(2S)-2-tert-butoxy-2-(4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-2- methylquinolin-3-yl)acetic acid
BI 224436
1155419-89-8 cas no
mw
| 442.51 |
3-Quinolineacetic acid, 4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-α-(1,1-dimethylethoxy)-2-methyl-, (αS,4R)-
hemi-succinate of (2S)-2-tert-butoxy-2-(4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-2-methylquinolin-3-yl)acetic acid)
BI 224436 is 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 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]
Novel hemi-succinate salt form of (2S)-2-tert-butoxy-2-(4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-2-methylquinolin-3-yl)acetic acid (presumed to be BI-224436) and its crystalline forms is desc in WO-2014055618.
Gilead, under license from BI, was developing BI-224436 for the oral treatment of HIV infection. In September 2011, this drug had entered phase 1 trials. Picks up from WO2012138670, claiming a process for the preparation of the same drug. Also see the concurrently published WO2014055603. This compound is claimed specifically in WO2009062285 and generically in WO2007131350.
Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1
ACS Med. Chem. Lett., 2014, 5 (4), pp 422–427
DOI: 10.1021/ml500002n
DOI: 10.1021/ml500002n
1H NMR: 12.4 (br, 1H), 8.52 (d, 1H, J = 4.4Hz), 7.94 (d, 1H, J = 7.9 Hz),7.65-7.61 (m, 1H), 7.45 (d,
1H, J = 8.2 Hz), 7.31-7.24 (m, 2H), 7.12 (d, 1H, J = 7.9 Hz), 6.94-6.92 (m, 1H), 4.99 (s, 1H), 4.57-4.47
(m, 2H), 3.37-3.30 (m, 2H), 2.86 (s, 3H), 0.82 (s, 9H).
1H, J = 8.2 Hz), 7.31-7.24 (m, 2H), 7.12 (d, 1H, J = 7.9 Hz), 6.94-6.92 (m, 1H), 4.99 (s, 1H), 4.57-4.47
(m, 2H), 3.37-3.30 (m, 2H), 2.86 (s, 3H), 0.82 (s, 9H).
13C NMR: 172.2, 158.4, 153.1, 150.1, 146.6,
146.1, 145.0, 141.0, 130.8 (br), 130.6 (br), 128.9, 128.0, 127.2, 127.1 (br) 126.4, 125.6, 118.0, 116.7,
109.1, 75.2, 70.8, 65.6, 27.7, 27.5, 24.9.
146.1, 145.0, 141.0, 130.8 (br), 130.6 (br), 128.9, 128.0, 127.2, 127.1 (br) 126.4, 125.6, 118.0, 116.7,
109.1, 75.2, 70.8, 65.6, 27.7, 27.5, 24.9.
HRMS: m/z calc. for C27H26N2O4 + H+: 443.1965, m/z found:
443.1951 (-3.2 ppm).
443.1951 (-3.2 ppm).
UPLC-MS: rt = 0.68 min, m/z 443.3 [M + H]+, purity: >99.9% @ 254 nm.
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