Indazolinone compositions useful as kinase inhibitors

A compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 and R2 are each independently hydrogen or a nitrogen protecting group;
• one of R3 or R4 is —R and the other one of R3 or R4 is -Q1—A-Q2-Y,
• wherein Q1 is —NRASO2—, —SO2NRA-, —NRACO—, —CONRA-, —OC(O)—, —C(O)O—, —OC(O)NRA, wherein each occurrence of RA is independently hydrogen or optionally substituded C1-4aliphatic;
• A is an optionally substituted C2-6 alkylidene chain wherein one or more methylene units of said C2-6 alkylidene chain is optionally replaced by —O—, —S—, —NRB—, —NRBCO—, —NRBCONRB—, —NRBCO2—, —CO—, —C(O)O—, or —OC(O)—, —CONRB—, —OC(O)NRB—, —SO2—, —SO2NRB—,—NRBSO2—, —NRBSO2NRB—, —C(O)C(O)—, or —C(O)C(RB)2C(O)—, and each occurrence of RB is independently hydrogen or optionally substituted group selected from C1-6 aliphatic, C1-6 heteroaliphatic, aryl or heteroaryl;
• Q2 is NRC, S, O, or C(RC)2, wherein each occurrence of RC is independently hydrogen or optionally substituted C1-4aliphatic;
• Y is an optionally substituted group selected from a 5-7-membered monocyclic or 8-10 membered bicyclic aryl, heteroaryl, heterocyclic or carbocyclic ring;
• R5 is —R;
• Z is CR6, wherein R6 is —R;
• and
• each occurrence of —R is independently hydrogen, Q(n)halogen, Q(n)CN, Q(n)NO2, or Q(n)R7, wherein n is zero or one, Q is an optionally substituted C1-4 alkylidene chain wherein one or more methylene units of Q is optionally replaced by —O—, —S—, —NR7—, —NR7CO—, —NR7CONR7—, —NR7CO2—, —CO —, —CO2—, —CONR7—, —OC(O)NR7—, —SO2—, —SO2NR7—, —NR7SO2—, —NR7SO2NR7—, —C(O)C(O)—, or —C(O)C(R7)2C(O)—, and each occurrence of R7 is independently hydrogen, an optionally substituted group selected from aliphatic, heteroaliphatic, aryl or heteroaryl, or two occurrences of R7 on the same nitrogen atom are taken together with the nitrogen atom to form an optionally substituted group selected from a 5-8-membered heterocyclic or 5-8-membered heteroaryl ring
• wherein one or more optional substituents on the unsaturated carbon atom of an aryl or heteroaryl group are independently selected from halogen;
• —Ro;
• —ORo;
• —SRo;
• 1,2-methylenedioxy;
• 1,2-ethylenedioxy;
• phenyl (Ph) optionally substituted with Ro;
• —O(Ph) optionally substituted with Ro;
• —(CH2)1-2(Ph), optionally substituted with Ro;
• —CH═CH(Ph), optionally substituted with Ro;
• —NO2;
• —CN;—N(Ro)2;
• —NRoC(O)Ro;
• —NRoC(S)Ro;
• —NRoC(O)N(Ro)2;
• —NRoC(S)N(Ro)2;
• —NRoCO2Ro;
• —NRoNRoC(O)Ro;
• —NRoNRoC(O)N(Ro)2;
• —NRoNRoCO2Ro;
• —C(O)C(O)Ro;
• —C(O)CH2C(O)Ro;
• —CO2Ro;
• —C(O)Ro;
• —C(S)Ro;
• —C(O)N(Ro)2;
• —C(S)N(Ro)2;
• —OC(O)N(Ro)2;
• —OC(O)Ro;
• —C(O)N(ORo)Ro;
• —C(NORo)Ro;
• —S(O)2Ro;
• —S(O)3Ro;
• —SO2N(Ro)2;
• —S(O)Ro;
• —NRoSO2N(Ro)2;
• —NRoSO2Ro;
• —N(ORo)Ro;
• —C(═NH)—N(Ro)2;
