Morphothiadin mesylate | CAS#1646361-04-7 | HBV capsid assembly modulator

MedKoo Cat#: 464581 | Name: Morphothiadin mesylate

Description:

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

Morphothiadin, also known GLS4, is a potent and selective inhibitor of hepatitis B virus. GLS4 demonstrated potent inhibitory activities in HBV HepG2.2.15 cell assay with an EC50 value of 1nM, and it also exhibited high potency against various drug-resistant HBV viral strains with EC50 values in the range of 10-20nM, more potent than the typical HBV polymerase inhibitors such as lamivudine, telbivudine, and entecavir. Pharmacokinetic profiles of GLS4 were favorable and safety evaluation including acute toxicity and repeated toxicity study indicated that GLS4 was safe enough to support clinical experiments in human.

Chemical Structure

Morphothiadin mesylate

CAS#1646361-04-7 (mesylate)

Theoretical Analysis

MedKoo Cat#: 464581

Name: Morphothiadin mesylate

CAS#: 1646361-04-7 (mesylate)

Chemical Formula: C23H28BrFN4O6S2

Exact Mass: 522.0737

Molecular Weight: 619.52

Elemental Analysis: C, 44.59; H, 4.56; Br, 12.90; F, 3.07; N, 9.04; O, 15.49; S, 10.35

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.

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Related CAS #

1793065-08-3 (R-isomer) 2093044-32-5 (S-isomer) 1092970-12-1 (racemic) 1646361-04-7 (mesylate)

Synonym

GLS 4 mesylate; GLS4 mesylate; GLS-4 mesylate; Morphothiadine mesilate; Morphothiadine mesylate

IUPAC/Chemical Name

ethyl 4-(2-bromo-4-fluorophenyl)-6-((2-methylmorpholino)methyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate mesylate

InChi Key

AZEFACFXPXKERN-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H24BrFN4O3S.CH4O3S/c1-3-30-22(29)18-17(12-28-7-8-31-13(2)11-28)26-20(21-25-6-9-32-21)27-19(18)15-5-4-14(24)10-16(15)23;1-5(2,3)4/h4-6,9-10,13,19H,3,7-8,11-12H2,1-2H3,(H,26,27);1H3,(H,2,3,4)

SMILES Code

O=C(C1=C(CN2CC(C)OCC2)NC(C3=NC=CS3)=NC1C4=CC=C(F)C=C4Br)OCC.OS(=O)(C)=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

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

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 619.52 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

