US2016375026A1PendingUtilityA1
Pyrrolopyrimidine compounds as kinase inhibitors
Est. expiryNov 15, 2032(~6.3 yrs left)· nominal 20-yr term from priority
A61P 35/00A61P 43/00A61P 37/00A61P 37/02A61P 29/00A61P 19/02A61P 17/00A61K 31/519C07D 487/04
51
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Claims
Abstract
Disclosed herein are methods of using pyrrolo[2,3-d]pyrimidine Btk inhibitors, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, and inflammatory diseases or conditions.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method for treating an autoimmune disease or condition, a heteroimmune disease or condition, or an inflammatory disease or condition comprising administering to a patient in need a therapeutically effective amount of a compound of Formula (I) having the structure:
wherein:
R 1 is halogen, —CN, —OH, —NH 2 , —SH, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 4 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl or substituted or unsubstituted C 3 -C 8 cycloalkyl;
G is substituted or unsubstituted C 2 -C 4 alkenyl, substituted or unsubstituted C 2 -C 4 alkynyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 1 -C 4 alkoxy, substituted or unsubstituted C 1 -C 4 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SCH 3 , —N(R 21 )S(═O) 2 R 23 , S(═O) 2 N(R 21 )(R 22 ), —S(═O)R 23 , —S(═O) 2 R 23 , —C(═O)R 23 , —OC(═O)R 23 , —CO 2 R 21 , N(R 21 )(R 22 ), —C(═O)N(R 21 )(R 22 ), —N(R 21 )C(═O)R 23 , N(R 21 )C(═O)OR 22 , N(R 21 )C(═O)N(R 21 )(R 22 ), or L a -Ar;
L a is a bond, —CH 2 —, —CH(OH)—, —C(O)—, —CH 2 O—, —OCH 2 —, —SCH 2 , —CH 2 S—, —N(R 21 )—, —N(R 21 )C(O)—, —C(O)N(R 21 )—, —N(R 21 )C(O)N(R 21 )—, —O—, —S—, —S(O) 2 —, —N(R 21 )S(O) 2 —, or —S(O) 2 N(R 21 )—;
Ar is a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl;
each R 24 is independently halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SCH 3 , —N(R 21 )S(═O) 2 R 23 , S(═O) 2 N(R 21 )(R 22 ), —S(═O)R 23 , —S(═O) 2 R 23 , —C(═O)R 23 , —OC(═O)R 23 , —CO 2 R 21 , N(R 21 )(R 22 ), —C(═O)N(R 21 )(R 22 ), —N(R 21 )C(═O)R 23 , N(R 21 )C(═O)OR 22 , —N(R 21 )C(═O)N(R 21 )(R 22 ), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted cycloalkyl;
each R 21 and R 22 is independently H, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 3 -C 8 cycloalkyl;
each R 23 is each independently substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 3 -C 8 cycloalkyl;
n is 0-4;
Y is an optionally substituted group selected from among C 1 -C 6 alkylene, C 1 -C 6 heteroalkylene, C 6 -C 12 arylene, C 3 -C 12 heteroarylene, C 1 -C 6 alkyleneC 6 -C 12 arylene, C 1 -C 6 alkyleneC 3 -C 12 heteroarylene, C 1 -C 6 alkyleneC 3 -C 8 cycloalkylene, C 1 -C 6 alkyleneC 2 -C 7 heterocycloalkylene, C 3 -C 8 cycloalkylene, C 2 -C 7 heterocycloalkylene, fused C 3 -C 8 cycloalkyleneC 2 -C 7 heterocycloalkylene, and spiro C 3 -C 8 cycloalkyleneC 2 -C 7 heterocycloalkylene;
Z is —C(═O)—, —N(R a )C(═O)—, or —N(R a )S(═O) x —, where x is 1 or 2, and R a is H, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 3 —C cycloalkyl;
R 6 is H or L-J-W;
R 7 and R 8 are independently H or L-J-W; or R 7 and R 8 taken together form a bond;
L and J are each independently a bond, substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted C 3 -C 8 cycloalkylene, substituted or unsubstituted C 1 -C 6 heteroalkylene, substituted or unsubstituted C 2 -C 7 heterocycloalkylene, substituted or unsubstituted C 6 -C 12 arylene, substituted or unsubstituted C 3 -C 12 heteroarylene, —CO—, —O—, or —S—;
W is H, or NR 25 R 26 ; and
R 25 and R 26 are each independently H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 3 —C cycloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 6 -C 12 aryl, or substituted or unsubstituted C 3 -C 12 heteroaryl; or
a pharmaceutically acceptable solvate, or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , wherein G is L a -Ar.
3 . The method of claim 2 , wherein L a is —O—; and Ar is phenyl.
4 . The method of claim 3 , wherein Y is C 2 -C 7 heterocycloalkylene or phenyl.
5 . The method of claim 4 , wherein Z is —C(═O)—, —NHC(═O)—, or —N(CH 3 )C(═O)—.
6 . The method of claim 5 , wherein R 6 and R 8 are H; R 7 is H or L-J-W; L is a bond; J is —CH 2 —; and W is NR 25 R 26 .
7 . The method of claim 6 , wherein R 25 is CH 3 and R 26 is CH 3 or cyclopropyl.
8 . The method of claim 1 , wherein n is 0.
9 . The method of claim 1 , wherein R 1 is —F, —Cl, —CH 3 , or —OCH 3 .
