NO121045B - - Google Patents
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- Publication number
- NO121045B NO121045B NO169099A NO16909967A NO121045B NO 121045 B NO121045 B NO 121045B NO 169099 A NO169099 A NO 169099A NO 16909967 A NO16909967 A NO 16909967A NO 121045 B NO121045 B NO 121045B
- Authority
- NO
- Norway
- Prior art keywords
- benzoxazin
- carbon atoms
- alkyl group
- alkyl
- mean hydrogen
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229940100198 alkylating agent Drugs 0.000 claims description 8
- 239000002168 alkylating agent Substances 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- -1 dimethyl-3,1-benzoxazin-2-one Chemical compound 0.000 description 5
- 239000007858 starting material Substances 0.000 description 4
- JWDYCNIAQWPBHD-UHFFFAOYSA-N 1-(2-methylphenyl)glycerol Chemical compound CC1=CC=CC=C1OCC(O)CO JWDYCNIAQWPBHD-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 2
- 241001279009 Strychnos toxifera Species 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229960005453 strychnine Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- HLVFKOKELQSXIQ-UHFFFAOYSA-N 1-bromo-2-methylpropane Chemical compound CC(C)CBr HLVFKOKELQSXIQ-UHFFFAOYSA-N 0.000 description 1
- BTUGGGLMQBJCBN-UHFFFAOYSA-N 1-iodo-2-methylpropane Chemical compound CC(C)CI BTUGGGLMQBJCBN-UHFFFAOYSA-N 0.000 description 1
- GTYZDORKFFSTLS-UHFFFAOYSA-N 2h-3,1-benzoxazine Chemical compound C1=CC=CC2=NCOC=C21 GTYZDORKFFSTLS-UHFFFAOYSA-N 0.000 description 1
- GZOJTRITAZODJV-UHFFFAOYSA-N 3,1-benzoxazin-2-one Chemical class C1=CC=CC2=COC(=O)N=C21 GZOJTRITAZODJV-UHFFFAOYSA-N 0.000 description 1
- HQQTZCPKNZVLFF-UHFFFAOYSA-N 4h-1,2-benzoxazin-3-one Chemical compound C1=CC=C2ONC(=O)CC2=C1 HQQTZCPKNZVLFF-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003179 convulsant agent Substances 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000012022 methylating agents Substances 0.000 description 1
- 230000001670 myorelaxant effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000003699 striated muscle Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/18—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/20—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 4
- C07D265/22—Oxygen atoms
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)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Fremgangsmåte ved fremstilling av nye, terapeutisk aktive N-alkyl-3,l-benzoxazin-2-oner.
Foreliggende oppfinnelse angår en fremgangsmåte ved fremstilling av nye, terapeutisk aktive N-alkyl-3,l-benzoxazin-2-oner med den generelle formel
, hvor R og R1er like eller forskjellige og betyr hydrogen, halogen, en nitrogruppe, en alkyl- eller alkoxygruppe med 1-lt karbon-
atomer, R2og R^ er like eller forskjellige og betyr hydrogen eller en alkylgruppe med 1- h karbonatomer, men kan ikke samtidig bety hydrogen, og R^er en alkylgruppe med 1-5 karbonatomer, og frem-gangsmåten er særpreget ved at en forbindelse med den generelle formel
, hvor R, R-p R2og R^har den ovenfor angitte betydning N-alkyleres med et egnet alkyleringsmiddel til innforing av en alkylgruppe med 1-5 karbonatomer på i og for seg kjent måte.
En fremgangsmåte er beskrevet i osterriksk patent nr. 268301
for fremstilling av nye 3,l-benzoxazin-2-oner med den generelle formel
, hvor R, R-p R2og R^har den foran angitte betydning.
Det har nu vist seg at ved å substituere, hydrogenet v.ed benzoxazinonets nitrogenatom med en alkylgruppe fåes nye forbindelser som oppviser en bemerkelsesverdig aktivitet innenfor terapien, spesielt på grunn av deres relakserende, antikonvulsive, beroligende og antiparkinsonske virkning.
De ifolge. foreliggende fremgangsmåte fremstilte forbindelser kan lett fremstilles ved alkyler.ing av de i det ovennevnte patent angitte forbindelser.
