阿拉韦罗

化合物

阿拉韦罗INN:Aplaviroc;开发代号:AK602GSK-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。

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
  • 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  checkY
461023-63-2  checkY
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
化学信息
化学式C33H43N3O6
摩尔质量577.72 g·mol−1
3D模型(JSmol英语JSmol
  • 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=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 checkY
  • Key:GWNOTCOIYUNTQP-FQLXRVMXSA-N checkY

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

参考资料

  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 . 

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