CY1205A - Penicillin derivatives - Google Patents

Penicillin derivatives Download PDF

Info

Publication number: CY1205A
Authority: CY; Cyprus
Prior art keywords: compound; formula; amino; salts; pharmaceutically acceptable
Prior art date: 1979-02-13

Application number

CY1205A

Other languages

English (en)

Original Assignee

Leo Pharm Prod Ltd

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.)

1979-02-13

Filing date

1980-01-25

Publication date

1983-12-31

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27449109&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CY1205(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1980-01-25 Application filed by Leo Pharm Prod Ltd filed Critical Leo Pharm Prod Ltd

1983-12-31 Publication of CY1205A publication Critical patent/CY1205A/en

Links

150000002960 penicillins Chemical class 0.000 title description 14
150000001875 compounds Chemical class 0.000 claims description 167
239000000203 mixture Substances 0.000 claims description 66
-1 1,4 - cyclohexadienyl Chemical group 0.000 claims description 60
239000002253 acid Substances 0.000 claims description 55
150000003839 salts Chemical class 0.000 claims description 51
238000000034 method Methods 0.000 claims description 46
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
231100000252 nontoxic Toxicity 0.000 claims description 26
230000003000 nontoxic effect Effects 0.000 claims description 26
150000007513 acids Chemical class 0.000 claims description 23
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 13
239000001257 hydrogen Substances 0.000 claims description 13
239000008194 pharmaceutical composition Substances 0.000 claims description 13
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
239000003112 inhibitor Substances 0.000 claims description 10
150000002148 esters Chemical class 0.000 claims description 9
HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical class OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims description 8
229910052757 nitrogen Inorganic materials 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 7
230000007062 hydrolysis Effects 0.000 claims description 7
238000006460 hydrolysis reaction Methods 0.000 claims description 7
208000035473 Communicable disease Diseases 0.000 claims description 6
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
229910052740 iodine Inorganic materials 0.000 claims description 6
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims description 4
239000003826 tablet Substances 0.000 claims description 4
241001465754 Metazoa Species 0.000 claims description 3
125000004442 acylamino group Chemical group 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
239000012752 auxiliary agent Substances 0.000 claims description 3
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
239000002775 capsule Substances 0.000 claims description 3
229940090805 clavulanate Drugs 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
238000007327 hydrogenolysis reaction Methods 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
239000011630 iodine Substances 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
230000037396 body weight Effects 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
150000001768 cations Chemical class 0.000 claims description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims description 2
239000006187 pill Substances 0.000 claims description 2
239000000126 substance Substances 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims 4
125000004970 halomethyl group Chemical group 0.000 claims 3
231100000331 toxic Toxicity 0.000 claims 2
230000002588 toxic effect Effects 0.000 claims 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
230000003197 catalytic effect Effects 0.000 claims 1
201000010099 disease Diseases 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 66
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
238000002360 preparation method Methods 0.000 description 50
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
239000000243 solution Substances 0.000 description 42
239000003921 oil Substances 0.000 description 33
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 32
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 31
229960003975 potassium Drugs 0.000 description 31
229910052700 potassium Inorganic materials 0.000 description 31
239000011591 potassium Substances 0.000 description 31
239000008346 aqueous phase Substances 0.000 description 30
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
229930182555 Penicillin Natural products 0.000 description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
238000003756 stirring Methods 0.000 description 16
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
239000000741 silica gel Substances 0.000 description 15
229910002027 silica gel Inorganic materials 0.000 description 15
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
238000002844 melting Methods 0.000 description 14
230000008018 melting Effects 0.000 description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
239000013078 crystal Substances 0.000 description 13
239000000843 powder Substances 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
238000004440 column chromatography Methods 0.000 description 12
239000000706 filtrate Substances 0.000 description 12
