Protein kinase inhibitors

A compound of formula I:

• (L)p(X)q I
• and pharmaceutically acceptable salts thereof;
• wherein:
• p is an integer of from 2 to 10;
• q is an integer of from 1 to 20;
• each L is a ligand independently selected from the group consisting of:
• (i) a moiety of formula III:
• 75
• wherein
• each Ra is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, aryl, heteroaryl and a covalent bond linking the moiety to the linker;
• each Rb is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, aryl, heteroaryl and a covalent bond linking the moiety to the linker;
• Rc is selected from the group consisting of aryl, alkaryl, heteroaryl and heterocycle;
• provided one and only one of Ra and Rb comprises a covalent bond linking the moiety to the linker;
• (ii) a moiety of formula IV:
• 76
• wherein
• Rd is selected from the group consisting of aryl, alkaryl, heteroaryl and heterocycle;
• Re is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl and a covalent bond linking the moiety to the linker;
• each Rf is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, aryl, heteroaryl and a covalent bond linking the moiety to the linker;
• provided one and only one of Re or Rf comprises a covalent bond linking the moiety to the linker;
• (iii) a moiety of formula V:
• 77
• wherein
• each Rg is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl and acyl;
• Rh is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl and acyl;
• Ri is a covalent bond linking the moiety to the linker;
• Q1 is NRi, O, S, alkylene or a covalent bond, where Ri is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• (iv) a moiety of formula VI:
• 78
• wherein
• each Rj is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl and a covalent bond linking the moiety to the linker;
• Rk is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, hydroxy, halogen and —CHO;
• each Q2 is independently NRj, O and S, where Rj is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• provided one and only one of Rj comprises a covalent bond linking the moiety to the linker;
• (v) a moiety of formula VII:
• 79
• wherein
• each Rl and Rm is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• Rn is a covalent bond linking the moiety to the linker;
• Q3 is NRn, O, S or alkylene;
• Q4 is NRn, O, S, alkylene or a covalent bond, where each Rn, in Q3 and Q4 is independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• each m is independently an integer from 1 to 3;
• (vi) a moiety of formula VIII:
• 80
• wherein
• each Ro is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• Rp is aryl or heteroaryl, wherein the aryl or heteroaryl group is substituted with a covalent bond linking the moiety to the linker or with —OZ′ where Z′ is a covalent bond linking the moiety to the linker;
• Z is 2H or O;
• m is an integer from 1 to 3;
• (vii) a moiety of formula IX:
• 81
• wherein
• each Rq is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, heteroaryl, heterocyclic and a covalent bond linking the moiety to the linker;
• each Rq, is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl and acyl;
• Rs is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl and acyl;
• Rr is aryl or heteroaryl, wherein the aryl or heteroaryl group is substituted with a covalent bond linking the moiety to the linker;
• provided one and only one of Rq or Rr comprises a covalent bond linking the moiety to the linker;
• (viii) a moiety of formula X:
• 82
• wherein
• each Rt is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• each Ru is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy, substituted thioalkoxy and a covalent bond linking the moiety to the linker;
• Q5 is NRt′, O, S or alkylene, where Rt, is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• each m is independently an integer from 1 to 3;
• provided one and only one of Ru comprises a covalent bond linking the moiety to the linker;
• (ix) a moiety of formula XI:
• 83
• wherein
• each Rv is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• Rv, is a covalent bond linking the moiety to the linker;
• each Rw is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• Q6 is NRw′, O, S or alkylene, where Rw′ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• Q6′ is NRv″, O, S or alkylene, where Rv″ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• each m is independently an integer from 1 to 3;
• (x) a moiety of formula XII:
• 84
