Claims
- 1. A compound of formula I: or a pharmaceutically acceptable salt thereof wherein:X is 1) —S—, 2) —S(O)m—, Y is 1) a bond, or 2) —C(R7)(R8)—m is an integer from 1 to 2; n is an integer from 1 to 10; p is a number chosen from 0, 1, 2, or 3; R1 is 1) hydrogen, provided X is S, 2) C1-10alkyl, 3) C2-10alkenyl, 4) C2-10alkynyl, 5) Cy, or 9) —NRdRe, wherein alkyl, alkenyl and alkynyl are optionally substituted with one to four substituents selected from Ra, and Cy is optionally substituted with one to four substituents independently selected from Rb; R2 is 1) hydrogen, 2) C1-10alkyl, 3) C2-10alkenyl, and 4) C2-10alkynyl, wherein alkyl, alkenyl and alkynyl are optionally substituted with one to four substituents independently selected from Ra; R3 is 1) C1-10alkyl, 2) Ar1, 3) Ar1-C1-10alkyl, 4) Ar1—Ar2, 5) Ar1—Ar2-C1-10alkyl, wherein the alkyl group is optionally substituted with one to four substituents selected from Ra, and Ar1 and Ar2 are optionally substituted with one to four substituents independently selected from Rb, R4 is 1) hydrogen, 2) C1-10alkyl, 3) C2-10alkenyl, 4) C2-10alkynyl, wherein alkyl, alkenyl and alkynyl are optionally substituted with one to four substituents independently selected from Ra; R5 is 1) hydroxy, 2) C1-10alkoxy, 3) C2-10alkenyloxy, 4) C2-10alkynyloxy, 5) Cy—O—, 6) Cy-C1-10alkoxy, 7) amino, 8) C1-10alkylamino, 9) di(C1-10alkyl)amino, 10) Cy-C1-10alkylamino, wherein alkyl, alkenyl and alkynyl are optionally substituted with one to four substituents selected from Ra, and Cy is optionally substituted with one to four substituents independently selected from Rb; R6 is 1) hydrogen, 2) C1-10alkyl, 3) C2-10alkenyl, 4) C2-10alkynyl, 5) Cy 6) —S(O)mRd, 7) —S(O)mNRdRe, 8) —C(O)Rd, 9) —CO2Rd, 10) —CO2(CRfRg)nCONRdRe, or 11) —C(O)NRdRe, wherein alkyl, alkenyl and alkynyl are optionally substituted with one to four substituents independently selected from Ra, and Cy is optionally substituted with one to four substituents indepdently selected from Rb; or R6 and an Rh attached to the carbon atom adjacent to the ring nitrogen together complete a 4-8 membered ring optionally containing one other heteroatom chosen from nitrogen, oxygen and sulfur; R7 is 1) hydrogen, 2) C1-10 alkyl, 3) C2-10 alkenyl, 4) C2-10 alkynyl, 5) Ar1, 6) Ar1-C1-10alkyl, 7) —ORd, 8) —O(CRfRg)nNRdRe, 9) —OC(O)Rd, 10) —OC(O)NRdRe, 11) halogen, 12) —SRd, 13) —S(O)mRd, 14) —S(O)2ORd, 15) —S(O)mNRdRe, 16) —NO2, 17) —NRdRe, 18) —NRdC(O)Re, 19) —NRdS(O)mRe, 20) —NRdC(O)ORe, or 21) —NRdC(O)NRdRe, wherein alkyl, alkenyl, alkynyl and Ar1 are optionally substituted with one to four substituents selected from a group independently selected from Rc; R8 is 1) hydrogen, 2) C1-10 alkyl, 3) C2-10 alkenyl, 4) C2-10 alkynyl, 5) Cy, or 6) Ar1-C1-10alkyl, wherein alkyl, alkenyl, alkynyl, Cy and Ar1 are optionally substituted with one to four substituents selected from a group independently selected from Rc; Ra is 1) halogen, 2) —ORd, 3) —OC(O)Rd, 4) —OC(O)NRdRe, 5) —O(CRfRg)nNRdRe, 6) —SRd, 7) —S(O)mRd, 8) —S(O)2ORd, 9) —S(O)mNRdRe, 10) —NRdRe, 11) —NRdC(O)Re, 12) —NRdC(O)ORe, 13) —NRdC(O)NRdRe, 14) —C(O)Rd, 15) —CO2Rd, 16) —C(O)NRdRe, 17) —CO2(CRfRg)nCONRdRe, 18) —CN, 19) —CRd(N—ORe), 20) —NO2, 21) CF3, 22) —OCF3, or 23) Cy optionally substituted with one to four substituents independently selected from Rc; Rb is 1) a group selected from Ra, 2) C1-10 alkyl, 3) C2-10 alkenyl, 4) C2-10 alkynyl, or 8) Ar1-C1-10alkyl, wherein alkyl, alkenyl, alkynyl and Ar1 are optionally substituted with one to four substituents selected from a group independently selected from Rc; Rc is 1) halogen, 2) amino, 3) C1-4alkylamino, 4) di(C1-4alkyl)amino 5) carboxy, 6) cyano, 