Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2001-08-24
2004-07-06
Wilson, James O. (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S054000, C536S118000, C514S025000
Reexamination Certificate
active
06759522
ABSTRACT:
This application is based upon and claims the benefit of priority from the prior Japanese Patent Application No. 11-051396, filed Feb. 26, 1999, the entire contents of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to novel sulforhamnosylacylglycerol derivatives. The novel sulforhamnosylacylglycerol derivatives of the present invention are useful as medicaments, more specifically, a DNA polymerase inhibitor and an anticancer agent.
2. Description of the Related Art
Sulfur-containing glycolipids contained in natural products derived from, e.g., algae and higher plants are known to have physiological activities.
For example, in a document of Ohta et al. (Chemical & Pharmaceutical Bulletin, 46(4), (1998)), it is described that a specific sulfoquinovosyldiacylglycerol derivative derived from red algae,
Gigartina tenella,
exhibits not only inhibitory activities against DNA polymerases &agr; and &bgr; of higher organisms but also an inhibitory activity against HIV-derived reverse-transcriptase.
Furthermore, in a document of Mizushina et al. (Biochemical Pharmacology 55, 537-541 (1998)), it is described that specific sulfoquinovosyldiacylglycerol derivatives derived from a pteridophyte exhibits inhibitory activities against a calf DNA polymerase &agr; and a rat DNA polymerase &bgr;, but does not have any influence on the inhibitory activity against HIV-derived reverse-transcriptase.
On the other hand, in a document of Sahara et al. (British Journal of Cancer, 75(3), 324-332 (1997)), it is described that a fraction of sulfoquinovosylmonoacylglycerols obtained from sea urchin intestine exhibits anticancer activities in-vivo and in-vitro.
However, sulfur-containing glycolipids disclosed in Ohta et al., Mizushina et al., and Sahara et al., are sulfoquinovosylacylglycerol derivatives having an &agr;-quinovose (i.e., 6-deoxy-&agr;-glucose) as a sugar component thereof. A sulfur-containing glycolipids having a rhamnose (i.e., 6-deoxymannose) as a sugar component has not yet been known.
Furthermore, National Patent Publication No. 5-501105 describes that a sulfoquinovosyldiacylglycerol derivative has an anti-virus activity. More specifically, it discloses that the derivative has an anti-HIV (human immunodeficiency virus) activity, however it does not disclose that the derivative has inhibitory activities against DNA polymerase and anticancer activities.
BRIEF SUMMARY OF THE INVENTION
An object of the present invention is to provide a novel sulforhamnosylacylglycerol derivative having a rhamnose as a sugar component and its use as a medicament.
The present invention provides compounds represented by the following General Formula (1):
wherein R
101
represents an acyl residue of a higher fatty acid, and R
102
represents a hydrogen atom or an acyl residue of a higher fatty acid.
Furthermore, the present invention also provides medicaments containing, as an active ingredient, at least one compound selected from the group consisting of the compounds represented by General Formula (1) and pharmaceutically acceptable salts thereof.
Additional objects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and obtained by means of the instrumentalities and combinations particularly pointed out hereinafter.
DETAILED DESCRIPTION OF THE INVENTION
In the specification, the term “carbon atoms” of a protecting group refers to the number of carbon atoms assuming that the protecting group is unsubstituted. To be more specific, when the group represented by R
1
is a substituted alkyl group, its number of carbon atoms is that of the alkyl group itself, and the number of carbon atoms of the substituent on the alkyl group is not counted. The same conditions are applicable to the case where the protecting group is other than the alkyl group.
First, the sulforhamnosylacylglycerol derivative (hereinafter, also referred to as “sulforhamnosylacylglycerol derivative of the present invention”) represented by General Formula (1) of the present invention will be more specifically explained.
The sulforhamnosylacylglycerol derivative of the present invention is represented by following General Formula (1):
wherein R
101
represents an acyl residue of a higher fatty acid, and R
102
represents a hydrogen atom or an acyl residue of a higher fatty acid.
In General Formula (1), R
101
represents an acyl residue of a higher fatty acid. The fatty acids providing the acyl residues represented by R
101
includes straight-chain or branched-chain, saturated or unsaturated higher fatty acids.
When the sulforhamnosylacylglycerol derivative of the present invention is used as a medicament, R
101
is preferably an acyl residue of a straight-chain saturated higher fatty acid in view of its anticancer activity, in particular, against a solid tumor, for example, gastric cancer and colon cancer, and more preferably a group represented by CH
3
(CH
2
)
n
CO— (wherein n is an integer of 12-24, preferably an even number of 12-24). The present inventors predict that sulforhamnosylacylglycerol derivatives, where R
101
of General Formula (1) of the invention is represented by CH
3
(CH
2
)
n
CO— (n>24), may also have an anticancer activity. However, the sulforhamnosylacylglycerol derivatives having such long-chain acyl residues are not used in practice in view of manufacturing cost and the like.
In General Formula (1) mentioned above, R
102
represents a hydrogen atom or an acyl residue of a higher fatty acid. The fatty acids providing the acyl residues include straight-chain or branched-chain, saturated or unsaturated higher fatty acids, and more specifically, include the same fatty acids as those mentioned above for R
101
.
When the sulforhamnosylacylglycerol derivatives of the present invention are used as a medicament, R
102
is preferably a hydrogen atom in view of their anticancer activities, in particular, against solid tumor, for example, gastric cancer and colon cancer.
In General formula (1), the sugar skeleton of the sulforhamnoside may be either a boat or chair configuration. However, the chair configuration is preferable in view of stability. Furthermore, the bonding between sulforhamnose and glycerol is either an &agr;- or &bgr;-bonding. However, when the sulforhamnosylacylglycerol derivatives of the present invention are used as a medicament, the &agr;-bonding is preferable in view of manufacturability. Furthermore, the absolute configuration of the carbon (asymmetric carbon) at the 2-position of the glycerol moiety may be either the S- or R-configuration.
Now, a method of preparing the sulforhamnosylacylglycerol derivatives of the present invention will be explained below.
The sulforhamnosylacylglycerol derivatives of the present invention can be prepared via (Step A) to (Step J) in accordance with the reaction procedure shown in Scheme 1 below:
(Step A) The hydroxyl group bonded to the C1 carbon of the D-mannose is converted into a 2-propenyl group. (Step B) The hydroxyl group of the C6 carbon of the mannose is protected. (Step C) The hydroxyl groups bonded to the C2, C3 and C4 carbons of the mannose are protected. (Step D) The protecting group of the C6 carbon previously protected is deprotected. (Step E) The hydroxyl group bonded to the C6 carbon is substituted with a group (for example, an alkylsulfonyloxy group or arylsulfonyloxy group) which can be converted to a carbonylthio group. (Step F) The C6 carbon is converted into a carbonylthio group. (Step G) The 2-propenyl group bonded to the C1 carbon is converted into a diol. (Step H) Both of the hydroxyl groups or only the hydroxyl group at the 1-position of the diol thus obtained are/is esterified with a desired higher fatty acid. (Step I) The carbonylthio group at the C6 carbon is converted into a sulfonate salt. (Step J) The protecting groups of C2, C3 and C4 carbons of the sulfonate salt obtained are
Fujita Tatsuya
Masaki Kazuyoshi
Nakayama Kotaro
Ohta Keisuke
Sahara Hiroeki
Crane Lawrence E
Frishauf Holtz Goodman & Chick P.C.
Toyo Suisan Kaisha Ltd.
Wilson James O.
LandOfFree
Sulforhamnosylacyglycerol derivatives and use thereof as... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Sulforhamnosylacyglycerol derivatives and use thereof as..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Sulforhamnosylacyglycerol derivatives and use thereof as... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3208472