14160-93-1

Usage

Chemical Properties

Yellow solid

InChI:InChI=1/C5H4ClN3O/c6-4-3(1-10)5(7)9-2-8-4/h1-2H,(H2,7,8,9)

Upstream product

• 5305-40-8 2,6-dichloro-pyrimidine carbaldehyde 

Downstream Products

• 155087-15-3 methyl 4-aminothieno[2,3-d]pyrimidine-6-carboxylate 
• 454685-81-5 4-amino-5-benzylmethylaminomethyl-6-chloropyrimidine 
• 949001-19-8 C₂₀H₂₅N₇O₂ 
• 916666-98-3 4-(6-amino-5-formyl-pyrimidin-4-yl)-piperazine-1-carboxylic acid (4-isopropoxy-phenyl)-amide 
• 454685-82-6 4-amino-5-benzylmethylaminomethyl-6-iodopyrimidine 
• 454685-84-8 5-{[(2-chloro-benzyl)-methyl-amino]-methyl}-6-iodo-pyrimidin-4-ylamine 
• 893444-52-5 C₁₅H₁₉ClN₄O₃ 
• 944342-88-5 4-amino-6-(4-benzyloxy-3-chloro-phenylamino)-pyrimidine-5-carbaldehyde 
• 1004956-70-0 C₁₁H₉FN₄O*ClH 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of 4-aminopyrimidine-5-cabaldehyde oximes as dual inhibitors of c-Met and VEGFR-2

The synergistically collaboration of c-Met/HGF and VEGFR-2/VEGF leads to development of tumor angiogenesis and progression of various human cancers. Therefore, inhibiting both HGF/c-Met and VEGF/VEGFR signaling may provide a novel and effective therapeutic approach for treating patients with abroad spectrum of tumors. Toward this goal, we designed and synthesized a series of derivatives bearing 4-aminopyrimidine-5-cabaldehyde oxime scaffold as potent dual inhibitors of c-Met and VEGFR-2. The cell proliferation assay in vitro demonstrated most target compounds have inhibition potency both on c-Met and VEGFR-2 with IC50values in nanomolar range, especially compound 14i, 18a and 18b. Based on the further enzyme assay in vitro, compound 18a was considered as the most potent one, the IC50s of which were 210?nM and 170?nM for c-Met and VEGFR-2, respectively. Following that, we docked the compound 10 and 18a with the proteins c-Met and VEGFR-2, and interpreted the SAR of these analogs. All the results indicate that 18a is a dual inhibitors of c-Met and VEGFR-2 that holds promising potential.

Lead optimization to improve the antiviral potency of 2-aminobenzamide derivatives targeting HIV-1 Vif-A3G axis

The viral infectivity factor (Vif)–apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) axis has been recognized as a valid target for developing novel small-molecule therapies for acquired immune deficiency syndrome (AIDS) or for enhancing innate immunity against viruses. Our previous work reported the novel Vif antagonist 2-amino-N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide (2) with strong antiviral activity. In this work, through optimizations of ring C of 2, we discovered the more potent compound 6m with an EC50 of 0.07 μM in non-permissive H9 cells, reflecting an approximately 5-fold enhancement of antiviral activity compared to that of 2. Western blotting indicated that 6m more strongly suppressed the defensive protein Vif than 2 at the same concentration. Furthermore, 6m suppressed the replication of various clinical drug-resistant HIV strains (FI, NRTI, NNRTI, IN and PI) with relatively high efficacy. These results suggested that compound 6m is a more potent candidate for treating AIDS.

Discovery and Evaluation of Pyrazolo[3,4-d]pyridazinone as a Potent and Orally Active Irreversible BTK Inhibitor

The identification and lead optimization of a series of pyrazolo[3,4-d]pyridazinone derivatives are described as a novel class of potent irreversible BTK inhibitors, resulting in the discovery of compound 8. Compound 8 exhibited high potency against BTK kinase and acceptable PK profile. Furthermore, compound 8 demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model.

