RU2002112986A - NEW FUZIDIC ACID DERIVATIVES - Google Patents

Claims (24)

1. The compound of General formula Ia

where Q ₁ , Q ₂ and Q ₃ are the same or different and represent, independently, the group - (CO) -; group - (CHON) -; group - (CHOR) -; group - (CHSH) -; group - (NH) -; a group - (CHNH ₂ ) - or a group - (CHNHR) -, where R represents an alkyl radical with 1-4 carbon atoms or an acyl radical with 1-4 carbon atoms; and where Q ₂ and Q ₃ may also represent, independently, a group - (CH ₂ ) -; Y represents hydrogen, hydroxy, an alkyl radical with 1-4 carbon atoms or an acyl radical with 1-4 carbon atoms; A represents an oxygen or sulfur atom; R ₁ represents an alkyl radical with 1-4 carbon atoms, an olefin group with 2-4 carbon atoms, a (C ₁ -C ₆ ) acyl group, a (C ₃ -C ₇ ) cycloalkylcarbonyl group or a benzoyl group, wherein R ₁ , optionally substituted with one or more halogen atoms and / or hydroxy, alkoxy or azido groups; and its pharmaceutically acceptable salts and readily hydrolyzable esters. 2. The compound according to claim 1 of general formula I

where Q ₁ and Q ₂ are the same or different and both represent a group - (CHOH) -, a group - (CO) - or a group - (CHSH) -; A represents an oxygen or sulfur atom; R ₁ represents an alkyl radical with 1-4 carbon atoms, an olefin group with 2-4 carbon atoms, a (C ₁ -C ₆ ) acyl group, a (C ₃ -C ₇ ) cycloalkylcarbonyl group or a benzoyl group, wherein R ₁ , optionally substituted with one or more halogen atoms and / or hydroxy, alkoxy or azido groups; and its pharmaceutically acceptable salts and readily hydrolyzable esters. 3. The compound according to claim 1 or 2, where Q ₁ and Q ₂ both represent a group

4. The compound according to any one of the preceding paragraphs, where the stereochemistry, when Q ₁ and Q ₂ belong to the group