• or —(CH2)0-2NHC(O)Ro, wherein each independent occurrence of Ro is selected from hydrogen, optionally substituted C1-6 aliphatic, an unsubstituted 5-6 membered heteroaryl or heterocyclic ring, phenyl, —O(Ph), or —CH2(Ph), or, two independent occurrences of Ro, on the same substituent or different substituents, taken together with the atom(s) to which each Ro group is bound, optionally form a 5-8-membered heterocyclyl, aryl, or heteroaryl ring or a 3-8-membered cycloalkyl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein one or more optional substituents on the aliphatic group of Ro are selected from NH2, NH(C1-4aliphatic), N(C1-4aliphatic)2, halogen, C1-4aliphatic, OH, O(C1-4aliphatic), NO2, CN, CO2H, CO2(C1-4aliphatic), O(haloC1-4 aliphatic), or haloC1-4aliphatic, wherein each of the foregoing C1-4aliphatic groups of Ro is unsubstituted;
• wherein one or more optional substituents on an aliphatic or heteroaliphatic group, or on a non-aromatic heterocyclic ring are independently selected from halogen;
• —Ro;
• —ORo;
• —SRo;
• 1,2-methylenedioxy;
• 1,2-ethylenedioxy;
• phenyl (Ph) optionally substituted with Ro;
• —O(Ph) optionally substituted with Ro;
• —CH═CH(Ph), optionally substituted with Ro;
• —NO2;
• —CN;
• —N(Ro)2;
• —NRoC(O)Ro;
• —NRoC(S)Ro;
• —NRoC(O)N(Ro)2;
• —NRoC(S)N(Ro)2;
• —NRoCO2Ro;
• —NRoNRoC(O)Ro;
• —NRoNRoC(O)N(Ro)2;
• —NRoNRoCO2Ro;
• —C(O)C(O)Ro;
• —C(O)CH2C(O)Ro;
• —CO2Ro;
• —C(O)Ro;
• —C(S)Ro;
• —C(O)N(Ro)2;—C(S)N(Ro)2;
• —OC(O)N(Ro)2;
• —OC(O)Ro;
• —C(O)N(ORo)Ro;
• —C(NORo)Ro;
• —S(O)2Ro;
• —S(O)3Ro;
• —SO2N(Ro)2;
• —S(O)Ro;
• —NRoSO2N(Ro)2;
• —NRoSO2Ro;
• —N(ORo)Ro;
• —C(═NH)—N(Ro)2;
• or —(CH2)0-2NHC(O)Ro, ═O, ═S, ═NNHR*, ═NN(R*)2, ═NNHC(O)R*, ═NNHCO2(alkyl), ═NNHSO2(alkyl), or ═NR*, where each R* is independently selected from hydrogen or an optionally substituted C1-6 aliphatic, wherein one or more optional substituents on the aliphatic group of R* are selected from NH2, NH(C1-4 aliphatic), N(C1-4 aliphatic)2, halogen, C1-4 aliphatic, OH, O(C1-4 aliphatic), NO2, CN, CO2H, CO2(C1-4 aliphatic), O(halo C1-4 aliphatic), or halo(C1-4 aliphatic), wherein each of the foregoing C1-4aliphatic groups of R* is unsubstituted;
• wherein one or more optional substituents on a nitrogen of a non-aromatic heterocyclic ring are independently selected from —R+, —N(R+)2, —C(O)R+, —CO2R+, —C(O)C(O)R+, —C(O)CH2C(O)R+, —SO2R+, —SO2N(R+)2, —C(═S)N(R+1)2, —C(═NH)—N(R+)2, or —NR+SO2R+;
• wherein R+is hydrogen, an optionally substituted C1-6 aliphatic, optionally substituted phenyl, optionally substituted —O(Ph), optionally substituted —CH2(Ph), optionally substituted —(CH2)1-2(Ph);
• optionally substituted —CH═CH(Ph);
• or an unsubstituted 5-6 membered heteroaryl or heterocyclic ring having one to four heteroatoms independently selected from oxygen, nitrogen, or sulfur, or, two independent occurrences of R+, on the same substituent or different substituents, taken together with the atom(s) to which each R+ group is bound, optionally form a 5-8-membered heterocyclyl, aryl, or heteroaryl ring or a 3-8-membered cycloalkyl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein one or more optional substituents on the aliphatic group or the phenyl ring of R+ are selected from NH2, NH(C1-4 aliphatic), N(C1-4 aliphatic)2, halogen, C1-4 aliphatic, OH, O(C1-4 aliphatic), NO2, CN, CO2H, CO2(C1-4 aliphatic), O(halo C1-4 aliphatic), or halo(C1-4 aliphatic), wherein each of the foregoing C1-4aliphatic groups of R+ is unsubstituted.