Camptothecin Analogue Compounds, a Process for Their Preparation and Pharmaceutical Compositions Containing Them

A compound selected from those of formula (I):

• wherein:
• Alk represents an alkyl group,
• R1, R2, R3, R4 and R5 are independently selected from a hydrogen atom, a halogen atom, an alkyl group, an alkenyl group, an alkynyl group, a polyhaloalkyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, a hydroxy group, a hydroxyalkyl group, an alkoxy group, an alkoxyalkyl group, a nitro group, a cyano group, an acyloxy group, a —C(O)—R group, and the groups —(CH2)p—NRaRb, —O—C(O)—NRaRb and —Z—Ar, wherein:
• R represents an alkyl group, an alkoxy group or an amino group optionally substituted on the nitrogen atom by one or two alkyl groups;
• p is an integer from 0 to 6;
• Ra and Rb independently represent a hydrogen atom, an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an acyl group, an optionally substituted aryl group or an optionally substituted arylalkyl group, or Ra and Rb together with the nitrogen atom carrying them form a pyrrolyl, piperidyl or piperazinyl group, wherein each of these cyclic groups may be optionally substituted;
• Z represents a bond, an oxygen atom, a sulphur atom or a group selected from —Z′—S(O)—, —S(O)r—Z′— and —Z′—(CRcRd)q—Z″—;
• Ar represents an optionally substituted aryl or an optionally substituted heteroaryl group;
• Z′ and Z″, which are the same or different, represent an oxygen atom, a sulphur atom, a group —NRe— or a bond;
• Rc, Rd and Re which are the same or different, represent a hydrogen atom or an alkyl group;
• q represents an integer from 1 to 6;
• and r represents an integer 1 or 2;
• or two adjacent groups from R2, R3, R4 and R5 together with the carbon atoms carrying them form a group -T-(CRgRh)t-T′-, wherein T and T′, which are the same or different, represent an oxygen atom, a sulphur atom or a group N—Ri;
• Rg and Rh, which are the same or different, represent a hydrogen atom or a halogen atom;
• t is an integer from 1 to 3 inclusive;
• and Ri represents a hydrogen atom, an alkyl group or a benzyl group,
• R80 and R90 independently represent a hydrogen atom, a hydroxy group, an alkyl group or an alkoxy group,
• R81 and R91 independently represent a hydrogen atom, an alkyl group, an alkenyl group or an alkynyl group, or, R81 and R91 together form a bond or an oxirane group, or two geminal groups, R80 and R81, and/or R90 and R91 together form an oxo group or a group —O—(CH2)t1—O—, t1 represents an integer from 1 to 3 inclusive,
• G represents a group *—XH or *—X—C(X′)-Alk′-G′, wherein:
• * represents the point of attachment to the C7 carbon atom;
• X and X′, which are the same or different, represent an oxygen atom, a sulphur atom, an amino group or an alkylamino group;
• Alk′ represents an alkylene, alkenylene or alkynylene chain;
• G′ represents a hydrogen atom or a group NR6R7 wherein:
• i) R6 and R7 represent, each independently of the other, a hydrogen atom, an alkyl group, a cycloalkyl group, an optionally substituted aryl group, an optionally substituted arylalkyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted heteroaryl group or an optionally substituted heteroarylalkyl group,
• ii) or R6 and R7 together with the nitrogen atom carrying them form a 5- to 8-membered monocyclic heterocycloalkyl group
• or a 5- to 11-membered bicyclic heterocycloalkyl group
• wherein:
• Y represents a nitrogen atom, an oxygen atom or a CH2 group and
• R8 represents a hydrogen atom, an alkyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, an optionally substituted aryl group, an optionally substituted arylalkyl group, an optionally substituted heterocycloalkyl group, an optionally substituted heterocycloalkylalkyl group, an optionally substituted heteroaryl group or an optionally substituted heteroarylalkyl group,
• its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base,
• it being understood that at least one of the substituents R1 to R5 represents a group —Z—Ar,
• and it being understood that:
• alkyl means a linear or branched chain of from 1 to 6 carbon atoms,
• alkenyl means a linear or branched chain of from 2 to 6 carbon atoms containing from 1 to 3 double bonds,
• alkynyl means a linear or branched chain of from 2 to 6 carbon atoms containing from 1 to 3 triple bonds,
• alkylene means a linear or branched divalent radical containing from 1 to 6 carbon atoms,
• alkenylene means a linear or branched divalent radical containing from 2 to 6 carbon atoms and from 1 to 3 double bonds,
• alkynylene means a linear or branched divalent radical containing from 2 to 6 carbon atoms and from 1 to 3 triple bonds,
• acyl means a linear or branched alkyl-carbonyl radical containing from 1 to 6 carbon atoms,
• alkoxy means an alkyl-oxy radical, the alkyl group of which is linear or branched and contains from 1 to 6 carbon atoms,
• acyloxy means an acyl-oxy radical, the acyl group of which is a linear or branched alkylcarbonyl radical,
• aryloxyalkyl means an aryl-oxy-alkyl group, the alkyl group of which is linear or branched and contains from 1 to 6 carbon atoms,
• arylalkyl, cycloalkylalkyl, heteroarylalkyl and heterocycloalkylalkyl mean aryl-alkyl, cycloalkyl-alkyl, heteroaryl-alkyl and heterocycloalkyl-alkyl radicals, the alkyl group of which is a linear or branched chain of from 1 to 6 carbon atoms,
• polyhaloalkyl means a linear or branched carbon chain containing from 1 to 3 carbon atoms and from 1 to 7 halogen atoms,
• halogen means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom,
• aryl means a phenyl, naphthyl, indanyl, indenyl, dihydronaphthyl or tetrahydronaphthyl group,
• cycloalkyl means a monocyclic or bicyclic hydrocarbon group containing from 3 to 11 carbon atoms and optionally being unsaturated with 1 or 2 unsaturated bonds,
• heteroaryl means a monocyclic or bicyclic group wherein at least one of the rings is aromatic, containing from 5 to 11 ring members and containing from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulphur,
• heterocycloalkyl means a mono- or bi-cyclic group which is saturated or unsaturated with 1 or 2 unsaturated bonds, containing from 4 to 11 ring members and containing from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulphur,
• the expression “optionally substituted” when referring to aryl or arylalkyl, cycloalkyl or cycloalkylalkyl, heteroaryl or heteroarylalkyl, and heterocycloalkyl or heterocycloalkylalkyl groups means that these respective aryl, cycloalkyl, heteroaryl and heterocycloalkyl groups may be substituted by from 1 to 3 identical or different substituents selected from a halogen atom and the groups alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, hydroxy, mercapto, cyano, nitro, amino optionally substituted by one or two alkyl groups, acyl, formyl, aminocarbonyl optionally substituted on the nitrogen atom by one or two alkyl groups, acylamino optionally substituted on the nitrogen atom by an alkyl group, alkoxycarbonyl, carboxy and sulpho,
• the expression “optionally substituted” when referring to the groups pyrrolyl, piperidyl or piperazinyl means that these groups may be substituted by from 1 to 3 identical or different groups selected from alkyl, alkoxy, aryl, arylalkyl, aryloxy and aryloxyalkyl.