1027493-33-9

Upstream product

• 4640-66-8 p-chlorobenzoylacetonitrile 
• 85-44-9 phthalic anhydride 
• 50508-66-2 (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone 

Downstream Products

• 1027493-34-0 2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-methylthiophen-2-yl]isoindoline-1,3-dione 
• 1027493-14-6 {2-Amino-5-methyl-4-[(4-(4-nitrophenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone 
• 1027493-10-2 {2-Amino-5-methyl-4-[(4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone 
• 1027493-20-4 {2-Amino-5-methyl-4-[(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone 
• 1027493-22-6 {2-Amino-4-[(4-(4-chloro-3-(trifluoromethyl)phenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone 
• 1394867-70-9 2-[3-(4-chlorobenzoyl)-5-methyl-4-[(4-phenylpiperazin-1-yl)methyl]thiophen-2-yl]isoindoline-1,3-dione 
• 1394867-71-0 2-[4-[(4-benzylpiperazin-1-yl)methyl]-3-(4-chlorobenzoyl)-5-methylthiophen-2-yl]isoindoline-1,3-dione 
• 1394867-82-3 2-{3-(4-chlorobenzoyl)-5-methyl-4-[(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)methyl]thiophen-2-yl}isoindoline-1,3-dione 
• 1394867-83-4 2-{3-(4-chlorobenzoyl)-4-[(4-(4-chloro-3-(trifluoromethyl)phenyl)piperazin-1-yl)methyl]-5-methylthiophen-2-yl}isoindoline-1,3-dione 
• 1027493-09-9 {2-Amino-5-methyl-4-[(4-phenylpiperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone 
• 1027493-16-8 [2-amino-4-((4-benzylpiperazin-1-yl)methyl)-5-methylthiophen-3-yl](4-chlorophenyl)methanone 
• 1027493-08-8 {2-Amino-4-[(4-(4-fluorophenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone 
• 1027493-11-3 {2-Amino-4-[(4-(4-chlorophenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone 
• 1027493-21-5 {2-Amino-4-[(4-(3-chlorophenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone 

Relevant academic research and scientific papers

Synthesis and biological evaluation of 2-amino-3-(4-chlorobenzoyl)-4-[(4- arylpiperazin-1-yl)methyl]-5-substituted-thiophenes. Effect of the 5-modification on allosteric enhancer activity at the A1 adenosine receptor

We have recently reported a detailed structure-activity relationship study around a wide series of 2-amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl) methyl]thiophene derivatives as potent allosteric enhancers of the A1 adenosine receptor. In the current study, we have continued to explore the potential of these molecules by synthesizing of a novel series of analogues that share a common 2-amino-3-(4-chlorobenzoyl)thiophene nucleus. Modifications were focused on varying the nature and the position of electron-withdrawing or electron-releasing groups on the phenyl of an arylpiperazine moiety attached at the 4-position of the thiophene ring by a methylene chain, combined with the presence of small alkyl groups (methyl or ethyl), bromine, or aryl moieties at the thiophene C-5 position. In this series of compounds, substitution at the 5-position had a fundamental effect on activity, with the 5-aryl group contributing additively to the allosteric enhancer activity. The thiophene C-5 aryl derivatives 4ad, 4ak, and 4al were the most active compounds in binding and functional experiments.

ALLOSTERIC ENHANCERS OF THE A1 ADENOSINE RECEPTOR

The present invention provides compounds of formula (I) wherein W, R1, R5 and R6 have a meaning as defined herein in the specification. The compounds of formula (I) are allosteric enhancers of the A1 adenosine receptor and, thus, may be employed for the treatment of conditions mediated by the A1 adenosine receptor. Accordingly, the compounds of formula (I) may be employed for treatment of pain, in particular, chronic pain such as neuropathic pain, and inflammatory pain, cardiac disease or disorder such as cardiac disarrhythmias, e.g., peroxysmal supraventricular tachycardia, angina, myocardial infarction and stroke, neurological disease or injury, sleep disorders, epilepsy and depression.

ALLOSTERIC MODULATORS OF THE A1 ADENOSINE RECEPTOR

The present invention provides compounds of formula (I) wherein R1, R2, R3, R4 and Q have a meaning as defined herein in the specification. The compounds of formula (I) are allosteric modulators of the A1 adenosine receptor and, thus, may be employed for the treatment of conditions mediated by the A1 adenosine receptor. Accordingly, the compounds of formula (I) may be employed for treatment of pain, in particular, chronic pain such as neuropathic pain; cardiac disease or disorder such as cardiac disarrhythmias, e.g., peroxysmal supraventricular tachycardia, angina, myocardial infarction and stroke; neurological disease or injury; sleep disorder; epilepsy; and depression.