The present invention relates to analogs of squalamine for use in the treatment of bacterial, fungal, viral or parasitic infections in humans or animals, as well as pharmaceutical or veterinary compositions comprising them.
In 1993, squalamine, a natural steroid, predominantly isolated tissues of a small shark Squalus acanthias, has proved to be a very active compound essentially having antiangiogenic activity against cells and viral and anti antibacterial activity.

Chemically, squalamine is an original molecule of amphiphilic character. It thus comprises a central portion apolar (a cholestane-type skeleton) and two pole ends (a polyamine chain and a sulfate group).

Initially, this water-soluble polyaminostérol aroused interest for its antiangiogenic and antimicrobial properties on a variety of gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa), fungi (Candia albicans, Candida tropicalis) and protozoa.

The natural source of squalamine is limited, have been sought like synthetic derivatives aminostéroïdiens squalamine. Have been described including derivatives or analogues comprising a polyamino chain in position 3 or 7 cycles 10, 13 Dimethyl, 17 octane cholestane or cholestene, optionally hydroxylated at the 7 position or respectively 3. In particular, derivatives of formula IIa - IIb - Ile - IId and II- 1 below were described as having a similar antibacterial activity to squalamine vis-à-vis various Gram positive and Gram negative multiresistant.

more particularly it has been suggested the application of these derivatives for curative treatment of pulmonary infections by aerosol route. However, the Applicant has observed that these compounds exhibited a significant cytotoxicity and that the compounds of formula IIc and IId exhibited weak activity against certain gram-negative bacteria such as E. coli.

Are known in particular WO 2011/067501 derivatives antibacterial aminostéroïdiens type polyamino cholestane or cholestene for locally topical application for the rapid mucocutaneous decolonization of Staphylococcus aureus, particularly in the form of ointment or cream.

U.S. Patent 5,856,535 also describes esters aminosterols, some of which exhibit inter alia inhibitory of angiogenesis activities, antiproliferative or antibacterial activities. However, the compounds disclosed therein are different from the compounds according to the present invention at least in that none of the compounds according to the present invention have a R'NH chain according to the general formula of the present invention for which m is equal to 4 as is apparent from the following description.

It has now been discovered similar compounds squalamine, with good antibacterial activity against gram-positive and gram-negative, while advantageously less cytotoxic than squalamine. These compounds have an interesting activity to prevent and / or inhibit and / or treat

bacterial, fungal, viral or parasitic in man or animal. These compounds are also compounds of choice as substitutes for antibiotics. According to a particular embodiment of the invention, it is intended for domestic mammals such as ruminants, horses, pigs, dogs and cats and wildlife. According to one embodiment even more special it is for pets, more specifically to dogs and cats, or rodents, and more specifically for dogs and cats.

The compounds of the invention provide excellent activity against bacteria, while preventing the emergence of resistance, which is a major asset as the problem of the emergence of resistance to conventional antibiotics has become a public health problem. By their mechanism of action, different from that of antibiotics, the compounds of the invention are therefore as excellent substitutes for antibiotics.

According to a particular embodiment of the invention, it is intended for domestic mammals such as ruminants, horses, pigs, dogs and cats and wildlife. According to one embodiment even more special it is for pets, more specifically to dogs and cats, or rodents, and more specifically for dogs and cats.

Thus, in a first aspect, the present invention relates to a compound of formula (I)

O

R'HNT ^ ^ "' R2 ^

in which

R is (Ci-C8) alkyl,

RI and R2 independently represent a hydrogen atom, a SO3H group or a hydroxy group,

R 'is - (CR a R b) NX (CRcRd) m- [Y- (CReRf) o] t-NR9Rio,

Ra, Rb, Rc, Rd, Re and Rf independently represent a hydrogen atom or a (Ci-Cs) alkyl or a (C 6 -Cio) aryl,

X and Y independently represent an -NR 1 group, 1-, -O- or a divalent heterocyclic group comprising at least one nitrogen atom, a 5 or 6-membered,

R9 and RIO independently represent a hydrogen atom or a (Ci-Cs) alkyl group or form together with the nitrogen atom which carries them, a heterocyclic group with 5 or 6 members, optionally substituted by one or two group (s) = 0 or = s,

Rl l represents a hydrogen atom or a (Ci-Cs) alkyl or a group - (CH 2 ) S -NH 2 ,

n, m, o and s independently represent an integer between 1 and 5,

t is 0, 1, 2 or 3,

wherein m is other than 4, and

with the exception of compounds in which t is equal to 1 and m + n + o is equal to 10, and stereoisomers, mixtures of stereoisomers and / or pharmaceutically acceptable salts thereof.

