Author: claimsbot

What is claimed is:

1. A compound of Formula I:
A – D – B(I)
or a pharmaceutically acceptable salt thereof, wherein
D is NHC(O)NH,
A is a substituted moiety of up to 40 carbon atoms of the formula: L(ML1 )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)0R7, NR7C(O)R7, QAr, 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(R7), O(CH2)m CHXa, CXa2, S(CH2)m and N(R7)(CH2)m, where m1-3, 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, NR7R7, NR7C(O)R7, and NR7C(O)OR7, with R7 as defined above.
2. A compound as in claim 1 wherein:
Ry is hydrogen, C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl having 0-3 heteroatoms, C2-10 alkenyl, C1-10 alkenoyl, C6-12 aryl, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C7-24 aralkyl, C7-24 alkaryl, substituted C1-10 alkyl, substituted C1-10 alkoxy, substituted C3-10 cycloalkyl having 0-3 heteroatoms selected from N, S and O, substituted C6-C14 aryl, substituted C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, substituted C7-24 alkaryl or substituted C7-C24 aralkyl, where Ry is a substituted group, it is substituted by halogen up to per halo,
Rz is hydrogen, C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl having 0-3 heteroatom, C2-10 alkenyl, C1-10 alkenoyl, C6-12 aryl, C3-12 hetaryl having 1-3 heteroatoms selected from, S, N and O, C7-24 alkaryl, C7-24 aralkyl, substituted C1-10 alkyl, substituted C1-10 alkoxy, substituted C6-C14 aryl, substituted C3 -C10 cycloalkyl having 0-3 heteroatoms selected from S, N and O, substituted C3-12 hetaryl having 1-3 heteroatoms selected from S, N and O, substituted C7-24 alkaryl or substituted C7-C24 aralkyl where Rz is a substituted group, it is substituted by halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl, C1-6 halo substituted alkyl up to per halo alkyl, C6-CI2 halo substituted aryl up to per halo aryl, C3-Cl2 halo substituted cycloalkyl up to per halo cycloalkyl having 0-3 heteroatoms selected from N, S and O, halo substituted C3-C12 hetaryl up to per halo hetaryl having 1-3 heteroatoms selected from O, N and S, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and C(O)Rg,
Ra and Rb are,
a) independently hydrogen,
a carbon based moiety selected from te group consisting of C, -Clo alkyl, C1-C10 alkoxy, C3-10 cycloalkyl, C2-10 alkenyl, C1-10 alkenoyl, C6-12 aryl, C3-12 hetaryl having 1-3 heteroatoms selected from O, N and S, C3-12 cycloalkyl having 0-3 heteroatoms selected from N, S and O, C7-24 aralkyl, C7-C24 alkaryl, substituted C1-10 alkyl, substituted C1-10 alkoxy, substituted C3-10 cycloalkyl, having 0-3 heteroatoms selected from N, S and O, substituted C6-12 aryl, substituted C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, substituted C7-24 aralkyl, substituted C7-24 alkaryl, where Ra and Rb are a substituted group, they are substituted by halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and C(O)Rg; or
OSi(Rf)3 where Rf is hydrogen, C1-10 alkyl, C1-10 alkoxy, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C6-12 aryl, C3-C12 hetaryl having 1-3 heteroatoms selected from O, S and N, C7-24 aralkyl, substituted C1-10 alkyl, substituted C1-C10 alkoxy, substituted C3-C12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, substituted C3-C12 heteraryl having 1-3 heteroatoms selected from O, S, and N, substituted C6-12 aryl, and substituted C7-24 alkaryl, where Rf is a substituted group it is substituted halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl, C7 -C24 alkaryl, C7-C24 aralkyl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and C(O)Rg,
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 with substituents selected from the group consisting of halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl, C7-C24 alkaryl, C7 -C24 aralkyl, halo substituted C1-6 alkyl up to per halo alkyl, halo substituted C6-C12 aryl up to per halo aryl, halo substituted C3-C12 cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and C(O)Rg,
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, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl, C7-C24 alkaryl, C7 -C24 aralkyl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and C(O)Rg,

