Delavirdine mesylate | CAS#147221-93-0 | HIV-1 inhibitor

MedKoo Cat#: 461233 | Name: Delavirdine mesylate

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Description:

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

Delavirdine mesylate is a non-nucleoside reverse transcriptase inhibitor of HIV-1.

Chemical Structure

Delavirdine mesylate

CAS#147221-93-0 (mesylate)

Theoretical Analysis

MedKoo Cat#: 461233

Name: Delavirdine mesylate

CAS#: 147221-93-0 (mesylate)

Chemical Formula: C23H32N6O6S2

Exact Mass: 552.1825

Molecular Weight: 552.66

Elemental Analysis: C, 49.99; H, 5.84; N, 15.21; O, 17.37; S, 11.60

Price and Availability

Size	Price	Availability
10mg	USD 250.00	2 Weeks
50mg	USD 550.00	2 Weeks
100mg	USD 850.00	2 Weeks

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Related CAS #

147221-93-0 (mesylate) 136817-59-9 (free base)

Synonym

Delavirdine mesylate; Delavirdine mesilate; Rescriptor; U-90152S; U 90152S; U90152S; U 90152T U-90152T; U90152T; U 90152E; U-90152E; U90152E;

IUPAC/Chemical Name

N-(2-(4-(3-(isopropylamino)pyridin-2-yl)piperazine-1-carbonyl)-1H-indol-5-yl)methanesulfonamide methanesulfonate

InChi Key

MEPNHSOMXMALDZ-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H28N6O3S.CH4O3S/c1-15(2)24-19-5-4-8-23-21(19)27-9-11-28(12-10-27)22(29)20-14-16-13-17(26-32(3,30)31)6-7-18(16)25-20;1-5(2,3)4/h4-8,13-15,24-26H,9-12H2,1-3H3;1H3,(H,2,3,4)

SMILES Code

O=C(N1CCN(C2=NC=CC=C2NC(C)C)CC1)C(N3)=CC4=C3C=CC(NS(=O)(C)=O)=C4.CS(=O)(O)=O

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

Shelf Life

>3 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

2934.99.03.00

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Delavirdine (U 90152) mesylate is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that selectively inhibits HIV-1 reverse transcriptase (RT) (IC50=0.26 μM) over DNA polymerase α (IC50=440 μM) and polymerase δ (IC50>550 μM).

In vitro activity:

A novel bisheteroarylpiperazine, U-90152 [1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4-[3-(1-methyl eth ylamino)pyridinyl]piperazine] inhibited recombinant HIV-1 RT at a 50% inhibitory concentration (IC50) of 0.26 microM (compared with IC50s of > 440 microM for DNA polymerases alpha and delta). U-90152 blocked the replication in peripheral blood lymphocytes of 25 primary HIV-1 isolates, including variants that were highly resistant to 3'-azido-2',3'-dideoxythymidine (AZT) or 2',3'dideoxyinosine, with a mean 50% effective dose of 0.066 +/- 0.137 microM. U-90152 had low cellular cytotoxicity, causing less than 8% reduction in peripheral blood lymphocyte viability at 100 microM. In experiments assessing inhibition of the spread of HIV1IIIB in cell cultures, U-90152 was much more effective than AZT. 3 microM U-90152 totally prevented the spread of HIV-1, and death and/or dilution of the original inoculum of infected cells prevented renewed viral growth after U-90152 was removed at day 24. U90152 drug retains significant activity against these mutant RTs (K103N and Y181C) in vitro (IC50s, approximately 8 microgramM). Reference: Antimicrob Agents Chemother. 1993 May;37(5):1127-31. https://pubmed.ncbi.nlm.nih.gov/7685995/

In vivo activity:

The excretion, disposition, brain penetration, and metabolism of delavirdine were investigated in CD-1 mice after oral administration of [14C]delavirdine mesylate at single doses of 10 and/or 250 mg/kg and multiple doses of 200 mg/kg/day. Delavirdine was absorbed and metabolized rapidly, that it constituted a minor component in circulation, that its pharmacokinetics were nonlinear, and that its metabolism to desalkyl delavirdine was capacity limited or inhibitable. Delavirdine did not significantly cross the blood-brain barrier; however, itsN-isopropylpyridinepiperazine metabolite—arising from amide bond cleavage—was present in brain at levels 2- to 3-fold higher than in plasma. The metabolism of delavirdine in the mouse was extensive and involved amide bond cleavage,N-desalkylation, hydroxylation at the C-6′ position of the pyridine ring, and pyridine ring-cleavage as determined by MS and/or1H and 13C NMR spectroscopies. N-desalkylation and amide bond cleavage were the primary metabolic pathways at low drug doses and, as the biotransformation of delavirdine to desalkyl delavirdine reached saturation or inhibition, amide bond cleavage became the predominant pathway at higher doses and after multiple doses. Reference: . Drug Metab Dispos. 1997 Jul;25(7):828-39. https://dmd.aspetjournals.org/content/25/7/828.long

