METHODS FOR TREATMENT OF FIBROTIC DISEASES
Methods for treatment of fibrotic diseases using compounds of formula I wherein R A is hydrogen, R 7 and R 8 are independently selected from H and SO 2 NR 3 R 4 , one of R 7 and R 8 is hydrogen, and R 1 , R 2 , R 3 , and R 4 are each independently selected from H, alkyl, heteroalkyl, cycloalkyl, arylcycloalkyl, aryl, heteroaryl, heterocycloalkyl, and each of NR 1 R 2 and NR 3 R 4 can independently combine to form a heterocycloalkyl, and wherein said alkyl, heteroalkyl, cycloalkyl, arylcycloalkyl, aryl, heteroaryl, or heterocycloalkyl may be optionally substituted, or a pharmaceutically acceptable salt, ester, amide, stereoisomer, geometric isomer or prodrug thereof.
1 . A method of treating and/or preventing a fibrotic disease, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I
wherein R A is hydrogen,
R 7 and R 8 are independently selected from H and SO 2 NR 3 R 4 ,
one of R 7 and R 8 is hydrogen, and
R 1 , R 2 , R 3 , and R 4 are each independently selected from H, alkyl, heteroalkyl, cycloalkyl, arylcycloalkyl, aryl, heteroaryl, heterocycloalkyl, and each of NR 1 R 2 and NR 3 R 4 can independently combine to form a heterocycloalkyl, and wherein said alkyl, heteroalkyl, cycloalkyl, arylcycloalkyl, aryl, heteroaryl, or heterocycloalkyl may be optionally substituted,
or a pharmaceutically acceptable salt, ester, amide, stereoisomer, geometric isomer or prodrug thereof.
2 . The method of claim 1 , wherein NR 1 R 2 and NR 3 R 4 are independently 6- to 15-membered heterocycloalkyl containing one nitrogen in the ring.
3 . The method of claim 1 , wherein the compound of formula I has the following structure:
or a pharmaceutically acceptable salt, ester, amide, stereoisomer, geometric isomer or prodrug thereof.
4 . The method of claim 1 , wherein the fibrotic disease is selected from the group consisting of pulmonary fibrosis, Dupuytren's contracture, scleroderma, systemic sclerosis, scleroderma-like disorders, sine scleroderma, liver cirrhosis, interstitial pulmonary fibrosis, keloids, chronic kidney disease, chronic graft rejection, and other scarring/wound healing abnormalities, post-operative adhesions, reactive fibrosis.
5 . The method of claim 4 , wherein said disorder is pulmonary fibrosis.
6 . The method of claim 4 , wherein said disorder is Dupuytren's contracture.
7 . The method of claim 4 , wherein said disorder is keloids.
8 . A method of treating pulmonary fibrosis comprising intranasally administering the compound of formula I
wherein R A is hydrogen, R 7 and R 8 are independently selected from H and SO 2 NR 3 R 4 , wherein one of R 7 and R 8 is hydrogen and wherein NR 1 R 2 and NR 3 R 4 are independently 6- to 15-membered heterocycloalkyl containing one nitrogen in the ring,
or a pharmaceutically acceptable salt, ester, amide, stereoisomer or geometric isomer thereof,
to a patient in need thereof.
9 . The method of claim 8 , wherein the compound of formula I has the following structure:
or a pharmaceutically acceptable salt, ester, amide, stereoisomer, geometric isomer or prodrug thereof.
10 . The method of claim 1 , wherein said administering is done through one or more of intravenous, parenteral, oral, inhalation (including aerosolized delivery), buccal, intranasal, rectal, intra-lesional intraperitoneal, intradermal, transdermal, subcutaneous, intra-arterial, intracardiac, intraventricular, intracranial, intratracheal, intrathecal administration, intramuscular injection, intravitreous injection, and topical application methods.