Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1989-05-04
1990-02-06
Lee, Mary C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544250, 544278, 514267, A61K 31505, C07D23900, C07D49100
Patent
active
048988677
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
1. Technical Field
The present invention relates to novel thienopyrimidine derivatives or pharmaceutically acceptable salts thereof, pharmaceutical compositions containing the same and aldose-reductase inhibitors.
2. Background Art
Kinoshita et al. reported that the aldose-reductase participates in crisis and development of complications of diabetes such as diabetic cataract, diabetic neuropathy, diabetic nephropathy and diabetic retinopathy (J. H. Kinoshita et al., Journal of the American Medical Association, 246, 257, (1981)). The aldose-reductase reduces aldoses such as glucose and galactose to polyols such as sorbitols. The polyol produced is relatively stable and rarely passes extracellularly, consequently accumulating intracellularly. Since the hyperglycemic status as in diabetes, promotes the activity of aldose-reductase, the polyols accumulate excessively in the lenses, neurons, vascular tissues, etc. Therefore, the osmotic pressure increases in these tissue cells, which results in swell of the tissues, damaged cellular function and tissue disorders. In view of these situations, it has been desired to develop compounds useful for remedy and prevention of various diabetic complications and excellent in aldose-reductose inhibiting activity by inhibiting the aldose-reductase and thus avoiding abnormal intracellular accumulation of polyols.
DISCLOSURE OF THE INVENTION
The inventors conducted extensive research in view of the above problems of the prior art and found that the novel thienopyrimidine derivatives represented below by the formula (I) and their salts exhibit outstanding aldose-reductase inhibitory effect and are useful as medicaments. Therefore, the invention has been accomplished.
The present invention provides thienopyrimidine derivatives of the formula (I) ##STR3## wherein R.sub.1 and R.sub.2 are the same or different and each represent hydrogen, halogen, lower alkyl, cycloalkyl or pheny, R.sub.1 and R.sub.2 taken together may form a ring with an alkylene chain, R.sub.3 represents lower alkyl or a group of the formula ##STR4## (in which R.sub.4 is lower alkyl, lower alkoxy or halogen, m is 0, 1 or 2, and R.sub.5 is hydrogen or halogen) and Z is oxygen or sulfur, or pharmaceutically acceptable salts thereof.
Examples of halogen atoms represented by R.sub.1, R.sub.2, R.sub.4 and R.sub.5 in the formula (I) are fluorine, chlorine, bromine and iodine. Examples of lower alkyl groups represented by R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are straight chain or branched chain C.sub.1 -C.sub.6 alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl and isohexyl. Examples of cycloalkyl groups represented by R.sub.1 and R.sub.2 are C.sub.3 -C.sub.7 cyclopropyl, cyclobutyl, cyclohexyl, etc. Examples of rings with an alkylene chain formed by R.sub.1 and R.sub.2 taken together are ##STR5## etc. Examples of lower alkoxy groups represented by R.sub.4 are straight chain or branched chain C.sub.1 -C.sub.6 alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentoxy and hexyloxy.
The salts of the compounds of the present invention are pharmaceutically acceptable salts thereof including salts of alkali metals such as sodium, potassium and lithium; salts of alkaline earth metals such as calcium and magnesium; salts of ammonium; salts of tetraalkylammoniums such as tetramethylammonium, tetraethylammonium, tetrapropylammonium and tetrabutylammonium; salts of mono-, di- or trialkylamines such as methylamine, ethylamine, isopropylamine, tert-butylamine, dimethtylamine, diethylamine, trimethylamine and triethylamine; salts of cycloalkylamines such as cyclopentylamine and cyclohexylamine; salts of phenyl(lower alkyl)amines such as benzylamine, phenethylamine and phenylpropylamine; salts of 5- or 6-membered heterocyclic compounds containing in its ring structure one or two nitrogen atoms as the heteroatom such as piperidine, piperazine, imidazoline and pyrrole; salts of mono-, d
REFERENCES:
patent: 4701528 (1987-10-01), Thompson et al.
Ichiro Yamawaki
Issei Okazaki
Kazuo Ogawa
Naruo Nomura
Yoichi Matsushita
Lee Mary C.
Taiho Pharmaceutical Company Limited
Whittenbaugh Robert C.
LandOfFree
Thienopyrimidine derivaties as aldose-reductase inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Thienopyrimidine derivaties as aldose-reductase inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Thienopyrimidine derivaties as aldose-reductase inhibitors will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-441984