US3884915A - 7-Alkylmercaptoacetamido cephalosporins - Google Patents

7-Alkylmercaptoacetamido cephalosporins Download PDF

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Publication number
US3884915A
US3884915A US366816A US36681673A US3884915A US 3884915 A US3884915 A US 3884915A US 366816 A US366816 A US 366816A US 36681673 A US36681673 A US 36681673A US 3884915 A US3884915 A US 3884915A
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United States
Prior art keywords
cephem
carboxylic acid
ylthiomethyl
amino
compound
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Expired - Lifetime
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US366816A
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English (en)
Inventor
Robert M Demarinis
John R E Hoover
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SmithKline Beecham Corp
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SmithKline Corp
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Publication date
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Priority to US366816A priority Critical patent/US3884915A/en
Priority to BE144859A priority patent/BE815668A/xx
Priority to JP49062453A priority patent/JPS5019768A/ja
Priority to FR7419079A priority patent/FR2231366B1/fr
Priority to GB2471574A priority patent/GB1436977A/en
Priority to DE19742426970 priority patent/DE2426970A1/de
Application granted granted Critical
Publication of US3884915A publication Critical patent/US3884915A/en
Assigned to SMITHKLINE BECKMAN CORPORATION reassignment SMITHKLINE BECKMAN CORPORATION CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). EFFECTIVE DATE: 03/04/82 Assignors: SMITHKLINE CORPORATION
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • C07D501/14—Compounds having a nitrogen atom directly attached in position 7
    • C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
    • C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
    • C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
    • C07D501/36—Methylene radicals, substituted by sulfur atoms

