US 2026/0234142 A1Published application

Pgdh inhibitors and methods of making and using

AssigneeMyoforte Therapeutics, Inc.

InventorsRoopa RAI, Robert BOOTH, Michael J. GREEN

Life of this patent

Estimating the term…

Abstract

Disclosed herein are compounds that can inhibit 15-hydroxyprostaglandin dehydrogenase. Such compounds may be administered to subjects that may benefit from modulation of prostaglandin levels.

Claims22

Dependent claims

A compound having the structure of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
X is selected from —OCH2—, —C(O)NH—, —NHC(O)—, —C(O)NMe-, —NMeC(O)—, —SCH2—, —S(O)CH2—, —SO2CH2—;
each Y is independently selected from N and CR11;
each R1 is independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR8, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
R2 is H and R3 is —CF3;
or
R2 and R3 are taken together to form oxo or thio;
each R4 is independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR8, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R5 is independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR8, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
R6 and R7 are independently selected at each occurrence from H, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, and C3-10cycloalkyl;
each R8 is independently selected from H, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R9 is independently selected from C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R10 is independently selected from H, C1-6alkyl, C1-6haloalkyl, and C3-10cycloalkyl;
each R11 is independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR8, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
n is 0, 1, 2, 3, 4, or 5;
m is 0, 1, 2, 3, or 4;
and
p is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
provided that said compound of Formula I is not

16 more elements

A compound having the structure of Formula IIa:

or a pharmaceutically acceptable salt thereof, wherein:
T, U, and Y are independently selected from N and CR5;
R1 is selected from C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
wherein the alkyl, cycloalkyl, aryl, or heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR8, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6 heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, and 5- to 10-membered heteroaryl;
R2 is H and R3 is —CF3;
or
R2 and R3 are taken together to form oxo or thio;
each R4 is independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR9, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
or
two R4 are taken together with the carbon atoms to which they are attached and any intervening atoms to form a C3-10cycloalkyl, and any remaining R4 are independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR9, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R5 is independently selected from H, halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR9, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
R6 and R7 are independently selected at each occurrence from H, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, and C3-10cycloalkyl;
each R8 is independently selected from H, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R9 is independently selected from C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R10 is independently selected from H, C1-6alkyl, C1-6haloalkyl, and C3-10cycloalkyl;
and
m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
and
p is 0, 1, or 2;
provided that the compound is not

17 more elements

A compound having the structure of Formula III:

or a pharmaceutically acceptable salt thereof, wherein:
each X is independently selected from N and CR7;
Y is selected from O, S, SO2, and C(R8)2;
R1 is selected from C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
wherein said alkyl, cycloalkyl, aryl, or heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halo, —NR9R10, —OR11, —C(O)R11, —C(O)OR11, —C(O)NR9R10, —SOR12, —SO2R12, —SO2NR9R10, —NR13C(O)R11, —NR13C(O)NR9R10, —NR13SO2R11, —NR13SO2NR9R10, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
R2 is H and R3 is —CF3;
or
R2 and R3 are taken together to form oxo or thio;
R4 and R5 are independently selected from C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, and C3-10cycloalkyl;
wherein each alkyl, heteroalkyl, haloalkyl, and cycloalkyl is independently optionally substituted with 1 to 3 substituents independently selected from halo, —NR9R10, —OR11, —C(O)R11, —C(O)OR11, —C(O)NR9R10, —SOR12, —SO2R12, —SO2NR9R10, —NR13C(O)R11, —NR13C(O)NR9R10, —NR13SO2R11, —NR13SO2NR9R10, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
or
R4 and R5 are taken together, along with the nitrogen atom to which they are attached, to form a 3- to 10-membered heterocycloalkyl optionally substituted with 1 to 3 substituents independently selected from halo, —NR9R10, —OR11, —C(O)R11, —C(O)OR11, —C(O)NR9R10, —SOR12, —SO2R12, —SO2NR9R10, —NR13C(O)R11, —NR13C(O)NR9R10, —NR13SO2R11, —NR13SO2NR9R10, C1-6alkyl, C1-6heteroalkyl, C1-6 haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R6 is independently selected from halo, —NR9R10, —OR11, —C(O)R11, —C(O)OR11, —C(O)NR9R10, —SOR12, —SO2R12, —SO2NR9R10, —NR13C(O)R11, —NR13C(O)NR9R10, —NR13SO2R11, —NR13SO2NR9R10, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
or
two R6's attached to the same carbon atom are taken together to form oxo, thio, or C3-10cycloalkyl, and any remaining R6's are independently selected from halo, —NR9R10, —OR11, —C(O)R11, —C(O)OR11, —C(O)NR9R10, —SOR12, —SO2R12, —SO2NR9R10, —NR13C(O)R11, —NR13C(O)NR9R10, —NR13SO2R11, —NR13SO2NR9R10, C1-6alkyl, C1-6 heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10 aryl, and 5- to 10-membered heteroaryl;
each R7 is independently selected from H, halo, —NR9R10, —OR11, —C(O)R11, —C(O)OR11, —C(O)NR9R10, —SOR12, —SO2R12, —SO2NR9R10, —NR13C(O)R11, —NR13C(O)NR9R10, —NR13SO2R11, —NR13SO2NR9R10, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R8 is independently selected from H, halo, —NR9R10, —OR11, —C(O)R11, —C(O)OR11, —C(O)NR9R10, —SOR12, —SO2R12, —SO2NR9R10, —NR13C(O)R11, —NR13C(O)NR9R10, —NR13SO2R11, —NR13SO2NR9R10, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
or
two R8's can be taken together to form a C3-10cycloalkyl optionally substituted with 1 to 3 substituents independently selected from halo, —NR9R10, —OR11, —C(O)R11, —C(O)OR11, —C(O)NR9R10, —SOR12, —SO2R12, —SO2NR9R10, —NR13C(O)R11, —NR13C(O)NR9R10, —NR13SO2R11, —NR13SO2NR9R10, C1-6alkyl, C1-6heteroalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
R9 and R10 are independently selected at each occurrence from H, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, and C3-10cycloalkyl;
each R11 is independently selected from H, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10 cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R12 is independently selected from C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10 cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R13 is independently selected from H, C1-6alkyl, C1-6haloalkyl, and C3-10 cycloalkyl;
m is 1 or 2;
and
n is 0, 1, 2, 3, or 4.

