Substituted bicyclic derivatives for the treatment of abnormal cell growth

Substituted bicyclic derivatives for the treatment of abnormal cell growth

  • CN 1,437,594 A
  • Filed: 06/14/2001
  • Published: 08/20/2003
  • Est. Priority Date: 06/22/2000
  • Status: Abandoned Application
First Claim
Patent Images

1. the compound of formula 1 Perhaps its pharmaceutically acceptable salt, solvate or prodrug, wherein:

  • M is 0 to 3 integer;

    P is 0 to 4 integer;

    R 1And R 2Be selected from H and C independently of one another 1-C 6Alkyl;

    R 3Be-(CR 1R 2) t(4 to 10 yuan of heterocycles), wherein t is 0 to 5 integer, described heterocyclic group randomly with a phenyl ring or C 5-C 8Cycloalkylfused, above-mentioned R 3Group-(CR 1R 2) t-part randomly comprises a carbon-to-carbon double bond or triple bond, and wherein t is 2 to 5 integer, and above-mentioned R 3Group comprises any optional condensed ring of pointing out above, randomly by 1-5 R 8Group replaces;

    R 4Be-(CR 16R 17) m-C ≡

    C-(CR 16R 17) tR 9,-(CR 16R 17) m-C=C-(CR 16R 17) t-R 9,-(CR 16R 17) m-C ≡

    C-(CR 16R 17) kR 13,-(CR 16R 17) m-C=C-(CR 16R 17) kR 13, perhaps-(CR 16R 17) tR 9, wherein with R 9Tie point be to pass through R 9The carbon atom of group, each k are 1 to 3 integers, and each t is 0 to 5 integer, and each m is 0 to 3 integer;

    Each R 5Be selected from halogen atom independently of one another, hydroxyl ,-NR 1R 2, C 1-C 6Alkyl, trifluoromethyl, C 1-C 6Alkoxyl group, trifluoromethoxy ,-NR 6C (O) R 1,-C (O) NR 6R 7,-SO 2NR 6R 7,-NR 6C (O) NR 7R 1And-NR 6C (O) OR 7Each R 6, R 6aAnd R 7Be independently selected from H, C 1-C 6Alkyl ,-(CR 1R 2) t(C 6-C 10Alkyl) and-(CR 1R 2) t(4 to 10 yuan of heterocycles), wherein t is 0 to 5 integer, 1 or 2 of described heterocyclic group becomes ring carbon atom randomly by oxo (=O) part replacement, and above-mentioned R 6And R 7The alkyl of group, aryl and heterocyclic moiety randomly are independently selected from halogen atom, cyano group, nitro ,-NR 1R 2, trifluoromethyl, trifluoromethoxy, C 1-C 6Alkyl, C 2-C 6Alkenyl, C 2-C 6Alkynyl group, hydroxyl, and C 1-C 61 to 3 substituting group of alkoxyl group replaces;

    Perhaps R 6And R 7, perhaps R 6aAnd R 7, when being connected, can form 4 to 10 yuan of heterocycles together with same nitrogen-atoms, this heterocycle is except being connected with described R 6, R 6aAnd R 7Nitrogen-atoms outside, can comprise 1 to 3 other heteroatom moiety, be selected from N, N (R 1), O, and S, condition is two O atoms, two S atoms or an O directly are not connected each other with a S atom;

