US 2010/0144726 A1 · NOVEL INDOLIC DERIVATIVES, THEIR PREPARATION PROCESSES AND THEIR USES IN PARTICULAR AS ANTIBACTERIALS

Abstract

The invention relates to the use of at least one compound of the formula (I), in which R and R3 are particularly a hydrogen atom, R1 is particularly a hydrogen atom or a methyl, ethyl or isobutyl mi group, R4, R5, R6 and R7 are independently a hydrogen atony, an alkoxyl group with 1 to 7 carbon atoms or a halogen atom, R2 is a hydrogen atom, an O− group or an OH group, B is an N-GP1 or NRc, group, GP1 being a Boc or Cbz group, and Rc is a hydrogen atom or a methyl or t-butyl group, for preparing a drug for treating conditions associated with bacterial infections, in particular for treating bacterial diseases.

Claims32

Dependent claims

1-24. (canceled)

A method for the treatment of pathologies associated with bacterial infections comprising the administration, to a patient in need thereof, of at least one compound of formula (I) below:

in which:
R represents a group chosen from one of the following groups:
a hydrogen atom;
an alkyl group comprising 1 to 7 carbon atoms, optionally substituted by a halogen, including the 2-chloroethyl group (—CH2CH2Cl);
an alkoxyl group comprising 1 to 7 carbon atoms;
a methylaryl group comprising 7 to 11 carbon atoms;
a —CH2—NRaRb group, Ra and Rb representing independently of each other a hydrogen atom or an alkyl group comprising 1 to 4 carbon atoms;
said —CH2—NRaRb group representing one of the following groups:
—CH2NH2, —CH2—NHMe or —CH2—NMe2;
a —CH2CH2NRaRb group, Ra and Rb being as defined above, said —CH2CH2—NRaRb group representing in particular one of the following groups:
—CH2CH2—NH2, —CH2CH2—NHMe or —CH2CH2—NMe2;
an NRaRb group, Ra and Rb being as defined above;
an —SO2Ar group, Ar representing an aryl group comprising 6 to 10 carbon atoms;
a group chosen from:
Boc, Fmoc, Cbz, Ac, CF3CO, C6H5CO;
a hydroxyl or alkoxyl group ORf, Rf representing an alkyl group comprising 1 to 7 carbon atoms, said alkyl group being able to be optionally substituted by an aryl group comprising 6 to 10 carbon atoms or by an NH2 group, Rf preferably representing a methyl group or a benzyl group;
or
a silylated group Si(Rg)3, the Rg groups being identical or different and representing independently of each other an alkyl group comprising 1 to 6 carbon atoms, R being able to represent for example an Me2t-BuSi, t-BuPh2Si or Si(Et)3 group;
R3 represents a hydrogen atom or a halogen atom chosen among Br, Cl, F or I;
R4, R5, R6 and R7 represent independently of each other a group chosen from one of the following groups:
a hydrogen atom;
an alkyl group comprising 1 to 4 carbon atoms;
a trifluoromethyl group;
a hydroxyl group;
an alkoxyl group comprising 1 to 7 carbon atoms;
a hydroxymethyl (—CH2OH) or alkoxymethyl (—CH2ORf) group, Rf being defined as above;
a trifluoromethoxyl group;
a halogen atom chosen among Br, Cl, F or I;
an amino group NH2;
an N-alkylamino group NHRa, Ra being as defined above;
an N,N-dialkylamino group NRaRb, in particular an N,N-dimethylamino group, Ra and Rb being as defined above;
or
R1 represents a group chosen from one of the following groups:
a hydrogen atom,
an alkyl group comprising 1 to 6 carbon atoms;
a methylaryl group comprising 7 to 11 carbon atoms;
a —(CH2)mNH-GP group, m being equal to 1 or 2, and GP representing a group chosen from the following groups:
Boc, Cbz, another carbamate group including Me3SiCH2CH2OCO (Teoc), an alkyl group comprising 1 to 4 carbon atoms, chosen from the following groups:
a methyl group, a benzyl group, an acyl group comprising 1 to 7 carbon atoms, chosen from the following groups:
an acetyl group, a benzoyl group or a trifluoroacetyl group;
a —(CH2)mNH2 or —(CH2)mNH2.X group, X representing HCl, HCOOH or HOOCCOOH, m being as defined above;
a —(CH2)mN(GP)(GP′) group, m and GP being as defined above, GP′ corresponding to the same definition as GP, and GP and GP′ being identical or different,
an aryl group comprising 6 to 10 carbon atoms, optionally substituted by an NO2 or methoxyl group,
a CH2OH or CH2SH group,
a CH2O-GP or CH2S-GP group, GP representing a group chosen from:
Ac, CF3CO, C6H5CO, CONH2, O- or S-benzyl and CSNH2,
R2 represents a group chosen from one of the following groups:
a hydrogen atom;
an O− group;
an OH group;
a COCH2ONH-GP, COCH2ONH2, or COCH2ONH2Y group, GP representing one of the following groups:
Boc, Fmoc, Ac, Bz or CF3CO and Y representing HCl, CF3COOH, HCOOH or HOOCCOOH;
this oxyamine function being very much used for preparing, after deprotection, oximes which can be highly functionalized;
an acyl group comprising 1 to 10 carbon atoms;
an alkoxyl group ORc, Rc representing an alkyl group comprising 1 to 10 carbon atoms;
an acyloxyl group OCORc, Rc being as defined above;
an ureido group OCONH2;
a thioureido group OCSNH2;
B represents a group chosen from one of the following groups:
a representing a single bond or a double bond;
A representing N or N+;
a representing a single bond when A represents N;
a representing a double bond when A represents N+ and R2 represents O−;
R′, R″ and R′″ representing, independently of each other, a group chosen from one of the following groups:
a hydrogen atom;
an OH group;
an alkoxyl group comprising 1 to 4 carbon atoms;
an NH2 group;
an N-alkylamino NHRa group, Ra being as defined above;
an N,N-dialkylamino NRaRb group, Ra and Rb being as defined above,
the R′ and R″ groups representing preferably together one of the following groups:
o,p-dimethoxyl (2,4-dimethoxyl);
di-m-dimethoxyl (3,5-dimethoxyl);
m,p-dimethoxyl (3,4-dimethoxyl) or OCH2O (methylenedioxyl), R′″ then representing a hydrogen atom;
the R′, R″ and R′″ groups representing preferably together one of the following groups:
3,4,5-trimethoxyl;
3,5-dimethoxy-4-hydroxyl or 3,4,5-trihydroxyl;
it being understood that, preferably, the R′, R″ and R′″ groups do not represent NO2 groups,
RIV representing one of the following groups:
a hydrogen atom,
an alkyl group comprising 1 to 4 carbon atoms;
an aryl group comprising 6 to 10 carbon atoms,
a CH2ORd group, Rd representing a group chosen from:
an alkyl group comprising 1 to 7 carbon atoms,
a methylaryl group comprising 7 to 11 carbon atoms, or
an Si(Re)3 group, the Re groups being identical or different and representing, independently of each other, an alkyl group comprising 1 to 6 carbon atoms;
GP1 representing a Boc or Cbz group;
Rc representing a hydrogen atom or an alkyl group comprising 1 to 4 carbon atoms, in particular a methyl or t-butyl group;
said compounds of formula (I) being able to be in the form of optical isomers, namely in the form of enantiomers and diastereoisomers or mixtures of these different forms, including racemic mixtures, or in the form, optionally, of salts of physiologically acceptable acids including hydrochlorides, formates or oxalates (HOOCCOOH),

