IL40447A - Delta3-cephalosporin compounds and process for their preparation from delta2-cephalosporin - Google Patents

Delta3-cephalosporin compounds and process for their preparation from delta2-cephalosporin

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Publication number
IL40447A
IL40447A IL40447A IL4044769A IL40447A IL 40447 A IL40447 A IL 40447A IL 40447 A IL40447 A IL 40447A IL 4044769 A IL4044769 A IL 4044769A IL 40447 A IL40447 A IL 40447A
Authority
IL
Israel
Prior art keywords
compound
alkyl
hydrogen
amino
tert
Prior art date
Application number
IL40447A
Original Assignee
Lilly Co Eli
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lilly Co Eli filed Critical Lilly Co Eli
Publication of IL40447A publication Critical patent/IL40447A/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D501/00Heterocyclic 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
    • C07D501/02Preparation
    • C07D501/04Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D501/00Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D501/00Heterocyclic 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
    • C07D501/14Compounds having a nitrogen atom directly attached in position 7
    • C07D501/16Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
    • C07D501/207-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
    • C07D501/247-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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D501/00Heterocyclic 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
    • C07D501/14Compounds having a nitrogen atom directly attached in position 7
    • C07D501/60Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 3 and 4
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Cephalosporin Compounds (AREA)

Claims (6)

