BI 224436

BI 224436
Systematic (IUPAC) name

(2S)-[4-(3,4-Dihydro-2H-chromen-6-yl)-3-quinolinyl][(2-methyl-2-propanyl)oxy]acetic acid
Clinical data
Legal status	Investigational
Pharmacokinetic data
Biological half-life	7 hrs (simulated)^[1]
Identifiers
ATC code	none
ChemSpider	27289461
Chemical data
Formula	C₂₄H₂₅NO₄
Molar mass	391.460 g/mol
SMILES CC(C)(C)O[C@@H](c1cnc2ccccc2c1c3ccc4c(c3)CCCO4)C(=O)O
InChI InChI=1S/C24H25NO4/c1-24(2,3)29-22(23(26)27)18-14-25-19-9-5-4-8-17(19)21(18)16-10-11-20-15(13-16)7-6-12-28-20/h4-5,8-11,13-14,22H,6-7,12H2,1-3H3,(H,26,27)/t22-/m0/s1 Key:DMWVBLFYARRIDL-QFIPXVFZSA-N

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]

References

↑ Pharmacodynamics of BI 224436 for HIV-1 in an in vitro hollow fiber infection model system
↑ Levin, Jules. 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. Conference Reports for NATAP. ICAAC Chicago Sept 17-20 2011.
↑ Gilead Negotiates Worldwide License to BI’s Early Clinical Stage HIV Program. Genetic Engineering and Biotechnology News. 6 Oct 2011.
↑ Highleyman, Liz. ICAAC: New Integrase Inhibitor BI 224436 Active against Raltegravir-Resistant HIV. HIVandHepatitis.com. 7 Oct 2011.

Antiviral drugs: antiretroviral drugs used against HIV (primarily J05)

Entry/fusion inhibitors
(Discovery and development)

gp41 (Enfuvirtide (ENF, T-20))
CCR5 (Maraviroc (MVC)
Vicriviroc^†, Cenicriviroc^†, PRO 140^†)
CD4 (Ibalizumab^†)
gp120 (Fostemsavir^†)

Reverse-transcriptase
inhibitors (RTIs)

Nucleoside and nucleotide (NRTI)	Nucleoside analogues/NRTIs: Abacavir (ABC)°^# Didanosine (ddI) Emtricitabine (FTC)° Lamivudine (3TC)°^# Stavudine (d4T)^# Zidovudine (AZT, ZDV)^# Amdoxovir^† Apricitabine^† Censavudine^† Elvucitabine^† Racivir^† Stampidine^† Zalcitabine (ddC)^◊ Nucleotide analogues/NtRTIs: Tenofovir disoproxil (TDF)°^# Tenofovir alafenamide (TAF)

Non-nucleoside (NNRTI) (Discovery and development)	(1st generation) Efavirenz (EFV)°^# Nevirapine (NVP)^# Delavirdine (DLV)^◊ (2nd generation) diarylpyrimidines (Etravirine (ETR) Rilpivirine (RPV)°) Doravirine

Integrase inhibitors
(Integrase strand transfer inhibitors (INSTI))

Dolutegravir (DTG)°
Elvitegravir (EVG)°
Raltegravir (RAL)°
BI 224436^†
Globoidnan A (experimental)
Cabotegravir^†
Bictegravir^†
MK-2048^†

Maturation inhibitors

Bevirimat^†
BMS-955176^§

Protease Inhibitors (PI)
(Discovery and development)

1st generation	Amprenavir (APV)^◊ Fosamprenavir (FPV) Indinavir (IDV)^◊ Lopinavir (LPV) Nelfinavir (NFV) Ritonavir (RTV)^# Saquinavir (SQV)^#

2nd generation	Atazanavir (ATV)°^# Darunavir (DRV)°^# Tipranavir (TPV)

Combined formulations

Abacavir/lamivudine°^#
Abacavir/dolutegravir/lamivudine°
Abacavir/lamivudine/zidovudine
Atazanavir/cobicistat
Darunavir/cobicistat
Efavirenz/emtricitabine/tenofovir°^#
Elvitegravir/cobicistat/emtricitabine/tenofovir°
Emtricitabine/rilpivirine/tenofovir°
Lamivudine/raltegravir
Lamivudine/zidovudine^#
Lopinavir/ritonavir°^#
Tenofovir/emtricitabine°^#

Pharmacokinetic boosters

Experimental agents

Uncoating inhibitors	TRIM5alpha (gene)

Transcription inhibitors	Tat antagonists

Translation inhibitors	Trichosanthin

Other	Abzyme BIT225^† Calanolide A Ceragenin Cyanovirin-N Diarylpyrimidines Epigallocatechin gallate (EGCG) KP-1461^† Foscarnet Fosdevirine^† Griffithsin Hydroxycarbamide Miltefosine Portmanteau inhibitors Scytovirin Seliciclib^† Synergistic enhancers Tre recombinase Zinc finger protein transcription factor

Failed agents	Aplaviroc Atevirdine Brecanavir Capravirine Dexelvucitabine Droxinavir Lasinavir Emivirine Lersivirine Lodenosine Loviride Mozenavir Palinavir Telinavir

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

°DHHS recommended initial regimen options. ^◊Formerly or rarely used agent.

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