发明名称 Antimicrobials
摘要 The present invention relates to novel phenyl oxazolidinone compounds of formula I, their pharmaceutically acceptable analogs, tautomeric forms, stereoisomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The invention also relates to the processes for the synthesis of novel compounds of formula I or their pharmaceutically acceptable analogs, tautomeric forms, stereoisomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The present invention also provides pharmaceutical compositions comprising novel compounds of formula I and methods of using them. The compounds of the present invention are useful as antimicrobial agents, effective against a number of aerobic and/or anaerobic Gram positive and/or Gram negative pathogens such as multi drug resistant species of Staphylococcus, Streptococcus, Enterococcus, Bacterioides, Clostridia, H. influenza, Moraxella, acid-fast organisms such as Mycobacterium tuberculosis as well as Linezolid resistant species of Staphylococcus and Enterococcus. ;
申请公布号 US8841306(B2) 申请公布日期 2014.09.23
申请号 US200913130440 申请日期 2009.11.18
申请人 Panacea Biotec Ltd. 发明人 Jain Rajesh;Trehan Sanjay;Das Jagattaran;Kanwar Sandeep;Magadi Sitaram Kumar;Sharma Sudhir Kumar
分类号 A61K31/33;C07D413/14;C07D417/12;C07D487/04;C07D413/12;C07D263/20 主分类号 A61K31/33
代理机构 Lowe Hauptman & Ham, LLP 代理人 Lowe Hauptman & Ham, LLP
主权项 1. A compound of Formula I, its tautomeric forms, stereoisomers polymorphs, salts or solvates thereof, wherein: ‘--- ’ is independently a single bond or absent; when ‘--- ’ is a single bond, ‘A’ represents carbon atom and when ‘--- ’ is absent, ‘A’ is CH or N; Y and Y′ are same or different and independently represent O or S; R1 and R2 are same or different and independently represent hydrogen, halogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C2-12 haloalkenyl, C2-12 haloalkynyl, C1-C12alkoxy, C1-12 haloalkoxy, C1-C6alkoxyC1-C6alkyl, C1-C6alkoxyC1-C6alkoxyC1C3alkyl, C3-20cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)n-cycloalkyl, —(CH2)n-heterocyclyl, —(CH2)n-aryl, —CH2)n-heteroaryl, —(CH2)nC(═Y)NR5R6, —(CH2)nC(═Y)OR5, —(CH2)nNR5R6, —(CH2)nOC(═Y)R5, —(CH2)nOC(═Y)OR5, —(CH2)nOC(═Y)NR5R6, —(CH2)nN(R5)C(═Y)OR6,—(CH2)nN(R5)C(═Y)NR5R6, —(CH2)nNR5C(═Y)R6, —(CH2)nC(═Y)R5, —(CH2)nYR5 wherein each methylene group may be substituted by one or more halogen atoms), —C(═Y)NR5R6, —OC(═Y)R5, —OC(═Y)NR5R6, —C(═Y)OR5, —OR5, —OC(═Y)OR5, —SR5, —NO2, —NR5R6, —N(R5)C(═Y)R6, —N(R5)—C(═Y)OR6, or —N(R5)C(═Y)NR5R6, each of which may be optionally substituted at any available position by one or more substituents Ra ; or R1 and R2 can together with the carbon atom to which they are attached form a 3 to 10 membered monocyclic ring, partially unsaturated or saturated, which may contain from one to three heteroatoms independently selected from O, S or N; the ring thus formed may be fused with one or two rings independently selected from the group comprising an aryl ring, a cycloalkyl ring, a heterocyclyl ring or monocyclic heteroaryl ring; the ring thus formed can be optionally substituted at any available position by one or more substituents Ra; R3 represents hydrogen, C1-12 alkyl, C2-12alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C2-12 haloalkenyl, C2-12 haloalkynyl, C1-C6alkoxyC1-C6alkyl, C1-C6alkoxyC1-C6alkoxyC1-C3alkyl, C3-20cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)n-cycloalkyl, —(CH2)n-heterocyclyl, —(CH2)n-aryl, —(CH2)n-heteroaryl, —(CH2)nYR5, —(CH2)nC(═Y)R5, —(CH2)nNR5R6, —(CH2)nC(═Y)NR5R6, —(CH2)nC(═Y)OR5, —(CH2)nOC(═Y)R5, —(CH2)nOC(═Y)OR5, —(CH2)nNR5C(═Y)R6, —(CH2)nN(R5)C(═Y)OR6, —(CH2)nN(R5)C(═Y)NR5R6, —(CH2)nOC(═Y)NR5R6, or —(CH2)nN(R5)C(═Y)NR5R6, (wherein each methylene group may be substituted by one or more halogen atoms), each of which may be optionally substituted at any available position by one or more substituents Ra; R4 represents aryl, heteroaryl, or —C(═Y)R5, each of which may be optionally substituted at any available position by one or more substituents Ra; with the proviso that when m is equal to 2 or 3, then R4 cannot be phenyl substituted with substituents selected from —OH, —OC1-4alkyl, —NH2, aminoacyl, —CH2—NH2 and aminoacylalkyl; Z represents C1-12alkyl, C2-12alkenyl, C2-12 alkynyl, C2-12 haloalkenyl, C2-12 haloalkynyl, C1-12 haloalkoxy, C1-C6alkoxyC1-C6alkoxyC1-C3alkyl, —C3-20cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)n-cycloalkyl, —(CH2)n-heterocyclyl, —(CH2)n-aryl, —CH2)n-heteroaryl, —(CH2)n—NCS, —C(═Y)R5, —C(═Y)OR6, —C(═Y)NR5R6, —OC(═Y)OR5, —(CH2)nOP(═O)R5R6, —(CH2)nNHP(═O)R5R6, —(CH2)nOC(═Y)OR5, —(CH2)nC(═Y)R5, —(CH2)nC(═Y)NR5R6, or —(CH2)nC(═Y)OR5, each of which may be optionally substituted at any available position by one or more substituents Ra; T, U, V and W are same or different and independently represent hydrogen or halogen; R5and R6 are same or different and are independently selected from hydrogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C2-12 haloalkenyl, C2-12 haloalkynyl, C3-8 cycloalkyl, heterocyclyl, aryl, heteroaryl, aryloxy, —(CH2)n-cycloalkyl, —(CH2)n-heterocyclyl, —(CH2)n-aryl, —(CH2)n-heteroaryl, each of which may be optionally substituted at any available position with halogen, hydroxyl, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 alkoxy, C1-12 alkylcarbonyl, C1-12 alkoxycarbonyl, C3-8 cycloalkyl, C1-12 haloalkyl, C1-12 haloalkoxy, C2-12 haloalkenyl, aryl, heterocyclyl, heteroaryl, —(CH2)n-aryl, —(CH2)n-heterocyclyl, —(CH2)n-heteroaryl, —(CH2)n-cycloalkyl, —CN, —OR7, —NO2, —NR7R8, —N(R7)C(═Y)R8, —N(R7)C(═Y)OR8, —N(R7)C(═Y)NR7R8, —C(═Y)R7, —C(═Y)NR7R8, —OC(═Y)R7, —OC(═Y)NR7R8, —C(═Y)OR7, —OC(═Y)OR7, —SR7, —S(O)dR7, —SO2NR7R8, —NR7SO2R8, —OP(═O)R7R8, —NHP(═O)R7R8, or —P(═O)R7R8; or R5 and R6 may be joined together along with the heteroatom to which they are joined to form a heterocyclic or heteroaryl ring which may additionally contain from one to three heteroatoms independently selected from O, S or N, the ring formed may optionally be substituted with one or more substituents selected from hydrogen, halogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C2-12 haloalkenyl, C2-12 haloalkynyl, C1-C6alkoxy, C1-12 haloalkoxy, C1-C6alkoxyC1-C6alkyl, C1-C6alkoxyC1-C6alkoxyC1-C3alkyl, C3-8 cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)n-cycloalkyl, —(CH2)n-heterocyclyl, —(CH2)n-aryl, —(CH2)n-heteroaryl, -C1-12 alkylcarbonyl, -C1-12 alkoxycarbonyl, —CN, —CF), —OCF3 —CH2CF3; —CF2CF3, —NO2, —NR7R8, —N(R7)C(═Y)R8, —N(R7)C(═Y)OR8, —N(R7)C(═Y)NR7R8, —C(═Y)R7, —C(═Y)NR7R8, —OC(═Y)R7, —OC(═Y)NR7R8, —OC(═Y)R7, —C(═Y)OR7, —SR7, —S(O)dR7, —SO2NR7R8; —NR7SO2R8, —OP(═O)R7R8, —NHP(═O)R7R8, or —P(O)R7R8; the ring thus formed may further be fused with 3 to 7 membered unsaturated or saturated ring, which may contain from one to three heteroatoms independently selected from O, S or N, the fused ring may optionally be substituted at any available position by one or more substituents Ra; Ra is independently selected