Imidazo[1,2-a]pyridine derivatives: preparation and pharmaceutical applications

Patent metadata

Field	Value
Publication number	US-9266882-B2
Application number	US-201414517614-A
Country	US
Kind code	B2
Filing date	Oct 17, 2014
Priority date	Mar 21, 2005
Publication date	Feb 23, 2016
Grant date	Feb 23, 2016

First claim

What is claimed is:

1. A compound having the structure of:

wherein:
R 1 is alkyl;
R 3 is selected from the group consisting of: H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted;
R 4 is selected from the group consisting of: H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted;
Z is selected from —CH 2 —, —CH 2 CH 2 —, —CH═CH— and C 3 -C 6 cycloalkyl, each of which may be optionally substituted;
each Y is independently selected from the group consisting of: H, halogen, —CN, —NO 2 , —CF 3 , —OCF 3 , alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxyaryl, alkoxyheteroaryl, alkenyloxy, alkynyloxy, cycloalkyloxy, cycloalkenyloxy, heterocycloalkyloxy, heterocycloalkenyloxy, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, arylalkyloxy, amino, alkylamino, acylamino, aminoalkyl, arylamino, sulfonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, aminoalkyl, alkoxyalky, —COOH—C(O)OR 6 , —COR 6 , —SH, —SR 7 , —OR 7 , acyl and —NR 8 R 9 each of which may be optionally substituted;
each R 6 is independently selected from the group consisting of: H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted;
each R 7 is independently selected from the group consisting of: H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted;
each R 8 and R 9 is independently selected from the group consisting of: H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted;
p is an integer selected from the group consisting of 0, 1, 2, and 3;
L is selected from the group consisting of:
a) Cy-L 1 -W—
b) Cy-L 1 -W-L 2 -;
c) Cy-(CH 2 ) k —W—;
d) L 1 -W-L 2 -;
e) Cy-L 1 -;
f) R 12 —W 1 -L 1 -W—; and
g) —(CR 20 R 21 ) m —(CR 22 R 23 ) n —(CR 24 R 25 ) o —NR 26 R 27 ;

