Claims
- 1. A pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises a synergistically effective amount of a compound of the formula (II): ##STR14## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable ester thereof wherein X is tetrazolyl attached via a nitrogen atom, said tetrazolyl moiety being unsubstituted or subsititued by a non-toxic carbonic salt, an in-vivo hydrolyzable carboxyl ester of the formula (b), (C), (d) or (e):
- --CO--O--CHR.sup.3 --O--CO--R.sup.4 (b)
- --CO--O--R.sup.5 --NR.sup.6 R.sup.7 (c)
- CO--OA.sup.1 (d)
- or
- CO--O--CHA.sup.2 A.sup.3 (e)
- wherein R.sup.3 is hydrogen, methyl or phenyl; R.sup.4 is alkyl of 1 to 6 carbon atoms, phenyl, phenylalkyl of 1 to 3 carbon atoms in the alkyl moiety, alkoxy of 1 to 6 carbon atoms, phenoxy or phenylalkoxy of 1 to 3 carbon atoms in the alkyl moiety; or R.sup.3 and R.sup.4 are joined to form a 1,2-diphenylene or 3,4-dimethoxy-1,2-diphenylene moiety; R.sup.5 is methylene or ethylene; R.sup.6 and R.sup.7 are each methyl or ethyl; A.sup.1 is alkyl of 1 to 6 carbon atoms unsubstituted or substituted by alkoxy of 1 to 7 carbon atoms; A.sup.2 is alkenyl of 2 to 7 carbon atoms unsubstituted or substituted by phenyl; phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms, and A.sup.3 is hydrogen; alkyl of 1 to 4 carbon atoms or phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; alkoxy of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms or aryl unsubstituted or substituted by hydroxy, halo, aryl, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, arylalkoxy of 1 to 6 carbon atoms in the alkyl moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, azido, mono-alkylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; azido; isocyani; cyano; nitro; bromo; chloro; or is a group of the sub-formula (a):
- --(CO).sub.n --NR.sup.1 R.sup.2 (a)
- wherein n is zero or one; R.sup.1 is hydrogen or alkyl of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms or arylcarbonyl unsubstituted or substituted by one or more hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms in the alkoxy moiety, aralkoxy of 1 to 10 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety or dialkylamino of 1 to 6 carbon atoms in each alkyl moiety; and R.sup.2 is hydrogen, alkyl of 1 to 6 carbon atoms, or alkanoyl of 1 to 6 carbon atoms, or R.sup.1 or R.sup.2 is methyl substituted by carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms or arylcarbonyl; or R.sup.2 is not methyl, the R.sup.2 moiety is substituted by hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms in the alkoxy moiety, arylalkoxy of 1 to 6 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms, arylthio, amino, alkylamino of 1 to 6 carbon atoms or di-alkylamino of 1 to 6 carbon atoms; or R.sup.1 and R.sup.2 are joined to form with the nitrogen atom to which they are attached, a 4-, 5- or 6-membered ring wherein the nitrogen atom is the only heteroatom and wherein aryl as used herein is phenyl, pyrrolyl, furyl, thienyl, indolyl, benzofuryl, or thionaphthyl, and an antibacterially effective amount of a penicillin, in combination with a pharmaceutically acceptable carrier.