Det foretrekkes spesielt å behandle utgangsmaterialet 351~benzoxazin-2-on opplost i et egnet, vannfritt opplosningsmiddel, f.eks. aceton, benzen eller toluen, med et egnet alkyleringsmiddel ved det anvendte opplosningsmiddels kokepunkt, idet det benyttes et alkyleringsmiddel ved hjelp av hvilket det er mulig å innfore en alkylgruppe med 1-5 karbonatomer. Disse alkyleringsmidler kan spesielt utgjores av alkylsulfater og-sulfonater og alkylhalogen-ider, og det anvendes fortrinnsvis et overskudd av alkyleringsmiddel slik at det fåes en fullstendig alkylering av utgangsproduk-tets nitrogenatom. Det hele filtreres så og vaskes med et ikke-polart vannfritt opplosningsmiddel, som benzen eller ethylether,
og det tilsvarende 3,l-benzoxazin-2-on-N-alkylat fåes ved inndamp-ning av filtratet under vakuum.
Fremstilling av noen 1,<*>+- og 6 - substituerte h H - 3}1~benzoxazin-2-(1H)-oner er beskrevet i II Farmaco (Pavia) Ed.
Sei. 21 (3), s. 5^ 9- 557 (1966). Disse forbindelser er angitt i artikkelen å ha terapeutisk aktivitet, men senere undersøkelser har vist at deres terapeutiske aktivitet var utilfredsstillende,
og disse forbindelser blir derfor ikke lenger fremstilt. De kjente forbindelser var substituert i ^-posisjonen enten bare med hydrogen eller med hydrogen og fenyl.
De ifdlge foreliggende fremgangsmåte fremstilte forbindelser oppviser derimot en bemerkelsesverdig relakserende virkning på spent, stripet muskulatur. Den myorelakserende virkning ble spesielt undersokt hvorved den antikonvulsive virkning sammenlignet med forskjellige konvulsive midler, som cardiazol, stryknin, og nikotin, og ved elektrisk sjokk, ble iaktatt, idet "Myanesin" 1,2-dihydroxy-3-(2-methylfenoxy)-propan ble anvendt som referansefor-bindelse.
I tabellen er den aktive dose 50% > (AD^q) angitt som represen-terer den substansmengde som er nodvendig for å beskytte 50% av de behandlede dyr mot krampe og dod.
Forsok ble utfort på hvite hanmus med en vekt av 20 - 25 g.
TABELL
Aktiv dose 50 mg/kg per os
Forbindelse Cardia- Stryknin Nikotin Elektro-<LD>50
zol Krampel Dod Krampe Dod sjokk- mg/kg krampe krampe per os 1 jM-^-trimethyl-
3 ,l--benzoxazin-
2-on 100 350 260 130 120 270 1000
^^-trimethyl-
S-brom-3,1-benz-
Dxazin-2-on 80 370 160 ^3 35 130 1270
"Myanesin" 235 695 5^0 3^0 360 275 1350
I 1 1 J 1 1 L i
Eksempel 1
1 trimethyl- 3 , l- benzoxazin- 2- on
5 g vannfritt kaliumkarbonat og 15 ml methyljodid ble satt til 5 g dimethyl-3,l-benzoxazin-2-on opplost i 60 ml vannfritt aceton. Blandingen ble oppvarmet i 2k timer med omroring under tilbakelopsdestillering, idet 5 ml methyljodid ble tilsatt under en femte og tiende time regnet fra reaksjonens begynnelse. Saltet ble filtrert og vasket med vannfritt benzen. Filtratet ble inn-dampet til torrhet under vakuum, og resten ble tatt opp med ether, og det ble oppnådd 3,5 g hvite krystaller av 1 ,l+-,lf-trimethyl-3,1-benzoxazin-2-on med et smeltepunkt av 95-96°C.
Eksempel 2
1,^- trime thyl- 6- brom- 3 , l- benzoxazin- 2- on
Det ble benyttet samme fremgangsmåte som i eksempel 1, men dimethyl-6-brom-3,l-benzoxazin-2-on ble anvendt som utgangsmateriale og methylsulfat som methyleringsmiddel.
Det ble oppnådd hvite krystaller av i, kj^-trimethyl-é-brom-3,l-benzoxazin-2-on med et smeltepunkt av 115-116°C efter rekrystallisering fra vandig alkohol.
Eksempel 3
1- isobutyl-^ , 1+- dimethyl- 3 , l- benzoxazin- 2- on
Det ble benyttet samme fremgangsmåte som eksempel 1, men l+,1+-dimethyl-3,l-benzoxazin-2-on ble anvendt som utgangsmateriale og isobutylbromid som alkyleringsmiddel.