239000003054 catalyst Substances 0.000 description 11
239000000543 intermediate Substances 0.000 description 11
239000012074 organic phase Substances 0.000 description 11
FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
239000006260 foam Substances 0.000 description 10
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 9
239000011780 sodium chloride Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
238000010790 dilution Methods 0.000 description 8
239000012895 dilution Substances 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
229960000723 ampicillin Drugs 0.000 description 7
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
235000019441 ethanol Nutrition 0.000 description 7
238000002329 infrared spectrum Methods 0.000 description 7
150000003254 radicals Chemical class 0.000 description 7
239000007787 solid Substances 0.000 description 7
OPYGFNJSCUDTBT-PMLPCWDUSA-N sultamicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(=O)OCOC(=O)[C@H]2C(S(=O)(=O)[C@H]3N2C(C3)=O)(C)C)(C)C)=CC=CC=C1 OPYGFNJSCUDTBT-PMLPCWDUSA-N 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
241000894006 Bacteria Species 0.000 description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
238000010521 absorption reaction Methods 0.000 description 6
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
239000003480 eluent Substances 0.000 description 6
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 6
239000003208 petroleum Substances 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
239000011734 sodium Substances 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
229940123930 Lactamase inhibitor Drugs 0.000 description 5
238000001914 filtration Methods 0.000 description 5
229940049954 penicillin Drugs 0.000 description 5
ZEMIJUDPLILVNQ-ZXFNITATSA-N pivampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OCOC(=O)C(C)(C)C)=CC=CC=C1 ZEMIJUDPLILVNQ-ZXFNITATSA-N 0.000 description 5
229960003342 pivampicillin Drugs 0.000 description 5
235000015497 potassium bicarbonate Nutrition 0.000 description 5
229910000028 potassium bicarbonate Inorganic materials 0.000 description 5
239000011736 potassium bicarbonate Substances 0.000 description 5
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 5
DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 5
235000009518 sodium iodide Nutrition 0.000 description 5
159000000000 sodium salts Chemical class 0.000 description 5
239000002904 solvent Substances 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
230000000844 anti-bacterial effect Effects 0.000 description 4
229940088710 antibiotic agent Drugs 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000000284 extract Substances 0.000 description 4
210000001035 gastrointestinal tract Anatomy 0.000 description 4
239000007788 liquid Substances 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
229960003081 probenecid Drugs 0.000 description 4
239000007858 starting material Substances 0.000 description 4
230000036325 urinary excretion Effects 0.000 description 4
125000001478 1-chloroethyl group Chemical group [H]C([H])([H])C([H])(Cl)* 0.000 description 3
OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 3
NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 description 3
208000035143 Bacterial infection Diseases 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
229930186147 Cephalosporin Natural products 0.000 description 3
239000003242 anti bacterial agent Substances 0.000 description 3
208000022362 bacterial infectious disease Diseases 0.000 description 3
239000002585 base Substances 0.000 description 3
239000000969 carrier Substances 0.000 description 3
229940124587 cephalosporin Drugs 0.000 description 3
150000001780 cephalosporins Chemical class 0.000 description 3
PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000003814 drug Substances 0.000 description 3
238000009472 formulation Methods 0.000 description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
239000010410 layer Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 3
RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 3
ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 3
229940086066 potassium hydrogencarbonate Drugs 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 3
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 3
GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 2
RYAGQMSEMGVLGY-UHFFFAOYSA-N 1-chloro-1-iodoethane Chemical group CC(Cl)I RYAGQMSEMGVLGY-UHFFFAOYSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 description 2
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
235000011054 acetic acid Nutrition 0.000 description 2
238000005903 acid hydrolysis reaction Methods 0.000 description 2
239000011149 active material Substances 0.000 description 2
150000003973 alkyl amines Chemical class 0.000 description 2
229960003022 amoxicillin Drugs 0.000 description 2
LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
229940075397 calomel Drugs 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
208000035195 congenital hypomyelinating 3 neuropathy Diseases 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000001035 drying Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000012458 free base Substances 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
239000007789 gas Substances 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
