1578153-27-1

Basic information

• Product Name: (3S)-4-{[(6R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(1,3-thiazol-2-yl)-3,6-dihydropyrimidin-4-yl]methyl}morpholine-3-carboxylic acid
• Synonyms: (3S)-4-{[(6R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(1,3-thiazol-2-yl)-3,6-dihydropyrimidin-4-yl]methyl}morpholine-3-carboxylic acid
• CAS NO: 1578153-27-1
• Molecular Weight: 494.931
• Mol File: 1578153-27-1.mol

Chemical Properties

• CAS DataBase Reference: (3S)-4-{[(6R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(1,3-thiazol-2-yl)-3,6-dihydropyrimidin-4-yl]methyl}morpholine-3-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (3S)-4-{[(6R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(1,3-thiazol-2-yl)-3,6-dihydropyrimidin-4-yl]methyl}morpholine-3-carboxylic acid(1578153-27-1)
• EPA Substance Registry System: (3S)-4-{[(6R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(1,3-thiazol-2-yl)-3,6-dihydropyrimidin-4-yl]methyl}morpholine-3-carboxylic acid(1578153-27-1)

Safety Data

• Hazardous Substances Data: 1578153-27-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Development:
(3S)-4-[(6R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(1,3-thiazol-2-yl)-3,6-dihydropyrimidin-4-yl]methylmorpholine-3-carboxylic acid is used as a precursor in the synthesis of new pharmaceuticals, leveraging its potential pharmacological properties for the development of novel therapeutic agents.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, (3S)-4-{[(6R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(1,3-thiazol-2-yl)-3,6-dihydropyrimidin-4-yl]methyl}morpholine-3-carboxylic acid serves as a subject of interest for research, given its unique structural features and functional groups. It may contribute to the discovery of new drug candidates or the optimization of existing ones.
Used in Drug Synthesis:
(3S)-4-[(6R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(1,3-thiazol-2-yl)-3,6-dihydropyrimidin-4-yl]methylmorpholine-3-carboxylic acid is utilized in drug synthesis processes, where its specific functional groups and stereochemistry can be exploited to create new molecules with desired biological activities.
Used in Antifungal Drug Development:
As a derivative of voriconazole, an established antifungal agent, (3S)-4-{[(6R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(1,3-thiazol-2-yl)-3,6-dihydropyrimidin-4-yl]methyl}morpholine-3-carboxylic acid is used in the development of new antifungal drugs, potentially offering improved efficacy, reduced side effects, or enhanced pharmacokinetic properties compared to existing treatments.
Used in Drug Delivery Systems:
(3S)-4-[(6R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(1,3-thiazol-2-yl)-3,6-dihydropyrimidin-4-yl]methylmorpholine-3-carboxylic acid may also be employed in the design of drug delivery systems, where its unique structural features could be used to improve the bioavailability, targeting, or release profile of therapeutic agents.

Upstream product

• 1579251-94-7 (R)-4-(2-chloro-4-fluoro-phenyl)-6-methyl-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester 
• 1578155-69-7 (4R)-6-(bromomethyl)-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dthydropyrimidine-5-carboxylic acid methyl ester 
• 106825-79-0 (S)-morpholine-3-carboxylic acid 
• 247037-77-0 4-(2-chloro-4-fluoro-phenyl)-6-methyl-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester 
• 105-45-3 acetoacetic acid methyl ester 
• 84194-36-5 2-chloro-4-fluorobenzaldehyde 
• 1187929-04-9 (3S)-morpholine-3-carboxylic acid hydrochloride salt 
• 67-56-1 methanol 

Relevant articles and documents

3-((R)-4-(((R)-6-(2-Bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholin-2-yl)propanoic Acid (HEC72702), a Novel Hepatitis B Virus Capsid Inhibitor Based on Clinical Candidate GLS4

The inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. On the basis of the preclinical properties and clinical results of GLS4, we carried out further investigation to seek a better candidate compound with appropriate anti-HBV potency, reduced hERG activity, decreased CYP enzyme induction, and improved pharmacokinetic (PK) properties. To this end, we have successfully found that morpholine carboxyl analogues with comparable anti-HBV activities to that of GLS4 showed decreased hERG activities, but they displayed strong CYP3A4 induction in a concentration-dependent manner, except for morpholine propionic acid analogues. After several rounds of modification, compound 58 (HEC72702), which had an (R)-morpholine-2-propionic acid at the C6 position of its dihydropyrimidine core ring, was found to display no induction of the CYP1A2, CYP3A4, or CYP2B6 enzyme at the high concentration of 10 μM. In particular, it demonstrated a good systemic exposure and high oral bioavailability and achieved a viral-load reduction greater than 2 log in a hydrodynamic-injected (HDI) HBV mouse model and has now been selected for further development.

Discovery and Pre-Clinical Characterization of Third-Generation 4-H Heteroaryldihydropyrimidine (HAP) Analogues as Hepatitis B Virus (HBV) Capsid Inhibitors

Described herein are the discovery and structure-activity relationship (SAR) studies of the third-generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the first- and second-generation 4-H HAPs. X-ray crystallographic study of analogue 12 (HAP_R01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen bonding interactions with capsid protein and coordinated waters. The representative analogue 10 (HAP_R10) was extensively characterized in vitro (ADMET) and in vivo (mouse PK and PD) and subsequently selected for further development as oral anti-HBV infection agent.

Crystal of dihydropyrimidine derivative and application thereof in pharmaceuticals

The invention relates to crystal of the compound (S)-4-(((R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(thiazole-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholine-3-formic acid (I) or its tautomer (Ia) and a pharmaceutical composition thereof, and further relates to application of the crystal or the pharmaceutical composition in the preparation of drugs, in particular to the application in the preparation of drugs for preventing, handling, treating, or alleviating hepatitis B virus infections.

PROCESS FOR THE PREPARATION OF 4-PHENYL-5-ALKOXYCARBONYL-2-THIAZOL-2-YL-1,4-DIHYDROPYRIMIDINE ANALOGUES

The present invention relates to a process for synthesizing a compound of formula (I), (I), wherein R1 is phenyl, which is unsubstituted, or once, twice or three times substituted by halogen; R2 is C1-6/su

SALTS OF (S)-4-[(R)-6-(2-CHLORO-4-FLUORO-PHENYL)-5-METHOXYCARBONYL-2-THIAZOL-2-YL-3,6- DIHYDRO-PYRIMIDIN-4-YLMETHYL]-MORPHOLINE-3-CARBOXYLIC ACID, SALT FORMER AND METHODS FOR PREPARING AND USING THE SAME

The present invention relates to salts of (S)-4-[(R)-6-(2-Chloro-4-fluoro-phenyl)-5- methoxycarbonyl-2-thiazol-2-yl-3,6-dihydro-pyrimidin-4-ylmethyl]-morpholine-3-carboxylic acid and an acid, the synthesis of the acid salts, and their use for the treatment of pathological disorders, particularly hepatitis B (HBV) infection.

PROCESSES FOR PREPARING DIHYDROPYRIMIDINE DERIVATIVES AND INTERMEDIATES THEREOF

The present invention relates to processes for preparing a dihydropyrimidine derivative having Formula (I) or a tautomer thereof having Formula (Ia), as well as a intermediate thereof. The processes of the invention have simple operation, high optical purity of product, high yield and convenient work-up, which is suitable for industrial production.

PROCESSES FOR PREPARING DIHYDROPYRIMIDINE DERIVATIVES AND INTERMEDIATES THEREOF

The present invention refers to processes for preparing a dihydropyrimidine compound having Formula (I), or a tautomer thereof having Formula (la), as well as a intermediate thereof. The process of the invention has simple operation, high optical purity of product, high yield and convenient work-up, which is suitable for industrial production.

Novel 6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis B virus infection

The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.

6-AMINO ACID HETEROARYLDIHYDROPYRIMIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION

The invention provides novel compounds having the general formula:, wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.