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Chemical compound
BI 224436
ATC code
Legal status
Elimination half-life 7 hrs (simulated)
[1]
(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
PubChem
CID
ChemSpider
UNII
CompTox Dashboard (
EPA )
Formula C 27 H 26 N 2 O 4
Molar mass 442.515 g·mol−1 3D model (
JSmol )
CC1=NC2=CC=CC=C2C(=C1[C@@H](C(=O)O)OC(C)(C)C)C3=C4C5=C(C=C3)OCCC5=CC=N4
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