where Rg is C1-10 alkyl; CN, CO2Rd, ORd, SRd, NO2, C(O) Re, NRdRe, NRd C(O)ORe and NRd C(O)Re, and Rd and Re are independently selected from the group consisting of hydrogen, C1-10, alkyl, C1-10 alkoxy, C3-10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, C6-12 aryl, C3-C12 hetaryl with 1-3 heteroatoms selected from O, N and S and C7 -C24 aralkyl, C7-C24 alkaryl, up to per halo substituted C1-C10 alkyl, up to per halo substituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, up to per halo substituted C6-C14 aryl, up to per halo substituted C3-C12 hetaryl having 1-3 heteroatoms selected from O, N, and S, halo substituted C7-C24 alkaryl up to per halo alkaryl, and up to per halo substituted C7-C24 aralkyl,
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, C1-C10 alkyl, C1-C10 alkoxy, C2-C10 alkenyl, C1-C10 alkenoyl, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C6-C14 aryl, C7-C24 alkaryl, C7 -C24 aralkyl, C3-C12 heteroaryl having 1-3 heteroatoms selected from O, N and S, C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, substituted C1-C10 alkyl, substituted C1-C10 alkoxy, substituted C2-C10 alkenyl, substituted C1-C10 alkenoyl, substituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, substituted C6-C12 aryl, substituted C3-CI2 hetaryl having 1-3 heteroatoms selected from O, N and S, substituted C7-C24 aralkyl, substituted C7-C24 alkaryl, substituted C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, and QAr;
R7 is independently selected from H, C1-C10 alkyl, C1-C10 alkoxy, C2-Cio alkenyl, C1-C1-C10 alkenoyl, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C6-C14 aryl, C3-C13 hetaryl having 1-3 heteroatoms selected from O, N and S, C7-C14 alkaryl, C7 -C24 aralkyl, C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, up to per-halosubstituted C1-C10 alkyl, up to per-halosubstituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, up to per-halosubstituted C6-C14 aryl, up to per-halosubstituted C3-C13 hetaryl having 1-3 heteroatoms selected from O, N and S, up to per-halosubstituted C7-C24 aralkyl, up to per-halosubstituted C7-C24 alkaryl, and up to per-halosubstituted C4-C23 alkheteroaryl; 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, C1-C10 alkyl, C1-C10 alkoxy, C2-C10 alkenyl, C1-C10 alkenoyl, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, C6-C14 aryl, C3-C13 hetaryl having 1-3 heteroatoms selected from O, N and S, C7-C24 alkaryl, C7-C24 aralkyl, C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, substituted C1-C10 alkyl, substituted C1-C10 alkoxy, substituted C2-C10 alkenyl, substituted C1-C10 alkenoyl, substituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, substituted C6-C12 aryl, substituted C7-C24 alkaryl, substituted C7-C24 aralkyl and substituted C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S; wherein if Z is a substituted group, the one or more substituents are selected from the group consisting of CN, CO2R7, COR7, C(O)NR7R7, OR7, SR7, NO2, NR7R7, NR7C(O)R7, and NR7C(O)OR7.
3. A compound as in claim 1 wherein M is one or more bridging groups selected from the group consisting of O, S, N(R7), (CH2)m, C(O), CH(OH), (CH2)mO, (CH2)mS, (CH2)mN(R7), O(CH2)mCHXa, CXa2, S(CH2)m and N(R7)(CH2)m, where m1-3, Xa is halogen and R7is as defined in claim 1.
4. A compound as in claim 1 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by OH.
5. A compound as in claim 1 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by a moiety having an ionizable hydrogen and a pKa of 10 or less.
6. A compound of claim 1 wherein B of Formula I is a substituted or unsubstituted six member aryl moiety or six member hetaryl moiety, said hetaryl moiety having 1 to 4 members selected from the group of hetaryl atoms consisting of nitrogen, oxygen and sulfur with the balance of the hetaryl moiety being carbon.
7. A compound of claim 1 wherein B of Formula I is an unsubstituted phenyl group, an unsubstituted pyridyl group, an unsubstituted pyrimidinyl, a phenyl group substituted by a substituent selected from the group consisting of halogen and Wn wherein W and n are as defined in claim 1, a pyrimidinyl group substituted by a substituent selected from the group constituting of halogen and Wn, whereas W and n are as defined in claim 1, or a substituted pyridyl group substituted by a substituent selected from the group consisting of halogen and Wn wherein W and n are as defined in claim 1.
8. A compound of claim 6 wherein B of Formula I is a substituted phenyl group, a substituted pyrimidinyl group, or substituted pyrridyl group substituted 1 to 3 times by 1 or more substituents selected from the group consisting of CN, halogen, C1-C10 alkyl, C1-C10 alkoxy, OH, up to per halo substituted C1-C10 alkyl, up to per halo substituted C1-C10 alkoxy or phenyl substituted by halogen up to per halo.