- 2. A composition according to claim 1 wherein X is a group of the sub-formula (i): ##STR15## wherein R is hydrogen, a non-toxic carboxyl salt, an in vivo hydrolyzable carboxy ester of the formula (b), (c), (d) or (e):
- --CO--O--CHR.sup.3 --O--CO--R.sup.4 (b)
- --CO--O--R.sup.5 --NR.sup.6 R.sup.7 (c)
- CO--OA.sup.1 (d)
- or
- CO--O--CHA.sup.2 A.sup.3 (e)
- wherein R.sup.3 is hydrogen, methyl or phenyl; R.sup.4 is alkyl of 1 to 6 carbon atoms, phenyl, phenylalkyl of 1 to 3 carbon atoms in the alkyl moiety, alkoxy of 1 to 6 carbon atoms, phenoxy or phenylalkoxy of 1 to 6 carbon atoms in the alkyl moiety; or R.sup.3 and R.sup.4 are joined to form a 1,2-diphenylene or 3,4-dimethoxy-1,2-diphenylene moiety; R.sup.5 is methylene or ethylene; R.sup.6 and R.sup.7 are each methyl or ethyl; A.sup.1 is alkyl of 1 to 6 carbon atoms unsubstituted or substituted by alkoxy of 1 to 7 carbon atoms; A.sup.2 is alkenyl of 2 to 7 carbon atoms unsubstituted or substituted by phenyl; phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; and A.sup.3 is hydrogen; alkyl of 1 to 4 carbon atoms or phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; alkoxy of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms or aryl unsubstituted or substituted by hydroxy, halo, aryl, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, arylalkoxy of 1 to 6 carbon atoms in the alkyl moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, azido, mono-alkylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; azido; isocyano; cyano; nitro; bromo; chloro; or is a group of the sub-formula (a):
- --(CO).sub.n --NR.sup.1 R.sup.2 (a)
- wherein n is zero or one; R.sup.1 is hydrogen or alkyl of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms or arylcarbonyl unsubstituted or substituted by one or more hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms in the alkoxy moiety, arylkoxy of 1 to 10 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; and R.sup.2 is hydrogen, alkyl of 1 to 6 carbon atoms, or alkanoyl of 1 to 6 carbon atoms, or R.sup.1 or R.sup.2 is methyl substituted by carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms or arylcarbonyl; or when R.sup.2 is not methyl, the R.sup.2 moiety is substituted by hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms in the alkoxy moiety, arylalkoxy of 1 to 6 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms, arylthio, amino, alkylamino of 1 to 6 carbon atoms or di-alkylamino of 1 to 6 carbon atoms; or R.sup.1 and R.sup.2 are joined to form with the nitrogen atom to which they are attached, a 4-, 5- or 6-membered ring wherein the nitrogen atom is the only heteroatom and wherein aryl as used herein is phenyl, pyrrolyl, furyl, thienyl, indolyl, benzofuryl, or thionaphthyl.
- 3. A composition according to claim 2 wherein R is hydrogen, alkoxy of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms or aryl unsubstituted or substituted by hydroxy, halo, aryl, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, arylalkoxy of 1 to 6 carbon atoms in the alkyl moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, azido, mono-alkenylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; azido, iso-cyano, cyano, nitro, bromo, chloro or is a group of the sub-formula (aa):
- --NR.sup.1 R.sup.2 (aa)
- wherein R.sup.1 is hydrogen or alkyl of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms or arylcarbonyl unsubstituted or substituted by one or more hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxy carbonyl of 1 to 6 carbon atoms in the alkoxy moiety, arylkoxy of 1 to 10 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; and R.sup.2 is hydrogen, alkyl of 1 to 6 carbon atoms, or alkanoyl of 1 to 6 carbon atoms, or R.sup.1 or R.sup.2 is methyl substituted by carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms or arylcarbonyl; or when R.sup.2 is not methyl, the R.sup.2 moiety is substituted by hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms in the alkoxy moiety, arylalkoxy of 1 to 6 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms, arylthio, amino, alkylamino of 1 to 6 carbon atoms or di-alkylamino of 1 to 6 carbon atoms; or R.sup.1 and R.sup.2 are joined to form with the nitrogen atom to which they are attached, a 4-, 5- or 6-membered ring wherein the nitrogen atom is the only heteroatom and wherein aryl as used herein is phenyl, pyrrolyl, furyl, thienyl, indolyl, benzofuryl, or thionaphthyl.
- 4. A composition according to claim 1 wherein the compound of the formula (II) is in the form of a salt wherein the salt is the sodium, potassium, aluminum, calcium, magnesium, triethylammonium, 2-hydroxyethylammonium, bis-(2-hydroxyethyl)ammonium, tri(2-hydroxyethyl)ammonium, bicyclohexylammonium, p-aminobenzoyldiethylaminoethanol hydrochloride, di-benzylammonium or N,N-bis-dehydroabietylammonium salt.
- 5. A composition according to claim 1 wherein the compound of the formula (II) is in the form of a pharmaceutically acceptable ester.
