Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-12-09
1998-06-09
Ramsuer, Robert W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514625, 544 581, 544168, 544400, 546221, 546233, 546234, 548550, A61K 3116, A61K 31535, C07D29514, C07C23335
Patent
active
057634386
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to a 2-acylaminopropanol compound which is a ceramide analogue, and a medical composition which contains the same as an active ingredient and exhibits effects as an antiviral agent or an agent for treating neuronal diseases.
BACKGROUND ART
It has been known that glycosphingolipids (hereinafter referred to as GSL) in which various sugars such as glucose, galactose, sialic acid, etc. are bound to a ceramide molecule exist as a constitutional component of cell surface membranes of mammal cells and they are closely related to a cellular function such as development, growth, differentiation, neoplastic transformation, immunoreaction, etc. through a receptor function of a physiologically active substance, an intercellular mutual recognition and interaction, etc.
Also, it has been known that in many infections by virus and bacteria, GSL is concerned in binding with them as a receptor of host cells, and particularly glucosylceramide described below binds to virus such as adenovirus, herpes virus, influenza virus, mumps virus, Sendai virus, rabies virus, rotavirus, Reovirus and HTLV virus (K-A Karlson, Trends in Pharmacol. Sci., vol. 12, pp. 265-272 (1991)). Further, there has been suggested possibility that galactosylceramide functions as a receptor of host cells with regard to human immunodeficiency virus (HIV) (Science, vol. 253, pp. 320-323 (1991)).
GSL is a complex glycolipid consisting of a ceramide long-chain aliphatic acid wherein (C.sub.13 H.sub.27 --CH.dbd.CH--CH(OH)--CH(NHCOR)--CH.sub.2 OH) links to an amino group of a sphingosine base via acid amide bonding and a hydrophilic sugar chain portion. Nearly 300 kinds of molecular species of GSL which are different in a sugar chain structure binding to a ceramide have been found and can be roughly classified into 6 basic sugar chain series (gala series, globo series, isoglobo series, lacto series, neolacto series and ganglio series). Among the above series, 5 series of GSL except for gala series are biosynthesized from glucosylceramide enzymatically produced by using ceramide and uridine diphosphate-glucose as a starting substance and further adding various sugars thereto.
Therefore, antagonistic inhibition of binding of a receptor of GSL such as glucosylceramide and/or galactosylceramide, etc. on the surface of a host cell membrane and virus leads to development of an antiviral agent showing a wide spectrum having an effect on viral infectious diseases.
The present inventors have previously found and reported that a 2-acylaminopropanol compound having a morpholino group, such as 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (hereinafter referred to as PDMP), etc. has an antiviral activity (Seikagaku vol. 65(8), p. 695 (1993)).
On the other hand, gangliosides are GSL containing sialic acid, and it is said that it has an activity to recoveries from injury of peripheral nerves and a disorder of central nervous system, i.e., acceleration of regeneration of neurons and a process of neurotransmission. Heretofore, effectiveness of exogenous gangliosides to various neuronal disease models has been investigated.
The present inventors have synthesized novel compounds into which other nitrogen-containing substituent is introduced in place of the above morpholino group and examined an antiviral activity thereof to find that they have a further strong antiviral activity as compared with the above PDMP, etc.
An object of the present invention is to provide a new type of an antiviral agent using such a novel 2-acylaminopropanol compound.
Another object of the present invention is to provide an agent for treating various diseases caused by disorders of central nervous system or peripheral nervous system, using a novel 2-acylaminopropanol compound which accelerates biosynthesis of endogenous GSL, particularly gangliosides in neurons.
DISCLOSURE OF THE INVENTION
The present inventors have studied variously in order to develop an antiviral agent based on a new mechanism and consequently found that a specific 2-acylaminopropanol
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Inokuchi Jin-ichi
Jinbo Masayuki
Nagai Takayuki
Yamada Haruki
Ramsuer Robert W.
Seikagaku Corporation
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