Metalloenzyme inhibitor compounds

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 10,085,984
App. No.: 15/857,950
Granted: Oct 2, 2018
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Provided are compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

Claims (214)

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof; wherein

A is N or CR 5 ;

W is N or CR 6 ;

X is N or CR 6 ;

Y is N or CR 6 ;

Z is N or CR 6 ;

provided that no more than two of W, X, Y, and Z are N;

R 1 is halogen, cyano, acyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, cycloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, NR a R b , NHSO 2 R c , CH 2 NR a R b , CH 2 NHSO 2 R d , CO 2 R e , COR f , S(O)R d , S(O) 2 R d , CH 2 OR f , or CR e R f OH, wherein any R 1 can be optionally substituted with 1-3 independent substituents R 7 ;

R 2 is hydrogen, halogen, cyano, alkyl, or haloalkyl;

or R 1 and R 2 together with the atoms to which they are attached form an aryl, heterocycloalkyl, or cycloalkyl ring;

R 3 is hydrogen, cyano, acyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, cycloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, NR a R b , NHSO 2 R c , CH 2 NR a R b , CH 2 NHSO 2 R d , CO 2 R e , COR f , CH 2 OR f , or CR e R f OH;

R 4 is alkyl, cycloalkyl, or haloalkyl;

R 5 is hydrogen, alkyl, haloalkyl, heteroalkyl, or cycloalkyl;

each occurrence of R 6 is, independently, hydrogen, halogen, cyano, haloalkyl, alkyl, cycloalkyl, alkoxy, haloalkyl, or carboxyl;

each occurrence of R 7 is, independently, halogen, alkyl, alkoxy, haloalkyl, carboxyl, aryl, aryl substituted with 1-3 independent halogen, —(CH 2 )nC(O)NR g R h , —S(O) 2 R i , —CO 2 R j , or NR g R h ,

each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

each occurrence of R a , R b , R c , R d , R e , and R f is, independently, hydrogen, acyl, alkoxyalkyl, alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C(O)OC 1-6 alkyl, C(O)C 1-6 alkyl, a nitrogen protecting group when attached to a nitrogen atom, or an oxygen protecting group when attached to an oxygen atom; or R a and R b together with the atoms to which they are attached form a heterocycloalkyl ring; or R e and R f together with the atoms to which they are attached form a cycloalkyl ring; and

each occurrence of R g , R h , R i , and R j is, independently, hydrogen, acyl, alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C(O)OC 1-6 alkyl, C(O)C 1-6 alkyl, or R g and R h together with the atoms to which they are attached form a heterocycloalkyl ring.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is halogen, cyano, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, cycloalkoxy, aryl, NR a R b , NHSO 2 R c , CH 2 NR a R b , CH 2 NHSO 2 R d , COR f , or CR e R f OH; or R 1 and R 2 together with the atoms to which they are attached form an aryl ring.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is halogen, alkyl, alkenyl, haloalkyl, alkoxy, haloalkoxy, cycloalkoxy, aryl, NR a R b , CH 2 NHSO 2 R d , or CR e R f OH; or R 1 and R 2 together with the atoms to which they are attached form an aryl ring.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is halogen, alkyl, haloalkyl, CH 2 NHSO 2 R d , or NR a R b ; and

R a , R b , and R d are, independently, hydrogen, alkyl, or haloalkyl.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is haloalkyl.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hydrogen or alkyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is alkyl or cycloalkyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is C 1-4 alkyl or C 3-5 cycloalkyl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 6 is, independently, hydrogen, halogen, cyano, alkoxy, haloalkyl, or carboxyl.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 6 is, independently, hydrogen, halogen, or cyano.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is CR 5 and R 5 is hydrogen, C 1-4 alkyl, or C 3-5 cycloalkyl.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is N.

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein no more than one of W, X, Y, and Z is N.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein W, X, Y, and Z are each independently CR 6 .

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is N.

16. The compound of claim 1 , wherein the compound is of Formula I-a: