Title compds. represented by the formula I [wherein W = (un)substituted (hetero)aryl; R1 = H, (un)substituted (cyclo)alkyl, alkenyl, etc.; R5, R6 = independently H, (un)substituted alkyl, aryl, etc.; and pharmaceutically acceptable salts thereof] were prepd. as allosteric enhancers of the A1 adenosine receptor. For example, II (R = iso-Pr) was provided in a multi-step synthesis starting from 3-(4-chlorophenyl)-3-oxopropionitrile. Certain invention compds., e.g. II (R = Me3CCH2), showed increasing the A1 specific binding of the agonist [3H]CCPA to human CHO-A1 membranes up to 5.5-fold at 10 μM concn., and exhibited about 6.3-fold increase in the Bmax value of the agonist [3H]CCPA at 10 μM. Thus, I and their pharmaceutical compns. are useful for the treatment of pain, in particular, chronic pain such as neuropathic pain, and inflammatory pain, cardiac disease or disorder such as cardiac disarrhythmias, e.g., paroxysmal supraventricular tachycardia, angina, myocardial infarction and stroke, neurol. disease or injury, sleep disorders, epilepsy and depression.
Preparation of 3-aroylthiophene-2-amines as allosteric enhancers of the A1 adenosine receptor
BARALDI, Pier Giovanni;ROMAGNOLI, Romeo;
2009
Abstract
Title compds. represented by the formula I [wherein W = (un)substituted (hetero)aryl; R1 = H, (un)substituted (cyclo)alkyl, alkenyl, etc.; R5, R6 = independently H, (un)substituted alkyl, aryl, etc.; and pharmaceutically acceptable salts thereof] were prepd. as allosteric enhancers of the A1 adenosine receptor. For example, II (R = iso-Pr) was provided in a multi-step synthesis starting from 3-(4-chlorophenyl)-3-oxopropionitrile. Certain invention compds., e.g. II (R = Me3CCH2), showed increasing the A1 specific binding of the agonist [3H]CCPA to human CHO-A1 membranes up to 5.5-fold at 10 μM concn., and exhibited about 6.3-fold increase in the Bmax value of the agonist [3H]CCPA at 10 μM. Thus, I and their pharmaceutical compns. are useful for the treatment of pain, in particular, chronic pain such as neuropathic pain, and inflammatory pain, cardiac disease or disorder such as cardiac disarrhythmias, e.g., paroxysmal supraventricular tachycardia, angina, myocardial infarction and stroke, neurol. disease or injury, sleep disorders, epilepsy and depression.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
