Morphothiadin

Category	Hepatitis B Virus (HBV)
CAS	1092970-12-1
Description	Morphothiadin is a potent inhibitor of Hepatitis B virus (HBV). It is active against both wild-type and adefovir-resistant HBV with IC50 value of 12 nM. Morphothiadin exhibits strong inhibitory effects against virus DNA in mouse models.

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Product Information

Synonyms	GLS4; Ethyl 4-(2-bromo-4-fluorophenyl)-6-(morpholin-4-ylmethyl)-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate
Molecular Weight	509.39
Molecular Formula	C21H22BrFN4O3S
Canonical SMILES	CCOC(=O)C1=C(NC(=NC1C2=C(C=C(C=C2)F)Br)C3=NC=CS3)CN4CCOCC4
InChI	InChI=1S/C21H22BrFN4O3S/c1-2-30-21(28)17-16(12-27-6-8-29-9-7-27)25-19(20-24-5-10-31-20)26-18(17)14-4-3-13(23)11-15(14)22/h3-5,10-11,18H,2,6-9,12H2,1H3,(H,25,26)
InChIKey	SQGRDKSRFFUBBU-UHFFFAOYSA-N
Purity	99.84%
Solubility	In vitro: 10 mM in DMSO
Appearance	Light yellow to yellow (Solid)
Storage	Powder: -20°C: 3 years 4°C: 2 years In solvent: -80°C: 6 months -20°C: 1 month
Complexity	719
Exact Mass	508.05800
In Vitro	Morphothiadin is a potent inhibitor on the replication of both wild-type and adefovir-resistant HBV with an IC50 of 12 nM. Morphothiadin (GLS4) shows no toxicity up to 25 μM. The cytotoxic dose whereby 50% of cells die (CC50) for primary hepatocytes is 115 μM for Morphothiadin (P<0.001). The CC90 is 190 μM for Morphothiadin (P<0.01) in HepAD38 cells. Morphothiadin strongly inhibits virus accumulation in the supernatant of HepAD38 cells at 25 nM to 100 nM (P<0.02). Results show a concentration-dependent decrease of core protein in cells treated with Morphothiadin.
In Vivo	The area under the concentration-time curve from 0 to 24 h (AUC0-24) of Morphothiadin (GLS4) is 556 h·ng/mL. After intravenous administration of 10 mg/kg Morphothiadin, the total plasma clearance and apparent volume distribution are 4.2 liters/h/kg and 7.38 liters/kg, respectively. The bioavailability of Morphothiadin is 25.5%. It is found that virus titers have increased 83.5-fold in mice treated with 3.75 mg/kg per day of Morphothiadin, 28.3-fold among mice treated with 7.5 mg/kg per day, but only 3- to 6-fold among mice treated with the higher doses of Morphothiadin. There is generally an inverse relationship between Morphothiadin dose and virus titer, with the greatest rebound seen in mice treated with 3.75 mg/kg per day of Morphothiadin (540-fold) and the smallest rebound in mice treated with 60 mg/kg per day (23-fold) (P<0.001). The Morphothiadin doses of >7.5 mg/kg per day significantly suppresses the virus replication cycle throughout the treatment period, while Morphothiadin doses of >15 mg/kg per day suppresses virus for up to 2 weeks after the end of treatment.
Target	HBV
XLogP3-AA	2.5