Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-08-07
1999-07-13
Davis, Zinna Northington
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546334, C07D21302, A61K 3144
Patent
active
059227435
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a pyridine derivative having an ability to act as a neurotrophic factor and a salt thereof.
BACKGROUND ART
It has been suggested that in Alzheimer's disease, which has recently been increasing in prevalence, degeneration and dysfunction of cholinergic neurons are intimately related to memory disorder and lowering of
It has been reported that NGF can suppress the degeneration and dysfunction of centrally cholinergic neurons of the central nervous system due to also can ameliorate maze learning disorder of aged rats and suppress in drug), 145, 579 (1986)!. These show that NGF can serve as a drug for curing Alzheimers disease. Furthermore, it has been confirmed that NGF can prevent death of hippocampal neuronal cells after cerebral ischemia in gerbils, and it can be presumed that NGF is a useful drug for curing secondary disorder of cerebral ischemia.
On the other hand, it has been clarified that NGF functions to promote recovery of peripheral neuropathy and is a useful drug for curing the peripheral neuropathy. In addition to NGF, many biomolecules having the ability to maintain the survival and functioning of neuronal cells or showing an ability to remedy degeneration have been found, and they are now called neurotrophic factors. Thus, it can be presumed that these neurotrophic factors are useful drugs for curing central neuronal degeneration and peripheral neuropathy. All the biomolecules called neurotrophic factors including NGF are proteins. In using proteins as drugs for curing central nerve disorders, it can be presumed from their properties that intracerebroventricular administration must be carried out. Thus, there are still many practical problems.
Accordingly, a drug comprising a low molecular weight compound having the ability to act as a neurotrophic factor capable of more simple administration has been desired. Thus, an object of the present invention is to provide a novel compound having the ability to act as a neurotrophic factor.
DISCLOSURE OF THE INVENTION
As a result of extensive studies on a large number of compounds to attain the above-mentioned object, the present inventors have found that some pyridine derivatives have the ability to act as a neurotrophic factor and have established the present invention.
That is, the present invention provides a pyridine derivative represented by the following formula: ##STR2## where R.sup.1 shows the ability group represented by any one of the following formulae (II)-1 to (II)-6: ##STR3## or a salt thereof, and a pyridine derivative represented by the following formula: ##STR4## where R.sup.2 shows an amino group or the ability group represented by any one of the following formulae (IV)-1 to (IV)-5: ##STR5## or a salt thereof.
In the present invention, a salt of pyridine derivative means a pharmacologically acceptable salt, and includes, for example, salts with a mineral acid such as hydrochloric acid, sulfuric acid, phosphoric acids nitric acid, etc., and salts with an organic acid such as citric acid, succinic acid, tartaric acid, methanesulfonic acid, etc.
The present compound can be prepared, for example, according to the following procedure:
First, a compound represented by the following formula: ##STR6## where R.sup.3 is a methyl group, a carboxyl group or an acetamide group, and a compound represented by the following formula: ##STR7## where R.sup.4 is a hydrogen atom, a carboxyl group or an acetamide group, are subjected to condensation in the presence of an alkali, whereby a compound represented by the following formula: ##STR8## where R.sup.3 and R.sup.4 have the same meanings as defined above, can be obtained.
An alkali for use in the condensation reaction includes, for example, potassium hydroxide, sodium hydroxide, sodium methoxide, potassium t-butoxide, potassium carbonate, sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc. As a reaction solvent, methanol, ethanol, n-propanol, isopropanol, t-butanol, etc. can be used alone or in a mixture with water. Rea
Hanabusa Kenji
Hanada Kazunori
Mizobe Fumio
Shirai Hirofusa
Takahashi Yuki
Davis Zinna Northington
Taisho Pharmaceutical Co. Ltd.
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