IP Library › Granted Patent US 7,652,020

Granted Patent B2

US 7,652,020 · App. 11/142,601 · Granted Jan 26, 2010

Compounds for the treatment of inflammatory disorders

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Patent No.: US 7,652,020
App. No.: 11/142,601
Granted: Jan 26, 2010
Kind: B2

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Abstract

This invention relates to compounds of the Formula (I): or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, ADAMs, TACE, TNF-α or combinations thereof.

Claims (263)

1. A compound of formula (I):

or a pharmaceutically acceptable salt or solution-phase solvate thereof, wherein:

A is:

J is O;

E is O;

T is O;

R 1 and R 2 , taken together with the N to which R 1 and R 2 are shown attached, represent a 4-8 membered heterocyclic ring having 1-3 heteroatoms including said N, said heterocyclic ring being optionally fused with aryl, heteroaryl, cycloalkyl, or heterocyclyl, wherein said 4-8 membered heterocyclic ring optionally with said fused aryl, heteroaryl, cycloalkyl or heterocyclyl is substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —SR 15 , —S(O) q N(R 15 )(R 16 ) wherein q is 1 it 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and —S(O) q R 15 wherein q is 1 to 2; and wherein each of the cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16 ;

R 10 is H;

R 20 is H;

R 30 is H;

R 40 is H;

R 50 is H;

W is —(CR 13 2 ) n —, wherein n is 1;

X is absent or present, and if present X is aryl, wherein said aryl is phenyl, which can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group of R 70 moieties below;

Y is absent;

Z is selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, said cycloalkyl, heterocyclyl, aryl, and heteroaryl being optionally fused with aryl, heterocyclyl, heteroaryl or cycloalkyl; wherein each of said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, optionally with said fused aryl, heterocyclyl, heteroaryl or cycloalkyl, can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group of R 70 moieties below;

R 13 is selected from the group consisting of hydrogen and alkyl;

each R 70 is a substituent for H where indicated and is the same or different and is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —SR 15 , —S(O) q N(R 15 )(R 16 ) wherein q is 1 to 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 —N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and —S(O) q R 15 wherein q is 1 to 2; and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16 ;

each R 15 , R 16 and R 17 are independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, or alternatively R 15 and R 16 taken together with the N to which they are shown attached, are joined to form a 4-8 membered heterocylic ring, wherein said 4-8 membered cycloalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group of R 75 moieties below;

each R 75 is independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl, and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 19 , —N(R 19 ) 2 , —C(O)OR 19 , —C(O)N(R 19 ) 2 , and —N(R 19 )S(O)R 19 ; and

each R 19 is independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

2. The compound of claim 1 wherein A is

wherein

a is 0 to 4;

x is 1 to 4; and

R 70 is selected from the group consisting of alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —SR 15 , —S(O) q N(R 15 )(R 16 ) wherein q is 1 it 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and S(O) q R 15 wherein q is 1 it 2; and wherein each of the cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15 , —O(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16 .

3. A compound of formula (I):

or a pharmaceutically acceptable salt or solution-phase solvate thereof, wherein A is

wherein

each x independently is 0 to 4;

J is O;

E is O;

T is O;

R 10 is H;

R 20 is H;

R 30 is H;

R 40 is H;

R 50 is H;

W is —(CR 13 2 ) n —, wherein n is 1;

Y is absent;

R 13 is selected from the group consisting of hydrogen and alkyl;

each R 70 is a substituent for H where indicated and is the same or different and is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15 , C(O)N(R 15 )(R 16 ), —SR 15 , S(O) q N(R 15 )(R 16 ) wherein q is 1 to 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and S(O) q R 15 wherein q is 1 to 2; and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16 ; and

each R 19 is independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

4. A compound of formula (I):

or a pharmaceutically acceptable salt or solution-phase solvate thereof, wherein:

A is:

wherein said —NR 1 R 2 is

wherein

each R 9 is a substituent for H where indicated and can be the same or different, each being independently selected from the group consisting of —OH, —OR 14 , —CO(O)OR 15 , —CO(O)N(R 15 )(R 16 ), alkyl, aryl, heteroaryl, alkenyl, alkynyl, cycloalkyl and heterocyclyl, wherein said alkyl, aryl, heteroaryl, alkenyl, alkynyl, cycloalkyl and heterocyclyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group of R 70 moieties;

