BI-224436 | CAS#1155419-89-8 | non-catalytic site integrase inhibitor

MedKoo Cat#: 522577 | Name: BI-224436

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

BI-224436

CAS#1155419-89-8

Theoretical Analysis

MedKoo Cat#: 522577

Name: BI-224436

CAS#: 1155419-89-8

Chemical Formula: C27H26N2O4

Exact Mass: 442.1893

Molecular Weight: 442.52

Elemental Analysis: C, 73.28; H, 5.92; N, 6.33; O, 14.46

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

Bulk Inquiry

Related CAS #

1155419-89-8

Synonym

BI-224436; BI 224436; BI224436.

IUPAC/Chemical Name

(S)-2-(tert-Butoxy)-2-(4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-2-methylquinolin-3-yl)acetic acid

InChi Key

MIXIIJCBELCMCZ-VWLOTQADSA-N

InChi Code

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

SMILES Code

O=C(O)[C@@H](OC(C)(C)C)C1=[C@]([C@]2=C3N=CC=C(CCO4)C3=C4C=C2)C5=CC=CC=C5N=C1C

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 442.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

1: Roberts RA, Campbell RA, Sikakana P, Sadler C, Osier M, Xu Y, Feng JY, Mitchell M, Sakowicz R, Chester A, Paoli E, Wang J, Burns-Naas LA. Species- Specific Urothelial Toxicity With an Anti-HIV Noncatalytic Site Integrase Inhibitor (NCINI) Is Related to Unusual pH-Dependent Physicochemical Changes. Toxicol Sci. 2021 Aug 30;183(1):105-116. doi: 10.1093/toxsci/kfab073. PMID: 34117767. 2: Sugiyama S, Akiyama T, Taoda Y, Iwaki T, Matsuoka E, Akihisa E, Seki T, Yoshinaga T, Kawasuji T. Discovery of novel HIV-1 integrase-LEDGF/p75 allosteric inhibitors based on a pyridine scaffold forming an intramolecular hydrogen bond. Bioorg Med Chem Lett. 2021 Feb 1;33:127742. doi: 10.1016/j.bmcl.2020.127742. Epub 2020 Dec 11. PMID: 33316407. 3: Shinde PB, Bhowmick S, Alfantoukh E, Patil PC, Wabaidur SM, Chikhale RV, Islam MA. De novo design based identification of potential HIV-1 integrase inhibitors: A pharmacoinformatics study. Comput Biol Chem. 2020 Oct;88:107319. doi: 10.1016/j.compbiolchem.2020.107319. Epub 2020 Jun 23. PMID: 32801062. 4: Sugiyama S, Iwaki T, Tamura Y, Tomita K, Matsuoka E, Arita S, Seki T, Yoshinaga T, Kawasuji T. Discovery of novel integrase-LEDGF/p75 allosteric inhibitors based on a benzene scaffold. Bioorg Med Chem. 2020 Sep 1;28(17):115643. doi: 10.1016/j.bmc.2020.115643. Epub 2020 Jul 10. PMID: 32773094. 5: Han Y, Mesplède T, Wainberg MA. Investigational HIV integrase inhibitors in phase I and phase II clinical trials. Expert Opin Investig Drugs. 2017 Nov;26(11):1207-1213. doi: 10.1080/13543784.2017.1378643. Epub 2017 Sep 28. PMID: 28956664. 6: Zhang X, Liu H, Jia Y. A palladium-catalyzed intramolecular carbonylative annulation reaction for the synthesis of 4,5-fused tricyclic 2-quinolones. Chem Commun (Camb). 2016 Jun 8;52(49):7665-7. doi: 10.1039/c6cc02600a. PMID: 27225232. 7: Fader LD, Carson R, Morin S, Bilodeau F, Chabot C, Halmos T, Bailey MD, Kawai SH, Coulombe R, Laplante S, Mekhssian K, Jakalian A, Garneau M, Duan J, Mason SW, Simoneau B, Fenwick C, Tsantrizos Y, Yoakim C. Minimizing the Contribution of Enterohepatic Recirculation to Clearance in Rat for the NCINI Class of Inhibitors of HIV. ACS Med Chem Lett. 2014 Apr 16;5(6):711-6. doi: 10.1021/ml500110j. PMID: 24944749; PMCID: PMC4060926. 8: Fader LD, Malenfant E, Parisien M, Carson R, Bilodeau F, Landry S, Pesant M, Brochu C, Morin S, Chabot C, Halmos T, Bousquet Y, Bailey MD, Kawai SH, Coulombe R, LaPlante S, Jakalian A, Bhardwaj PK, Wernic D, Schroeder P, Amad M, Edwards P, Garneau M, Duan J, Cordingley M, Bethell R, Mason SW, Bös M, Bonneau P, Poupart MA, Faucher AM, Simoneau B, Fenwick C, Yoakim C, Tsantrizos Y. Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1. ACS Med Chem Lett. 2014 Jan 22;5(4):422-7. doi: 10.1021/ml500002n. PMID: 24900852; PMCID: PMC4027581. 9: Demeulemeester J, Chaltin P, Marchand A, De Maeyer M, Debyser Z, Christ F. LEDGINs, non-catalytic site inhibitors of HIV-1 integrase: a patent review (2006 - 2014). Expert Opin Ther Pat. 2014 Jun;24(6):609-32. doi: 10.1517/13543776.2014.898753. Epub 2014 Mar 25. PMID: 24666332. 10: Fenwick C, Amad M, Bailey MD, Bethell R, Bös M, Bonneau P, Cordingley M, Coulombe R, Duan J, Edwards P, Fader LD, Faucher AM, Garneau M, Jakalian A, Kawai S, Lamorte L, LaPlante S, Luo L, Mason S, Poupart MA, Rioux N, Schroeder P, Simoneau B, Tremblay S, Tsantrizos Y, Witvrouw M, Yoakim C. Preclinical profile of BI 224436, a novel HIV-1 non-catalytic-site integrase inhibitor. Antimicrob Agents Chemother. 2014 Jun;58(6):3233-44. doi: 10.1128/AAC.02719-13. Epub 2014 Mar 24. PMID: 24663024; PMCID: PMC4068430. 11: Karmon SL, Markowitz M. Next-generation integrase inhibitors : where to after raltegravir? Drugs. 2013 Mar;73(3):213-28. doi: 10.1007/s40265-013-0015-5. PMID: 23413196.