# US 2010/0166801 A1 · Sulfoglycolipid antigens, their process of preparation, and their use against tuberculosis

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- Number: US 2010/0166801 A1
- Document ID: US20100166801A1
- Status: Published application
- Kind: A1
- Application number: 12/524,091
- Filed: 2008-01-11
- Published: 2010-07-01
- Earliest claimed: 2007-01-24
- Assignees: Centre National de la Recherche Scientifique (CNRS)
- Inventors: Germain Puzo; Jacques Prandi; Martine Gilleron; Gennaro De Libero; Julie Guiard; Lucia Mori; Samantha Paoletti
- Web page: https://patentgrep.com/patent/US20100166801A1

## CPC

- C07H 13/06: Fatty acids
- A61P 31/04: Antibacterial agents
- A61P 31/06: for tuberculosis
- G01N 33/5695: {Mycobacteria}
- G01N 2333/35: from Mycobacteriaceae (F)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to compounds of the following general formula (I) their process of preparation and their use in the treatment or the prophylaxis of tuberculosis.

## Claims

### Claim at position 1

1-29. (canceled)

### Claim 30

A compound of general formula (I):
wherein:
R2′, R3′, identical or different, are independently chosen from H, SO3H or SO3−/M+, provided that at least one of R2′, R3′ is SO3H or SO3−/M+;
M+ is the cation of a metal, such as Na+, K+;
R2, R3, identical or different, are independently chosen from:
a) fatty acyl groups
b)
where X is an unsaturated linear or ramified hydrocarbon chain optionally substituted with one or more substituents;
where at least one of R2, R3 is b);
and its enantiomers, diastereoisomers, mixtures thereof and pharmaceutically acceptable salts or esters.

### Claim 31 (depends on 30)

A compound of formula (I) according to claim 30, wherein R2′ is SO3H or SO3−/M+ and R3′ is H.

### Claim 32 (depends on 30)

A compound according to claim 30 wherein X is of formula (b-1):
—CRi═CRj—Y (b-1)
where:
Y is a saturated or unsaturated, linear or ramified hydrocarbon chain optionally substituted with one or more substituents;
Ri, Rj, identical or different, are independently chosen from H, Alkyl.

### Claim 33 (depends on 32)

A compound according to claim 32, wherein Ri is Methyl and Rj is H.

### Claim 34 (depends on 32)

A compound according to claim 32, wherein Y is a saturated linear alkyl chain optionally substituted with one to ten alkyl groups.

### Claim 35 (depends on 30)

A compound according to claim 30, wherein the b) chain is of formula (b-2):
where r is an integer chosen from 1, 2 or 3;
l is an integer chosen from 0 to 10;
q is an integer chosen from 0 to 50;
provided that l+q≧1;
T2 is an alkyl;
each Ti, identical or different, are independently chosen from alkyl groups.

### Claim 36 (depends on 35)

A compound according to claim 35, wherein r is 1;
l is 1, 2 or 3;
q is an integer chosen from 10 to 20;
T2 is a methyl;
each Ti is methyl, and the carbon atom to which Ti is attached exhibits a (S) configuration.

### Claim 37 (depends on 30)

A compound according to claim 30, wherein said fatty acyl groups are chosen from the group comprising:
wherein m is 14 or 16 and n is an integer from 2 to 10,
wherein m is 14 or 16 and n is an integer from 2 to 10.

### Claim 38 (depends on 30)

A compound according to claim 30, wherein R2 is a) fatty acyl group and R3 is b) —C═O—X.

### Claim 39 (depends on 30)

A compound according to claim 30 of formula (II):
where R2′, R3′, q, T2, Ti are defined as above,
or the corresponding salt thereof;
and its enantiomers, diastereoisomers, mixtures thereof and pharmaceutically acceptable salts.

### Claim 40 (depends on 39)

A compound according to claim 39, wherein:
l=1, q=14 and r=1;
l=2, q=14 and r=1;
l=3, q=14 and r=1;
l=4, q=14 and r=1;
l=1, q=14 and r=2;
l=2, q=14 and r=2;
l=3, q=14 and r=2;
l=4, q=14 and r=2;
l=1, q=12 and r=1;
l=2, q=12 and r=1;
l=3, q=12 and r=1;
l=4, q=12 and r=1;
l=1, q=12 and r=2;
l=2, q=12 and r=2;
l=3, q=12 and r=2;
l=4, q=12 and r=2;
l=1, q=16 and r=1;
l=2, q=16 and r=1;
l=3, q=16 and r=1;
l=4, q=16 and r=1;
l=1, q=16 and r=2;
l=2, q=16 and r=2;
l=3, q=16 and r=2; or
l=4, q=16 and r=2;
and where p is 6 to 22 and T2 and Ti are methyl.

### Claim 41 (depends on 30)

A compound according to claim 30 chosen from the group consisting in:
and their corresponding salts,
and its enantiomers, diastereoisomers, mixtures thereof and pharmaceutically acceptable salts.

### Claim 42 (depends on 30)

A pharmaceutical composition comprising at least one compound as defined in claim 30 in association with a pharmaceutically acceptable vehicle.

### Claim 43 (depends on 42)

A pharmaceutical composition according to claim 42 in a form intended for administration by oral or injectable route.

### Claim 44 (depends on 42)

A pharmaceutical composition according to claim 42, characterized in that it comprises one or more other products useful for the treatment or the prophylaxis of tuberculosis, such as BCG or mycobacterial proteins.

### Claim 45 (depends on 30)

Products comprising:
at least one compound according to claim 30,
and at least one other product useful for the treatment or the prophylaxis of tuberculosis, such as BCG or mycobacterial proteins,
as a combined preparation for simultaneous, separate or sequential use in the treatment or the prophylaxis of tuberculosis.

### Claim 46 (depends on 30)

A method for the treatment or the prophylaxis of tuberculosis comprising the administration of at least one compound according to claim 30.

### Claim 47

An in vitro method for diagnosing tuberculosis comprising the following steps:
providing a biological sample from a PPD positive individual;
contacting said sample with a compound of formula (X):
where
R2′, R3′, identical or different, are independently chosen from H, SO3H or SO3−/M+, provided that at least one of R2′, R3′ is SO3H or SO3−/M+;
M+ is the cation of a metal, such as Na+, K+.
R2, R3, identical or different, are independently chosen from:
a) fatty acyl groups
b)
where X is an unsaturated linear or ramified hydrocarbon chain optionally substituted with one or more substituents;
and its enantiomers, diastereoisomers, mixtures thereof and pharmaceutically acceptable salts or esters,
assessing T lymphocytes activation;
and comparing T lymphocytes activation after and before administration of the compound.

### Claim 48

A kit for diagnosing tuberculosis comprising:
a compound of formula (X):
where
R2, R3, identical or different, are independently chosen from H, SO3H or SO3−/M+, provided that at least one of R2′, R3′ is SO3H or SO3−/M+;
M+ is the cation of a metal, such as Na+, K+.
R2, R3, identical or different, are independently chosen from:
a) fatty acyl groups
b)
where X is an unsaturated linear or ramified hydrocarbon chain optionally substituted with one or more substituents;
and its enantiomers, diastereoisomers, mixtures thereof and pharmaceutically acceptable salts or esters,
dendritic cells; and
means for detecting T lymphocytes activation.

### Claim 49

Ligands to the compounds of formula (X):
where
R2′, R3′, identical or different, are independently chosen from H, SO3H or SO3−/M+, provided that at least one of R2′, R3′ is SO3H or SO3−/M+;
M+ is the cation of a metal, such as Na+, K+.
R2, R3, identical or different, are independently chosen from:
a) fatty acyl groups
b)
where X is an unsaturated linear or ramified hydrocarbon chain optionally substituted with one or more substituents;
and its enantiomers, diastereoisomers, mixtures thereof and pharmaceutically acceptable salts or esters.

### Claim 50 (depends on 30)

A process of preparation of a compound of formula (I) according to claim 30 comprising the steps of:
sulfonating, and
acylating with corresponding compounds of formulae (IV) and (IV′):
R2X (IV)
R3Y (IV′)
where R2 and R3 are defined as in formula (I) and X and Y independently represent a halogen atom or a OH group,
a compound of formula (III):
where each of P4, P5, P4′, P5′ identical or different represents H or a OH— protecting group or P4 and P5 and/or P4′ and P5′ form together a cyclic OH-protecting group;
wherein the sulfonating and acylating reactions are conducted in any order, successively or alternatively.

### Claim 51 (depends on 50)

The process according to claim 50 further comprising protecting and/or deprotecting steps.

### Claim 52 (depends on 50)

The process according to claim 50 further comprising the step of isolating the obtained compound.

### Claim 53 (depends on 50)

The process according to claim 50, wherein the compound of formula (IV′-a):
is obtained from a corresponding compound of formula (V′):
by a Wittig reaction, by using a compound of formula (VI):
followed by a saponification.