1476847-49-0

Upstream product

• 137571-73-4 5,7-dihydroxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one 
• 83-30-7 acide 2,4,6-trihydroxybenzoique 
• 100-39-0 benzyl bromide 
• 532394-23-3 5-hydroxy-7-methoxy-2,2-dimethyl-benzo[1,3]dioxin-4-one 

Downstream Products

• 1476847-50-3 2-(benzyloxy)-6-hydroxy-4-methoxybenzaldehyde 
• 1476847-51-4 1-[4-(benzyloxy)-6-methoxy-1-benzofuran-2-yl]ethan-1-one 
• 1476847-52-5 1-(4-(benzyloxy)-6-methoxybenzofuran-2-yl)-2-bromoethanone 
• 1476848-33-5 2-(4-(benzyloxy)-6-methoxybenzofuran-2-yl)-6-methylimidazo[1,2-b]pyridazine 
• 1476848-37-9 (S)-6-(4-(benzyloxy)-6-methoxybenzofuran-2-yl)-2-(1-fluoroethyl)imidazo[2,1-b][1,3,4]thiadiazole 
• 1476847-54-7 6-(4-(benzyloxy)-6-methoxybenzofuran-2-yl)-2-bromoimidazo[2,1-b][1,3,4]thiadiazole 

Relevant academic research and scientific papers

Synthesis and evaluation of novel and potent protease activated receptor 4 (PAR4) antagonists based on a quinazolin-4(3H)-one scaffold

Protease activated receptor 4 (PAR4) is an important target in antiplatelet therapy to reduce the risk of heart attack and thrombotic complications in stroke. PAR4 antagonists can prevent harmful and stable thrombus growth, while retaining initial thrombus formation, by acting on the late diffusion stage of platelet aggregation, and may provide a safer alternative to other antiplatelet agents. To date, only two PAR4 antagonists, BMS-986120 and BMS-986141 have entered clinical trials for thrombosis. Thus, the development of a potent and selective PAR4 antagonist with a novel chemotype is highly desirable. In this study, we explored the activity of quinazolin-4(3H)-one-based PAR4 antagonists, beginning with their IDT analogues. By repeated structural optimisation, we developed a series of highly selective PAR4 antagonists with nanomolar potency on human platelets. Of these, 13 and 30g, with an 8-benzo[d]thiazol-2-yl-substituted quinazolin-4(3H)-one structure, showed optimal activity (h. PAR4-AP PRP IC50 = 19.6 nM and 6.59 nM, respectively) on human platelets. Furthermore, 13 and 30g showed excellent selectivity for PAR4 versus PAR1 and other receptors (IC50s > 10 μM) on human platelets. And 13 and 30g were lack of cross-reactivity for PAR1 or PAR2 (PAR1 AP FLIPR IC50 > 3162 nM, PAR2 AP FLIPR IC50 > 1000 nM) in the calcium mobilization assays. Metabolic stability assays and cytotoxicity tests of 13 and 30g indicated that these compounds could sever as promising drug candidates for the development of novel PAR4 antagonists. In summary, the quinazolin-4(3H)-one-based analogues are the first reported chemotypes with excellent activity and selectivity against PAR4, and, in the current study, we expanded the structural diversity of PAR4 antagonists. The two compounds, 13 and 30g, found in our study could be promising starting points with great potential for further research in antiplatelet therapy.

Discovery of Potent Protease-Activated Receptor 4 Antagonists with in Vivo Antithrombotic Efficacy

In an effort to identify novel antithrombotics, we have investigated protease-activated receptor 4 (PAR4) antagonism by developing and evaluating a tool compound, UDM-001651, in a monkey thrombosis model. Beginning with a high-throughput screening hit, we identified an imidazothiadiazole-based PAR4 antagonist chemotype. Detailed structure-activity relationship studies enabled optimization to a potent, selective, and orally bioavailable PAR4 antagonist, UDM-001651. UDM-001651 was evaluated in a monkey thrombosis model and shown to have robust antithrombotic efficacy and no prolongation of kidney bleeding time. This combination of excellent efficacy and safety margin strongly validates PAR4 antagonism as a promising antithrombotic mechanism.

HETEROCYCLIC COMPOUNDS AS INHIBITORS OF PLATELET AGGREGATION

The present invention provides compounds of Formula I: wherein Y, AA, W, R3, R2, R4, R5, R6, R7, X1, X2, X3, X4 and X5 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug or esters or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

IMIDAZOTHIADIAZOLE AND IMIDAZOPYRIDAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION

The present invention provides imidazothiadiazole compounds of Formula (I); Wherein W,Y, R0, R2, R4, Ra, Rb, X1, X2, X3 and X4 are as defined herein,, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

IMIDAZOTHIADIAZOLE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION

The present invention provides imidazothiadiazole compounds of Formula (I) wherein A, B, D, Rx, R1, R2, R3, X1, X2 and s are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments.

IMIDAZOTHIADIAZOLE AND IMIDAZOPYRAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION

The present invention provides thiazole compounds of Formula I wherein W, Y, R0, R2, R4, R5, R6, R7, X1, X2, X3 and X4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

PAR4 AGONIST PEPTIDES

The present invention provides PAR4 agonist peptides. These peptides are useful for developing robust PAR4 receptor assays.