Patents by Inventor Ronald W. Ratcliffe
Ronald W. Ratcliffe has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 5140030Abstract: Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids. I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, triazolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of I from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.Type: GrantFiled: August 16, 1990Date of Patent: August 18, 1992Assignee: MerckInventors: Burton G. Christensen, Ronald W. Ratcliffe, John C. Chabala
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Patent number: 5021565Abstract: Described is a new process for producing new 2-substituted alkyl-3-carboxycarbapenems, involving condensation of a 2-oxocarbapenam-3-carboxylic ester with a stabilized ylide followed by ester deblocking. The resulting carbapenem compounds, which are not readily available from other known synthetic routes, show interesting antibacterial activity.Type: GrantFiled: June 21, 1990Date of Patent: June 4, 1991Assignee: Merck & Co., Inc.Inventors: Ronald W. Ratcliffe, Mary F. Woods
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Patent number: 4957912Abstract: Novel antibiotics of the formula: ##STR1## and its salts, esters and amides wherein R is acyl;B is H, OMe, Me or SR wherein R is lower alkyl or aryl;A.sup.1 is hydrogen, hydroxy, or an organic group; and,X is a divalent radical selected from --O--, --CH.sub.2 --, or --NY-- where Y is hydrogen or lower alkyl of from 1 to 6 carbon atoms such as methyl, ethyl, i-propyl, n-butyl, n-pentyl, n-hexyl and the like, formyl or benzyl.This invention is directed to novel antibiotics, novel intermediates useful in their preparation, and processes for preparing the novel antibiotics. The novel antibiotics are effective against gram-negative bacteria including Proteus vulgaris, E. coli and Salmonella schottmulleri, and gram-positive bacteria including Staphylococcus aureas and Bacillus subtilis and are useful in combatting bacterial infections in animals or humans in addition to various industrial applications.Type: GrantFiled: December 23, 1985Date of Patent: September 18, 1990Assignee: Merck & Co., Inc.Inventors: Burton G. Christenson, Ronald W. Ratcliffe
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Patent number: 4952397Abstract: Compounds of the formula: ##STR1## wherein ##STR2## is a quaternized, monocyclic or bicyclic heteroaryl group, substituted by an acid moiety, and their preparation and use as antibiotics are disclosed.Type: GrantFiled: November 23, 1988Date of Patent: August 28, 1990Assignee: Merck & Co., Inc.Inventors: James V. Heck, Ronald W. Ratcliffe
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Patent number: 4892869Abstract: Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, triazolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of 1 from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.Type: GrantFiled: January 19, 1989Date of Patent: January 9, 1990Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, Ronald W. Ratcliffe, John C. Chabala
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Patent number: 4833167Abstract: Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, diaklylamino, triazolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of I from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.Type: GrantFiled: June 10, 1985Date of Patent: May 23, 1989Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, John C. Chabala, Ronald W. Ratcliffe
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Patent number: 4820817Abstract: Disclosed is a process for preparing 3-substituted-thio-6-(1'-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene -2-carboxylic acids (I) ##STR1## wherein X is a leaving group such as chloro, bromo, tosyl, mesyl or the like; and R.sup.8 is, inter alia, selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl. The compounds I as well as their pharmaceutically acceptable O- and carboxyl derivatives are useful as antibiotics.Type: GrantFiled: October 15, 1985Date of Patent: April 11, 1989Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, Ronald W. Ratcliffe
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Patent number: 4783453Abstract: Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, triazolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of I from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.Type: GrantFiled: September 8, 1987Date of Patent: November 8, 1988Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, Ronald W. Ratcliffe, John C. Chabala
