坎利酮

坎利酮
臨床資料
商品名（英语：Drug nomenclature）	Contaren, Luvion, Phanurane, Spiroletan
其他名稱	Aldadiene; SC-9376; RP-11614; 7α-Desthioacetyl-δ6-spironolactone; 6,7-Dehydro-7α-desthioacetylspironolactone; 17-Hydroxy-3-oxo-17α-pregna-4,6-diene-21-carboxylic acid γ-lactone
AHFS/Drugs.com	国际药品名称
藥物類別（英语：Drug class）	抗鹽皮質激素
ATC碼	C03DA03 (WHO) ;
藥物動力學數據
血漿蛋白結合率	95%
生物半衰期	16.5 hours
识别信息
	IUPAC命名法 10,13-Dimethylspiro[2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-17,5'-oxolane]-2',3-dione; ;
CAS号	976-71-6
PubChem CID	13789;
ChemSpider	13192 ;
UNII	78O20X9J0U;
ChEMBL	ChEMBL1463345 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID3045930 ;
ECHA InfoCard	100.012.322
化学信息
化学式	C22H28O3
摩尔质量	340.46 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES O=C5\C=C4\C=C/[C@@H]1[C@H](CC[C@]3([C@H]1CC[C@]32OC(=O)CC2)C)[C@@]4(C)CC5;
	InChI InChI=1S/C22H28O3/c1-20-9-5-15(23)13-14(20)3-4-16-17(20)6-10-21(2)18(16)7-11-22(21)12-8-19(24)25-22/h3-4,13,16-18H,5-12H2,1-2H3/t16-,17+,18+,20+,21+,22-/m1/s1 ; Key:UJVLDDZCTMKXJK-WNHSNXHDSA-N ;

坎利酮（英語：Canrenone，商品名有：Contaren、Luvion、Phanurane、Spiroletan等），别名坎利酸内酯或烯睾丙内酯。是一种有机化合物，分子式为C₂₂H₂₈O₃，属于甾体类抗鹽皮質激素^[3]^[4]，临床上可用作醛固酮拮抗剂治疗水肿、心衰、高血压、肝腹水等疾病^[5]，在意大利、比利时等国也用作利尿劑^[6]^[7]^[8]^[9]，同时也是螺内酯的活性代謝產物^[10]^[2]。坎利酮可被赭曲霉等微生物发酵作用对11号碳进行羟基化，得到11α-羟基坎利酮^[11]^[5]。坎利酮同时也是螺内酯和依普利酮的原料^[12]。

坎利酮抗鹽皮質激素作用比螺内酯强，但抗雄激素作用要弱于螺内酯^[13]^[14]，不过利用其抗雄激素作用可用于治疗女性多毛症（英语：Hirsutism）^[15]。作为利尿剂，螺内酯转化成系列代谢产物后，坎利酮贡献了约10-25%的保钾利尿作用（英语：Potassium-sparing diuretic），7α-硫代甲基螺内酯（英语：7α-Thiomethylspironolactone）则主要贡献了约80%^[16]^[17]^[18]。

参考文献

^ Müller J. Regulation of Aldosterone Biosynthesis: Physiological and Clinical Aspects. Springer Science & Business Media. 6 December 2012: 164–. ISBN 978-3-642-83120-1.
^ ^2.0 ^2.1 Gardiner P, Schrode K, Quinlan D, Martin BK, Boreham DR, Rogers MS, et al. Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites. Journal of Clinical Pharmacology. April 1989, 29 (4): 342–347. PMID 2723123. S2CID 29457093. doi:10.1002/j.1552-4604.1989.tb03339.x.
^ Losert W, Casals-Stenzel J, Buse M. Progestogens with antimineralocorticoid activity. Arzneimittel-Forschung. 1985, 35 (2): 459–471. PMID 4039568.
^ Fernandez MD, Carter GD, Palmer TN. The interaction of canrenone with oestrogen and progesterone receptors in human uterine cytosol. British Journal of Clinical Pharmacology. January 1983, 15 (1): 95–101. PMC 1427833  . PMID 6849751. doi:10.1111/j.1365-2125.1983.tb01470.x.
^ ^5.0 ^5.1 黄达明，杜卓蓉，张志才，等. 基于正交试验的根霉固态转化坎利酮工艺条件优化. 中国酿造. 2018, 37 (1): 155-160. doi:10.11882/j.issn.0254-5071.2018.01.033.
^ Elks J. The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014: 210–. ISBN 978-1-4757-2085-3.
^ Hill R, Makin H, Kirk D, Murphy G. Dictionary of Steroids. CRC Press. 23 May 1991: 656–. ISBN 978-0-412-27060-4.
^ Romanelli RG, Gentilini P. Cross reactivity due to positive canrenone interference. Gut. May 2004, 53 (5): 772–773. PMC 1774040  . PMID 15082604.
^ Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000: 167–. ISBN 978-3-88763-075-1.
^ Clark MA, Harvey RA, Finkel R, Rey JA, Whalen K. Pharmacology. Lippincott Williams & Wilkins. 15 December 2011: 286–. ISBN 978-1-4511-1314-3.
^ 刘晓，刘逸寒，别松涛，等. 赭曲霉的高密度培养对坎利酮转化的影响. 生物技术. 2012, 21 (5): 82-87. doi:10.3969/j.issn.1004-311X.2011.05.134.
^ 张映华，熊志刚，邱国福，等. 依普利酮中间体坎利酮的合成工艺改进. 中国药物化学杂志. 2005, 15 (4): 241-243. doi:10.3969/j.issn.1005-0108.2005.04.013.
^ Coelingh Benni H, Vemer H. Chronic Hyperandrogenic Anovulation. CRC Press. 15 December 1990: 152–. ISBN 978-1-85070-322-8.
^ Seldin DW, Giebisch GH. Diuretic Agents: Clinical Physiology and Pharmacology. Academic Press. 23 September 1997: 630–. ISBN 978-0-08-053046-8.
^ Sobbrio GA, Granata A, Panacea A, Trimarchi F. Effectiveness of short term canrenone treatment in idiopathic hirsutism. Minerva Endocrinologica. 1989, 14 (2): 105–108. PMID 2761494.
^ Maron BA, Leopold JA. Mineralocorticoid receptor antagonists and endothelial function. Current Opinion in Investigational Drugs. September 2008, 9 (9): 963–969. PMC 2967484  . PMID 18729003.
^ International Agency for Research on Cancer; World Health Organization. Some Thyrotropic Agents. World Health Organization. 2001: 325–. ISBN 978-92-832-1279-9.
^ Agusti G, Bourgeois S, Cartiser N, Fessi H, Le Borgne M, Lomberget T. A safe and practical method for the preparation of 7α-thioether and thioester derivatives of spironolactone. Steroids. January 2013, 78 (1): 102–107. PMID 23063964. S2CID 8992318. doi:10.1016/j.steroids.2012.09.005.

