4-amino-3-acylnaphthyridine derivatives

Details 4-amino-3-acylnaphthyridine derivatives 4-amino-3-acylnaphthyridine derivatives

1997-07-03

1999-09-14

Dentz, Bernard

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

546123, C07D47104

Patent

active

059525045

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention is related to new 4-amino-3-acylnaphthyridine derivatives or their pharmaceutically acceptable salts, which are useful as anti-ulcer or gastric juice-secretion suppressor, to a method for producing them and intermediates for the method.


BACKGROUND OF THE INVENTION

It has been reported that the gastrointestinal ulcers may be caused by an excessive secretion of acids such as hydrochloric acid or pepsin as well as by an action of anti-inflammatory agents such as indomethacin, toxic chemicals, pathogenic virus or toxic microorganisms. In particular, it had been reported that H.sup.+ /K.sup.+ ATPase, a proton carrying enzyme which occurs in gastric mucosa, is involved in the formation of ulcer caused by a secretion of excess gastric juices.
EP 339768A, EP 0334491A and U.S. Pat. No. 4,343,804 disclose 4-aminoquinoline derivatives having an effective anti-gastric juice secretion activity.
The present inventors surprisingly found out that if quinoline nucleus of 4-aminoquinoline derivatives of the prior arts is replaced with naphthyridine parent-nucleus, the resulting new compounds showed potent anti-ulcer, anti-gastric juice secretion and anti-H.sup.+ /K.sup.+ ATPase activities.


SUMMARY OF THE INVENTION

Therefore, an object of the present invention is to provide new 4-amino-3-acylnaphthyridine derivatives represented by the following general formula (I): ##STR2## wherein R.sub.1 is hydrogen atom, a C.sub.1 -C.sub.6 lower alkyl group, a C.sub.1 -C.sub.6 lower alkoxy group, C.sub.1 -C.sub.6 lower alkoxyalkyl group, a C.sub.3 -C.sub.6 cycloalkyl group, a C.sub.3 -C.sub.6 cycloalkyl C.sub.1 -C.sub.6 alkyl group, a substituted or unsubstituted phenyl, or a phenyl C.sub.1 -C.sub.6 alkyl group of which phenyl group may be substituted; -C.sub.6 alkoxy group, a C.sub.1 -C.sub.6 alkylthio group, or a group of a formula: NR.sub.6 R.sub.7 wherein R.sub.6 and R.sub.7, identical to or different from each other, are independently hydrogen atom or a C.sub.1 -C.sub.6 lower alkyl group, or R.sub.6 and R.sub.7 may form together 5-membered or 6-membered cycloalkyl group; -C.sub.6 alkoxy group, a C.sub.1 -C.sub.6 alkylthio group, an amino group substituted with one or two C.sub.1 -C.sub.6 alkyl groups, a halogen atom, a cyano group, a C.sub.1 -C.sub.6 alkanoyl group, or trifluoromethyl group; alkyl group; -C.sub.6 alkoxy group, an amino group substituted with one or two C.sub.1 -C.sub.6 alkyl groups, a C.sub.1 -C.sub.6 alkylthio group, a halogen atom, a cyano group, a hydroxycarbamoyl group, a carboxy group, a C.sub.1 -C.sub.6 alkanoyl group, or trifluoromethyl group, or an alkyl group which forms together with R.sub.4 a 5-membered or 6-membered cycloalkyl group; and said halogen atom means fluorine, chlorine or bromine atom,
For the present invention, if a carbon atom to which R.sub.4 other than hydrogen atom is bonded is asymmetric, the compounds (I) may have optically active isomers such as enantiomers, racemic mixtures, or mixtures thereof, all of them are embraced within scope of the present invention.
According to the present invention, a method for producing the compounds is also provided.
The above and other objects and features of the present invention will be apparent to the skilled in the art from the following detailed description.


DETAILED DESCRIPTION OF THE INVENTION

The pharmaceutically acceptable salts of the compound (I) of the present invention include acid-addition salts of the compound (I) with pharmaceutically acceptable organic and inorganic acids, for example hydrochloric, sulfuric, phosphoric, citric, formic, acetic, fumaric, maleic, malonic, tartaric, methanesulfonic, or p-toluene sulfonic acid.
The compound represented by the general formula (I) may be prepared by reacting the compound represented by the general formula (II) ##STR3## wherein, R.sub.1, R.sub.2, and R.sub.3 have the same meanings as defined above; and X is a leaving group which may be substituted with an amine group, and may be exemplified by a halogen atom, OS(O).sub.2 R.sub.8 or OP(O) (O

REFERENCES:
patent: 4343804 (1982-08-01), Munsen, Jr. et al.
Saccomani et al., Biochimica et Biophysica Acta, 1977, 465, 311-330.
Fiske et al., "The Colorimetric Determination of Phosphorus", The Journal of Biological Chemistry, 1925, 66, 375-440.
Brezin et al., "Survival Following Massive Resection of Small and Large Bowel; Water, Electrolyte and Blood Volume Studies", Gastroenterology, 1954, 26, 895-905.
Chien et al., "Synthesis and Antimalarial Evaluation of Some 1,7-Naphthyridines and 2,9-Diazaanthracenes", J. Med. Chem., 1968, 11(1), 164-167.

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