1027492-97-2

Upstream product

• 7677-96-5 spiro[1,3-benzodioxole-2,4’-piperidine] 
• 1027493-30-6 2-[5-bromo-4-bromomethyl-3-(4-chloro-benzoyl)-thiophen-2-yl]-isoindole-1,3-dione 
• 1456734-95-4 2-[5-bromo-3-(4-chlorobenzoyl)-4-(spiro-benzo[1,3-d]-dioxol-2-yl)-piperidin-1-ylmethyl-thiophen-2-yl]-isoindole-1,3-dione 

Relevant academic research and scientific papers

Synthesis and biological effects of novel 2-amino-3-(4-chlorobenzoyl)-4- substituted thiophenes as allosteric enhancers of the A1 adenosine receptor

Allosteric enhancers for the A1 adenosine receptor represent a novel and unique drug design strategy to augment the response to endogenous adenosine in a site- and event-specific manner.We have previously investigated a detailed structure-activity relationship study around a wide series of 2-amino-3-aroyl-4-[(4-arylpiperazin-1-yl)methyl]thiophene derivatives as potent allosteric enhancers of the A1 adenosine receptor. In this manuscript we report our investigation on the influence on allosteric enhancer activity of further substitution at the 4-position of the 2-amino-3-(4-chlorobenzoyl)- thiophene system to explore bulk tolerance by replacement of the arylpiperazine moiety with a series of fused indole nuclei corresponding to 1,2,3,4-tetrahydropyrazino[1,2-a ]indole, 1,2,3,4,10,10a-hexahydropyrazino[1,2- a]indole, tet-rahydro- γ-carboline, tetrahydroisoquinoline, spiro-1,3-benzodioxolepiperidine, aliphatic tertiary amine, N-alkylaniline, aryl ether and aryl thioether templates. The 1,2,3,4-tetrahydropyrazino[1,2- a]indole derivatives 3-ec and 3- were the most active compounds in binding (saturation and competition) and functional cAMP studies, being able to potentiate agonist [3H]CCPA binding to the A1 receptor. This study also shows that it is possible to obtain a good separation between allosteric enhancement and antagonistic activity at the A1 adenosine receptor.

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.