IP Library › Granted Patent US 12,486,302

Granted Patent B2

US 12,486,302 · App. 17/564,893 · Granted Dec 2, 2025

Somatostatin receptor antagonist compounds and methods of using the same

Inventors: Stephen Paul Arns (North Vancouver, CA); James Brian Jaquith (Cobourg, CA); Davy Jeremy Baudelet (Vancouver, CA); Eric Roy Simonson (Vancouver, CA); Richard Tom Liggins (Coquitlam, CA); Nag Sharwan Kumar (Surrey, CA); Tom Han Hsiao Hsieh (Vancouver, CA)

Assignee: CDRD VENTURES INC.

C07K7/06 C07K7/02 A61K38/00

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Quick Facts

Patent No.: US 12,486,302
App. No.: 17/564,893
Granted: Dec 2, 2025
Kind: B2

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Abstract

The present invention is directed to somatostatin receptor antagonist compounds having the structure of Formula I: compositions comprising the same, and methods of using such compounds and compositions. The compounds may be useful in the prevention or treatment of hypoglycemia.

Claims (162)

1 . A compound having the structure of Formula I:

or a salt thereof, wherein:

R C is OH or NHR 16 , wherein R 16 is H or C 1-6 alkyl optionally substituted with one or more substituents;

R N is selected from the group consisting of:

(i) H;

(ii) C 1-6 alkyl;

(iii) —C(O)R 17 , wherein R 17 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

(iv) —C(O)C 1-6 alkylene-C(O)OR 18 , wherein R 18 is H or C 1-6 alkyl optionally substituted with one or more substituents;

(v) C(O)C 1-6 alkylene-N(R 20 )C(O)R 19 , wherein R 19 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, and wherein R 20 is H or C 1-6 alkyl;

(vi) —C(O)C 1-6 alkylene-NR 21 R 22 , wherein each of R 21 and R 22 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

(vii) —C(O)C 1-6 alkylene-C(O)NR 23 R 24 , wherein each of R 23 and R 24 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

(viii) —C(O)C 1-6 alkylene-S(O) 2 R 25 , wherein R 25 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; and

(ix) —S(O) 2 R 26 , wherein R 26 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

R 1 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, —C 1-6 alkylene(C 6-10 aryl) and —C 1-6 alkylene (5- to 10-membered heteroaryl), wherein the C 1-6 alkyl, the C 6-10 aryl, the C 6-10 aryl of —C 1-6 alkylene(C 6-10 aryl), the 5- to 10-membered heteroaryl and the 5- to 10-membered heteroaryl of —C 1-6 alkylene (5- to 10-membered heteroaryl) are optionally substituted with one or more substituents, and wherein the C 1-6 alkylene of —C 1-6 alkylene(C 6-10 aryl) and —C 1-6 alkylene (5- to 10-membered heteroaryl) is optionally substituted with one or more substituents;

R 3 is selected from the group consisting of:

(i) C 6-10 aryl which is optionally substituted with one or more substituents;

(ii) 5- to 10-membered heteroaryl which is optionally substituted with one or more substituents;

(iii) —C 1-6 alkylene(C 6-10 aryl), wherein the C 6-10 aryl is optionally substituted with one or more substituents, and wherein the C 1-6 alkylene is optionally substituted with one or more substituents;

(iv) —C 1-6 alkylene (5- to 10-membered heteroaryl), wherein the 5- to 10-membered heteroaryl is optionally substituted with one or more substituents, and wherein the C 1-6 alkylene is optionally substituted with one or more substituents;

(v) —C 1-6 alkylene-NR 27 C(O)R 28 , wherein:

R 27 is H or C 1-6 alkyl;

R 28 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, and —NR 29 R 30 , wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; and

wherein each of R 29 and R 30 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

(vi) —(C 6-10 arylene)-C(O)NR 31 R 32 or —C 1-6 alkylene-(C 6-10 arylene)-C(O)NR 31 R 32 , wherein each of R 31 and R 32 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

(vii) —(C 6-10 arylene)-NR 33 R 34 or —C 1-6 alkylene-(C 6-10 arylene)-NR 33 R 34 , wherein:

each of R 33 and R 34 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, —C(O)R 35 , —C(O)NR 36 R 37 , and —SO 2 R 38 , wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

R 35 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents;

each of R 36 and R 37 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; and

R 38 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

(viii) —(C 6-10 arylene)-SO 2 NR 39 R 40 or —C 1-6 alkylene-(C 6-10 arylene)-SO 2 NR 39 R 40 , wherein each of R 39 and R 40 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

