactone on adrenal function have been reported; however, one study noted an increase in urinary excretion of 17-ketosteroids in most of the patients treated with 150 mg/day orally. It is metabolized to several derivatives in the liver, all of which preserve the lactone D-ring. These metabolites, as well as some unmetabolized drug, are excreted in the urine.
• External Links: RxList; Drugs.com

Toronto Research Chemicals - T154800

Antineoplastic; non-selective steroidal aromatase inhibitor that prevents the conversion from androgen to estrogen. Used in in the treatment of familial male precocious puberty. An effective anti-tumor agent.

参考文献

• Dunkel, L.: Mol. Cell. Endocrinol., 254, 207 (2006)
• Eugster, E. A.: Treat. Endocrinol., 3, 141 (2006)
• Holbeck, S.L. et al.: Mol. Cancer Therap., 9, 1451 (2006)