PROCESSES AND INTERMEDIATES FOR MAKING A JAK INHIBITOR

This invention relates to processes and intermediates for making {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, useful in the treatment of diseases related to the activity of Janus kinases (JAK) including inflammatory disorders, autoimmune disorders, cancer, and other diseases.

Preparation methods of JAK inhibitor and salt thereof

The present invention relates to preparation methods of a JAK inhibitor and a salt thereof. The preparation method comprises: (1) carrying out a Suzuki coupling reaction on (R)-3-(4-boronic acid-1H-pyrazol-1-yl)-3-cyclopentylpropionitrile and 6-halogen-5-(2-methoxyvinyl)pyrimidin-4-ylamine to generate (3R)-cyclopentyl-3-[4-(5-(2-methoxyvinyl)pyrimidin-4-ylamine)pyrazol-1-yl]propionitrile; and (2)carrying out a protection group removing and ring-closure reaction on the (3R)-cyclopentyl-3-[4-(5-(2-methoxyvinyl)pyrimidin-4-ylamine)pyrazol-1-yl]propionitrile to generate a JAK inhibitor ruxolitinib. According to the present invention, the new ruxolitinib preparation route is provided, wherein each reaction of the route has the high yield, the total yield of the route is high, the purity of theobtained product is good, the post-treatment of the reaction is simple, and column chromatography is not required; by adopting the route, the required raw materials or catalysts and other materials are relatively easy to obtain; and compared to the method in the prior art, the method of the present invention is economical and is suitable for industrial production.

Intermediate of JAK inhibitor, and preparation method thereof

The present invention relates to a novel key intermediate of a JAK inhibitor ruxolitinib, and a preparation method thereof, wherein the chemical name of the intermediate is (R)-3-(4-boric acid-1H-pyrazole-1-yl)-3-cyclopentylpropionitrile. According to the present invention, the new ruxolitinib preparation route is provided, wherein each reaction of the route has the high yield, the total yield ofthe route is high, the purity of the obtained product is good, the post-treatment of the reaction is simple, and column chromatography is not required; by adopting the route, the required raw materials or catalysts and other materials are relatively easy to obtain; and compared to the method in the prior art, the method of the present invention is economical and is suitable for industrial production.

Substituted aminopyrimidine compounds and their method and use thereof

The invention relates to a new aminopyrimidine compound and an application thereof as a drug for treating disorder or diseases related to PI3-kinase abnormity in a free form or a pharmaceutically acceptable salt and preparation form. The invention also relates to a pharmaceutical composition which contains the new aminopyrimidine compound and an application of the pharmaceutical composition in treating mammal disorder or diseases and especially treating human disorder or diseases related to the PI3-kinase abnormity, such as treatment of immunity and inflammatory diseases of PI3-kinase regulation which plays a leading role in a leucocyte function and treatment of proliferative diseases which are related to PI3-kinase activity and include but not limited to leukaemia and solid tumor.

BTK INHIBITOR

Provided are a series of BTK inhibitors, and specifically disclosed are a compound, pharmaceutically acceptable salt thereof, tautomer thereof or prodrug thereof represented by formula (I), (II), (III) or (IV).

Substituted pyrimidine derivatives with Akt inhibiting activity, and preparation method and application thereof

The invention relates to novel substituted pyrimidine derivatives with Akt inhibiting activity and a preparation method thereof, a pharmaceutical composition comprising the substituted pyrimidine derivatives and salts thereof, and application of the substituted pyrimidine derivatives and salts thereof in preparing drugs for preventing and/or treating tumors. The structural formula of the compounds is disclosed as Formula (I) or Formula (II). The compounds have the advantages of novel structure, outstanding Akt inhibiting activity, high safety and low preparation cost, and have favorable application prospects in preparing antineoplastic drugs.

PROCESSES AND INTERMEDIATES FOR MAKING A JAK INHIBITOR

This invention relates to processes and intermediates for making {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, useful in the treatment of diseases related to the activity of Janus kinases (JAK) including inflammatory disorders, autoimmune disorders, cancer, and other diseases.