Nova Patents
IL155202A

Biaryl compounds as serine protease inhibitors

Abstract

Compounds of formula (I) are useful as inhibitors of trypsin like serine protease enzymes such as thrombin, factor VIIa, factor Xa, TF/FVIIa, and trypsin. These compounds could be useful to treat and/or prevent clotting disorders, and as anticoagulating agents.

IL155202A, drawing sheet 1
Sheet 1 of 296

Term

No projected expiry on record.

  1. Priority
  2. Filed
  3. Published
  4. Today

34 claims: 24 independent, 10 dependent

  1. 1
    What is claimed is 1. The compound represented by the structure -OCH3;and R' is selected from the group consisting of -CHO, -CO2H, and -CO2MEM;and pharmaceutically acceptable salts thereof;wherein MEM designates a methoxyethoxymethyl group.
  2. 2
    The compound represented by the structure wherein R is selected from the group consisting of OH OH , and and R' is selected from the group consisting of-CHO, -CO2H, and -CO2MEM;and pharmaceutically acceptable salts thereof;wherein MEM designates a methoxyethoxymethyl group.
  3. 3
    The compound represented by the structure wherein R is selected from the group consisting of
  4. 4
    The compound represented by the structure wherein R is selected from the group consisting of and R' is selected from the group consisting of OH and pharmaceutically acceptable salts thereof.
  5. 5
    The compound represented by the structure wherein R is selected from the group consisting of 0 l 2 -OBn, -OCH3, and ch 2 nh 2 and pharmaceutically acceptable salts thereof.
  6. 6
    The compound represented by the structure NHR' Ν' H H .N. h 3 co 2 c ELCO״C O wherein R is selected from the group consisting of z TIPS -OSO2CF3, and R' is -H or and pharmaceutically acceptable salts thereof. Ί. The compound represented by the structure wherein R is selected from the group consisting of -OBn,-OH,-OSO2CF3, Π~\ , [j~\ ־ ־ CH=CH 2, and-H;c) S X R' is selected from the group consisting of -CHO, -CO2H, and -CO2MEM;and R is selected from the group consisting of and pharmaceutically acceptable salts thereof.
  7. 7
    8. The compound represented by the structure wherein R is selected from the group consisting of -OBn, -OH, -OSO2CF3, ,___. , -CH=CH 2;R' is -H or -Boc;and R is -CO 2 MEM or -CO 2 H;and pharmaceutically acceptable salts thereof;wherein MEM designates a methoxyethoxymethyl group.
  8. 8
    9. The compound represented by the structure NHR' RO,C wherein R is -CH3 and R’ is selected from the group consisting of CH 3 ch 3 ch 3 and pharmaceutically acceptable salts thereof.
  9. 9
    10. The compound represented by the structure wherein R is and R’ is selected from the group consisting of ;and pharmaceutically acceptable salts thereof.
  10. 11
    12. The compound represented by the structure wherein R is -CH3 and R’ is selected from the group consisting of and pharmaceutically acceptable salts thereof.
  11. 12
    13. The compound represented by the structure H .N. wherein at least one R is selected from the group consisting of -OCH 3 , -OH, -OSO2CF3, -CH=CH2-, -OCH2CO2C2H5, -OCH 2 CONH 2 , 0 CH, י /OAc , \ / \ , -OBn , -OH, -OSO2CF3, υ OAc Ί Λ , -OCH3, -OBn, -H, -OBn, and -CH=CH 2 ;x s' R' is selected from the group consisting of -CHO, -CO2H, -CO2MEM, NHBoc and R is selected from the group consisting of -H, -CH3 and -Bn;and pharmaceutically acceptable salts thereof;wherein MEM designates a methoxyethoxymethyl group.
  12. 13