Det ble oppnådd l-isobutyl-^-j^-dimethyl-3,l-benzoxazin-2-on som så ut som en klar, lett gulaktig olje og hadde et infrarddt spektrum med de folgende karakteristiske bånd: 1715 cm""'" (v s), 1610 cm'<1>(s), 1500 cm<_1>(s), 765 - 750 cm"<1>dobbeltbånd.,
Eksempel h
l- isobutyl- W , 1+- dimethyl- 6- brom- 3 , l- benzoxazin- 2- on
Det ble benyttet samme fremgangsmåte som i eksempel 1, men ^,1+-dimethyl-6-brom-3,l-benzoxazin-2-on ble anvendt som utgangsmateriale og isobutyljodid som alkyleringsmiddel.
Det ble oppnådd hvite krystaller av 1-isobutyl-^,^-dimethyl-6-brom-3,l-benzoxazin-2-on med et smeltepunkt av 76 - 8o°C efter rekrystallisering fra en blanding av petroleumsether og benzen.
Claims (1)
- Fremgangsmåte ved fremstilling av nye, terapeutisk aktive forbindelser med den generelle formel, hvor R og R.^ er like eller forskjellige og betyr hydrogen, halogen, en nitrogruppe, en alkyl-eller alkoxygruppe med 1- <*> + karbonatomer, Rg og R^ er like eller forskjellige og betyr hydrogen eller en alkylgruppe med l-^ karbonatomer, men kan ikke samtidig bety hydrogen, og R^ er en alkylgruppe med 1-5 karbonatomer, karakterisert ved at en forbindelse med den generelle formel, hvor R, Rp R2 og R^ har den ovenfor angitte betydning, N-alkyleres med et egnet alkyleringsmiddel til innforing av en alkylgruppe med 1-5 karbonatomer på i og for seg kjent måte.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2105166 | 1966-08-03 | ||
| IT1800566 | 1966-08-03 | ||
| IT1516667 | 1967-04-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO121045B true NO121045B (no) | 1971-01-11 |
Family
ID=27272868
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO169228A NO121275B (no) | 1966-08-03 | 1967-08-01 | |
| NO169099A NO121045B (no) | 1966-08-03 | 1967-09-29 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO169228A NO121275B (no) | 1966-08-03 | 1967-08-01 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US3526621A (no) |
| BE (2) | BE702201A (no) |
| CH (1) | CH478828A (no) |
| DE (2) | DE1695756C3 (no) |
| DK (2) | DK118877B (no) |
| ES (2) | ES343737A1 (no) |
| FR (2) | FR6494M (no) |
| GB (1) | GB1135899A (no) |
| IL (1) | IL28427A (no) |
| NL (2) | NL6710332A (no) |
| NO (2) | NO121275B (no) |
| SE (2) | SE331997B (no) |
| YU (2) | YU31634B (no) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4301283A (en) * | 1979-09-27 | 1981-11-17 | Sterling Drug Inc. | Process for preparing 2-oxo-dihydrobenzo(d)(1,3)-oxazines |
| DE3026534A1 (de) * | 1980-07-12 | 1982-03-18 | C.H. Boehringer Sohn, 6507 Ingelheim | 3,1-benzoxazin-2-one, ihre herstellung und verwendung |
| DE3217012A1 (de) * | 1982-05-06 | 1983-11-10 | Dr. Karl Thomae Gmbh, 7950 Biberach | Benzoxazin-2-one, deren herstellung und diese verbindungen enthaltende arzneimittel |
| IL106507A (en) * | 1992-08-07 | 1997-11-20 | Merck & Co Inc | Pharmaceutical compositions containing benzoxazinones and some novel compounds of this type |
| US5519021A (en) * | 1992-08-07 | 1996-05-21 | Merck & Co., Inc. | Benzoxazinones as inhibitors of HIV reverse transcriptase |
| WO1995020389A1 (en) * | 1994-01-28 | 1995-08-03 | Merck & Co., Inc. | Benzoxazinones as inhibitors of hiv reverse transcriptase |
| WO1998014436A1 (en) * | 1996-10-02 | 1998-04-09 | Dupont Pharmaceuticals Company | 4,4-disubstituted-1,4-dihydro-2h-3,1-benzoxazin-2-ones useful as hiv reverse transcriptase inhibitors and intermediates and processes for making the same |
| US5874430A (en) | 1996-10-02 | 1999-02-23 | Dupont Pharmaceuticals Company | 4,4-disubstitued-1,4-dihydro-2H-3,1-benzoxazin-2-ones useful as HIV reverse transcriptase inhibitors and intermediates and processes for making the same |