for C-3 and C-11 atoms, it represents 3α-OH and 11α-OH, respectively, and the C-16 atom to which group A is attached has the configuration - (S) denoted 16β. 5. The compound according to any one of the preceding paragraphs, where one of Q ₁ or Q ₂ represents - (CO) -. 6. The compound according to any one of the preceding paragraphs, where A represents oxygen. 7. The compound according to any one of the preceding paragraphs, where R ₁ represents a (C ₁ -C ₄ ) -alkyl group optionally substituted with one or more substituents selected from the group consisting of azido, hydroxy and halogen, and the halogen is selected from fluorine, chlorine and bromine. 8. The compound according to any one of the preceding paragraphs, where R ₁ represents a (C ₁ -C ₄ ) -alkyl group substituted by one or more halogen groups selected from fluorine and chlorine. 9. The compound according to any one of the preceding paragraphs, where R ₁ selected from the group consisting of ethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2-azidoethyl, 2-hydroxyethyl, propyl and isopropyl, 1, 3-difluoroisopropyl, tert-butyl, acetyl, propionyl, chloroacetyl and trifluoroacetyl. 10. The compound according to any one of the preceding paragraphs, where R ₁ selected from the group consisting of ethyl, 2,2,2-trichloroethyl, 2-azidoethyl, isopropyl, tert-butyl and acetyl. 11. The compound according to any one of the preceding paragraphs, where the bond between C-24 and C-25 is a double bond. 12. The compound of formula I, selected from the group consisting of 17 (S), 20 (S) -dihydrofusidic acid (compound 101), 17 (S), 20 (S), 24.25-tetrahydrofusidic acid (compound 102), 11-dehydro-17 (S), 20 (S) -dihydrofusidic acid (compound 103), 3-dehydro-17 (S), 20 (S) -dihydrofusidic acid (compound 104), 16-deacetoxy-16β-propionyloxy-17 (S), 20 (S) -dihydrofusidic acid (compound 105), 16-deacetoxy-16β- (3’-chloropropionyloxy) -17 (S), 20 (S) -dihydrofusidic acid (compound 106), 16-deacetoxy-16β- (2’-methylpropionyloxy) -17 (S), 20 (S) -dihydrofusidic acid (compound 107), 16-deacetoxy-16β-cyclopropylcarbonyloxy-17 (S), 20 (S) -dihydrofusidic acid (compound 108), 16-deacetoxy-16β-chloroacetoxy-17 (S), 20 (S) -dihydrofusidic acid (compound 109), 16-deacetoxy-16β-bromoacetoxy-17 (S), 20 (S) -dihydrofusidic acid (compound 110), 16-deacetoxy-16β-benzoyloxy-17 (S), 20 (S) -dihydrofusidic acid (compound 111), 16-deacetoxy-16β- (4’-fluorobenzoyloxy) -17 (S), 20 (S) -dihydrofusidic acid (compound 112), 16-deacetoxy-16β-cyclohexylcarbonyloxy-17 (S), 20 (S) -dihydrofusidic acid (compound 113), 16-deacetoxy-16β-acryloyloxy-17 (S), 20 (S) -dihydrofusidic acid (compound 114), 16-deacetoxy-16β-isopropylthio-17 (S), 20 (S) -dihydrofusidic acid (compound 115), 16-deacetoxy-16β-ethylthio-17 (S), 20 (S) -dihydrofusidic acid (compound 116), 16-deacetoxy-16β- (2 ’, 2’, 2’-trichloroethylthio) -17 (S), 20 (S) -dihydrofusidic acid (compound 117), 16-deacetoxy-16β-tert-butylthio-17 (S), 20 (S) -dihydrofusidic acid (compound 118), 16-deacetoxy-16β-methoxymethylthio-17 (S), 20 (S) -dihydrofusidic acid (compound 119), 16-deacetoxy-16β-isopropylthio-17 (S), 20 (S), 24.25-tetrahydrofusidic acid (compound 120), 16-deacetoxy-16β-acetylthio-17 (S), 20 (S) -dihydrofusidic acid (compound 121), 16-deacetoxy-16β-benzoylthio-17 (S), 20 (S) -dihydrofusidic acid (compound 122), 16-deacetoxy-16β-ethoxy-17 (S), 20 (S) -dihydrofusidic acid (compound 123), 16-deacetoxy-16β- (2 ’, 2’, 2’-trifluoroethoxy) -17 (S), 20 (S) -dihydrofusidic acid (compound 124), 16-deacetoxy-16β-propoxy-17 (S), 20 (S) -dihydrofusidic acid (compound 125), 16-deacetoxy-16β-isopropoxy-17 (S), 20 (S) -dihydrofusidic acid (compound 126), 16-deacetoxy-16β- (1 ’, 3’-difluoroisopropoxy) -17 (S), 20 (S) -dihydrofusidic acid (compound 127), 16-deacetoxy-16β-methoxymethoxy-17 (S), 20 (S) -dihydrofusidic acid (compound 128), 16-deacetoxy-16β- (2 ’, 2’, 2’-trichloroethoxy) -17 (S), 20 (S) -dihydrofusidic acid (compound 129), 16-deacetoxy-16β- (2’-azidoethoxy) -17 (S), 20 (S) -dihydrofusidic acid (compound 130), 16-deacetoxy-16β- (2’-hydroxyethoxy) -17 (S), 20 (S) -dihydrofusidic acid (compound 131), and their pharmaceutically acceptable salts and readily hydrolyzable esters. 13. The compound according to claim 12, selected from the group consisting of sodium salt of 17 (S), 20 (S) -dihydrofusidic acid and diethanolamine salt of 17 (S), 20 (S) -dihydrofusidic acid. 14. The stereoisomer of the compound of formula I or Ia in pure form or a mixture of such stereoisomers. 15. A pharmaceutical composition comprising a compound according to any one of claims 1-14, alone or together with a pharmaceutically acceptable non-toxic carrier and / or excipient and, optionally, together with one or more other therapeutically active components. 16. A pharmaceutical composition comprising 17 (S), 20 (S) -dihydrofusidic acid of formula 10, alone or together with a pharmaceutically acceptable non-toxic carrier and / or excipient, one or together with pharmaceutically acceptable non-toxic carriers and / or excipients and, optionally , together with one or more therapeutically active components. 17. The pharmaceutical composition according to claim 15 or 16 in the form of a topical preparation. 18. The pharmaceutical composition according to the preceding paragraph in the form of an ointment. 19. A method of treating a patient in need of antimicrobial treatment, comprising administering to said patient an effective amount of one or more compounds according to any one of claims 1 to 14, optionally, together or along with one or more other therapeutically active components. 20. The compound according to any one of claims 1 to 14, useful for the manufacture of drugs. 21. The compound according to any one of claims 1 to 14, useful for the manufacture of a medicament for the systemic treatment of infectious diseases. 22. The compound according to any one of claims 1 to 14, useful for the manufacture of a medicament for topical treatment of infectious diseases of the skin and / or eyes. 23. The compound according to item 22, where the drug also contains one or more other therapeutically active components. 24. The compound according to item 22 or 23, where the drug is intended for concomitant administration with one or more other therapeutically active components.