wherein
Cy is selected from the group consisting of C 1 -C 15 alkyl, aminoalkyl, heteroalkyl, heterocycloalkyl, cycloalkyl, aryl, aryloxy and heteroaryl, each of which may be optionally substituted;
L 1 is selected from the group consisting of a bond, C 1 -C 5 alkyl and C 2 -C 5 alkenyl, each of which may be optionally substituted;
L 2 is selected from the group consisting of C 1 -C 5 alkyl and C 2 -C 5 alkenyl, each of which may be optionally substituted;
k is 0, 1, 2, 3, 4 or 5;
W is selected from the group consisting of a bond, —O—, —S—, —S(O)—, —S(O) 2 —, —N(R 10 )—, —C(O)N(R 10 )—, —SO 2 N(R 10 )—, —N(R 10 )C(O)—, —N(R 10 )SO 2 —, —N(R 10 )C(O)N(R 11 )—, —C(O)N(R 10 )C(O)N(R 11 )— and —N(R 10 )C(O)N(R 11 )C(O)—;
W 1 is selected from the group consisting of a bond, —O—, —S—, —S(O)—, —S(O) 2 —, —N(R 10 )—, —C(O)N(R 10 )—, —SO 2 N(R 10 )—, —N(R 10 )C(O)—, —N(R 10 )SO 2 —, —N(R 10 )C(O)N(R 11 )—, —C(O)N(R 10 )C(O)N(R 11 )— and —N(R 10 )C(O)N(R 11 )C(O)—;
each R 10 and R 11 is independently selected from the group consisting of: H, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 10 heteroalkyl, C 4 -C 9 cycloalkyl, C 4 -C 9 heterocycloalkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl and acyl, each of which may be optionally substituted;
each R 20 , R 21 , R 22 , R 23 , R 24 and R 25 is independently selected from the group consisting of: H, halogen, —CN, —NO 2 , —CF 3 , —OCF 3 , alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, cycloalkylheteroalkyl, heterocycloalkylheteroalkyl, heteroarylheteroalkyl, arylheteroalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxyaryl, alkoxyheteroaryl, alkenyloxy, alkynyloxy, cycloalkylkoxy, heterocycloalkyloxy, aryloxy, arylalkyloxy, phenoxy, benzyloxy heteroaryloxy, amino, alkylamino, acylamino, aminoalkyl, arylamino, alkoxycarbonyl, alkylaminocarbonyl, sulfonyl, alkylsulfonyl, aminosulfonyl, arylsulfonyl, arylsulfinyl —COOH, —C(O)OR 5 , —COR 5 , —SH, —SR 6 , —OR 6 and acyl, each of which may be optionally substituted; or
R 20 and R 21 when taken together may form a group of formula ═O or ═S, and/or
R 22 and R 23 when taken together may form a group of formula ═O or ═S, and/or
R 24 and R 25 when taken together may form a group of formula ═O or ═S;
each R 26 and R 27 is independently selected from the group consisting of: H, halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, cycloalkylheteroalkyl, heterocycloalkylheteroalkyl, heteroarylheteroalkyl, arylheteroalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxyaryl, alkenyloxy, alkynyloxy, cycloalkylkoxy, heterocycloalkyloxy, aryloxy, arylalkyloxy, heteroaryloxy, amino, alkylamino, aminoalkyl, acylamino, arylamino, phenoxy, benzyloxy, COOH, alkoxycarbonyl, alkylaminocarbonyl, sulfonyl, alkylsulfonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, aminosulfonyl, SR 5 , acyl and G, each of which may be optionally substituted, or
R 26 and R 27 when taken together with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl group, each of which may be optionally substituted;
m, n and o are each integers that are independently selected from the group consisting of 0, 1, 2, 3 and 4; and
G is a group of formula: -L 3 W 3
wherein
L 3 is selected from the group consisting of C 1 -C 5 alkyl and C 2 -C 5 alkenyl, each of which may be optionally substituted;
W 3 is selected from the group consisting of —OR 12 , —SR 12 , —S(O)R 12 , —S(O) 2 R 12 , —N(R 12 ) 2 , —C(O)N(R 12 ) 2 , —SO 2 N(R 12 ) 2 , —NR 12 C(O)—, —NR 12 SO 2 R 12 , —NR 12 C(O)N(R 12 ) 2 , —C(O)NR 12 C(O)N(R 12 ) 2 and —N(R 12 )C(O)N(R 12 )C(O)R 12 ; and
each R 12 is independently selected from the group consisting H, halogen, —CN, —NO 2 , —CF 3 , —OCF 3 , alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, cycloalkylheteroalkyl, arylheteroalkyl, heterocycloalkylheteroalkyl, heteroarylheteroalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxyaryl, alkenyloxy, alkynyloxy, cycloalkylkoxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, arylalkyloxy, phenoxy, benzyloxy, amino, alkylamino, aminoalkyl, acylamino, arylamino, sulfonylamino, sulfinylamino, —COOH, —COR 5 , —COOR 5 , —CONHR 5 , —NHCOR 5 , —NHCOOR 5 , —NHCONHR 5 , C(═NOH)R 5 , -alkylNCOR 5 , alkoxycarbonyl, alkylaminocarbonyl, sulfonyl, alkylsulfonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, aminosulfonyl, SR 6 and acyl, each of which may optionally be substituted;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein
L is L 1 -W-L 2 -;
L 1 and L 2 are the same or different and are indep

Assignees

• Mei Pharma Inc

Inventors

• Lee Ken Chi Lik
• Sun Eric T
• Wang Haishan

Classifications

• A61P37/00

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• A61P35/00

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• A61P9/00

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• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title