[Müller2012-1] Müller J. Regulation of Aldosterone Biosynthesis: Physiological and Clinical Aspects. Springer Science & Business Media. 6 December 2012: 164–. ISBN 978-3-642-83120-1.

[pmid2723123-2] 2.0 ^2.1 Gardiner P, Schrode K, Quinlan D, Martin BK, Boreham DR, Rogers MS, et al. Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites. Journal of Clinical Pharmacology. April 1989, 29 (4): 342–347. PMID 2723123. S2CID 29457093. doi:10.1002/j.1552-4604.1989.tb03339.x.

[pmid4039568-3] Losert W, Casals-Stenzel J, Buse M. Progestogens with antimineralocorticoid activity. Arzneimittel-Forschung. 1985, 35 (2): 459–471. PMID 4039568.

[pmid6849751-4] Fernandez MD, Carter GD, Palmer TN. The interaction of canrenone with oestrogen and progesterone receptors in human uterine cytosol. British Journal of Clinical Pharmacology. January 1983, 15 (1): 95–101. PMC 1427833  . PMID 6849751. doi:10.1111/j.1365-2125.1983.tb01470.x.

[:0-5] 5.0 ^5.1 黄达明，杜卓蓉，张志才，等. 基于正交试验的根霉固态转化坎利酮工艺条件优化. 中国酿造. 2018, 37 (1): 155-160. doi:10.11882/j.issn.0254-5071.2018.01.033.

[Elks2014-6] Elks J. The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014: 210–. ISBN 978-1-4757-2085-3.

[HillMakin1991-7] Hill R, Makin H, Kirk D, Murphy G. Dictionary of Steroids. CRC Press. 23 May 1991: 656–. ISBN 978-0-412-27060-4.

[pmid15082604-8] Romanelli RG, Gentilini P. Cross reactivity due to positive canrenone interference. Gut. May 2004, 53 (5): 772–773. PMC 1774040  . PMID 15082604.

[IndexNominum2000-9] Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000: 167–. ISBN 978-3-88763-075-1.

[ClarkHarvey2011-10] Clark MA, Harvey RA, Finkel R, Rey JA, Whalen K. Pharmacology. Lippincott Williams & Wilkins. 15 December 2011: 286–. ISBN 978-1-4511-1314-3.

[11] 刘晓，刘逸寒，别松涛，等. 赭曲霉的高密度培养对坎利酮转化的影响. 生物技术. 2012, 21 (5): 82-87. doi:10.3969/j.issn.1004-311X.2011.05.134.

[12] 张映华，熊志刚，邱国福，等. 依普利酮中间体坎利酮的合成工艺改进. 中国药物化学杂志. 2005, 15 (4): 241-243. doi:10.3969/j.issn.1005-0108.2005.04.013.

[BenniVemer1990-13] Coelingh Benni H, Vemer H. Chronic Hyperandrogenic Anovulation. CRC Press. 15 December 1990: 152–. ISBN 978-1-85070-322-8.

[SeldinGiebisch1997-14] Seldin DW, Giebisch GH. Diuretic Agents: Clinical Physiology and Pharmacology. Academic Press. 23 September 1997: 630–. ISBN 978-0-08-053046-8.

[pmid2761494-15] Sobbrio GA, Granata A, Panacea A, Trimarchi F. Effectiveness of short term canrenone treatment in idiopathic hirsutism. Minerva Endocrinologica. 1989, 14 (2): 105–108. PMID 2761494.

[pmid18729003-16] Maron BA, Leopold JA. Mineralocorticoid receptor antagonists and endothelial function. Current Opinion in Investigational Drugs. September 2008, 9 (9): 963–969. PMC 2967484  . PMID 18729003.

[CancerOrganization2001-17] International Agency for Research on Cancer; World Health Organization. Some Thyrotropic Agents. World Health Organization. 2001: 325–. ISBN 978-92-832-1279-9.

[pmid23063964-18] Agusti G, Bourgeois S, Cartiser N, Fessi H, Le Borgne M, Lomberget T. A safe and practical method for the preparation of 7α-thioether and thioester derivatives of spironolactone. Steroids. January 2013, 78 (1): 102–107. PMID 23063964. S2CID 8992318. doi:10.1016/j.steroids.2012.09.005.

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[2]

[11]

[12]

[1]

[13]

[14]

[15]

[16]

[17]

[18]