9. A compound of claim 1, wherein L, the six member cyclic structure bound directly to D, is a substituted or unsubstituted 6 member aryl moiety or a substituted or unsubstituted 6 member hetaryl moiety, wherein said hetaryl moiety has 1 to 4 members selected from the group of heteroatoms consisting of nitrogen, oxygen and sulfur with the balance of said hetaryl moiety being carbon, wherein the one or more substituents are selected from the group consisting of halogen and Wn wherein W and n are as defined in claim 1.
10. A compound of claim 8, wherein L, the 6 member cyclic structure bound directly to D, is a substituted phenyl, unsubstituted phenyl, substituted pyrimidinyl, unsubstituted pyrimidinyl, substituted pyridyl or unsubstituted pyridyl group.
11. A compound of claim 1, wherein said substituted cyclic moiety L1 comprises a 5 to 6 membered aryl moiety or hetaryl moiety, wherein said heteraryl moiety comprises 1 to 4 members selected from the group of heteroatoms consisting of nitrogen, oxygen and sulfur.
12. A compound of claim 1, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
13. A compound of claim 3, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
14. A compound of claim 6, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
15. A compound of claim 8, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
16. A compound of claim 9, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
17. A compound of claim 10, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
18. A compound of claim 14, wherein M is one or more bridging groups selected from the group consisting of O, S, N(R7), (CH2)m, C(O), CH(OH), (CH2)mO, (CH2)mS, (CH2)mN(R7), O(CH2)m, CHXa, CXa2, S(CH2)m, and N(R7)(CH2)m, where m1-3, Xa is halogen and R7 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 up to per halo.
19. A compound of claim 15, wherein M is one or more bridging groups selected from the group consisting of O, S, N(R7), (CH2)m, C(O), CH(OH), (CH2)mO, (CH2)mS, (CH2)mN(R7), O(CH2)m CHXa, CXa2, S(CH2)m and N(R7)(CH2)m, where m1-3, Xa is halogen and R7 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 up to per halo.
20. A compound of claim 16, wherein M is one or more bridging groups selected from the group consisting of O, S, N(R7), (CH2)m, C(O), CH(OH), (CH2)mO, (CH2)mS, (CH2)mN(R7), O(CH2)m CHXa, CXa2, S(CH2)m and N(R7)(CH2)m, where m1-3, Xa is halogen and R7 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 up to per halo.
21. A compound of claim 17, wherein M is one or more bridging groups selected from the group consisting of O, S, N(R7), (CH2)m, C(O), CH(OH), (CH2)mO, (CH2)mS, (CH2)mN(R7), O(CH2)m CHXa, CXa2, S(CH2)m and N(R7)(CH2)m, where m1-3, Xa is halogen and R7 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 up to per halo.
22. A compound of claim 1 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, CN, OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
23. A compound of claim 13 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, CN, OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
24. A compound of claim 18 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, CN, OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
25. A compound of claim 19 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, CN, OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
26. A compound of claim 20 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, CN, OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
27. A compound of claim 21 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, CN, OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
28. A compound of claim 1 wherein L1 is substituted by C(O)Rx.
29. A compound of claim 1 wherein L1 is substituted by SO2Rx.
30. A compound of claim 1 wherein L1 is substituted only by C(O)Rx.
31. A compound of claim 1 wherein L1 is substituted only by SO2Rx.
32. A compound of claim 1 wherein L1 is substituted by C(O)Rx or SO2Rx, wherein Rx is NRaRb.
33. A compound of claim 13 wherein L1 is substituted by C(O)Rx or SO2Rx, wherein Rx is NRaRb, and 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.
34. A compound of claim 18 wherein L1 is substituted by C(O)Rx or SO2Rx, wherein Rx is NRaRb and Ra and Rb are independently 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.
35. A compound of claim 19 wherein L1 is substituted by C(O)R,, wherein Rx is NRaRb and Ra and Rb are independently 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.
36. A compound of claim 20 wherein L1 is substituted by C(O)Rx or SO2Rx, wherein Rx is NRaRb and Ra and Rb are independently 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.
37. A compound of claim 21 wherein L1 is substituted by C(O)Rx or SO2Rx, wherein Rx is NRaRb and Ra and Rb are independently 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.
38. A compound of Formula I:
A – D – B(I)
or a pharmaceutically acceptable salt thereof, wherein
D is NHC(O)NH,
A is a substituted moiety of up to 40 carbon atoms of the formula: L(ML1)q, where L is a 6 membered aryl moiety or a 6 membered hetaryl moiety 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, QAr, 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(R7), O(CH2)m CHXa, CXa2, S(CH2)m and N(R7)(CH2)m, where m1-3, and Xa is halogen;