    14. The compound represented by the structure wherein at least one R is selected from the group consisting of -CH=CH2, ־OSO2CF3, -OCH2CO2C2H5, -OCH2CONH2, -O-CH2-CH2-OAc, -OH, -OCH2CO2H, -O-CH2-CH2-OH, -CH(OH)CH 2 OH, -CH 2 OH, -CO 2 H, , -OBn, -OH, -OCH3, -OBn, -OH, -OC 2 H 5 , -OBn, -OCH3, and -CH(OH)CH3;and R' is selected from the group consisting of -CH3, -CH2C6H5, -Bn, -H;and pharmaceutically acceptable salts thereof.
  13. 14
    15. The compound represented by the structure wherein at least one R is selected from the group consisting of -CH=CH2, -CH(OH)CH 2 OH, -CH=O, -CH2OH, -CO 2 H, -OCH 3 , -CH=CH 2 ;and pharmaceutically acceptable salts thereof.
  14. 15
    16. The compound represented by the structure and pharmaceutically acceptable salts thereof.
  15. 16
    17. The compound represented by the structure wherein R is selected from the group consisting of -CH3, -C2H5, -CH(CH3)2, 0 ;^^C(CH 3 ) 3 R' is selected from the group consisting of -OBn, -OH, -OSO2CF3, and -CH=CH2;R is selected from the group consisting of -CO2H, -CO2MEM, or -CHO;and R' is selected from the group consisting of C r 3 ch 3 x^ Jx^ x CH 3 , and . JL ;and pharmaceutically acceptable salts thereof;^CH wherein MEM designates a methoxyethoxymethyl group.
  16. 17
    18. The compound represented by the structure wherein R is selected from the group consisting of -CH3, -C2H5, -CH(CH 3 )2, , and -H;^^C(CH 3 ) 3 R' is -H or alkyl;and R is selected from the group consisting of
  17. 18
    19. The compound of claim 18 wherein said alkyl is CH 3 .
  18. 19
    20. The compound represented by the structure wherein R is selected from the group consisting of R' is -H, -CH=CH 2 ;and R is -H or alkyl;and pharmaceutically acceptable salts thereof.
  19. 20
    21. The compound of claim 20 wherein said alkyl is -CH3.
  20. 21
    22. The compound represented by the structure wherein R is selected from the group consisting of , -CH=CH2, and -H;R' is -H or alkyl;and R is selected from the group consisting of and ;and pharmaceutically acceptable salts thereof.
  21. 22
    23. The compound of claim 22 wherein said alkyl is -CH3.
  22. 23
    24. The compound represented by the structure wherein N is located at position 3 or 4 in the phenyl ring;R is selected from the group consisting of -CHO, -CO2H, and NH H and R' is -H or alkyl;and pharmaceutically acceptable salts thereof.
  23. 24
    25. The compound of claim 24 wherein said alkyl is -CH 3 .
  24. 25
    26. The compound represented by the structure wherein R is selected from the group consisting of -CH 3 , -C 2 H 5 , -CH2C6H5, -C(CH3)3, -CH2-CCI3, and R' is -H or alkyl;and pharmaceutically acceptable salts thereof.
  25. 26
    27. The compound of claim 26 wherein alkyl is CH 3 .
  26. 27
    28. The compound represented by the structure wherein at least one R is selected from the group consisting of -CH=CH 2 , -OCH 3 , -OBn, -OH, and -H;R' is R is selected from the group consisting of CF 3 , and CH 3 and R' is -H;and pharmaceutically acceptable salts thereof.
  27. 29
    30. The compound of claim 29 wherein said alkyl is -CH3.
  28. 30
    31. The compound represented by the structure wherein R is -H or -CO2H;R' is selected from the group consisting of -CHO, -CO2H, and and R is -H or alkyl;and pharmaceutically acceptable salts thereof.
  29. 31
    32. The compound of claim 31 wherein said alkyl is -CH3.
  30. 32
    33. The compound represented by the structure -CH(OH)-CH=CH 2 ;R' is -Boc or -H;and R is -H or alkyl;and pharmaceutically acceptable salts thereof.
  31. 33
    34. The compound of claim 33 wherein said alkyl is -CH3.
  32. 34
    35. The compound represented by the structure wherein R is alkyl and R’ is selected from the group consisting of and pharmaceutically acceptable salts thereof.
Independent claims32