Sumitomo Chemical Company, Limited

Smithkline Corporation

Shigeho Inaba

Hisao Yamamoto

Isamu Maruyama

Michihiro Yamamoto

Kikuo Sasajima

Kikuo Ishizumi

Masaru Nakao

Kazuo Mori

Masao Koshiba

Junki Katsube

Keiichi Ono

Toshiyuki Hirohashi

Shigenari Katayama

Mitsuhiro Akatsu

Yoshiaki Takebayashi

Shigeaki Morooka

Tsuyoshi Kobayashi

Yoshiharu Kume

Takahiro Izumi

Kenji Kobayashi

Masaharu Takayama

Michio Kimura

Atsuyuki Kojima

Katsumi Tamoto

Hiromi Sato

Yoshito Kameno

Toshitsugu Fukumaru

Hiroyuki Mizote

Yoshihiro Tanaka

Tadashi Okamoto

Hiroshi Noguchi

Toshiaki Komatsu

Toshio Atsumi

Clifton A Baile

Yasuo Motoike

Shinichi Kaneko, Deceased

Izumi Yanagihara

Shigeru Sakai

Sumio Kitagawa

Takeshi Nakajima

Roger G Parish

Takeshi Akase

Novel benzisoxazole compounds of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are each hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, ar(C.sub.1 -C.sub.3)alkoxy or halogen or, when taken together, they form C.sub.1 -C.sub.2 alkylenedioxy, Alk is C.sub.1 -C.sub.4 alkylene and A is a group of the formula: ##STR2## (wherein R.sub.3 and R.sub.4 are each C.sub.1 -C.sub.4 alkyl or, when taken together with the adjacent nitrogen atom, they represent a 5-6 membered nitrogen-containing heterocyclic ring which may contain any additional hetero atom and R.sub.5 is C.sub.1 -C.sub.4 alkyl or aryl), and non-toxic salts thereof, which possess various pharmaceutical activities.

Benzisoxazole derivatives

1-Polyhaloalkyl-2(1H)-quinazoline derivatives of the formula, ##STR1## wherein R is polyhaloalkyl having C.sub.2 -C.sub.4 alkyl; and R.sub.1, R.sub.2 and R.sub.3 are individually hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, nitro, trifluoromethyl or halogen, have excellent anti-inflammatory and analgesic activities with very low toxicity. These quinazolinone derivatives can be prepared, for example, by reacting a trihalogenoacetamidobenzophenone derivative with ammonia.

1-Polyhaloalkyl-2(1H)-quinazolinone derivatives

Imidazo- and pyrimido[2,1-b]quinazolines of the formula, ##STR1## wherein R.sub.1 and R.sub.2 are independently hydrogen, halogen, trifluoromethyl, nitro, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, or R.sub.1 and R.sub.2 may together represent methylenedioxy; R.sub.3 is hydrogen, C.sub.1-4 alkyl, phenyl or substituted phenyl of the formula, ##STR2## (wherein R is halogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy); R.sub.4 is hydrogen, C.sub.1-4 alkyl or aralkyl; and A is C.sub.2-3 alkylene wich may be optionally substituted by one or two C.sub.1-2 alkyl radicals, and pharmaceutically acceptable acid addition salts thereof, are prepared by reacting a compound of the formula, ##STR3## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and A are as defined above; and X is oxygen or sulfur, with a halogenating agent at a temperature of about 30.degree. C. to about 180.degree. C. In the above imidaxo- and pyrimido[2,1-b]quinazolines, those having C.sub.1-4 alkyl, or ##STR4## as R.sub.3 are novel compounds and show antidepressant and/or antihypertensive activities.

Imidazo- and pyrimido[2,1-b]quinazolines and preparation thereof

Viral infections caused by viruses which belong to, e.g. Pox, Herpes, Adeno, Myxo, Paramyxo groups are controlled by administering an effective amount of quinazoline derivatives of the formula ##STR1## wherein R.sub.1 is cyclo, C.sub.3 -C.sub.8 alkyl, cyclo C.sub.3 -C.sub.8 alkyl C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy C.sub.1 -C.sub.4 alkyl, C.sub.2-C.sub.5 alkenyloxy C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkylthio C.sub.1 -C.sub.4 alkyl, polyhalo C.sub.1- C.sub.4 alkyl, a group of the formula ##STR2## (wherein m is an integer of 1 to 3; and R.sub.4 and R.sub.5 are individually C.sub.1 -C.sub.4 alkyl, and may form together with the adjacent nitrogen atom an unsubstituted or C.sub.1 -C.sub.4 alkyl substituted 3 to 6 membered saturated heterocyclic ring, which may contain another nitrogen or oxygen atom) or a group of the formula --C.sub.n H.sub.2n --R.sub.6 (wherein n is 0 or an integer of 1 to 3; and R.sub.6 is a phenyl group, a substituted phenyl group or an aromatic or non-aromatic 3 to 6 membered heterocyclic ring which contains one or two hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur atom, and may be optionally substituted by one or two C.sub.1 -C.sub.4 alkyl, and further, those substituents on adjacent carbon atoms may be joined to form a benzene or cyclohexane ring); R.sub.2 is hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfonyl, trifluoromethyl or nitro; and R.sub.3 is phenyl, substituted phenyl, cyclo C.sub.3 -C.sub.6 alkyl, pyridyl, furyl, nitrofuryl, thienyl, nitrothienyl, methylthienyl or pyrimidinyl.

Nitroquinazolinone compounds having antiviral properties

Novel benzisoxazole compounds of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are each hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, ar(C.sub.1 14 C.sub.3) alkoxy or halogen or, when taken together, they form C.sub.1 -C.sub.2 alkylenedioxy, Alk is C.sub.1 -C.sub.4 alkylene and A is a group of the formula: ##STR2## (wherein R.sub.3 and R.sub.4 are each C.sub.1 -C.sub.4 alkyl or, when taken together with the adjacent nitrogen atom, they represent a 5-6 membered nitrogen-containing heterocyclic ring which may contain any additional hetero atom and R.sub.5 is C.sub.1 -C.sub.4 alkyl or aryl), and non-toxic salts thereof, which possess various pharmaceutical activities.

3-(Piperazinoalkyl)-benz-2,1-isoxazoles

Novel cyclopropylmethylamine compounds of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are each hydrogen or halogen and R.sup.3 is hydrogen or methyl, and their non-toxic salts, which possess various useful pharmacological activities and can be produced by reduction of the corresponding compounds of the formula: ##STR2## wherein R.sup.1, R.sup.2 and R.sup.3 are each as defined above or their non-toxic salts, or by condensation of the corresponding compounds of the formula: ##STR3## wherein R.sup.1 and R.sup.2 are each defined above, and X is a conventional interchangeable group such as halogen or sulfonyloxy with methylamine or dimethylamine.

Cyclopropylmethylamine derivatives

Novel cyclopropylmethylamine compounds of the formula: ##STR1## wherein Ar.sup.1 represents a phenyl group having one or more substituents selected from the group consisting of halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy and trifluoromethyl, of which at least one is present at the o- or m-position, Ar.sup.2 represents an unsubstituted phenyl group or a phenyl group substituted with one or more substituents selected from the group consisting of halogen and C.sub.1 -C.sub.4 alkyl, R represents hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.2 -C.sub.4 hydroxyalkyl and R' represents C.sub.1 -C.sub.4 alkyl or C.sub.2 -C.sub.4 hydroxyalkyl, and their non-toxic salts, which possess various useful pharmacological activities and can be produced by reduction of the corresponding compounds of the formula: ##STR2## wherein Ar.sup.1, Ar.sup.2, R and R' are each as defined above or by condensation of the corresponding compounds of the formula: ##STR3## wherein Ar.sup.1 and Ar.sup.2 are each as defined above and X is a conventional leaving (removable) group with amines of the formula: ##STR4## wherein R and R' are each as defined above.

Novel cyclopropylmethylamine derivatives

3,4-Dihydro-2(1H)-quinazolinone derivatives of the formula, ##STR1## wherein R.sub.1 and R.sub.2 signify individually a hydrogen atom, a lower alkyl group, a lower alkoxy group, a nitro group, a trifluoromethyl group, a lower alkylthio group, a lower alkylsulfonyl group or a halogen atom; R.sub.3 signifies a phenyl group, a halophenyl group, a lower alkylphenyl group, a lower alkoxyphenyl group, a trifluoromethylphenyl group, a lower cycloalkyl group, a lower cycloalkenyl group, a pyridyl group, a pyrrolyl group, a furyl group, a thienyl group or a naphthyl group; R.sub.4 signifies a lower alkyl group, a lower alkenyl group, an aralkyl group, a lower cycloalkylalkyl group, a lower cycloalkyl group, a lower alkoxyalkyl group, a lower alkylthioalkyl group, a lower hydroxyalkyl group, a lower alkanoyloxyalkyl group, a phenyl group, a halophenyl group, a trifluoromethylphenyl group, a lower alkylphenyl group a lower alkoxyphenyl group, a pyridyl group or a group of the formula ##STR2## wherein n signifies an integer of 1 to 4; and R.sub.5 and R.sub.6 signify individually a lower alkyl group, provided that they may form together with the adjacent nitorgen atom an optionally substituted 5- or 6-membered heterocyclic ring, which may further contain a hetero atom); and R signifies a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkoxyalkyl group, a lower alkylthioalkyl group, an aralkyl group, a lower cycloalkylalkyl group, a lower trihalomethylalkyl group or a group of the formula ##STR3## (wherein n, R.sub.5 and R.sub.6 signify the same as defined above), which have excellent pharmacological properties such as central nervous system depressant, anti-inflammatory, analgestic and anti-microbial activities, can be produced by reducing a compound of the formula, ##STR4## wherein R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 have the same meanings as defined above; and X.sub.1, X.sub.2 and X.sub.3 signify individually a halogen atom, or by the substitution reaction of the ring nitrogen atom of a 1 or 3-unsubstituted 3,4-dihydro-2(1H)-quinazolinone derivative.

