2-Oxo-1-(((substituted sulfonyl)amino)carbonyl)azetidines

Claim 2

1 2-Oxo-1-[[(substituted sulfonyl)amino]carbonyl]-azetidines having a substituent in the 1-position and an amino substituent or acylamino substituent in the 3-position, or a salt thereof; wherein Z is oxygen or sulfur, and R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (R c ), phenylalkyl, (substituted-phenyl)alkyl, R c -alkyl or -NR a R b wherein R a and R b are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl., substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of R a and R b is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NH 2 ), alkanoylamino, arylcarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, alkylamino, dialkylamino, phenylamino, (substituted phenyl)-amino, hydroxy, cyano(-C=N), alkoxy, phenyloxy, (substituted phenyl)oxy, phenylalkoxy, (substituted phenyl)alkoxy, R c as defined above, R c -alkyl, R c -alkoxy, alkylsulfonyl, alkylmethyleneamino, (alkyl-CH=N-), phenylmethyleneamino or (substituted phenyl)methyleneamino.

Claim 3

A B-lactam in accordance with claim_1 having a substitucnt in the 1-position an amino substituent or acylamino substituent in the 3-position, and a methoxy substituent in the 3-position, or a salt thereof.

Claim 4

A ß-lactam in accordance with claim 1 wherein Z is oxygen.

Claim 5

A.ß-lactam in accomance with claim 1 having a . substituent in the 1-position . and an amino substituent or acylamino substituent in the 3-position, or a salt thereof. '

Claim 6

A B-lactam in accordance with claim 1 havina the formula or a salt thereof; wherein R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (R c ), phenylalkyl, (substituted-phenyl)alkyl, R c -alkyl or -NR a R b wherein R a and R b are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of R a and R b is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NH 2 ), alkanoylamino, arylcarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, alkylamino, dialkylamino, phenylamino, (substituted phenyl)-amino, hydroxy, cyano(-C≡N), alkoxy, phenyloxy, (substituted phenyl)oxy, phenylalkoxy, (substituted phenyl)alkoxy, R as defined above, R c -alkyl, R c -alkoxy, alkylsulfonyl, alkylmethyleneamino, (alkyl-CH=N-), phenylmethyleneamino or (substituted phenyl)methyleneamino; R 1 is acyl; R 2 is hydrogen or methoxy; R3 and R4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R 3 and R 4 is hydrogen and the other is alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, -CH 2 X 1 (wherein X 1 is azido, amino, hydroxy, alkanoylamino. alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, halogen, benzylthio, (substituted phenyl)methylthio, triphenylmethylthio, cyano or mercapto), -S-X 2 or -O-X2 (wherein X 2 is alkyl, phenyl, substituted phenyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, or heteroarylcarbonyl), or (wherein one of X 3 and X 4 is hydrogen and the other is hydrogen or alkyl, or X 3 and X 4 when taken together with the carbon atom to which they are attached form a cycloalkyl group, and X 5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, phenylalkylcarbonyl, (substituted phenyl)alkylcarbonyl, carboxyl, alkoxycarbonyl, aminocarbonyl, (substituted amino)-carbonyl, or cyano); and Z is oxygen or sulfur.

Claim 7

A ß-lactam in accordance with claim 5 wherein R 2 is hydrogen.

Claim 8

A ß-lactam in accordance with claim 6 wherein R 3 is hydrogen and R 4 is hydrogen or methyl.

Claim 9

A B-lactam in accordance with claim 7 wherein Z is oxygen.

Claim 10

A ß-lactam in accordance with claim 5 wherein Z is oxygen.

Claim 11

A ß-lactam in accordance with claim 5 having the formula or a salt thereof.

Claim 12

A B-lactam in accordance with claim 10 wherein R a and R b each is hydrogen.

Claim 13

A ß-lactam in accordance with claim 5 wherein R 1 is R 11 is 2-amino-4-thiazolyl and R 13 is alkyl or carboxy substituted alkyl.

