IP Library › Granted Patent US 12,485,123
Granted Patent B2
US 12,485,123 · App. 17/792,878 · Granted Dec 2, 2025

1

Inventors: Qian Zhang (Danville, CA); Sanjeev Gangwar (Foster City, CA); Ashvinikumar V. Gavai (Princeton Junction, NJ); Qiang Cong (Palo Alto, CA); Yam B. Poudel (Fremont, CA); Liqi He (San Jose, CA); Prasanna Sivaprakasam (Plainsboro, NJ); Christine M. Tarby (Lawrenceville, NJ)
Assignee: Bristol-Myers Squibb Company
A61K31/519A61K31/5377A61K39/3955C07D487/04C07D519/00
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Quick Facts
Patent No.
US 12,485,123
App. No.
17/792,878
Granted
Dec 2, 2025
Kind
B2
Abstract

Compounds according to formula I are useful as agonists of Toll-like receptor 7 (TLR7). Such compounds can be used in cancer treatment, especially in combination with an anti-cancer immunotherapy agent, or as a vaccine adjuvant.

Claims (89)

1 . A compound having a structure according to formula I

wherein

Ar is

W is H, halo, C 1 -C 3 alkyl, CN, (C 1 -C 4 alkanediyl) OH,

each X is independently N or CR 2 ;

R 1 is (C 1 -C 5 alkyl),

(C 2 -C 5 alkenyl),

(C 1 -C 8 alkanediyl) 0-1 (C 3 -C 6 cycloalkyl),

(C 1 -C 8 alkanediyl) 0-1 (C 5 -C 10 spiroalkyl),

(C 2 -C 8 alkanediyl) OH,

(C 2 -C 8 alkanediyl)O(C 1 -C 3 alkyl),

(C 1 -C 4 alkanediyl) 0-1 (5-6 membered heteroaryl),

(C 1 -C 4 alkanediyl) 0-1 phenyl,

(C 1 -C 4 alkanediyl) CF 3 ,

(C 2 -C 8 alkanediyl) N [C(═O)](C 1 -C 3 alkyl),

or

(C 2 -C 8 alkanediyl) NR x R y ;

each R 2 is independently H, O(C 1 -C 3 alkyl), S (C 1 -C 3 alkyl), SO 2 (C 1 -C 3 alkyl), C 1 -C 3 alkyl, O(C 3 -C 4 cycloalkyl), S(C 3 -C 4 cycloalkyl), SO 2 (C 3 -C 4 cycloalkyl), C 3 -C 4 cycloalkyl, Cl, F, CN, or [C(═O)] 0-1 NR x R y ;