from hydrogen, halogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C2-12 haloalkenyl, C2-12 haloalkynyl, oxo, C1 -12 alkoxy, C1-C6alkoxyC1-C6 alkyl, C 1-C6alkoxyC1-C6 alkoxyC1-C3alkyl, C1-12 haloalkoxy, C3-8 cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)n-cycloalkyl, —(CH2)n-heterocyclyl, —(CH2)n-aryl, —(CH2)n-heteroaryl, —C1-12 alkylcarbonyl, —C1-12 alkoxycarbonyl, —CN, —YR7, —(CH2)nYR7, —NO2, ═NOR7, —NR7R8, —N(R7)C(═Y)R8, —N(R7)C(═Y)OR8, —N(R7)C(═Y)NR7R8, —C(═Y)R7, —C(═Y)NR7R8, —OC(═Y)R7, —OC(═Y)NR7R8, —C(═Y)OR7, —OC(═Y)OR7, —SR7, —S(O)dR7, —SO2NR7R8, —OP(═O)R7R8, —NHP(═O)R7R8, —P(O)R7R8, —(CH2)nCN, —YR7, —(CH2)nYR7, —NO2, ═NOR7, —(CH2)nNR7R8, —(CH2)nN(R7)C(═Y)R8, —(CH2)nN(R7)C(═Y)OR8, —(CH2)nN(R7)C(═Y)NR7R8, —(CH2)nC(═Y)R7, —(CH2)nC(═Y)NR7R8, —(CH2)nOC(═Y)R7, —(CH2)nOC(═Y)NR7R8, —(CH2)nC(═Y)OR7, —(CH2)nOC(═Y)OR7, —(CH2)nSR7, —(CH2)nS(O)dR7, —(CH2)nSO2NR7R8, —(CH2)nOP(═O)R7R8, (CH2)nNHP(═O)R7R8, or —(CH2)nP(O)R7R8; each of which may optionally be substituted at any available position by one or more substituents selected from hydrogen, halogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C2-12 haloalkenyl, C2-12 haloalkynyl, oxo, C1-C12 alkoxy, C1-12 haloalkoxy, C1-C6alkoxyC1-C6alkyl, C1-C6alkoxyC1-C6alkoxyC1-C3alkyl, C3-8 cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)n-cycloalkyl, —(CH2)n-heterocyclyl, —(CH2)n-aryl, —(CH2)n-heteroaryl, —C1-12 alkylcarbonyl, —C1-12 alkoxycarbonyl, —CN, —OR9, —(CH2)nOR9, —CF3, —NO2, —NR9R10, —N(R9)C(═Y)R10, —N(R9)C(═Y)OR10, —N(R9)C(═Y)NR9R10, —C(═Y)R9, —C(═Y)NR9R10, —OC(═Y)R9, —OC(═Y)NR9R10, —OC(═Y)OR9, —C(═Y)OR9, —SR9, —S(O)dR9, —SO2NR9R10; —NR9SO2R10, —OP(═O)R9R10, —NHP(═O)R9R10, —P(O)R9R10, —(CH2)nCN, —OR9, —(CH2)nOR9, —CF3, —NO2, —(CH2)nNR9R10, —(CH2)nN(R9)C(═Y)R10, —(CH2)nN(R9)C(═Y)OR10, —(CH2)nN(R9)C(═Y)NR9R10, —(CH2)nC(═Y)R9, —(CH2)nC(═Y)NR9R10, —(CH2)nOC(═Y)R9, —(CH2)nOC(═Y)NR9R10, —(CH2)nOC(═Y)OR9, —(CH2)nC(═Y)OR9, —(CH2)nSR9, —(CH2)nS(O)dR9, —(CH2)nSO2NR9R10; —(CH2)nNR9SO2R10, —(CH2)nOP(═O)R9R10, (CH2)nNHP(═O)R9R10, or —(CH2)nP(O)R9R10; R7 and R8 are independently selected from hydrogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C2-12 haloalkenyl, C3-8 cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)n-cycloalkyl, —(CH2)n-heterocyclyl, —(CH2)n-aryl, or —(CH2)n-heteroaryl, each of which may be optionally substituted with halogen, hydroxyl or C1-6 alkoxy, or R7 and R8 may be joined together along with the heteroatom to which they are attached to form a heterocyclic or heteroaryl ring which may contain from one to three heteroatoms independently selected from O, S or N, each of which may be optionally substituted with halogen, hydroxyl, C1-6 alkyl or C1-6 alkoxy; R9 and R10 are independently selected from hydrogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C1-12 haloalkyl, C2-12 haloalkenyl, C3-8 cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)n-cycloalkyl, —(CH2)n-heterocyclyl, —(CH2)n-aryl, or —(CH2)n-heteroaryl, each of which may be optionally substituted with halogen, hydroxyl or C1-6 alkoxy, or R9 and R10 may be joined together along with the heteroatom to which they are attached to form a heterocyclic or heteroaryl ring which may contain from one to three heteroatoms independently selected from O, S or N, each of which may be optionally substituted with halogen, hydroxyl, C1-6 alkyl or C1-6 alkoxy; m is 1, 2, 3 or 4; m′ is 0, 1, 2, 3 or 4; n is 1, 2, 3 or 4; d is 1 or 2.
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