Prostaglandin conjugates and derivatives for treating glaucoma and ocular hypertension

Patent metadata

Field	Value
Publication number	US-10016441-B2
Application number	US-201715448805-A
Country	US
Kind code	B2
Filing date	Mar 3, 2017
Priority date	Oct 15, 2014
Publication date	Jul 10, 2018
Grant date	Jul 10, 2018

Abstract

Prostaglandin conjugates and derivatives and methods for their use to treat glaucoma and/or lower intraocular pressure are disclosed. Additionally, ophthalmic pharmaceutical compositions useful in the treatment of eye diseases such as glaucoma and elevated intraocular pressure are disclosed. Such compositions comprise an effective amount of prostaglandin conjugates or derivatives of the present invention.

First claim

What is claimed is:

1. A compound represented by Formula (I):

in which A is selected from the group consisting of:

where:
n is 1-6;
R 1 , R 2 , R 3 independently=OH or O—NO 2 ;
R 4 , R 5 independently=H, alkyl, or heteroalkyl; or R 4 and R 5 can combine to form cyclic alkyl or cyclic heteroalkyl; and
R 6 independently=H, NO 2 , organic nitrate, organic nitrite, metal—NO complex, sodium nitroprusside (SNP), dinitrosyl iron thiol complex (DNICs), N-nitrosamine, N-hydroxy-N-nitrosamine, N-nitrosimine, nitrosimine, C-nitroso, diazetine dioxide, furoxan, benzofuroxan, oxatriazole-5-imine, sydnonimine, oxime, hydroxylamine, N-hydroxyguanidine, or hydroxyurea.

2. The compound of claim 1 wherein the compound is a pharmaceutically acceptable salt of a compound according to Formula (I).

3. A compound selected from the group consisting of: Isopropyl (Z)-7-((1R,2R,3R,5S)-3,5-bis(nitrooxy)-2-((R,E)-3-(nitrooxy)-4-(3-(trifluoromethyl)phenoxy)but-1-en-1-yl)cyclopentyl)hept-5-enoate and (Z)-2-((((Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((R,E)-3-hydroxy-4-(3-(trifluoromethyl)phenoxy)but-1-en-1-yl)cyclopentyl)hept-5-enoyl)oxy)methoxy)-1-(pyrrolidin-1-yl)diazene 1-oxide.

4. The compound of claim 3 , wherein the compound is a pharmaceutically acceptable salt.

Assignees

• Novartis Ag

Inventors

• Ellis David Archer
• Scheibler Lukas
• Sharif Najam A

Classifications

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K31/5575 Primary

  having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha · CPC title

• A61K31/559

  having heterocyclic rings containing hetero atoms other than oxygen · CPC title