Diphenyl substituted cycloalkanes, compositions containing such compounds and methods of use

1. A compound represented by formula I-1:

and the pharmaceutically acceptable salts and esters thereof wherein:

“a” is an integer selected from 1, 2 and 3; and b and c are each integers independently selected from 0, 1 and 2;

“A” represents a methylene or ethylene group;

each R 1a is independently selected from the group consisting of: —H, —F, —Cl, —Br, —C 1-6 alkyl, —CN, —OH, —OC 1-6 alkyl, -fluoroC 1-6 alkyl, -fluoroC 1-6 alkoxy, —N(R a ) 2 , C 1-6 alkylN(R a ) 2 , —NHC(O)C 1-4 alkyl, —C(O)NHC 1-4 alkyl and —C(O)N(C 1-4 alkyl) 2 ;

each R 1b is independently selected from the group consisting of: —H, —F, —C 1-6 alkyl, —OH, —OC 1-6 alkyl, -fluoroCl 1-6 alkyl, -fluoroCl 1-6 alkoxy, —N(R a ) 2 and —C 1-6 alkylN(R a ),

or one R 1b group can represent oxo and the other is as previously defined;

R 1 represents —H or is selected from the group consisting of:

a) halo, —OH, —CO 2 R a , —C(O)NR a R b , —N(R a ) 2 S(O) 2 NR a R b , —NO 2 , —SO 2 NR b C(O)R a , —NR b SO 2 R a , —NR b C(O)R a , —C(O)SO 2 NR a R b , —NR b C(O)NR a R b , —NR b CO 2 R a , —OC(O)NR a R b —C(O)NR b NR a R b , —CN, —S(O) p R a and —OSO 2 R a ,

b) —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, —OC 1-10 alkyl, —OC 3-10 alkenyl and —OC 3-10 alkynyl, said groups being optionally substituted with: —OH, —CO 2 R a , —C(O)NR a R b , —C(O)N(R a )C 1-6 alkenyl, —C(O)N(R a )C 1-6 alkynyl, —N(R a ) 2 , —S(O) 2 NR a R b , —SO 2 NR b C(O)R a , —NR b SO 2 R a , —NR b C(O)R a , —C(O)SO 2 NR a R b , —NR b C(O)NR a R b , —NR b CO 2 R a , —OC(O)NR a R b , —C(O)NR b NR a R b , —S(O) p R a , Aryl, and up to 5 fluoro groups;

c) Aryl optionally substituted with 1-2 members selected from the group consisting of: —F, —Cl, —Br, —C 1-6 alkyl, —C 3-6 cycloalkyl, —CN, —OH, —OC 1-6 alkyl, -fluoroC 1-6 alkyl, -fluoroC 1-6 alkoxy, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl) 2 , —C 1-6 alkylNH 2 , —C 1-6 alkyl-NHC 1-4 alkyl, —C 1-6 alkylN(C 1-4 alkyl) 2 , —C 1-6 alkyl-CN, —NHC(O)C 1-4 alkyl, —C(O)NHC 1-4 alkyl and —C(O)N(C 1-4 alkyl) 2 ;

each p independently represents an integer selected from 0, 1 and 2;

R 4 and R 5 are each independently selected from the group consisting of —H, —C 1-6 alkyl, —OC 1-6 alkyl, —OH, -fluoro, -fluoroC 1-6 alkyl, -fluoroC 1-6 alkoxy, —N(R a ) 2 , and

CR 4 R 5 can represent a group selected from carbonyl, thiocarbonyl, C═NR a and a 3-7 membered cycloalkyl ring,

Y is quinolinyl;

each R a is independently selected from the group consisting of —H and:

(a) —C 1-10 alkyl, —C 3-6 cycloalkyl, —C 3-10 alkenyl, or —C 3-10 alkynyl, optionally substituted with 1-3 fluoro groups or 1-2 members selected from the group consisting of: —OH, —OC 1-6 alkyl, —CN, —NH 2 , —NHC 1-4 alkyl, and —N(C 1-4 alkyl) 2 ;

