Oxamide derivatives useful as raf-kinase inhibitors

Oxamide derivatives of formula I

• A-D-B (I)
• wherein
• D is a bivalent oxamide moiety, or a derivative therof,
• A is a unsubstituted or substituted moiety of up to 40 carbon atoms of the formula:
• -L-(M-L′)α, where L is a 5, 6 or 7 membered cyclic structure, preferably selected from the group consisting of aryl, heteroaryl, arylene and heteroarylene, bound directly to D, L′ comprises an optionally substituted cyclic moiety having at least 5 members, preferably selected from the group consisting of aryl, heteroaryl, aralkyl, cycloalkyl and heterocyclyl, M is a bond or a bridging group having at least one atom, α is an integer of from 1-4;
• and each cyclic structure of L and L′ contains 0-4 members of the group consisting of nitrogen, oxygen and sulfur, wherein L′ is preferably substituted by at least one substituent selected from the group consisting of —SOβRx, —C(O)Rx and —C(NRy)Rz
• B is a substituted or unsubstituted, up to tricyclic aryl or heteroaryl moiety of up to 30 carbon atoms, preferably of up to 20 carbon atoms, comprising at least one 5-, 6-, or 7-membered cyclic structure, preferably a 5- or 6-membered cyclic structure, bound directly to D containing 0-4 members of the group consisting of nitrogen, oxygen and sulfur, wherein said cyclic structure directly bound to D is preferably selected from the group consisting of aryl, heteroaryl and heterocyclyl, 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 L′ is additionally substituted, the substituents are selected from the group consisting of halogen, up to per-halo, and Wγ, where γ is 0-3;
• wherein each W is independently selected from the group consisting of —CN, —CO2R, —C(O)NR5R5, —C(O)—R5, —NO2, —OR5, —SR5, —SO2R5, —SO3H, —NR5R5, —NR5C(O)OR5, —NR5C(O)R5, -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 groups consisting of —CN, —CO2R, —C(O)NR5R5, —C(O)—R5, —NO2, —OR5, —SR5, —SO2R5, —SO3H, —NR5R5, —NR5C(O)OR5, —NR5C(O)R5 and halogen up to per-halo;
• with each R5 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(R5)—, —(CH2)β, —C(O)—, —CH(OH)—, —(CH2)βO—, —(CH2)βS—, —(CH2)βN(R5)—, —O(CH2)β, —CHHal-, —CHal2-, —S—(CH2).— and —N(R5)(CH2)β— where β=1-3, and Hal is halogen;
• and
• Ar is 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 Zδ1 wherein δ1 is 0 to 3 and each Z is independently selected from the group consisting —CN, —CO2R5, —C(O)NR5R5, —C(O)—R5, —NO2, —OR5, —SR5, —SO2R5, —SO3H, —NR5R5, —NR5C(O)OR5, —NR5C(O)R5, 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, —CO2R5, —C(O)NR5R5, —C(O)—R5, —NO2, —OR5, —SR5, —SO2R5, —SO3H, —NR5R5, —NR5C(O)OR5, —NR5C(O)R5, and the pharmaceutically acceptable derivatives, salts and solvates thereof.