In the context of the present invention:

- The "alkyl" radicals are saturated hydrocarbon radicals, straight or branched chain of 1 to 8 carbon atoms, especially 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms. These include, when linear, methyl, ethyl, propyl, butyl, pentyl, hexyl. These include, when branched, the isopropyl, tert-butyl, 2-methylbutyl, 2-methylpentyl and 1-methylpentyl.

- By "aryl" is meant within the meaning of the present application, an aromatic hydrocarbon system, mono or bicyclic 6 to 10 carbon atoms. Among the aryl radicals, there may be mentioned phenyl or naphthyl, and more particularly the phenyl radical.

- For group "hétérocyclyclique" is meant within the meaning of the present application, a hydrocarbon system mono- or bicyclic saturated, unsaturated or aromatic comprising one or more heteroatoms such as O, N or S. The heterocyclic groups include the heteroaryl or heterocycloalkyl groups.

- "heteroaryl" groups refer to aromatic systems mono or Bicy clique, and having from 5 to 7 members (ring atoms), including 5 to 6 members,

5 comprising one or more heteroatoms selected from nitrogen, oxygen or sulfur.

Among the heteroaryl radicals include imidazolyl, pyrazinyl, thienyl, oxazolyl, pyrrolyl and furazanyl.

- Radicals "heterocycloalkyl" refer to mono- or bicyclic ring systems, saturated 5 to 7 members (ring atoms), including 5 to 6 members,

10 comprising one or more heteroatoms selected from N, O or S. Among the heterocycloalkyls that may especially be mentioned pyrazolidine, piperidine, morpholine and piperazine.

- As used herein, the term "pharmaceutically acceptable" refers to compounds, compositions and / or dosage forms which are, within the scope of a judgment

15 valid medical, suitable for use in contact with the cells of humans and lower animals without undue toxicity, irritation, undue allergic response and the like and are commensurate with a reasonable benefit / risk.

- The term "pharmaceutically acceptable salts" refers to the addition salts of inorganic and organic acids, pharmaceutically acceptable, and

20 addition salts of pharmaceutically acceptable bases of compounds of the present invention. These salts include acid addition salts, that is to say, organic acid salts or mineral of a compound having a basic function such as an amine, or basic addition salts is -to say, alkali or organic salts of a compound having an acidic function such as a carboxylic acid. These salts can be

25 prepared in situ during the final isolation and / or purification of the compounds. In particular, acid addition salts can be prepared by separately reacting the purified compound with an organic or inorganic acid and isolating the salt thus formed. Examples of acid addition salts there are the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate,

30 borate, benzoate, lactate, phosphate, tosylate, citrate, maléate, fumarate, succinate, tartrate, naphthylate, mésylate, glucoheptanate, lactobionate, sulfamates, malonates, salicylates, propionates, méthylènebis-b-hydroxynaphtoates, acide gentisique, iséthionates, di-p-

toluoyltartrates, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonates, cyclohexyl sulfamates and quinateslaurylsulfonate, and the like. (See for example SM Berge et al, "Pharmaceutical Salts," J. Pharm Sci., 66:. P.1-19 (1977)).

- Basic addition salts can also be prepared by reacting 5 separately the purified compound in its acid form with an organic or inorganic base and isolating the salt thus formed. Examples of base addition salts include sodium, potassium, calcium, barium, zinc, magnesium and aluminum. Sodium and potassium salts are preferred. Basic addition salts can in particular be prepared from hydrides or alkali metal hydroxides or alkaline earth 10 which include sodium hydride, sodium hydroxide, potassium hydroxide, calcium hydroxide, aluminum hydroxide, lithium hydroxide, magnesium hydroxide, zinc hydroxide.

