咯利普兰

咯利普兰
臨床資料
ATC碼	未分配;
法律規範狀態
法律規範	Investigational;
藥物動力學數據
生物利用度	75%
药物代谢	Liver via CYP2C8, CYP2C9, CYP2C19 and CYP2D6
生物半衰期	3 hours
排泄途徑	Urine (80%)
识别信息
	IUPAC命名法 (RS)-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-one; ;
CAS号	61413-54-5
PubChem CID	5092;
IUPHAR/BPS	5260;
DrugBank	DB04149 ;
ChemSpider	4913 ;
UNII	K676NL63N7;
KEGG	D01783 ;
ChEBI	CHEBI:104872 ;
ChEMBL	ChEMBL63 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID3044124 ;
ECHA InfoCard	100.057.046
化学信息
化学式	C16H21NO3
摩尔质量	275.35 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES COc1ccc(cc1OC1CCCC1)C1CNC(=O)C1;
	InChI InChI=1S/C16H21NO3/c1-19-14-7-6-11(12-9-16(18)17-10-12)8-15(14)20-13-4-2-3-5-13/h6-8,12-13H,2-5,9-10H2,1H3,(H,17,18) ; Key:HJORMJIFDVBMOB-UHFFFAOYSA-N ;

咯利普兰是一种选择性的磷酸二酯酶-4的抑制剂，1990 年代初由先灵股份公司发开发为一种潜在的抗抑郁药，^[2]是一些公司开发药物的原型分子。 ^[3] 临床试验表明其治疗指数太窄，不引起显着胃肠道副作用的前提下，它无法给药足够高的剂量，因而咯利普兰被停用。 ^[3]

咯利普兰的多个特点使其成为研究的持续重点。许多神经退化障碍涉及大脑中积累的错误折叠和聚集的蛋白质，正常细胞内有一种称为蛋白酶体可以处理这些蛋白质。然而，在阿尔茨海默病和其他一些疾病中，这些蛋白酶体活性受损，导致有毒聚集体的积累。小鼠的研究表明，咯利普兰能够提高蛋白酶体的活性并减少聚集体。初步证据表明，咯利普兰可以改善蛋白质积聚小鼠的空间记忆。 ^[4]咯利普兰也同时作为一种充分表征的 PDE4 抑制剂继续得到研究。 ^[3]它用于研究 PDE4抑制是否可用于自身免疫性疾病、 ^[5]阿尔茨海默病、 ^[6]认知增强、^[7]脊髓损伤、^[8]哮喘和慢性阻塞性肺病等呼吸系统疾病。 ^[9]

参考

^ ^1.0 ^1.1 ^1.2 ^1.3 Krause, W; Kühne, G; Sauerbrey, N. Pharmacokinetics of (+)-rolipram and (−)-rolipram in healthy volunteers. European Journal of Clinical Pharmacology. 1990, 38 (1): 71–75. PMID 2328751. S2CID 25683209. doi:10.1007/BF00314807.
^ Zhu, J; Mix, E; Winblad, B. The antidepressant and antiinflammatory effects of rolipram in the central nervous system.. CNS Drug Reviews. Winter 2001, 7 (4): 387–98. PMC 6741679  . PMID 11830756. doi:10.1111/j.1527-3458.2001.tb00206.x.
^ ^3.0 ^3.1 ^3.2 McKenna, JM and Muller, GW.
^ Myeku, Natura. Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling.. Nature Medicine. December 21, 2015, 22 (1): 46–53. PMC 4787271  . PMID 26692334. doi:10.1038/nm.4011.
^ Phosphodiesterase 4-targeted treatments for autoimmune diseases. BMC Med. Apr 2013, 11 (1): 96. PMC 3616808  . PMID 23557064. doi:10.1186/1741-7015-11-96.
^ Phosphodiesterases as therapeutic targets for Alzheimer's disease. ACS Chem Neurosci. Nov 2012, 3 (11): 832–44. PMC 3503343  . PMID 23173065. doi:10.1021/cn3000907.
^ Neuroenhancement: status quo and perspectives. Eur Arch Psychiatry Clin Neurosci. Nov 2008, 258 (Suppl 5): 110–4. PMID 18985306. doi:10.1007/s00406-008-5022-2.
^ The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp Neurol. Feb 2008, 209 (2): 321–32. PMC 2692909  . PMID 17720160. doi:10.1016/j.expneurol.2007.06.020.
^ Phosphodiesterase 4 inhibitors for the treatment of asthma and COPD. Curr. Med. Chem. 2006, 13 (27): 3253–62. PMID 17168849. doi:10.2174/092986706778773040.