• wherein
• each Rx is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, heteroaryl and heterocyclic;
• Ry is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl and substituted alkynyl;
• Rz is a covalent bond linking the moiety to the linker;
• E is CH or N;
• (xi) a moiety of formula XIII:
• 85
• wherein
• each Raa is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, heteroaryl and heterocyclic;
• Rab is alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substitued amino, thioalkoxy, substituted thioalkoxy, wherein the alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substitued amino, thioalkoxy or substituted thioalkoxy group is substituted with a covalent bond linking the moiety to the linker;
• D is a covalent bond, NRab′, O or S, where Rab′ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• E is CH or N;
• (xii) a moiety of formula XIV:
• 86
• wherein
• Rac is a covalent bond linking the moiety to the linker;
• Rad is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, heteroaryl and heterocyclic;
• Rae is aryl or heteroaryl;
• (xiii) a moiety of formula XV:
• 87
• wherein
• Raf is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl and acyl;
• each Rag is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• Rah is aryl or heteroaryl;
• Ral is aryl or heteroaryl, wherein the aryl or heteroaryl group is substituted with a covalent bond linking the moiety to the linker;
• Q7 is NRaf′, O, S or alkylene, where Raf′ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• m′ is 1 or 2;
• (xiv) a moiety of formula XVI:
• 88
• wherein
• each Raj is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• Ral is aryl or heteroaryl;
• each Rak is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, heteroaryl, heterocyclic, and a covalent bond linking the moiety to the linker;
• Q8 is NRal′, O, S or alkylene, where Ral′, is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• m is an integer from 1 to 3;
• provided one and only one of Rak comprises a covalent bond linking the moiety to the linker;
• (xv) a moiety of formula XVII:
• 89
• wherein
• Ram is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl and a covalent bond linking the moiety to the linker;
• Ran is selected from the group consisting of 4-phosphonomethylphenyl, 4-phosphonodifluoromethylphenyl, 3-carboxy-4-carboxymethoxyphenyl and 3,4-dihydroxyphenyl;
• Rao is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• each Rap is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• W is N or CH;
• Y is O, S, NH, N—Z′, CH2 or CH—Z′, where Z′ is a covalent bond linking the moiety to the linker;
• m is an integer from 1 to 3;
• ----- is an optional double bond;
• provided one and only one of Ram and Y comprises a covalent bond linking the moiety to the linker;
• (xvi) a moiety of formula XVIII:
• 90
• wherein
• each Raq is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy, substituted thioalkoxy, a covalent bond linking the moiety to the linker and —NH—Z′, where Z′ is a covalent bond linking the moiety to the linker;
• Rar is selected from the group consisting of 4-phosphonomethylphenyl, 4-phosphonodifluoromethylphenyl, 3-carboxy-4-carboxymethoxyphenyl and 3,4-dihydroxyphenyl;
• Q9 is NRaq′, O, S or alkylene, where Raq′ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• m is an integer from 1 to 3;
• provided one and only one of Raq comprises a covalent bond linking the moiety to the linker;
• (xvii) a moiety of formula XIX:
• 91
• wherein
• Ras is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl and a covalent bond linking the moiety to the linker;
• Rat is selected from the group consisting of 4-phosphonomethylphenyl, 4-phosphonodifluoromethylphenyl, 3-carboxy-4-carboxymethoxyphenyl and 3,4-dihydroxyphenyl;
• Rau is aryl or heteroaryl, wherein the aryl or heteroaryl group is substituted with a covalent bond linking the moiety to the linker or with —OZ′, where Z′ is a covalent bond linking the moiety to the linker;
• Rav is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl and alkaryl;
• provided one and only one of Ras and Rau comprises a covalent bond linking the moiety to the linker;
• (xviii) a moiety of formula XX:
• 92
• wherein
• each Raw is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• each Rax is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy, substituted thioalkoxy, a covalent bond linking the moiety to the linker and —OZ′, where Z′ is a covalent bond linking the moiety to the linker;