23 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/448,007Filed 13 Jan 2026
Priority: 23 Jan 2020
Published: 13 Aug 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/4184
1,3-Diazoles: condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/437
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring…
A61K 31/4453
Non condensed piperidines, e.g. piperocaine: only substituted in position 1, e.g. propipocaine, diperodon

Family

Application62/965,062Us provisional application · filed 23 Jan 2020
Application63/007,755Us provisional application · filed 9 Apr 2020
Application63/029,184Us provisional application · filed 22 May 2020
Application63/092,116Us provisional application · filed 15 Oct 2020
Application63/110,803Us provisional application · filed 6 Nov 2020
Application63/133,965Us provisional application · filed 5 Jan 2021
Application17/484,398Continuation · filed 24 Sep 2021
Application17/725,220Continuation · filed 20 Apr 2022
Application18/531,523Continuation · filed 6 Dec 2023
Application19/448,007Continuation
US 11,345,702 B1Related patent
US 11,891,389 B2Related patent
US 12,559,493 B2Related patent
US 2022/0267325 A1Published application
US 2024/0262820 A1Published application
US 2026/0234142 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Disclosed herein are compounds that can inhibit 15-hydroxyprostaglandin dehydrogenase. Such compounds may be administered to subjects that may benefit from modulation of prostaglandin levels.

A compound having the structure of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
X is selected from —OCH2—, —C(O)NH—, —NHC(O)—, —C(O)NMe-, —NMeC(O)—, —SCH2—, —S(O)CH2—, —SO2CH2—;
each Y is independently selected from N and CR11;
each R1 is independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR8, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
R2 is H and R3 is —CF3;
or
R2 and R3 are taken together to form oxo or thio;
each R4 is independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR8, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R5 is independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR8, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
R6 and R7 are independently selected at each occurrence from H, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, and C3-10cycloalkyl;
each R8 is independently selected from H, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R9 is independently selected from C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
each R10 is independently selected from H, C1-6alkyl, C1-6haloalkyl, and C3-10cycloalkyl;
each R11 is independently selected from halo, —NR6R7, —OR8, —C(O)R8, —C(O)OR8, —C(O)NR6R7, —SOR9, —SO2R9, —SO2NR6R7, —NR10C(O)R8, —NR10C(O)NR6R7, —NR10SO2R8, —NR10SO2NR6R7, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-10aryl, and 5- to 10-membered heteroaryl;
n is 0, 1, 2, 3, 4, or 5;
m is 0, 1, 2, 3, or 4;
and
p is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
provided that said compound of Formula I is not

16 more elements

Facts

Application

19/448,007Filed 13 Jan 2026

Priority

23 Jan 2020

Published

13 Aug 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/4184
1,3-Diazoles: condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/437
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring…
A61K 31/4453
Non condensed piperidines, e.g. piperocaine: only substituted in position 1, e.g. propipocaine, diperodon

Family

Application62/965,062Us provisional application · filed 23 Jan 2020

Application63/007,755Us provisional application · filed 9 Apr 2020

Application63/029,184Us provisional application · filed 22 May 2020

Application63/092,116Us provisional application · filed 15 Oct 2020

Application63/110,803Us provisional application · filed 6 Nov 2020

Application63/133,965Us provisional application · filed 5 Jan 2021

Application17/484,398Continuation · filed 24 Sep 2021

Application17/725,220Continuation · filed 20 Apr 2022

Application18/531,523Continuation · filed 6 Dec 2023

Application19/448,007Continuation

US 11,345,702 B1Related patent

US 11,891,389 B2Related patent

US 12,559,493 B2Related patent

US 2022/0267325 A1Published application

US 2024/0262820 A1Published application

US 2026/0234142 A1This patent

From the US filing history. Foreign family members aren’t listed.