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 nl 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 are selected from the group consisting of CN, CO2R7, COR7, C(O)NR7R7, OR7, SR7, NO2, NR7R7, NR7C(O)R7, and NR7C(O)OR7, with R7 as defined above; and
wherein M is one or more bridging groups selected from the group consisting of O, S, N(R7), (CH2)m, C(O), CH(OH), (CH2)mO, (CH2)mS, (CH2)mN(R7), O(CH2)m CHXa, CXa2, S(CH2)m and N(R7)(CH2)m, where m1-3, Xa is halogen.
39. A compound of Formula I:
A – D – B(1)
or a pharmaceutically acceptable salt thereof, wherein
D is NHC(O)NH,
A is a substituted moiety of up to 40 carbon atoms of the formula: L(ML1)q, where L is a substituted or unsubstituted phenyl or peritoneal moiety bound directly to D, L1 comprises a substituted phenyl, peritoneal or pyrimidinyl moiety, M is a bridging group having at least one atom, q is an integer of from 1-3; and
B is a substituted or unsubstituted phenyl or pyridine group bound directly to D,
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, and;
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, QAr, 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, OR, SR, 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(R7), O(CH2)m CHXa, CXa2, S(CH2)m and N(R)(CH2)m, where m1-3, and Xa is halogen;
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, NR7R7, NR7C(O)R7, and NR7C(O)OR7 ; and
wherein M is one or more bridging groups selected from the group consisting of O, S, N(R7), (CH2)m, C(O), CH(OH), (CH2)mO, (CH2)mS, (CH2)mN(R7), O(CH2)m CHXa, CXa2, S(CH2)m and N(R7)(CH2)m, where m1-3, Xa is halogen.
40. A compound as in claim 38 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by OH.
41. A compound as in claim 38 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by a moiety having an ionizable hydrogen and a pKa of 10 or less.
42. A compound as in claim 39 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by OH.
43. A compound as in claim 39 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by a moiety having an ionizable hydrogen and a pKa of 10 or less.
44. A compound as in claim 38 wherein substituents for B and L and additional substituents for L1, are selected from the group consisting of C1-C10 alkyl up to per halo substituted C1-C10 alkyl, CN, OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
45. A compound as in claim 39 wherein substituents for B and L and additional substituents for L1, are selected from the group consisting of C1-C10 alkyl up to per halo substituted C1-C10 alkyl, CN, OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
46. A compound of claim 38 wherein L1 is substituted by C(O)Rx or SO2Ra.
47. A compound of claim 39 wherein L1 is substituted by C(O)Rx or SO2Rx.
48. A compound of claim 46 wherein Rx is NRaRb and Ra and Rb are independently hydrogen and 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.
49. A compound of claim 47 wherein Rx is NRaRb and Ra and Rb are independently hydrogen and 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.
50. A compound of claim 1 which is a pharmaceutically acceptable salt of a compound of formula I selected from the group consisting of
a) basic salts of organic acids and inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, trifluorosulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, and mandelic acid; and
b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline cations, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
51. A compound of claim 2 which is a pharmaceutically acceptable salt of a compound of formula I selected from the group consisting of
a) basic salts of organic acids and inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, trifluorosulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, and mandelic acid; and
b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline cations, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
52. A compound of claim 33 which is a pharmaceutically acceptable salt of a compound of formula I selected from the group consisting of
a) basic salts of organic acids and inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, trifluorosulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, and mandelic acid; and
b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline cations, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
53. A compound of claim 38 which is a pharmaceutically acceptable salt of a compound of formula I selected from the group consisting of
a) basic salts of organic acids and inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, trifluorosulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, and mandelic acid; and
b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline cations, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
54. A compound of claim 39 which is a pharmaceutically acceptable salt of a compound of formula I selected from the group consisting of
a) basic salts of organic acids and inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, trifluorosulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, and mandelic acid; and
b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline cations, alkaline earth cations, the ammnonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
55. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt of a compound of formula I, and a physiologically acceptable carrier.
56. A pharmaceutical composition comprising a compound of claim 2 consistent with formula I or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.
57. A pharmaceutical composition comprising a compound of claim 33 consistent with formula I or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.
58. A pharmaceutical composition comprising a compound of claim 38 consistent with formula I or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.
59. A pharmaceutical composition comprising a compound of claim 39 consistent with formula I or a pharmaceutically acceptable salt thereof and a physiologically acceptable carrier.
60. A compound selected from the group consisting of
3-tert butyl phenyl ureas of Table 1 above;
5-tert butyl-2-methoxyphenyl ureas of Table 2 above;
5-(trifluoromethyl)-2 phenyl ureas of Table 3 above;
3-(trifluoromethyl)-4 chlorophenyl ureas of Table 4 above;
3-(trifluoromethyl)-4-bromophenyl ureas of Table 5 above;
5-(trifluoromethyl)-4-chloro-2 methoxyphenyl ureas of Table 6 above; and ureas 101-103 in Table 7 above.
61. A compound selected from the group consisting of
the 3-tert butyl phenyl ureas:
N-(3-tert-butylphenyl)-N-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl urea and
N-(3-tert-butylphenyl)-N-(4-(4-acetylphenoxy)phenyl urea;

