Derivatives of alpha-D-neuraminic acid, process of their preparation, their use and pharmaceutical preparations based thereon

• Main Authors: PHAN THO VAN, JIN BETTY, WU WEN-YANG, DANYLEC BASIL, VON ITZSTEIN LAURENCE MARK
• Format: Patent
• Language: English
• Published: 13.06.2001
• Edition: 7
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; CHEMISTRY; DERIVATIVES THEREOF; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SUGARS

Neuraminic acid derivs. of formula (I) and (Ia) and their salts are new. A = O, S or C in (I) and N or C in (Ia). R1 = COOH, P(O)(OH)2, NO2, SOOH, SO3H, tetrazol, CH2CHO, CHO or CH(CHO)2. R2 = H, OR6, F, Cl, Br, CN, NHR6, SR6 or CH2X. X = NHR6, halo or OR6. R6 = H, 1-4C acyl, linear or cyclic 1-6C alkyl (or a halo substd. analogue), allyl or aryl (opt. substd. by halo, OH, NO2, NH2 or COOH. R3, R3' = independently H, CN, NH(R6)2, N3, SR6, =N-OR6, OR6, guanidino, N(OR6)R6, NR6 -NHR6-N(R6)2, NR6-O, pyrimidino or pyrimidinomethyl. R4 = NHR6, SR6, OR6, COOR6, NO2, C(R6)3, CH2COOR6, CH2NO2 or CH2NHR6. R5 = CH2-YR6, CH(YR6)-CH2-YR6 or CH(YR6)CH(YR6)CH2-YR6. Y = O, S, NH or H, provided that (i) when R3 or R3' is OR6 or H, and A is O or S, then (I) cannot have both (a) R2 as H and (b) R4 as NH-acyl. (ii) R6 is a covalent bond when Y is H. In (Ia), when R3 or R3' is OR6 or H, and A is N, then (Ia) cannot have both (a) R2 as H and (b) R4 as NH-acyl, and (ii) R6 is a covalent bond when Y is H. 14 compounds are specifically claimed including sodium 5-acetamido -4-azido-2,3,4,5-tetradeoxy -D-galacto-non-2-enopyransonate. In the present invention there are disclosed derivatives of alpha-D-neuraminic acid of the general formula Ib, in which Re3b represents (alk)ixNRe6bRe7b, CN or Ni3, wherein alk represents methylene, x is 0 or 1, Re6b represents hydrogen, alkyl containing 1 to 6 carbon atoms, aryl having 6 to 14 carbon atoms, arylalkyl containing 6 to 14 carbon atoms in the aryl moiety and 1 to 6 carbon atoms in the alkyl moiety, amidino, NRe7bRe8b or unsaturated or saturated three- through seven-membered ring containing one to four hetero atoms being independently selected from a group comprising nitrogen, oxygen or sulfur, Re7b represents hydrogen, alkyl containing 1 to 6 carbon atoms or allyl; or NRe6bRe7b forms 5- or 6-membered ring optionally containing one to three additional hetero atoms being independently selected from a group comprising nitrogen, oxygen or sulfur, Re8b represents hydrogen or alkyl containing 1 to 6 carbon atoms and Re4b represents NHCORe9b, wherein Re9b represents hydrogen, alkyl containing 1 to 4 carbon atoms, a halogen substituted alkyl containing 1 to 4 carbon atoms, aryl having 6 to 14 carbon atoms or a halogen substituted aryl having 6 to 14 carbon atoms or their pharmaceutically acceptable salts, esters or salts of those esters. In the present invention there is also claimed a process for preparing such derivatives and use thereof for preparing a medicament for treating viral diseases, as well as pharmaceutical preparations based on those derivatives.