Substituted cyclic compounds, preparation method and pharmaceutical compositions containing them

A compound of formula (I):

• R-A-R′ (I)
• wherein
• ♦ A represents
• a ring system of formula (II):
• 51
• wherein
• X represents oxygen, sulphur or nitrogen or C(H)q (wherein q is 0, 1 or 2) or NR0 (wherein R0 represents hydrogen, linear or branched (C1-C6)alkyl, aryl, aryl-(C1-C6)alkyl in which the alkyl moiety is linear or branched) or SO2Ph,
• Y represents nitrogen or C(H)q (wherein q is 0, 1 or 2),
• Z represents nitrogen or C(H)q (wherein q is 0, 1 or 2), but X, Y and Z cannot represent three hetero atoms simultaneously,
• B represents a benzene or pyridine nucleus,
• the symbol .... means that the bonds may be single or double, it being understood that the valency of the atoms is respected,
• wherein R substitutes the ring B and R′ substitutes the ring containing X, Y and Z, or R and R′ substitute the ring B,
• a ring system of formula (III)
• 52
• wherein
• X′ represents oxygen or sulphur or C(H)q (wherein q is 0, 1 or 2),
• Y′ represents C(H)q (wherein q is 0, 1 or 2) or NR0 wherein R0 is as defined hereinbefore,
• Z′ represents C(H)q (wherein q is 0, 1 or 2) or NR0 wherein R0 is as defined hereinbefore,
• T′ represents oxygen or sulphur or C(H)q (wherein q is 0, 1 or 2),
• it being understood that, when Y′ or Z′ represents a hetero atom, the other three variables ((X′, Z′, T′) and (X′, Y′, T′), respectively) cannot represent a hetero atom,
• the symbol .... is as defined hereinbefore,
• B′ represents:
• benzene,
• naphthalene when X′, Y′, Z′ and T′ do not simultaneously represent C(H)q (wherein q is 0, 1 or 2),
• or pyridine when X′ and T′ simultaneously represent C(H)q (wherein q is 0, 1 or 2),
• wherein R substitutes the ring B′ and R′ substitutes the ring containing X′, Y′, Z′ and T′, or R and R′ substitute the ring B′,
• a ring system of formula (IV):
• 53
• representing the ring systems (IVa-d)
• 54
• wherein
• n is an integer such that 0≦n≦3,
• W represents oxygen, sulphur or nitrogen, or [C(H)q]p (wherein q is 0, 1 or 2, and p is 1 or 2) or NR0 wherein R0 is as defined hereinbefore,
• the symbol .... is as defined hereinbefore,
• wherein R′ substitutes the ring
• 55
• and R substitutes one or other of the two other rings,
• or biphenyl wherein R substitutes one of the benzene rings and R′ substitutes the other, or R and R′ substitute the same benzene ring,
• it being understood that the ring systems of formulae (II), (III) and (IV) and the biphenyl group may be unsubstituted or substituted (in addition to the substituents R and R′) by from 1 to 6 radicals, which may be the same or different, selected from Ra, ORa, CORa, COORa, OCORa, OSO2CF3 and halogen,
• wherein Ra represents hydrogen, unsubstituted or substituted linear or branched (C1-C6)alkyl, unsubstituted or substituted linear or branched (C2-C6)alkenyl, unsubstituted or substituted linear or branched (C2-C6)alkynyl, linear or branched (C1-C6)polyhaloalkyl, unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C3-C8)cycloalkyl-(C1-C6)alkyl in which the alkyl group is linear or branched, unsubstituted or substituted (C3-C8)cycloalkenyl, unsubstituted or substituted (C3-C8)cycloalkenyl-(C1-C6)alkyl in which the alkyl group is linear or branched, aryl, aryl-(C1-C6)alkyl in which the alkyl moiety is linear or branched, aryl-(C1-C6)alkenyl in which the alkenyl moiety is linear or branched, heteroaryl, heteroaryl-(C1-C6)alkyl in which the alkyl moiety is linear or branched, heteroaryl-(C1-C6)alkenyl in which the alkenyl moiety is linear or branched, unsubstituted or substituted linear or branched (C1-C6)heterocycloalkyl, unsubstituted or substituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkyl-(C1-C6)alkyl in which the alkyl moiety is linear or branched, or substituted or unsubstituted heterocycloalkenyl-(C1-C6)alkyl in which the alkyl moiety is linear or branched,
• ♦ R represents:
• a group of formula (V):
• 56
• wherein
• Q represents sulphur or oxygen,
• R1 represents NR′aR″a or OR1a (wherein R′a and R″a, which may be the same or different, may take any of the values of Ra and may also form, together with the nitrogen atom carrying them, a 5- to 10-membered cyclic group which may contain, in addition to the nitrogen atom by which it is linked, from one to three hetero atoms selected from oxygen, sulphur and nitrogen,
• and R1a may take any of the values of Ra except for the hydrogen atom),
• a group of formula (VI):
• 57
• wherein
• R2 represents Ra as defined hereinbefore,
• R3 represents COR′a, CSR′a, CONR′aR″a, CSNR′aR″a, COOR′a, CSOR′a or S(O)vR′a (wherein R′a and R″a, which may be the same or different, are as defined hereinbefore and may also form, together with the nitrogen atom carrying them, a cyclic group as defined hereinbefore, and v is 1 or 2),
