US 2020/0277256 A1Published application

Selective ship inhibitors for treating disease

AssigneesThe Research Foundation for The State University of New York, Syracuse University

InventorsWilliam G. Kerr, John D. Chisholm

Life of this patent

Estimating the term…

Abstract

The present disclosure provides compositions that inhibit the SH2-containing inositol 5′-phosphatase (SHIP), as well as methods using such compositions for use in treating or ameliorating the effects of a medical condition in a subject.

Claims30

Dependent claims

A compound of Formula I:

or a pharmaceutically acceptable salt or solvate thereof, wherein
A is C2-C12 aryl, C2-C12 heteroaryl, C1-C12 heteroalkyl, or absent;
X is C or C(R3);
R1 is C1-C6alkyl-N(R4)(R5), wherein the alkyl is optionally substituted with 1, 2, or 3 groups, each independently selected from C1-C12 alkyl or C0-C12 alkyl(C6-C12 aryl);
R2 is H or C1-C6alkyl;
R3 is H or C6-C12 aryl;
R4 is H or C1-C6alkyl;
R5 is H or C1-C6alkyl, wherein R2 and R5 are taken together from the nitrogen atoms to which they are bound to form a heterocycle or spiro-heterocycle;
Z is —S(O)2OR6, —S(O)2N(R7)(R8), —P(O)2OR9, —P(S)(OR10)2, or —S(O)2R11;
R6 is C1-C12alkyl, C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1-C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, wherein alkyl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O-C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R7 is H, C1-C6alkyl, or C1-C6alkenyl, wherein alkyl and alkenyl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R8 is H, C1-C6alkyl, or C1-C6alkenyl, wherein alkyl and alkenyl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R9 is H, C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R10 is H, C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R11 is C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, wherein alkyl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
wherein R11 is optionally taken together with R1 to form a covalent bond;
R12 is a protecting group;
n is 0 or 1;
and
m is 0 or 1.

17 more elements

A compound of Formula III:

or a pharmaceutically acceptable salt or solvate thereof, wherein
X is N or C(H);
Y is N or C(H);
R1 is C1-C6alkyl-N(R4)(R5), wherein the alkyl is optionally substituted with 1, 2, or 3 groups, each independently selected from C1-C12 alkyl or C0-C12 alkyl(C6-C12 aryl);
R2 is H or C1-C6alkyl;
R4 is H or C1-C6alkyl;
R5 is H or C1-C6alkyl, wherein R2 and R5 are taken together from the nitrogen atoms to which they are bound to form a heterocycle or spiro-heterocycle;
Z is —S(O)2OR6, —S(O)2N(R7)(R8), —P(O)2OR9, —P(S)(OR10)2, or —S(O)2R11;
R6 is C1-C12alkyl, C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1-C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, wherein alkyl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O-C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R7 is H, C1-C6alkyl, or C1-C6alkenyl, wherein alkyl and alkenyl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R8 is H, C1-C6alkyl, or C1-C6alkenyl, wherein alkyl and alkenyl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R9 is H, C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R10 is H, C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R11 is C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, wherein alkyl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
wherein R11 is optionally taken together with R1 to form a covalent bond;
R12 is a protecting group;
n is 0 or 1;
and
m is 0 or 1.

16 more elements

A compound of Formula IV:

or a pharmaceutically acceptable salt or solvate thereof, wherein
R1 is C1-C6alkyl-N(R4)(R5), wherein the alkyl is optionally substituted with 1, 2, or 3 groups, each independently selected from C1-C12 alkyl or C0-C12 alkyl(C6-C12 aryl);
R2 is H or C1-C6alkyl;
R3 is H or C6-C12 aryl;
R4 is H or C1-C6alkyl;
R5 is H or C1-C6alkyl, wherein R2 and R5 are taken together from the nitrogen atoms to which they are bound to form a heterocycle or spiro-heterocycle;
Z is —S(O)2OR6, —S(O)2N(R7)(R8), —P(O)2OR9, —P(S)(OR10)2, or —S(O)2R11;
R6 is C1-C12alkyl, C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1-C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, wherein alkyl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O-C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R7 is H, C1-C6alkyl, or C1-C6alkenyl, wherein alkyl and alkenyl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R8 is H, C1-C6alkyl, or C1-C6alkenyl, wherein alkyl and alkenyl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R9 is H, C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R10 is H, C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R11 is C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, wherein alkyl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
wherein R11 is optionally taken together with R1 to form a covalent bond;
R12 is a protecting group;
n is 0 or 1;
and
m is 0 or 1.

