US 11,987,648 B2
Cyclohexapeptides as selective somatostatin SST5 receptor agonists
Giles Albert Brown, Cambridge (GB); Miles Stuart Congreve, Cambridge (GB); Conor Scully, Cambridge (GB); Rebecca Paul, Cambridge (GB); and Andrea Bortolato, Cambridge (GB)
Assigned to Heptares Therapeutics Limited, Cambridge (GB)
Appl. No. 17/284,399
Filed by Heptares Therapeutics Limited, Cambridge (GB)
PCT Filed Oct. 14, 2019, PCT No. PCT/GB2019/052911
§ 371(c)(1), (2) Date Apr. 9, 2021,
PCT Pub. No. WO2020/074926, PCT Pub. Date Apr. 16, 2020.
Claims priority of application No. 1816637 (GB), filed on Oct. 12, 2018.
Prior Publication US 2021/0363188 A1, Nov. 25, 2021
Int. Cl. C07K 7/64 (2006.01); A61K 38/00 (2006.01); A61P 5/02 (2006.01); A61P 35/00 (2006.01)
CPC C07K 7/64 (2013.01) [A61P 5/02 (2018.01); A61P 35/00 (2018.01); A61K 38/00 (2013.01)] 21 Claims
 
1. A compound of the formula (1):

OG Complex Work Unit Chemistry
or a salt thereof, wherein;
W is CH or N;
X and Y are CH2 or O, wherein one of X and Y is CH2 and the other of X and Y is O;
Z is CHR7, NR8 or O;
m is 1 or 2;
n is 0 to 3;
each R1 is independently selected from halo, C1-C3 alkyl and C1-C3 alkoxy, wherein the C1-C3 alkyl and alkoxy groups are optionally substituted with up to 6 fluorine atoms;
q is 0 to 2;
R2 is selected from H and C1-C3 alkyl optionally substituted with up to 6 fluorine atoms;
R3 is selected from optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted aryl and optionally substituted heteroaryl;
R4 is H or optionally substituted C1-C3 alkyl, where the C1-C3 alkyl group is optionally joined to R5 to form a ring;
R5 is selected from optionally substituted C1-C6 alkyl, optionally substituted aryl and optionally substituted heteroaryl, where R5 is optionally joined to R4 to form a ring;
R6 is selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted O-aryl or optionally substituted O-heteroaryl;
R7 is selected from H, optionally substituted C1-C6 alkyl, CONR10R11, OCONR10R11, OCOR10, OCOOR10, COOR10 or OR12;
R8 is selected from H, CONR10R11 or COOR10;
R10 and R11 are independently selected from H, optionally substituted C1-C6 alkyl and optionally substituted C2-C6 alkyl where any one atom in the C2-C6 alkyl group is replaced by a heteroatom selected from N, O and S, or wherein R10 and R11 are optionally joined to form a ring; and
R12 is optionally substituted aryl or optionally substituted heteroaryl.