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US 6,187,754 B1Granted
Sialyl-Lewisa and sialyl-Lewisx epitode analogues
AssigneeGlycoTech Corp.
InventorReinhold Oehrlein
Life of this patent
Estimating the term…
Abstract
Sialyl-Lewisa and sialyl-Lewisx epitope analogues, in which the natural N-acetyl group of the N-acetylglucosamine monomer is replaced by various hydroxylated aromatic substituents.
Claims46
A compound of the formula I or II
- in which
- Z is an α-bonded L-fucose of the formula III
- R1 is a monocyclic or bicyclic C6-C10aryl or C2-C9heteroaryl which is substituted by at least one OH and can be substituted, once or more than once, by a substituent selected from the group comprising halogen, halo-C1-C18alkyl, nitro, C1-C18alkyl, C1-C18alkoxy, amino, mono-C1-C18alkylamino, di-C1-C18alkylamino, benzylamino, sulfhydryl, thio-C1-C18alkyl and C1-C18alkylcarboxamide;
- R2 is C1-C18alkyl, monosubstituted or polysubstituted C1-C18alkyl, C3-C8cycloalkyl or monosubstituted or polysubstituted C3-C8cycloalkyl, where one or more CH2 groups in the alkyl and in the cycloalkyl can be replaced, independently of each other, by oxygen, sulfur or an imino group and the substituents are selected from the group comprising OH, SH, NH2, carboxamide and C(O)OR, in which R is H or C1-C18alkyl;
- R3 is a methyl group or hydroxymethyl group;
- and
- X is —C(O)—, —C(S)—, —S(O)2—, —C(O)Y— or —C(S)Y—, where Y is NH, O, S, S-C1-C6alkylene, NH-C1-C6alkylene or O-C1-C6alkylene.
4 more elements
A process for preparing compounds of formula I
- wherein
- (a) a compound of the formula V
- R7—X′—R1 (V),
- in which
- (a′) R7 is halogen, X′ is —C(O)—, —C(S)—, —S(O)2—, —C(O)Y— or —C(S)Y—, where Y is NH, O, S, S-C1-C6alkylene, NH-C1-C6alkylene or O-C1-C6alkylene;
- and R1 is a monocyclic or bicyclic C6-C10aryl or C2-C9heteroaryl which is substituted by at least one OH and can be substituted, once or more than once, by a substituent selected from the group comprising halogen, halo-C1-C18alkyl, nitro, C1-C18alkyl, C1-C18alkoxy, amino, mono-C1-C18alkylamino, di-C1-C18alkylamino, benzylamino, sulfhydryl, thio-C1-C18alkyl and C1-C18alkylcarboxamide;
- or
- (a″) R7 is C(O) or C(S), X′ is —N═ and R1 is as defined above, or
- (a′″) R7 is OH, X′ has the abovementioned meanings of X and R1 is as already defined above,
- is reacted, directly after the in-situ activation, with a compound of the formula IV
- in which R2 is C1-C18alkyl, monosubstituted or polysubstituted C1-C18alkyl, C3-C8cycloalkyl or monosubstituted or polysubstituted C3-C8cycloalkyl, with it being possible for one or more CH2 groups, in the alkyl or in the cycloalkyl, to be replaced, independently of each other, by oxygen, sulfur or an imino group and with the substituents being selected from the group comprising OH, SH, NH2, carboxamide and C(O)OR, in which R is H or C1-C18alkyl;
- and the individual R4s are, independently of each other, hydrogen or a protecting group, with the elimination of any protecting groups which are present, to form a compound of the formula VI
- in which R2, R1 and X are as previously defined;
- (b) the compound of the formula VI is reacted with uridine diphosphate galactose in the presence of β(1→4)galactosyl transferase, and then with cytidine monophosphate sialic acid in the presence of sialyl transferase, to form a compound of the formula VII
- in which R1, R2, R3 and X are as previously defined, and
- (c) the resulting product is reacted with guanosine diphosphate fucose in the presence of fucosyl transferase to form a compound of the formula I.
13 more elements
Dependencies are inferred from the claim text.