230000002779 inactivation Effects 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
229960003085 meticillin Drugs 0.000 description 2
239000002674 ointment Substances 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
239000008024 pharmaceutical diluent Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
239000012286 potassium permanganate Substances 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
230000002035 prolonged effect Effects 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
238000011084 recovery Methods 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000000926 separation method Methods 0.000 description 2
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
239000012258 stirred mixture Substances 0.000 description 2
239000001117 sulphuric acid Substances 0.000 description 2
235000011149 sulphuric acid Nutrition 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
125000004665 trialkylsilyl group Chemical group 0.000 description 2
230000002485 urinary effect Effects 0.000 description 2
VTNDHSZKSSVBGD-TYNCELHUSA-N (2s,5r,6r)-6-[(3-carboxyquinoxaline-2-carbonyl)amino]-3,3-dimethyl-4,4,7-trioxo-4$l^{6}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound C1=CC=C2N=C(C(O)=O)C(C(=O)N[C@H]3[C@@H]4N(C3=O)[C@H](C(S4(=O)=O)(C)C)C(O)=O)=NC2=C1 VTNDHSZKSSVBGD-TYNCELHUSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
208000031462 Bovine Mastitis Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
101100452593 Caenorhabditis elegans ina-1 gene Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
239000001828 Gelatine Substances 0.000 description 1
241000713385 Idiodes Species 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
101100128278 Mus musculus Lins1 gene Proteins 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
101100391171 Schizosaccharomyces pombe (strain 972 / ATCC 24843) for3 gene Proteins 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
241000212342 Sium Species 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
239000004133 Sodium thiosulphate Substances 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Inorganic materials [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
150000003939 benzylamines Chemical class 0.000 description 1
239000003782 beta lactam antibiotic agent Substances 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
ZYASDBCEYAHPMS-UHFFFAOYSA-N bis(chloromethyl) sulfate Chemical compound ClCOS(=O)(=O)OCCl ZYASDBCEYAHPMS-UHFFFAOYSA-N 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
125000005997 bromomethyl group Chemical group 0.000 description 1
239000000872 buffer Substances 0.000 description 1
FAOSYNUKPVJLNZ-UHFFFAOYSA-N butylstannane Chemical compound CCCC[SnH3] FAOSYNUKPVJLNZ-UHFFFAOYSA-N 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 1
229960003669 carbenicillin Drugs 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
229960003324 clavulanic acid Drugs 0.000 description 1
238000011281 clinical therapy Methods 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
238000011340 continuous therapy Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000008298 dragée Substances 0.000 description 1
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
230000029142 excretion Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000013505 freshwater Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
239000008101 lactose Substances 0.000 description 1
JMRXTGCDVQLAFM-JSYANWSFSA-M lithium;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Li+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 JMRXTGCDVQLAFM-JSYANWSFSA-M 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
AMWRITDGCCNYAT-UHFFFAOYSA-L manganese oxide Inorganic materials [Mn].O[Mn]=O.O[Mn]=O AMWRITDGCCNYAT-UHFFFAOYSA-L 0.000 description 1
PPNAOCWZXJOHFK-UHFFFAOYSA-N manganese(2+);oxygen(2-) Chemical class [O-2].[Mn+2] PPNAOCWZXJOHFK-UHFFFAOYSA-N 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
DGEYTDCFMQMLTH-UHFFFAOYSA-N methanol;propan-2-ol Chemical compound OC.CC(C)O DGEYTDCFMQMLTH-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
VPFXWMDVXYAJGV-UHFFFAOYSA-N n,n-dimethylbut-2-enamide Chemical compound CC=CC(=O)N(C)C VPFXWMDVXYAJGV-UHFFFAOYSA-N 0.000 description 1
WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
238000010915 one-step procedure Methods 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000008063 pharmaceutical solvent Substances 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
239000012264 purified product Substances 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000000523 sample Substances 0.000 description 1
238000006748 scratching Methods 0.000 description 1
230000002393 scratching effect Effects 0.000 description 1
230000009291 secondary effect Effects 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
229910001961 silver nitrate Inorganic materials 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000007939 sustained release tablet Substances 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
150000004684 trihydrates Chemical class 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
239000003981 vehicle Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D503/00—Heterocyclic compounds containing 4-oxa-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxapenicillins, clavulanic acid derivatives; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)