[PK-1] 1.0 ^1.1 ^1.2 ^1.3 Krause, W; Kühne, G; Sauerbrey, N. Pharmacokinetics of (+)-rolipram and (−)-rolipram in healthy volunteers. European Journal of Clinical Pharmacology. 1990, 38 (1): 71–75. PMID 2328751. S2CID 25683209. doi:10.1007/BF00314807.

[Zhu_387–98-2] Zhu, J; Mix, E; Winblad, B. The antidepressant and antiinflammatory effects of rolipram in the central nervous system.. CNS Drug Reviews. Winter 2001, 7 (4): 387–98. PMC 6741679  . PMID 11830756. doi:10.1111/j.1527-3458.2001.tb00206.x.

[McKenna-3] 3.0 ^3.1 ^3.2 McKenna, JM and Muller, GW.

[Myeku_46-53-4] Myeku, Natura. Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling.. Nature Medicine. December 21, 2015, 22 (1): 46–53. PMC 4787271  . PMID 26692334. doi:10.1038/nm.4011.

[5] Phosphodiesterase 4-targeted treatments for autoimmune diseases. BMC Med. Apr 2013, 11 (1): 96. PMC 3616808  . PMID 23557064. doi:10.1186/1741-7015-11-96.

[6] Phosphodiesterases as therapeutic targets for Alzheimer's disease. ACS Chem Neurosci. Nov 2012, 3 (11): 832–44. PMC 3503343  . PMID 23173065. doi:10.1021/cn3000907.

[7] Neuroenhancement: status quo and perspectives. Eur Arch Psychiatry Clin Neurosci. Nov 2008, 258 (Suppl 5): 110–4. PMID 18985306. doi:10.1007/s00406-008-5022-2.

[8] The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp Neurol. Feb 2008, 209 (2): 321–32. PMC 2692909  . PMID 17720160. doi:10.1016/j.expneurol.2007.06.020.

[9] Phosphodiesterase 4 inhibitors for the treatment of asthma and COPD. Curr. Med. Chem. 2006, 13 (27): 3253–62. PMID 17168849. doi:10.2174/092986706778773040.

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臨床資料

ATC碼	未分配
法律規範狀態
法律規範	Investigational
藥物動力學數據
生物利用度	75%^[1]
药物代谢	Liver via CYP2C8, CYP2C9, CYP2C19 and CYP2D6^[1]
生物半衰期	3 hours^[1]
排泄途徑	Urine (80%)^[1]
识别信息
IUPAC命名法 (RS)-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-one
CAS号	61413-54-5 ^Y
PubChem CID	5092
IUPHAR/BPS	5260
DrugBank	DB04149^N
ChemSpider	4913^Y
UNII	K676NL63N7
KEGG	D01783^N
ChEBI	CHEBI:104872^Y
ChEMBL	ChEMBL63^Y
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID3044124
ECHA InfoCard	100.057.046
化学信息
化学式	C₁₆H₂₁NO₃
摩尔质量	275.35 g·mol⁻¹
3D模型（JSmol（英语：JSmol））	交互式图像
SMILES COc1ccc(cc1OC1CCCC1)C1CNC(=O)C1
InChI InChI=1S/C16H21NO3/c1-19-14-7-6-11(12-9-16(18)17-10-12)8-15(14)20-13-4-2-3-5-13/h6-8,12-13H,2-5,9-10H2,1H3,(H,17,18)^Y Key:HJORMJIFDVBMOB-UHFFFAOYSA-N^Y

咯利普兰

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