MASP-2 inhibitors and methods of use

Patent metadata

Field	Value
Publication number	US-11807641-B2
Application number	US-202017112896-A
Country	US
Kind code	B2
Filing date	Dec 4, 2020
Priority date	Dec 4, 2019
Publication date	Nov 7, 2023
Grant date	Nov 7, 2023

Abstract

The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds, and methods of making and using such compounds.

First claim

The invention claimed is:

1. A compound having the following Structure (I):

or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:
R 1 is a substituted aryl or a substituted or unsubstituted heteroaryl;
R 2 is methyl;
R 4 is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl;
R 5 is hydrogen, alkyl, haloalkyl, cycloalkyl, phosphonalkyl, (CH 2 ) m C(═O)OR 6 , C(═O)R 6 , C(═O)OR 6 , (CH 2 ) m NR 6 S(O) 2 R 7 , or C(═O)NR 6 R 7 ;
R 6 and R 7 are, at each occurrence, independently hydrogen, alkyl, haloalkyl, cycloalkyl, or arylalkyl;
L 1 is a direct bond, —CR 8a R 8b —, —S(O) t —, NR 8c , or —O—;
R 8a and R 8b are each independently hydrogen or alkyl, or R 8a and R 8b , together with the carbon to which they are attached form an optionally substituted 3-6 membered cycloalkyl;
R 8c is hydrogen, alkyl, haloalkyl, (C═O)alkyl, (C═O)Oalkyl, (C═O)cycloalkyl, (C═O)Ocycloalkyl, (C═O)aryl, (C═O)Oaryl, (C═O)heteroaryl, (C═O)Oheteroaryl, (C═O)heterocyclyl, (C═O)O heterocyclyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted arylalkyl, a substituted or unsubstituted heteroarylalkyl, a substituted or unsubstituted cycloalkylalkyl, or a substituted or unsubstituted heterocyclylalkyl;
m is 1, 2, 3, 4, 5, or 6; and
t is 0, 1, or 2.

2. The compound of claim 1 , wherein R 1 is a substituted phenyl.

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

4. The compound of claim 1 , wherein R 1 is a substituted or unsubstituted heteroaryl.

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

6. The compound of claim 1 , wherein R 4 is a substituted or unsubstituted aryl.

7. The compound of claim 1 , wherein R 4 is a substituted or unsubstituted phenyl.

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

9. The compound of claim 1 , wherein R 4 is a substituted or unsubstituted heteroaryl.

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

11. The compound of claim 1 , wherein R 5 is hydrogen, alkyl, phosphonalkyl, (CH 2 ) m NR 6 S(O) 2 R 7 , or (CH 2 ) m C(═O)OR 6 .

12. The compound of claim 11 , wherein R 5 has one of the following structures:

13. The compound of claim 1 , wherein L 1 is a direct bond, —O—, or —CH 2 —.

14. The compound of claim 1 , wherein L 1 is —CR 8a R 8b — and R 8a and R 8b together with the carbon to which they are attached form an optionally substituted 3, 4, or 5 membered cycloalkyl.

15. A compound having one of the structures:

or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof of claim 1 and a pharmaceutically acceptable carrier or excipient.

17. A method for relieving the symptoms from a MASP-2-associated disease or disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 1 .

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

Assignees

• Omeros Corp

Inventors

• Cicirelli Michael
• Cutshall Neil S
• Gage Jennifer Lynn
• Goldstein Sara Rebecca
• Keshipeddy Santosh Kumar
• Kwon Do Yeon
• Lemus Robert Huerta
• Little Thomas L
• Metz Markus
• Nguyen Jeremiah H
• Nollert Von Specht Peter Kurt
• Price Loren Michael
• Tsoung Jennifer
• Vaddela Sudheer Babu

Classifications

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D207/16

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D211/60

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D401/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D401/10

  linked by a carbon chain containing aromatic rings · CPC title