| US5932726A (en) * | 1996-12-16 | 1999-08-03 | Dupont Pharmaceuticals Company | Asymmetric synthesis of benzoxazinones |
| US6358948B1 (en) | 1999-05-04 | 2002-03-19 | American Home Products Corporation | Quinazolinone and benzoxazine derivatives as progesterone receptor modulators |
| US6509334B1 (en) * | 1999-05-04 | 2003-01-21 | American Home Products Corporation | Cyclocarbamate derivatives as progesterone receptor modulators |
| UA73119C2 (en) * | 2000-04-19 | 2005-06-15 | American Home Products Corpoir | Derivatives of cyclic thiocarbamates, pharmaceutical composition including noted derivatives of cyclic thiocarbamates and active ingredients of medicines as modulators of progesterone receptors |
| EP1756072A2 (en) * | 2004-04-27 | 2007-02-28 | Wyeth | Purification of progesterone receptor modulators |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3047573A (en) * | 1962-07-31 | N-alkylamido substituted | ||
| US2940971A (en) * | 1960-06-14 | Tetrahydrooxazenones | ||
| US1951807A (en) * | 1931-04-17 | 1934-03-20 | Holimann La Roche Inc | 4-phenalkyl-3-keto-3.4-dihydro-1.4-benzoxazines and process for the manufacture of same |
| US2947745A (en) * | 1958-08-11 | 1960-08-02 | Smith Kline French Lab | Substituted phenoxazine sedative agents |
| US3280120A (en) * | 1964-03-09 | 1966-10-18 | Rexall Drug Chemical | Substituted benzoxazines, process therefor and intermediates |
-
1967
- 1967-07-25 US US655749A patent/US3526621A/en not_active Expired - Lifetime
- 1967-07-26 NL NL6710332A patent/NL6710332A/xx unknown
- 1967-07-29 DE DE1695756A patent/DE1695756C3/de not_active Expired
- 1967-07-31 GB GB35019/67A patent/GB1135899A/en not_active Expired
- 1967-07-31 IL IL28427A patent/IL28427A/en unknown
- 1967-08-01 YU YU1526/67A patent/YU31634B/xx unknown
- 1967-08-01 FR FR116413A patent/FR6494M/fr not_active Expired
- 1967-08-01 NO NO169228A patent/NO121275B/no unknown
- 1967-08-02 BE BE702201D patent/BE702201A/xx not_active Expired
- 1967-08-02 SE SE11055/67A patent/SE331997B/xx unknown
- 1967-08-02 CH CH1088467A patent/CH478828A/de not_active IP Right Cessation
- 1967-08-02 ES ES343737A patent/ES343737A1/es not_active Expired
- 1967-08-02 DK DK394667AA patent/DK118877B/da unknown
- 1967-09-25 NL NL6713047A patent/NL6713047A/xx unknown
- 1967-09-28 FR FR122591A patent/FR93909E/fr not_active Expired
- 1967-09-28 DE DE1695780A patent/DE1695780C3/de not_active Expired
- 1967-09-28 YU YU1900/67A patent/YU31636B/xx unknown
- 1967-09-29 DK DK485367AA patent/DK111568B/da unknown
- 1967-09-29 SE SE13396/67A patent/SE337823B/xx unknown
- 1967-09-29 NO NO169099A patent/NO121045B/no unknown
- 1967-09-30 ES ES345647A patent/ES345647A2/es not_active Expired
- 1967-10-02 BE BE704583D patent/BE704583A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE1695780C3 (de) | 1979-08-23 |
| ES343737A1 (es) | 1968-10-16 |
| DK118877B (da) | 1970-10-19 |
| BE704583A (no) | 1968-04-02 |
| GB1135899A (en) | 1968-12-04 |
| BE702201A (no) | 1968-02-02 |
| DK111568B (da) | 1968-09-16 |
| US3526621A (en) | 1970-09-01 |
| DE1695756B2 (de) | 1978-02-09 |
| DE1695780A1 (de) | 1971-04-29 |
| YU31636B (en) | 1973-10-31 |
| FR6494M (no) | 1968-11-25 |
| YU152667A (en) | 1973-02-28 |
| NL6710332A (no) | 1968-02-05 |
| NL6713047A (no) | 1968-10-21 |
| YU190067A (en) | 1973-02-28 |
| NO121275B (no) | 1971-02-08 |
| ES345647A2 (es) | 1968-11-16 |
| CH478828A (de) | 1969-09-30 |
| IL28427A (en) | 1971-04-28 |
| SE337823B (no) | 1971-08-23 |
| SE331997B (no) | 1971-01-25 |
| YU31634B (en) | 1973-10-31 |
| DE1695756A1 (de) | 1972-03-02 |
| DE1695780B2 (de) | 1978-12-21 |
| DE1695756C3 (de) | 1978-10-05 |
| FR93909E (fr) | 1969-06-06 |
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