1. WHAT WE CLAIM IS: A process for producing a compound of the formula S R-NH-CH-CH CH, 0=C N C-CH„-R' COOR" wherein R is hydrogen; .mino where X is amino, butoxycarbony nydrpxy, carboxyl, or to Cj-alkanoyloxy; where X is oxygen or sulfur or a chemical bond, y is an integer of from 0 to 2, and z is an integer of from 1 to 2 , and Q in each of the above phenyl rings is hydrogen, C^ to C^ ^^y^ Cj to Cj- alkoxy, nitro, hydroxy, chloro, bromo, fluoro, trifiuoro-methyl, carfcoxymethyl (KOOC-CH2-) or carbamoylnethyl (H2NIfi:(0)CH2-) , —62— 40447/4 Z-C CH II li Z-C C-CH-CO- ; where Y is sulfur, and each Z separately denotes hydrogen, or taken together with the carbons to which they are bonded, complete a benzo-ring, wherein e to to Cj-alkanoyl where X is oxygen or sulfur C2 to -haloalkanoyl where halogen is luorine, chlorine, or bromine, or R' is cyano or -0Y where Y is to C1Q-alkyl, C3 to C10-alkenyf, C3 to C10-alfcynyl , to C3-alkyl-X-C2 to C&-alky1 where X is oxygen or sulfur C2 to C4-alkanoyloxy-C2 to C^-alkyl, (furyl)-^ to C3-alkyl, 3' -tetrahydrofuryl 40447/3 tetrahydrofuryl-Cj to Cj-alkyl phenyl or benzyl, which are substituted on ring carbon atoms thereof with Cj to C^-alkyl, to Cg-alkoxy, Cj to Cj-alkoxycarbonyl, fluorine, chlorine, bromine, nitro, cyano or trifluoromethyl ; and R" is hydrogen a zwitterionic charge, a salt with pharmaceutically acceptable cation, C4 to C6-tert-alkyl, benzyl , methoxybenzyl or nitrobenzyl 2 which comprises reacting the corresponding ^ -compounds : C00R" where R' arid R" are defined as above and R'" is phenoxyacetyl , thio-pheneacetyl or phenylacetyl, with an oxidizing agent to produce the 3 3 corresponding ^ sulfoxide and then reducing to produce said -cephalosporin ester compound and if desired optionally cleaVing the R'" group from the seven position to provide the R group as defined above, and when desired preparing the salts.
2. A process according to claim 1, wherein the compound produced is that in which R is hydrogen, R' is cyano, " is a to Cg-tert-alkyl , -or a to C-^-aromatic hydrocarbon sulfonic acid salt of such a compound. 40447/3
3. A process according to claim 1 or 2 wherein the compound 3 produced is tert-batty1 7-amino-3-cyanomethyl-^ -cephem-4-carboxylate or a p-toluenesulfonate salt thereof.
4. A process according to claim 1 wherein the compound produced is that in which R is hydrogen, R' is -0Y, Y is to C1Q-alkyl, and R" is C4 to Cg-tert-alkyl or a to C-^-aromatic hydrocarbon sulfonic acid salt of such a compound.
5. A process according to claim 1 or 4 wherein the compound produced is tert-butyl 7-amino-3-methoxy-methyl-^-cephem-4-carboxylic acid, or a p-toluenesulfonate salt thereof.
6. A process according to claim 1, wherein the compound produced is that in which R is butoxycarbonylamino, hydroxy where X is amino, protected amino, to C^-alltoxy, -C00H, or to Cg-iilkanoyloxy, and Q is hydrogen, R' is -0Y, Y is to C^-allcyl, and R" is hydrogen, or a sodium or potassium salt of such a compound. 7* A process according to claim 1 or 6, wherein the compound 3 produced is 7-(D-21 amino-2 'phenyl-acetamido) -5-methoxymethyl ^ -cephem-4-carboxylic acid* 8i A process according to claim 1 or 6, wherein the compound produced is 7^ [o-^-hydroxy-^-phenyl-acetaiiiido -3-methoxymethyl-j$-cephem-4-carboxylic acid or the sodium or potassium salt of such a compound* -65 - 40447/3 9. A compound of the formula S ^ \ R-NH-CH»CH CH_ I I i 2 0=C-N C-CH-- 2 c I I C00R'; wherein R is hydrogen; amine where X is amino., butoxycarbonyy hydroxy, carboxyl, or to C -alkanoyloxy; where X is oxygen or sulfur or a chemical bond, y is an integer of from 0 to 2, and z is an integer of from 1 to 2; and Q in each of the above phenyl rings is hydrogen, Cj to alkyl Cj to Cj-alkoxy, nitro, hydroxy, chloro, brorao, fluoro, trifluoro-methyi, carboxymethyi (H00C-CH2-) or carbamoylmethyl (H_N|C(0)CH7-) , where Y is sulfur, and each Z taken together with the carbons to which they are bonded, complete benzo-ring, C-CH-CO- il l2 N N R ■ 0 1 2 wherein each of R and R is hydrogen., or methyl; 2-sydnone-3-C^ to C^-alkanoyl-, Cj to CjQ-alkanoyl, to C^-alkenoyl, Cj to C7~alk l-X-Cj to Cg-alkanoyl where X is oxygen or sulfur, Cj to C7~alkenyl-X-Cj to C^-alkanoyl where X is oxygen or sulfur, to CjQ-haloakanoyl where halogen is fluorine, chlorine, or bromine, or C2 to CjQ-cyanoalkanoyl ; R» is cyano or -0Y where Y is Cj to C10-alkyl Cj to C^g-alkenyl C2 to CjQ-haloalkyl, C.to C^-alkyl-X-C^ to C^-alkyl where X is oxygen or sulfur, C2 to C^-alkanoyloxy-C2 to C,-alkyl, C2 to to (_6-alkyl (furyl)-C. to C,-alkyl, 1 3· tetrahydrofuryl tetrahydrofuryl-Cj to Cg-alkyl phenyl or benzyl, which a o substituted on ring carbon atoms thereof with to C^-alkyl, to C^-alkoxy, to Cj-alkoxycarbonyl, fluorine, chlorine, bromine, nitro, cyano or trifluoromethyl ; 40447/3 and R" is hydrogen a zwitterionic charge, a salt with pharmaceutically acceptable cation, C4 to Cg-tert-alkyl , benzyl, methoxybenzyl or nitx-obenzyl . 10. The compound of claim 9, wherein R is hydrogen, R' is cyano R" is a C4 to C^-tert-alkyl , or a to C^-aromatic hydrocarbon sulfonic acid salt of such a compound. 11. The compound of claim 9 or 10, wherein the compound is tert- 3 butyl 7-amino-3-cyanomethyl-^ -cephem-4-carboxylate or a p-toluenesul-fonate salt thereof. 12. The compound of claim 9 wherein R is hydrogen, R* is -0Y, Y is C to C1()-alkyl. and R" is to Cg-tert-alkyl or a C& to C12~ arorofctic hydrocarbon sulfonic acid salt of such a compound. 13. The compound of claim 9 or 12, wherein the compound is tert- 3 butyl 7-amino-3-methoxymethyl-^ -cephem-4-carboxylic acid, or a p-toluenesulfonate salt thereof. 14. The compound of claim 9, wherein R is X butoxycarbonylamino, hydroxy where X is amino, a protoetod amino, C^, to C^-alkoxy, -CCOH, or to Cj-alkanoyloxy, and Q is hydrogen, R' is -0Y, Y is to CjQ-alkyl, and R" is hydrogen, or a sodium or potassium salt of such a compound. 40447/3 15. The compound of claim 9 or 14, wherein the compound is 7-(D-2 ' -amino-2 ' -phenylacetamido) -3-methoxymeth l ^-cephem-4-carboxylic acid. 16. The compound of claim 9 or 14 , wherein the compound is 7- |)-¾^-hydroxy-_Y-phenylacetamido~J -3-methoxymethyl-^-cephem-4-carboxylic acid or the sodium or potassium salt of such a compound. S.HOROWITZ fT CO. AGENTS FOR APPLICANTS
IL40447A 1968-02-07 1969-02-06 Delta3-cephalosporin compounds and process for their preparation from delta2-cephalosporin IL40447A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US70352368A 1968-02-07 1968-02-07
US79084269A 1969-01-13 1969-01-13
US79088669A 1969-01-13 1969-01-13

