Compounds for treatment of inflammation, diabetes and related disorders

A compound, or salt, hydrate or solvate thereof, represented by at least one of the following Formulas I-XIII:

• wherein the stereocenters marked with an asterisk (*) are R- or S-;
• the bond represented by a dashed line plus a solid line is a double bond or a single bond;
• and wherein
• R1, R2, R3, R4, R5, R6 and R7 independently represent a hydrogen atom, or an optionally substituted C1-C20 linear or branched alkyl, chloroalkyl or fluoroalkyl;
• optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C20 aryl, linear or branched alkylaryl, linear or branched alkenylaryl;
• COOR where R independently represents a hydrogen atom, or an optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl, sodium, potassium, calcium, magnesium, ammonium, tromethamine;
• CONR′R″, where R′ and R″ independently represent a hydrogen atom, or an optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl or where NR′R″ represents a cyclic moiety selected from morpholine, piperidine, piperazine;
• optionally substituted C1-C6 amidoalkyl;
• NH2;
• C1-C20 alkylamino, bis(alkylamino), cycloalkylamino or cyclic amino;
• OH;
• optionally substituted C1-C20 alkoxy, optionally substituted C1-C20 alkanoyl;
• optionally substituted C1-C20 acyloxy;
• halo;
• optionally substituted C1-C20 alkylcarboxylamino;
• cyano;
• nitro;
• SO2NR′″R″″ where R′″ and R″″ are independently H, C1-C20 alkyl or aryl;
• SO2R′″ where R′″ is H, C1-C20 alkyl or aryl;
• SO3R′″ where R′″ is H, C1-C20 alkyl or aryl;
• and C4-C8 heterocycles selected from tetrazolyl, imidazolyl, pyrrolyl, pyridyl or indolyl;
• R8 and R9 independently represent a hydrogen atom, or an optionally substituted C1-C20 linear or branched alkyl;
• optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C10 aryl or heteroaryl;
• COOR where R is H, optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl, sodium, potassium, calcium, magnesium, ammonium, or tromethamine;
• CONR′R″, where R′ and R″ are independently H, alkoxy, optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl, optionally substituted C3-C10 cycloalkyl or cycloalkenyl or optionally substituted C6-C10 aryl or heteroaryl, or where NR′R″ represents a cyclic moiety selected from morpholine, piperidine, hydroxypiperidine, imidazole, piperazine, or methylpiperazine;
• NH2;
• C1-C20 alkylamino, bis(alkylamino), cycloalkylamino or cyclic amino;
• OH;
• C1-C20 alkoxy;
• C1-C20 alkanoyl;
• C1-C20 acyloxy;
• halo;
• C1-C20 alkylcarboxylamino;
• cyano;
• nitro;
• SO2NR′″R″″ where R′″ and R″″ are independently H, C1-C20 alkyl or aryl;
• SO2R′″ where R′″ is H, C1-C20 alkyl or aryl;
• SO3R′″ where R′″ is H, C1-C20 alkyl or aryl;
• or tetrazolyl;
• R10 and R11 independently represent a hydrogen atom or an optionally substituted C1-C20 linear or branched alkyl;
• optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C10 aryl or heteroaryl;
• COOR where R represents a hydrogen atom or an optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl, sodium, potassium, calcium, magnesium, ammonium, or tromethamine;
• CONR′R″, where R′ and R″ independently represent a hydrogen atom, optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl or where NR′R″ represents a cyclic moiety selected from morpholine, piperidine, or piperazine;
• NH2;
• C1-C20 alkylamino, bis(alkylamino), cycloalkylamino or cyclic amino;
• OH;
• C1-C20 alkoxy;
• C1-C20 alkanoyl;
• C1-C20 acyloxy;
• halo;
• C1-C20 alkylcarboxylamino;
• cyano;
• nitro;
• SO2NR′″R″″ where R′″ and R″″ independently represent a hydrogen atom, C1-C20 alkyl or aryl;
• SO2R′″ where R′″ represents a hydrogen atom, C1-C20 alkyl or aryl;
• SO3R′″ where R′″ represents a hydrogen atom, C1-C20 alkyl or aryl;
• or tetrazolyl;
• R12, R13, R18, R19 and R20 independently represent a hydrogen atom;
• or an optionally substituted C1-C20 linear or branched alkyl;
• optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C10 aryl or heteroaryl;
• COOR where R represents an optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl, sodium, potassium, calcium, magnesium, ammonium, or tromethamine;
• CONR′R″, where R′ and R″ independently represent a hydrogen atom, optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl or where NR′R″ represents a cyclic moiety selected from morpholine, piperidine and piperazine;
• C1-C20 alkanoyl;
• C1-C20 alkylamido;
• C6-C20 aroyl or heteroaroyl;
• SO2R′″ where R′″ represents a hydrogen atom, C1-C20 alkyl or aryl;
• morpholinocarbonylmethyl;
• piperazinocabonylmethyl;
• or piperadinocabonylmethyl;
• R12 and R13 may be absent, or R12 and R13 together may be an optionally substituted heterocyclic ring selected from morpholine, piperidine, piperazine, and N-methylpiperidine;
• R14 represents a hydrogen atom, or an optionally substituted C1-C20 linear or branched alkyl including chloroalkyl and fluoroalkyl;
• optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C10 aryl or heteroaryl;
• COOR where R represents a hydrogen atom, optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl, sodium, potassium, calcium, magnesium, ammonium, or tromethamine;
• CONR′R″, where R′ and R″ independently represent a hydrogen atom, or an optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl or where NR′R″ represents a cyclic moiety selected from morpholine, piperidine and piperazine;
• cyano;
• and tetrazolyl
• R15, R16 and R17 independently represent a hydrogen atom, or an optionally substituted C1-C20 linear or branched alkyl including chloroalkyl and fluoroalkyl;
• optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C10 aryl or heteroaryl;
• COOR where R represents a hydrogen atom, or an optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl, sodium, potassium, calcium, magnesium, ammonium, and tromethamine;
• CONR′R″, where R′ and R″ independently represent a hydrogen atom, an optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl or where NR′R″ represents a cyclic moiety selected from morpholine, piperidine, and piperazine;
• NH2;
• C1-C20 alkylamino, bis(alkylamino), cycloalkylamino or cyclic amino;
• OH;
• C1-C20 alkoxy;
• C1-C20 alkanoyl;
• C1-C20 acyloxy;
• halo;
• C1-C20 alkylcarboxylamino;
• cyano;
• nitro;
• SO2NR′″R″″ where R′″ and R″″ independently represent a hydrogen atom, C1-C20 alkyl or aryl;
• SO2R′″ where R′″ independently represents a hydrogen atom, C1-C20 alkyl or aryl;
• SO3R′″ where R′″ independently represents a hydrogen atom, C1-C20 alkyl or aryl;
• or tetrazolyl
• X independently represents O;
• N;
• S;
• S═O;
• SO2;
• or NR′″″, where R′″″ independently represents a hydrogen atom or optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl, optionally substituted C1-C20 acyl, optionally substituted C1-C20 acyloxy and optionally substituted C1-C20 alkoxycarbonyl;
• Y independently represents an oxygen atom, sulfur atom or NH radical;
• Z independently represents
• ORa, wherein Ra represents a hydrogen atom, or an optionally substituted C1-C20 linear or branched alkyl, chloroalkyl or fluoroalkyl, optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C10 aryl or heteroaryl;
• optionally substituted C6-C20 aroyl or heteroaroyl;
• optionally substituted C1-C20 alkanoyl;
• or SO2R′″ where R′″ represents a hydrogen atom, C1-C20 alkyl or aryl;
• NRbRc, wherein Rb and Rc independently represent a hydrogen atom, or an optionally substituted C1-C20 linear or branched alkyl, chloroalkyl or fluoroalkyl optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C10 aryl or heteroaryl;
• optionally substituted C3-C10 cycloalkyl or cycloalkenyl;
• COOZ1 where Z1 represents an optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl;
• optionally substituted C6-C20 aroyl or heteroaroyl;
• optionally substituted C1-C20 alkanoyl;
• or SO2R′″ where R′″ represents a hydrogen atom, or an C1-C20 alkyl or aryl;
• or wherein Rb and Rc together may be joined to form a 3-6 membered ring selected from aziridine, morpholine, piperidine or piperazine;
• and
• CRdReRf, wherein Rd, Re and Rf independently represents represent a hydrogen atom, or an optionally substituted C1-C20 linear or branched alkyl, chloroalkyl or fluoroalkyl, optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C10 aryl or heteroaryl;
• optionally substituted C3-C10 cycloalkyl or cycloalkenyl;
• COOR where R represents a hydrogen atom, or an optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl, sodium, potassium, calcium, magnesium, ammonium, or tromethamine;
• NH2;
• C1-C20 alkylamino, bis(alkylamino);
• cycloalkylamino or cyclic amino;
• OH;
• optionally substituted C1-C20 alkoxy, trifluoromethoxy;
• optionally substituted C1-C20 alkanoyl;
• optionally substituted C1-C20 acyloxy;
• optionally substituted C6-C20 aroyl or heteroaroyl;
• halo;
• cyano;
• nitro;
• optionally substituted C1-C20 alkylcarboxylamino;
• SO2NR′″R″″ where R′″ and R″″ independently represent a hydrogen atom, C1-C20 alkyl or aryl;
• SO2R′″ where R′″ independently represents a hydrogen atom, C1-C20 alkyl or aryl;
• or SO3R′″ where R′″ independently represents a hydrogen atom, C1-C20 alkyl or aryl;
• or
• the grouping —C(═Y)Z may represent hydrogen or R12 or may be absent
• Q is selected from the group consisting of
• ORa where Ra independently represents a hydrogen atom, or an optionally substituted C1-C20 linear or branched alkyl, chloroalkyl or fluoroalkyl;
• optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C10 aryl or heteroaryl;
• optionally substituted C6-C20 aroyl or heteroaroyl;
• optionally substituted C1-C20 alkanoyl;
• and SO2R′″ where R′″ independently represents a hydrogen atom, C1-C20 alkyl or aryl;
• and
• NRbRc where Rb and Rc independently represent a hydrogen atom, or an optionally substituted C1-C20 linear or branched alkyl, chloroalkyl or fluoroalkyl;
• optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C10 aryl or heteroaryl;
• optionally substituted C3-C10 cycloalkyl or cycloalkenyl;
• COOZ1 where Z1 represents an optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl or optionally substituted C6-C10 aryl;
• optionally substituted C6-C20 aroyl or heteroaroyl;
• optionally substituted C1-C20 alkanoyl;
• or SO2R′″ where R′″ independently represents a hydrogen atom, or an C1-C20 alkyl or aryl;
• or herein Rb and Rc represent together a 3-6 membered ring such as aziridine, morpholine, piperidine, piperazine and the like;
• and
• SRg, SORg or SO2Rg where Rg represents a hydrogen atom or an optionally substituted C1-C20 linear or branched alkyl, chloroalkyl or fluoroalkyl;
• optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C1-C20 acyl;
• optionally substituted C1-C20 alkoxycarbonyl;
• C2-C20 alkoxy;
• optionally substituted C6-C10 aryl or heteroaryl;
• and optionally substituted C6-C10 aroyl or heteroaroyl;
• Group A represents an optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C20 aryl, linear or branched alkylaryl, linear or branched alkenylaryl;
• optionally substituted heteroaryl selected from pyridine, indole, morpholine, piperidine, tetrazolyl and piperazine;
• CORh where Rh represents an optionally substituted C1-C20 linear or branched alkyl;
• optionally substituted C2-C20 linear or branched alkenyl;
• optionally substituted C6-C20 aryl, linear or branched alkylaryl, linear or branched alkenylaryl;
• optionally substituted heteroaryl selected from pyridine, indole, morpholine, piperidine, piperazine, or tetrazolyl;
• Group B represents a OH, C1-C20 alkoxy;
• SO2Ri where Ri represents a hydrogen atom or linear or branched C1-C20 alkyl.
• Group Het represents a heterocyclic ring selected from pyridyl, indolyl, tetrazolyl, imidazolyl, morphonyl, piperidinyl, piperazinyl or thiophenyl.