Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-04-14
1999-12-28
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514313, 514314, 546169, 546171, C07D21540, C07D40112, A61K 3147
Patent
active
060082305
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to new heterocyclic compounds and pharmaceutically acceptable salts thereof.
More particularly, it relates to new heterocyclic compounds and pharmaceutically acceptable salts thereof which have inhibitory activities of vacuolar type H.sup.+ -adenosine triphosphatases (H.sup.+ -ATPases), especially osteoclast H.sup.+ -ATPase, and inhibitory activities of bone resorption, and therefore are useful for the prevention and/or the treatment of bone diseases caused by abnormal bone metabolism in human being or animals as the inhibitors of bone resorption or the inhibitors of bone metastasis.
And further, the present invention relates to processes for the preparation of said compounds, to a pharmaceutical composition comprising the same and to a method for the prevention and/or the treatment of above-mentioned diseases in human being or animals, and to a use of said compounds and pharmaceutically acceptable salts thereof for the prevention and/or the treatment of above-mentioned diseases in human being or animals.
BACKGROUND ART
Some heterocyclic compounds have been known as described in, for example, J. Chem. Soc. Pak. (1995), 17(4), 232-6; J. Am. Chem. Soc. (1994), 116(24), 11014-19; or Chem. Pharm. Bull. (1990), 38(10), 2841-6. However, it is not known that said compounds have inhibitory activities of vacuolar type H.sup.+ -ATPases or inhibitory activities of bone resorption.
DISCLOSURE OF THE INVENTION
The object heterocyclic compounds of this invention are new and can be represented by the following general formula [I]: ##STR4## wherein R.sup.1 is a heterocyclic group or aryl, each of which may be substituted with suitable substituent(s), ##STR5## is a group of the formula: ##STR6## in which R.sup.2 is hydrogen, halogen, lower alkyl, lower alkoxy or halo (lower) alkyl, halo(lower)alkyl, halo(lower)alkyl, and ##STR7## is a group of the formula: ##STR8## in which R.sup.5 is hydrogen or lower alkyl, alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, a heterocyclicthio group, acyl, acylamino, aryl, substituted aryl or a heterocyclic group, and alkenyl, substituted lower alkenyl, azido, amino, substituted amino, hydrazino, substituted hydrazino, semicarbazido, substituted semicarbazido, thiosemicarbazido, substituted thiosemicarbazido, hydroxy, substituted hydroxy, mercapto, substituted mercapto, acyl or a substituted or unsubstituted heterocyclic group, or ##STR9## in which R.sup.10 is hydrogen or lower alkyl, substituent selected from the group consisting of a heterocyclic group and lower alkoxy, each hydrogen.
The object compound [I] or its salt can be prepared by processes as illustrated in the following reaction schemes. ##STR10## wherein substituent selected from the group consisting of hydroxy and lower alkoxy, and lower alkyl optionally substituted with substituent(s) selected from the group consisting of hydroxy, lower alkoxy and a heterocyclic group; or form a heterocyclic group optionally substituted with lower alkyl, substituted or unsubstituted N-containing heterocyclic-N-yl group, ##STR11## are each as defined above.
In the above and subsequent description of the present specification, suitable examples of the various definitions to be included within the scope of the invention are explained in detail in the following.
The term "lower" is intended to mean a group having 1 to 6 carbon atom(s), unless otherwise provided.
In this respect, the term "lower" in lower alkenyl moiety or lower alkynyl moiety in the various definitions is intended to mean a group having 2 to 6 carbon atoms.
In this respect, the term "lower" in lower alkenoyl moiety, lower alkynoyl moiety and cyclo(lower)alkyl moiety in the various definitions is intended to mean a group having 3 to 6 carbon atoms.
Suitable "heterocyclic group" and all heterocyclic moieties in the various definitions mentioned in this specification and claims such as in the terms "heterocyclic(lower)alkyl", "heterocycli
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Kawai Yoshio
Kayakiri Natsuko
Oku Teruo
Satoh Shigeki
Urano Yasuharu
Fujisawa Pharmaceutical Co. Ltd.
Rao Deepak R.
Shah Mukund J.
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