UA79117C2 - Bicyclic 6-alkyliden penems as beta-lactamase inhibitors, process for preparation thereof and the pharmaceutical composition based thereon - Google Patents
Bicyclic 6-alkyliden penems as beta-lactamase inhibitors, process for preparation thereof and the pharmaceutical composition based thereon Download PDFInfo
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- UA79117C2 UA79117C2 UA20041109833A UA20041109833A UA79117C2 UA 79117 C2 UA79117 C2 UA 79117C2 UA 20041109833 A UA20041109833 A UA 20041109833A UA 20041109833 A UA20041109833 A UA 20041109833A UA 79117 C2 UA79117 C2 UA 79117C2
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- UA
- Ukraine
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- optionally substituted
- oxo
- thia
- carboxylic acid
- ene
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract 3
- 238000000034 method Methods 0.000 title claims description 37
- 125000002619 bicyclic group Chemical group 0.000 title claims description 24
- 238000002360 preparation method Methods 0.000 title description 70
- 239000003781 beta lactamase inhibitor Substances 0.000 title description 2
- 229940126813 beta-lactamase inhibitor Drugs 0.000 title description 2
- 150000002961 penems Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 166
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 7
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 7
- 239000000203 mixture Substances 0.000 claims description 305
- 229910052799 carbon Inorganic materials 0.000 claims description 116
- FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 claims description 111
- 159000000000 sodium salts Chemical class 0.000 claims description 111
- -1 substituted Chemical class 0.000 claims description 106
- 238000006243 chemical reaction Methods 0.000 claims description 81
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 75
- 125000001072 heteroaryl group Chemical group 0.000 claims description 48
- 125000003118 aryl group Chemical group 0.000 claims description 45
- 125000004494 ethyl ester group Chemical group 0.000 claims description 31
- 150000001721 carbon Chemical group 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 230000003115 biocidal effect Effects 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 20
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 125000004122 cyclic group Chemical group 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 230000015572 biosynthetic process Effects 0.000 claims description 14
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- 125000003710 aryl alkyl group Chemical group 0.000 claims description 12
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- 239000003782 beta lactam antibiotic agent Substances 0.000 claims description 11
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- 125000004429 atom Chemical group 0.000 claims description 9
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- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 5
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- 239000011734 sodium Substances 0.000 claims description 4
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- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 4
- LZDUSDGRALPEID-UHFFFAOYSA-N 5,5-dimethylpiperidin-2-one Chemical compound CC1(C)CCC(=O)NC1 LZDUSDGRALPEID-UHFFFAOYSA-N 0.000 claims description 3
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- 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 3
- 229960000433 latamoxef Drugs 0.000 claims description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
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- 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 claims description 2
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 claims description 2
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- 229960000603 cefalotin Drugs 0.000 claims description 2
- UOCJDOLVGGIYIQ-PBFPGSCMSA-N cefatrizine Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)[C@H](N)C=2C=CC(O)=CC=2)CC=1CSC=1C=NNN=1 UOCJDOLVGGIYIQ-PBFPGSCMSA-N 0.000 claims description 2
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- JETQIUPBHQNHNZ-NJBDSQKTSA-N (2s,5r,6r)-3,3-dimethyl-7-oxo-6-[[(2r)-2-phenyl-2-sulfoacetyl]amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound C1([C@H](C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)S(O)(=O)=O)=CC=CC=C1 JETQIUPBHQNHNZ-NJBDSQKTSA-N 0.000 claims 1
- OKBVVJOGVLARMR-QMTHXVAHSA-N (6R,7R)-7-[[2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino)-1-oxoethyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1C(N)=NC(C(=NOCC(O)=O)C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QMTHXVAHSA-N 0.000 claims 1
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- AUNFUDYEFLJJKP-UHFFFAOYSA-N oxazine-2-carbaldehyde Chemical compound O=CN1OC=CC=C1 AUNFUDYEFLJJKP-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 1
- JSSXHAMIXJGYCS-UHFFFAOYSA-N piperazin-4-ium-2-carboxylate Chemical compound OC(=O)C1CNCCN1 JSSXHAMIXJGYCS-UHFFFAOYSA-N 0.000 description 1
- SUDYQKKBKMGXKU-UHFFFAOYSA-N piperazine-1,3-dicarboxylic acid Chemical compound OC(=O)C1CN(C(O)=O)CCN1 SUDYQKKBKMGXKU-UHFFFAOYSA-N 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- PNNRZXFUPQQZSO-UHFFFAOYSA-N pyran Chemical compound [CH]1OC=CC=C1 PNNRZXFUPQQZSO-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 150000003463 sulfur Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- BKWCJIGGAIADBJ-UHFFFAOYSA-N thiazine-2-carboxylic acid Chemical compound OC(=O)N1SC=CC=C1 BKWCJIGGAIADBJ-UHFFFAOYSA-N 0.000 description 1
- ULSZVNJBVJWEJE-UHFFFAOYSA-N thiazolidine-2-carboxylic acid Chemical compound OC(=O)C1NCCS1 ULSZVNJBVJWEJE-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- 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
- C07D499/88—Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/881—Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with a hydrogen atom or an unsubstituted hydrocarbon radical, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D499/86—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 with only atoms other than nitrogen atoms directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/861—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 with only atoms other than nitrogen atoms directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with a hydrocarbon radical or a substituted hydrocarbon radical, directly attached in position 6
-
- 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
- C07D499/88—Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US37705202P | 2002-05-01 | 2002-05-01 | |
PCT/US2003/013428 WO2003093279A1 (en) | 2002-05-01 | 2003-04-30 | BICYCLIC 6-ALKYLIDENE-PENEMS AS ß-LACTAMASES INHIBITORS |
Publications (1)
Publication Number | Publication Date |
---|---|
UA79117C2 true UA79117C2 (en) | 2007-05-25 |
Family
ID=29401437
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
UA20041109833A UA79117C2 (en) | 2002-05-01 | 2003-04-30 | Bicyclic 6-alkyliden penems as beta-lactamase inhibitors, process for preparation thereof and the pharmaceutical composition based thereon |
Country Status (21)
Country | Link |
---|---|
US (3) | US7112582B2 (pt) |
EP (2) | EP1988093A1 (pt) |