Publications (1)

Publication Number Publication Date
IL40447A true IL40447A (en) 1976-02-29

Family

ID=27418758

Family Applications (2)

Application Number Title Priority Date Filing Date
IL40447A IL40447A (en) 1968-02-07 1969-02-06 Delta3-cephalosporin compounds and process for their preparation from delta2-cephalosporin
IL41553A IL41553A (en) 1968-02-07 1969-02-06 3-bromomethyl-delta2-cephalosporin compounds and process for preparing the same

Family Applications After (1)

Application Number Title Priority Date Filing Date
IL41553A IL41553A (en) 1968-02-07 1969-02-06 3-bromomethyl-delta2-cephalosporin compounds and process for preparing the same

Country Status (11)

Country Link
JP (3) JPS524558B1 (en)
BE (1) BE728053A (en)
CH (1) CH534694A (en)
DK (1) DK140726B (en)
FI (1) FI56535C (en)
FR (3) FR2001491B1 (en)
GB (2) GB1265333A (en)
IL (2) IL40447A (en)
LU (1) LU57932A1 (en)
NL (1) NL173407C (en)
SE (3) SE384511B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2132883A1 (en) * 1970-07-08 1972-01-13 Ciba Geigy Ag Cephem compounds
JPS53164082U (en) * 1977-05-31 1978-12-22
JPS5899787U (en) * 1981-12-28 1983-07-07 奥野電器株式会社 lamp socket
EP0300546B1 (en) * 1987-07-10 1995-08-09 Gist-Brocades N.V. Process for the preparation of cephem compounds and cephalosporin derivatives

Also Published As

Publication number Publication date
FR2001491B1 (en) 1973-07-13
JPS524559B1 (en) 1977-02-04
BE728053A (en) 1969-08-07
GB1265332A (en) 1972-03-01
LU57932A1 (en) 1969-09-17
FR2001491A1 (en) 1969-09-26
SE384511B (en) 1976-05-10
JPS4924076B1 (en) 1974-06-20
FR2085656A1 (en) 1971-12-31
GB1265333A (en) 1972-03-01
DK140726B (en) 1979-11-05
IL41553A (en) 1976-02-29
NL6902013A (en) 1969-08-11
DK140726C (en) 1980-03-31
FR2085656B1 (en) 1974-08-23
NL173407C (en) 1984-01-16
FR2095486A5 (en) 1972-02-11
SE407064B (en) 1979-03-12
NL173407B (en) 1983-08-16
SE7512818L (en) 1975-11-14
FI56535C (en) 1980-02-11
JPS524558B1 (en) 1977-02-04
CH534694A (en) 1973-03-15
SE418616B (en) 1981-06-15
FI56535B (en) 1979-10-31

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