86 more elements

Process for the preparation of a compound of formula (I-5-bis) below:

in which:
R5 and R6 represent independently of each other a group chosen from one of the following groups:
a hydrogen atom;
an alkyl group comprising 1 to 4 carbon atoms;
a trifluoromethyl group;
a trifluoromethoxyl group;
a hydroxyl group;
an alkoxyl group comprising 1 to 7 carbon atoms;
a halogen atom, in particular Br, Cl, F or I;
an amino group NH2;
an N-alkylamino group NHRa, Ra being as defined above;
an N,N-dialkylamino group NRaRb, Ra and Rb being as defined above,
R′ represents a group chosen from one of the following groups:
a hydrogen atom;
an OH group;
an alkoxyl group comprising 1 to 4 carbon atoms;
an NH2 group;
an N-alkylamino group NHRa, Ra being as defined above;
an N,N-dialkylamino group NRaRb, Ra and Rb being as defined above,
said process being characterized in that it comprises a stage of oxidation preferably with MnO2 in toluene or with AMCPB in dichloromethane or Javel water in a DCM/water mixture, preferably with MnO2 in toluene, preferably at 100° C., of a compound of formula (I-1-bis) below:
R5, R6 and R′ being as defined above.

18 more elements

Dependencies are inferred from the claim text.

Novel indolic derivatives, their preparation processes and their uses in particular as antibacterials

Life of this patent

Novel indolic derivatives, their preparation processes and their uses in particular as antibacterials

Life of this patent

Abstract

Claims32