Definitions

  • the compounds of this invention are prepared by acwhich have antibacterial activity.
  • the in- 5 ylation of an aqueous solution of the sodium salt of the vention relates to compounds possessing an alkylmerappropriate 7-aminocephalosporanic acid nucleus, captoacetamido substituent at position 7 of the cephem where A CH Sl-let, with an appropriately substituted nucleus and an S-hetero substituent at position 3. alkylmercapto-acetic acid chloride.
  • the compounds of this invention are represented by The 7-amino e halo orin nuclei where A the following structure: 0 CH SHet are prepared by known methods from 7-aminocephalosporanic acid (7-ACA) and the appro- S priate heterocyclic mercaptan compound. RSCH ZCONH ⁇
  • the cephalosporins of this invention possess antibacterial activity. They are active against both Gram- A positive and Gram-negative organisms. Minimum in- OOM hibitory concentrations (MIC) ranged from 0.2 to
  • M is hydrogen or an alkali metal or ammonium cat-
  • the compounds are formulated and administered by ion; and injection in the same manner as other cephalosporins A is Z
  • Het is a five or six memb red with the dose depending on the subject and infection heterocyclic ring containing two to four atoms selected b i t t d,
  • pound Preferred compounds are those where Het is unsub- E. (01! Kleb. pneumo. stltuted or methyl substituted trrazolyl, tetrazolyl, ox- 5O pa SC p0 azolyl, oxadiazolyl, thiazolyl or thradlazolyl.
  • EXAMPLE 3 7-Ethylmercaptoacetamido-3-( l-methyl-1,2,3,4- tetrazol-S-ylthiomethyl)-A -cephem-4-carboxylic acid
  • the procedure as described in Example 2 was followed utilizing 2.95 g. (0.009 mol.) of 7-amino-3-(1- methyl- 1 ,2,3,4-tetrazol-5-ylthiomethy1)-A -cephem-4- carboxylic acid in 60 ml. of 3 percent sodium bicarbonate and 60 ml. of acetone and 1.38 g. (0.010 mol.) of ethylmercaptoacetyl chloride in 20 ml. of acetone.
  • EXAMPLE 6 7-Methylmercaptoacetamido-3-(4-methyl-l ,2,4- triazol-3-ylthiomethyl)-A -ccphem-4-carboxylic acid
  • the procedure as described in Example 2 was followed utilizing 3.92 g. (0.013 mol.) of 7-amino-3-(4- methyl-l ,2,4-triazol-3-ylthiomethyl)-A -cephem-4- carboxylic acid in 80 ml. of 3 percent sodium bicarbonate and 80 ml. of acetone and 1.7 g. (0.013 mol.) of methylmercaptoacetyl chloride in 25 ml. of acetone.
  • the acidified (pH 3.5) aqueous solution was extracted with ethyl acetate then concentrated in vacuo to yield, upon cooling, 7-methylmercaptoacetamido-3-(4- methyl-l ,2,4-triazol-3-ylthiomethyl)-A -cephem-4- carboxylic acid.
  • the acid was dissolved in methanol, the solution was filtered, and a percent solution of sodium methoxide in methanol was added to pH 6.8. Addition of ether to this solution caused precipitation of the sodium salt which was collected and recrystallized from methanol-ether to give 0.62g. of pure material.
  • EXAMPLE 7 7-amino-3-( 3-ethyll ,2,4-thiadiazol-5-ylthiomethyl A -cephem-4-carboxylic acid 7-amino-3-thiazol-5-ylthiomethyl)-A -cephem-4- carboxylic acid 7-amino-3-(2-methylthiazol-5-ylthiomethyl)-A cephem-4-carboxylic acid 7-amino-3-(4-methylthiazol-5-ylthiomethyl )-A cephem-4-carboxylic acid 7-amino-3-( 2,4-dimethylthiazol-S-ylthiomethyl )-A cephem-4-carboxylic acid 7-amino-3-( 2-ethylthiazol-5-ylthiomethyl )-A cephem-4-carboxylic acid 7-amino-3-(4-ethylthiazol-5-ylthiomethyl)-A cephem-4-car
  • EXAMPLE 1 1 An injectable pharmaceutical composition is formed by adding sterile water or sterile saline solution (2 ml.)
  • R is lower alkyl of one to six carbon atoms
  • M is hydrogen or an alkali metal or ammonium cation
  • A is CH SI-Iet, where Het is a five or six membered heterocyclic ring containing two to four atoms selected from the group consisting of N, O and S, unsubstituted or substituted with from one to two groups selected from lower alkyl, alkoxyalkyl or trifluoromethyl, each alkyl or alkoxy having from one to four carbon atoms.
  • R is methyl, ethyl or propyl.
  • a compound as claimed in claim 3 being the compound 7-methylmercaptoacetamido-3-( l-methyll ,2,3,4-tetrazol-5-ylthiomethyl)-A -cephem-4- carboxylic acid.
  • a compound as claimed in claim 3 being the compound 7-ethylmercaptoacetamido-3-( l-rnethyll ,2,3,4-tetrazol-5-ylthiomethyl)-A -cephem-4- carboxylic acid.
  • a compound as claimed in claim 3 being the compound 7-n-propylmercaptoacetamido-3-( l-methyll ,2,3 ,4-tetrazol-5-ylthiomethyl)-A -cephem-4- carboxylic acid.
  • a compound as claimed in claim 3 being the compound 7-methylmercaptoacetamido-3-(4-methyll ,2,4-triazol-5-ylthiomethyl)-A -cephem-4-carboxylic acid.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Cephalosporin Compounds (AREA)
US366816A 1973-06-04 1973-06-04 7-Alkylmercaptoacetamido cephalosporins Expired - Lifetime US3884915A (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
US366816A US3884915A (en) 1973-06-04 1973-06-04 7-Alkylmercaptoacetamido cephalosporins
BE144859A BE815668A (fr) 1973-06-04 1974-05-29 7-alkylmercaptoacetamidocephalosporines
JP49062453A JPS5019768A (enrdf_load_stackoverflow) 1973-06-04 1974-05-31
FR7419079A FR2231366B1 (enrdf_load_stackoverflow) 1973-06-04 1974-05-31
GB2471574A GB1436977A (en) 1973-06-04 1974-06-04 7-alkylthioacetamido cephaosporins
DE19742426970 DE2426970A1 (de) 1973-06-04 1974-06-04 7-alkylmercaptoacetamidocephalosporine, ihre salze, verfahren zu ihrer herstellung und arzneimittel

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US366816A US3884915A (en) 1973-06-04 1973-06-04 7-Alkylmercaptoacetamido cephalosporins

Publications (1)

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US3884915A true US3884915A (en) 1975-05-20

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US366816A Expired - Lifetime US3884915A (en) 1973-06-04 1973-06-04 7-Alkylmercaptoacetamido cephalosporins

