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BI 224436

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Chemical compound

Pharmaceutical compound

BI 224436
Clinical data

ATC code	none
Legal status
Legal status	Investigational
Pharmacokinetic data
Eliminationhalf-life	7 hrs (simulated)^[1]
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
PubChemCID	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 aninvestigational new drug under development for the treatment ofHIV infection. BI 224436 is the first non-catalytic siteintegrase inhibitor (NCINI). It inhibits HIV replication via binding to aconserved allosteric pocket of the HIVintegrase enzyme. This makes the drug distinct in its mechanism of action compared toraltegravir andelvitegravir, which bind at thecatalytic site.^[2] In October 2011,Gilead Sciences purchased exclusive rights to develop BI 224436 and several related compounds under investigation inBoehringer Ingelheim’s noncatalytic site integrase inhibitor program.^[3]^[4]

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

^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 fromthe 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 numberNCT01276990 for "Safety and Pharmacokinetics of Multiple Rising Oral Doses of BI 224436 in Healthy Male Volunteers." atClinicalTrials.gov

Entry/fusion inhibitors
(Discovery and development)

Integrase inhibitors
(Integrase strand transfer inhibitors (INSTI))

Protease Inhibitors (PI)
(Discovery and development)

1^st generation	Amprenavir (APV)^‡ Fosamprenavir (FPV) Indinavir (IDV)^◊ Lopinavir (LPV) Nelfinavir (NFV)^◊ Ritonavir (RTV)^# Saquinavir (SQV)^◊
2^nd generation	Atazanavir (ATV)°^# Darunavir (DRV)°^# Tipranavir (TPV)^◊ TMC-310911^§

Non-nucleoside (NNRTI)
(Discovery and development)

1^st generation	Efavirenz (EFV)^# Nevirapine (NVP)^# Delavirdine (DLV)^‡
2^nd generation	diarylpyrimidines Dapivirine (DPV) Etravirine (ETR) Rilpivirine (RPV) Doravirine (DOR) Elsulfavirine (ESV)

Pharmacokinetic boosters

Experimental agents

Uncoating inhibitors	TRIM5alpha (gene)
Transcription inhibitors	Tat antagonists
Translation inhibitors	Trichosanthin
BNAbs	Elipovimab
Other	Abzyme BIT225^† Calanolide A Ceragenin Cyanovirin-N Diarylpyrimidines Epigallocatechin gallate (EGCG) Foscarnet Fosdevirine^† Griffithsin Hydroxycarbamide KP-1461^† Miltefosine North-methanocarbathymidine 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

°DHHSrecommendedinitial regimen options.^◊Formerly or rarely used agent.

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