7) C1-4alkyl, 8) arylC1-4alkyl, 9) Ar1, 10) hydroxy, 11) C1-4alkoxy, 12) aryloxy, or 13) CF3; Rd and Re are independently selected from hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, Cy and Cy C1-10alkyl, wherein alkyl, alkenyl, alkynyl and Cy are optionally substituted with one to four substituents independently selected from Rc; or Rdand Re together with the atoms to which they are attached form a heterocyclic ring of 4 to 7 members containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and nitrogen; Rf and Rg are independently selected from hydrogen, C1-10alkyl, Cy and Cy-C1-10alkyl; or Rf and Rg together with the carbon to which they are attached form a ring of 4 to 7 members containing 0-2 heteroatoms independently selected from oxygen, sulfur and nitrogen; Rh is 1) a group selected from Ra, 2) C1-10 alkyl, 3) C2-10 alkenyl, 4) C2-10 alkynyl, 5) Cy, 6) oxo, wherein alkyl alkenyl, alkynyl, and Cy are optionally substituted with one to four substituents selected from a group independently selected from Rc; or two Rh groups attached to adjacent ring atoms together complete 4-8 membered aromatic or non-aromatic ring containing 0-2 heteroatom selected from oxygen, sulfur and nitrogen; or two Rh groups attached to the same ring atom together complete a 4-8 membered ring containing 0-2 heteroatom selected from oxygen, sulfur and nitrogen; with the proviso that when Rh is chosen from 1) —ORd, 2) —OC(O)Rd, 3) —OC(O)NRdRe, 4) —O(CRfRg)nNRdRe, 5) —SRd, 6) —S(O)mRd, 7) —S(O)2ORd, 8) —S(O)mNRdRe, 9) —NRdRe, 10) —NRdC(O)Re, 11) —NRdC(O)ORe, 12) —NRdC(O)NRdRe, or 13) —NO2, 14) halogen, 15) —CN, and 16) —CRd(N—ORe), it is not attached to an atom adjacent to the ring nitrogen; Cy is cycloalkyl, heterocyclyl, aryl or heteroaryl; Ar1 and Ar2 are independently selected from aryl and heteroaryl.
- 2. A compound of claim 1 wherein X is S or SO2.
- 3. A compound of claim 1 wherein Y is a bond.
- 4. A compound of claim 1 wherein R1 is C1-10 alkyl optionally substituted with one to four substituents selected from Ra, or Cy optionally substituted with one to four substituents selected from Rb.
- 5. A compound of claim 1 whrein R1 is C1-5alkyl optionally substituted with a group selected from NRdRe, NO2, phenyl, hydroxy and 1-imidazolyl.
- 6. A compound of claim 1 wherein R1 is aryl or heteroaryl each optionally substituted with one to two substituents selected from Rb.
- 7. A compound of claim 1 wherein R1 is phenyl optionally substituted with one or two substituents selected from halogen and NRdRe.
- 8. A compound of claim 1 wherein R2 and R4 are each hydrogen, R5 is OH, and R3 is Ar1-C1-3alkyl or Ar1-Ar2-C1-3alkyl wherein Ar1 and Ar2 are each optionally substituted with one to four groups independently selected from Rb.
- 9. A compound of claim 8 wherein R3 is optionally substituted benzyl or optionally substituted Ar2-benzyl, where Ar2 is optionally substituted phenyl, or optionally substituted 5- or 6-membered heteroaryl.
- 10. A compound of claim 8 wherein R3 is benzyl, benzyl substituted with a group selected from hydroxy, C1-5alkoxy, NHC(O)Re, OC(O)NRdRe, and C(O)NRdRe, or 4-(Ar2)-benzyl wherein Ar2 is phenyl substituted with one to two groups selected from C1-5alkyl, hydroxy, C1-5alkoxy and NRdRe, or Ar2 is 2-ethyl-4-thiazolyl.
- 11. A compound of claim 1 having the formula Ia: whereinX is 1) S or 2) SO2; R1 is 1) C11-5alkyl optionally substituted with one to two substituents selected from Ra; 2) aryl or heteroaryl each optionally substituted with one to two substituents selected from Rb; R3 is 1) Ar1-C1-3alkyl, or 2) Ar1-Ar2-C1-3alkyl; R6 is 1) hydrogen or 2) C1-5alkyl; Ra, Rb, Ar1 and Ar2 are as defined in claim 1.