R 3 is H, halo, OH, CN,

NH 2 ,

NH [C(═O)] 0-1 (C 1 -C 8 alkyl),

N(C 1 -C 5 alkyl) 2 ,

NH [C(═O)] 0-1 (C 1 -C 4 alkanediyl) 0-1 (C 3 -C 8 cycloalkyl),

NH [C(═O)] 0-1 (C 1 -C 4 alkanediyl) 0-1 (C 4 -C 10 bicycloalkyl),

NH [C(═O)] 0-1 (C 1 -C 4 alkanediyl) 0-1 (C 5 -C 10 spiroalkyl),

N(C 3 -C 6 cycloalkyl) 2 ,

O(C 1 -C 4 alkanediyl) 0-1 (C 3 -C 8 cycloalkyl),

O(C 1 -C 4 alkanediyl) 0-1 (C 4 -C 8 bicycloalkyl),

O(C 1 -C 4 alkanediyl) 0-1 (C 5 -C 10 spiroalkyl),

O(C 1 -C 4 alkanediyl) 0-1 (C 1 -C 6 alkyl),

N [C 1 -C 3 alkyl]C(═O) (C 1 -C 6 alkyl),

NH(SO 2 ) (C 1 -C 8 alkyl),

NH(SO 2 ) (C 1 -C 4 alkanediyl) 0-1 (C 3 -C 8 cycloalkyl),

NH(SO 2 ) (C 1 -C 4 alkanediyl) 0-1 (C 4 -C 10 bicycloalkyl),

NH(SO 2 ) (C 1 -C 4 alkanediyl) 0-1 (C 5 -C 10 spiroalkyl),

a 6-membered aromatic or heteroaromatic moiety,

a 5-membered heteroaromatic moiety, or

a moiety having the structure

R 4 is NH 2 ,

NH(C 1 -C 5 alkyl),

N(C 1 -C 5 alkyl) 2 ,

NH(C 1 -C 4 alkanediyl) 0-1 (C 3 -C 8 cycloalkyl),

NH(C 1 -C 4 alkanediyl) 0-1 (C 4 -C 10 bicycloalkyl),

NH(C 1 -C 4 alkanediyl) 0-1 (C 5 -C 10 spiroalkyl),

N(C 3 -C 6 cycloalkyl) 2 ,

or

a moiety having the structure

R 5 is H, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 3 -C 6 cycloalkyl, halo, O(C 1 -C 5 alkyl), (C 1 -C 4 alkanediyl) OH, (C 1 -C 4 alkanediyl)O(C 1 -C 3 alkyl), phenyl, NH(C 1 -C 5 alkyl), 5 or 6 membered heteroaryl,

R 6 is NH 2 ,

(NH) 0-1 (C 1 -C 5 alkyl),

N(C 1 -C 5 alkyl) 2 ,

(NH) 0-1 (C 1 -C 4 alkanediyl) 0-1 (C 3 -C 8 cycloalkyl),

(NH) 0-1 (C 1 -C 4 alkanediyl) 0-1 (C 4 -C 10 bicycloalkyl),

(NH) 0-1 (C 1 -C 4 alkanediyl) 0-1 (C 5 -C 10 spiroalkyl),

N(C 3 -C 6 cycloalkyl) 2 ,

or

a moiety having the structure

R x and R y are independently H or C 1 -C 3 alkyl or R x and R y combine with the nitrogen to which they are bonded to form a 3- to 7-membered heterocycle;

n is 1, 2, or 3;

and

p is 0, 1, 2, or 3;

wherein in R 1 , R 2 , R 3 , R 4 , R 5 , and R 6

an alkyl, cycloalkyl, alkanediyl, bicycloalkyl, spiroalkyl, cyclic amine, 6-membered aromatic or heteroaromatic moiety, 5-membered heteroaromatic moiety or a moiety of the formula

is optionally substituted with one or more substituents selected from OH, halo, CN, (C 1 -C 3 alkyl), O(C 1 -C 3 alkyl), C(═O) (C 1 -C 3 alkyl), SO 2 (C 1 -C 3 alkyl), NR x R y , (C 1 -C 4 alkanediyl) OH, (C 1 -C 4 alkanediyl)O(C 1 -C 3 alkyl);

and

an alkyl, alkanediyl, cycloalkyl, bicycloalkyl, spiroalkyl, or a moiety of the formula

may have a CH 2 group replaced by O, SO 2 , CF 2 , C(═O), NH,

N [C(═O)] 0-1 (C 1 -C 3 alkyl),

N [C(═O)] 0-1 (C 1 -C 4 alkanediyl) 0-1 CF 3 ,

or

N [C(═O)] 0-1 (C 1 -C 4 alkanediyl) 0-1 (C 3 -C 8 cycloalkyl).

2 . The compound according to claim 1 , having a structure according to formula (Ia)

3 . The compound according to claim 1 , having a structure according to formula (Ib)

4 . The compound according to claim 3 , wherein R 3 is

5 . The compound according to claim 4 , wherein R 1 is

and

R 5 is H or Me.

6 . The compound according to claim 1 , having a structure according to formula (Ic)

7 . The compound according to claim 6 , wherein R 4 is

8 . The compound according to claim 7 , wherein R 1 is

and

R 5 is H or Me.

9 . A compound having a structure according to formula (Id)

wherein W is

10 . A compound having a structure according to formula (Ie)

wherein

R 1 is

R 5 is H or Me; and

R 7 is H, C 1 -C 8 alkyl, or C 3 -C 6 cycloalkyl; wherein the cycloalkyl group optionally has a CH 2 group replaced by O, NH, or N(C 1 -C 3 )alkyl.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 20, 2022
From: ZHANG, QIAN; GANGWAR, SANJEEV; GAVAI, ASHVINIKUMAR V.; CONG, QIANG; POUDEL, YAM B.; HE, LIQI; SIVAPRAKASAM, PRASANNA; TARBY, CHRISTINE M.
To: BRISTOL-MYERS SQUIBB COMPANY
Reel/Frame 061482/0386 →
Continuity (3)
Provisional Application 63057661 · Jul 28, 2020
Provisional Application 62966092 · Jan 27, 2020
Related Publication 20230130516A1 · Apr 27, 2023
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