10 . A method for treating an autoimmune disease or condition, a heteroimmune disease or condition, or an inflammatory disease or condition comprising administering to a patient in need a therapeutically effective amount of a compound of Formula (I) having the structure:
wherein:
R 1 is halogen, —CN, —OH, —NH 2 , —SH, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 4 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted heteroaryl or substituted or unsubstituted C 3 -C 8 cycloalkyl;
G is substituted or unsubstituted C 2 -C 4 alkenyl, substituted or unsubstituted C 2 -C 4 alkynyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, unsubstituted C 1 -C 4 alkoxy, unsubstituted C 1 -C 4 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, halogen, —CN, —NO 2 ,
—OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SCH 3 , —N(R 21 )S(═O) 2 R 23 , S(═O) 2 N(R 21 )(R 22 ), —S(═O)R 23 , —S(═O) 2 R 23 , —C(═O)R 23 , —OC(═O)R 23 , —CO 2 R 21 , N(R 21 )(R 22 ), —C(═O)N(R 21 )(R 22 ), —N(R 21 )C(═O)R 23 , N(R 21 )C(═O)OR 22 , N(R 21 )C(═O)N(R 21 )(R 22 ), or
L a -Ar;
L a is a bond, —CH 2 —, —CH(OH)—, —C(O)—, —CH 2 O—, —SCH 2 , —CH 2 S—, —N(R 21 )—, —N(R 21 )C(O)—, —C(O)N(R 21 )—, —N(R 21 )C(O)N(R 21 )—, —O—, —S—, —S(O)—, —S(O) 2 —, —N(R 21 )S(O) 2 —, or —S(O) 2 N(R 21 )—;
Ar is a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl;
each R 24 is independently halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SCH 3 , —N(R 21 )S(═O) 2 R 23 , S(═O) 2 N(R 21 )(R 22 ), —S(═O)R 23 , —S(═O) 2 R 23 , —C(═O)R 23 , —OC(═O)R 23 , —CO 2 R 21 , N(R 21 )(R 22 ), —C(═O)N(R 21 )(R 22 ), —N(R 21 )C(═O)R 23 , N(R 21 )C(═O)OR 22 , N(R 21 )C(═O)N(R 21 )(R 22 ), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted cycloalkyl;
each R 21 and R 22 is independently H, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 3 -C 8 cycloalkyl;
each R 23 is each independently substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 3 -C 8 cycloalkyl;
n is 0-4;
Y is an optionally substituted group selected from among C 1 -C 6 alkylene, C 1 -C 6 heteroalkylene, C 6 -C 12 arylene, C 3 -C 12 heteroarylene, C 1 -C 6 alkyleneC 6 -C 12 arylene, C 1 -C 6 alkyleneC 3 -C 12 heteroarylene, C 1 -C 6 alkyleneC 3 -C 8 cycloalkylene, C 1 -C 6 alkyleneC 2 -C 7 heterocycloalkylene, C 3 -C 8 cycloalkylene, C 2 -C 7 heterocycloalkylene, fused C 3 -C 8 cycloalkyleneC 2 -C 7 heterocycloalkylene, and spiro C 3 -C 8 cycloalkyleneC 2 -C 7 heterocycloalkylene;
Z is —C(═O)—, —N(R a )C(═O)—, —S(═O) x —, or —N(R a )S(═O) x , where x is 1 or 2, and R a is H, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 3 -C 8 cycloalkyl;
R 6 is H or L-J-W;
R 7 and R 8 are independently H or L-J-W; or R 7 and R 8 taken together form a bond;
L and J are each independently a bond, substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted C 3 -C 8 cycloalkylene, substituted or unsubstituted C 1 -C 6 heteroalkylene, substituted or unsubstituted C 2 -C 7 heterocycloalkylene, substituted or unsubstituted C 6 -C 12 arylene, substituted or unsubstituted C 3 -C 12 heteroarylene, —CO—, —O—, or —S—;
W is H, or NR 25 R 26 ; and
R 25 and R 26 are each independently H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 3 —C cycloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 6 -C 12 aryl, or substituted or unsubstituted C 3 -C 12 heteroaryl; or
a pharmaceutically acceptable solvate, or a pharmaceutically acceptable salt thereof.
11 . The method of claim 10 , wherein G is L a -Ar.
12 . The method of claim 11 , wherein L a is —O—; and Ar is phenyl.
13 . The method of claim 12 , wherein Y is C 2 -C 7 heterocycloalkylene or phenyl.
14 . The method of claim 13 , wherein Z is —C(═O)—, —NHC(═O)—, or —N(CH 3 )C(═O)—.
15 . The method of claim 14 , wherein R 6 and R 8 are H; R 7 is H or L-J-W; L is a bond; J is —CH 2 —; and W is NR 25 R 26 .
16 . The method of claim 15 , wherein R 25 is CH 3 and R 26 is CH 3 or cyclopropyl.
17 . The method of claim 10 , wherein n is 0.
18 . The method of claim 10 , wherein R 1 is —F, —CH 3 , or —OCH 3 .
19 . A method for treating an autoimmune disease or condition, a heteroimmune disease or condition, or an inflammatory disease or condition comprising administering to a patient in need a therapeutically effective amount of any one compound selected from:
or a pharmaceutically acceptable solvate, or pharmaceutically acceptable salt thereof; wherein
R is methyl, —CN, fluoro, chloro, hydroxy, —NH 2 , or —CO 2 H; and
X is methyl, ethyl, propyl, isopropyl, cyclopropyl, tert-butyl, or trifluoromethyl.Join the waitlist — get patent alerts
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