	Solvent	mg/mL	mM
Solubility
	DMSO	53.0	95.90
	Ethanol	7.0	12.67

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 552.66 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

Formulation protocol:

1. Dueweke TJ, Poppe SM, Romero DL, Swaney SM, So AG, Downey KM, Althaus IW, Reusser F, Busso M, Resnick L, et al. U90152, a potent inhibitor of human immunodeficiency virus type 1 replication. Antimicrob Agents Chemother. 1993 May;37(5):112731. doi: 10.1128/AAC.37.5.1127. PMID: 7685995; PMCID: PMC187915. 2. Romero MA, Mobley CB, Mumford PW, Roberson PA, Haun CT, Kephart WC, Healy JC, Beck DT, Young KC, Martin JS, Lockwood CM, Roberts MD. Acute and chronic resistance training downregulates select LINE-1 retrotransposon activity markers in human skeletal muscle. Am J Physiol Cell Physiol. 2018 Mar 1;314(3):C379-C388. doi: 10.1152/ajpcell.00192.2017. Epub 2017 Dec 20. PMID: 29351416. 3. Chang M, Sood VK, Wilson GJ, Kloosterman DA, Sanders PE, Hauer MJ, Zhang W, Branstetter DG. Metabolism of the HIV-1 reverse transcriptase inhibitor delavirdine in mice. Drug Metab Dispos. 1997 Jul;25(7):828-39. PMID: 9224777.

In vitro protocol:

In vivo protocol:

1. Chang M, Sood VK, Wilson GJ, Kloosterman DA, Sanders PE, Hauer MJ, Zhang W, Branstetter DG. Metabolism of the HIV-1 reverse transcriptase inhibitor delavirdine in mice. Drug Metab Dispos. 1997 Jul;25(7):828-39. PMID: 9224777.