R 11 and R 12 taken together with the carbon to which each R 11 and R 12 are shown attached are fused heteroaryl or fused cycloalkyl, wherein said fused heteroaryl and fused cycloalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group of R 70 moieties; and

x is 0 to 4, and when x is greater than 1, each R 9 moiety can be the same or different, each moiety being independently selected from the group of R 9 moieties;

J is O;

E is O;

T is O;

R 10 is H;

R 20 is H;

R 30 is H;

R 40 is H;

R 50 is H;

W is —(CR 13 2 ) 2 —, wherein n is 1;

Y is absent;

R 13 is selected from the group consisting of hydrogen and alkyl;

each R 70 is a substituent for H where indicated and is the same or different and is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —SR 15 , —S(O) q N(R 15 )(R 16 ) wherein q is 1 to 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and —S(O) q R 15 wherein q is 1 to 2; and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16 ; and

each R 19 is independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

5. A compound of formula (I):

or a pharmaceutically acceptable salt or solution-phase solvate thereof, wherein:

A is:

wherein said —NR 1 R 2 is

wherein

each R 9 is a substituent for H where indicated and can be the same or different, each being independently selected from the group consisting of —OH, —OR 14 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), alkyl, aryl, heteroaryl, alkenyl, alkynyl, cycloalkyl and heterocyclyl, wherein said alkyl, aryl, heteroaryl, alkenyl, alkynyl, cycloalkyl and heterocyclyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group of R 70 moieties;

x is 0 to 4, and when x is greater than 1, each R 9 moiety can be the same or different, each moiety being independently selected from the group of R 9 moieties;

G is selected from the group consisting of CH 2 , NR 7 , O, S, or SO 2 ;

R 7 is selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl, heteroaryl, heterocyclyl, alkenyl, alkynyl, arylalkyl, alkylcarbonyl, and alkoxycarbonyl, wherein each of the aryl, heteroaryl and heterocyclyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group of R 70 moieties;

J is O;

E is O;

T is O;

R 10 is H;

R 20 is H;

R 30 is H;

R 40 is H;

R 50 is H;

W is —(CR 13 2 ) n —, wherein n is 1;

Y is absent;

R 13 is selected from the group consisting of hydrogen and alkyl;

each R 70 is a substituent for H where indicated and is the same or different and is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —SR 15 , —S(O) q N(R 15 )(R 16 ) wherein q is 1 to 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and —S(O) q R 15 wherein q is 1 to 2; and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16 ; and

each R 19 is independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

6. A compound of formula (I):

or a pharmaceutically acceptable salt or solution-phase solvate thereof, wherein:

A is:

J is O;

E is O;

T is O;

—NR 1 R 2 is selected from the group consisting of

wherein

x is 0 to 4, and when xis greater than 1, each R 70 moiety can be the same or different, each moiety being independently selected from the group of R 70 moieties;

R 14 is alkyl;

each R 18 is the same or different and is independently H or alkyl;

each R 70 is a substituent for H where indicated and is the same or different and is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15, —C(O)N(R 15 )(R 16 ), —SR 15 , —S(O) q N(R 15 )(R 16 ) wherein q is 1 to 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 13 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R ‥)C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and —S(O) q R 15 wherein q is 1 to 2; and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16;

each R 75 is independently selected from the group consisting of alkyl, cycloalkyt, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl, and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 19 , —N(R 19 ) 2 , —C(O)OR 19 , —C(O)N(R 19 ) 2 , and —N(R 19 )S(O)R 19 ;

each R 19 is independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

R 10 is H;

R 20 is H;

R 30 is H;

R 40 is H;

R 50 is H;

W is —(CR 13 2 ) n —, wherein n is 1;

Y is absent;

R 13 is selected from the group consisting of hydrogen and alkyl.

7. The compound of claim 5 wherein said —NR 1 R 2 is selected from the group consisting of:

wherein

x is 0 to 4, and when x is greater than 1, each R 70 moiety can be the same or different, each moiety being independently selected from the group of R 70 moieties.