Among the compounds of general formula (I), a first subgroup of compounds consists of compounds wherein RI and R2 independently represent a hydrogen 15 atom or a hydroxy group,

Among the compounds of general formula (I), a second subgroup of compounds consists of compounds for which R is a (Ci-C4) alkyl, especially methyl or isopropyl.

Among the compounds of general formula (I), a third subgroup of compounds consists of 20 compounds for which X is -NH-.

Among the compounds of general formula (I), a fourth subgroup of compounds consists of compounds wherein R9 and RIO represent a hydrogen atom.

Among the compounds of general formula (I), a fifth subgroup of compounds consists of 25 compounds for which Ra, Rb, R c , Rd, Re and Rf represents a hydrogen atom.

Among the compounds of general formula (I), a sixth subgroup of compounds consists of compounds for which Y is -NR11- group, with R l denoting a hydrogen atom or a (Ci-C4) alkyl or a group - (CH 2 ) s NH 2 30 wherein s is 1, 2 or 3.

Among the compounds of general formula (I), a seventh subgroup of compounds consists of compounds for which m is equal to 2, 3, 4, or 5, more preferably 2 or 3.

Among the compounds of general formula (I), an eighth subgroup of compounds consists of 5 of the compounds for which n is equal to 2, 3, 4 or 5, more preferably 2 or 3.

Among the compounds of general formula (I), a ninth subgroup of compounds consists of compounds for which o is 2 or 3.

Among the compounds of general formula (I), a tenth subgroup of compounds consists of 10 compounds wherein the group -NHR 'is selected from:

H

According to a particular embodiment of this tenth subgroup of compounds, the group -NHR 'is selected from:

-N NH,

H H

'N' NH0

H

NHL

H

,NH,

-N

H

H

H

,NH„

-N NH "

H

and

The subgroups defined above, taken alone or in combination, are also part of the invention.

5 Accordingly, the present invention relates to a compound as defined above, characterized in that it is defined by at least one of the following subgroups:

- first subgroup of compounds of formula (I) wherein RI and R2 independently represent a hydrogen atom or hydroxy,

10 - second subgroup of compounds of formula (I) wherein R is (Ci-C4) alkyl, especially methyl or isopropyl,

- third subgroup of compounds of formula (I) wherein X is -NH-,

- fourth subgroup of compounds of formula (I) wherein R 9 and R 15 represent a hydrogen atom,

- fifth subgroup of compounds of formula (I) for which Ra, Rb, Rc, Rd, Re and Rf represent a hydrogen atom,

- sixth subgroup of compounds of formula (I) wherein Y is -NR11- group, with R 1 representing a hydrogen atom or a (Ci-C4) alkyl or

20 a - (CH 2 ) s NH 2 wherein s is 1, 2 or 3,

- seventh subgroup of compounds of formula (I) wherein m is

2, 3, 4 or 5, more preferably 2 or 3,

- eighth subgroup of compounds of formula (I) for which n is equal to 2,

3, 4 or 5, more preferably 2 or 3,

- ninth subgroup of compounds of formula (I) wherein o is 2 or 3,

- tenth subgroup of compounds of formula (I) wherein the group NHR 'is selected from:

NH„

,NH„

H

H

NH,

H

H

,NH„

-N

H

H

,NH„

and

or

- or by the combination of the subgroups as defined above.

According to a particular embodiment, the present invention relates to a compound as defined above, characterized in that it represents (Γ)

O

OR

( ) in which

R, RI and R2 are as defined above,

n and m are independently the integer 2 or 3,

R3 and R4 independently represent a hydrogen atom, a group

(Ci-Cs) alkyl or a group - (CH 2 ) s NH 2 , and

R5 represents a hydrogen atom, a group - (CH 2 ) P -NH 2 , a group - (CH 2 ) p -NH- (CH 2 ) q -NH 2 or - (CH 2 ) p-NH- (CH 2) q -NH- (CH 2 ) r-NH2, p, q, r and s independently represent an integer which can vary between 1 and 5,

5, and stereoisomers, mixtures of stereoisomers and / or pharmaceutically acceptable salts thereof.

According to a particular embodiment, the present invention relates to a compound as defined hereinbefore, especially a compound of formula (Γ), characterized 10 in that R represents a group (Ci-C4) alkyl and preferably methyl or isoproyle.