CY1205A 1979-02-13 1980-01-25 Penicillin derivatives CY1205A (en)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB7905020		1979-02-13
GB7921341		1979-06-19
GB7927761		1979-08-09
GB7939473		1979-11-14

Publications (1)

Publication Number	Publication Date
CY1205A true CY1205A (en)	1983-12-31

Family

ID=27449109

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CY1205A CY1205A (en)	1979-02-13	1980-01-25	Penicillin derivatives

Country Status (33)

Country	Link
US (2)	US4840944A (hu)
AR (1)	AR230286A1 (hu)
AT (1)	AT368507B (hu)
AU (1)	AU532531B2 (hu)
CA (1)	CA1230113A (hu)
CH (2)	CH646436A5 (hu)
CS (1)	CS234015B2 (hu)
CY (1)	CY1205A (hu)
DD (1)	DD149529A5 (hu)
DE (2)	DE3005164C2 (hu)
DK (1)	DK160943C (hu)
ES (1)	ES8101596A1 (hu)
FI (2)	FI73220C (hu)
FR (1)	FR2449089A1 (hu)
GB (2)	GB2108107B (hu)
GR (1)	GR74091B (hu)
HK (1)	HK5684A (hu)
HU (1)	HU182604B (hu)
IE (2)	IE49881B1 (hu)
IL (1)	IL59203A (hu)
IT (1)	IT1147306B (hu)
KE (1)	KE3309A (hu)
LU (1)	LU82164A1 (hu)
MA (1)	MA18731A1 (hu)
MY (1)	MY8500006A (hu)
NL (1)	NL8000775A (hu)
NZ (1)	NZ192762A (hu)
PH (1)	PH16326A (hu)
PL (1)	PL125079B1 (hu)
PT (1)	PT70805A (hu)
SE (2)	SE446186B (hu)
SG (1)	SG43783G (hu)
YU (1)	YU42659B (hu)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4420426A (en)	1979-03-05	1983-12-13	Pfizer Inc.	6-Alpha-halopenicillanic acid 1,1-dioxides
US4714761A (en) *	1979-03-05	1987-12-22	Pfizer Inc.	6,6-dihalopenicillanic acid 1,1-dioxides and process
SE449103B (sv) *	1979-03-05	1987-04-06	Pfizer	Sett att framstella penicillansyra-1,1-dioxid samt estrar derav
US4309347A (en) *	1979-05-16	1982-01-05	Pfizer Inc.	Penicillanoyloxymethyl penicillanate 1,1,1',1'-tetraoxide
US4244951A (en) *	1979-05-16	1981-01-13	Pfizer Inc.	Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide
US4364957A (en) *	1979-09-26	1982-12-21	Pfizer Inc.	Bis-esters of alkanediols as antibacterial agents
US4342768A (en) *	1979-10-22	1982-08-03	Pfizer Inc.	Bis-esters of 1,1-alkanediols with 6-beta-hydroxymethylpenicillanic acid 1,1-dioxide and beta-lactam antibiotics
US4432970A (en) *	1979-11-23	1984-02-21	Pfizer Inc.	6-beta-Halopenicillanic acid 1,1-dioxides as beta-lactamase inhibitors
US4340539A (en)	1980-01-21	1982-07-20	Bristol-Myers Company	Derivatives of 6-bromo penicillanic acid
FI67553C (fi) *	1980-01-21	1985-04-10	Bristol Myers Co	Foerfarande foer framstaellning av en terapeutiskt anvaendbar 2beta-klormetyl-2alfa-metylpenam-3alfa-karboxylsyrasulfon sater och estrar daerav
IL61880A (en) *	1980-01-21	1984-11-30	Bristol Myers Co	2beta-chloromethyl-2alpha-methylpenam-3alpha-carboxylic acid sulfone derivatives,their preparation and pharmaceutical compositions containing them
US4488994A (en) *	1980-09-08	1984-12-18	Pfizer Inc.	Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide
IE51516B1 (en) *	1980-10-06	1987-01-07	Leo Pharm Prod Ltd	1,1-dioxapenicillanoyloxymethyl 6-(d-alpha-amino-alpha-phenylacetamido)penicillanate napsylate
IL64009A (en) *	1980-10-31	1984-09-30	Rech Applications Therap	Crystalline 1,1-dioxopenicillanoyloxymethyl 6-(d-alpha-amino-alpha-phenylacetamido)penicillanate tosylate hydrates,their production and pharmaceutical compositions containing them
US4474698A (en) *	1980-12-11	1984-10-02	Pfizer Inc.	Process for preparing esters of penicillanic acid sulfone
US4380512A (en) *	1980-12-11	1983-04-19	Bristol-Myers Company	2β-Chloromethyl-2α-methylpenam-3α-carboxylic acid sulfone and salts and esters thereof
US4321196A (en)	1981-03-23	1982-03-23	Pfizer Inc.	Bis-esters of methanediol with acetonides of ampicillin or amoxicillin and penicillanic acid 1,1-dioxide
US4419284A (en)	1981-03-23	1983-12-06	Pfizer Inc.	Preparation of halomethyl esters (and related esters) of penicillanic acid 1,1-dioxide
IN157669B (hu) *	1981-03-23	1986-05-17	Pfizer
US4376076A (en)	1981-03-23	1983-03-08	Pfizer Inc.	Bis-esters of 1,1-alkanediols with 6-beta-hydroxymethylpenicillanic acid 1,1-dioxide
IN159362B (hu) *	1981-03-23	1987-05-09	Pfizer
US4381263A (en) *	1981-03-23	1983-04-26	Pfizer Inc.	Process for the preparation of penicillanic acid esters
US4393001A (en)	1981-03-23	1983-07-12	Pfizer Inc.	Intermediates for production of 1,1-dioxopenicillanoyloxymethyl 6-(2-amino-2-phenylacetamido)penicillanates
US4444687A (en) *	1981-06-08	1984-04-24	Bristol-Myers Company	2β-Chloromethyl-2α-methylpenam-3α-carboxylic acid sulfone methylene diol mixed esters
EP0074777B1 (en) *	1981-09-09	1987-10-14	Pfizer Inc.	Antibacterial 6-(2-amino-2-(4-acyloxy-phenyl) acetamido) penicillanoyloxymethyl esters
US4540687A (en) *	1981-09-09	1985-09-10	Pfizer Inc.	Antibacterial 6'-(2-amino-2-[4-acyloxyphenyl]acetamido)penicillanoyloxymethyl penicillanate 1,1-dioxide compounds
US4582829A (en) *	1981-09-09	1986-04-15	Pfizer Inc.	Antibacterial 6'-(2-amino-2-[4-acyloxyphenyl]acetamido)penicillanoyloxymethyl penicillanate 1,1-dioxide compounds
US4351840A (en) *	1981-09-18	1982-09-28	Pfizer Inc.	Antibacterial esters of resorcinol with ampicillin and penicillanic acid 1,1-dioxide derivatives
US4457924A (en) *	1981-12-22	1984-07-03	Pfizer, Inc.	1,1-Alkanediol dicarboxylate linked antibacterial agents
US4359472A (en)	1981-12-22	1982-11-16	Pfizer Inc.	Bis-hydroxymethyl carbonate bridged antibacterial agents
US4452796A (en) *	1982-06-14	1984-06-05	Pfizer Inc.	6-Aminoalkylpenicillanic acid 1,1-dioxides as beta-lactamase inhibitors
EP0084730A1 (en) *	1982-01-22	1983-08-03	Beecham Group Plc	Esters of penicillin derivatives with beta-lactamase inhibitors, their preparation and their use
US4444686A (en) *	1982-01-25	1984-04-24	Pfizer Inc.	Crystalline penicillin ester intermediate
US4432987A (en) *	1982-04-23	1984-02-21	Pfizer Inc.	Crystalline benzenesulfonate salts of sultamicillin
IT1190897B (it) *	1982-06-29	1988-02-24	Opos Biochimica Srl	Procedimento per la preparazione dell'estere 1-etossicarbonilossietilico dell'acido 6-(d(-)-alfa aminoalfa fenilacetamido)-penicillanico
EP0126090A1 (en) *	1982-10-26	1984-11-28	Beecham Group Plc	Beta-lactam compounds, preparation and use
US4530792A (en) *	1982-11-01	1985-07-23	Pfizer Inc.	Process and intermediates for preparation of 1,1-dioxopenicillanoyloxymethyl 6-beta-aminopenicillanate
IL67637A0 (en) *	1983-01-07	1983-05-15	Orvet Bv	Preparation of 1'-ethoxycarbonyl-oxyethyl esters of penicillins and novel intermediates
US4868297A (en) *	1982-12-06	1989-09-19	Pfizer Inc.	Process for preparing sultamicillin and analogs
US4462934A (en)	1983-03-31	1984-07-31	Pfizer Inc.	Bis-esters of dicarboxylic acids with amoxicillin and certain hydroxymethylpenicillanate 1,1-dioxides
US4536393A (en) *	1983-06-06	1985-08-20	Pfizer Inc.	6-(Aminomethyl)penicillanic acid 1,1-dioxide esters and intermediates therefor
JPH01139584A (ja) *	1987-11-25	1989-06-01	Yoshitomi Pharmaceut Ind Ltd	ペニシラン酸化合物の製造法
KR910009271B1 (ko) *	1989-06-20	1991-11-08	김영설	1,1-디옥소페닐실라노일 옥시메틸 D-6-[α-(메틸렌아미노)페닐-아세트아미도]-페니실라네이트와 그의 파라-톨루엔술폰산염
WO1991016326A1 (en) *	1990-04-13	1991-10-31	Pfizer Inc.	Process for sultamicillin intermediate
ES2161602B1 (es) *	1999-04-08	2003-02-16	Asturpharma S A	Sintesis de 6-(d-alfa-(bencilidenaminofenilacetamido))penicilanato de 1,1-dioxopenicilanoiloximetilo y analogos. nuevos intermedios para la sintesis de sultamicilina.
WO2007004239A1 (en) *	2005-07-06	2007-01-11	Morepen Laboratories Limited	New polymorphic form of sultamicillin tosylate and a process therefor
TR201922977A2 (tr) *	2019-12-31	2021-07-26	T C Erciyes Ueniversitesi	Penisilin türevleri ve bunların sentezlenmesi için yöntem
CN115385934A (zh) *	2022-10-26	2022-11-25	北京纳百生物科技有限公司	一种舒巴坦半抗原及其合成方法和应用