JP (2) | JP4602759B2 (pt) |
KR (1) | KR20050007368A (pt) |
CN (2) | CN101570545A (pt) |
AR (1) | AR039774A1 (pt) |
AU (1) | AU2003231205A1 (pt) |
BR (1) | BR0309757A (pt) |
CA (1) | CA2483538A1 (pt) |
CR (3) | CR7508A (pt) |
EC (1) | ECSP045397A (pt) |
IL (1) | IL164899A0 (pt) |
MX (1) | MXPA04010663A (pt) |
NO (1) | NO20044549L (pt) |
NZ (1) | NZ536182A (pt) |
RU (1) | RU2339640C2 (pt) |
SG (1) | SG162614A1 (pt) |
TW (1) | TW200307687A (pt) |
UA (1) | UA79117C2 (pt) |
WO (1) | WO2003093279A1 (pt) |
ZA (1) | ZA200409686B (pt) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR039476A1 (es) * | 2002-05-01 | 2005-02-23 | Wyeth Corp | Proceso para preparar derivados de 6-alquiliden penem |
US20040132708A1 (en) * | 2002-05-01 | 2004-07-08 | Wyeth | Process for preparing 6-alkylidene penem derivatives |
AR039475A1 (es) * | 2002-05-01 | 2005-02-23 | Wyeth Corp | 6-alquiliden-penems triciclicos como inhibidores de beta-lactamasa |
AR039774A1 (es) * | 2002-05-01 | 2005-03-02 | Wyeth Corp | 6-alquiliden-penems biciclicos como inhibidores de beta-lactamasas |
BRPI0413908A (pt) * | 2003-08-25 | 2006-10-24 | Revaax Pharmaceuticals Llc | formulação farmacêutica neuroterapêutica em forma de dosagem oral, composto, e, método de tratamento de um distúrbio comportamental ou um distúrbio cognitivo |
TW200716104A (en) * | 2005-06-01 | 2007-05-01 | Wyeth Corp | Tricyclic 6-alkylidene-penems as class-D β -lactamases inhibitors |
TW200716102A (en) * | 2005-06-01 | 2007-05-01 | Wyeth Corp | Bicyclic 6-alkylidene-penems as class-D β -lactamases inhibitors |
CA2616468A1 (en) * | 2005-07-27 | 2007-03-08 | Wyeth | Tricyclic 6-alkylidene-penem .beta.-lactamase inhibitors and .beta.-lactam antibiotic combination: a broad spectrum antibiotic |
BRPI0613927A2 (pt) * | 2005-07-27 | 2011-02-15 | Wyeth Corp | uso de cefepima ou um sal farmaceuticamente aceitável desta e um composto da fórmula i ou um sal farmaceuticamente aceitável ou éster deste hidrolisável in vivo; composição; embalagem; e produto |
GT200600380A (es) * | 2005-08-24 | 2007-03-29 | Proceso para la preparacion de inhibidores de beta-lactamasa | |
US20090018332A1 (en) * | 2007-06-28 | 2009-01-15 | Wyeth | Processes For Preparing Bicyclic Oxazine Carboxaldehyde and Beta-Lactamase Inhibitors |
CN104119858A (zh) * | 2013-04-27 | 2014-10-29 | 海洋王照明科技股份有限公司 | 一种铱金属配合物有机电致磷光材料及其制备方法和有机电致发光器件 |
CN104119857A (zh) * | 2013-04-27 | 2014-10-29 | 海洋王照明科技股份有限公司 | 一种铱金属配合物有机电致磷光材料及其制备方法和有机电致发光器件 |
AU2017223132B2 (en) | 2016-02-23 | 2019-12-05 | Pfizer Inc. | 6,7-Dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide compounds |
CN108473510B (zh) * | 2016-04-28 | 2021-10-29 | 豪夫迈·罗氏有限公司 | 制备2-吡唑并[1,5-a]吡嗪-2-基吡啶并[1,2-a]嘧啶-4-酮的方法 |
PE20190800A1 (es) | 2016-08-15 | 2019-06-10 | Bayer Cropscience Ag | Derivados del heterociclo biciclico condensado como agentes de control de plagas |
Family Cites Families (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2004A (en) * | 1841-03-12 | Improvement in the manner of constructing and propelling steam-vessels | ||
US4206067A (en) * | 1978-10-02 | 1980-06-03 | Chevron Research Company | Thermally stabilized erosion-inhibited functional fluids containing perhalometal compounds and an organic base |
DE3176517D1 (en) | 1980-04-24 | 1987-12-17 | Beecham Group Plc | Beta-lactam compounds, their preparation and use |
EP0120613A1 (en) | 1983-03-02 | 1984-10-03 | Beecham Group Plc | Penem derivatives and precursors |
GB8402086D0 (en) | 1984-01-26 | 1984-02-29 | Beecham Group Plc | Compounds |
FI82471C (fi) | 1984-01-26 | 1991-03-11 | Beecham Group Plc | Foerfarande foer framstaellning av farmakologiskt aktiva 6-metylenpenemderivater. |
