×

N-substituted-heteroaryloxy-aryl-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors

  • US 6,900,201 B2
  • Filed: 04/25/2003
  • Issued: 05/31/2005
  • Est. Priority Date: 04/26/2002
  • Status: Expired due to Fees
0
Associated Cases
0
Associated Defendants
0
Product Citations
0
Petitions
65
Forward Citations
1
Assignment
First Claim
Patent Images

1. A compound of the formula:

  • embedded imagewherein said ring X is a 5 membered heterocyclic ring selected from the group consisting of;

    embedded imagewherein each dashed line represents an optional double bond;

    wherein each of R1, R2, R3, R4, R5, R6, R10, R11, and R12 is independently selected from the group consisting of hydrogen, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C6-C10)aryl, (C3-C10)heteroaryl, (C3-C8)cycloalkyl and (C3-C10)heterocyclyl;

    wherein each of said R1, R2, R3, R4, R5, R6, R10, R11, and R12 (C1-C4)alkyl, (C6-C10)aryl, (C3-C10)heteroaryl, (C3-C8)cycloalkyl and (C3-C10)heterocyclyl may be optionally substituted on any of the ring carbon atoms capable of supporting an additional substituent with one to three substituents per ring independently selected from halo, (C1-C4)alkyl, (C1-C4)alkoxy, —

    CN, —

    OH and —

    NH2;

    wherein each of said R1, R2, R3, R4, R5, R6, R10, R11, and R12 (C3-C10)heteroaryl, and (C3-C10)heterocyclyl may optionally be substituted on any ring nitrogen atom able to support an additional substituent independently selected from the group consisting of (C1-C4)alkyl and (C1-C4)alkyl-(C═

    O)—

    ;

    A is (C6-C10)arylene or (C3-C10)heteroarylene;

    wherein said A (C6-C10)arylene or (C3-C10)heteroarylene may be optionally substituted on any of the ring carbon atoms capable of supporting an additional substituent by one or two substituents per ring independently selected from F, Cl, Br, CN, OH, (C1-C4)alkyl, (C1-C4)perfluoroalkyl, (C1-C4)perfluoroalkoxy, (C1-C4)alkoxy and (C3-C8)cycloalkyloxy;

    Y is selected from the group consisting of a bond, —

    O—

    , —

    S—

    , >

    C═

    O, >

    SO2, >

    S═

    O, —

    CH2O—

    , —

    OCH2—

    , —

    CH2S—

    , —

    SCH2—

    , —

    CH2SO—

    , —

    CH2SO2—

    , —

    SOCH2—

    , —

    SO2CH2—

    , >

    NR14, —

    [N(R14)]CH2—

    , —

    CH2[N(R14)]—

    , —

    CH2—

    , —

    CH═

    CH—

    , —

    C≡

    C—

    , —

    [N(R14)]—

    SO2— and

    —

    SO2[N(R14)]—

    ;

    R14 is selected from the group consisting of hydrogen and (C1-C4)alkyl;

    B is a heterocyclylene containing at least one nitrogen atom;

    wherein one ring nitrogen atom of B is bonded to one carbon atom of G;

    with the proviso that the group —

    B—

    G cannot be methylazetidinyl or methylpiperidinyl;

    wherein said B may be optionally substituted on any of the ring carbon atoms capable of supporting an additional substituent by one or two substituents per ring independently selected from F, Cl, Br, CN, OH, (C1-C4)alkyl, (C1-C4)perfluoroalkyl, (C1-C4)perfluoroalkoxy, (C1-C4)alkoxy, (C3-C8)cycloalkyloxy, (C6-C10)aryl, (C3-C8)cycloalkyl, (C3-C10)heteroaryl and (C3-C10)heterocyclyl;

    G is (C1-C6)alkyl or R15—

    (CR16R17)p—

    ;

    p is an integer from zero to four;

    wherein said G (C1-C6)alkyl may be optionally substituted on any of the carbon atoms capable of supporting an additional substituent by one to three substituents per (C1-C6)alkyl independently selected from F, Cl, Br, CN, OH, (C1-C4)perfluoroalkyl, (C1-C4)perfluoroalkoxy, (C1-C4)alkoxy, —

    NH2, (C1-C4)alkyl-NH—

    , [(C1-C4)alkyl]2—

    N— and

    (C3-C8)cycloalkyloxy;

    R15 is selected from the group consisting of (C3-C8)cycloalkyl, (C6-C10)aryl, (C3-C10)heteroaryl and (C3-C10)heterocyclyl;

    wherein each of said R15(C6-C10)aryl, (C3-C8)cycloalkyl, (C3-C10)heteroaryl and (C3-C10)heterocyclyl may be optionally substituted on any of the ring carbon atoms capable of supporting an additional substituent by one to three substituents per ring independently selected from F, Cl, Br, CN, OH, (C1-C4)alkyl, (C1-C4)perfluoroalkyl, (C1-C4)perfluoroalkoxy, (C1-C4)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, —

    NH2, (C1-C4)alkyl-NH—

    , [(C1-C4)alkyl]2—

    N— and

    (C3-C8)cycloalkyloxy;

    wherein each of said R15 (C3-C8)cycloalkyl and (C3-C10)heterocyclyl may also optionally be substituted by oxo;

    wherein each of said R15(C3-C10)heteroaryl and (C3-C10)heterocyclyl may optionally be substituted on any ring nitrogen atom able to support an additional substituent independently selected from the group consisting of (C1-C4)alkyl and (C1-C4)alkyl-(C═

    O)—

    ;

    each of R16 and R17 are independently selected from the group consisting of hydrogen and (C1-C4)alkyl;

    or R16 and R17 may optionally be taken together with the carbon to which they are attached to form a 3 to 8-membered carbocyclic ring;

    or a pharmaceutically acceptable salt thereof.

View all claims
  • 1 Assignment
Timeline View
Assignment View
    ×
    ×