106475-47-2

Upstream product

• 5909-24-0 4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester 
• 62-53-3 aniline 
• 53554-29-3 ethyl 3,4-dihydro-2-methylthio-4-oxopyrimidine-5-carboxylate 

Downstream Products

• 211245-55-5 (2-Methanesulfanyl-4-phenylamino-pyrimidin-5-yl)-methanol 
• 211245-56-6 2-methanesulfanyl-4-phenylamino-pyrimidine-5-carboxaldehyde 
• 211245-58-8 2-Methanesulfanyl-8-phenyl-8H-pyrido[2,3-d]pyrimidin-7-one 
• 211245-59-9 2-methanesulfinyl-8-phenyl-8H-pyrido[2,3-d]pyrimidin-7-one 
• 185040-34-0 (4-ethylamino-2-methanesulfanyl-pyrimidin-5-yl)-methanol 
• 857200-26-1 2-(methylthio)-4-(phenylamino)pyrimidine-5-carboxylic acid 
• 1315513-45-1 2-Methylsulfanyl-4-phenylamino-5-pyrimidinecarboxylic acid fluoride 
• 1315513-46-2 7-Amino-2-methylsulfanyl-5-oxo-8-phenyl-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide 
• 1315513-49-5 tert-Butyl 4-[4-(7-amino-6-carbamoyl-5-oxo-8-phenyl-5,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)-3-methoxyphenyl]piperidine-1-carboxylate 
• 1315513-78-0 7-Amino-2-[2-methoxy-4-(1-methylpiperid-4-yl)phenylamino]-5-oxo-8-phenyl-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide 
• 1315513-84-8 7-Amino-2-[2-methoxy-4-(2-pyrrolidin-1-ylethyl)phenylamino]-5-oxo-8-phenyl-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide 
• 1315513-48-4 7-amino-2-methanesulfinyl-5-oxo-8-phenyl-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide 
• 1315513-47-3 7-amino-2-methanesulfonyl-5-oxo-8-phenyl-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide 
• 500880-36-4 2-(methylthio)-4-(phenylamino)pyrimidine-5-carboxamide 

Relevant academic research and scientific papers

Discovery of the c-Jun N-Terminal Kinase Inhibitor CC-90001

As a result of emerging biological data suggesting that within the c-Jun N-terminal kinase (JNK) family, JNK1 and not JNK2 or JNK3 may be primarily responsible for fibrosis pathology, we sought to identify JNK inhibitors with an increased JNK1 bias relative to our previous clinical compound tanzisertib (CC-930). This manuscript reports the synthesis and structure-activity relationship (SAR) studies for a novel series of JNK inhibitors demonstrating an increased JNK1 bias. SAR optimization on a series of 2,4-dialkylamino-pyrimidine-5-carboxamides resulted in the identification of compounds possessing low nanomolar JNK inhibitory potency, overall kinome selectivity, and the ability to inhibit cellular phosphorylation of the direct JNK substrate c-Jun. Optimization of physicochemical properties in this series resulted in compounds that demonstrated excellent systemic exposure following oral dosing, enabling in vivo efficacy studies and the selection of a candidate for clinical development, CC-90001, which is currently in clinical trials (Phase II) in patients with idiopathic pulmonary fibrosis (NCT03142191).

High activity, high selectivity and high biocompatibility BODIPY-pyrimidine derivatives for fluorescence target recognition and evaluation of inhibitory activity

BODIPY-Pyrimidine (BP) is a highly selective, highly active, and highly biocompatible fluorescent drug, which is characterized by its own activity combined with a fluorophore. The combination of pyrimidines with good biological activity and fluorophores to obtain new compounds with both anti-tumor activity and fluorescent targeting probe functions is the focus of this research. In terms of biological activity, in vitro cytotoxicity of the compounds on four human cancer cells (HepG2, HeLa, A-459, and HCT-116) and the human normal cell line L-02 was studied. BP-4 has good antiproliferative activity, and its IC50 values are 19.12 ± 2.29, 13.47 ± 3.80, 18.59 ± 7.42, 14.57 ± 2.44 and 92.48 ± 6.03 μM, respectively. Good biocompatibility with tumor cells can be observed in cell imaging. The anti-tumor mechanism of the compound was further studied by flow cytometry. After BP-2, BP-3 and BP-4 treated HeLa cells, the percentage of apoptotic cells was 19.07%, 22.09% and 27.3%, respectively. The cell cycle study found that, compared with the positive control 5-FU (48.05%), the compounds BP-2, BP-3 and BP-4 all increased the proportion of HeLa cells in the G1 phase, reaching 57.65%, 55.46% and 53.58%, respectively. In vivo bioimaging results show that all three compounds can be targeted and accurately expressed in tumor tissues. In addition, molecular docking analyzes the possible interaction between the compound and the active site of thymidylate synthase.