EP0150984B1 (en) | 1984-01-30 | 1991-09-11 | Pfizer Inc. | 6-(substituted) methylenepenicillanic and 6-(substituted) hydroxymethylpenicillanic acids and derivatives thereof |
EP0167050A1 (en) * | 1984-06-21 | 1986-01-08 | Beecham Group Plc | Clavulanate compounds, their preparation and use and intermediates thereof |
GB8518416D0 (en) | 1985-07-22 | 1985-08-29 | Beecham Group Plc | Compounds |
GB8518421D0 (en) | 1985-07-22 | 1985-08-29 | Beecham Group Plc | Compounds |
GB8518422D0 (en) | 1985-07-22 | 1985-08-29 | Beecham Group Plc | Compounds |
DE3752124T2 (de) | 1986-01-17 | 1998-03-26 | Beecham Group Plc | Verfahren zur Herstellung von Penem Derivaten und Zwischenprodukte zu dieser Herstellung |
US4891369A (en) * | 1986-12-03 | 1990-01-02 | Taiho Pharmaceutical Company, Limited | 2β-Substituted-methylpenicillanic acid derivatives, and salts and esters thereof |
DE3725375A1 (de) * | 1987-07-31 | 1989-02-09 | Bayer Ag | Stabile oxapenem-3-carbonsaeuren |
GB8724566D0 (en) | 1987-10-20 | 1987-11-25 | Roussel Lab Ltd | Chemical compounds |
GB8729614D0 (en) | 1987-12-18 | 1988-02-03 | Beecham Group Plc | Novel compounds |
GB8729613D0 (en) | 1987-12-18 | 1988-02-03 | Beecham Group Plc | Novel compounds |
NZ237202A (en) | 1990-02-23 | 1994-01-26 | Bristol Myers Squibb Co | Composition containing beta-lactam antibiotic and cationic oligopeptide |
EP0447704A1 (en) | 1990-03-21 | 1991-09-25 | Smithkline Beecham Farmaceutici S.p.A. | N-Acylated azacyclic compounds, processes for their preparations and their use as medications |
GB9116236D0 (en) | 1991-07-27 | 1991-09-11 | Smithkline Beecham Plc | Novel compounds |
GB9222700D0 (en) * | 1992-10-29 | 1992-12-09 | Smithkline Beecham Plc | Chemical compounds |
US5349045A (en) | 1993-01-26 | 1994-09-20 | United States Surgical Corporation | Polymer derived from cyclic amide and medical devices manufactured therefrom |
GB9326248D0 (en) | 1993-12-23 | 1994-02-23 | Smithkline Beecham Plc | Pharmaceutical formulations |
CZ286898B6 (en) | 1994-04-25 | 2000-07-12 | Smithkline Beecham Plc | Pharmaceutical preparation |
US5629322A (en) | 1994-11-15 | 1997-05-13 | Merck & Co., Inc. | Cyclic amidine analogs as inhibitors of nitric oxide synthase |
AU1705400A (en) * | 1998-10-15 | 2000-05-01 | Sarawak Medichem Pharmaceuticals, Inc. | Method and composition for treating and preventing tuberculosis |
GB9928290D0 (en) * | 1999-12-01 | 2000-01-26 | Univ Belfast | Process for preparing ambient temperature ionic liquids |
EP1199077A1 (en) * | 2000-10-19 | 2002-04-24 | Amura Limited | Stable compositions of oxapenem-3-carboxylic acids by Co-lyophilisation with pharmaceutical carriers |
GB0106428D0 (en) * | 2001-03-15 | 2001-05-02 | Amura Ltd | Antibacterial composition |
AR039476A1 (es) * | 2002-05-01 | 2005-02-23 | Wyeth Corp | Proceso para preparar derivados de 6-alquiliden penem |
AR039774A1 (es) | 2002-05-01 | 2005-03-02 | Wyeth Corp | 6-alquiliden-penems biciclicos como inhibidores de beta-lactamasas |
AR039475A1 (es) | 2002-05-01 | 2005-02-23 | Wyeth Corp | 6-alquiliden-penems triciclicos como inhibidores de beta-lactamasa |
US20040132708A1 (en) * | 2002-05-01 | 2004-07-08 | Wyeth | Process for preparing 6-alkylidene penem derivatives |
AR046041A1 (es) * | 2003-10-03 | 2005-11-23 | Aventis Pharma Inc | Procedimiento para la preparacion de compuestos heterociclicos n-amino sustituidos |
TW200716102A (en) * | 2005-06-01 | 2007-05-01 | Wyeth Corp | Bicyclic 6-alkylidene-penems as class-D β -lactamases inhibitors |