According to a particular embodiment, the present invention relates to a compound as defined hereinbefore, especially a compound of formula (Γ), characterized in that n is 2 and m is 3, n is equal to 2 and m is 2 or n is

15 3 and m is equal to 3.

According to a particular embodiment, the present invention relates to a compound as defined hereinbefore, especially a compound of formula (Γ), characterized in that R3 and R4 independently represent a hydrogen atom, a methyl group or a group - (CH 2 ) s -NH 2 , wherein s is 2 or 3.

20 In yet another particular embodiment, the present invention relates to a compound as defined hereinbefore, especially a compound of formula (Γ), characterized in that R5 represents a hydrogen atom, a group - (CH 2 ) P -NH 2 , a group - (CH 2 ) p -NH- (CH 2 ) q -NH 2 or - (CH 2 ) p -NH- (CH 2) q -NH- (CH 2 ) r-NH2 , where p is 2 or 3, q is 2 and r is 2.

25 In yet another particular embodiment, the invention relates to a compound as defined hereinbefore, especially a compound of formula (Γ), characterized in that n and m are simultaneously equal to 3. According to a preferred variant of this particular embodiment, preferred are the compounds for which R3 represents a group - (CH 2 ) s -NH 2 wherein s is equal to 3 or a (Ci-Cs) alkyl,

30, preferably methyl, and R4 and R5 are hydrogen atoms. According to another preferred variant of this particular embodiment, are also preferred compounds for which R3 and R4 are hydrogen and R5 is a group

- (CH 2 ) P NH 2 wherein p is 3. It can be mentioned in particular as representatives compounds of this particular embodiment the compounds (11) and (39) as defined below.

According to a particular embodiment n is equal to m.

The present invention also relates to a compound of formula (Ia)

O

OR

i i

HH (Ia) wherein

R, RI and R2 are as defined above, and

R5 represents a hydrogen atom or a group - (CH 2 ) P -NH 2 , where p is 2 or 3,

and stereoisomers, mixtures of stereoisomers and / or pharmaceutically acceptable salts thereof.

According to a preferred embodiment, the present invention is directed to compounds of formula (Ia) in which R is methyl or isopropyl.

The present invention also relates to a compound of formula (Ib)

O

OR

R6.

■ CH, f- CH2-^N-f C H 2 ^ N .

7 2 I J U 2 I H

R

HH (Ib) wherein

R, RI and R2 are as defined above,

u is 0, 1, 2 or 3, preferably 1, 2 or 3,

R6 and R7 independently represent a hydrogen atom or a (Ci-C8) alkyl, preferably a hydrogen atom or a (Ci-C 4 ) alkyl,

and stereoisomers, mixtures of stereoisomers and / or pharmaceutically acceptable salts 5 thereof.

The present invention also relates to a compound of formula (Ic)

H3C O

in which

10 R, RI, R2, n and m are as defined above, and

R8 is (Ci-C8) alkyl, preferably methyl, or a group - (CH 2 ) s NH 2 , with s being an integer which can vary between 1 and 5, preferably equal to 2 or 3 ,

and stereoisomers, mixtures of stereoisomers and / or pharmaceutically acceptable salts 15 thereof.

According to a preferred embodiment, the present invention is directed to compounds of formula (Ic) in which when R8 represents - (CH 2 ) S NH 2 , then n = m = s.

20 According to a preferred embodiment, the present invention is directed to compounds of formula (Ic) in which when R8 is methyl, then n is equal to m.

According to a preferred embodiment of the present invention, a compound of 25 formula (I) is selected from:

