859517-49-0

Upstream product

• 3934-20-1 2,6-Dichloropyrimidine 
• 121124-97-8 3-formyl-4-methoxyphenylboronic acid 

Downstream Products

• 1187660-13-4 C₂₃H₂₄N₄O₄ 
• 1187660-61-2 C₄₆H₆₇N₇O₈ 
• 1187660-60-1 C₃₇H₅₂N₆O₉S 
• 1187660-15-6 C₃₆H₅₀N₆O₇ 
• 1187660-62-3 C₃₂H₄₃N₇O₄ 
• 1187660-14-5 C₃₁H₄₂N₆O₅ 
• 1312603-22-7 [5-(2-chloropyrimidin-4-yl)-2-methoxyphenyl]methanol 
• 1312603-65-8 [4-(3-allyloxymethyl-4-methoxyphenyl)-pyrimidin-2-yl]-[3-allyloxymethyl-4-(2-pyrrolidin-1-yl-ethoxy)phenyl]amine 
• 1107660-23-0 4-(3-allyloxymethyl-4-methoxyphenyl)-2-chloropyrimidine 

Relevant academic research and scientific papers

Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7, 26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27) ,16,21,23-decaene (SB1518), a potent Janus Kinase 2/Fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma

Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2 V617F), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a treatment for myelofibrosis (MF). Herein, we describe the design and synthesis of a series of small molecule 4-aryl-2-aminopyrimidine macrocycles and their biological evaluation against the JAK family of kinase enzymes and FLT3. The most promising leads were assessed for their in vitro ADME properties culminating in the discovery of 21c, a potent JAK2 (IC50 = 23 and 19 nM for JAK2 WT and JAK2V617F, respectively) and FLT3 (IC50 = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC50 = 1280 and 520 nM, respectively). Further profiling of 21c in preclinical species and mouse xenograft and allograft models is described. Compound 21c (SB1518) was selected as a development candidate and progressed into clinical trials where it is currently in phase 2 for MF and lymphoma.

4-ARYL-2-ANILINO-PYRIMIDINES AS PLK KINASE INHIBITORS

The present invention relates to compounds of Formula (Ia) or (Ib), the N-oxide forms, pharmaceutically acceptable addition salts, quaternary amines, stereoisomers, tautomers, racemics, metabolites, prodrugs, hydrates, or solvates thereof, wherein Y1, m, n, R1; X1; X2; R2; X3; X4; R3; and R4 have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to compounds that are kinase inhibitors useful for the treatment of disease states mediated by kinase, especially PLK4, in particular such compounds that are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

2-(AMINO-SUBSTITUTED)-4-ARYL PYRAMIDINES AND RELATED COMPOUNDS USEFUL FOR TREATING INFLAMMATORY DISEASES

A heterocyclic inhibitor having the formula (I), with the variables defined herein, which is useful for treating inflammatory and other physiological disorders in which PKC-theta isoform plays a role.