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1303491A (hu) *	1970-03-24	1973-01-17
GB1335718A (en) *	1971-05-05	1973-10-31	Leo Pharm Prod Ltd	Penicillin esters salts thereof and methods for their preparation
US3838152A (en) *	1971-10-07	1974-09-24	American Home Prod	Poly alpha-amino penicillins
GB1467604A (en) *	1974-06-27	1977-03-16	Toyama Chemical Co Ltd	Bis-type penicillins and process for producing the same
GB1573614A (en) *	1976-02-25	1980-08-28	Leo Pharm Prod Ltd	Amidinopenicillanoyloxyalkyl cephalosporanates
GB1578128A (en) *	1976-03-30	1980-11-05	Leo Pharm Prod Ltd	Amidinopenicillanoyloxyalkyl amoxycillinates
GB1579931A (en) *	1976-04-15	1980-11-26	Leo Pharm Prod Ltd	Bis-penicillanoyl-oxy-alkanes
IN149747B (hu) *	1977-06-07	1982-04-03	Pfizer
US4197240A (en) *	1977-12-23	1980-04-08	Yeda Research And Development Co. Ltd.	Penicillin derivatives
US4244951A (en) *	1979-05-16	1981-01-13	Pfizer Inc.	Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide

1980
- 1980-01-21 IE IE2654/83A patent/IE49881B1/en unknown
- 1980-01-21 IE IE111/80A patent/IE49880B1/en not_active IP Right Cessation
- 1980-01-23 IL IL59203A patent/IL59203A/xx unknown
- 1980-01-24 US US06/118,063 patent/US4840944A/en not_active Expired - Lifetime
- 1980-01-25 GB GB08221654A patent/GB2108107B/en not_active Expired
- 1980-01-25 PH PH23555A patent/PH16326A/en unknown
- 1980-01-25 CY CY1205A patent/CY1205A/en unknown
- 1980-01-25 GB GB8002682A patent/GB2044255B/en not_active Expired
- 1980-01-30 NZ NZ192762A patent/NZ192762A/en unknown
- 1980-01-31 AR AR279816A patent/AR230286A1/es active
- 1980-01-31 YU YU244/80A patent/YU42659B/xx unknown
- 1980-02-05 AT AT0061580A patent/AT368507B/de not_active IP Right Cessation
- 1980-02-07 NL NL8000775A patent/NL8000775A/nl not_active Application Discontinuation
- 1980-02-07 CA CA000345227A patent/CA1230113A/en not_active Expired
- 1980-02-08 MA MA18928A patent/MA18731A1/fr unknown
- 1980-02-08 PT PT70805A patent/PT70805A/pt active IP Right Revival
- 1980-02-11 CH CH110080A patent/CH646436A5/de not_active IP Right Cessation
- 1980-02-11 DD DD80218994A patent/DD149529A5/de unknown
- 1980-02-11 FI FI800411A patent/FI73220C/fi not_active IP Right Cessation
- 1980-02-12 SE SE8001099A patent/SE446186B/sv not_active IP Right Cessation
- 1980-02-12 DK DK059480A patent/DK160943C/da not_active IP Right Cessation
- 1980-02-12 ES ES488494A patent/ES8101596A1/es not_active Expired
- 1980-02-12 IT IT19865/80A patent/IT1147306B/it active Protection Beyond IP Right Term
- 1980-02-12 CS CS80929A patent/CS234015B2/cs unknown
- 1980-02-12 PL PL1980221964A patent/PL125079B1/pl unknown