- (1) isopropyl-3P-norspermino deoxycholate,

- (2) isopropyl 3P-norspermidino-deoxycholate,

CLAIMS
1. A compouild of formula (I)
in which
R represents a (CI-Cs)alkyl group;
R1 and R2 independently represent a hydrogen atom, an SOjH group or a
hydroxyl group,
R' represents a group (CRaRb)n-X-(CRcRd)m-[Y-(CReRt)o]t-NR9R~o,
Ra, Rb, &, Rd, Re and Rf independently represent a hydrogen atom, a (CICs)
alkyl group or a (Cs-C~o)arylg roup,
X and Y independently represent a group -NR1 I-, a group -0- or a 5-membered
or 6-membered divalent heterocyclic group comprising at least one nitrogen
atom,
R9 and R10 indepeildently represent a hydrogen atom, a (CI-Cs)alkyl group or
form, together with the nitrogen atom that bears them, a 5-membered or 6-
membered heterocyclic group, optionally substituted with one or two groups =O
or =S,
R11 represents a hydrogen atom, a (CI-Cs)allyl group or a -(CHz),-NH2 group,
n, m, o and s independently represent an integer between 1 and 5,
t is equal to 0, 1,2 or 3,
in which m is other than 4, and
with the exception of the compounds for which t is equal to 1 and m+n+o is
equal to 10,
and also the stereoisomers, mixtures of stereoisomers, andlor pharmaceutically
acceptable salts thereof.
2. The compound as claimed in claim 1, characterized in that it is defined by at
least one of the following subgroups:
AS ORIGINALLY FILED
- first subgroup of compounds of formula (I) in which R1 and R2
independently represent a hydrogen atom or a hydroxyl group,
- second subgroup of compounds of fornlula (I) for which R is a (CIC4)
alkyl group, in particular a methyl or isopropyl group.
5 - third subgroup of compounds of formula (I) for which X is an -NHgroup,
- fourth subgroup of compounds of formula (I) in which R9 and R10
represent a hydrogen atom,
- fifth subgroup of compounds of formula (I) for which R,, Rh, Rc, Rd, Re
10 and Rf represent a hydrogen atom,
- sixth subgroup of compounds of formula (I) for wlnch Y is a group -
NR1 I-, with R11 representing a hydrogen atom, a (CI-C4)alkyl group or a -(CH2),-NH2
group in which s is equal to l , 2 or 3,
- seventh subgroup of compounds of formula (I) for which m is equal to 2,
15 3, 4 or 5, more preferentially 2 or 3,
- eighth subgroup of compounds of formula (I) for which n is equal to 2,
3,4 or 5, more preferentially 2 or 3,
- ninth subgroup of compounds of formula (I) for which o is equal to 2 or
3,
20 - tenth subgroup of compounds of fonnula (I) for which the group -NHR'
is chosen from:
AS ORIGINALLY FILED
H
- N - N ~ N H z - N H~ N ' - ' - " N H ,
r' and
NH2 H2N
or
- or by the combination of the subgroups as defined above.
3. The compound as claimed in claim 1 or 2, characterized in that it represents
5 formula (1')
in which
R, R1 and R2 are as defined in claim 1 or 2,
n and m independently represent the integer 2 or 3,
R3 and R4 independently represent a hydrogen atom, a (CI-Cs)alkyl group or a
-(CH2),-NHz group, and
R5 represents a hydrogen atom, a (CHz),-NHz, group, a -(CH2)p-NH-(CH~)q-
NH2 group or a -(CHz),-NH-(CHZ),-NH-(CHZ)g~ro-uNpH, Z
p, q, r and s independently represent an integer which may range between 1 and
5,
AS ORIGJIYALLY FILED
and also the stereoisomers, mixtures of stereoisomers, and/or pharmace~~tically
acceptable salts thereof.
4. The compound as claimed in any one of claims 1 to 3, characterized in that
R represents a (CI-C4)alkyl group, preferentially a methyl or an isopropyl.
5 5. The compound as claimed in any one of claims 1 to 4, characterized in that
n is equal to 2 and m is equal to 3, n is equal to 2 and m is equal to 2, or n is equal to 3 and
m is equal to 3.
6. The compound as claimed in any one of claims 3 to 5, characterized in that
R3 and R4 independently represent a hydrogen atom, a methyl group or a -(CH2),-NH2
10 group, in which s is equal to 2 or 3.
7. The compound as claimed in any one of claims 3 to 5, characterized in that
R5 represents a hydrogen atom, ~-(CHZ)~-NgHro~u,p , a -(CH2)p-NH-(CH2)q-NHzg roup or
a -(CH2),-NI-I-(CH2),-NH-(CHz)[g-rNoHuzp , in which p is equal to 2 or 3, q is equal to 2
and r is equal to 2.
15 8. The compound as claimed in any one of the preceding claims, characterized
in that it represents the formula (Ia)
in which
R, R1 and R2 are as defined in any one of claims 3 to 5, and
R5 represents a hydrogen atom or a -(CHZ)~-NHg~ro up, in which p is equal to
2or 3,
and also the stereoisomers, mixtures of stereoisomers, andlor pharmaceutically
acceptable salts thereof.
9. The compound as claimed in any one of claims 1 to 7, characterized in that
25 it represents formula (Ib)
AS ORIGINALLY FILED
in which
R, R1 and R2 are as defined in any one of claims 3 to 5,
u is equal to 0, 1, 2 or 3, preferentially equal to 1, 2 or 3,
R6 and R7 independently represent a hydrogen atom or a (CI-Cs)alkyl group,
preferably a hydrogen atom or a (CI-C4)aryl group,
and also the stereoisomers, mixtures of stereoisomers, andlor pharmaceutically
acceptable salts thereof.
10. The compound as claimed in any one of claims 1 to 7, characterized in that
10 it represents formula (Ic)
in which
R, R1, R2, n and m are as defined in any one of claims 3 to 5, and
R8 represents a (CI-C8)alkyl group, preferably amethyl group, or ~(CHZ)~-NHZ
group, with s being an integer which may range between 1 and 5, preferably
equal to 2 or 3,
and also the stereoisomers, mixtures of stereoisomers, andlor phar~naceutically
acceptable salts thereof.
11. The compound of formula (I) as defined in claim 1, chosen from the
20 following conlpounds:
(1) isopropyl3p-norsperminodeoxycholate,
(2) isopropyl3P-norspermidinodeoxycholate,
(3) methyl 3P-norsperminodeoxycholate,
AS OFUGINALLY FILED
(4) methyl 38-norspermidinodeoxycholate,
(5) methyl 3P-norspermidinocholate,
(6) isopropyl 3p-norspern~inocl~olate,
(7) isopropyl3P-norspermidinocholate,
(8) methyl 3[3-norsper~~~inochenodeoxycholate,
(9) methyl 3P-~~orspermidinochenodeoxycholate,
(10) isopropyl3P-norsperminochenodeoxycholate,
(12) methyl 3P-norsperminoursodeoxycholate,
(13) methyl 3p-norspem~idinoursodeoxycholate,
(14) isopropyl 3P-norsper~~lldinoursodeoxycholate,
(15) isopropyl3p-norsperminolithocholate,
(16) isopropyl 3P-norspermidinolithocholate,
(17) methyl 3p-norsperminolithocholate,
(18) methyl 3P-norspermidinolithocholate,
(19) methyl 3P-(tetraethylenepentamine)deoxycholate,
(20) methyl 3P-(pentaethylenehexamine)deoxycholate,
(21) isopropyl3P-(pentaethylenehexamine)cholate,
(22) methyl 3P-(pentaethylenehexamine)chenodeoxycholate,
(23) isopropyl3~-@entaethylenehexamine)chenodeoxycholate,
(24) isopropyl3~-(pentaethylenehexamine)ursodeoxycholate,
(25) methyl 3P-(pentaethylenehexamine)lithocholate,
(26) isopropyl3P-@entaethylenehexamine)lithocholate,
(27) isopropyl3P-(pentaethylenehexamine)deoxycholate,
(28) isopropyl3~-(tris(3-aminopropyl)amine)deoxycholate,
(29) isopropyl 3P-(tris(2-aminoethyl)amine)deoxycholate,
(30) isopropyl3~-(bis(3-aminopropyl)1nethylamine)deoxycl~olate,
(31) methyl 30-(bis(3-aminopropyI)methylamine)deoxycholate,
(32) methyl 3~-(tris(3-ami11opropyl)amine)deoxycholate,
30 (33) methyl 3P-(his(3-aminopropyl)methylamine)cholate,
(34) isopropyl3~-(tris(3-aminopropyl)a1nine)cholate,
(35) isopropyl 3P-(tris(2-aminoethyl)amine)cholate,
AS ORIGINALLY FILED
(36) isopropyl3~-(bis(3-aminopropyl)methylamine)cholate,
(37) methyl 3~-(bis(3-aminopropyl)methylan1ine)chenodeoxycl1olate,
(38) methyl 3~-(tris(3-aminopropyl)a11~i11e)chenodeoxycl1olate,
(39) isopropyl 3~-(tris(3-a1ninopropyl)ami11e)chenodeoxycholate,
(40) isopropyl3~-(tris(2-a~~~i1~oetl~yl)am~ne)chenodeoxycholate,
(41) isopropyl3~-(bis(3-an~inopropyl)methylamine)chenodeoxycholate,
(42) isopropyl 3P-(tris(3-aminopropyl)amine)ursodeoxycholate,
(43) isopropyl3~-(tris(2-aminoethyI)amine)ursodeoxycholate,
(44) isopropyl3~-(bis(3-minopropyl)methylamine)ursodeoxycholate,
(45) methyl 3P-(bis(3-aminopropyl)methylamine)lithocholate,
(46) methyl 30-(tris(3-aminopropyl)amine)lithocholate,
(47) isopropyl3~-(tris(3-aminopropyl)amine)lithocholate,
(48) isopropyl 3P-(tris(2-aminoethyl)amine)lithocholate,
(49) isopropyl 3p-(bis(3-aminopropyl)methylamine)lithocholate,
(50) methyl 3P-(pentaethylenehexamine)ursodeoxycholate,
(51) isopropyl3P-norsperminoursodeoxycholate,
(52) methyl 3P-(tris(3-a~ninopropyl)amine)ursodeoxycholate,
(53) methyl 3~-(bis(3-aminopropyI)methylamine)ursodeoxycholate,
or a pharmaceutically acceptable salt thereof, and more particularly chosen from
20 compounds (I), (lo), (1 I), (18), (39) and (20).
12. The compound of formula (I) as claimed in any one of the preceding claims,
for its use as a medicament.
13. A pharmaceutical or veterinary composition comprising a compound of
formula (I) as defined in any one of claims 1 to 11 and a pharmaceutically acceptable
25 excipient.
14. A pharmaceutical or veterinary composition comprising at least one
compound of formula (I) as defined in any one of claims 1 to 11 and at least one antib~otic,
other than such a compound of formula (I), more particularly from the beta-lactamine family,
aminosides, macrolides, polypeptides, sulfamides, quinolones, nitro-imidazoles, nitrofuran
30 derivatives, benzyl-pyrimidine nucleus derivatives, tetracyclines or phenicols, such as
doxycycline or chloramphellicol, penicillin, ampicillin, amoxicillin, cloxacillin,
dicloxacillin, oxacillin, nafcillin, cephalexin, cephapirin, cefazolin, ceftiofur, cefoperazone,
AS ORIGINALLY FILED
cefovecin, cefquinome, thimaphenicol, florfenicol, terrainycin, erythromycin, spiramycin,
tylosin, josamycin, tilmicosin, tulathromycin, gamithromycin, tildipirosin, clindamycin,
lincomycin, pirlimycin, tiamulin, valnemulin, oxol~nic acid, flurnequine, enrofloxacin,
danofloxacin, ibafloxacin, marbofloxacin, difloxacin, obifloxacin, pradofloxacin,
5 rifampicin, rifaximin, sulfamethizole, sulfathiazole, sulfadimidine, sulf2methoxazole,
sulfadiazine, sulfadimethoxine, sulfamethoxypyridazine, trimethoprim, baquiloprim,
metronidazole, dimetridazole, ronidazole, nitrofurantoin, fi~razolidoneo r furaltadone, and
even more particularly doxycycline.
15. The compound as claimed in any one of claims 1 to 11, for its use for
10 preventing andlor inhibiting andlor treating bacterial, fungal, viral or parasitic infections in
man or animals.
16. The use of a compound as claimed in any one of claims 1 to 11, for
potentiating the antibiotic activity of antibiotic compounds which may be chosen from the
antibiotic compounds as described in claim 14.
17. A process for preparing a compound of formula (I) as defined in any one of
claims 1 to 11, comprising a step of reductive amination of the compound of formula (11)
in which R, R1 and R2 are as defined in one of claims 1,2 or 3,
with an amine of formula R'NHz in which R' is as defined in claim 1, in the
20 presence of a reducing agent such as titanium tetraisopropoxide, zirconium
tetraisopropoxide, NaBHXN, NaBH4 or a mixture thereof, to obtain said compound of
formula (I).