8. A compound of formula (I):

or a pharmaceutically acceptable salt or solution-phase solvate thereof, wherein:

A is:

wherein said —NR 1 R 2 is

wherein

x is 0 to 4, and when x is greater than 1, each R 70 moiety can be the same or different, each moiety being independently selected from the group of R 70 moieties;

J is O;

E is O;

T is O;

R 10 is H;

R 20 is H;

R 30 is H;

R 40 is H;

R 50 is H;

W is —(CR 13 2 ) n —, wherein n is 1;

Y is absent;

R 13 is selected from the group consisting of hydrogen and alkyl;

each R 70 is a substituent for H where indicated and is the same or different and is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —SR 15 , —S(O) q N(R 15 )(R 16 ) wherein q is 1 to 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and —S(O) q R 15 wherein q is 1 to 2; and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16 ; and

each R 75 is independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl, and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 19 , —N(R ) 2 , —C(O)OR 19 , —C(O)N(R 19 ) 2 , and —N(R 19 )S(O)R 19 ; and

each R 19 is independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

9. The compound of claim 1 wherein R 1 and R 2 , taken together with the N to which R 1 and R 2 are shown attached, represent a 4-6 membered heterocyclic ring having 1-3 heteroatoms including said N, said heterocyclic ring being substituted with at least one aryl.

10. The compound of claim 1 wherein Z is selected from the group consisting of H, aryl and heteroaryl.

11. The compound of claim 10 wherein Z is selected from the group consisting of H, phenyl, indolyl, benzimidazolyl, pyrazolyl, thienyl, pyridi nyl, thiazolyl, thiadiazolyl, imidazolyl, pyrrolidinyl, pyrazinyl, triazolyl, tetrazolyl and tetrazinyl, wherein said phenyl, indolyl, benzimidazolyl, pyrazolyl, thienyl, pyridinyl, thiazolyl, thiadiazolyl, imidazolyl, pyrrolidinyl, pyrazinyl, triazolyl, tetrazolyl and tetrazinyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of R 70 moieties.

12. The compound of claim 11 wherein Z is selected from the group consisting of

wherein

x is 0 to 4, and when xis greater than 1, each R 70 moiety can be the same or different, each moiety being independently selected from the group of R 70 moieties.

13. The compound of claim 11 wherein Z is phenyl.

14. The compound of claim 13 wherein said phenyl is substituted with at least one substituent selected from the group consisting of cyano, alkoxy, halogen, alkyl, haloalkyl, hydroxy, aryl, heteroaryl, aryloxy, amino and tetrazole.

15. The compound of claim 11 wherein Z is thienyl.

16. The compound of claim 15 wherein said thienyl is substituted with at least one substituent selected from the group consisting of cyano, alkoxy, halogen, alkyl, haloalkyl, hydroxy, aryl, heteroaryl, aryloxy, amino and tetrazole.

17. The compound of claim 11 wherein Z is pyrazolyl.

18. The compound of claim 17 wherein said pyrazolyl is substituted with at least one substituent selected from the group consisting of cyano, alkoxy, halogen, alkyl, haloalkyl, hydroxy, aryl, heteroaryl, aryloxy, amino and tetrazole.

19. The compound of claim 11 wherein Z is pyridinyl.

20. The compound of claim 19 wherein said pyridinyl is substituted with at least one substituent selected from the group consisting of cyano, alkoxy, halogen, alkyl, haloalkyl, hydroxy, aryl, heteroaryl, aryloxy, amino and tetrazole.

21. The compound of claim 11 wherein Z is imidazolyl.

22. The compound of claim 21 wherein said imidazolyl is substituted with at least one substituent selected from the group consisting of cyano, alkoxy, halogen, alkyl, haloalkyl, hydroxy, aryl, heteroaryl, aryloxy, amino and tetrazole.

23. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt or solution-phase solvate thereof.

24. The compound of claim 23 selected from the group consisting of:

or a pharmaceutically acceptable salt, or solution-phase solvate thereof.

25. A compound selected from the group consisting of:

or a pharmaceutically acceptabie salt or solution-phase solvate thereof.

26. A pharmaceutical composition comprising at least one compound of claim 1 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

27. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt or solution-phase solvate thereof.