5 OXO-5,8-DIHYDROPYRIDO[2,3-d]PYRIMIDINE DERIVATIVES AS CAMKII KINASE INHIBITORS FOR TREATING CARDIOVASCULAR DISEASES

The present invention relates to 5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine derivatives, to their preparation and to their therapeutic use.

Novel and orally active 5-(1,3,4-oxadiazol-2-yl)pyrimidine derivatives as selective FLT3 inhibitors

5-(1,3,4-Oxadiazol-2-yl)pyrimidine derivative 1 was identified as a new class of FLT3 inhibitor from our compound library. With the aim of enhancement of antitumor activity of 2 prepared by minor modification of1, structure optimization of side chains at the 2-, 4-, and 5-positions of the pyrimidine ring of 2 was performed to improve the metabolic stability. Introduction of polar substituents on the 1,3,4-oxadiazolyl group contributed to a significant increase in the metabolic stability. As a result, a series of compounds showed increased efficacy against MOLM-13 xenograft model in mice by oral administration.

Pyridopyrimidinone derivatives for treatment of neurodegenerative disease

This invention provides pyridopyrimidines and 4-aminopyrimidines that are useful for treating cell proliferatives disorders, such as cancer and restenosis. We have now discovered a group of 7,8-dihydro-2 (amino and thio)pyrido[2,3-d]pyrimidines and 2,4-di

Heteroalkylamino-substituted bicyclic nitrogen heterocycles

The invention provides compounds represented by the formula: wherein R1, R2, R3, R4, and n are as defined in the Summary of the Invention; and individual isomers, racemic or non-racemic mixtures of isomers, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds, methods for their use as therapeutic agents, and methods of preparation thereof.

Pyrido[2,3-D]pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation

This invention provides pyridopyrimidines and 4-aminopyrimidines that are useful for treating cell proliferative disorders, such as cancer and restenosis. We have now discovered a group of 7,8-dihydro-2-(amino and thio)pyrido[2,3-d]pyrimidines and 2,4-dia

Bicyclic nitrogen heterocycles

Amino-substituted dihydropyrimido[4,5-d]pyrimidinones of the formula in which R1 represents hydrogen, lower alkyl, aryl, aryl-lower alkyl, heteroaryl, heteroaryl-lower alkyl, lower cycloalkyl or lower cycloalkyl-lower alkyl, R2 represents lower alkyl, aryl, aryl-lower alkyl, heteroaryl, heteroaryl-lower alkyl, lower cycloalkyl or lower cycloalkyl-lower alkyl, and R3 represents hydrogen, lower alkyl, aryl, aryl-lower alkyl, heteroaryl, heteroaryl-lower alkyl, lower cycloalkyl, lower cycloalkenyl or lower cycloalkyl-lower alkyl, and pharmaceutically acceptable salts thereof are protein kinase inhibitors. They can be used in the treatment or prophylaxis of inflammatory, immunological, oncological, bronchopulmonary, dermatological and cardiovascular disorders, in the treatment of asthma, central nervous system disorders or diabetic complications or for the prevention of graft rejection following transplant surgery.

Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases

The identification of 8-ethyl-2-phenylamino-8H-pyrido [2,3-d]pyrimidin-7-one (1) as an inhibitor of Cdk4 led to the initiation of a program to evaluate related pyrido [2,3-d]pyrimidin-7-ones for inhibition of cyclin-dependent kinases (Cdks). Analysis of m