(b) Aryl or Ar—C 16 alkyl—, the aryl portions being optionally substituted with 1-2 of —C 1-6 alkyl, —CN, —OH, —OC 1-6 alkyl, -fluoroC 1-6 alkyl, -fluoroC 1-6 alkoxy, —C 1-6 alkylNH 2 , —C 1-6 alkylNHC 1-4 alkyl, —C 1-6 alkylN(C 1-4 alkyl) 2 , —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl) 2 , —NHC(O)C 1-4 alkyl, —C(O)NHC 1-4 alkyl, —C(O)N(C 1-4 alkyl) 2 , —CO 2 H and —CO 2 C 1-6 alkyl groups, and 1-3 —F, —Cl or —Br groups; and the alkyl portion of Ar—C 1-6 alkyl—being optionally substituted with —OH, —OC 1-6 alkyl, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl) 2 , and 1-3 fluoro groups;

each R b is independently selected from the group consisting of: —H, —NH 2 , and —C 1-10 alkyl optionally substituted with members selected from the group consisting of 1-3 fluoro groups and 1-2 of —OH, —OC 1-6 alkyl, —NH 2 , —NHC 1-4 alkyl and —N(C 1-4 alkyl) 2 ;

and when present in the same moiety, (a) R a and R b , (b) two R a groups or (c) two R b groups can be taken in combination with the atom or atoms to which they are attached and any intervening atoms and represent a 4-7 membered ring containing 0-3 heteroatoms selected from O, S(O) p and N, and the 4-7 membered ring may be optionally substituted with a member selected from the group consisting of —C 1-6 alkyl, —C 2-6 acyl and oxo.

2. The compound of claim 1 of structural formula Ia-1:

and the pharmaceutically acceptable salts and esters thereof, wherein “a” is an integer selected from 1, 2 and 3; and b and c are each integers independently selected from 0, 1 and 2; provided that the sum of “a”+b+c is from 1 to 5.

3. The compound of claim 1 of structural formula Ib-1:

and the pharmaceutically acceptable salts and esters thereof wherein: “a” is an integer selected from 2 and 3; and b and c are integers independently selected from 0 and 1; provided that the sum of “a”+b+c is from 2 to 4.

4. The compound of claim 3 wherein “a” is 2, and b and c are integers selected from 0 and 1.

5. The compound of claim 1 wherein of the three R 1a groups shown in the generic structural drawing of formula I-1, two R 1a groups represent —H and one R 1a group is selected from the group consisting of: —F, —Cl, —C 1-6 alkyl, —CN, —OC 1-6 alkyl, -fluoroC 1-6 alkyl, -fluoroC 1-6 alkoxy, —N(R a ) 2 , —C 1-6 alkylN(R a ) 2 , —NHC(O)C 1-4 alkyl, —C(O)NHC 1-4 alkyl and —C(O)N(C 1-4 alkyl) 2 .

6. The compound of claim 1 wherein both R 1b groups represent —H.

7. The compound of claim 1 wherein R 1b represents a member selected from the group consisting of:

a) —C(O)NR a R b , —N(R a ) 2 , —S(O) 2 NR a R b , —SO 2 NR b C(O)R a , —NR b SO 2 R a , —NR b C(O)R a , —CN, —S(O) p R a and —OSO 2 R a ; and

b) —C 1-10 alkyl, —C 3-6 alkenyl, —C 3-6 alkynyl, —OC 1-10 alkyl, —OC 3-6 alkenyl and —OC 3-6 alkynyl, said groups being optionally substituted with a member selected form the group consisting of: —CO 2 R a , —C(O)NR a R b , —C(O)N(R a )C 1-6 alkenyl, —C(O)N(R a )C 1-6 alkynyl, —N(R a ) 2 , —S(O) 2 NR a R b , —SO 2 NR b C(O)R a , —NR b SO 2 R a , NR b C(O)R a , —S(O) p R a , Aryl, and up to 5 fluoro groups.

8. The compound of claim 1 wherein —(CR 4 R 5 )—represents —CH 2 —.

9. The compound of claim 1 of structural formula Ic-1:

wherein R 4 and R 5 are both —H;

R 1 is selected from the group consisting of:

a) —OC(O)NR a R b , and —C(O)NR a R b ; and

b) C 1-3 alkyl substituted with a member selected from: —C(O)—NR a R b .

10. A pharmaceutical composition comprised of a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.