Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2001-09-10
2003-02-11
Richter, Johann (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S054000, C536S118000, C514S025000
Reexamination Certificate
active
06518410
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a novel immunosuppressive agent. More specifically, the present invention relates to a novel immunosuppressive agent containing, as an effective ingredient, a certain &agr;/&bgr;-sulfoquinovosylacylglycerol derivative and/or a salt thereof.
The present invention also relates to an anticancer agent, and in particular to an anticancer agent comprising, as an effective ingredient, a certain &bgr;-sulfoquinovosylacylglycerol derivative and/or a salt thereof.
Further, the present invention also relates to a DNA polymerase &agr; inhibitor comprising, as an effective ingredient, a certain &bgr;-sulfoquinovosylacylglycerol derivative and/or a salt thereof.
The &bgr;-sulfoquinovosylacylglycerol derivatives that are the effective ingredients of the anticancer agent, immunosuppressive agent and DNA polymerase &agr; inhibitor of the present invention, are novel compounds. The present invention also relates to the novel &bgr;-sulfoquinovosylacylglycerol derivatives.
2. Description of the Related Art
In clinical treatment presently performed, transplantation can be employed to treat chemotherapeutically untreatable diseases. Transplantation is the technology for treating a disease by replacing partly or entirely of a diseased organ with a healthy organ taken from another individual. Organ transplantation has been performed with respect to a wide variety of organs such as kidney, liver, lung, intestine, heart, pancreas, and cornea. The number of organ transplantations has been increased.
The immune response of skin is inherently high. However, skin transplantation can be made successfully if a graft skin transplanted from one person to another can be kept alive for at least a few weeks. This is because new dermal tissue, if a graft epidermis is kept alive for a few weeks, can regenerate itself, thereby recovering from a dermal tissue damage. Therefore, it is possible to make physical recuperation of serious and extensive burn or laceration by transplanting a dermal tissue from another person.
The most fearful problem residing in tissue or organ transplantation is a rejection caused by a recipient's immune response.
Under these circumstances, in order to develop an immunosuppressive agent capable of preventing the rejection in a recipient, thereby attaining permanent fixation of a transplanted organ, intensive studies have been conducted since the 1970s, particularly in European countries and U.S.A.
On the other hand, an immunosuppressive agent may also be important in treating autoimmune diseases such as rheumatism and collagen disease, since it can mitigate the symptoms to a certain degree.
Up to the present, cyclosporin A and FK506, etc., have been developed as immunosuppressive agents. However, the functional mechanisms of these immunosuppressive agents resemble each other and their chronic toxicity is a matter of concern. Thus, to attain prolonged life in next-generation organ transplantation, another type of immunosuppressive agent is desired which has a lower toxicity based on a different chemical structure, and thus, different functional mechanism can be expected.
It has been found that naturally-occurring sulfur-containing glycolipids have pharmaceutical activities such as an anticancer effect (Sahara et al., British Journal of Cancer, 75(3), 324-332, (1997)); inhibitory activities against DNA polymerase (Mizushina et al., Biochemical Pharmacology, 55, 537-541 (1998), Ohta et al., Chemical & Pharmaceutical Bulletin, 46(4), 1998)); and HIV suppressive effect (National Patent Publication No. 5-501105). However, it has not yet been found that a sulfur-containing glycolipid, in particular, a sulfoquinovosylacylglycerol derivative, has an immunosuppressive activity.
Further, almost all of the sulfoquinovosylacylglycerol derivatives described in the documents are derived from natural products. Thus, the bonding between the sugar moiety and the glycerol moiety is an &agr;-configuration. A &bgr;-sulfoquinovosylacylglycerol in which the bonding between the sugar moiety and the glycerol moiety is a &bgr;-configuration, has not yet been known.
BRIEF SUMMARY OF THE INVENTION
An object of the present invention is to provide a novel immunosuppressive agent. More specifically, the object of the present invention is to provide an immunosuppressive agent showing low toxicity and usability of long-term administration, and high immunosuppressive activity as well.
Other objects of the present invention is to provide a novel anticancer agent and DNA polymerase &agr; inhibitor.
The present inventors have conducted studies to attain the aforementioned object. As a result, they found that specific sulfoquinovosylacylglycerol derivatives have a remarkable immunosuppressive activity and accomplished the present invention. The present invention provides an immunosuppressive agent containing, as an active ingredient, at least one compound selected from the group consisting of:
compounds represented by Formula (1-1):
where 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, and
a pharmaceutically acceptable salt thereof.
The present invention also provides an anticancer agents and DNA polymerase &agr; inhibitor containing, as an active ingredient, at least one compound selected from the group consisting of:
compounds represented by Formula (1-2):
where R
101
and R
102
have the same meaning as R
101
and R
102
in General formula (1-1), respectively, and
a pharmaceutically acceptable salt thereof.
The &bgr;-sulfoquinovosylacylglycerol derivatives represented by General formula (1-2) mentioned above are novel compounds. The present invention also provides the &bgr;-sulfoquinovosylacylglycerol derivatives represented by General formula (1-2).
Additional objects and advantages of the present 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 present invention. The objects and advantages of the present invention may be realized and obtained by means of the instrumentalities and combinations particularly pointed out hereinafter.
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Fujita Tatsuya
Masaki Kazuyoshi
Nakayama Kotaro
Ohta Keisuke
Sahara Hiroeki
Crane L E
Frishauf Holtz Goodman & Chick P.C.
Richter Johann
Toyo Suisan Kaisha Ltd.
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