| abstract |
The present invention addresses the problem of providing a medicinal composition and, in particular, a compound suitable for treating nocturia. Under the expectation that nocturnal urinary frequency could be reduced via an antidiuretic action, said antidiuretic action being induced by inhibiting placental leucine aminopeptidase (P-LAP) that is an AVP-metabolic enzyme at night and thus maintaining and/or increasing endogenous AVP concentration, extensive studies were made on compounds capable of inhibiting P-LAP. As a result, it was discovered that a (2R)-3-amino-2-[(4-substituted pyridin-2-yl)methyl]-2-hydroxypropanoic acid derivative has an excellent P-LAP inhibiting effect. By testing the antidiuretic action using drinking water-loaded rats, furthermore, it was discovered that the aforesaid compound has an effect of suppressing urine production due to an increase in endogenous AVP concentration based on the inhibition of P-LAP. Thus, the present invention provides a compound that is likely usable as a therapeutic agent for nocturia based on a mechanism of inhibiting P-LAP. |