×

Omega-carboxy aryl substituted diphenyl ureas as p38 kinase inhibitors

  • US 20030105091A1
  • Filed: 03/04/2002
  • Published: 06/05/2003
  • Est. Priority Date: 01/13/1999
  • Status: Abandoned Application
First Claim
Patent Images

1. A method of treating a disease mediated by p38 within a host, said method comprising administering to said host a compound of Formula I:

  • A-D-B 



    (I)or a pharmaceutically acceptable salt thereof, wherein D is —

    NH—

    C(O)—

    NH—

    , A is a substituted moiety of up to 40 carbon atoms of the formula;

    -L-(M-L1)q, where L is a 5 or 6 membered cyclic structure bound directly to D, L1 comprises a substituted cyclic moiety having at least 5 members, M is a bridging group having at least one atom, q is an integer of from 1-3; and

    each cyclic structure of L and L1 contains 0-4 members of the group consisting of nitrogen, oxygen and sulfur, and B is a substituted or unsubstituted, up to tricyclic aryl or heteroaryl moiety of up to 30 carbon atoms with at least one 6-member cyclic structure bound directly to D containing 0-4 members of the group consisting of nitrogen, oxygen and sulfur, wherein L1 is substituted by at least one substituent selected from the group consisting of —

    SO2Rx, —

    C(O)Rx and —

    C(NRy) Rz, Ry is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally halosubstituted, up to per halo;

    Rz is hydrogen or a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen;

    Rx is Rz or NRaRb where Ra and Rb are a) independently hydrogen, a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen, or —

    OSi(Rf)3 where Rf is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen;

    or b) Ra and Rb together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O substituted by halogen, hydroxy or carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen;

    or c) one of Ra or Rb is —

    C(O)—

    , a C1-C5 divalent alkylene group or a substituted C1-C5 divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C1-C5 divalent alkylene group are selected from the group consisting of halogen, hydroxy, and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen;

    where B is substituted, L is substituted or L1 is additionally substituted, the substituents are selected from the group consisting of halogen, up to per-halo, and Wn, where n is 0-3;

    wherein each W is independently selected from the group consisting of —

    CN, —

    CO2R7, —

    C(O)NR7R7, —

    C(O)—

    R7, —

    NO2, —

    OR7, —

    SR7, —

    NR7R7, —

    NR7C(O)OR7, —

    NR7C(O)R7, —

    Q—

    Ar, and carbon based moieties of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by one or more substituents independently selected from the group consisting of —

    CN, —

    CO2R7, —

    C(O)R7, —

    C(O)NR7R7, —

    OR7, —

    SR7, —

    NR7R7, —

    NO2, —

    NR7C(O)R7, —

    NR7C(O)OR7 and halogen up to per-halo;

    with each R7 independently selected from H or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, wherein Q is —

    O—

    , —

    S—

    , —

    N(R7)—

    , —

    (CH2)m

    , —

    C(O)—

    , —

    CH(OH)—

    , —

    (CH2)mO—

    , —

    (CH2)mS—

    , —

    (CH2)mN(7)—

    , —

    O(CH2)m

    CHXa

    , —

    CXa2

    , —

    S—

    (CH2)m— and



    N(R7)(CH2)m

    , where m=1-3, and Xa is halogen; and

    Ar is a 5- or 6-member aromatic structure containing 0-2 members selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by halogen, up to per-halo, and optionally substituted by Zn1, wherein n1 is 0 to 3 and each Z is independently selected from the group consisting of —

    CN, —

    CO2R7, —

    C(O)R7, —

    C(O)NR7R7, —

    NO2, —

    OR7, —

    SR7

    NR7R7, —

    NR7C(O)OR7, —

    NR7C(O)R7, and a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by one or more substituents selected from the group consisting of —

    CN, —

    CO2R7, —

    COR7, —

    C(O)NR7R7, —

    OR7, —

    SR7, —

    NO2, —

    NR7, —

    NR7C(O)R7, and —

    NR7C(O)OR7, with R7 as defined above.

View all claims
  • 2 Assignments
Timeline View
Assignment View
    ×
    ×