30292-75-2

Upstream product

• 141-97-9 ethyl acetoacetate 
• 766-80-3 1-bromomethyl-3-chlorobenzene 
• 587-04-2 m-Chlorobenzaldehyde 
• 15725-23-2 2-acetyl-3-(3-chloro-phenyl)-acrylic acid ethyl ester 

Downstream Products

• 1091602-30-0 C₁₇H₁₈ClN₃O₄S 
• 909379-04-0 6-[(3-chlorophenyl)methyl]-5-methyl-4H-[1,2,4]triazolo[5,1-b]pyrimidin-7-one 
• 1272367-39-1 2-(3-chlorobenzyl)-3-methyl-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitrile 
• 1335026-81-7 2-amino-6-(3-chlorobenzyl)-5-methyl[1,2,4]triazolo[1,5-a]-pyrimidin-7(4H)-one 
• 1006660-22-5 C₁₈H₁₅ClN₄O 

Relevant academic research and scientific papers

Synthesis and Pharmacological Evaluation of Triazolopyrimidinone Derivatives as Noncompetitive, Intracellular Antagonists for CC Chemokine Receptors 2 and 5

CC chemokine receptors 2 (CCR2) and 5 (CCR5) are involved in many inflammatory diseases; however, most CCR2 and CCR5 clinical candidates have been unsuccessful. (Pre)clinical evidence suggests that dual CCR2/CCR5 inhibition might be more effective in the treatment of such multifactorial diseases. In this regard, the highly conserved intracellular binding site in chemokine receptors provides a new avenue for the design of multitarget ligands. In this study, we synthesized and evaluated the biological activity of a series of triazolopyrimidinone derivatives in CCR2 and CCR5. Radioligand binding assays first showed that they bind to the intracellular site of CCR2, and in combination with functional assays on CCR5, we explored structure-affinity/activity relationships in both receptors. Although most compounds were CCR2-selective, 39 and 43 inhibited β-arrestin recruitment in CCR5 with high potency. Moreover, these compounds displayed an insurmountable mechanism of inhibition in both receptors, which holds promise for improved efficacy in inflammatory diseases.

Antischistosomal Activity of Pyrido[1,2-a]benzimidazole Derivatives and Correlation with Inhibition of β-Hematin Formation

The extensive use of praziquantel against schistosomiasis raises concerns about drug resistance. New therapeutic alternatives targeting critical pathways within the parasite are therefore urgently needed. Hemozoin formation in Schistosoma presents one such target. We assessed the in vitro antischistosomal activity of pyrido[1,2-a]benzimidazoles (PBIs) and investigated correlations with their ability to inhibit β-hematin formation. We further evaluated the in vivo efficacy of representative compounds in experimental mice and conducted pharmacokinetic analysis on the most potent. At 10 μM, 48/57 compounds resulted in >70% mortality of newly transformed schistosomula, whereas 37 of these maintained >60% mortality of adult S. mansoni. No correlations were observed between β-hematin inhibitory and antischistosomal activities against both larval and adult parasites, suggesting possible presence of other target(s) or a mode of inhibition of crystal formation that is not adequately modeled by the assay. The most active compound in vivo showed 58.7 and 61.3% total and female worm burden reduction, respectively. Pharmacokinetic analysis suggested solubility-limited absorption and high hepatic clearance as possible contributors to the modest efficacy despite good in vitro activity. The PBIs evaluated in this report thus merit further optimization to improve their efficacy and to elucidate their possible mode of action.

7-HYDROXY-PYRAZOLO[1,5-A] PYRIMIDINE COMPOUNDS AND THEIR USE AS CCR2 RECEPTOR ANTAGONISTS

The compounds of formula (I) are antagonists of the CCR2 receptor Wherein R1-7 and A are as defined in the claims.

7-HYDROXY-PYRAZOLO[1,5-A] PYRIMIDINE COMPOUNDS AND THEIR USE AS CCR2 RECEPTOR ANTAGONISTS

The compounds of formula (I) are antagonists of the CCR2 receptor Wherein R1-7 and A are as defined in the claims.

4H- [1, 2, 4] TRIAZOLO [5, 1 -B] PYRIMIDIN-7 -ONE DERIVATIVES AS CCR2B RECEPTOR ANTAGONISTS

The present invention relates to novel compounds for use in the compositions, to processes for their preparation, to intermediates useful in their preparation and to their use as therapeutic agents. The present invention also relates to pharmaceutical com

Carbonic anhydrase inhibitors: Synthesis and inhibition studies against mammalian isoforms I-XV with a series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides

A series of 2-(hydrazinocarbonyl)-3-substitutedphenyl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy- functionalities, as well as the perfluorophenyl moiety have been synthesized and

2-OXO-2H-CHROMENE COMPOUNDS

Compounds of structural formula (1) modulate CRTH2 activity and are of utility in, for example, respiratory diseases formula (1): in which: A represents a direct bond, an optionally substituted alkylene or alkenylene group, or a group of formula Z-(optionally substituted)alkylene; B represents a direct bond, an optionally substituted alkylene or alkenylene group, or a group of formula Z-(optionally substituted)alkylene or (optionally substituted)alkylene-Z; Z represents an oxygen atom, an NH or N-alkyl group, or a group of formula S(O)n, in which n = 0 to 2; X represents a carboxylic acid, tetrazole, 3-hydroxyisoxazole, hydroxamic acid, phosphinate, phosphonate, phosphonamide, sulfonic acid or a group of formula C(=O)NHSO2W or SO2NHC(=O)W; W represents an optionally substituted aryl or heteroaryl group or an optionally substituted alkyl or cycloalkyl group; Y represents an optionally substituted phenyl or 5- or 6-membered heteroaryl group, Ra, Rb, and Rc independently represent hydrogen, acyl, alkoxy, alkoxycarbonyl, alkylamino, alkylsulfinyl, alkylsulfonyl, alkylthio, -NH2, aminoalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, cyano, dialkylamino, halo, haloalkoxy, haloalkyl, alkyl, alkenyl, -OH, optionally substituted aryl, optionally substituted heteroaryl, heterocycloalkyl, aminoacyl, aminosulfonyl, acylamino, sulfonylamino, heteroarylalkyl, cyclic amino, aryloxy, heteroaryloxy, arylalkyloxy or heteroarylalkyloxy.