IP Library › Granted Patent US 9,937,167

Granted Patent B2

US 9,937,167 · App. 15/370,973 · Granted Apr 10, 2018

SHIP1 modulators and methods related thereto

Inventors: Lloyd F. Mackenzie (North Vancouver, CA); Thomas B. Macrury (Point Roberts, WA); Curtis Harwig (Vancouver, CA); David Bogucki (Surrey, CA); Jeffery R. Raymond (Vancouver, CA); Jeremy D. Pettigrew (Burnaby, CA); Vladimir Khlebnikov (Edmonton, CA); Rudong Shan (Edmonton, CA)

Assignee: Aquinox Pharmaceuticals (Canada) Inc.

A61K31/4965 A61K31/05 A61K31/085 A61K31/09 A61K31/095 A61K31/10 A61K31/12 A61K31/122 A61K31/135 A61K31/155 A61K31/165 A61K31/166 A61K31/167 A61K31/192 A61K31/277 A61K31/4164 A61K31/4196 A61K31/4402 A61K31/443 A61K31/444 A61K31/4406 A61K31/4439 A61K31/4465 A61K31/495 A61K31/496

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Quick Facts

Patent No.: US 9,937,167
App. No.: 15/370,973
Granted: Apr 10, 2018
Kind: B2

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Abstract

Compounds of formula (I): where n, R 1 , R 4a , R 4b , R 5 , R 7 and R 8 are defined herein, or pharmaceutically acceptable salts thereof, are described herein. The disclosed compounds have activity as SHIP1 modulators, and thus may be used to treat any of a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of formula (I) in combination with a pharmaceutically acceptable carrier or diluent are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof.

Claims (240)

1. A method for treating a disease, disorder or condition in a mammal, wherein the disease, disorder or condition is selected from Sezary Syndrome, Hodgkin's Disease, Non-Hodgkin's Lymphoma, multiple myeloma, hypereosinophilic syndromes, mastocytosis or thrombocythemia and wherein the method comprises administering to the mammal in need thereof an effective amount of a compound of formula (I):

wherein:

is selected from:

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

R 1 is —R 9a —C(R 10 ) 2 —R 9b —, —R 9a —C(O)—R 9b —, —R 9a —S(O) t —R 9b (where t is 0, 1 or 2), —R 9a —OR 9b —,

—R 9a —C(O)N(R 11a )—R 9b —, —R 9a —N(R 11a )C(O)—R 9b — or —R 9a —N(R 11a )—R 9b —; provided that when A is

R 1 is not —R 9a —C(R 10 ) 2 —R 9b —;

R 2 and R 3 are each independently selected from hydrogen, alkyl or —R 9 —OR 11 , provided that at least one of R 2 and R 3 is —R 9 —OR 11 when R 6 is hydrogen;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

R 5 is independently selected from hydrogen, oxo, cyano, nitro, halo, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 9 —OR 11 , —R 9 —C(O)R 11 , —R 9 —C(O)OR 11 , —R 9 —N(R 11 )R 12 , —R 9 —C(O)N(R 11 )R 12 , —R 9 —N(R 11 )C(O)R 12 , —R 9 —N(R 11 )—R 14 —N(R 11 )R 12 , —R 9 —N(R 11 )C(O)—R 9 —N(R 11 )R 12 , —R 9 —N(R 11 )C( O)N(R 11 )—OR 12 , —R 9 —N(R 11 )C(═NR 11 )N(R 11 )R 12 , —R 9 —N(R 11 )S(O) p R 11 (where p is 1 or 2), —R 9 —N(R 11 )C(S)N(R 11 )R 12 or —R 9 —N(R 11 )C(O)—R 9 —N(R 11 )S(O) p R 12 (where p is p 1 or 2);

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 , R 9a and R 9b is independently a direct bond or a straight or branched alkylene chain;

each R 10 is independently hydrogen, alkyl, —OR 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —N(R 11 )R 12 or —N(R 11 )C(O)R 11 ;

each R 11 , R 11a and R 12 is independently hydrogen, alkyl, alkenyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl; and

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

provided that compounds of formula (I) do not include the following compounds:

(1S,2R,4aS,8aS)-1-(3-methoxy-5-methylphenoxymethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol;

(1S,2R,4aS,8aS)-1-(3,5-dimethoxyphenoxymethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol;

(1S,2R,4aS,8aS)-1[3,5-bis(propan-2-yloxy)phenoxymethyl]-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol;

(1R,2R,8aS)-1-((3,5-dimethoxyphenylsulfonyl)methyl)-2,5,5,8a -tetramethyldecahydronaphthalen-2-ol;

(1R,2R,4aS,8aS)-1-{[(3-methoxy-5-methylphenyl)sulfanyl]methyl}-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol;

(1R,2R,4aS,8aS)-1-{[(3-methoxyphenyl)sulfanyl]methyl}-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol; and

(1R,2R, 4aS,8aS)-1-{[(3,5-dimethoxyphenyl)sulfanyl]methyl}-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol.