Claim 14

A ß-lactam in accordance with claim 1 having the formula or a salt thereof; wherein R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (R c ), phenylalkyl, (substituted-phenyl)alkyl, R c -alkyl or -NR a R b wherein R a and R b are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of R a and R b is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NH 2 ), alkanoylamino, arylcarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, alkylamino, dialkylamino, phenylamino, (substituted phenyl)- amino, hydroxy, cyano(-C=N), alkoxy, phenyloxy, (substituted phenyl)oxy, phenylalkoxy, (substituted phenyl)alkoxy, R c as defined above, R c -alkyl, R c -alkoxy, alkylsulfonyl, alkylmethyleneamino, (alkyl-CH= N -), phenylmethyleneamino or (substituted phenyl)methyleneamino. R 2 is hydrogen or methoxy; R 3 and R 4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl, or one or R 3 and R 4 is hydrogen and the other is alkoxycarbonyl, aken-1-yl, alkyn-1-yl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, -CH 2 X 1 (wherein X 1 is azido, amino; hydroxy, alkanoylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, halogen, benzylthio, (substituted phenyl)methylthio, triphenylmethylthio, cyano or mercapto), -S-X 2 or -O-X 2 (wherein X 2 , is alkyl, phenyl, substituted phenyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, or heteroarylcarbonyl), or (wherein one of X 3 and X 4 is hydrogen and the other is hydrogen or alkyl, or X 3 and X 4 when taken together with the carbon atom to which they are attached form a cycloalkyl group, and X 5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, phenylalkylcarbonyl, (substituted phenyl)alkylcarbonyl, carboxyl, alkoxycarbonyl, aminocarbonyl, (substituted amino)-carbonyl, or cyano); and Z is oxygen or sulfur, and the amino group can be in a protected form.

Claim 15

A ß-lactam in accordance with claim 13 wherein R 2 is hydrogen.

Claim 16

The compound in accordance with claim 5, (S)-[1-[[[(4-methylphenyl)sulfonyl]amino]carbonyl]-2-oxo-3-azetidinyl]carbamic acid, phenylmethyl ester.

Claim 17

The compound in accordance with claim 5, [3S(Z)]-3-[[(2-amino-4-thiazolyl)(methoxyimino)-acetyl]amino]-N-[(4-methylphenyl)sulfonyl]-2-oxo-1-azetidinecarboxamide.

Claim 18

The compound in accordance with claim 5, [3S(Z)]-3-[[(2-amino-4-thiazolyl)(methoxyimino)-acetyl]amino]-N-(methylsulfonyl)-2-oxo-l-azetidinecarboxamide, potassium salt.

Claim 19

The compound in accordance with claim 5, [3S-[3α(Z),4β]]-3-[[(2-amino-4-thiazolyl)(methoxy- imino)acetyl]amino]-4-methyl-N-(methylsulfonyl)-2-oxo-l-azetidinecarboxamide, potassium salt.

Claim 20

The compound in'accordance with claim 5, [3S-[3α(Z),4β]]-3-[[(2-amino-4-thiazolyl)[(1-carboxy-l-methylethoxy)imino]acetyl]amino]-4-methyl-N-(methylsulfonyl)-2-oxo-l-azetidinecarboxamide, dipotassium salt.

Claim 21

The compound in accordance with claim 5, [3S (Z) -3- [[(2-amino-4-thiazolyl) (methoxy- imino)acetyl]amino]-N-(methylsulfonyl)-2- oxo-1-azetidinecarbothioamide, potassium salt.

Claim 22

The compound in accordance with claim 5, [3S(Z)]-2-[[[1-(2-amino-4-thiazolyl)-2-[[1-[[(methylsulfonyl)amino]carbonyl]-2-oxo-3- azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid, dipotassium salt.

Claim 23

The compound in accordance with claim 5 [3S(Z)]-3-[[(2-amino-4-thiazolyl)(methoxy- imino)acetyllamino]-N-(aminosulfonyl)-2-oxo-l-azetidinecarboxamide, ammonium salt.