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Patent number: 4782051Abstract: Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, trizolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of I from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.Type: GrantFiled: August 17, 1987Date of Patent: November 1, 1988Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, John C. Chabala, Ronald W. Ratcliffe
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Patent number: 4748162Abstract: Disclosed are 6-substituted-2-carbamimidoyl-pen-2-em-3-carboxylic acids (I) having the representative structure: ##STR1## wherein R.sup.6, and R.sup.7 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, alkoxyl, halo, OH, COOH, alkenyl, aryl and aralkyl; A is a direct, single bond connecting the indicated S and C atoms, or A is a cyclic or acyclic connecting group selected, inter alia, from alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl; R.sup.1 and R.sup.2, which define the carbamimidoyl function, are, inter alia, independently selected from hydrogen, alkyl, aryl; additionally, said carbamimidoyl is characterized by cyclic structures achieved by the joinder of the two nitrogen atoms via their substituents and by their joinder to connecting group A; additionally, "carbamimidiums" are disclosed by quarternization of one of the nitrogen atoms of said carbamimidoyl.Type: GrantFiled: April 30, 1984Date of Patent: May 31, 1988Assignee: Merck & Co., Inc.Inventors: William J. Leanza, Burton G. Christensen, Frank P. DiNinno, Ronald W. Ratcliffe
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Patent number: 4745188Abstract: Disclosed is a process for preparing 3- and 6-substituted-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acids: ##STR1## wherein: X is a leaving group such as chloro, bromo, tosyl, mesyl or the like; and R.sup.6, R.sup.7 and R.sup.8 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl. Such compounds (I), as well as their pharmaceutically acceptable salt, ester and amide derivatives, are useful as antibiotics.Type: GrantFiled: July 29, 1985Date of Patent: May 17, 1988Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, Ronald W. Ratcliffe
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Patent number: 4739048Abstract: Disclosed is a process for the total synthesis of thienamycin from L-aspartic acid via intermediate III: ##STR1##Type: GrantFiled: July 12, 1985Date of Patent: April 19, 1988Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, Ronald W. Ratcliffe, Thomas N. Salzmann
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Patent number: 4736025Abstract: Disclosed is a process for the total synthesis of thienamycin from L-aspartic acid via intermediate III: ##STR1## R=H, blocking group or salt cation.Type: GrantFiled: January 13, 1983Date of Patent: April 5, 1988Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, Ronald W. Ratcliffe, Thomas N. Salzmann
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Patent number: 4729993Abstract: Carbapenems having the formula: ##STR1## wherein ##STR2## is mono- or bicyclic quaternary heteroaryl, their preparation and antibiotic use are disclosed.Type: GrantFiled: December 13, 1984Date of Patent: March 8, 1988Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, Ronald W. Ratcliffe, James V. Heck, Thomas N. Salzmann, David H. Shih
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Patent number: 4725594Abstract: Carbapenems having the formula: ##STR1## wherein: R.sup.1 is H;R.sup.4 and R.sup.5 are independently H, CH.sub.3 --, CH.sub.3 CH.sub.2 --, (CH.sub.3).sub.2 CH--, HOCH.sub.2 --, CH.sub.3 CH(OH)--, (CH.sub.3).sub.2 C(OH)--, FCH.sub.2, F.sub.2 CH--, F.sub.3 C--, CH.sub.3 CH(F)--, CH.sub.3 CF.sub.2 --, (CH.sub.3).sub.2 C(F)--; X is --S--, --SO--, --SO.sub.2 --, --O-- or --NH; L is a bridging group comprising substituted or unsubstituted C.sub.1 --C.sub.4 straight, C.sub.2 -C.sub.6 branched or C.sub.3 -C.sub.7 cycloalkyl groups wherein the substituents are selected from C.sub.1 -C.sub.6 alkyl, O--C.sub.1 -C.sub.6 alkyl, S--C.sub.1 -C.sub.6 alkyl, CF.sub.3, N(C.sub.1 -C.sub.6 alkyl).sub.2 ; Y is a carboxy-containing substituent; Het is internally alkylated heteroarylium, ##STR2## or externally alkylated heteroarylium, ##STR3## their preparation and antibiotic use are disclosed.Type: GrantFiled: December 13, 1984Date of Patent: February 16, 1988Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, James V. Heck, Ronald W. Ratcliffe, Thomas N. Salzmann
