Nippon Chemiphar Co., Ltd.

Taiho Pharmaceutical Company Limited

Kanebo, Limited

Shigeru Yamabe

Yasuo Fujimoto

Naobumi Ishida

Ronald G Micetich

Toru Yamanaka

Tomio Yamazaki

Yoshihiro Tanaka

Kiyosato Nyu

Shoji Ryu

Yoshio Suzuki

Makoto Kajitani

Motoaki Tanaka

Takeshi Ishizawa

Goro Tsukamoto

Fumio Sakamoto

Shoji Ikeda

Ronald J Micetich

Shuichi Ueda

Shoji Hirata

This invention provides a penicillin derivative of the formula ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and represent hydrogen, C.sub.1-6 alkyl, C.sub.1-6 hydroxyalkyl, C.sub.3-9 acyloxyalkyl, C.sub.8-13 benzyloxyalkyl, C.sub.2-7 alkoxyalkyl, C.sub.2-7 alkoxycarbonyl, C.sub.3-8 alkenyloxycarbonyl, C.sub.3-8 alkynyloxycarbonyl, phenyl, amino, cyano, formyl, trifluoromethyl, C.sub.2-6 acyl, carbamoyl, C.sub.2-7 alkylcarbamoyl, benzyloxycarbonylamino, C.sub.2-7 alkoxycarbonylamino; and R.sub.3 is hydrogen, a group for forming a pharmaceutically acceptable salt, or a penicillin carboxyl protecting group, with the proviso that both of R.sub.1 and R.sub.2 are not hydrogen or C.sub.2-7 alkoxycarbonyl at the same time and that when one of R.sub.1 and R.sub.2 is hydrogen, the other is not C.sub.2-7 alkoxycarbonyl, or a pharmaceutically acceptable acid addition salt, process for preparing the derivative, and a pharmaceutical composition containing the derivative.

Penicillin derivatives

A penicillin derivative represented by the following formula ##STR1## wherein R.sub.1 is hydrogen or trialkylsilyl; R.sub.2 is hydrogen, trialkylsilyl or COOR.sub.2 ' wherein R.sub.2 ' is hydrogen, C.sub.1-18 alkyl, C.sub.2-7 alkoxymethyl, C.sub.3-8 alkylcarbonyloxymethyl, C.sub.4-9 alkylcarbonyloxyethyl, (C.sub.5-7 cycloalkyl)carbonyloxymethyl, C.sub.9-14 benzylcarbonyloxyalkyl, C.sub.3-8 alkoxycarbonylmethyl, C.sub.4-9 alkoxycarbonylethyl, phthalidyl, crotonolacton-4-yl, .gamma.-butyrolacton-4-yl, halogenated C.sub.1-6 alkyl substituted with 1 to 3 halogen atoms, C.sub.1-6 alkoxy- or nitro-substituted or unsubstituted benzyl, benzhydryl, tetrahydropyranyl, dimethylaminoethyl, dimethylchlorosilyl, trichlorosilyl, (5-substituted C.sub.1-6 alkyl or phenyl or unsubstituted-2-oxo-1,3-dioxoden-4-yl)methyl, C.sub.8-13 benzoyloxyalkyl or group for forming a pharmaceutically acceptable salt; and R.sub.3 has the same meaning as above R.sub.2 '.

A penicillin derivative represented by the following formula ##STR1## wherein R.sub.1 and R.sub.2 are each the same or different and represent hydrogen, C.sub.1-18 alkyl, mononitro-substituted benzyl or group for forming a pharmaceutically acceptable salt and R.sub.3 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.2-7 alkoxymethyl, C.sub.3-8 alkylcarbonyloxymethyl, C.sub.4-9 alkylcarbonyloxyethyl, (C.sub.5-7 cycloalkyl)carbonyloxymethyl, C.sub.9-14 benzylcarbonyloxyalkyl, C.sub.3-8 alkoxycarbonylmethyl, C.sub.4-9 alkoxycarbonylethyl, phthalidyl, crotonolacton-4-yl, .gamma.-butyrolacton-4-yl, halogenated C.sub.1-6 alkyl substituted with 1 to 3 halogen atoms, C.sub.1-6 alkoxy- or nitro-substituted or unsubstituted benzyl, benzhydryl, tetrahydropyranyl, dimethylaminoethyl, dimethylchlorosilyl, trichlorosilyl, (5-substituted C.sub.1-6 alkyl or phenyl or unsubstituted-2-oxo-1,3-dioxoden-4-yl)methyl, C.sub.8-13 benzoyloxyalkyl and group for forming a pharmaceutically acceptable salt.

