Inhibitors of soluble adenylyl cyclase

Patent metadata

Field	Value
Publication number	US-2020157084-A1
Application number	US-201716097087-A
Country	US
Kind code	A1
Filing date	Apr 28, 2017
Priority date	Apr 28, 2016
Publication date	May 21, 2020
Grant date	—

Abstract

Provided are 6-amino substituted 2,6-diamino-4-choropyrimidine compounds which are specific inhibitors of soluble adenylyl cyclase. The compounds can be formulated with pharmaceutical carriers and used for reducing cyclic AMP levels. The compositions can be used for treatment of various conditions including ocular hypotony.

First claim

1 . A compound having the following structure:

wherein
X is a substituted or unsubstituted C 1 to C 3 aliphatic group and R 3 is selected from the group consisting of:

wherein n is 0 or 1, and

2 . The compound of claim 1 , wherein X is an unsubstituted C 1 to C 3 alkanediyl group having the following structure:

and m is 2 or 3.

3 . The compound of claim 1 , wherein X is an unsubstituted C 1 to C 3 aliphatic group having the following structure:

wherein *, individually at each occurrence, indicate R or S stereochemistry.

4 . The compound of claim 1 , wherein the compound has one of the following structures:

5 . A composition comprising one or more compounds having the following structure in a pharmaceutical carrier:

wherein
R 1 is a substituted or unsubstituted C 1 -C 5 aliphatic group, and
R 2 is H or a substituted or unsubstituted phenyl group.

6 . The composition of claim 5 , wherein R 2 is a substituted phenyl group having the following structure:

7 . The composition of claim 5 , wherein R 1 is a substituted C 1 -C 5 alkanediyl group having one of the following structures:

wherein r is 1, 2, 3, 4, or 5, or

wherein s is 1, 2, 3, 4, or 5.

8 . The composition of claim 5 , wherein R 1 is a substituted C 1 -C 5 alkyl group having one of the following structures:

wherein t is 1, 2, 3, 4, or 5, and
R 4 and R 5 are each independently a substituted or unsubstituted C 1 -C 5 alkanediyl alkyl group.

9 . The composition of claim 5 , wherein R 1 is a substituted C 1 -C 5 aliphatic group having the following structure:

10 . The composition of claim 5 , wherein the compound has the following structure:

wherein
X is a substituted or unsubstituted C 1 to C 3 aliphatic group and R 3 is selected from the group consisting of:

wherein n is 0 or 1, and

11 . The composition of claim 10 , wherein X is an unsubstituted C 1 to C 3 alkanediyl group having the following structure:

and m is 2 or 3.

12 . The composition of claim 10 , wherein X is a substituted unsubstituted C 1 to C 3 aliphatic group having the following structure:

wherein *, individually at each occurrence, indicate R or S stereochemistry.

13 . The composition of claim 5 , wherein the one or more compounds is selected from the group consisting of:

and combinations thereof.

14 . A method of treatment of ocular hypotony comprising administering to an individual in need of treatment a composition of claim 5 .

15 . The method of claim 14 , wherein the individual has been surgically treated for glaucoma.

Assignees

• Univ Cornell
• Univ Of Bayreuth
• Tri Inst Therapeutics Discovery Inst

Inventors

• Buck Jochen
• Levin Lonny
• Ramos-Espiritu Lavoisier
• Steegborn Clemens
• Sato Ayumu
• Okamoto Rei
• Michino Mayako

Classifications

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D409/14 Primary

  containing three or more hetero rings · CPC title

• C07D403/14 Primary

  containing three or more hetero rings · CPC title