the 5-tert-butyl-2-methoxyphenyl ureas:
N-(5-tert-butyl-2-methoxyphenyl)-N-(4-(1,3-dioxoisoindolin-5-yloxy)phenyl) urea,
N-(5-tert-butyl-2-methoxyphenyl)-N-(4-(1-oxoisoindolin-5-yloxy)phenyl) urea,
N-(5-tert-butyl-2-methoxyphenyl)-N-(4-(4-methoxy-3 -(N-methylcarbamoyl)phenoxy)phenyl) urea and
N-(5-tert-butyl-2-methoxyphenyl)-N-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl) urea;

the 2-methoxy-5-trifluoromethyl)phenyl ureas:
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(4-(2-carbamoyl-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-5 -(trifluoromethyl)phenyl)-N-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(4-(2-(N-methylcarbamoyl)-4-pyridylthio)phenyl) urea,
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea and
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea;

the 4-chloro-3-(trifluoromethyl)phenyl ureas:
N-(4-chloro-3-(trifluoromethyl)phenyl)-N-(3-(2-carbamoyl-4-pyridyloxy)phenyl) urea,
N-(4-chloro-3 -(trifluoromethyl)phenyl)-N-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(4-chloro-3-(trifluoromethyl)phenyl)-N-(4-(2-carbamoyl-4-pyridyloxy)phenyl) urea and
N-(4-chloro-3-(trifluoromethyl)phenyl) -N-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea.

the 4-romo-3-(trifluoromethyl)phenyl ureas:
N-(4-bromo-3-(trifluoromethyl)phenyl)-N-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(4-bromo-3 -(trifluoromethyl)phenyl)-N-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(4-bromo-3 -(trifluoromethyl)phenyl)-N-(3-(2-(N-methylcarbamoyl)-4-pyridylthio)phenyl) urea,
N-(4-bromo-3-(trifluoromethyl)phenyl)-N-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea and
N-(4-bromo-3 -(trifluoromethyl)phenyl)-N-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea; and

the 2-methoxy-4-chloro-5-(trifluoromethyl)phenyl ureas:
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea and
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N-(3 -chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea.
62. A method for the treatment of a cancerous cell growth mediated by raf kinase, comprising administering a compound of Formula I of claim 1.
63. A method for the treatment of a cancerous cell growth mediated by raf kinase, comprising administering a compound of Formula I of claim 33.
64. A method for the treatment of a cancerous cell growth mediated by raf kinase, comprising administering a compound of Formula I of claim 38.
65. A method for the treatment of a cancerous cell growth mediated by raf kinase, comprising administering a compound of Formula I of claim 39.
66. A method for the treatment of a cancerous cell growth mediated by raf kinase, comprising administrating a compound selected from the group consisting of
3-tert butyl phenyl ureas of Table 1 above;
5-tert butyl-2-methoxyphenyl ureas of Table 2 above;
5-(trifluoromethyl)-2 phenyl ureas of Table 3 above;
3-(trifluoromethyl)-4 chlorophenyl ureas of Table 4 above;
3-(trifluoromethyl)-4-bromophenyl ureas of Table 5 above;
5-(trifluoromethyl)-4-chloro-2 methoxyphenyl ureas of Table 6 above; and ureas 101-103 in Table 7 above.
67. A method for the treatment of a cancerous cell growth mediated by raf kinase, comprising administrating a compound selected from the group consisting of
the 3-tert butyl phenyl ureas:
N-(3-tert-butylphenyl)-N-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl urea and
N-(3-tert-butylphenyl)-N-(4-(4-acetylphenoxy)phenyl urea;

the 5-tert-butyl-2-methoxyphenyl ureas:
N-(5-tert-butyl-2-methoxyphenyl)-N-(4-(1,3-dioxoisoindolin-5-yloxy)phenyl) urea,
N-(5-tert-butyl-2-methoxyphenyl)-N-(4-(1-oxoisoindolin-5-yloxy)phenyl) urea,
N-(5-tert-butyl-2-methoxyphenyl)-N-(4-(4-methoxy-3 -(N-methylcarbamoyl)phenoxy)phenyl) urea and
N-(5-tert-butyl-2-methoxyphenyl)-N-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl) urea;

the 2-methoxy-5-trifluoromethyl)phenyl ureas:
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(3-(2-carbamoyl-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(4-(2-carbamoyl-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(4-(2-(N-methylcarbamoyl)-4-pyridylthio)phenyl) urea,
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea and
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea;

the 4-chloro-3-(trifluoromethyl)phenyl ureas:
N-(4-chloro-3-(trifluoromethyl)phenyl)-N-(3-(2-carbamoyl-4-pyridyloxy)phenyl) urea,
N-(4-chloro-3-(trifluoromethyl)phenyl)-N-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(4-chloro-3-(trifluoromethyl)phenyl)-N-(4-(2-carbamoyl-4-pyridyloxy)phenyl) urea and
N-(4-chloro-3 -(trifluoromethyl)phenyl)-N-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea;

the 4-romo-3-(trifluoromethyl)phenyl ureas:
N-(4-bromo-3-(trifluoromethyl)phenyl)-N-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(4-bromo-3 -(trifluoromethyl)phenyl)-N-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(4-bromo-3-(trifluoromethyl)phenyl)-N-(3 -(2-(N-methylcarbamoyl)-4-pyridylthio)phenyl) urea,
N-(4-bromo-3 -(trifluoromethyl)phenyl)-N-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea and
N-(4-bromo-3 -(trifluoromethyl)phenyl)-N-(3 -chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea; and

the 2-methoxy-4-chloro-5-(trifluoromethyl)phenyl ureas:
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N-(3 -(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea and
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A toy comprising:
a toy vehicle comprising:
a vehicle frame;
a set of wheels, each wheel operatively connected to said vehicle frame;
an electrical generator, operatively connected to said vehicle frame, for receiving kinetic energy and converting at least a portion of received kinetic energy into electrical current;
a linkage for transmitting kinetic energy resulting from movement of at least one wheel of said set of wheels to said electrical generator; and
a first element of an electrical connector, wherein said first element is operatively connected to said frame, capable of engaging a second element to establish a connection for the conveyance of electrical energy, and capable of being disengaged from a second element;

a toy body comprising:
a body frame;
an electrical device operatively attached to said body frame; and
a second element of said electrical connector, wherein said second element is operatively connected to said body, capable of engaging said first element of said electrical connector to establish a connection for the conveyance of electrical energy, and capable of being disengaged from said first element.
2. A toy, as claimed in claim 1, wherein:
said electrical device comprises a light.
3. A toy, as claimed in claim 1, wherein:
said electrical device comprises a capacitor and a light;
wherein said capacitor is capable of storing electrical energy when said second element is connected to said first element and said electrical generator is providing electrical current to said capacitor, and providing stored electrical energy to said light for a substantial period of time after said second element is disengaged from said first element.
4. A toy, as claimed in claim 1, further comprising;
a speaker, operatively connected to said frame.
5. A toy, as claimed in claim 4, wherein:
said electrical device comprises a memory device for storing a signal suitable for application to said speaker.
6. A toy, as claimed in claim 5, wherein:
said signal emulating the sound of a vehicle engine.
7. A toy, as claimed in claim 5, wherein:
said signal conveys an adventure play theme when played on said speaker.
8. A toy, as claimed in claim 4, further comprising:
a memory device that is separate from said body and capable of providing a signal to said speaker when said first element is disengaged from said second element.
9. A toy, as claimed in claim 1, wherein:
said linkage conveys kinetic energy produced by rotation of said at least one wheel of said set of wheels about an axis of rotation.
10. A toy, as claimed in claim 9, wherein:
said axis of rotation is substantially perpendicular to the plane of said at least one wheel.
11. A toy, as claimed in claim 9, wherein:
said axis of rotation intersects said at least one wheel.
12. A toy, as claimed in claim 9, wherein:
said axis of rotation does not intersect said at least one wheel.
13. A toy, as claimed in claim 1, wherein:
said linkage comprising an arm that has a first end and a second end that is separated from said first end;
wherein said at least one wheel is pivotally attached to said first end of said arm; and
wherein said second end is pivotally connected to said frame so that said arm can rotate about a pivot point.
14. A toy, as claimed in claim 13, wherein:
said electrical generator converts kinetic energy produced by rotation of said arm about said pivot point in one direction of rotation and not in the other direction of rotation.
15. A toy comprising:
a vehicle frame;
a set of wheels, each wheel operatively connected to said vehicle frame;
an electrical generator, operatively connected to said vehicle frame, for receiving kinetic energy and converting at least a portion of received kinetic energy into electrical current;
a linkage for transmitting kinetic energy resulting from reciprocating rotational movement of at least one wheel of said set of wheels about an pivot axis that is separated from an axis of rotation of said at least one wheel.
16. A toy, as claimed in claim 1, wherein:
said linkage comprises an arm having a first end and a second end that is separated from said first end;
wherein said at least one wheel is pivotally attached to said first end of said arm and is capable of rotating about a first pivot axis;
wherein said second end of said arm is pivotally connected to said frame and is capable of rotating about a second pivot axis that is different than said first pivot axis.
17. A toy, as claimed in claim 1, wherein:
said linkage comprising a first stop and a second stop that limit the rotation of said arm about said second pivot axis to less than 360\xb0.
18. A toy, as claimed in claim 3, wherein:
said first and second stops limit the rotation of said arm about said second pivot axis to less than about 90\xb0.
19. A toy, as claimed in claim 1, wherein:
said electrical generator converts kinetic energy produced by rotation of said arm about said second pivot axis in one direction of rotation and not in the other direction of rotation.
20. A toy, as claimed in claim 1, further comprising:
a first element of an electrical connector, wherein said first element is operatively connected to said vehicle frame, capable of engaging a second element to establish a connection for the conveyance of electrical energy, and capable of being disengaged from a second element;
a body comprising:
a body frame;
an electrical device operatively attached to said body frame; and
a second element of an electrical connector, wherein said second element is operatively connected to said body, capable of engaging said first element of said electrical connector to establish a connection for the conveyance of electrical energy, and capable of being disengaged from said first element.