A penicillin derivative represented by the following formula, a pharmaceutically acceptable salt thereof and an ester thereof: ##STR1## wherein n is 0, 1 or 2 and process for preparing the same.

Penicillin derivatives and process for preparation

This invention provides a penicillin derivative of the formula and a salt thereof ##STR1## wherein X represents chlorine atom or bromine atom and R represents hydrogen atom or penicillin carboxy-protecting radical, and a process for preparing the derivative of the formula (I) and a salt thereof by reacting a compound of the formula ##STR2## wherein R is as defined above with a chlorinating reagent or brominating reagent and, when required, forming a salt thereof.

A 1,1-dioxopenicillanic acid ester represented by formula (I) ##STR1## wherein R represents a methyl or phenyl group. The ester of formula (I) may be prepared by reacting 1,1-dioxopenicillanic acid or its salt with a compound represented by formula (III) ##STR2## wherein R is as defined above, and X represents a halogen atom, or by oxidizing a compound of formula (V) ##STR3## wherein R is as defined above. The ester of the formula (I) is useful as a .beta.-lactamase inhibitor and may be used in association with a .beta.-lactam antibiotic.

Ester of 1,1-dioxopenicillanic acid, and use thereof as .beta.-lactamase

Acetic acid derivatives having the formula, ##STR1## wherein X represents an oxygen or two hydrogen atoms, Y represents CH or N, A represents an oxygen or sulfur atom, and R represents hydroxy, amino or a lower alkoxy group having 1 to 5 carbon atoms possess excellent antiinfammatory activities.

Acetic acid derivatives

A compound of the formula (I), ##STR1## wherein R.sub.1 represents a halogen atom, or a hydroxy, nitro, amino, trihalogenomethyl or lower alkoxy group having 1 to 5 carbon atoms, and R.sub.2 represents a hydroxy or amino group is an antiinflammatory agent.

Dibenzothiepin derivatives and a process for producing the same

Acetic acid derivatives having the formula, ##STR1## wherein X represents an oxygen or two hydrogen atoms, Y represents CH or N, A represents an oxygen or sulfur atom, and R represents hydroxy, amino or a lower alkoxy group having 1 to 5 carbon atoms possess excellent antiinflammatory activities.

Acetic acid derivatives of 5,6-dihydrobenzo[b]pyrido[3,2-f]thiepine and

A compound of the formula, ##STR1## wherein R represents a hydroxy or amino group is an antiinflammatory and analgesic agent.

9-(.beta.-hydroxyethyl) piperazinyl-carbonyl-2-trifluoromethyl-10, 11-dihydrodibenzo[b,f]thiepin is prepared and disclosed as having antiinflamatory action.

Benzo[b,f]thiepan derivitives

Propionic acid derivatives having the formula ##STR1## wherein X represents an oxygen or two hydrogen atoms, Y represents CH or N, A represents an oxygen or sulfur atom, and R represents hydroxy, amino, or a lower alkoxy group having 1 to 5 carbon atoms are antiinflammatory agents.

Propionic acid derivatives

Novel benzo [b,f] thiepin derivatives possessing strong anti-flammatory action and presenting few adverse reactions, of the formula (I) ##STR1## wherein R represents a fluorine atom, or a trifluoromethyl or 1-5C lower alkoxy group, and R.sub.3 and R.sub.4 each represent a 1-4C lower alkyl group or R.sub.3 and R.sub.4 together with the adjacent nitrogen atom to which they are attached form a heterocyclic group. Pharmaceutical compositions comprising an anti-inflammatory effective amount of the compound according to formula (I) in the presence of an inert carrier.

Benzo[b,f]thiepin derivatives and process for producing the same

Dihydrodibenzo[b,f]thiepin compounds of formula (I) and process for making them. These compounds have antiinflammatory action. ##STR1## wherein R represents a hydrogen, fluorine atom, a trifluoromethyl, 1-5C lower alkoxy, hydroxy, hydroxyethoxy, aminoethoxy group or the group of the formula --OCH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2 OH, Y represents a hydroxy group or the group of the formula ##STR2## (R.sub.3 and R.sub.4 represent a 1-4C lower alkyl group or R.sub.3 and R.sub.4 may jointly form a heterocyclic group together with an adjacent nitrogen atom.

Growing community of inventors

Kobe, Japan

Shigeru Yamabe