(ix) —(C 6-10 arylene)-(C 1-6 alkylene)-NR 41 R 42 or —C 1-6 alkylene-(C 6-10 arylene)-(C 1-6 alkylene)-NR 41 R 42 , wherein:

each of R 41 and R 42 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, —C(O)R 43 , and —C(O)NR 44 R 45 , wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

R 43 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; and

each of R 44 and R 45 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents;

(x) —(C 6-10 arylene)-OR 46 or —C 1-6 alkylene-(C 6-10 arylene)-OR 46 , wherein R 46 is selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; and

(xi) —C 1-6 alkylene-(C 6-10 arylene)-N(R 47 )—C(O)—CHR 48 —NR 49 R 50 , wherein R 47 is H or CH 3 , R 48 is H or C 1-6 alkyl optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, COOH, —NH 2 , C(O)NH 2 , and —N(H)C(O)NH 2 , and each of R 49 and R 50 is independently H, CH 3 or acetyl;

R 4 is selected from the group consisting of:

(i) —C 1-6 alkylene-N(R 53 )C(O)NR 51 R 52 , wherein each of R 51 and R 52 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, and wherein R 53 is H or C 1-6 alkyl;

(ii) —C 1-6 alkylene-(C 6-10 arylene)-N(R 59 )C(O)R 58 , wherein R 58 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, and wherein R 59 is H or C 1-6 alkyl;

(iii) —C 1-6 alkylene-(C 6-10 arylene)-N(R 64 )SO 2 R 63 , wherein R 63 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, and wherein R 64 is H or C 1-6 alkyl;

(iv) —C 1-6 alkylene-(C 6-10 arylene)-(C 1-6 alkylene)-NR 67 R 68 , wherein:

each of R 67 and R 68 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, —C(O)R 69 , and —C(O)NR 70 R 71 ;

R 69 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; and

each of R 70 and R 71 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl;

(v) —C 1-6 alkylene-(C 6-10 arylene)-NR 72 R 73 , wherein each of R 72 and R 73 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; and

(vi) —C 1-6 alkylene-(C 6-10 arylene)-CN;

R 5 is selected from the group consisting of:

(i) —NR 79 R 80 , wherein each of R 79 and R 80 is independently selected from the group consisting of H, C 1-6 alkyl, —C(O)R 81 , and —C(═NR 82 )NR 83 R 84 , or R 79 and R 80 , together with the N atom to which they are attached, form 5- to 10-membered heteroaryl or 5- to 10-membered heterocycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents, and wherein the 5- to 10-membered heteroaryl and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents,

R 81 is selected from the group consisting of H, —NH 2 , C 1-16 alkyl, C 1-6 haloalkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; and

each of R 82 , R 83 , and R 84 is independently selected from the group consisting of H, C 1-16 alkyl, C 1-6 haloalkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; and

(ii) —N + R 85 R 86 R 87 , wherein each of R 85 , R 86 , and R 87 is independently C 1-6 alkyl;

n 1 is 1, 2, 3, 4, 5, or 6;

R 6 is C 1-6 alkyl optionally substituted with one or more substituents;

R 8 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, —C 1-6 alkylene(C 6-10 aryl) and —C 1-6 alkylene (5- to 10-membered heteroaryl), wherein the C 1-6 alkyl, the C 6-10 aryl, the C 6-10 aryl of —C 1-6 alkylene(C 6-10 aryl), the 5- to 10-membered heteroaryl and the 5- to 10-membered heteroaryl of —C 1-6 alkylene (5- to 10-membered heteroaryl) are optionally substituted with one or more substituents, and wherein the C 1-6 alkylene of —C 1-6 alkylene(C 6-10 aryl) and —C 1-6 alkylene (5- to 10-membered heteroaryl) is optionally substituted with one or more substituents;

R 9 is H or C 1-6 alkyl;

R 10 is H or C 1-6 alkyl;

R 11 is H or C 1-6 alkyl;

R 12 is H or C 1-6 alkyl;

R 13 is H or C 1-6 alkyl;

R 14 is H or C 1-6 alkyl;

