Granted Patent B2

US 12,269,804 · App. 16/962,443 · Granted Apr 8, 2025

Inventors: Sudipta Mahajan (Framingham, MA); Marc Saul Weinberg (Encinitas, CA); Diego Sebastian D'Astolfo (San Diego, CA); Kevin M. Cottrell (Cambridge, MA); Mark A. Morris (Somerville, MA); John Patrick Maxwell (Hingham, MA)

Assignee: VERTEX PHARMACEUTICALS INCORPORATED

C07D241/44C07D403/12C07D405/14C07D491/048C07D491/08C12N9/22C12N15/11C12N15/907C12N2310/20C12N2800/80

Abstract

Claims (38)

1. A compound of formula (III):

wherein

X is O;

Y is a bond, O, or NR; wherein R is H or C 1 -C 4 alkyl;

R 2 is

a) a 5- or 6-membered aryl or heteroaryl ring containing one or two heteroatoms selected from the group consisting of N, O, and S, wherein the aryl and the heteroaryl ring may be substituted by 0, 1, 2, or 3 substituents R3 independently selected from the group consisting of CN, halo, C 1 -C 4 -alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C(═O) NHR 1′ , and a 5- or 6-membered heterocycloalkyl or heteroaryl ring wherein each ring contains 1, 2, or 3 heteroatoms selected from N, O, and S; wherein R1′ is C 1 -C 4 alkyl; or wherein two R3 groups connected to adjacent carbon atoms of the aryl or heteroaryl ring may form a fused 5- or 6-membered ring which may contain a heteroatom selected from O, N, and S; or

b) COOR 4 wherein R4 is C 1 -C 4 -alkyl or benzyl;

wherein each C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, and C 1 -C 4 -haloalkoxy may further be substituted with OR 5 or NR 6 R 7 wherein each of R 5 , R 6 , and R 7 is independently H, C 1 -C 4 alkyl, or C 3 -C 6 cycloalkyl; or wherein R 6 and R 7 and the nitrogen atom to which they are attached form a saturated 5- or 6-membered ring that may contain 0 or 1 further heteroatom selected from N, O, and S and wherein the ring may be further substituted by C 1 -C 4 -alkyl; and

wherein W is N and Z is O.

2. The compound of claim 1 , wherein

R 2 is a 5- or 6-membered aryl or heteroaryl ring containing one or two heteroatoms selected from the group consisting of N, O, and S, wherein the aryl and the heteroaryl ring may be substituted by 0, 1, or 2 substituents R 3 independently selected from the group consisting of CN, halo, C 1 -C 4 -alkyl or C 3 -C 6 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, and C(═O) NHR 1′ wherein R 1′ is C 1 -C 4 -alkyl; or wherein two R 3 groups connected to adjacent carbon atoms of the aryl or heteroaryl ring may form a fused 5-membered ring which may contain a heteroatom selected from O, N, and S.

3. The compound of claim 1 , wherein R 2 is:

wherein #denotes where R 2 is connected to the rest of the compound of formula (I); and

o is 0, 1, or 2.

4. The compound of claim 1 , wherein R 2 is:

5. The compound of claim 1 , wherein each R 3 is independently selected from the group consisting of CN, halo, NO 2 , C 1 -C 2 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 2 -alkoxy, C 1 -C 2 -haloalkoxy, and C(═O) NHR 1′ wherein R 1′ is C 1 -C 2 alkyl.

6. The compound of claim 1 , wherein two R 3 groups connected to adjacent carbon atoms of the aryl or heteroaryl ring may form a fused 5-membered ring which may contain a heteroatom selected from O, N, and S.

7. The compound of claim 1 , selected from the following compounds:

Compound

No.

Compound

1

2

3

4

5

6

13

14

15

16

19

20

21

22

28

8. A kit or composition for editing one or more target genomic regions, comprising:

a genome editing system; and a compound of claim 1 or a pharmaceutically acceptable salt or a co-crystal thereof.

Assignments (1)

Continuity (2)

References Cited (229)