- 1980-02-12 FR FR8003061A patent/FR2449089A1/fr active Granted
- 1980-02-12 HU HU80310A patent/HU182604B/hu unknown
- 1980-02-12 LU LU82164A patent/LU82164A1/fr unknown
- 1980-02-12 GR GR61189A patent/GR74091B/el unknown
- 1980-02-12 AU AU55462/80A patent/AU532531B2/en not_active Ceased
- 1980-02-12 DE DE3005164A patent/DE3005164C2/de not_active Expired
- 1980-02-12 DE DE3050895A patent/DE3050895C2/de not_active Expired
- 1980-12-04 US US06/213,083 patent/US4342772A/en not_active Expired - Lifetime
1983
- 1983-07-21 KE KE3309A patent/KE3309A/xx unknown
- 1983-07-23 SG SG43783A patent/SG43783G/en unknown
- 1983-11-11 CH CH608183A patent/CH645902A5/de not_active IP Right Cessation
1984
- 1984-01-12 HK HK56/84A patent/HK5684A/xx not_active IP Right Cessation
- 1984-09-05 SE SE8404462A patent/SE461913B/sv unknown
1985
- 1985-12-30 MY MY6/85A patent/MY8500006A/xx unknown
1987
- 1987-02-11 FI FI870555A patent/FI76807C/fi not_active IP Right Cessation

Also Published As

Publication number	Publication date
DE3005164C2 (de)	1986-06-26
YU42659B (en)	1988-10-31
CH645902A5 (de)	1984-10-31
SE8404462D0 (sv)	1984-09-05
FI800411A (fi)	1980-08-14
AR230286A1 (es)	1984-03-01
IE832654L (en)	1980-08-13
US4840944A (en)	1989-06-20
FI73220C (fi)	1987-09-10
FR2449089A1 (fr)	1980-09-12
ES488494A0 (es)	1980-12-16
DE3005164A1 (de)	1980-08-21
IE49880B1 (en)	1986-01-08
AU532531B2 (en)	1983-10-06
PL125079B1 (en)	1983-03-31
FI76807B (fi)	1988-08-31
LU82164A1 (fr)	1980-09-24
CH646436A5 (de)	1984-11-30
GR74091B (hu)	1984-06-06
IL59203A (en)	1982-12-31
PH16326A (en)	1983-09-05
HU182604B (en)	1984-02-28
DE3050895C2 (hu)	1989-05-03
DK59480A (da)	1980-08-14
HK5684A (en)	1984-01-20
CA1230113A (en)	1987-12-08
PT70805A (en)	1980-03-01
DK160943C (da)	1991-10-21
SE461913B (sv)	1990-04-09
GB2108107A (en)	1983-05-11
US4342772A (en)	1982-08-03
NL8000775A (nl)	1980-08-15
IE49881B1 (en)	1986-01-08
GB2044255A (en)	1980-10-15
YU24480A (en)	1983-04-30
FR2449089B1 (hu)	1983-06-10
IT1147306B (it)	1986-11-19
IL59203A0 (en)	1980-05-30
KE3309A (en)	1983-08-19
SE446186B (sv)	1986-08-18
SG43783G (en)	1985-01-11
FI870555A (fi)	1987-02-11
PL221964A1 (hu)	1980-12-01
ES8101596A1 (es)	1980-12-16
DD149529A5 (de)	1981-07-15
IT8019865A0 (it)	1980-02-12
AU5546280A (en)	1980-08-21
SE8001099L (sv)	1980-08-14
MY8500006A (en)	1985-12-31
FI73220B (fi)	1987-05-29
AT368507B (de)	1982-10-25
DK160943B (da)	1991-05-06
NZ192762A (en)	1984-10-19
FI870555A0 (fi)	1987-02-11
GB2044255B (en)	1983-05-11
CS234015B2 (en)	1985-03-14
ATA61580A (de)	1982-02-15
SE8404462L (sv)	1984-09-05
FI76807C (fi)	1988-12-12
GB2108107B (en)	1983-09-01
MA18731A1 (fr)	1980-10-01