1. A method by which a signed client certificate is created for use by a client device in establishing mutually authenticated secure communications with a backend server of an application service, the communications to be secured by a client privatepublic key pair, the backend server storing a validation server public key used by the backend server to confirm a certificate signature of the signed client certificate, comprising:
at the client device, generating a first message and sending it to a device validation server, the generating including (1) generating the client privatepublic key pair using a random number generator, (2) generating a certificate signing request including the client public key and a certificate hash value; (3) encrypting the certificate signing request together with a device-specific authentication token and a locator value for the backend server, the encrypting producing encrypted values and performed using a domain token shared among a plurality of client devices, and (4) forming the first message to include the encrypted values and a hash of the domain token;
at the device validation server, (1) receiving the first message and confirming the hash of the domain token, (2) decrypting the encrypted values using the domain token to obtain decrypted values including the certificate signing request, the device-specific authentication token and the locator value, (3) generating the certificate signature from the decrypted values using a digital signature process and a validation server private key, and (4) securely sending the certificate signature to the client device; and
at the client device, forming the signed client certificate including the client public key and the certificate signature received from the device validation server.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A macromolecule that is a functional heavy chain antibody, a functional single domain heavy chain antibody or a functional VH domain comprising a first immunoglobulin single variable domain having a first antigen or epitope binding specificity and a second immunoglobulin single variable domain having a second antigen or epitope binding specificity wherein one or both of said first and second variable domains bind to human serum albumin, and the first and the second immunoglobulin variable domains are heavy chain variable domains, wherein the first or second variable domains comprises a sequence selected from SEQ ID NOs. 112-116, and wherein the amino acid at position 103 of the functional heavy chain antibody, the functional single domain heavy chain antibody or the functional VH domain is arginine (R) or wherein the amino acid at position 103 is replaced with arginine (R), said position 103 determined according to Kabat numbering.
2. The macromolecule according to claim 1, wherein the first or second variable domains comprises SEQ ID NO. 112.