Dimethylarginine dimethylaminohydrolase inhibitors and methods of use thereof

摘要

The present disclosure provides DDAH modulators. Thus, the present disclosure provides a method of treating a patient suffering from a disorder characterized by excessive NO production and/or elevated DDAH activity, the method comprising administering to said patient an effective amount of a compound of one of formulae I-X. The present disclosure also provides a pharmaceutical composition comprising a compound of one of formulae I-X.

主权项

1. A method of treating an individual suffering from idiopathic pulmonary fibrosis, the method comprising administering to the individual an effective amount of a pharmaceutical formulation comprising:
a) a dimethylarginine dimethylaminohydrolase (DDAH) inhibitor of one of the following formulas: wherein Q1 is N or CH; R1 is selected from alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, cyano, halogen, acyl, aminoacyl, nitro, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl; R2, R3, R4, and R5 are independently selected from hydrogen, alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, cyano, halogen, acyl, aminoacyl, nitro, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl; and m is an integer from zero to four; wherein R1 is selected from alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, cyano, halogen, acyl, aminoacyl, nitro, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl; R2, R3, R4, and R5 are independently selected from is selected from alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, cyano, halogen, acyl, aminoacyl, nitro, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl; and m is an integer from zero to four; wherein R1 is selected from alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, cyano, halogen, acyl, aminoacyl, nitro, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl; R2, R3, R4, and R5 are independently selected from is selected from alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, cyano, halogen, acyl, aminoacyl, nitro, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl; and m is an integer from zero to four; and b) a flowable formulation suitable for delivery by inhalation, wherein said pharmaceutical formulation is administered locally to the airways wherein the DDAH inhibitor is administered in a dosage range of from about 1 μg to 10 mg.