Publication	Publication Date	Title
CY1205A (en)	1983-12-31	Penicillin derivatives
US4168314A (en)	1979-09-18	6-(1'-Hydroxyethyl)-2-aminoethylthio-pen-2-em-3-carboxylic acid
KR830001903B1 (ko)	1983-09-19	페니실란산유도체의 제조방법
DE2801644A1 (de)	1978-08-17	Heteromonocyclische und heterobicyclische derivate der ungesaettigten 7-acylamido-3-cephem-4-carbonsaeure, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische oder veterinaer- zubereitung
IE54771B1 (en)	1990-01-31	Derivatives of ampicillin and amoxicillin with beta-lactamase inhibitors
US4231928A (en)	1980-11-04	Antibacterial agents
US4081545A (en)	1978-03-28	Penicillins
US4325960A (en)	1982-04-20	6-Amidinopenicillanic acid derivatives including the radical of a β-lactamase inhibitor
US4172895A (en)	1979-10-30	6-(1'-Hydroxyethyl)-2-aminoethylthio-oxapen-2-em-3-carboxylic acid
US4407751A (en)	1983-10-04	Processes for preparing β-lactams
US4629726A (en)	1986-12-16	Penem carboxylic acids
US3654265A (en)	1972-04-04	Synthetic penicillin
US3951957A (en)	1976-04-20	Chloromethyl ester of penicillins
NZ196055A (en)	1984-11-09	2beta-chloromethyl-2alpha-methylpenam-3alpha-carboxylic acid sulphone,esters thereof,pharmaceutical compositions,and intermediates
FR2696179A1 (fr)	1994-04-01	Dérivés de thioalkylthiocarbacéphalosporine, procédé pour leurs préparations et formulation pharmaceutique les contenant pour le traitement ou la prophylaxie des infections bactériennes.
GB2113681A (en)	1983-08-10	B-lactam antibiotics
JPS58128387A (ja)	1983-07-30	新規β−ラクタム化合物およびその製法と用途
GB2051046A (en)	1981-01-14	Penicillanic acid derivatives
US4200747A (en)	1980-04-29	7-2-Indolyl acetamido cephalosporin derivatives
KR830001902B1 (ko)	1983-09-19	폐니실란산유도체의 제조방법
US4554160A (en)	1985-11-19	Penicillin esters, salts thereof and methods for their preparation
GB2119363A (en)	1983-11-16	Penicillanic acid derivatives
US4112228A (en)	1978-09-05	7-(D-α-Hydroxy-2-arylacetamido)-3-(2-carboxyalkyl-2,3-dihydro-s-triazolo-[4,3-b]pyridazin-3-on-6-ylthiomethyl)-3-cephem-4-carboxylic acids and derivatives
EP0219926A2 (en)	1987-04-29	Cephalosporins, processes for their preparation and pharmaceutical compositions containing them
JPH01180885A (ja)	1989-07-18	β−ラクタム化合物及びその製造方法