Claim 24

The compound in accordance with claim 5, [3S(Z)]-3-[[(2-amino-4-thiazolyl)(methoxyimino)-acetyl]amino]-N-[[(1-methylethyl)amino]sulfonyl]-2-oxo-1-azetidinecarboxamide, sodium salt.

Claim 25

The compound in accordance with claim 5, [3S(Z)]-3-[[(2-amino-4-thiazolyl) (methoxyimino)-acetyl]amino]-2-oxo-N-[(phenylamino)sulfonyl]-1-azetidinecarboxamide, sodium salt.

Claim 26

The compound in accordance with claim 5, [3S(Z)]-3-[[(2-amino-4-thiazolyl)(methoxyimino)-acetyl)amino]-N-[(.dimethylamino)sulfonyl]-2-oxo-1-azetidinecarboxamide, sodium salt.

Claim 27

. 26. The compound in accordance with claim 5, [3S(Z)]-2-[[[1-(2-amino-4-thiazolyl)-2-[[1-[[(aminosulfonyl)amino]carbonyl]-2-oxo-3- azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid, disodium salt.

Claim 28

The compound in accordance with claim 13, (S)-N-(methylsulfonyl)-2-oxo-3-amino-1-azetidinecarboxamide, hydrochloride salt.

Claim 29

The compound in accordance with claim 13, (S)-3-amino-N-(methylsulfonyl)-2-oxo-1-azetidinecarboxamide, inner salt.

Claim 30

The compound in accordance with claim 13, [3S-[3α,4β]]-3-amino-4-methyl-N-(methylsulfonyl)-2-oxo-l-azetidinecarboxamide, trifluoroacetic acid salt.

Claim 31

The compound in accordance with claim 13, (S)-3-amino-N-(methylsulfonyl)-2-oxo-1-azetidinecarbothioamide, trifluoroacetic acid salt.

Claim 32

The compound in accordance with claim 13, (S)-3-amino-N-(aminosulfonyl)-2-oxo-l-azetidinecarboxamide, inner salt.

Claim 33

The compound in accordance with claim 13, (S)-3-amino-N-[(methylamino)sulfonyl]-2-oxo-l-azetidinecarboxamide, inner salt.

Claim 34

The compound in accordance with claim 13, (S)-3-amino-2-oxo-N-[[(4-pyridyl)amino]sulfonyl]-1-azetidinecarboxamide.

Claim 35

The compound in accordance with claim 13, (S)-1-[[[(4-methylphenyl)sulfonyl]amino]carbonyl]-2-oxo-3-aminoazetidine, triethylammonium salt.

Claim 36

A compound according to claim 1 of the formula wherein Y can be hydrogen, alkyl, substituted-alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl.

Claim 37

A compound according to claim 1 of the formula wherein n can be zero or one and X can be methylene, oxygen or a nitrogen atom which can be substituted with alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)-alkyl, amino, alkylamino, dialkylamino, alkylidenamino, aralkylidenamino, alkylsulfonyl, carboxy, carboxyalkyl and the like.

Claim 38

A compound according to claim 1 of the formule. wherein W can be hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl.

Claim 39

A process for preparing a β-lactam of any of the preceding claims having a substituent in the 1-position and an amino substituent or a protected form thereof or an acylamino substituent in the 3-position, or a salt thereof; wherein Z is oxygen or sulfur, and R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (R c ), phenylalkyl, (substituted-phenyl)alkyl, R c alkyl or -NR a R b wherein R a and R b are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of R a and R b is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NH 2 ), alkanoylamino, arylcarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, alkylamino, dialkylamino, phenylamino, (substituted phenyl)-amino, hydroxy, cyano(-C≡N), alkoxy, phenyloxy, (substituted phenyl)oxy, phenylalkoxy, (substituted phenyl)alkoxy, R as defined above, Rc-alkyl, R c -alkoxy, alkylsulfonyl, alkylmethyleneamino, (alkyl-CH=N-), phenylmethyleneamino or (substituted phenyl)methyleneamino.

