1092970-12-1

Basic information

• Product Name: 4-ethyl 4-(2-bromo-4-fluorophenyl)-6-(morpholinomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate
• CAS NO: 1092970-12-1
• Molecular Weight: 509.399
• Mol File: 1092970-12-1.mol

Chemical Properties

• Boiling Point: 577.2±60.0 °C(Predicted)
• Density: 1.58±0.1 g/cm3(Predicted)
• CAS DataBase Reference: 4-ethyl 4-(2-bromo-4-fluorophenyl)-6-(morpholinomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: 4-ethyl 4-(2-bromo-4-fluorophenyl)-6-(morpholinomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate(1092970-12-1)
• EPA Substance Registry System: 4-ethyl 4-(2-bromo-4-fluorophenyl)-6-(morpholinomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate(1092970-12-1)

Safety Data

• Hazardous Substances Data: 1092970-12-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-ethyl 4-(2-bromo-4-fluorophenyl)-6-(morpholinomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate is used as a potential pharmaceutical compound for its structural features, which may contribute to its interaction with biological systems. The heterocyclic ring system and functional groups could play a role in targeting specific receptors or enzymes, making it a candidate for drug development.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, 4-ethyl 4-(2-bromo-4-fluorophenyl)-6-(morpholinomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate serves as a subject for further research and analysis. Its chemical properties, such as the carboxylate group, can be studied to understand its reactivity and potential binding affinity to biological targets, aiding in the design of new therapeutic agents.
Used in Drug Discovery:
4-ethyl 4-(2-bromo-4-fluorophenyl)-6-(morpholinomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate is utilized in drug discovery processes to identify its potential as a lead compound. Its unique structural elements may offer novel mechanisms of action or selectivity profiles, which could be optimized through medicinal chemistry approaches to develop effective drugs.

Upstream product

• 59142-68-6 2-bromo-4-fluorobenzaldehyde 
• 110-91-8 morpholine 
• 1092953-04-2 ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(thiazol-2-yl)-1,4-dihydro-pyrimidine-5-carboxylate 
• 141-97-9 ethyl acetoacetate 
• 1092952-98-1 ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate 

Relevant articles and documents

Design, synthesis and evaluation of heteroaryldihydropyrimidine analogues bearing spiro ring as hepatitis B virus capsid protein inhibitors

GLS4, a potent antiviral drug candidate, has been widely studied and entered into phase II clinical trials. Nevertheless, the therapeutic application of GLS4 is limited due to poor water solubility, short half-life, and low bioavailability. In order to improve the hydrophilicity and pharmacokinetic (PK) properties of GLS4, herein, we retained the dominant fragments, and used a scaffold hopping strategy to replace the easily metabolized morpholine ring of GLS4 with diverse sizes of spiro rings consisting of hydrogen bond donor and acceptor substituents. Potent in vitro anti-HBV activity and low cytotoxicity were observed for compound 4r (EC50 = 0.20 ± 0.00 μM, CC50 > 87.03 μM), which was more potent than the positive control lamivudine (EC50 = 0.37 ± 0.04 μM, CC50 > 100.00 μM) in this assay and was about a quarter as effective as GLS4 (EC50 = 0.045 ± 0.01 μM, CC50 > 99.20 μM). Preliminary structure-activity relationship (SAR) analysis and molecular docking studies were carried out to explore potential interactions and binding mode between compounds and target protein. In terms of the physicochemical properties, 4r was predicted to be consistent with the rule-of-five, which means 4r may have favourable absorption and permeation. Finally, ADMET and PK characteristics of 4r and GLS4 were predicted to be comparable in most aspects, implying that the two compounds may have similar profiles in vivo.

Design, synthesis, and evaluation of novel heteroaryldihydropyrimidine derivatives as non-nucleoside hepatitis B virus inhibitors by exploring the solvent-exposed region

In continuation of our efforts toward the discovery of potent non-nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have explored the solvent-exposed protein region of heteroaryldihydropyrimidine derivatives. Herein, the morpholine ring of GLS4 was replaced with substituted sulfonamides and triazoles to generate novel non-nucleoside HBV inhibitors with desirable potency. In in vitro biological evaluation, several derivatives showed good anti-HBV DNA replication activity compared to lamivudine. In particular, compound II-1 displayed the most potent activity against HBV DNA replication (IC50?=?0.35?±?0.04?μM). The preliminary structure–activity relationships of the new compounds were summarized, which may help in discovering more potent anti-HBV agents via rational drug design.

Dihydropyrimidine prodrug, preparation method and applications thereof

The invention discloses a dihydropyrimidine prodrug, a preparation method and applications thereof, wherein the compound has a structure defined in the specification. The invention further relates toa preparation method of the compound, a pharmaceutical composition, and applications of the compound in the preparation of anti-HBV drugs.

Discovery of hepatitis B virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (GLS4)

Inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. Herein we described our lead optimization studies including the synthesis, molecular docking studies and structure-activity relationship (SAR) studies of a series of novel heteroaryldihydropyrimidine (HAP) inhibitors of HBV capsid assembly inhibitors, and the discovery of a potent inhibitor of HBV capsid assembly of GLS4 (ethyl 4-[2-bromo-4-fluorophenyl]-6-[morpholino-methyl]-2-[2-thiazolyl]-1,4-dihydro-pyrimidine-5-carboxylate) which is now in clinical phase 2. GLS4 demonstrated potent inhibitory activities in HBV HepG2.2.15 cell assay with an EC50value of 1 nM, and it also exhibited high potency against various drug-resistant HBV viral strains with EC50values in the range of 10–20 nM, 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.