阿拉韦罗

阿拉韦罗
临床资料
给药途径	Oral
ATC码	未分配;
法律规范状态
法律规范	Development terminated;
识别信息
	IUPAC命名法 4-(4-{[(3R)-1-butyl-3-[(R)-cyclohexylhydroxymethyl]-2,5-dioxo- 1,4,9-triazaspiro[5.5]undecan-9-yl]methyl}phenoxy)benzoic acid; ;
CAS号	461443-59-4 ; 461023-63-2
PubChem CID	3001322;
IUPHAR/BPS	805;
ChemSpider	2272720 ;
UNII	98B425P30V; HCl: 04D148Z3VR ;
KEGG	D06557 ;
ChEMBL	ChEMBL1255794;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID6047317 ;
化学信息
化学式	C33H43N3O6
摩尔质量	577.72 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES CCCCN1C(=O)[C@H](NC(=O)C12CCN(CC2)CC3=CC=C(C=C3)OC4=CC=C(C=C4)C(=O)O)[C@@H](C5CCCCC5)O;
	InChI InChI=1S/C33H43N3O6/c1-2-3-19-36-30(38)28(29(37)24-7-5-4-6-8-24)34-32(41)33(36)17-20-35(21-18-33)22-23-9-13-26(14-10-23)42-27-15-11-25(12-16-27)31(39)40/h9-16,24,28-29,37H,2-8,17-22H2,1H3,(H,34,41)(H,39,40)/t28-,29-/m1/s1 ; Key:GWNOTCOIYUNTQP-FQLXRVMXSA-N ;

阿拉韦罗（INN：Aplaviroc；开发代号：AK602和GSK-873140）是一种 CCR5 进入抑制剂，属于2,5-二酮哌嗪类，^[1]为治疗HIV感染而开发。^[2]^[3]它是由葛兰素史克开发的。

2005年10月，由于肝毒性问题，所有阿拉韦罗研究均停止。^[4]^[5]一些作者声称，疗效不佳的证据可能导致该药物的开发终止；^[6]ASCENT研究是已终止的试验之一，该研究表明阿拉韦罗即使在高浓度下对许多患者也无效。^[7]

参见

CCR5受体拮抗剂（英语：CCR5 receptor antagonist）

参考资料

^ Borthwick AD. 2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products. Chemical Reviews. July 2012, 112 (7): 3641–3716. PMID 22575049. doi:10.1021/cr200398y.
^ Maeda K, Ogata H, Harada S, Tojo Y, Miyakawa T, Nakata H, et al. Determination of binding sites of a unique CCR5 inhibitor AK602 on human CCR5 (PDF). 11th conference on retroviruses and opportunistic infections. San Francisco, CA. 2004. （原始内容 (PDF)存档于November 3, 2005）.
^ Nakata H, Maeda K, Miyakawa T, Shibayama S, Matsuo M, Takaoka Y, et al. Potent anti-R5 human immunodeficiency virus type 1 effects of a CCR5 antagonist, AK602/ONO4128/GW873140, in a novel human peripheral blood mononuclear cell nonobese diabetic-SCID, interleukin-2 receptor gamma-chain-knocked-out AIDS mouse model. Journal of Virology. February 2005, 79 (4): 2087–2096. PMC 546550 . PMID 15681411. doi:10.1128/jvi.79.4.2087-2096.2005.
^ Aplaviroc (GSK-873,140). AIDSmeds.com. October 25, 2005 [September 5, 2008]. （原始内容存档于January 13, 2007）.
^ Nichols WG, Steel HM, Bonny T, Adkison K, Curtis L, Millard J, et al. Hepatotoxicity observed in clinical trials of aplaviroc (GW873140). Antimicrobial Agents and Chemotherapy. March 2008, 52 (3): 858–865. PMC 2258506 . PMID 18070967. doi:10.1128/aac.00821-07.
^ Moyle G. The Last Word on Aplaviroc: A CCR5 Antagonist With Poor Efficacy. The Body. December 19, 2006 [September 5, 2008]. （原始内容存档于6 October 2008）.
^ Currier J, Lazzarin A, Sloan L, Clumeck N, Slims J, McCarty D, et al. Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study. Antiviral Therapy. 2008, 13 (2): 297–306. PMID 18505181. S2CID 21839689. doi:10.1177/135965350801300204 .

延伸阅读

Horster S, Goebel FD. Serious doubts on safety and efficacy of CCR5 antagonists : CCR5 antagonists teeter on a knife-edge. Infection. April 2006, 34 (2): 110–113. PMID 16703305. S2CID 38463200. doi:10.1007/s15010-006-6206-1.

[1] Borthwick AD. 2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products. Chemical Reviews. July 2012, 112 (7): 3641–3716. PMID 22575049. doi:10.1021/cr200398y.

[2] Maeda K, Ogata H, Harada S, Tojo Y, Miyakawa T, Nakata H, et al. Determination of binding sites of a unique CCR5 inhibitor AK602 on human CCR5 (PDF). 11th conference on retroviruses and opportunistic infections. San Francisco, CA. 2004. （原始内容 (PDF)存档于November 3, 2005）.

[3] Nakata H, Maeda K, Miyakawa T, Shibayama S, Matsuo M, Takaoka Y, et al. Potent anti-R5 human immunodeficiency virus type 1 effects of a CCR5 antagonist, AK602/ONO4128/GW873140, in a novel human peripheral blood mononuclear cell nonobese diabetic-SCID, interleukin-2 receptor gamma-chain-knocked-out AIDS mouse model. Journal of Virology. February 2005, 79 (4): 2087–2096. PMC 546550 . PMID 15681411. doi:10.1128/jvi.79.4.2087-2096.2005.

[4] Aplaviroc (GSK-873,140). AIDSmeds.com. October 25, 2005 [September 5, 2008]. （原始内容存档于January 13, 2007）.

[5] Nichols WG, Steel HM, Bonny T, Adkison K, Curtis L, Millard J, et al. Hepatotoxicity observed in clinical trials of aplaviroc (GW873140). Antimicrobial Agents and Chemotherapy. March 2008, 52 (3): 858–865. PMC 2258506 . PMID 18070967. doi:10.1128/aac.00821-07.

[6] Moyle G. The Last Word on Aplaviroc: A CCR5 Antagonist With Poor Efficacy. The Body. December 19, 2006 [September 5, 2008]. （原始内容存档于6 October 2008）.

[7] Currier J, Lazzarin A, Sloan L, Clumeck N, Slims J, McCarty D, et al. Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study. Antiviral Therapy. 2008, 13 (2): 297–306. PMID 18505181. S2CID 21839689. doi:10.1177/135965350801300204 .

[1]

[2]

[3]

[4]

[5]

[6]

[7]