- 6. A composition according to claim 1 wherein the compound of the formula (II) is:
- sodium 9-(5-acetamidotetrazoly)deoxyclavulanate,
- sodium 9-(5-ethoxycarbonyltetrazol-1-yl)deoxyclavulanate,
- disodium 9-(5-carboxylatotetrazol-1-yl)deoxyclavulanate,
- dipotassium 9-(5-carboxylatotetrazol-1yl)deoxyclavulanate,
- sodium 9-(tetrazol-1yl)deoxyclavulanate,
- potassium 9-(tetrazol-1yl)deoxyclavulanate,
- potassium 9-(5-methyltetrazol-1-yl)deoxyclavulanate,
- potassium 9-(5-phenyltetrazol-1yl)deoxyclavulanate,
- potassium 9-(5tert-butyltetrazol-1yl)deoxyclavulanate, or
- methyxy-methyl 9-(tetrazol-2-yl)deoxyclavulanate.
- 7. A composition according to claim 1 wherein the penicillin is benzylpenicillin, phenoxymethylpenicillin, carbenicillin, azidocillin, propicillin, ampicillin, amoxycillin, epicillin, ticarcillin, cyclacillin, pirbenicillin, azlocillin, mezlocillin, sulbenicillin or piperacillin.
- 8. A composition according to claim 1 wherein the penicillin is amoxycillin or ampicillin.
- 9. A composition according to claim 8 wherein the amoxycillin is in the form of sodium amoxycillin or amoxycillin trihydrate and the ampicillin is in the form of ampicillin trihydrate.
- 10. A composition according to claim 1 wherein the ratio of synergist to penicillin is from 10:1 to 1:15.
- 11. A method of treating bscterial infections in humans and animals which comprises administering to a human or animal in need thereof a synergistically effective amount of a compound of the formula (II): ##STR16## a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable ester thereof wherein X is tetrazolyl attached via a nitrogen atom, said tetrazolyl moiety being unsubstituted or substituted by a non-toxic carboxyl salt, an in-vivo hydrolyzable carboxyl ester of the formula (b), (C), (d) or (e):
- --CO--O--CHR.sup.3 --O--CO--R.sup.4 (b)
- --CO--O--R.sup.5 --NR.sup.6 R.sup.7 (c)
- CO--OA.sup.1 (d)
- or
- CO--O--CHA.sup.2 A.sup.3 (e)
- wherein R.sup.3 is hydrogen, methyl or phenyl; R.sup.4 is alkyl of 1 to 6 carbon atoms, phenyl, phenylalkyl of 1 to 3 carbon atoms in the alkyl moiety, alkoxy of 1 to 6 carbon atoms, phenoxy or phenylalkoxy of 1 to 3 carbon atoms in the alkyl moiety; or R.sup.3 and R.sup.4 are joined to form a 1,2-diphenylene or 3,4-dimethoxy-1,2-diphenylene moiety; R.sup.5 is methylene or ethylene; R.sup.6 and R.sup.7 are each methyl or ethyl; A.sup.1 is alkyl of 1 to 6 carbon atoms unsubstituted or substituted by alkoxy of 1 to 7 carbon atoms; A.sup.2 is alkenyl of 2 to 7 carbon atoms unsubstituted or substituted by phenyl; phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms, and A.sup.3 is hydrogen; alkyl of 1 to 4 carbon atoms or phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; alkoxy of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms or aryl unsubstituted or substituted by hydroxy, halo, aryl, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, arylalkoxy of 1 to 6 carbon atoms in the alkyl moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, azido, mono-alkylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; azido; isocyani; cyano; nitro; bromo; chloro; or is a group of the sub-formula (a):
- --(CO).sub.n --NR.sup.1 R.sup.2 (a)
- wherein n is zero or one; R.sup.1 is hydrogen or alkyl of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms or arylcarbonyl unsubstituted or substituted by one or more hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms in the alkoxy moiety, aralkoxy of 1 to 10 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; and R.sup.2 is hydrogen, alkyl of 1 to 6 carbon atoms, or alkanoyl of 1 to 6 carbon atoms, or R.sup.1 or R.sup.2 is methyl substituted by carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms or arylcarbonyl; or R.sup.2 is not methyl, the R.sup.2 moiety is substituted by hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms in the alkoxy moiety, arylalkoxy of 1 to 6 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms, arylthio, amino, alkylamino of 1 to 6 carbon atoms or di-alkylamino of 1 to 6 carbon atoms; or R.sup.1 and R.sup.2 are joined to form with the nitrogen atom to which they are attached, a 4-, 5- or 6-membered ring wherein the nitrogen atom is the only heteroatom and wherein aryl as used herein is phenyl, pyrrolyl, furyl, thienyl, indolyl, benzofuryl, or thionaphthyl, and an antibacterially effective amount of a penicillin, in combination with a pharmaceutically acceptable carrier.