TW200716104A (en) * | 2005-06-01 | 2007-05-01 | Wyeth Corp | Tricyclic 6-alkylidene-penems as class-D β -lactamases inhibitors |
BRPI0613927A2 (pt) * | 2005-07-27 | 2011-02-15 | Wyeth Corp | uso de cefepima ou um sal farmaceuticamente aceitável desta e um composto da fórmula i ou um sal farmaceuticamente aceitável ou éster deste hidrolisável in vivo; composição; embalagem; e produto |
-
2003
- 2003-04-28 AR ARP030101471A patent/AR039774A1/es unknown
- 2003-04-29 TW TW092110033A patent/TW200307687A/zh unknown
- 2003-04-30 JP JP2004501418A patent/JP4602759B2/ja not_active Expired - Fee Related
- 2003-04-30 BR BR0309757-9A patent/BR0309757A/pt not_active IP Right Cessation
- 2003-04-30 CN CNA2009101331547A patent/CN101570545A/zh active Pending
- 2003-04-30 KR KR10-2004-7017597A patent/KR20050007368A/ko not_active Application Discontinuation
- 2003-04-30 UA UA20041109833A patent/UA79117C2/uk unknown
- 2003-04-30 WO PCT/US2003/013428 patent/WO2003093279A1/en active Application Filing
- 2003-04-30 SG SG200607462-9A patent/SG162614A1/en unknown
- 2003-04-30 EP EP08004917A patent/EP1988093A1/en not_active Withdrawn
- 2003-04-30 CA CA002483538A patent/CA2483538A1/en not_active Abandoned
- 2003-04-30 RU RU2004135082/04A patent/RU2339640C2/ru not_active IP Right Cessation
- 2003-04-30 MX MXPA04010663A patent/MXPA04010663A/es active IP Right Grant
- 2003-04-30 AU AU2003231205A patent/AU2003231205A1/en not_active Abandoned
- 2003-04-30 NZ NZ536182A patent/NZ536182A/en not_active IP Right Cessation
- 2003-04-30 CN CN038097338A patent/CN1649883B/zh not_active Expired - Fee Related
- 2003-04-30 EP EP03724340A patent/EP1499621A1/en not_active Ceased
- 2003-05-01 US US10/427,380 patent/US7112582B2/en not_active Expired - Fee Related
-
2004
- 2004-10-06 CR CR7508A patent/CR7508A/es not_active Application Discontinuation
- 2004-10-22 NO NO20044549A patent/NO20044549L/no not_active Application Discontinuation
- 2004-10-28 IL IL16489904A patent/IL164899A0/xx unknown
- 2004-10-29 EC EC2004005397A patent/ECSP045397A/es unknown
- 2004-11-30 ZA ZA200409686A patent/ZA200409686B/xx unknown
-
2006
- 2006-06-06 US US11/447,814 patent/US20060217361A1/en not_active Abandoned
-
2008
- 2008-08-21 US US12/195,706 patent/US7812014B2/en not_active Expired - Fee Related
-
2009
- 2009-08-21 CR CR10986A patent/CR10986A/es not_active Application Discontinuation
- 2009-08-21 CR CR10983A patent/CR10983A/es not_active Application Discontinuation
-
2010
- 2010-06-02 JP JP2010127126A patent/JP2010215652A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
US20060217361A1 (en) | 2006-09-28 |
CN101570545A (zh) | 2009-11-04 |
JP2005533017A (ja) | 2005-11-04 |
IL164899A0 (en) | 2005-12-18 |
ECSP045397A (es) | 2005-01-03 |
NO20044549L (no) | 2005-01-25 |
US20080312203A1 (en) | 2008-12-18 |
RU2004135082A (ru) | 2006-01-20 |
AU2003231205A1 (en) | 2003-11-17 |
JP4602759B2 (ja) | 2010-12-22 |
CN1649883B (zh) | 2010-05-26 |
RU2339640C2 (ru) | 2008-11-27 |
NZ536182A (en) | 2006-10-27 |
EP1988093A1 (en) | 2008-11-05 |
CR10983A (es) | 2009-09-09 |
US7112582B2 (en) | 2006-09-26 |
ZA200409686B (en) | 2007-09-26 |
CR7508A (es) | 2005-01-05 |
TW200307687A (en) | 2003-12-16 |
AR039774A1 (es) | 2005-03-02 |
US7812014B2 (en) | 2010-10-12 |
KR20050007368A (ko) | 2005-01-17 |
EP1499621A1 (en) | 2005-01-26 |
BR0309757A (pt) | 2005-03-08 |
CA2483538A1 (en) | 2003-11-13 |
SG162614A1 (en) | 2010-07-29 |
CN1649883A (zh) | 2005-08-03 |
WO2003093279A1 (en) | 2003-11-13 |
JP2010215652A (ja) | 2010-09-30 |
MXPA04010663A (es) | 2005-04-20 |
US20040077622A1 (en) | 2004-04-22 |
CR10986A (es) | 2009-09-09 |
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