Quinazolinone derivatives and a process for production thereof

1,4-Substituted-2(1H)-quinazolinone derivatives are prepared by contactng a 2-aminophenyl ketone derivative with an alkaline agent such as alkali metal, alkali metal hydride, alkali metal amide, etc., reacting the thus obtained metal salt of 2-aminophenyl ketone derivative with a reactive ester of alcohols, reacting the thus obtained 2-(N-mono-substituted amino)-phenyl ketone derivative with a lower alkyl haloformate or a benzyl haloformate, and reacting the thus obtained carbamate derivative with ammonia. The 1,4-substituted-2(1H)-quinazolinone derivatives have excellent pharmacological properties, particularly as anti-inflammatory and analgesic effects.

Process for preparing quinazolinone derivatives and their

Novel N-substituted heterocyclic derivatives represented by the formula, ##STR1## wherein R is hydrogen or lower alkanoyl; R.sub.1 is hydrogen, lower alkyl, lower alkoxy, halogen, nitro, trifluoromethyl, amino or N-lower alkanoylamino; R.sub.2 is hydrogen, halogen, amino or N-lower alkanoylamino; W is oxygen, sulfur, sulfinyl or sulfonyl; and Y is ##STR2## (wherein R.sub.3 is hydrogen, lower alkyl or lower alkanoyl; and R.sub.4 is hydrogen, halogen or lower alkyl), and pharmaceutically acceptable salts thereof, which have excellent anti-inflammatory, analgesic, sedative, anti-convulsive or anti-hypertensive activities.

N-substituted heterocyclic derivatives and preparation thereof

Novel 1-substituted benzodiazepine derivatives and salt thereof having the formula, ##STR1## wherein R.sub.1 is a hydrogen atom, a halogen atom, a nitro group, a cyano group, a lower alkoxy group or a trifluoromethyl group; R.sub.2 is a pyridyl group or a group of the formula ##STR2## wherein R.sub.5 and R.sub.6 represent individually a hydrogen atom, a halogen atom, a lower alkyl group or a trifluoromethyl group); R.sub.3 is a hydrogen atom or a lower alkyl group; R.sub.4 is a lower alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl group; m is 1 or 2; and n is an integer of 1 to 4, and a process for preparation thereof and pharmaceutical use of the same. The benzodiazepine derivatives are effective as tranquillizers, muscle-relaxants and hypnotics.

Benzodiazepine derivatives

Novel compounds of the formula: ##STR1## wherein R is a hydrogen or fluorine atom, W is an oxygen atom or an ethylenedioxy or ethylenedithio group and Z is a certain secondary amino group, which are useful as central nervous system depressants, can be prepared by the reaction of a compound of the formula: ##STR2## wherein X is a halogen atom and R and W are each as defined above with a secondary amine of the formula: H--Z wherein Z is as defined above, in case of W being ethylenedioxy or ethylenedithio, optionally followed by hydrolysis and can be reduced to give a compound of the formula: ##STR3## wherein R and Z are each as defined above, which are useful as antipsychotic and/or analgesic agents.

CNS depressant .gamma.-(secondary amino)-ortho-nitro-butyrophenones

2(1H)-Quinazolinone derivatives, which are useful as anti-inflammatory agents, are prepared by heating or hydrolyzing an acylurea derivative. The acylurea derivative can be prepared by either reacting an indole derivative with an oxidizing agent or reacting an imidazolidine derivative with water, an alkanol or ammonia.

Production of quinazolinone compounds

Acylhydrazone compounds having excellent pyschotropic activity which are represented by the formula: ##STR1## wherein Z is selected from the groups having the formulas: ##STR2## wherein n is an integer of from 0 to 2 and R.sup.1 -R.sup.12 are as defined hereinbelow.

Acylhydrazones and anti-psychotic compositions thereof

Indolylacetic acid derivatives, which have excellent anti-inflammatory, antipyretic and analgesic activities, represented by the formula, ##STR1## wherein X.sub.1 and X.sub.2 are each methylene; A is an unsubstituted ethylenically unsaturated hydrocarbon chain having up to 5 carbon atoms; m is 0 or 1; n is 1 or 2; R.sub.3 is alkyl having up to 4 carbon atoms; cycloalkyl having 3 to 7 carbon atoms, unsubstituted or C.sub.1 -C.sub.4 alkyl-, nitro-, trifluoromethyl-, methylenedioxy-, ethylenedioxy- or halogen-substituted phenyl, or halogen-, C.sub.1 -C.sub.4 alkyl- or phenyl-substituted or benzene ring-condensed C.sub.3 -C.sub.7 cycloalkyl, or unsubstituted or halogen-, C.sub.1 -C.sub.4 alkyl- or phenyl-substituted or benzene ring-condensed C.sub.5 -C.sub.6 cycloalkenyl; and B is ##STR2## .

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Shigeho Inaba