15 more elements

A compound of Formula V:

or a pharmaceutically acceptable salt or solvate thereof, wherein
R1 is C1-C6alkyl-N(R4)(R5), wherein the alkyl is optionally substituted with 1, 2, or 3 groups, each independently selected from C1-C12 alkyl or C0-C12 alkyl(C6-C12 aryl);
R2 is H or C1-C6alkyl;
R3 is H or C6-C12 aryl;
R4 is H or C1-C6alkyl;
R5 is H or C1-C6alkyl, wherein R2 and R5 are taken together from the nitrogen atoms to which they are bound to form a heterocycle or spiro-heterocycle;
Z is —S(O)2OR6, —S(O)2N(R7)(R8), —P(O)2OR9, —P(S)(OR10)2, or —S(O)2R11;
R6 is C1-C12alkyl, C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1-C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, wherein alkyl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O-C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R7 is H, C1-C6alkyl, or C1-C6alkenyl, wherein alkyl and alkenyl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R8 is H, C1-C6alkyl, or C1-C6alkenyl, wherein alkyl and alkenyl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R9 is H, C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R10 is H, C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R11 is C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, wherein alkyl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
wherein R11 is optionally taken together with R1 to form a covalent bond;
R12 is a protecting group;
n is 0 or 1;
and
m is 0 or 1.

15 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/656,284Filed 17 Oct 2019
Priority: 17 Oct 2018
Published: 3 Sep 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07C 309/47
Containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton: having at least one of the sulfo groups bound…
C07C 311/37
Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso…
A61P 35/00
Antineoplastic agents
C07C 309/76
Having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton: containing nitrogen…

Family

Application62/746,793Us provisional application · filed 17 Oct 2018
US 11,952,328 B2Related patent
US 2020/0277256 A1This patent

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

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Abstract

A compound of Formula I:

or a pharmaceutically acceptable salt or solvate thereof, wherein
A is C2-C12 aryl, C2-C12 heteroaryl, C1-C12 heteroalkyl, or absent;
X is C or C(R3);
R1 is C1-C6alkyl-N(R4)(R5), wherein the alkyl is optionally substituted with 1, 2, or 3 groups, each independently selected from C1-C12 alkyl or C0-C12 alkyl(C6-C12 aryl);
R2 is H or C1-C6alkyl;
R3 is H or C6-C12 aryl;
R4 is H or C1-C6alkyl;
R5 is H or C1-C6alkyl, wherein R2 and R5 are taken together from the nitrogen atoms to which they are bound to form a heterocycle or spiro-heterocycle;
Z is —S(O)2OR6, —S(O)2N(R7)(R8), —P(O)2OR9, —P(S)(OR10)2, or —S(O)2R11;
R6 is C1-C12alkyl, C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1-C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, wherein alkyl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O-C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R7 is H, C1-C6alkyl, or C1-C6alkenyl, wherein alkyl and alkenyl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R8 is H, C1-C6alkyl, or C1-C6alkenyl, wherein alkyl and alkenyl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R9 is H, C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R10 is H, C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
R11 is C1-C12alkyl, or C1-C12alkenyl, —C(O)C1-C12alkyl, —C(O)OC1C12alkyl, —C(O)N(C1-C12alkyl)2 or C6-C12 aryl, wherein alkyl, alkenyl, and aryl are optionally substituted with 1, 2, or 3 groups, each independently selected from halo, —OH, C1-C6alkyl, C1-C6-haloalkyl, —O—C1-C6alkyl, —NO2, —N(H)(R12), and —CN;
wherein R11 is optionally taken together with R1 to form a covalent bond;
R12 is a protecting group;
n is 0 or 1;
and
m is 0 or 1.

17 more elements

Facts

Application

16/656,284Filed 17 Oct 2019

Priority

17 Oct 2018

Published

3 Sep 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07C 309/47
Containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton: having at least one of the sulfo groups bound…
C07C 311/37
Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso…
A61P 35/00
Antineoplastic agents
C07C 309/76
Having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton: containing nitrogen…