R 15 is H or C 1-6 alkyl; and

L is selected from the group consisting of:

wherein X is S or O; and

chiral centre *1 is in the S configuration or the R configuration;

chiral centre *2 is in the S configuration or the R configuration;

chiral centre *3 is in the S configuration or the R configuration;

chiral centre *4 is in the S configuration or the R configuration;

chiral centre *5 is in the S configuration or the R configuration;

chiral centre *6 is in the S configuration or the R configuration;

chiral centre *7 is in the S configuration or the R configuration; and

chiral centre *8 is in the S configuration or the R configuration,

provided that:

i) when R C is NH 2 , R N is H or —C(O)CH 2 N 3 , R 1 is

R 3 is

R 5 is NH 2 , n 1 is 4, R 6 is —CH(OH)(CH 3 ), R 8 is

each of R 9 , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 is H, and L is

then R 4 is not

and

ii) when R C is NH 2 , R N is H, R 1 is

R 5 is NH 2 , n 1 is 4, R 6 is —CH(CH 3 ) 2 , R 8 is —CH(OH)(CH 3 ), each of R 9 , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 is H, and L is

then R 4 is not

2 . The compound or salt of claim 1 , wherein R 4 is selected from the group consisting of:

(i) —C 3-4 alkylene-N(R 53 )C(O)NR 51 R 52 , wherein each of R 51 and R 52 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, and wherein R 53 is H or C 1-6 alkyl;

(ii) —C 1-2 alkylene-(C 6 arylene)-N(R 59 )C(O)R 58 , wherein R 58 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, and wherein R 59 is H or C 1-6 alkyl;

(iii) —C 1-2 alkylene-(C 6 arylene)-N(R 64 )SO 2 R 63 , wherein R 63 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, and wherein R 64 is H or C 1-6 alkyl;

(iv) —C 1-2 alkylene-(C 6 arylene)-(C 1-2 alkylene)-NR 67 R 68 , wherein:

each of R 67 and R 68 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, —C(O)R 69 , and —C(O)NR 70 R 71 ;

R 69 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; and

each of R 70 and R 71 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl;

(v) —C 1-2 alkylene-(C 6 arylene)-NR 72 R 73 , wherein each of R 72 and R 73 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; and

(vi) —C 1-2 alkylene-(C 6 arylene)-CN.

3 . The compound or salt of claim 1 , wherein R 4 is selected from the group consisting of —C 3-4 alkylene-N(R 53 )C(O)NR 51 R 52 , —C 1-2 alkylene-(C 6 arylene)-N(R 59 )C(O)R 58 , —C 1-2 alkylene-(C 6 arylene)-N(R 64 )SO 2 R 63 , —C 1-2 alkylene-(C 6 arylene)-(C 1-2 alkylene)-NR 67 R 68 , —C 1-2 alkylene-(C 6 arylene)-NR 72 R 73 , and —C 1-2 alkylene-(C 6 arylene)-CN, wherein each of R 51 , R 52 , R 53 , R 59 , and R 64 is H, each of R 58 and R 63 is independently C 6-10 aryl, each of R 67 and R 68 is independently selected from the group consisting of H, —C(O)R 69 , and —C(O)NR 70 R 71 , wherein R 69 is C 1-6 alkyl and each of R 70 and R 71 is H, and each of R 72 and R 73 is independently selected from the group consisting of H and C 1-6 alkyl.

4 . The compound or salt of claim 1 , wherein R 4 is

5 . The compound or salt of claim 1 , wherein R 4 is —C 2-3 alkylene-N(R 53 )C(O)NR 51 R 52 , R 53 is H, and each of R 51 and R 52 is H.

6 . The compound or salt of claim 1 , wherein R 4 is —C 1 alkylene-(C 6 arylene)-N(R 59 )C(O)R 58 , R 59 is H, and R 58 is phenyl.

7 . The compound or salt of claim 1 , wherein R 4 is —C 1 alkylene-(C 6 arylene)-N(R 64 )SO 2 R 63 , R 64 is H, and R 63 is phenyl.

8 . The compound or salt of claim 1 , wherein R 4 is —C 1 alkylene-(C 6 arylene)-(C 1 alkylene)-NR 67 R 68 , wherein each of R 67 and R 68 is H or wherein R 67 is H, R 68 is —C(O)NR 70 R 71 , and each of R 70 and R 71 is H.

9 . The compound or salt of claim 1 , wherein R 4 is —C 1 alkylene-(C 6 arylene)-NR 72 R 73 and R 72 is H and R 73 is C 1-6 alkyl.

10 . The compound or salt of claim 1 , wherein R 4 is —C 1 alkylene-(C 6 arylene)-CN.

11 . The compound or salt of claim 1 , wherein R 5 is —NR 79 R 80 and each of R 79 and R 80 is independently selected from the group consisting of H, C 1-6 alkyl, —C(O)R 81 , and —C(═NR 82 )NR 83 R 84 , wherein R 81 is C 1-6 alkyl and each of R 82 , R 83 , and R 84 is H.

