Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-01-19
2002-01-08
Gitomer, Ralph (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C514S025000, C514S071000
Reexamination Certificate
active
06337390
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a novel compound with the anti-viral activity and a drug and anti-viral agent containing said compound as th e effective ingredient, more specifically relates to a medicine and anti-HV active compound comprising the sulfated nonulonic acid.
2. Description of the Related Arts
Azidothymidine (AZT) and dideoxy inosine (DDI) have been used as the AIDS remedy. These agents are to inhibit the reverse transcriptase of HIV, bringing about apothanasic effect to patients, while posing problems that the chronic administration of AZT causes myelopathy and that the DDI administration results in side reactions such as acute pancreatitis and peripheral neuropathy. Furthermore, the use of either drug eventually results in the generation of virus resistant to these drugs.
Recently, the sulfated polysaccharide has been expected as a promising AIDS remedy. It is well known that polysulfated compounds such as dextransulfate (I) (Japanese Patent Laid-Open Publication No. Sho63-45233), polyvinyl alcohol sulfate (II) (Antimicrob. Agents Chemother. 34, 134-138 (1990)), oligosaccharide sulfate (Japanese Patent Laid-Open Publication No. Hei2-304025) inhibit the proliferation of HIV. These compounds are produced simply by binding the sulfate group to polysaccharides, oligosaccharides or organic polymeric molecules.
In addition, the sulfated modified cyclodextrin (III) is cyclodextrin to which lipid-soluble groups such as aryl-, alkyl-groups are introduced, and also has the proliferation inhibiting activity against retroviruses, HV in particular (Japanese Patent Laid-Open Publication No. Hei4-136001).
In addition, as a virucide comprising the sulfated polysaccharide as the active ingredient is disclosed the one using an acyl derivative of a sulfated oligosaccharide glycoside (Japanese Patent Laid-Open Publication No. Hei6-256373).
At first, it was conceived that the virucidic activity of sulfated polysaccharides was due to their reverse transcriptase inhibiting activities, and now it is thought to be due to the interaction between the sulfated polysaccharide and the coat protein gp120 of HIV.
However, since sulfated polysaccharides generally have the inhibitory activity for the blood coagulation system (anticoagulant activity), they have not been accepted as the suitable medicine.
DISCLOSURE OF THE INVENTION
This invention has been developed in view of the above-mentioned problems, aiming at providing the anti-viral compound with a relatively weak anti-blood coagulating activity and a low cytotoxicity, especially the one with the anti-HIV activity.
The present inventors have actively pursued the study to resolve the above-mentioned problems, establishing that the following compounds are useful for attaining the above-described purpose and completing the present invention.
(1) A compound having all hydroxyl groups of the sugar moiety of glycoside comprising monosaccharide-lipid sulfated or the salt thereof, wherein said lipid moiety is bound to the anomeric position of said sugar moiety.
(2) The compound or the salt thereof according to (1), wherein said sugar and lipid moieties are connected by the O-glycosidic linkage or the S-glycosidic linkage.
(3) The compound or the salt thereof according to (2), wherein said lipid is linear, and said linear lipid has a branched structure.
(4) A compound or the salt thereof, wherein all hydroxyl groups of nonuloic acid moiety of the glycoside comprising a monosaccharide-lipid with said lipid bound to the anomeric position of nonuroic acid derivative are sulfated.
(5) A compound or the salt thereof, wherein all hydroxyl groups of sialic acid moiety or KDN moiety of the glycoside comprising a monosaccaride-lipid with said lipid bound to the anomeric position of sialic acid or KDN are sulfated.
(6) The compounds or the salts thereof according to (5), wherein the binding of said sialic acid moiety or KDN moiety to the lipid moiety is either the O-glycosidic of S-glycosidic linkage at position 2 of said moiety or the amidic linkage at position 1 of said residue.
(7) The compound or the salt thereof according to (6), wherein said lipid is a linear lipid, and this lipid has a branched structure.
(8) The compound or the salt thereof according to (7), wherein said branched chain is localized at position 2 of the main chain of said lipid moiety.
(9) The compound or the salt thereof according to (8), wherein said lipid moiety has a forked two chain structure due to said branching.
(10) The compound or the salt thereof according to (9), wherein said lipid moiety has an alkyl group with the skeleton-forming carbon atoms from 1 to 4 at said branching site.
(11) The compound or the salt thereof according to (9) or (10), wherein the total number of said lipid skeleton-forming atoms is from 22 to 60.
(12) The compound or the salt thereof according to (11), wherein said branched chain comprises a carbon-carbon unsaturated bond.
(13) The compound or the salt thereof according to (11), wherein said branched chain is linear.
(14) The compound or the salt thereof according to (11), wherein said branched chain has an ester linkage or ether linkage, respectively.
(15) The compound or the salt thereof according to (14), wherein said ester linkage or ether linkage is localized at positions 1 or 2 of said branched chain.
(16) The compound or the salt thereof according to (11), wherein the number of skeleton-forming atoms is from 10 to 28 per one branched chain.
(17) The compound or the salt thereof according to (16), wherein the number of skeleton-forming atoms is from 18 to 26 per one branched chain.
(18) The compound or the salt thereof according to (17), wherein the number of skeleton-forming atoms is from 24 per one branched chain.
(19) The compound or the salt thereof according to (18), wherein said forked branched chains are of the same length, respectively.
(20) The compound or the salt thereof according to (19), wherein said forked branched chains are of the same, respectively.
(21) The compound or the salt thereof according to (20), wherein said branched chain has the ester bond or the ether linkage at its position 1 or 2.
(22) The compound or the salt thereof according to (21), wherein said branched chain is linear.
(23) A medicine comprising the compound according to anyone of (1) to (3) in a pharmaceutically effective dosage.
(24) An antiviral drug containing the compound according to anyone of (1) to (3) in a pharmaceutically effective dose.
(25) An anti-HIV drug containing the compound according to anyone of (1) to (3) in a pharmaceutically effective dose.
(26) A drug containing the compound according to anyone of (1) to (21) in a pharmaceutically effective dose.
(27) An antiviral drug containing the compound according to anyone of (1) to (21) in a pharmaceutically effective dose.
(28) An anti-HIV drug containing the compound according to anyone of (1) to
(21) in a pharmaceutically effective dose.
Drugs (23 and 26), furthermore, antiviral drugs (24 and 27), especially anti-HIV drugs (24 and 27) containing compounds according to any one of the above-described (1) to (22) are within the scope of the present invention. However, since drugs, anti-viral drugs and anti-HIV drugs containing the compounds according to any one of the above-described (5) to (22) in pharmaceutically effective doses have lower anti-coagulant activity as well as lower biological toxicity than those containing compounds according to any one of the above-described (1) to (3), the former group of drugs are pharmaceutically useful. It has been confirmed that, of the above-described compounds, particularly, those having 24 skeleton-forming atoms per one branched chain (24), furthermore, each of said branched chains of which has the same structure, is linear and has the ether bond at its position 1 or 2, are pharmaceutically useful (examples 12, 13, 29, 50 and 59).
BEST MODE FOR CARRYING OUT THE INVENTION
Definition of the Terms
As used in this specification, by the term “nonuloic acid” is meant the same nonuloic acid as used general
Fujita Shuji
Numata Masaaki
Nunomura Shigeki
Sugimoto Mamoru
Suzuki Kazuo
Gitomer Ralph
Khare Devesh
Nissan Food Products Co., Ltd.
Oliff & Berridg,e PLC
LandOfFree
Compounds comprising sulfated nonulonic acid having... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compounds comprising sulfated nonulonic acid having..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compounds comprising sulfated nonulonic acid having... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2842834