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Patent number: 4707547Abstract: Disclosed are 6- and 6,6-disubstituted-3-substituted amino-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylic acids (I): ##STR1## wherein R.sup.1 and R.sup.2 are, inter alia, independently selected from the group consisting of hydrogen, substituted and unsubstituted: alkyl, aryl, and aralkyl; and R' and R" are independently selected from the group consisting of: H, substituted and unsubstituted alkyl and aralkyl, or together form a substituted or unsubstituted cyclic group.Such compounds and their pharmaceutically acceptable salt, 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 compounds and compositions when an antibiotic effect is indicated.Type: GrantFiled: May 2, 1986Date of Patent: November 17, 1987Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, Ronald W. Ratcliffe
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Patent number: 4675317Abstract: Disclosed are 6- and 6,6-disubstituted-2-substituted thio-pen-2-em-3-carboxylic acids of the following structure: ##STR1## wherein: R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently selected from: hydrogen; substituted and unsubstituted: alkyl, cycloalkyl, halo, alkoxyl, alkenyl, aralkyl, aryl, heterocyclyl, heteroaryl, and heterocyclylalkyl; W is an electron withdrawing group, and, for example, is selected from: --COR.sup.5, --CN, SO.sub.2 C.sub.6 H.sub.5 ; R.sup.5 is hydrogen; substituted and unsubstituted: alkyl, aryl, aralkyl, heteroaryl, heterocyclyl, or heterocyclylalkyl; or R.sup.5 may be --OR.sup.6, --NR.sup.7 R.sup.8, and --SR.sup.9 ; wherein R.sup.6 is H; substituted and unsubstituted: alkyl, alkenyl, or a group which defines --CO.sub.2 R.sup.6 as a pharmaceutically acceptable ester wherein R.sup.6 is, for example, phthalidyl, or 5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl; R.sup.7 and R.sup.Type: GrantFiled: January 25, 1983Date of Patent: June 23, 1987Assignee: Merck & Co., Inc.Inventors: Frank P. DiNinno, William J. Leanza, Ronald W. Ratcliffe, David A. Muthard
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Patent number: 4650794Abstract: Disclosed are 6-(1-hydroxyethyl)-2-carbamimidoyl-pen-2-em-3-carboxylic acids (I) having the representative structure: ##STR1## wherein: A is a direct, single bond connecting the indicated S and C atoms, or A is a cyclic or acyclic connecting group selected, inter alia, from alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl; R.sup.1 and R.sup.2, which define the carbamimidoyl function, are, inter alia, independently selected from hydrogen, alkyl, aryl, alkoxy, amino; additionally, said carbamimidoyl is characterized by cyclic structures achieved by the joinder of the two nitrogen atoms via their substituents and by their joinder to connecting group A; additionally, "carbamimidiums" are disclosed by quaternization of one of the nitrogen atoms of said carbamimidoyl. Such compounds as well as their pharmaceutically acceptable salt, ester and amide derivatives are useful as antibiotics.Type: GrantFiled: April 29, 1982Date of Patent: March 17, 1987Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, Frank P. DiNinno, William J. Leanza, Ronald W. Ratcliffe
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Patent number: 4610820Abstract: In a process for the total synthesis of thienamycin from L-aspartic acid via intermediate III: ##STR1## R=H, blocking group or salt cation there is disclosed a process for preparing III via ##STR2## wherein R is a protecting group.Type: GrantFiled: October 11, 1985Date of Patent: September 9, 1986Assignee: Merck & Co., Inc.Inventors: Burton G. Christensen, Ronald W. Ratcliffe, Thomas N. Salzmann
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Patent number: 4610823Abstract: Disclosed is a synthesis for preparing substituted 2-thioxopenams which are useful in the synthesis of penem antibiotics 7 which may be conducted in an enantiospecific manner; said process proceeds from azetidinone 1 via the azetidinone acetic ester 2, the 4-metallothiozetidinone 3, and the 4-dithiocarbonylazetidinone 4 to the substituted 2-thioxopenam 5: ##STR1## wherein: R.sup.6 and R.sup.7 are independently selected from: hydrogen; R.sup.6 NH-- (R.sup.6 is acyl or H); substituted and unsubstituted: alkyl, alkenyl, alkynyl, aryl, heterocyclyl, heteroaryl, cycloalkyl, and cycloalkenyl; wherein said substituents are, inter alia: halo (chloro, bromo, fluoro, iodo), hydroxyl, cyano, carboxyl, amino, and the above-recited values for R.sup.6 and R.sup.7 ; in functional terms,R.sup.2 is a group which potentially forms a stable carbonium ion, for example: trityl (--C(C.sub.6 H.sub.5).sub.Type: GrantFiled: January 25, 1983Date of Patent: September 9, 1986Assignee: Merck & Co., Inc.Inventors: Frank P. DiNinno, William J. Leanza, Ronald W. Ratcliffe