12 . The compound or salt of claim 11 , wherein R 5 is —NR 79 R 80 and each of R 79 and R 80 is independently selected from the group consisting of H and C 1-6 alkyl.

13 . The compound or salt of claim 12 , wherein R 5 is —NH 2 , —NHCH 3 or —N(CH 3 ) 2 .

14 . The compound or salt of claim 13 , wherein R 5 is —NH 2 .

15 . The compound or salt of claim 13 , wherein R 5 is —NHCH 3 .

16 . The compound or salt of claim 13 , wherein R 5 is —N(CH 3 ) 2 .

17 . The compound or salt of claim 1 , wherein n 1 is 3 or 4.

18 . The compound or salt of claim 17 , wherein n 1 is 4.

19 . The compound or salt of claim 1 , wherein R C is OH or NH 2 .

20 . The compound or salt of claim 19 , wherein R C is NH 2 .

21 . The compound or salt of claim 1 , wherein R N is selected from the group consisting of:

(i) H;

(ii) C 1-6 alkyl;

(iii) —C(O)R 17 , wherein R 17 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl;

(iv) —C(O)C 1-6 alkylene-C(O)OR 18 , wherein R 18 is H or C 1-6 alkyl;

(v) —C(O)C 1-6 alkylene-N(R 20 )C(O)R 19 , wherein R 19 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, and wherein R 20 is H or C 1-6 alkyl;

(vi) —C(O)C 1-6 alkylene-NR 21 R 22 , wherein each of R 21 and R 22 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl;

(vii) —C(O)C 1-6 alkylene-C(O)NR 23 R 24 , wherein each of R 23 and R 24 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl;

(viii) —C(O)C 1-6 alkylene-S(O) 2 R 25 , wherein R 25 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; and

(ix) —S(O) 2 R 26 , wherein R 26 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl.

22 . The compound or salt of claim 21 , wherein R N is selected from the group consisting of:

(i) H;

(ii) C 1-6 alkyl;

(iii) —C(O)R 17 , wherein R 17 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl;

(iv) —C(O)C 1-3 alkylene-C(O)OR 18 , wherein R 18 is H or C 1-6 alkyl;

(v) —C(O)C 1-3 alkylene-N(R 20 )C(O)R 19 , wherein R 19 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, and wherein R 20 is H or C 1-6 alkyl;

(vi) —C(O)C 1-3 alkylene-NR 21 R 22 , wherein each of R 21 and R 22 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl;

(vii) —C(O)C 1-3 alkylene-C(O)NR 23 R 24 , wherein each of R 23 and R 24 is independently selected from the group consisting of H, C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; and

(viii) —C(O)C 1-3 alkylene-S(O) 2 R 25 , wherein R 25 is selected from the group consisting of C 1-6 alkyl, C 6-10 aryl, and 5- to 10-membered heteroaryl.

23 . The compound or salt of claim 21 , wherein R N is selected from the group consisting of H, C 1-6 alkyl, —C(O)R 17 , —C(O)C 1-6 alkylene-C(O)OR 18 , —C(O)C 1-6 alkylene-N(R 20 )C(O)R 19 , —C(O)C 1-6 alkylene-NR 21 R 22 , —C(O)C 1-6 alkylene-C(O)NR 23 R 24 , and —C(O)C 1-6 alkylene-S(O) 2 R 25 , wherein R 17 is C 1-6 alkyl or 5- to 6-membered heteroaryl, R 18 is C 1-6 alkyl, R 19 is C 1-6 alkyl or C 6 aryl, each of R 20 , R 21 , R 22 , R 23 and R 24 is H, and R 25 is C 6 aryl.

24 . The compound or salt of claim 23 , wherein R N is selected from the group consisting of H, C 1-3 alkyl, —C(O)R 17 , —C(O)C 1-3 alkylene-C(O)OR 18 , —C(O)C 1-3 alkylene-N(R 20 )C(O)R 19 , —C(O)C 1-3 alkylene-NR 21 R 22 , —C(O)C 1-3 alkylene-C(O)NR 23 R 24 , and —C(O)C 1-3 alkylene-S(O) 2 R 25 , wherein R 17 is C 1-6 alkyl or 5- to 6-membered heteroaryl, R 18 is C 1-3 alkyl, R 19 is C 1-3 alkyl or C 6 aryl, each of R 20 , R 21 , R 22 , R 23 and R 24 is H, and R 25 is C 6 aryl.

