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US4232030A Expired / Lapsed US ⏱️ 0.0 years remaining

Substituted N-methylene derivatives of thienamycin sulfoxide and sulfone

Assignee: Merck and Co Inc
•
Filing: 1977-09-15
•
Granted: 1980-11-04
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Expires: 1997-09-15
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Abstract

Abstract Disclosed are substituted N-methylene derivatives of thienamycin sulfoxide (I, n=1) and sulfone (I, n=2) which may be represented by the following structural formula: <IMAGE> I wherein X and Y are selected from the group consisting of hydrogen, R, OR, SR, and NR1R2 wherein, inter alia, R is substituted or unsubstituted: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl; R1 and R2 are hydrogen or R. Such compounds and their pharmaceutically acceptable salt, ether, ester and amide derivatives are useful as antibiotics. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

Inventors

  • 👤 Burton G. Christensen
  • 👤 William J. Leanza
  • 👤 Kenneth J. Wildonger

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-09 14:34
CPC Classifications
C; C07; C07D; C07D477/00; C07D477/10; C07D477/12; C07D477/16; C07D477/20; A; A61; A61P; A61P31/00; A61P31/04; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/10; C07F7/18; C07F7/1804

Claims Analysis

Total Claims: 24
Claim 1
Independent Claim 272 words
A compound having the structure: ##STR240## and the pharmaceutically acceptable salts thereof wherein: n is 1 or 2; R 3 is selected from the group consisting of: hydrogen, formyl, acetyl, propionyl, butyryl, chloroacetyl, methoxyacetyl, aminoacetyl, methoxycarbonyl, ethoxycarbonyl, methylcarbamoyl, ethylcarbamoyl, phenylthiocarbonyl, 3-aminopropionyl, 4-aminobutyryl, N-methylaminoacetyl, N,N-dimethylaminoacetyl, N,N,N-trimethylaminoacetyl, 3-(N,N-dimethyl)aminopropionyl, 3-(N,N,N-trimethyl)amino propionyl, N,N,N-triethylaminoacetyl, pyridiniumacetyl, guanylthioacetyl, guanidinoacetyl, 3-guanidinopropionyl, N 3 -methylguanidinopropionyl, hydroxyacetyl, 3-hydroxypropionyl, acryloyl, propynol, malonyl, phenoxycarbonyl amidinoacetyl, acetamidinoacetyl, amidinopropionyl, acetamidinopropionyl, guanylureidoacetyl, guanylcarbamoyl, carboxymethylaminoacetyl, sulfoacetylaminoacetyl, phosphonoacetylaminoacetyl, N 3 -dimethylaminoacetamidinopropionyl, ureidocarbonyl, dimethylaminoguanylthioacetyl, 3-(1-methyl-4-pyridinium)propionyl, 3-(5-aminoimidazol-1-yl)propionyl, 3-methyl-1-imidazoliumacetyl, 3-sydnonylacetyl, o-aminomethylbenzoyl, o-aminobenzoyl, ##STR241## M is hydrogen or an alkali or alkaline earth metal cation; R 3' is selected from the group consisting of: hydrogen, methyl, t-butyl, phenacyl, p-bromophenacyl; pivaloyloxymethyl, 2,2,2-trichloroethyl, allyl, 3-methyl-2-butenyl, 2-methyl-2-propenyl, benzyl, benzylhydryl, p-t-butylbenzyl, phthalidyl, phenyl, 5-indanyl, acetylthiomethyl, acetoxymethyl, propionyloxymethyl, methallyl, 3-butenyl, 4-pentenyl, 2-butenyl, acetoxyacetylmethyl, pivaloylacetylmethyl, diethylamino, dimethylaminoethyl, methoxymethyl, p-acetoxybenzyl, p-pivaloylbenzyl, p-isopropoxybenzyl, 5-indanylmethyl, benzyloxymethyl, methylthioethyl, dimethylaminoacetoxymethyl, crotonolacton-3-yl, acetamidomethyl, acetylthioethyl, pivaloylthiomethyl, methylthiomethyl; X and Y are independently selected from the group consisting of hydrogen, R, --OR, S-R and NR 1 R 2 R 1 and R 2 are independently selected from the group consisting of hydrogen; alkyl having 1-6 carbon atoms; alkenyl having 3-6 carbon atoms; cycloalkyl, cycloalkylalkyl, cycloalkenyl and cycloalkenylalkyl having 3-6, 4-7 4-6 and 4-7 carbon atoms, respectively; benzyl; p-methoxybenzyl, p-dimethylaminobenzyl, cinnamyl; 2-thienylmethyl, 3-thienylmethyl, 2-furylmethyl, 1-methyl-5-tetrazolylmethyl; and R is selected from the group consisting of hydrogen; alkyl having from 1-6 carbon atoms; aminoalkyl having 1-6 carbon atoms, aminoalkenyl having 1-6 carbon atoms; alkenyl having 2-6 carbon atoms; alkoxyalkyl having 2-6 carbon atoms; mono-, di- and triloweralkylaminoalkyl having 2-12 carbon atoms; perhaloalkyl having from 1-6 carbon atoms; alkylthioalkyl having 2-6 carbon atoms; phenyl; benzyl; 2-, 3- and 4-pyridyl and 2-thiazolyl.
