Fluorinated glucosamine analogs useful for modulating post-translational glycosylations on cells
AssigneesHealth Research, Inc., The Brigham and Women's Hospital, Inc.
InventorsRobert Sackstein, Charles J. Dimitroff, Ralph J. Bernacki, Moheswar Sharma, Khushi L. Matta, Brajeswar Paul
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Abstract
The present invention provides compositions and methods for inhibiting cell migration, e.g., lymphocytes and inflammation. The invention also provides an improved process for preparing fluorinated N-acetylglucosamines.
Claims45
A method of inhibiting migration of a leukocyte, comprising contacting a leukocyte with a fluorinated N-acetylglucosamine.
A method of inhibiting cell proliferation, comprising contacting a cell with a fluorinated N-acetylglucosamine.
A method of modulating differentiation of a cell, comprising contacting the cell with a fluorinated N-acetylglucosamine.
A method of inhibiting migration of a hematopoietic cell, comprising contacting the hematopoietic cell with a fluorinated N-acetylglucosamine.
A method of decreasing an amount of HECA-452 epitope on a glycoprotein on a cell, comprising contacting the cell with a fluorinated N-acetylglucosamine.
A method of inhibiting inflammation of a tissue in a subject, comprising administering to the subject a composition comprising a fluorinated N-acetylglucosamine.
In a method for preparing fluorinated N-acetylglucosamine comprising the intermediate step of preparing benzyl acetamido-2-deoxy-3,6-di-O-benzyl-2-deoxy-D-glucopyranoside from benzyl 2-acetamido-3-O-benzyl-4,6-benzylidene-2-deoxy-D-glucopyranoside, the improvement comprising (i) hydrolyzing benzyl 2-acetamido-3-O-benzyl-4,6-benzylidene-2-deoxy-D-glucopyranoside under appropriate conditions to form benzyl 2-acetamido-3-O-benzyl-2-deoxy-D-glucopyranoside;
- (ii) reacting benzyl 2-acetamido-3-O-benzyl-2-deoxy-D-glucopyranoside with a tin compound to form a tin complex comprising benzyl 2-acetamido-3-O-benzyl-2-deoxy-D-glucopyranoside;
- and (iii) reacting the tin complex with a benzylating agent under appropriate conditions to form benzyl 2-acetamido-3-O-benzyl-3,6-di-O-benzyl-2-deoxy-D-glucopyranoside.
A method of making a compound having the formula (I):
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- which comprises reacting N-acetyl-D-glucosamine with a benzylating agent under appropriate conditions to produce a compound having the formula (II):
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- reacting the compound (II) with a benzaldehyde under appropriate conditions to produce a compound having the formula (III):
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- reacting the compound (III) with a benzylating agent under appropriate conditions to produce a compound having the formula (IV):
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- reacting compound (IV) with a hydrolyzing agent under appropriate conditions to produce a compound having the formula (V):
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- reacting compound (V) with a tin compound to produce a tin complex comprising compound (V) and reacting the tin complex with a benzylating agent under appropriate conditions to produce compound (I).
Dependencies are inferred from the claim text.