• a group of formula (VII):
• 58
• wherein v is as defined hereinbefore and R4 represents NR′aR″a, NRaCOR′a, NRaCSR′a, NRaCONR′aR″a, NRaCSNR′aR″a or NRaCOOR′a, wherein Ra, R′a and R″a are as defined hereinbefore,
• or, when A represents a ring system of formula (II) or (III) or biphenyl, forms, together with two adjacent carbon atoms of the cyclic structure A carrying it,
• a ring of formula (VIII):
• 59
• the ring formed containing from 5 to 7 atoms and it being possible for the said ring to contain from 1 to 3 hetero atoms selected from nitrogen, sulphur and oxygen, and one or more unsaturations, and being optionally substituted by one or more radicals, which may be the same or different, selected from Ra, ORa, CORa, COORa, OCORa, NR′aR″a, NRaCOR′a CONR′aR″a, cyano, oxo, SRa, S(O)Ra, SO2Ra, CSRa, NRaCSR′a, CSNR′aR″a, NRaCONR′aR″a NRaCSNR′aR″a and halogen,
• wherein Ra, R′a and R″a, which may be the same or different, are as defined hereinbefore and R′a and R″a may also form, together with the nitrogen atom carrying them, a cyclic group as defined hereinbefore,
• ♦ and R′ represents a group of formula (IX):
• -G-R5 (IX)
• wherein
• G represents an alkylene chain —(CH2)t— (wherein t is an integer such that 0≦t≦4 when A represents a tricyclic structure and such that 1≦t≦4 when A represents a bicyclic structure), optionally substituted by one or more radicals, which may be the same or different, selected from Ra, ORa, COORa, CORa (in which Ra is as defined hereinbefore) or halogen,
• and R5 represents
• 60
• wherein Q, Ra, R′a and R″a (which may be the same or different) are as defined hereinbefore, it being possible for R′a and R″a to form, together with the nitrogen atom carrying them, a cyclic group as defined hereinbefore,
• it being understood that:
• “heterocycloalkyl” is taken to mean any saturated mono- or poly-cyclic group containing from 5 to 10 atoms containing from 1 to 3 hetero atoms selected from nitrogen, oxygen and sulphur,
• “heterocycloalkenyl” is taken to mean any non-aromatic mono- or poly-cyclic group containing one or more unsaturations, containing from 5 to 10 atoms and which may contain from 1 to 3 hetero atoms selected from nitrogen, oxygen and sulphur,
• the term “substituted” used in respect of the expressions “alkyl”, “alkenyl” and “alkynyl” indicates that the groups in question are substituted by one or more radicals, which may be the same or different, selected from hydroxy, linear or branched (C1-C6)alkoxy, linear or branched (C1-C6)alkyl, linear or branched (C1-C6)polyhaloalkyl, amino and halogen,
• the term “substituted” used in respect of the expressions “cycloalkyl”, “cycloalkylalkyl”, “cycloalkenyl”, “cycloalkenylalkyl”, “heterocycloalkyl”, “heterocycloalkenyl”, “hetero-cycloalkylalkyl” and “heterocycloalkenylalkyl” indicates that the cyclic moiety of the groups in question is substituted by one or more radicals, which may be the same or different, selected from hydroxy, linear or branched (C1-C6)alkoxy, linear or branched (C1-C6)alkyl, linear or branched (C1-C6)polyhaloalkyl, amino and halogen,
• “aryl” is taken to mean any aromatic, mono- or poly-cyclic group containing from 6 to 22 carbon atoms, and also the biphenyl group,
• “heteroaryl” is taken to mean any aromatic mono- or poly-cyclic group containing from 5 to 10 atoms containing from 1 to 3 hetero atoms selected from nitrogen, oxygen and sulphur,
• it being possible for the “aryl” and “heteroaryl” groups to be substituted by one or more radicals, which may be the same or different, selected from hydroxy, linear or branched (C1-C6)alkoxy, linear or branched (C1-C6)alkyl, linear or branched (C1-C6)polyhaloalkyl, cyano, carboxy, nitro, amino and halogen,
• 10 it being understood that:
• when A represents indole, there cannot be any substituents in the 2-position,
• when A represents indole and R represents —NHCOR′a, —NHCOOR′a or NHCONR′aR″a, then G-R5 cannot represent —(CH2)2—NHCORb wherein Rb represents (C1-C4)alkyl or CF3,
• when A represents benzofuran or benzothiophene, there cannot be any COPh (wherein Ph is substituted or unsubstituted) in the 2-position,
• when A represents benzofuran or benzothiophene, R cannot represent —NRaCORc, —NHSO2Rc, —NHCOCH2Rc, or NHCONHRc, wherein Rc represents heterocyclic or aryl,
• when A represents tetrahydronaphthalene, R5 cannot represent CONR′aR″a,
• when A represents hydrocarbon ring system and R5 represents NHCOR′a, then R cannot represent COOR′a,
• the compound of formula (I) cannot represent:
• N-{8-[(acetylamino)methyl]-2-naphthyl}-2-methylpropanamide,
• N-(2-{5-[(4-ethoxyanilino)sulphonyl]-1H-indol-3-yl}ethyl)acetamide,
• 8-[(acetylamino)methyl]-N-isopropyl-2-naphthamide,
• its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base.