2. The method of claim 1 , wherein the compound of formula (I) has the following formula (Ia):

wherein:

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

R 1 is —R 9a —C(O)—R 9b —, —R 9a —S(O)—R 9b — (where t is 0, 1, or 2), —R 9a —O—R 9b —, —R 9a —C(O)N(R 11a )—R 9b —, —R 9a —N(R 11a )C(O)—R 9b — or —R 9a —N(R 11a )—R 9b —;

R 2 and R 3 are each independently selected from hydrogen, alkyl or —R 9 —OR 11 , provided that at least one of R 2 and R 3 is —R 9 —OR 11 when R 6 is hydrogen;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

R 5 is independently selected from hydrogen, oxo, cyano, nitro, halo, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 9 —OR 11 , —R 9 —C(O)R 11 , —R 9 —C(O)OR 11 , —R 9 —N(R 11 )R 12 , —R 9 —C(O)N(R 11 )R 12 , —R 9 —N(R 11 )C(O)R 12 , —R 9 —N(R 11 )—R 14 —N(R 11 )R 12 , —R 9 —N(R 11 )C(O)—R 9 —N(R 11 )R 12 , —R 9 —N(R 11 )C(O)N(R 11 )—OR 12 , —R 9 —N(R 11 )C(═NR 11 )N(R 11 )R 12 , —R 9 —N(R 11 )S(O) p R 11 (where p is 1 or 2), —R 9 —N(R 11 )C(S)N(R 11 )R 12 or —R 9 —N(R 11 )C(O)—R 9 —N(R 11 )S(O) p R 12 (where p is 1 or 2);

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 , R 9a and R 9b is independently a direct bond or a straight or branched alkylene chain;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

3. The method of claim 2 , wherein the compound of formula (Ia) is a compound of formula (Ia) wherein R 1 is —R 9a —C(O)—R 9b — and has the following formula (Ia1):

wherein:

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

R 2 and R 3 are each independently selected from hydrogen, alkyl or —R 9 —OR 11 , provided that at least one of R 2 and R 3 is —R 9 —OR 11 when R 6 is hydrogen;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

R 5 is independently selected from hydrogen, oxo, cyano, nitro, halo, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 9 —OR 11 , —R 9 —C(O)R 11 , —R 9 —C(O)OR 11 ,—R 9 —N(R 11 )R 12 , —R 9 —C(O)N(R 11 )R 12 , —R 9 —N(R 11 )C(O)R 12 , —R 9 —N(R 11 )—R 14 —N(R 11 )R 12 , —R 9 —N(R 11 )C(O)—R 9 —N(R 11 )R 12 , —R 9 —N(R 11 )C(O)N(R 11 )—OR 12 , —R 9 —N(R 11 )C(═NR 11 )N(R 11 )R 12 , —R 9 —N(R 11 )S(O) p R 11 (where p is 1 or 2 ), —R 9 —N(R 11 )C(S)N(R 11 )R 12 or —R 9 —N(R 11 )C(O)—R 9 —N(R 11 )S(O) p R 12 (where p is 1 or 2);

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 is independently a direct bond or a straight or branched alkylene chain;

R 9a and R 9b are each independently a direct bond or a straight or branched alkylene chain; each R 11 and R 12 is independently hydrogen, alkyl, alkenyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl; and

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

4. The method of claim 2 , wherein the compound of formula (Ia) is a compound of formula (Ia) wherein R 1 is —R 9 —S(O) t —R 9 — and has the following formula (Ia3):

wherein:

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

t is 0, 1 or 2;

R 2 and R 3 are each independently selected from hydrogen, alkyl or —R 9 —OR 11 , provided that at least one of R 2 and R 3 is —R 9 —OR 11 when R 6 is hydrogen;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 is independently a direct bond or a straight or branched alkylene chain;

R 9a and R 9b are each independently a direct bond or a straight or branched alkylene chain;

each R 11 and R 12 is independently hydrogen, alkyl, alkenyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl; and