- 12. A compound of claim 11 wherein R1 is C1-15alkyl optionally substituted with a group selected from NRdRe, NO2, phenyl, hydroxy and 1-imidazolyl.
- 13. A compound of claim 11 wherein R1 is phenyl optionally substituted with one or two substituents selected from halogen and NRdRe.
- 14. A compound of claim 11 wherein R3 is benzyl, benzyl substituted with a group selected from hydroxy, C1-5alkoxy, NHC(O)Re, OC(O)NRdRe, and C(O)NRdRe, or 4-(Ar2)-benzyl wherein Ar2 is phenyl substituted with one to two groups selected from C1-5alkyl, hydroxy, C1-5alkoxy and NRdRe, or Ar2 is 2-ethyl-4-thiazolyl.
- 15. A compound of claim 1 having the formula Ib: whereinX is 1) S or 2) SO2; R1 is 1) C1-5alkyl optionally substituted with a group selected from NRdRe, NO2, phenyl, hydroxy and 1-imidazolyl; 2) phenyl optionally substituted with one or two substituents selected from halogen and NRdRe; R6 is 1) hydrogen or 2) C1-5alkyl; Rb1 and Rb2 are independently selected from 1) hydrogen, 2) C1-5alkyl, 3) hydroxy, 4) C1-5alkoxy and 5) NRdRe; Rdand Re are as defined in claim 1.
- 16. A compound of claim 1 having formula Ic: whereinX is 1) S or 2) SO2; R1 is 1) C1-5alkyl optionally substituted with a group selected from NRdRe, NO2, phenyl, hydroxy and 1-imidazolyl; 2) phenyl optionally substituted with one or two substituents selected from halogen and NRdRe; R6 is 1) hydrogen or 2) C1-5alkyl; Rb3 is 1) hydrogen, 2) hydroxy, 3) C1-5alkoxy, 4) NHC(O)Re, 5) OC(O)NRdRe, or 6) C(O)NRdRe, Rd and Re are as defined above for formula I.
- 17. A compound of claim 1 selected from the group consisting of:qR1R6Rb1/Rb20PhHH/OCH30PhHOCH3/OCH32PhHH/OCH32PhCH3H/OCH32PhHOCH3/OCH324-Br-PhHOCH3/OCH323-Br-PhHOCH3/OCH322-Br-PhHOCH3/OCH32HOCH3/OCH32HOCH3/OCH32CH3HOCH3/OCH324-(PhCH2NH)PhHOCH3/OCH323- (PhCH2NH)PhHOCH3/OCH32HOCH3/OCH32HOCH3/OCH32HOCH3/OCH32HOCH3/OCH32(CH3)2N(CH2)3NH(CH2)2HOCH3/OCH32NO2(CH2)3HOCH3/OCH32HOCH3/OCH32HOCH2CH2HOCH3/OCH32PhHH/CN2PhHOCH3/CN1PhHOCH3/OCH32PhHOCH3/N(CH3)22PhHOCH3/OH2PhHOCH3/CH2CH32PhCH2HOCH3/OCH3qR1R6Rb30PhHH0PhHOH2PhHOH2PhH2PhH2PhH2PhH
- 18. A method for inhibiting cell adhesion in a mammal which comprises administering to said mammal an effective amount of a compound of claim 1.
- 19. A method for the treatment of diseases, disorders, conditions or symptoms mediated by cell adhesion in a mammal which comprises administering to said mammal an effective amount of a compound of claim 1.
- 20. A method for the treatment of asthma in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of claim 1.
- 21. A method for the treatment of allergic rhinitis in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of claim 1.
- 22. A method for the treatment of multiple sclerosis in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of claim 1.
- 23. A method for the treatment of atherosclerosis in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of claim 1.
- 24. A method for the treatment of inflammation in a mammal which comprises administering to said mammal an effective amount of a compound of claim 1.
- 25. A method for the treatment of inflammatory bowel disease in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of claim 1.
- 26. A pharmaceutical composition which comprises a compound of claim 1 and a pharmaceutically acceptable carrier thereof.
Parent Case Info
This application claims priority under U.S. provisional application 60/213,155 filed on Jun. 22, 2000, which is hereby incorporated by reference in its entirety.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
5721250 |
Morriello et al. |
Feb 1998 |
A |
5948792 |
Tsuchiya et al. |
Sep 1999 |
A |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/213155 |
Jun 2000 |
US |