Imidazole derivatives and process for preparing the same

Details Imidazole derivatives and process for preparing the same Imidazole derivatives and process for preparing the same

1996-06-10

1999-08-03

Morris, Patricia L.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

5483361, 5483381, 5483415, A61K 31415, C07D23360, C07D23361

Patent

active

059326077

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to therapeutic agents, which are novel imidazole derivatives, and is particularly concerned to imidazole derivatives being anticholinergic agents, especially selective antagonists against muscarinic acetylcholine receptor, process for preparing the same, and pharmaceutical compositions comprising them.


BACKGROUND TECHNOLOGIES

The anticholinergic agents exhibit anticonvulsant action and antisecretory action and have usefulness as the therapeutic agents for functional disorders of intestine, bladder, etc. At present, alkaloids such as atropine, aminoalkanol esters such as oxybutynin and propantheline bromide, their quaternary ammonium salts and the like have been known as the anticholinergic agents, and they are blocking agents for muscarinic acetylcholine receptor. However, because of their poor selectivity among organs in the antagonistic action, the side effects are caused and has posed problems. Therefore, the development of highly selective anticholinergic drug is desired in clinic.
Though, there is a report on antagonists against muscarinic acetylcholine receptor, having imidazole group as a substituent, (Japanese Unexamined Patent Publication No. Hei 4-103581), these compounds are different from the inventive compounds in the structure, and yet they don't have adequate activity to satisfy.
The invention provides drugs having higher selectivity and more potent antagonistic activity on muscarinic acetylcholine receptor on smooth muscle than muscarinic acetylcholine receptor on heart.


DISCLOSURE OF THE INVENTION

The inventors had focused on imidazole derivatives for the purpose aforementioned. As a result of diligent studies, so have found that imidazole derivatives represented by the general formula (1) ##STR2## group, R.sub.2 is a cyano group; a carboxyl group; a CONR.sub.7 R.sub.8 group (wherein R.sub.7 and R.sub.8 each independently represent hydrogen atom or lower alkyl group, or R.sub.7 and R.sub.8 may form a ring by alkylene chain which may contain hetero atom) or a COOR.sub.9 group (wherein R.sub.9 is a lower alkyl group), R.sub.3 is a hydrogen atom or a lower alkyl group, R.sub.4, R.sub.5 and R.sub.6 each independently represent hydrogen atom, lower alkyl group which may have substituent or cycloalkyl groups, or may form a condensed ring at the positions of R.sub.5 and R.sub.6 with benzene ring, and m is an integer from 1 to 6!, or a general formula (2) ##STR3## group, R.sub.2 is a cyano group, a carboxyl group, a CONR.sub.7 R.sub.8 group (wherein R.sub.7 and R.sub.8 each independently represent hydrogen atom or lower alkyl group, or R.sub.7 and R.sub.8 may form a ring by alkylene chain which may contain hetero atom) or COOR.sub.9 group (wherein R.sub.9 is a lower alkyl group), R.sub.3 is a hydrogen atom or a lower alkyl group, R.sub.4, R.sub.5 and R.sub.6 each independently represent hydrogen atom, lower alkyl group which may have substituent or cycloalkyl group, or may form a condensed ring at the positions of R.sub.5 and R.sub.6 with benzene ring, R.sub.10 is a lower alkyl group or an aralkyl group which may have substituent, m is an integer from 1 to 6, and Z is a halogen atom!, antagonistic activity on muscarine receptor of smooth muscles of alimentary canal, trachea, bladder, etc., and have brought the invention to completion.
By this reason, the inventive compounds are useful for the treatment of motility disorders of alimentary canal such as irritable bowel syndrome, diverticulum disease, functional diarrhea, esophageal achalasia and cardiospasm, treatment of biliary and urethral spasms, urinary incontinence, etc, treatment of chronic respiratory obstructive diseases, and the like.
The term "substituents" applied to phenyl group shown in the invention indicates halogen, lower alkyl group, lower alkoxy group, nitro group, phenyl group, etc. The term "halogens" indicate fluorine, chlorine, bromine and iodine.
For the "lower alkyl groups" indicate straight or branched chain with the number of carbons from 1 to 6, such as methyl, ethyl and

REFERENCES:
patent: 4073921 (1978-02-01), Miller, I et al.
patent: 4225723 (1980-09-01), Miller, II et al.
patent: 4320134 (1982-03-01), Iizuka et al.
patent: 4605661 (1986-08-01), Hirsch et al.
patent: 4923865 (1990-05-01), Cossement et al.
Kaiser et al, "Synthesis and Antimuscarinic, etc" CA 117:233975, 1992.
Cram and Hammond, "Organic Chemistry" McGraw-Hill Book Co, NY (1964) 2nd Ed, pp. 565-567.

Affiliated with

Also associated with

Rating

Imidazole derivatives and process for preparing the same does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Imidazole derivatives and process for preparing the same, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Imidazole derivatives and process for preparing the same will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-849882