Cyclic and acyclic hydrazine derivatives compositions including them and uses thereof
The present invention relates to compositions and methods for treating a disease in an animal, which disease is responsive to inhibiting of the functional cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide by administering to a mammal in need thereof an effective amount of a cyclic or acyclic hydrazine derivative including those of formulas II or III: or compositions thereof, thereby treating the disease. The present invention particularly, relates to a method of treating diarrhea and polycystic kidney disease.
1. A compound represented by formula II:
wherein:
R 2 is substituted aryl, substituted with 1 or 2 halo groups;
X and X 1 are independently halo;
is a single or double bond; and
n is 1;
or a pharmaceutically acceptable salt thereof.
2. A compound represented by formula III:
wherein:
R 1 is substituted alkyl, substituted with an aryl group that is optionally substituted with a hydroxy group;
X and X 1 are independently halo; and
is a single or double bond;
or a pharmaceutically acceptable salt thereof.
3. A compound which is:
6-(3,5-dibromo-4-hydroxyphenyl)-2-(3-hydroxybenzyl)-4,5-dihydropyridazin-3(2H)-one or
(3-bromo-4-chlorophenyl)(3-(3,5-dibromo-4-hydroxyphenyl)-4,5-dihydro-1 H-pyrazol-1-yl)methanone, or
a pharmaceutically acceptable salt thereof.
4. A pharmaceutical composition comprising a therapeutically effective amount of a compound as defined in any one of claims 1 , 2 , and 3 and a pharmaceutically acceptable carrier.
5. A method for treating diarrhea in an animal in need thereof comprising administering to the animal an effective amount of the composition of claim 4 , thereby treating diarrhea.