1263422-34-9

Upstream product

• 1351373-56-2 6,8-dibromo-3-iodo-imidazo[1,2-a]pyrazine 
• 860173-33-7 4-(cyclopropylaminocarbonyl)phenylboronic acid pinacol ester 
• 130290-79-8 4-tetrahydropyranmethylamine 

Downstream Products

• 1263422-32-7 4-(6-(4-cyanophenyl)-8-((tetrahydro-2H-pyran-4-yl)methylamino)imidazo[1,2-a]pyrazin-3-yl)-N-cyclopropylbenzamide 
• 1263422-30-5 N-cyclopropyl-4-(6-phenyl-8-((tetrahydro-2H-pyran-4-yl)methylamino)imidazo[1,2-a]pyrazin-3-yl)benzamide 

Relevant academic research and scientific papers

Discovery of imidazo[1,2- b ]pyridazine derivatives: Selective and orally available Mps1 (TTK) kinase inhibitors exhibiting remarkable antiproliferative activity

Monopolar spindle 1 (Mps1) is an attractive oncology target due to its high expression level in cancer cells as well as the correlation of its expression levels with histological grades of cancers. An imidazo[1,2-a]pyrazine 10a was identified during an HTS campaign. Although 10a exhibited good biochemical activity, its moderate cellular as well as antiproliferative activities needed to be improved. The cocrystal structure of an analogue of 10a guided our lead optimization to introduce substituents at the 6-position of the scaffold, giving the 6-aryl substituted 21b which had improved cellular activity but no oral bioavailability in rat. Property-based optimization at the 6-position and a scaffold change led to the discovery of the imidazo[1,2-b]pyridazine-based 27f, an extremely potent (cellular Mps1 IC50 = 0.70 nM, A549 IC50 = 6.0 nM), selective Mps1 inhibitor over 192 kinases, which could be orally administered and was active in vivo. This 27f demonstrated remarkable antiproliferative activity in the nanomolar range against various tissue cancer cell lines.

FUSED IMIDAZOLE DERIVATIVE HAVING TTK INHIBITORY ACTION

Provided are a compound represented by general formula (1) and having a TTK inhibitory action and a medicine containing the compound. In formula (1), (X, Y, V, W) is (—N═, ═CR1—, ═N—, —CR7═), (—CR2═, ═N—, ═N—, —CR7═), etc.; A is an (un)substituted aromatic hydrocarbon ring, etc.; L is a single bond, —C(═O)—NRA—, etc.; Z is a group represented by the formula —NR3R4 or a group represented by the formula —OR5; R1 to R3, R6, and R7 each is a hydrogen atom, etc.; R4 and R5 each is an (un)substituted alkyl, etc.; and R8 is an (un)substituted cycloalkyl, etc.