25 . The compound or salt of claim 24 , wherein R N is H.

26 . The compound or salt of claim 1 , wherein R 1 is —C 1-3 alkylene(C 6-10 aryl), wherein the C 6-10 aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxy, —NO 2 , and C 1-6 alkoxy.

27 . The compound or salt of claim 26 , wherein R 1 is —C 1-2 alkylene(C 6 aryl), wherein the C 6 aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxyl, —NO 2 , and C 1-6 alkoxy.

28 . The compound or salt of claim 27 , wherein R 1 is

wherein R 88 is H, halogen, hydroxyl or C 1-3 alkoxy.

29 . The compound or salt of claim 28 , wherein R 88 is Cl.

30 . The compound or salt of claim 1 , wherein R 3 is —C 1-3 alkylene(C 6-10 aryl), wherein the C 6-10 aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxy, —NO 2 , and C 1-6 alkoxy.

31 . The compound or salt of claim 30 , wherein R 3 is —C 1-2 alkylene(C 6 aryl), wherein the C 6 aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxyl, —NO 2 , and C 1-6 alkoxy.

32 . The compound or salt of claim 31 , wherein R 3 is

wherein R 89 is H, halogen, hydroxyl or C 1-3 alkoxy.

33 . The compound or salt of claim 32 , wherein R 89 is Cl or hydroxyl.

34 . The compound or salt of claim 33 , wherein R 89 is hydroxyl.

35 . The compound or salt of claim 1 , wherein R 6 is C 1-6 alkyl optionally substituted with hydroxyl.

36 . The compound or salt of claim 35 , wherein R 6 is selected from the group consisting of —CH(CH 3 )OH, —CH(CH 3 ) 2 , —C(CH 3 ) 3 , —CH 2 OH and —CH 2 CH 3 .

37 . The compound or salt of claim 36 , wherein R 6 is —CH(CH 3 )OH.

38 . The compound or salt of claim 1 , wherein R 8 is —C 1-3 alkylene(C 6-10 aryl), wherein the C 6-10 aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxy, —NO 2 , and C 1-6 alkoxy.

39 . The compound or salt of claim 38 , wherein R 8 is —C 1-2 alkylene(C 6 aryl), wherein the C 6 aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxyl, —NO 2 , and C 1-6 alkoxy.

40 . The compound or salt of claim 39 , wherein R 8 is

wherein R 151 is H, halogen, hydroxyl or C 1-3 alkoxy.

41 . The compound or salt of claim 40 , wherein R 151 is Cl or hydroxyl.

42 . The compound or salt of claim 41 , wherein R 151 is hydroxyl.

43 . The compound or salt of claim 1 , wherein each of R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 is independently H or C 1-3 alkyl.

44 . The compound or salt of claim 43 , wherein each of R 9 , R 10 , R 11 , R 13 , R 14 , and R 15 is H.

45 . The compound or salt of claim 43 , wherein R 12 is H or CH 3 .

46 . The compound or salt of claim 45 , wherein R 12 is H.

47 . The compound or salt of claim 1 , wherein L is

48 . The compound or salt of claim 1 , wherein chiral centre *1 is in the S configuration, chiral centre *2 is in the S configuration, chiral centre *3 is in the S configuration, chiral centre *4 is in the R configuration, chiral centre *5 is in the S configuration, chiral centre *6 is in the S configuration, chiral centre *7 is in the R configuration, and chiral centre *8 is in the R configuration.

49 . A pharmaceutical composition comprising a compound as defined in claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

50 . A method of inhibiting an activity of an SSTR2 receptor in a subject, the method comprising administering a compound of claim 1 or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

51 . A method of preventing or treating hypoglycemia in a subject, the method comprising administering a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

52 . The method of 51 , wherein the hypoglycemia is insulin-induced hypoglycemia.

53 . A method of treating diabetes in a subject, the method comprising administering a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 29, 2021

From: ARNS, STEPHEN PAUL; JAQUITH, JAMES BRIAN; BAUDELET, DAVY JEREMY; SIMONSON, ERIC ROY; LIGGINS, RICHARD TOM; KUMAR, NAG SHARWAN; HSIEH, TOM HAN HSIAO

To: CDRD VENTURES INC.

Reel/Frame 058502/0318 →

Continuity (3)

Continuation 16076826

Provisional Application 62293216 · Feb 9, 2016

Related Publication 20220112242A1 · Apr 14, 2022

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