Claim 40

A process according to claim 38 wherein said β-lactam which is unsubstituted in the 1-position is reacted with a compound of the formula

Claim 41

40 . A process according to claim 38 wherein R is an amino or substituted amino group, wherein said β-lactam which is unsubstituted in the 1-position is reacted with a compound of the formula X=C=N-SO 2 -Y wherein Y is a leaving group such as a halogen and the intermediate resulting therefrom is then reacted with an amine of the formula HNR a R b -

Claim 42

A process according to claims 38 through 40 wherein the product has an acylamino substituent in the 3-position and said acylamino substitutent is introduced by acylating a product thereof having an amino substituent in the 1-position.

Claim 43

A process according to claims 38 through 41 wherein Z is oxygen.

Claim 44

43 . A process according to claim 42 wherein R is amino.

Claim 45

44 . A process according to claims 38 through 43 wherein the product has a methoxy substituent in the 3-position.

Claim 46

A process according to claims 38 through 44 wherein the product has the formula or a salt thereof; wherein R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (R c ), phenylalkyl, (substituted-phenyl)alkyl, R c -alkyl or -NR a R b wherein R a and R b are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of R a and R b is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NH 2 ), alkanoylamino, arylcarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, alkylamino, dialkylamino, phenylamino, (substituted phenyl)-amino, hydroxy, cyano-(-C≡N) , alkoxy, phenyloxy, (substituted phenyl)oxy, phenylalkoxy, (substituted phenyl)alkoxy, R c as defined above, R c -alkyl, R c -alkoxy, alkylsulfonyl, alkylmethyleneamino, (alkyl-CH=N-), phenylmethyleneamino or (substituted phenyl)methyleneamino; R 1 ' amino, protected amino or acylamino; R 2 is hydrogen or methoxy; R 3 and R 4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R 3 and R 4 is hydrogen and the other is alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, -CH 2 X 1 (wherein X 1 is azido, amino, hydroxy, alkanoylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, halogen, benzylthio, (substituted phenyl)methylthio, triphenylmethylthio, cyano or mercapto), -S-X 2 or -O-X 2 (wherein X 2 is alkyl, phenyl, substituted phenyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, or heteroarylcarbonyl), or (wherein one of X 3 and X 4 is hydrogen and the other is hydrogen or alkyl, or X 3 and X 4 when taken together with the carbon atom to which they are attached form a cycloalkyl group, and X 5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, phenylalkylcarbonyl, (substituted phenyl)alkylcarbonyl, carboxyl, alkoxycarbonyl, aminocarbonyl, (substituted amino)-carbonyl, or cyano); and Z is oxygen or sulfur.

Claim 47

A process according to claim 4 5 wherein R 1 is acylamino and said product is obtained by acylating a product wherein R 1 ' is amino.

Claim 48

A process in accordance with claims 4 5 an4 46 wherein R 2 is hydrogen.

Claim 49

A process in accordance with claim 47 wherein R 3 is hydrogen and R 4 is hydrogen or methyl.

Claim 50

A process in accordance with claim 48 wherein Z is oxygen.

Claim 51

A process in accordance with claims 45 and 46 wherein Z is oxygen.

Claim 52

A process in accordance with claim 45 and 46 wherein the product has the formula wherein R 1 is acyl or a salt thereof.

Claim 53

A process in accordance with claim 51 wherein R a and R b each is hydrogen.

Claim 54

A process in accordance with claims 45 and 46 wherein R 1 .' is acylamino of the formula R 11 is 2-amino-4-thiazolyl and R 13 is alkyl or carboxy substituted alkyl.

Claim 55

A process in accordance with claim 45 wherein the product is of the formula or a salt thereof, or a form thereof wherein the amino group is protected.

Claim 56

A process according to claim 38 wherein the product is of the formula Wherein Y can be hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl.

Claim 57

A process according to claim 38 wherein the product is of the formula wherein n can be zero or one and X can be methylene, oxygen or a nitrogen atom which can be substituted with alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)-alkyl, amino, alkylamino, dialkylamino, alkylidenamino, aralkylidenamino, alkyl sulfonyl, carboxy, carboxyalkyl and the like.

Claim 58

A process according to claim 38 wherein the product is of the formula wherein W can be hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl.