Methods of use comprising deuterated pyrazino[2,1-a]isoquinolines

摘要

This invention in one embodiment is directed to a compound of Formula Ia;;
where the designation (R) indicates that the designated carbon has the (R) stereochemistry; and wherein Z1 is hydrogen or fluorine; Z2 is hydrogen, deuterium, or fluorine; Z3 is deuterium; Z4 is fluorine; m is an integer from 0 to 10; n is an integer from 0 to 2; provided that: the sum of m+n does not exceed 10; and when both Z1 and Z2 are hydrogen, the sum of m+n is greater than 0, and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating diseases and conditions that are beneficially treated by administering an antihelminthic agent, such as praziquantel.

主权项

1. A method of disrupting cell permeability to calcium ions in a parasitic cell, comprising contacting said cell with a compound of Formula Ia:or a pharmaceutically acceptable salt thereof, wherein:
Z1 is hydrogen or fluorine; Z2 is hydrogen, deuterium, or fluorine; Z3 is deuterium; Z4 is fluorine; m is 2, 4, 6, 8 or 10; and n is 0 or 2;provided that:
the sum of m and n does not exceed 10.