Aplaviroc

Aplaviroc
Clinical data
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	Development terminated;
Identifiers
	IUPAC name 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 Number	461443-59-4 ; HCl: 461023-63-2 ;
PubChem CID	3001322;
IUPHAR/BPS	805;
ChemSpider	2272720 ;
UNII	98B425P30V; HCl: 04D148Z3VR ;
KEGG	D06557 ;
ChEMBL	ChEMBL1255794;
CompTox Dashboard (EPA)	DTXSID6047317 ;
Chemical and physical data
Formula	C33H43N3O6
Molar mass	577.722 g·mol−1
3D model (JSmol)	Interactive image;
	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 ;
	(verify)

Aplaviroc (INN, codenamed AK602 and GSK-873140) is a CCR5 entry inhibitor that belongs to a class of 2,5-diketopiperazines^[1] developed for the treatment of HIV infection.^[2]^[3] It was developed by GlaxoSmithKline.

In October 2005, all studies of aplaviroc were discontinued due to liver toxicity concerns.^[4]^[5] Some authors have claimed that evidence of poor efficacy may have contributed to termination of the drug's development;^[6] the ASCENT study, one of the discontinued trials, showed aplaviroc to be under-effective in many patients even at high concentrations.^[7]

References

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

Aplaviroc

See also

References

Further reading