• each m is independently an integer from 1 to 3;
• provided one and only one of Rax comprises a covalent bond linking the moiety to the linker;
• (xix) a moiety of formula XXI:
• 93
• wherein
• each Ray is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• Raz is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkaryl, acyl and a covalent bond linking the moiety to the linker;
• Rba is aryl or heteroaryl;
• Rbb is aryl or heteroaryl, wherein the aryl or heteroaryl group is substituted with a covalent bond linking the moiety to the linker or with —OZ′, where Z′ is a covalent bond linking the moiety to the linker;
• m is an integer from 1 to 3;
• provided one and only one of Raz or Rbb comprises a covalent bond linking the moiety to the linker;
• (xx) a moiety of formula XXII:
• 94
• wherein
• Rbc is a covalent bond linking the moiety to the linker;
• A and B are independently selected from the group consisting of 2H, O and S;
• (xxi) a moiety of formula XXIII:
• 95
• wherein
• each Rbd is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl and a covalent bond linking the moiety to the linker;
• A and B are independently selected from the group consisting of 2H, O and S;
• F and G are independently —CH2— or —CH2CH2—;
• r is an integer from 0 to 2;
• provided one and only one of Rbd comprises a covalent bond linking the moiety to the linker;
• (xxii) a moiety of formula XXIV:
• 96
• wherein
• Rbe is a covalent bond linking the moiety to the linker;
• (xxiii) a moiety of formula XXV:
• 97
• wherein
• each Rbf is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy and substituted thioalkoxy;
• each Rbg is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl and a covalent bond linking the moiety to the linker;
• Rbh is aryl, heteroaryl or heterocyclic;
• Q10 is NRbf′, O, S or alkylene, where Rbf′ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• m is an integer from 1 to 3;
• provided one and only one of Rbg comprises a covalent bond linking the moiety to the linker;
• (xxiv) a moiety of formula XXVI:
• 98
• wherein
• Rbi is a covalent bond linking the moiety to the linker;
• (xxv) a moiety of formula XXVII:
• 99
• wherein
• each Rbj is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl and a covalent bond linking the moiety to the linker;
• Q11 is NRbj′, O, S or alkylene, where Rbj′ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or acyl;
• provided one and only one of Rbj comprises a covalent bond linking the moiety to the linker;
• (xxvi) a moiety of formula XXVIII:
• 100
• wherein
• each Rbk is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acyl, acylamino, acyloxy, alkoxy, substituted alkoxy, amino, substituted amino, aminoacyl, aminoacyloxy, aryl, carboxyl, carboxyalkyl, cyano, cycloalkyl, substituted cycloalkyl, halogen, heteroaryl, heterocyclic, hydroxy, oxyacylamino, nitro, thioalkoxy, substituted thioalkoxy, —SO—Rbk′ and —SO2—Rbk′, where Rbk′ is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, heteroaryl or heterocyclic;
• Rbl is aryl or heteroaryl, wherein the aryl or heteroaryl group is substituted with a covalent bond linking the moiety to the linker or with —(CH2)u—Z′, where Z′ is a covalent bond linking the moiety to the linker and u is an integer from 1 to 3;
• m is an integer from 1 to 3;
• (xxvii) a moiety of formula XXIX:
• 101
• wherein
• Rbn is selected from the group consisting of alkoxy, substituted alkoxy, hydroxy and —OZ′, where Z′ is a covalent bond linking the moiety to the linker;
• Rbo is aryl or heteroaryl;
• Rbp is acyl, alkoxycarbonyl and a covalent bond linking the moiety to the linker;
• provided one and only one of Rbn and Rbp comprises a covalent bond linking the moiety to the linker;
• and each X is a linker independently selected from a group of the formula:
• —Xa—Z—(Ya—Z)m′—Yb—Z—Xa—
• wherein
• m′ is an integer of from 0 to 20;
• Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)O—, —C(S)O—, —C(S)NR— or a covalent bond;
• Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cycloalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, or a covalent bond;
• Ya and Yb at each separate occurrence are selected from the group consisting of:
• —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —N=C(R)—NR′—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
• where n is 0, 1 or 2;
• and
• R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic.