W0 2011/000721 A1 I||||||||||||||||||||||||||||||||||||||||||||||||||||||||| - Questel

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Therefore, there is a need in the field of medicine for new compounds which are effective in inhibiting infections mediated by immune system lectins, including DC-SIGN which would be active as well as scarcely cytotoxic. In addition, langerin is known as a mannose-binding lectin which has been associated with a protective action against HIV infection. Since langerin is found in epidermis and mucosa, it is important for topical applications that the active component shows selectivity for DC-SIGN rather than for langerin. Accordingly, there is also a need for new compounds which are effective and highly selective towards DC-SIGN rather than other targets, like langerin. SUMMARY OF THE INVENTION The present invention, accordingly, provides new inhibitors of infections, which do not favour the emergence of resistant strains, has lower toxicity, may be applied topically and could cross mucoses significantly better compared to the already known compounds. In addition, the compounds disclosed in the invention are more selective towards DC-SIGN than towards other targets, in particular with respect to langerin. OBJECT OF THE INVENTION In a first object, the present invention discloses the antimicrobial compounds of claims 1 to 12. In a second object, the present invention concerns a process for the preparation of the compounds of the invention. As per a third object, the compounds of the invention are disclosed as a medicament for the treatment and/or prevention of HIV; Ebola, Dengue, Hepatitis C, SARS or tuberculosis infections as per claims 13 to 17.
It is a forth object of the invention a pharmaceutical preparation comprising one or more of the compounds of the invention as per claims 18 to 20. DESCRIPTION OF THE FIGURES Fig. 1 shows the results of the trans-infection of CD4+ T lymphocytes by BaL- virus after exposure to BTHP1/DC-SIGN+ cells preincubated with the virus and with variable quantities of compound 12. The results are averages for lymphocytes donated by three random donors. Fig. 2 shows the results of the trans-infection of CD4+ T lymphocytes assays for compound 2b and 12. Fig. 3 shows the results of the trans-infection of CD4+ T lymphocytes with BaL-virus for compound 12 and 2b when the experiment is performed washing the B- THP-1/DC-SIGN+ cells after incubation with the inhibitors and before incubation with the virus. Fig. 4 shows the results of the trans-infection of CD4+ T lymphocytes obtained from two different donors by BaL-virus after exposure to BTHP1/DC-SIGN+ cells preincubated with the virus and with variable quantities of compound 12. Donor P 1 is genetically not susceptible to HIV infection, donor P2 is genetically susceptible to HIV infection Fig. 5 shows the results of the trans-infection of CD4+ T lymphocytes by HIV-1 strain V6 after exposure to BTHP1/DC-SIGN+ cells preincubated with the virus and with variable quantities of compound 12. The results are averages for lymphocytes donated by three random donors. Fig. 6 shows the results of the trans-infection of CD4+ T lymphocytes by HIV-1 strain V17 after exposure to BTHP1/DC- SIGN+ cells preincubated with the virus and with variable quantities of compound 12. The results are averages for lymphocytes donated by three random donors. Fig. 7 shows the percentage of 7-AAD positive BTHP1/DC- SIGN+ cells in the absence or in the presence of the inhibitors. Fig. 8 shows the results of the trans-infection of CD4+ T lymphocytes by HIV-1 strain IHB after exposure to BTHP1/DC-SIGN+ cells preincubated with the virus
Page 1 and 2: (12) INTERNATIONAL APPLICATION PUBL
Page 3: mannose disaccharide (Manα1-2Man),
Page 7 and 8: M' is a saccharidic or pseudo-sacch
Page 9 and 10: wherein Q and n are above disclosed
Page 12 and 13: wherein R is as above disclosed,
Page 14 and 15: may be made of gold, silver, Fe 2 O
Page 16 and 17: Within the compound of formula (I)
Page 18 and 19: wherein R and R 2 are as above repo
Page 20 and 21: through the Y linker and n is 1 to
Page 22 and 23: and (12a) 12b. As per a third aspec
Page 24 and 25: H wherein Q is selected from — N
Page 26 and 27: According to a second object of the
Page 28 and 29: wherein aj is 32 and J is a third g
Page 30 and 31: eactions requiring anhydrous condit
Page 32 and 33: To a solution of the silylmannopyra
Page 34 and 35: 3H, CH 3 CO), 1.99 (s, 3H, CH 3 CO)
Page 36 and 37: To a solution of the compound 9 (12
Page 38 and 39: (C2 D ), 70.36 (C6 M ), 70.01 (C6 M
Page 40 and 41: EXAMPLE 2 Synthesis of compound 12a
Page 42 and 43: 13 C-NMR (100 MHz, D2 O) δ (ppm):
Page 44 and 45: (the R5 tropic laboratory-adapted s
Page 46 and 47: derived from 1 (see above); G3Man32
Page 48 and 49: CLAIMS: 1 A compound of general for
Page 50: OCH 3 ), hydroxymethyl (-CH 2 OH),
Page 53 and 54: alkyl chain, C1-C8 linear or branch
Page 55 and 56:
7 . A compound having the general f
Page 57 and 58:
H wherein Q is selected from — N
Page 59:
or methyl substituted 1,3-thiazole;
Page 62 and 63:
wherein R 2 may be hydroxyl (-0H),
Page 64 and 65:
12. A compound according to claim 1
Page 66:
or methyl substituted 1,3-thiazole;
Page 82 and 83:
INTERNATIONAL SEARCH REPORT C(Conti
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W0 2011/000721 A1 I||||||||||||||||||||||||||||||||||||||||||||||||||||||||| - Questel

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