28. A pharmaceutical composition comprising at least one compound of claim 27 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

29. A compound of formula (I):

or a pharmaceutically acceptable salt or solution-phase solvate thereof, wherein:

A is:

J is O;

E is O;

T is O;

—NR 1 R 2 is selected from the group consisting of

wherein x is 1 to 4;

R 10 is H;

R 20 is H;

R 30 is H;

R 40 is H;

R 50 is H;

W is —(CR 13 2 ) n —, wherein n is 1;

Y is absent;

R 13 is selected from the group consisting of hydrogen and alkyl;

each R 70 is a substituent for H where indicated and is the same or different and is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —SR 15 , —S(O) q N(R 15 )(R 16 ) wherein q is 1 to 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and —S(O) q R 15 wherein q is 1 to 2; and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16;

each R 19 is independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

30. A compound of formula (I):

or a pharmaceutically acceptable salt or solution-phase solvate thereof, wherein:

A is:

J is O;

E is O;

T is O;

R 10 is H;

R 20 is H;

R 30 is H;

R 40 is H;

R 50 is H;

W is —(CR 13 2 ) n —, wherein n is 1;

Y is absent;

R 13 is selected from the group consisting of hydrogen and alkyl;

each R 70 is a substituent for H where indicated and is the same or different and is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —SR 15 , —S(O) q N(R 15 )(R 16 ) wherein q is 1 to 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16, —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and —S(O) q R 15 wherein q is 1 to 2; and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15, —C(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16 ; and

each R 19 is independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

31. The compound of claim 30 , wherein A is

32. The compound of claim 30 , wherein said —NR 1 R 2 is

wherein

33. The compound of claim 30 , wherein said —NR 1 R 2 is selected from the group consisting of

34. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt or solution-phase solvate thereof.

35. A pharmaceutical composition comprising at least one compound of claim 30 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

36. A compound of formula (I):

or a pharmaceutically acceptable salt or solution-phase solvate thereof, wherein:

A is selected from the group consisting of:

a is 1;

J is O;

E is O;

G is selected from the group consisting of CH 2 , NH, O, S, or SO 2

T is O;

R 10 is H;

R 20 is H;

R 30 is H;

R 40 is H;

R 50 is H;

W is —(CR 13 2 ) n —, wherein n is 1;

X is absent or present, and if present X is aryl, wherein said aryl is phenyl, which is substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group of R 70 moieties below;

Y is absent;

Z is selected from the group consisting of heteroaryl and heterocyclyl, each of said heteroaryl and heterocyclyl being optionally fused with aryl, heterocyclyl, heteroaryl or cycloalkyl; wherein each of said Z heteroaryl, and heterocyclyl optionally with said fused aryl, heterocyclyl, heteroaryl or cycloalkyl, can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group of R 70 moieties below;

R 13 is selected from the group consisting of hydrogen and alkyl;

each R 70 is a substituent for H where indicated and is the same or different and is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —CF 3 , —OCF 3 , —OR 15 , —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —SR 15 , —S(O) q N(R 15 )(R 16 ) wherein q is 1 to 2, —C(═NOR 15 )R 16 , —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 17 )S(O) 2 N(R 16 )(R 15 ), —N(R 17 )S(O)N(R 16 )(R 15 ), —N(R 17 )C(O)N(R 16 )(R 15 ), —CH 2 —N(R 17 )C(O)N(R 16 )(R 15 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , and —S(O) q R 15 wherein q is 1 to 2; and wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl are independently unsubstituted or substituted by 1 to 5 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —N(R 15 )(R 16 ), —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), and —N(R 15 )S(O)R 16 ; and

each R 15 , R 16 and R ∫ are independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, or alternatively R 15 and R 16 taken together with the N to which they are shown attached, are joined to form a 4-8 membered heterocylic ring, wherein said 4-8 membered cycloalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group of R 75 moieties below;

each R 19 is independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

37. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt or solution-phase solvate thereof.

38. A pharmaceutical composition comprising at least one compound of claim 36 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

39. A pharmaceutical composition comprising at least one compound of claim 3 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

40. A pharmaceutical composition comprising at least one compound of claim 4 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

41. A pharmaceutical composition comprising at least one compound of claim 5 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

42. A pharmaceutical composition comprising at least one compound of claim 8 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

43. A pharmaceutical composition comprising at least one compound of claim 23 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

44. A pharmaceutical composition comprising at least one compound of claim 25 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

45. A pharmaceutical composition comprising at least one compound of claim 6 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

46. A pharmaceutical composition comprising at least one compound of claim 29 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

47. A pharmaceutical composition comprising at least one compound of claim 34 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

48. A pharmaceutical composition comprising at least one compound of claim 37 or a pharmaceutically acceptable salt or solution-phase solvate thereof, and at least one pharmaceutically acceptable carrier.

Assignments (1)

CHANGE OF NAME Recorded Aug 30, 2012

From: SCHERING CORPORATION

To: MERCK SHARP & DOHME CORP.

Reel/Frame 028884/0151 →