Fredericamycin derivatives

A compound according to the general formula Ia or Ib:

• wherein in each,
• R1 is H, C1-C6 alkyl, cycloalkyl, or C1-C4 alkylcycloalkyl;
• R2 is C1-C14 alkyl, C2-C14 alkenyl, 1,3-butadienyl, 1-butane, C1-C4 alkylaryl, heteroaryl, C1-C4 alkylheteroaryl, cycloalkyl, C1-C4 alkyl-cycloalkyl, heterocycloalkyl, C1-C4 alkylheterocycloalkyl, CmH2m+o−p Y″p, CH2NHCOR21, CH2NHCSR21, CH2S(O)nR21, with n=0, 1, 2, CH2SCOR21, CH2OSO2—R21, CHO, CH═NOH, CH(OH)R21, —CH═NOR21, —CH═NOCOR21, —CH═NOCH2CONR21R22, —CH═NOCH(CH3)CONR21R22, —CH═NOC(CH3)2CONR21R22, —CH═N—NHCO—R23, —CH═N—NHCO—CH2NHCOR21, —CH═N—O—CH2NHCOR21, —CH═N—NHCS—R23, —CH═CR24R25 (trans or cis), COOH, COOR21, CONR21R22, —CH═NR21, —CH═N—NR21R22,
• —CH═N—NHSO2
• aryl, or —CH═N—NHSO2 heteroaryl,
• wherein m is 1 to 6, o is 1, p is 1 to 2m+o;
• m is 2 to 6, o is −1, p is 1 to 2m+o;
• or
• m is 4 to 6, o is −2, p is 1 to 2m+o;
• Y″ is independently from each other selected from the group consisting of halogen, OH, OR21, NH2, NHR21, NR21R22, SH and SR21;
• and
• wherein X′ is NR215, O, or S;
• and R211, R212, R213, R214, R215 are independently from each other H or C1-C6 alkyl;
• R21, R22 are independently from each other C1-C14 alkyl, C1-C14 alkanoyl, C1-C6 alkylhydroxy, C1-C6 alkylamino, C1-C6alkylamino-C1-C6 alkyl, C1-C6 alkylamino-di-C1-C6 alkyl, cycloalkyl, C1-C4 alkylcycloalkyl, heterocycloalkyl, C1-C4 alkylheterocycloalkyl, aryl, aryloyl, C1-C4 alkylaryl, heteroaryl, heteroaryloyl, C1-C4 alkylheteroaryl, cycloalkanoyl, C1-C4 alkanoylcycloalkyl, heterocycloalkanoyl, C1-C4 alkanoylheterocycloalkyl, C1-C4 alkanoylaryl, C1-C4 alkanoylheteroaryl, or mono- and di-sugars linked through a C atom which would carry an OH group in the sugar, wherein the sugars are independently from each other selected from the group consisting of glucuronic acid and its stereo isomers at all optical atoms, aldopentoses, and aldohexoses, including their desoxy compounds;
• R23 independently of R21, is R21, a CH2-pyridinium salt, or a CH2-tri-C1-C6 alkylammonium salt;
• R24 independently of R21, is R21, H, CN, COCH3, COOH, COOR21, CONR21R22, NH2, or NHCOR21;
• R25 independently of R21, is R21, H, CN, COCH3, COOH, COOR21, CONR21R22, NH2, or NHCOR21;
• or
• R24, R25 together are C4-C8 cycloalkyl;
• R3 is C2-C14 alkyl, C2-C14 alkenyl, C2-C14 alkinyl, aryl, C1-C4 alkylaryl, heteroaryl, C1-C4 alkylheteroaryl, wherein the aryls or heteroaryls may be substituted with another aryl, C1-C4 alkylaryl, O-aryl, C1-C4 alkyl-O-aryl, heteroaryl, C1-C4 alkylheteroaryl, O-heteroaryl or C1-C4 alkyl-O-heteroaryl,
• cycloalkyl, C1-C4 alkylcycloalkyl, heterocycloalkyl, C1-C4 alkylheterocycloalkyl, CmH2m+o−pY′p, CH2NHCOR31, CH2NHCSR31, CH2S(O)nR31, CH2SCOR31, CH2OSO2—R31, CHO, CH═NOH, CH(OH)R31, —CH═NOR31, —CH═NOCOR31, —CH═NOCH2CONR31R32, —CH═NOCH(CH3)CONR31R32, —CH═NOC(CH3)2CONR31R32, —CH═N—NHCO—R33, —CH═N—NHCO—CH2NHCOR31, —CH═N—O—CH2NHCOR31, —CH═N—NHCS—R33, —CH═CR34R35 (trans or cis), COOH, COOR31, CONR31R32, —CH═NR31, —CH═N—NR31R32,
• (with X′ ═NR315, O, S, and R311, R312, R313, R314, R315 being independently from each other H or C1-C6 alkyl), —CH═N—NHSO2 aryl, or —CH═N—NHSO2-heteroaryl,
• wherein m is 2-6, o is 1 or −1, and p is 1 to 2m+o;
• or
• m is 4-6, o is −3 and p is 1 to 2m+o;
• and
• Y′ is independently from each other selected from the group consisting of halogen, OH, OR31, NH2, NHR31, NR31R32, SH, and SR31;
• and
• wherein n is 0, 1 or 2;
• R31, R32 mean independently from each other C1-C14 alkyl, C1-C14 alkanoyl, C1-C6 alkylhydroxy, C1-C6 alkylamino, C1-C6 alkylamino-C1-C6 alkyl, C1-C6 alkylamino-di-C1-C6 alkyl, cycloalkyl, C1-C4 alkylcycloalkyl, heterocycloalkyl, C1-C4 alkylheterocycloalkyl, aryl, aryloyl, C1-C4 alkylaryl, heteroaryl, heteroaryloyl, C1-C4 alkylheteroaryl, cycloalkanoyl, C1-C4 alkanoylcycloalkyl, heterocycloalkanoyl, C1-C4 alkanoylheterocycloalkyl, C1-C4 alkanoylaryl, C1-C4 alkanoylheteroaryl, alkanoylaryl, C1-C4 alkanoylheteroaryl, or mono- and di-sugars linked through a C atom which would carry an OH group in the sugar, wherein the sugars are independently from each other selected from the group consisting of glucuronic acid and its stereo isomers at all optical atoms, aldopentoses, and aldohexoses, including their desoxy compounds;
• R33 independently of R31, is R31, a CH2-pyridinium salt, or a CH2-tri-C1-C6 alkylammonium salt;
• R34 independently of R21, is R31, H, CN, COCH3, COOH, COOR21, CONR31R32, NH2, or NHCOR31;
• or
• R35 independently of R31, is R31, H, CN, COCH3, COOH, COOR31, CONR31R32, NH2, or NHCOR31;
• R34, R35 together are C4-C8 cycloalkyl;
• R5 is H, C1-C6 alkyl, cycloalkyl, C1-C4 alkylcycloalkyl, heterocycloalkyl, C1-C4 alkylheterocycloalkyl, aryl, C1-C4 alkylaryl, heteroaryl, or C1-C4 alkylheteroaryl;
• R4, R6, R7 independently from each other are H, C1-C6 alkyl, or CO—R41;
• R41 independently of R21, is R21;
• X is O, S, NH, or N—R8, wherein R8 independently from R5 is R5, or R5 and R8, together with the N, form a ring with 4, 5, 6, 7, or 8 members, which may optionally contain still another heteroatom selected from the group consisting of N, O, and S;
• or X—R5 may together be H;
• Y is O, S, or NR9, wherein R9 is H or C1-C6 alkyl;
• or a stereoisomer, tautomer or physically tolerable salt thereof.