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US (1) US3884915A (enrdf_load_stackoverflow)
JP (1) JPS5019768A (enrdf_load_stackoverflow)
BE (1) BE815668A (enrdf_load_stackoverflow)
DE (1) DE2426970A1 (enrdf_load_stackoverflow)
FR (1) FR2231366B1 (enrdf_load_stackoverflow)
GB (1) GB1436977A (enrdf_load_stackoverflow)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4058609A (en) * 1976-06-28 1977-11-15 Smithkline Corporation 7-Dithioacetamido cephalosporins
US4059578A (en) * 1974-09-09 1977-11-22 Smithkline Corporation 7-Substituted mercaptoacetamido cephamycins
US4101657A (en) * 1975-01-13 1978-07-18 Smithkline Corporation Cephamycins as antibacterial agents
US4158733A (en) * 1975-06-18 1979-06-19 Smithkline Corporation 7β-Acyloxy-3-acetoxymethyl cephalosporins
US4286089A (en) * 1974-12-27 1981-08-25 Smithkline Corporation 7-Acyl-3-(substituted tetrazolyl thiomethyl)cephalosporins

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3297692A (en) * 1961-04-03 1967-01-10 Lilly Co Eli 7-alkylmercaptoacetamidocephalosporanic acid
US3445463A (en) * 1965-06-17 1969-05-20 Lilly Co Eli 3-(cyclic acyl)oxymethyl cephalosporins
US3776906A (en) * 1972-03-16 1973-12-04 Bristol Myers Co 7-(d-(alpha-amino-alpha-phenyl-,2-thienyl-and 3-thienyl-acetamido))-3-thienyl-acetamido))-3-(1,2,5-thiadiazol-3-yl)carbonylthiomethyl-3-cephem-4-carboxylic acids
US3776907A (en) * 1972-06-12 1973-12-04 Bristol Myers Co 7-(d-(alpha-amino-alpha-phenyl-,2-thienyl-and 3-thienyl-acetamido))-3-(1,2,3-thiadiazol-4-or 5-yl)-carbonylthiomethyl-3-cephem-4-carboxylic acids

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3297692A (en) * 1961-04-03 1967-01-10 Lilly Co Eli 7-alkylmercaptoacetamidocephalosporanic acid
US3445463A (en) * 1965-06-17 1969-05-20 Lilly Co Eli 3-(cyclic acyl)oxymethyl cephalosporins
US3776906A (en) * 1972-03-16 1973-12-04 Bristol Myers Co 7-(d-(alpha-amino-alpha-phenyl-,2-thienyl-and 3-thienyl-acetamido))-3-thienyl-acetamido))-3-(1,2,5-thiadiazol-3-yl)carbonylthiomethyl-3-cephem-4-carboxylic acids
US3776907A (en) * 1972-06-12 1973-12-04 Bristol Myers Co 7-(d-(alpha-amino-alpha-phenyl-,2-thienyl-and 3-thienyl-acetamido))-3-(1,2,3-thiadiazol-4-or 5-yl)-carbonylthiomethyl-3-cephem-4-carboxylic acids

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4059578A (en) * 1974-09-09 1977-11-22 Smithkline Corporation 7-Substituted mercaptoacetamido cephamycins
US4286089A (en) * 1974-12-27 1981-08-25 Smithkline Corporation 7-Acyl-3-(substituted tetrazolyl thiomethyl)cephalosporins
US4101657A (en) * 1975-01-13 1978-07-18 Smithkline Corporation Cephamycins as antibacterial agents
US4158733A (en) * 1975-06-18 1979-06-19 Smithkline Corporation 7β-Acyloxy-3-acetoxymethyl cephalosporins
US4058609A (en) * 1976-06-28 1977-11-15 Smithkline Corporation 7-Dithioacetamido cephalosporins
US4137314A (en) * 1976-06-28 1979-01-30 Smithkline Corporation 7-Dithioacetamido cephalosporins and pharmaceutical compositions and methods employing them having antibacterial activity

Also Published As

Publication number Publication date
DE2426970A1 (de) 1974-12-19
JPS5019768A (enrdf_load_stackoverflow) 1975-03-01
FR2231366A1 (enrdf_load_stackoverflow) 1974-12-27
FR2231366B1 (enrdf_load_stackoverflow) 1977-11-04
BE815668A (fr) 1974-11-29
GB1436977A (en) 1976-05-26

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Owner name: SMITHKLINE BECKMAN CORPORATION

Free format text: CHANGE OF NAME;ASSIGNOR:SMITHKLINE CORPORATION;REEL/FRAME:004080/0769

Effective date: 19820304

Owner name: SMITHKLINE BECKMAN CORPORATION, PENNSYLVANIA

Free format text: CHANGE OF NAME;ASSIGNOR:SMITHKLINE CORPORATION;REEL/FRAME:004080/0769

Effective date: 19820304