    Each R 8Be independently selected from oxo (=O), halogen atom, cyano group, nitro, trifluoromethoxy, trifluoromethyl, azido-, hydroxyl, C 1-C 6Alkoxyl group, C 1-C 10Alkyl, C 2-C 6Alkenyl, C 2-C 6Alkynyl group ,-C (O) R 6,-C (O) OR 6,-OC (O) R 6,-NR 6C (O) R 7,-NR 6SO 2NR 7R 1,-NR 6C (O) NR 1R 7,-NR 6C (O) OR 7,-C (O) NR 6R 7,-NR 6R 7,-NR 6OR 7,-SO 2NR 6R 7,-S (O) j(C 1-C 6Alkyl), wherein j is 0 to 2 integer ,-(CR 1R 2) t(C 6-C 10Aryl) ,-(CR 1R 2) t(4 to 10 yuan of heterocycles) ,-(CR 1R 2) qC (O) (CR 1R 2) t(C 6-C 10Aryl) ,-(CR 1R 2) qC (O) (CR 1R 2) t(4 to 10 yuan of heterocycles) ,-(CR 1R 2) tO (CR 1R 2) q(C 6-C 10Aryl) ,-(CR 1R 2) tO (CR 1R 2) q(4 to 10 yuan of heterocycles) ,-(CR 1R 2) qS (O) j(CR 1R 2) t(C 6-C 10Aryl) and-(CR 1R 2) qS (O) j(CR 1R 2) t(4 to 10 yuan of heterocycles), wherein j is 0,1 or 2, q and t are 0 to 5 integer independently of one another, described R 81 or 2 of the heterocyclic moiety of group becomes ring carbon atom randomly by oxo (=O) part replacement, and above-mentioned R 8The alkyl of group, alkenyl, alkynyl group, aryl and heterocyclic moiety randomly are independently selected from halogen atom, cyano group, nitro, trifluoromethyl, trifluoromethoxy, azido-,-OR 6,-C (O) R 6,-C (O) OR 6,-OC (O) R 6,-NR 6C (O) R 7,-C (O) NR 6R 7,-NR 6R 7,-NR 6OR 7, C 1-C 6Alkyl, C 2-C 6Alkenyl, C 2-C 6Alkynyl group ,-(CR 1R 2) t(C 6-C 10Aryl) and-(CR 1R 2) t(4 to 10 yuan of heterocycles), wherein t is that 1 to 3 substituting group of 0 to 5 integer replaces;

    R 9Right and wrong fragrance monocycle condenses or bridged bicyclic, perhaps volution, and wherein said ring contains 3-12 carbon atom, and wherein 0-3 carbon atom randomly is independently selected from N, O, S (O) jWherein j be 0 to 2 integer and-NR 1-heteroatom moiety displacement, condition is two O atoms, two S (O) jPart, an O atom and a S (O) jPart, a N atom and a S atom, perhaps a N atom directly is not connected in described ring each other with an O atom, and the carbon atom of described ring is randomly by 1 or 2 R 8Group replaces;

    Each R 11Be independently selected from R 8The substituting group that provides in the definition is except R 11Be not oxo (=O);

    R 12Be R 6,-OR 6,-OC (O) R 6,-OC (O) NR 6R 7,-OCO 2R 6,-S (O) jR 6,-S (O) jNR 6R 7,-NR 6R 7,-NR 6C (O) R 7,-NR 6SO 2R 7,-NR 6C (O) NR 6aR 7,-NR 6SO 2NR 6aR 7,-NR 6CO 2R 7, CN ,-C (O) R 6, perhaps halogen atom, wherein j is 0 to 2 integer;

    R 13Be-NR 1R 14Perhaps-OR 14R 14Be H, R 15,-C (O) R 15,-SO 2R 15,-C (O) NR 15R 7,-SO 2N 15R 7, perhaps-CO 2R 15R 15Be R 18,-(CR 1R 2) t(C 6-C 10Aryl) ,-(CR 1R 2) t(4 to 10 yuan of heterocycles), wherein t is 0 to 5 integer, this heterocyclic 1 or 2 one-tenth ring carbon atoms are randomly by oxo (=O) part replacement, above-mentioned R 15The aryl of group and heterocyclic moiety are randomly by 1-3 R 8Substituting group replaces;

    Each R 16And R 17Be independently selected from H, C 1-C 6Alkyl and-CH 2OH, perhaps R 16And R 17Formation-CH together 2CH 2-or-CH 2CH 2CH 2-;

    R 18Be C 1-C 6Alkyl, wherein not with N or O atomic linkage or not with S (O) pBonding, wherein j is that each carbon atom of 0 to 2 integer is randomly by R 12Replace;

    Comprising not with halogen atom, SO or SO 2The CH that group or N, O or S atom connect 3(methyl), CH 2The above-mentioned substituting group of (methylene radical) or CH (methyne) group randomly is selected from hydroxyl, halogen atom, C 1-C 4Alkyl, C 1-C 4Alkoxyl group and-NR 1R 2Group replace.

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