Tri-substituted 2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel 3,6 disubstituted pyran derivatives

1. A 3,6-substituted pyran group-containing compound having the structural formula:

wherein

A, A′ are each phenyl;

B is optionally substituted C 4 -C 14 aryl;

Z is a chemical bond;

R is H or C 1-8 alkyl;

W is selected from the group consisting of hydrogen and —OH, wherein when W is hydrogen, B is described by the following formula:

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, —CN, —COOR 4 , —OH, —NO 2 , —NH 2 , —NHR 4 , —SO 2 NH 2 , —NHSO 2 R 8 , —OCF 3 or —OR 8 ;

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;

n is 0; and

m is 1

or a pharmaceutically acceptable derivative or salt thereof.

2. The compound of claim 1 , wherein at least one of A and A′ are:

where R 1 is selected from the group consisting of C 1-4 alkyl, C 2-6 alkenyl, C 2-6 optionally halogenated alkynyl, C 2-6 hydroxyalkynyl, halo, —CN, —COOR, where R is C 1-18 alkyl, C 5-10 cycloalkyl, C 2-18 alkenyl, —OH, —NO 2 , —NH 2 , —OR 2 where R 2 is C 1-8 alkyl, C 5-6 cycloalkyl, or C 2-8 alkenyl.

3. The compound of claim 1 , wherein B is selected from the group

where R 1′ is selected from the group consisting of C 1-4 alkyl, C 2-6 alkenyl, C 2-6 optionally halogenated alkynyl, C 2-6 hydroxyalkynyl, halo, —CN, —COOR, where R is C 1-18 alkyl, C 5-10 cycloalkyl, C 2-18 alkenyl, —OH, —NO 2 , —NH 2 , —OR 2 where R 2 is C 1-8 alkyl, C 5-6 cycloalkyl, or C 2-8 alkenyl; and

wherein R 2 have the meaning of R 1′ and also a 5 or 6 membered heterocycle containing 1 or more heteroatoms selected from the group consisting of N, O, and S, and wherein X is N, O, or S.

4. The compound of claim 2 , wherein B is selected from the group

where R 1′ is selected from the group consisting of C 1-4 alkyl, C 2-6 alkenyl, C 2-6 optionally halogenated alkynyl, C 2-6 hydroxyalkynyl, halo, —CN, —COOR, where R is C 1-18 alkyl, C 5-10 cycloalkyl, C 2-18 alkenyl, —OH, —NO 2 , —NH 2 , —OR 2 where R 2 is C 1-8 alkyl, C 5-6 cycloalkyl, or C 2-8 alkenyl; and

wherein R 2 have the meaning of R 1′ and also a 5 or 6 membered heterocycle containing 1 or more heteroatoms selected from the group consisting of N, O, and S, and wherein X is N, O, or S.

5. The compound of claim 3 , wherein A and A′ are both unsubstituted phenyl.

6. The compound of claim 1 , having the formula

7. The compound of claim 2 , having the formula

8. The compound of claim 3 , having the formula

9. The compound of claim 1 , having the formula

10. The compound of claim 2 , having the formula

11. The compound of claim 3 , having the formula

12. The compound of claim 1 , having a formula selected from the group consisting of:

13. The compound of claim 2 , having a formula selected from the group consisting of:

14. The compound of claim 3 , having a formula selected from the group consisting of:

15. The compound of claim 5 , having a formula selected from the group consisting of:

16. The compound of claim 1 , selected from the group consisting of:

Cis-(6-benzhydryl-tetrahydropyran-3-yl)-(4-hydroxy-benzyl)-amine (16h);

Cis-(6-benzhydryl-tetrahydropyran-3-yl)-(1H-iodo-5-ylmethyl)-amine (16n);

Cis-(6-benzhydryl-tetrahydropyran-3-yl)-(4-amino-benzyl)-amine (16o);

Cis-(6-benzhydryl-tetrahydropyran-3-yl)-(3,4-dichloro-benzyl)-amine (16i);

(2S, 4R, 5R)-2-benzhydryl-5-(4-methoxy-benzylamino)-tetrahydropyran-4-ol (−)29a;

(2S, 4R, 5R)-2-benzhydryl-5-(4-fluoro-benzylamino)-tetrahydro-pyran-4-ol (−)29b;

(2S, 4R, 5R)-2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol (−) 29d;

(2S, 4R, 5R)-2-benzhydry 1 -5-(2,4-dimethoxy-benzylamino)-tetrahydropyran-4-ol (−)-29e;

(2S, 4R, 5R)-2-benzhydry 1 -5-(3,5-dimethoxy-benzylamino)-tetrahydropyran-4-ol (−)-29f;

(2S, 4R, 5R)-2-benzhydryl-5-(4-hydroxy-benzylamino)-tetrahydropyran-4-ol (−)32a;

(2R, 4S, 5S)-2-benzhydryl-5-(4-hydroxy-benzylamino)-tetrahydro-pyran-4-ol (+)32a;

cis-(3S, 6S)-(6-benzhydryl-tetrahydropyran-3-yl)-(4-hydroxy-benzyl)-amine (−)37a; and

cis-(3R, 6R)-(6-benzhydryl-tetrahydropyran-3-yl)-(4-hydroxy-benzyl)-amine (+)37a.

17. The compound of claim 1 , selected from the group consisting of:

(2S, 4R, 5R)-2-benzhydryl-5-(4-methoxy-benzylamino)-tetrahydropyran-4-ol (−)29a;

(2S, 4R, 5R)-2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol (−) 29d;

(2S, 4R, 5R)-2-benzhydryl-5-(2,4-dimethoxy-benzylamino)-tetrahydropyran-4-ol (−)-29e;

(2S, 4R, 5R)-2-benzhydryl-5-(3,5-dimethoxy-benzylamino)-tetrahydropyran-4-ol (−)-29f;

(2S, 4R, 5R)-2-benzhydryl-5-4-hydroxy-benzylamino)-tetrahydropyran-4-ol (−)32a;

(2R, 4S, 5S)-2-benzhydryl-5-(4-hydroxy-benzylamino)-tetrahydro-pyran-4-ol (+)32a;

cis-(3S, 6S)-(6-benzhydryl-tetrahydropyran-3-yl)-(4-hydroxy-benzyl)-amine (−)37a; and

cis-(3R, 6R)-(6-benzhydryl-tetrahydropyran-3-yl)-(4-hydroxy-benzyl)-amine (+)37a.

18. A compound having the following formula:

or a pharmaceutically acceptable salt thereof.