Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-10-05
2000-09-05
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546301, 546290, 514256, 514345, 514423, 514463, 514530, 514546, 544335, 548530, 549453, 560121, 560126, 560129, 560231, 562503, 562553, A61K 3144, C07D21360
Patent
active
061143642
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to 2,3-di-substituted cyclopentanone derivatives, process for producing the same, and medicinal use thereof, especially new neuron differentiation accelerator.
BACKGROUND ART
It is demonstrated that the nerve growth factor (hereinafter referred to as "NGF") shows, in vitro, manifesting a regenerative activity on nerve cells of senile animals because NGF has an activity for elongating neurite and regulating aproduction of aneurotransmitter [("Age," Vol. 8, page 19 (1985)]. On the other hand, it is known that the PC 12 cells which are the cells of the strain produced by cloning a species of brown cells of murine adrenal medulla, are caused by addition of NGF to cease propagation and succumb to differentiation into sympathetic nerve-like cells having neurite. Since the NGF has these activities, this has been drawn attention as an antidemential pharmaceutical compositions in recent years. It has been studied that fibroblast growth factor or Interleukin 6 etc. besides NGF induces the growth of neurite by using these cell. Further also, recently, it has shown that SUTAROSUPORIN of a low molecular substance likewise induce elongation of neurite ["Neurochemistry," Vol. 26, pp. 200-220 (1987)].
Since SUTAROSUPORIN mentioned above is a low molecular substance, which differs from NGF, the development for medical use is expected. However, this is not utilized at the present time because of a strong toxicity.
Recently, the physiologically active substance NK 175203 produced by the microorganism of Streptomyces sp. NK 175203 (FERM BP-4372) has been found to have an activity for inducing elongation of neurite (WO 95/31992).
The physiologically active substance NK 175203 (hereinafter referred to as "cystacyclin") is expected to develop into medicine because it is a low molecular compound manifesting low toxicity. But the product amount is only a little because it is produced by the microorganism. Thus, there has been demanded for supply of a low molecular compound obtained by chemical synthesis, which has low toxicity and has a strong activity for promoting induction of neurite.
DISCLOSURE OF THE INVENTION
As the results of the various studies for the structure analysis of cystacyclin and the derivatives thereof, the present inventors have found that cyclopentanone derivative needs at least one substituted lower alkyl group as a substituent on the ring of cyclopentanone in order to having the activity for promoting nerve differentiation. The preferable compound in the activity is a cyclopentanone derivative having one substituted lower alkyl group on the ring of cyclopentanone and an another substituent in the next position. The present inventors have found that the more preferable compounds are 2,3-di-substituted cyclopentanone derivatives shown as the general formula (I) described below or the pharmacologically acceptable salt thereof and completed the present invention.
The present invention relates to a 2-substituted lower alkyl-3-substituted cyclopentanone derivative or the pharmacologically acceptable salt thereof, and the process for the production thereof and a pharmaceutical composition comprising it.
In more detail, the present invention relates to 2,3-di-substituted cyclopentanone derivative represented by the following the general formula (I) ##STR2## wherein X is O, S, SO, SO.sub.2, or NH; Y is a hydrocarbon residue having 1-6 carbon atoms, which is substituted or unsubstituted, and having a whole molecular weight of from 15-400 in the residue, and may contain 1 or 2 hetero atoms in the ring when the hydrocarbon residue is a cyclic group, and residue having 1-4 carbon atoms, which is substituted or unsubstituted, production thereof, and a pharmaceutical composition comprising it.
The present invention provides a novel compound having an activity for accelerating differentiation of neurons. The compound of the present invention having two or more asymmetric carbon atoms therein may be an optically active substance or optically inactive substance and it is suitable
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Masuda Kuniko
Morino Tomio
Saito Seiichi
Aulakh Charanjit S.
Nippon Kayaku Co. Ltd.
Rotman Alan L.
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