1: Shelton MJ, Hewitt RG, Adams J, Della-Coletta A, Cox S, Morse GD. Pharmacokinetics of ritonavir and delavirdine in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2003 May;47(5):1694-9. PubMed PMID: 12709342; PubMed Central PMCID: PMC153300. 2: Friedland GH, Pollard R, Griffith B, Hughes M, Morse G, Bassett R, Freimuth W, Demeter L, Connick E, Nevin T, Hirsch M, Fischl M. Efficacy and safety of delavirdine mesylate with zidovudine and didanosine compared with two-drug combinations of these agents in persons with HIV disease with CD4 counts of 100 to 500 cells/mm3 (ACTG 261). ACTG 261 Team. J Acquir Immune Defic Syndr. 1999 Aug 1;21(4):281-92. PubMed PMID: 10428106. 3: Borin MT, Cox SR, Herman BD, Carel BJ, Anderson RD, Freimuth WW. Effect of fluconazole on the steady-state pharmacokinetics of delavirdine in human immunodeficiency virus-positive patients. Antimicrob Agents Chemother. 1997 Sep;41(9):1892-7. PubMed PMID: 9303380; PubMed Central PMCID: PMC164031. 4: White JG. In situ determination of delavirdine mesylate particle size in solid oral dosage forms. Pharm Res. 1999 Apr;16(4):545-8. PubMed PMID: 10227710. 5: Ferry JJ, Herman BD, Carel BJ, Carlson GF, Batts DH. Pharmacokinetic drug-drug interaction study of delavirdine and indinavir in healthy volunteers. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Jul 1;18(3):252-9. PubMed PMID: 9665503. 6: Shelton MJ, Hewitt RG, Adams JM, Cox SR, Chambers JH, Morse GD. Delavirdine malabsorption in HIV-infected subjects with spontaneous gastric hypoacidity. J Clin Pharmacol. 2003 Feb;43(2):171-9. PubMed PMID: 12616670. 7: Bergren MS, Chao RS, Meulman PA, Sarver RW, Lyster MA, Havens JL, Hawley M. Solid phases of delavirdine mesylate. J Pharm Sci. 1996 Aug;85(8):834-41. PubMed PMID: 8863273. 8: Morse GD, Fischl MA, Shelton MJ, Cox SR, Driver M, DeRemer M, Freimuth WW. Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother. 1997 Jan;41(1):169-74. PubMed PMID: 8980774; PubMed Central PMCID: PMC163679. 9: Voorman RL, Maio SM, Payne NA, Zhao Z, Koeplinger KA, Wang X. Microsomal metabolism of delavirdine: evidence for mechanism-based inactivation of human cytochrome P450 3A. J Pharmacol Exp Ther. 1998 Oct;287(1):381-8. PubMed PMID: 9765359. 10: Tran JQ, Petersen C, Garrett M, Hee B, Kerr BM. Pharmacokinetic interaction between amprenavir and delavirdine: evidence of induced clearance by amprenavir. Clin Pharmacol Ther. 2002 Dec;72(6):615-26. PubMed PMID: 12496743. 11: Gao P. Determination of the composition of delavirdine mesylate polymorph and pseudopolymorph mixtures using 13C CP/MAS NMR. Pharm Res. 1996 Jul;13(7):1095-104. PubMed PMID: 8842052. 12: Chang M, Sood VK, Kloosterman DA, Hauer MJ, Fagerness PE, Sanders PE, Vrbanac JJ. Identification of the metabolites of the HIV-1 reverse transcriptase inhibitor delavirdine in monkeys. Drug Metab Dispos. 1997 Jul;25(7):814-27. PubMed PMID: 9224776. 13: Adams WJ, Aristoff PA, Jensen RK, Morozowich W, Romero DL, Schinzer WC, Tarpley WG, Thomas RC. Discovery and development of the BHAP nonnucleoside reverse transcriptase inhibitor delavirdine mesylate. Pharm Biotechnol. 1998;11:285-312. Review. PubMed PMID: 9760685. 14: Been-Tiktak AM, Boucher CA, Brun-Vezinet F, Joly V, Mulder JW, Jost J, Cooper DA, Moroni M, Gatell JM, Staszewski S, Colebunders R, Stewart GJ, Hawkins DA, Johnson MA, Parkin JM, Kennedy DH, Hoy JF, Borleffs JC. Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial. Int J Antimicrob Agents. 1999 Jan;11(1):13-21. PubMed PMID: 10075273. 15: Scott LJ, Perry CM. Delavirdine: a review of its use in HIV infection. Drugs. 2000 Dec;60(6):1411-44. Review. PubMed PMID: 11152019. 16: Kuo YC, Chung CY. Solid lipid nanoparticles comprising internal Compritol 888 ATO, tripalmitin and cacao butter for encapsulating and releasing stavudine, delavirdine and saquinavir. Colloids Surf B Biointerfaces. 2011 Dec 1;88(2):682-90. doi: 10.1016/j.colsurfb.2011.07.060. Epub 2011 Aug 6. PubMed PMID: 21865017. 17: Veldkamp AI, van Heeswijk RP, Hoetelmans RM, Meenhorst PL, Mulder JW, Lange JM, Beijnen JH. Rapid quantification of delavirdine, a novel non-nucleoside reverse transcriptase inhibitor, in human plasma using isocratic reversed-phase high-performance liquid chromatography with fluorescence detection. J Chromatogr B Biomed Sci Appl. 1999 Apr 30;727(1-2):151-7. PubMed PMID: 10360434. 18: Tran JQ, Gerber JG, Kerr BM. Delavirdine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2001;40(3):207-26. Review. PubMed PMID: 11327199. 19: Chang M, Sood VK, Wilson GJ, Kloosterman DA, Sanders PE, Hauer MJ, Fagerness PE. Metabolism of the human immunodeficiency virus type 1 reverse transcriptase inhibitor delavirdine in rats. Drug Metab Dispos. 1997 Feb;25(2):228-42. PubMed PMID: 9029054. 20: Cheng CL, Smith DE, Carver PL, Cox SR, Watkins PB, Blake DS, Kauffman CA, Meyer KM, Amidon GL, Stetson PL. Steady-state pharmacokinetics of delavirdine in HIV-positive patients: effect on erythromycin breath test. Clin Pharmacol Ther. 1997 May;61(5):531-43. PubMed PMID: 9164415.