Claim 2
Dependent Claim 272 words
A compound having the structure: ##STR240## and the pharmaceutically acceptable salts thereof wherein: n is 1 or 2; R 3 is selected from the group consisting of: hydrogen, formyl, acetyl, propionyl, butyryl, chloroacetyl, methoxyacetyl, aminoacetyl, methoxycarbonyl, ethoxycarbonyl, methylcarbamoyl, ethylcarbamoyl, phenylthiocarbonyl, 3-aminopropionyl, 4-aminobutyryl, N-methylaminoacetyl, N,N-dimethylaminoacetyl, N,N,N-trimethylaminoacetyl, 3-(N,N-dimethyl)aminopropionyl, 3-(N,N,N-trimethyl)amino propionyl, N,N,N-triethylaminoacetyl, pyridiniumacetyl, guanylthioacetyl, guanidinoacetyl, 3-guanidinopropionyl, N 3 -methylguanidinopropionyl, hydroxyacetyl, 3-hydroxypropionyl, acryloyl, propynol, malonyl, phenoxycarbonyl amidinoacetyl, acetamidinoacetyl, amidinopropionyl, acetamidinopropionyl, guanylureidoacetyl, guanylcarbamoyl, carboxymethylaminoacetyl, sulfoacetylaminoacetyl, phosphonoacetylaminoacetyl, N 3 -dimethylaminoacetamidinopropionyl, ureidocarbonyl, dimethylaminoguanylthioacetyl, 3-(1-methyl-4-pyridinium)propionyl, 3-(5-aminoimidazol-1-yl)propionyl, 3-methyl-1-imidazoliumacetyl, 3-sydnonylacetyl, o-aminomethylbenzoyl, o-aminobenzoyl, ##STR241## M is hydrogen or an alkali or alkaline earth metal cation; R 3' is selected from the group consisting of: hydrogen, methyl, t-butyl, phenacyl, p-bromophenacyl; pivaloyloxymethyl, 2,2,2-trichloroethyl, allyl, 3-methyl-2-butenyl, 2-methyl-2-propenyl, benzyl, benzylhydryl, p-t-butylbenzyl, phthalidyl, phenyl, 5-indanyl, acetylthiomethyl, acetoxymethyl, propionyloxymethyl, methallyl, 3-butenyl, 4-pentenyl, 2-butenyl, acetoxyacetylmethyl, pivaloylacetylmethyl, diethylamino, dimethylaminoethyl, methoxymethyl, p-acetoxybenzyl, p-pivaloylbenzyl, p-isopropoxybenzyl, 5-indanylmethyl, benzyloxymethyl, methylthioethyl, dimethylaminoacetoxymethyl, crotonolacton-3-yl, acetamidomethyl, acetylthioethyl, pivaloylthiomethyl, methylthiomethyl; X and Y are independently selected from the group consisting of hydrogen, R, --OR, S-R and NR 1 R 2 R 1 and R 2 are independently selected from the group consisting of hydrogen; alkyl having 1-6 carbon atoms; alkenyl having 3-6 carbon atoms; cycloalkyl, cycloalkylalkyl, cycloalkenyl and cycloalkenylalkyl having 3-6, 4-7 4-6 and 4-7 carbon atoms, respectively; benzyl; p-methoxybenzyl, p-dimethylaminobenzyl, cinnamyl; 2-thienylmethyl, 3-thienylmethyl, 2-furylmethyl, 1-methyl-5-tetrazolylmethyl; and R is selected from the group consisting of hydrogen; alkyl having from 1-6 carbon atoms; aminoalkyl having 1-6 carbon atoms, aminoalkenyl having 1-6 carbon atoms; alkenyl having 2-6 carbon atoms; alkoxyalkyl having 2-6 carbon atoms; mono-, di- and triloweralkylaminoalkyl having 2-12 carbon atoms; perhaloalkyl having from 1-6 carbon atoms; alkylthioalkyl having 2-6 carbon atoms; phenyl; benzyl; 2-, 3- and 4-pyridyl and 2-thiazolyl.
Claim 3
Dependent Claim 19 words
A compound according to claim 1 wherein Y is --NR 1 R 2 and X is hydrogen or R.
Claim 4
Dependent Claim 21 words
A compound according to claim 1 wherein Y is --NR 1 R 2 and X is --NR 1 R 2 .
Claim 5
Dependent Claim 19 words
A compound according to claim 1 wherein Y is --NR 1 R 2 and X is --OR or --SR.
Claim 6
Dependent Claim 26 words
