BI 224436

BI 224436
Clinical data
ATC code	none;
Legal status
Legal status	Investigational;
Pharmacokinetic data
Elimination half-life	7 hrs (simulated)
Identifiers
	IUPAC name (2S)-[4-(2,3-Dihydropyrano[4,3,2-de]quinolin-7-yl)-2-methyl-3-quinolinyl] [(2-methyl-2-propanyl)oxy]acetic acid;
CAS Number	1155419-89-8;
PubChem CID	66561902;
ChemSpider	32698770;
UNII	99A996378Y;
CompTox Dashboard (EPA)	DTXSID601029847 ;
Chemical and physical data
Formula	C27H26N2O4
Molar mass	442.515 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=NC2=CC=CC=C2C(=C1[C@@H](C(=O)O)OC(C)(C)C)C3=C4C5=C(C=C3)OCCC5=CC=N4;
	InChI InChI=1S/C27H26N2O4/c1-15-21(25(26(30)31)33-27(2,3)4)23(17-7-5-6-8-19(17)29-15)18-9-10-20-22-16(12-14-32-20)11-13-28-24(18)22/h5-11,13,25H,12,14H2,1-4H3,(H,30,31)/t25-/m0/s1; Key:MIXIIJCBELCMCZ-VWLOTQADSA-N;

BI 224436 was an investigational new drug under development for the treatment of HIV infection. BI 224436 is the first non-catalytic site integrase inhibitor (NCINI). It inhibits HIV replication via binding to a conserved allosteric pocket of the HIV integrase enzyme. This makes the drug distinct in its mechanism of action compared to raltegravir and elvitegravir, which bind at the catalytic site.^[2] In October 2011, Gilead Sciences purchased exclusive rights to develop BI 224436 and several related compounds under investigation in Boehringer Ingelheim’s noncatalytic site integrase inhibitor program.^[3]^[4]

Clinical trials were abandoned in advance of Phase 1.^[5]

References

^ Brown A, McSharry J, Kulawy R (17 September 2011). Pharmacodynamics of BI 224436 for HIV-1 in an in vitro hollow fiber infection model system. 51st Interscience conference on antimicrobial agents and chemotherapy. Chicago. pp. 17–20.
^ Fenwick C, Bethell R, Cordingley M, Edwards P, Quinson AM, Robinson P, Simoneau B, Yoakim C (17 September 2011). Levin J (ed.). BI 224436, a non-catalytic site integrase inhibitor, is a potent inhibitor of the replication of treatment-naïve and raltegravir-resistant clinical isolates of HIV-1. 51st Interscience Conference on Antimicrobials and Chemotherapy. Chicago: ICAAC.
^ "Gilead Negotiates Worldwide License to BI's Early Clinical Stage HIV Program". Genetic Engineering and Biotechnology News. 6 October 2011. Archived from the original on 23 January 2013.
^ Highleyman L (7 October 2011). "ICAAC: New Integrase Inhibitor BI 224436 Active against Raltegravir-Resistant HIV". HIVandHepatitis.com.
^ Clinical trial number NCT01276990 for "Safety and Pharmacokinetics of Multiple Rising Oral Doses of BI 224436 in Healthy Male Volunteers." at ClinicalTrials.gov