- 12. A method according to claim 11 wherein X is a group of the sub-formula (i): ##STR17## wherein R is hydrogen, a non-toxic carboxyl salt, an in vivo hydrolyzable carboxy ester of the formula (b), (c), (d) or (e):
- --CO--O--CHR.sup.3 --O--CO--R.sup.4 (b)
- --CO--O--R.sup.5 --NR.sup.6 R.sup.7 (c)
- CO--OA.sup.1 (d)
- or
- CO--O--CHA.sup.2 A.sup.3 (e)
- wherein R.sup.3 is hydrogen, methyl or phenyl; R.sup.4 is alkyl of 1 to 6 carbon atoms, phenyl, phenylalkyl of 1 to 3 carbon atoms in the alkyl moiety, alkoxy of 1 to 6 carbon atoms, phenoxy or phenylalkoxy of 1 to 3 carbon atoms in the alkyl moiety; or R.sup.3 and R.sup.4 are joined to form a 1,2-diphenylene or 3,4-dimethoxy-1,2-diphenylene moiety; R.sup.5 is methylene or ethylene; R.sup.6 and R.sup.7 are each methyl or ethyl; A.sup.1 is alkyl of 1 to 6 carbon atoms unsubstituted or substituted by alkoxy of 1 to 7 carbon atoms; A.sup.2 is alkenyl of 2 to 7 carbon atoms unsubstituted or substituted by phenyl; phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; and A.sup.3 is hydrogen; alkyl of 1 to 4 carbon atoms or phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; alkoxy of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms or aryl unsubstituted or substituted by hydroxy, halo, aryl, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, arylalkoxy of 1 to 6 carbon atoms in the alkyl moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, azido, mono-alkylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; azido; isocyano; cyano; nitro; bromo; chloro; or is a group of the sub-formula (a):
- --(CO).sub.n --NR.sup.1 R.sup.2 (a)
- wherein n is zero or one; R.sup.1 is hydrogen or alkyl of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms or arylcarbonyl unsubstituted or substituted by one or more hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms in the alkoxy moiety, arylkoxy of 1 to 10 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; and R.sup.2 is hydrogen, alkyl of 1 to 6 carbon atoms, or alkanoyl of 1 to 6 carbon atoms, or R.sup.1 or R.sup.2 is methyl substituted by carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms or arylcarbonyl; or when R.sup.2 is not methyl, the R.sup.2 moiety is substituted by hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms in the alkoxy moiety, arylalkoxy of 1 to 6 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms, arylthio, amino, alkylamino of 1 to 6 carbon atoms or di-alkylamino of 1 to 6 carbon atoms; or R.sup.1 or R.sup.2 are joined to form with the nitrogen atom to which they are attached, a 4-, 5- or 6-membered ring wherein the nitrogen atom is the only heteroatom and wherein aryl as used herein is phenyl, pyrrolyl, furyl, thienyl, indolyl, benzofuryl, or thionaphthyl.
- 13. A method according to claim 11 wherein R is hydrogen, alkoxy of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms or aryl unsubstituted or substituted by hydroxy, halo, aryl, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, arylalkoxy of 1 to 6 carbon atoms in the alkyl moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, azido, mono-alkenylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; azido, iso-cyano, cyano, nitro, bromo, chloro or is a group of the sub-formula (aa):
- --NR.sup.1 R.sup.2 (aa)
- wherein R.sup.1 is hydrogen or alkyl of 1 to 6 carbon atoms, alkanoyl of 1 to 6 carbon atoms or arylcarbonyl unsubstituted or substituted by one or more hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxy carbonyl of 1 to 6 carbon atoms in the alkoxy moiety, arylkoxy of 1 to 10 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms in the alkyl moiety, arylthio, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety or di-alkylamino of 1 to 6 carbon atoms in each alkyl moiety; and R.sup.2 is hydrogen, alkyl of 1 to 6 carbon atoms, or alkanoyl of 1 to 6 carbon atoms, or R.sup.1 or R.sup.2 is methyl substituted by carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms or arylcarbonyl; or when R.sup.1 or R.sup.2 is not methyl, the R.sup.1 or R.sup.2 moiety is substituted by hydroxy, halo, carboxy, alkanoyl of 1 to 6 carbon atoms, alkanoyloxy of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms in the alkoxy moiety, arylalkoxy of 1 to 6 carbon atoms in the alkoxy moiety, arylcarbonyl, alkylthio of 1 to 6 carbon atoms, arylthio, amino, alkylamino of 1 to 6 carbon atoms or di-alkylamino of 1 to 6 carbon atoms; or R.sup.1 and R.sup.2 are joined to form with the nitrogen atom to which they are attached, a 4-, 5- or 6-membered ring wherein the nitrogen atom is the only heteroatom and wherein aryl as used herein is phenyl, pyrrolyl, furyl, thienyl, indolyl, benzofuryl, or thionaphthyl.
- 14. A method according to claim 11 wherein the compound of the formula (II) is in the form of a salt wherein the salt is the sodium, potassium, aluminum, calcium, magnesium, triethylammonium, 2-hydroxyethylammonium, bis-(2-hydroxyethyl)ammonium, tri(2-hydroxyethyl)ammonium, bicyclohexylammonium, p-aminobenzoyldiethylaminoethanol hydrochloride, di-benzylammonium or N,N-bis-dehydroabietylammonium salt.
- 15. A method according to claim 11 wherein the compound of the formula (II) is in the form of a pharmaceutically acceptable ester.
- 16. A method according to claim 11 wherein the compound of the formula (II) is:
- sodium 9-(5-acetamidotetrazolyl)deoxyclavulanate,
- sodium 9-(5-ethoxycarbonyltetrazol-1-yl)deoxyclavulanate,
- disodium 9-(5-carboxylatotetrazol-1-yl)deoxyclavulanate,
- dipotassium 9-(5-carboxylatotetrazol-1-yl)deoxyclavulanate,
- sodium 9-(tetrazol-1-yl)deoxyclavulanate,
- potassium 9-(tetrazol-1-yl)deoxyclavulanate,
- potassium 9-(5-methyltetrazol-1yl)deoxyclavulanate,
- potassium 9-(5-phenyltetrazol-1-yl)deoxyclavulanate,
- potassium 9-(5-tert-butyltetrazol-1-yl)deoxyclavulanate, or
- methoxy-methyl 9-(tetrazol-2-yl)deoxyclavulanate.
- 17. A method according to claim 11 wherein the penicillin is benzylpenicillin, phenoxymethylpenicillin, carbenicillin, azidocillin, propicillin, ampicillin, amoxycillin, epicillin, ticarcillin, cyclacillin, pirbenicillin, azlocillin, mezlocillin, sulbenicillin or piperacillin.
- 18. A method according to claim 11 wherein the penicillin is amoxycillin or ampicillin.
- 19. A method according to claim 18 wherein the amoxycillin is in the form of sodium amoxycillin or amoxycillin trihydrate and the ampicillin is in the form of ampicillin trihydrate.
- 20. A method according to claim 11 wherein the ratio of synergist to penicillin is from 10:1 to 1:15.
Priority Claims (2)
Number |
Date |
Country |
Kind |
8039447 |
Dec 1980 |
GBX |
|
8118110 |
Jun 1981 |
GBX |
|
CROSS-REFERENCE
This is a division of Ser. No. 325,979, filed Nov. 30, 1981, now abandoned.
Non-Patent Literature Citations (2)
Entry |
Newall et al., Chemical Abstracts 92, 22497a. |
Newall, Chemical Abstracts, 95, 97651k (1981). |
Divisions (1)
|
Number |
Date |
Country |
Parent |
325979 |
Nov 1981 |
|