A compound according to claim 1 wherein Y is selected from the group consisting of hydrogen, R, --OR and --SR, and X is --OR or --SR.
Claim 7
Dependent Claim 8 words
A compound according to claim 2 wherein n=1.
Claim 8
Dependent Claim 73 words
A compound according to claim 2 wherein: R 1 and R 2 are independently selected from the group consisting of: hydrogen; alkyl having 1-6 carbon atoms; and alkenyl having 3-6 carbon atoms; and R is independently selected from the group consisting of: hydrogen; alkyl; alkoxyalkyl; mono- and dialkylaminoalkyl wherein the alkyl moieties each comprise 1-6 carbon atoms; aminoalkyl having 1-6 carbon atoms; perfluoroalkyl; alkylthioalkyl; phenyl; benzyl; 2-,3- and 4-pyridyl and 2- and 4-thiazolyl.
Claim 9
Dependent Claim 61 words
A compound according to claim 7 wherein: R is selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, methoxymethyl, aminomethyl, aminoethyl, aminopropyl, dimethylaminomethyl, methylaminomethyl, trifluoromethyl, methylthiomethyl, ethylthiomethyl, phenyl, benzyl, 2-, 3- and 4-pyridyl and 2-thiazolyl, 4-thiazolyl; and R 1 and R 2 are independently selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, and allyl.
Claim 10
Dependent Claim 56 words
A compound according to claim 7 wherein: R 1 and R 2 independently are selected from the group consisting of hydrogen, alkyl having 1 to 6 carbon atoms, and alkenyl having 3 to 6 carbon atoms; and R is selected from the group consisting of hydrogen and alkyl and aminoalkyl having 1 to 6 carbon atoms.
Claim 11
Dependent Claim 10 words
The compound according to claim 7 having the structure: ##STR242##
Claim 12
Dependent Claim 10 words
The compound according to claim 9 having the structure: ##STR243##
Claim 13
Dependent Claim 10 words
The compound according to claim 3 having the structure: ##STR244##
Claim 14
Dependent Claim 19 words
The compound according to claim 9 having the structure: ##STR245## wherein A is a pharmaceutically acceptable anionic salt moiety.
Claim 15
Dependent Claim 10 words
The compound according to claim 9 having the structure: ##STR246##
Claim 16
Dependent Claim 14 words
The compound according to claim 7 having the structure: ##STR247## wherein R is 3-pyridyl.
Claim 17
Dependent Claim 14 words
The compound according to claim 7 having the structure: ##STR248## wherein R is 4-thiazolyl.
Claim 18
Dependent Claim 10 words
The compound according to claim 9 having the structure: ##STR249##
Claim 19
Dependent Claim 10 words
The compound according to claim 9 having the structure: ##STR250##
Claim 20
Dependent Claim 10 words
The compound according to claim 8 having the structure: ##STR251##
Claim 21
Dependent Claim 10 words
The compound according to claim 9 having the structure: ##STR252##
Claim 22
Dependent Claim 10 words
The compound according to claim 9 having the structure: ##STR253##
Claim 23
Dependent Claim 10 words
The compound according to claim 9 having the structure: ##STR254##
Claim 24
Dependent Claim 23 words
An antibiotic pharmaceutical composition consisting essentially of a therapeutically effective amount of a compound according to claim 1 and a pharmaceutical carrier therefor.

References Cited (Backward Citations)

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US3862181A Cited
US4022773A Cited
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US4000161A Cited
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USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1983-11-04 1984-05-05 1984-11-04 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1987-11-04 1988-05-05 1988-11-04 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1991-11-04 1992-05-05 1992-11-04 $7700.00 Window Closed / Lapsed

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