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

5. The method of claim 2 , wherein the compound of formula (Ia) is a compound of formula (Ia) wherein R 1 is —R 9a —O—R 9b — and has the following formula (Ia4):

wherein:

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

R 2 and R 3 are each independently selected from hydrogen, alkyl or —R 9 —OR 11 , provided that at least one of R 2 and R 3 is —R 9 —OR 11 when R 6 is hydrogen;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 is independently a direct bond or a straight or branched alkylene chain;

R 9a and R 9b are each independently a direct bond or a straight or branched alkylene chain;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

6. The method of claim 2 , wherein the compound of formula (Ia) is a compound of formula (Ia) wherein R 1 is —R 9a —C(O)N(R 11a )—R 9b — and has the following formula (Ia5):

wherein:

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

R 2 and R 3 are each independently selected from hydrogen, alkyl or —R 9 —OR 11 , provided that at least one of R 2 and R 3 is —R 9 —OR 11 when R 8 is hydrogen;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 is independently a direct bond or a straight or branched alkylene chain;

R 9a and R 9b are each independently a direct bond or a straight or branched alkylene chain;

R 11a is hydrogen, alkyl, alkenyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl; and

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

7. The method of claim 2 , wherein the compound of formula (Ia) is a compound of formula (Ia) wherein R 1 is —R 9a —N(R 11a )C(O)—R 9b — and has the following formula (Ia6):

wherein:

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

R 2 and R 3 are each independently selected from hydrogen, alkyl or —R 9 —OR 11 , provided that at least one of R 2 and R 3 is —R 9 —OR 11 when R 8 is hydrogen;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 is independently a direct bond or a straight or branched alkylene chain;

R 9a and R 9b are each independently a direct bond or a straight or branched alkylene chain; and

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

8. The method of claim 2 , wherein the compound of formula (Ia) is a compound of formula (Ia) wherein R 1 is —R 9a —N(R 11a )—R 9b — and has the following formula (Ia7):

wherein:

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

R 2 and R 3 are each independently selected from hydrogen, alkyl or —R 9 —OR 11 , provided that at least one of R 2 and R 3 is —R 9 —OR 11 when R 6 is hydrogen;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 is independently a direct bond or a straight or branched alkylene chain;

R 9a and R 9b are each independently a direct bond or a straight or branched alkylene chain; and

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein the compound of formula (I) has the following formula (Ic):

wherein:

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

R 1 is —R 9a —C(R 10 ) 2 —R 9b —, —R 9a —C(O)—R 9b —, —R 9a —S(O) t —R 9b — (where t is 0, 1 or 2), —R 9a —O—R 9b —, —R 9a —C(O)N(R 11a )—R 9b —, —R 9a —N(R 11a )C(O)—R 9b — or —R 9a —N(R 11a )—R 9b —;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 , R 9a and R 9b is independently a direct bond or a straight or branched alkylene chain;

each R 10 is independently hydrogen, alkyl, —OR 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —N(R 11 )R 12 or —N(R 11 )C(O)R 11 ;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

10. The method of claim 9 , wherein the compound of formula (Ic) is a compound of formula (Ic) wherein R 1 is —R 9a —N(R 11a )C(O)—R 9b — and has the following formula (Ic1):

wherein:

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

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 is independently a direct bond or a straight or branched alkylene chain;

R 9a and R 9b are each independently a direct bond or a straight or branched alkylene chain;

each R 10 is independently hydrogen, alkyl, —OR 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —N(R 11 )R 12 or —N(R 11 )C(O)R 11 ;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

11. The method of claim 1 , wherein the compound of formula (I) has the following formula (Id):

wherein:

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

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 , R 9a and R 9b is independently a direct bond or a straight or branched alkylene chain;

each R 10 is independently hydrogen, alkyl, —OR 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —N(R 11 )R 12 or —N(R 11 )C(O)R 11 ;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

12. The method of claim 11 , wherein the compound of formula (Id) is a compound of formula (Id) wherein R 1 is —R 9a —C(R 10 ) 2 —R 9b — and has the following formula (Id1):

wherein:

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

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 is independently a direct bond or a straight or branched alkylene chain;

R 9a and R 9b are each independently a direct bond or a straight or branched alkylene chain;

each R 10 is independently hydrogen, alkyl, —OR 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —N(R 11 )R 12 or —N(R 11 )C(O)R 11 ;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

13. The method of claim 1 , wherein the compound of formula (I) has the following formula (Ie):

wherein:

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

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 , R 9a and R 9b is independently a direct bond or a straight or branched alkylene chain;

each R 10 is independently hydrogen, alkyl, —OR 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —N(R 11 )R 12 or —N(R 11 )C(O)R 11 ;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

14. The method of claim 13 , wherein the compound of formula (Ie) is a compound of formula (Ie) wherein R 1 is —R 9a —C(R 10 ) 2 —R 9b — and has the following formula (Ie1):

wherein:

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

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 is independently a direct bond or a straight or branched alkylene chain;

R 9a and R 9b are each independently a direct bond or a straight or branched alkylene chain; and

each R 10 is independently hydrogen, alkyl, —OR 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —N(R 11 )R 12 or —N(R 11 )C(O)R 11 ;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

15. The method of claim 1 , wherein the compound of formula (I) has the following formula (If):

wherein:

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

R 1 is —R 9a —C(R 10 ) 2 —R 9b —, —R 9a —C(O)—R 9b —, —R 9a —S(O) t —R 9b — (where t is 0, 1 or 2), —R 9a —OR—R 9b —, —R 9a —C(O)N(R 11a )—R 9b —, —R 9a —N(R 11a )C(O)—R 9b — or —R 9a —N(R 11a )—R 9b —;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 , R 9a and R 9b is independently a direct bond or a straight or branched alkylene chain;

each R 10 is independently hydrogen, alkyl, —OR 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —N(R 11 )R 12 or —N(R 11 )C(O)R 11 ;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

16. The method of claim 15 , wherein the compound of formula (If) is a compound of formula (If) wherein R 1 is —R 9a —C(R 10 ) 2 —R 9b — and has the following formula (If1):

wherein:

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

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 is independently a direct bond or a straight or branched alkylene chain;

R 9a and R 9b are each independently a direct bond or a straight or branched alkylene chain;

each R 10 is independently hydrogen, alkyl, —OR 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —N(R 11 )R 12 or —N(R 11 )C(O)R 11 ;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

17. The method of claim 1 , wherein the compound of formula (I) is a compound of formula (I) wherein:

is selected from:

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

R 1 is —R 9a —C(R 10 ) 2 —R 9b —, —R 9a —C(O)—R 9b —, —R 9a —S(O) t —R 9b — (where t is 0, 1 or 2), —R 9a —O—R 9b —, or —R 9a —C(O)N(R 11a )—R 9b — or —R 9a —N(R 11a )C(O)—R 9b —;

R 4a and R 4b are each independently selected from hydrogen, alkyl, —R 9 —OR 11 or —C(O)OR 11 ;

each R 6 and R 8 is independently selected from hydrogen, alkyl, halo or haloalkyl;

R 7 is hydrogen, alkyl, halo or haloalkyl;

each R 9 , R 9a and R 9b is independently a direct bond or a straight or branched alkylene chain;

each R 10 is independently hydrogen, alkyl, —OR 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —N(R 11 )R 12 or —N(R 11 )C(O)R 11 ;

R 14 is a straight or branched alkylene chain;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

18. The method of claim 1 , wherein the disease, disorder or condition is Sezary Syndrome, Hodgkin's Disease or Non-Hodgkin's Lymphoma.

19. The method of claim 1 , wherein the disease, disorder or condition is multiple myeloma.

20. The method of claim 1 , wherein the disease, disorder or condition is hypereosinophilic syndromes, mastocytosis or thrombocythemia.

Assignments (5)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 27, 2020

From: AQUINOX PHARMACEUTICALS (CANADA) INC.

To: NEOLEUKIN THERAPEUTICS, INC.

Reel/Frame 053322/0111 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2017

From: MACKENZIE, LLOYD F.; MACRURY, THOMAS B.; HARWIG, CURTIS; BOGUCKI, DAVID; RAYMOND, JEFFERY R.; PETTIGREW, JEREMY D

To: AQUINOX PHARMACEUTICALS INC.

Reel/Frame 040971/0756 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2017

From: NAEJA PHARMACEUTICAL INC.

To: AQUINOX PHARMACEUTICALS INC.

Reel/Frame 040973/0986 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2017

From: KHLEBNIKOV, VLADIMIR; SHAN, RUDONG

To: NAEJA PHARMACEUTICAL INC.

Reel/Frame 040984/0761 →

CHANGE OF NAME Recorded Jan 13, 2017

From: AQUINOX PHARMACEUTICALS INC.

To: AQUINOX PHARMACEUTICALS (CANADA) INC.

Reel/Frame 041041/0607 →

Continuity (3)

Division 14759622

Provisional Application 61750695 · Jan 9, 2013

Related Publication 20170224682A1 · Aug 10, 2017