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PMID: 37974964; PMCID: PMC10650354. 4: Wang M, Zhang J, Dou Y, Liang M, Xie Y, Xue P, Liu L, Li C, Wang Y, Tao F, Zhang X, Hu H, Feng K, Zhang L, Wu Z, Chen Y, Zhan P, Jia H. Design, Synthesis, and Biological Evaluation of Novel Thioureidobenzamide (TBA) Derivatives as HBV Capsid Assembly Modulators. J Med Chem. 2023 Oct 26;66(20):13968-13990. doi: 10.1021/acs.jmedchem.3c01022. Epub 2023 Oct 15. PMID: 37839070. 5: Vermes T, Kielpinski M, Henkel T, Pericàs MA, Alza E, Corcuera A, Buschmann H, Goldner T, Urban A. An automated microfluidic platform for the screening and characterization of novel hepatitis B virus capsid assembly modulators. Anal Methods. 2022 Jan 6;14(2):135-146. doi: 10.1039/d1ay01227d. PMID: 34918017. 6: Ma Y, Zhao S, Ren Y, Cherukupalli S, Li Q, Woodson ME, Bradley DP, Tavis JE, Liu X, Zhan P. Design, synthesis and evaluation of heteroaryldihydropyrimidine analogues bearing spiro ring as hepatitis B virus capsid protein inhibitors. Eur J Med Chem. 2021 Dec 5;225:113780. doi: 10.1016/j.ejmech.2021.113780. Epub 2021 Aug 19. PMID: 34438123; PMCID: PMC10591454. 7: Zhang S, He X, Liu L, Fan Y, Chen J, Yang L, Cui Y, Fan D. Assessing right ventricular systolic function using ultrasonic speckle-tracking imaging in repaired Tetralogy of Fallot with different pulmonary artery branch angles. Echocardiography. 2021 Jan;38(1):89-96. doi: 10.1111/echo.14948. Epub 2020 Dec 3. PMID: 33594857. 8: Zhang H, Wang F, Zhu X, Chen Y, Chen H, Li X, Wu M, Li C, Liu J, Zhang Y, Ding Y, Niu J. Antiviral Activity and Pharmacokinetics of the Hepatitis B Virus (HBV) Capsid Assembly Modulator GLS4 in Patients With Chronic HBV Infection. Clin Infect Dis. 2021 Jul 15;73(2):175-182. doi: 10.1093/cid/ciaa961. PMID: 32649736; PMCID: PMC8516514. 9: Zhao N, Jia B, Zhao H, Xu J, Sheng X, Luo L, Huang Z, Wang X, Ren Q, Zhang Y, Zhao X, Cui Y. A First-in-Human Trial of GLS4, a Novel Inhibitor of Hepatitis B Virus Capsid Assembly, following Single- and Multiple-Ascending-Oral-Dose Studies with or without Ritonavir in Healthy Adult Volunteers. Antimicrob Agents Chemother. 2019 Dec 20;64(1):e01686-19. doi: 10.1128/AAC.01686-19. PMID: 31636065; PMCID: PMC7187578. 10: Yu J, Jia H, Guo X, Desta S, Zhang S, Zhang J, Ding X, Liang X, Liu X, Zhan P. Design, synthesis, and evaluation of novel heteroaryldihydropyrimidine derivatives as non-nucleoside hepatitis B virus inhibitors by exploring the solvent-exposed region. Chem Biol Drug Des. 2020 Jun;95(6):567-583. doi: 10.1111/cbdd.13512. Epub 2020 Apr 22. PMID: 30825248. 11: Tu T, Budzinska MA, Vondran FWR, Shackel NA, Urban S. Hepatitis B Virus DNA Integration Occurs Early in the Viral Life Cycle in an In Vitro Infection Model via Sodium Taurocholate Cotransporting Polypeptide-Dependent Uptake of Enveloped Virus Particles. J Virol. 2018 May 14;92(11):e02007-17. doi: 10.1128/JVI.02007-17. PMID: 29437961; PMCID: PMC5952132. 12: Ren Q, Liu X, Yan G, Nie B, Zou Z, Li J, Chen Y, Wei Y, Huang J, Luo Z, Gu B, Goldmann S, Zhang J, Zhang Y. 3-((R)-4-(((R)-6-(2-Bromo-4-fluorophenyl)-5-(et hoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholin-2-yl)p ropanoic Acid (HEC72702), a Novel Hepatitis B Virus Capsid Inhibitor Based on Clinical Candidate GLS4. J Med Chem. 2018 Feb 8;61(3):1355-1374. doi: 10.1021/acs.jmedchem.7b01914. Epub 2018 Jan 30. PMID: 29381358. 13: Wang J, Zhang H, Zhang Y, Jiang D, Li J, Goldmann S, Ren Q, Fei R, Wang X, Wei L. Influences on viral replication and sensitivity to GLS4, a HAP compound, of naturally occurring T109/V124 mutations in hepatitis B virus core protein. J Med Virol. 2017 Oct;89(10):1804-1810. doi: 10.1002/jmv.24830. Epub 2017 May 23. PMID: 28401569. 14: Boucle S, Lu X, Bassit L, Ozturk T, Russell OO, Amblard F, Coats SJ, Schinazi RF. Synthesis and antiviral evaluation of novel heteroarylpyrimidines analogs as HBV capsid effectors. Bioorg Med Chem Lett. 2017 Feb 15;27(4):904-910. doi: 10.1016/j.bmcl.2017.01.010. Epub 2017 Jan 6. PMID: 28094179; PMCID: PMC5314961. 15: Ren Q, Liu X, Luo Z, Li J, Wang C, Goldmann S, Zhang J, Zhang Y. Discovery of hepatitis B virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (GLS4). Bioorg Med Chem. 2017 Feb 1;25(3):1042-1056. doi: 10.1016/j.bmc.2016.12.017. Epub 2016 Dec 19. PMID: 28082068. 16: Zhou X, Li L, Deng P, Chen X, Zhong D. Characterization of metabolites of GLS4 in humans using ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Rapid Commun Mass Spectrom. 2013 Nov 15;27(21):2483-92. doi: 10.1002/rcm.6710. PMID: 24097405. 17: Zhou X, Gao ZW, Meng J, Chen XY, Zhong DF. Effects of ketoconazole and rifampicin on the pharmacokinetics of GLS4, a novel anti-hepatitis B virus compound, in dogs. Acta Pharmacol Sin. 2013 Nov;34(11):1420-6. doi: 10.1038/aps.2013.76. Epub 2013 Sep 23. PMID: 24056704; PMCID: PMC4006461. 18: Wu G, Liu B, Zhang Y, Li J, Arzumanyan A, Clayton MM, Schinazi RF, Wang Z, Goldmann S, Ren Q, Zhang F, Feitelson MA. Preclinical characterization of GLS4, an inhibitor of hepatitis B virus core particle assembly. Antimicrob Agents Chemother. 2013 Nov;57(11):5344-54. doi: 10.1128/AAC.01091-13. Epub 2013 Aug 19. PMID: 23959305; PMCID: PMC3811253. 19: Wang XY, Wei ZM, Wu GY, Wang JH, Zhang YJ, Li J, Zhang HH, Xie XW, Wang X, Wang ZH, Wei L, Wang Y, Chen HS. In vitro inhibition of HBV replication by a novel compound, GLS4, and its efficacy against adefovir-dipivoxil-resistant HBV mutations. Antivir Ther. 2012;17(5):793-803. doi: 10.3851/IMP2152. Epub 2012 Jun 6. PMID: 22668794.