Tri-substituted 2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel, 3,6-disubstituted pyran derivatives
Novel 3,6-disubstituted pyrans, optionally with a further substituent at the 4-position, are monoamine reuptake inhibitors with activity profiles of anti-depressants.
1. A compound having formula X:
or a pharmaceutically acceptable salt thereof, wherein:
A and A′ are individually selected from the group of optionally substituted C 4 -C 14 aryl and heteroaryl wherein heteroatoms of heteroaryl A and/or A′ are selected from the group consisting of O, N, and S;
Z is a chemical bond or —Y—(CH 2 ) o ;
Y is NH or O;
o is 0, 1, 2, 3, or 4;
and
W 3 is an alkyl amine or an aryl amine.
2. The compound of claim 1 having formula:
or a pharmaceutically acceptable salt thereof, wherein:
m and n are 0-4;
Z is a chemical bond or —Y—(CH 2 ) o —;
Y is NH or O;
o is 0, 1, 2, 3, or 4;
at least one of A and A′ are selected from the group consisting of:
p is 0-6;
R 1 is C 1-4 alkyl, C 2-6 alkenyl, C 2-6 optionally halogenated alkynyl, C 2-6 hydroxyalkynyl, halo, —CN, —COOR 4 , —OH, —NO 2 , —NH 2 , —NHR 4 , —SO 2 NH 2 , —NHSO 2 R 8 , —OCF 3 , or —OR 8 ;
R 2 has the meaning of R 1 or a 5 or 6 membered heterocycle containing 1 or more heteroatoms selected from the group consisting of N, O, and S;
X 2 is N, O, or S;
R 4 is H, C 1-18 alkyl, C 5-10 cycloalkyl, or C 2-18 alkylene;
R 8 is C 1-8 alkyl, C 5-6 cycloalkyl, C 2-8 alkenyl, or a 5 or 6-member aromatic ring including heterocyclic rings;
B is selected from the group consisting of:
3. The compound of claim 1 having formula:
or a pharmaceutically acceptable salt thereof, wherein:
m and n are 0-4;
Z is selected from the group consisting of a chemical bond and —Y—(CH 2 ) o ;
Y is NH or O;
o is 0, 1, 2, 3, or 4;
at least one of A and A′ are selected from the group consisting of:
p is 0-6;
R 1 is C 1-4 alkyl, C 2-6 alkenyl, C 2-6 optionally halogenated alkynyl, C 2-6 hydroxyalkynyl, halo, —CN, —COOR 4 , —OH, —NO 2 , —NH 2 , —NHR 4 , —SO 2 NH 2 , —NHSO 2 R 8 , —OCF 3 , or -Ole;
R 2 has the meaning of R 1 or a 5 or 6 membered heterocycle containing 1 or more heteroatoms selected from the group consisting of N, O, and S;
X 2 is N, O, or S;
R 4 is H, C 1-18 alkyl, C 5-10 cycloalkyl, or C 2-18 alkylene; and
R 8 is C 1-8 alkyl, C 5-6 cycloalkyl, C 2-8 alkenyl, or a 5 or 6-member aromatic ring including heterocyclic rings; and
B is selected from the group consisting of: