DK143984B - Analogifremgangsmaade til fremstilling af derivater af pyrido (2,3-b) benzothiazepin-(1,5). - Google Patents
Analogifremgangsmaade til fremstilling af derivater af pyrido (2,3-b) benzothiazepin-(1,5). Download PDFInfo
- Publication number
- DK143984B DK143984B DK153478AA DK153478A DK143984B DK 143984 B DK143984 B DK 143984B DK 153478A A DK153478A A DK 153478AA DK 153478 A DK153478 A DK 153478A DK 143984 B DK143984 B DK 143984B
- Authority
- DK
- Denmark
- Prior art keywords
- pyrido
- benzothiazepin
- product
- preparing derivatives
- analogy procedure
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 11
- 239000000047 product Substances 0.000 description 11
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 229960001340 histamine Drugs 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- FHGWEHGZBUBQKL-UHFFFAOYSA-N 1,2-benzothiazepine Chemical compound S1N=CC=CC2=CC=CC=C12 FHGWEHGZBUBQKL-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 3
- 230000001387 anti-histamine Effects 0.000 description 3
- 239000000739 antihistaminic agent Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000001956 orexigenic effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 229940092253 ovalbumin Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241001239379 Calophysus macropterus Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102100026456 POU domain, class 3, transcription factor 3 Human genes 0.000 description 1
- 101710133393 POU domain, class 3, transcription factor 3 Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 208000008784 apnea Diseases 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940052491 bordetella pertussis Drugs 0.000 description 1
- 239000004044 bronchoconstricting agent Substances 0.000 description 1
- 230000003435 bronchoconstrictive effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229940047135 glycate Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000006286 nutrient intake Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Description
(m (19) DANMARK \Rg
|j| (12) FREMUEGGELSESSKRIFT od 143984 B
DIREKTORATET FOR PATENT- 06 VAREMÆRKEVÆSENET
(21) Ansøgning nr. 1534/78 (51) |nt.CI.3 C 07 D 513/04 (22) Indleveringsdag 6. apr. 1978 (24) Løbedag 6. apr. 1978 (41) Aim. tilgængelig 8. okt. 1978 (44) Fremlagt 9· nov. 1981 (86) International ansøgning nr. - (86) International indleveringsdag - (86) Videreførelsesdag - (62) Stamansøgning nr. -
(30) Prioritet 7. apr. 1977* 14692/77* GB
(71) Ansøger SOCIETE ANONYME HEXACHIMIE* 92504 Rueil Malmaison, FR.
(72) Opfinder Charles Hoffmann, FR: Etienne Bouley, FR.
(74) Fuldmægtig Firmaet Chas. Hude.
(54) Analogifremgangsmåde til fremstilling af derivater af pyride (2,3-b)benzothiazepln-(1,5)·
Den foreliggende opfindelse angår en analogifremgangsmåde til frem- stilling af hidtil ukendte derivater af pyrido[2,3-b]benzothiazepin- _j_ (1,5) , substitueret i 5-stilling med en piperazinylgruppe, svarende X) til følgende formel: T)
O
d- t 3 2 U398Å e/ ^sr - r / (I) OCX« eller ugiftige syreadditionssalte af disse derivater.
I formlen I er R et hydrogenatom eller en alkylgruppe med 1 til 5 kulstofatomer med lige eller forgrenet kæde, specielt methyl-gruppen.
Fremgangsmåden ifølge opfindelsen er ejendommelig ved, at man lader en piperazin med formlen: A~\ H - - R (II) hvor R har den ovennævnte betydning, reagere med en 5-halogen-pyrido-[2,3-b]benzothiazepin-(1,5) med formlen: ah'X)
N S
hvor X er et halogenatom, især chlor, hvilken reaktion udføres i et aromatisk opløsningsmiddel, især toluen, ved opløsningsmidlets kogepunkt.
De omhandlede forbindelser har interessante farmakologiske egenskaber, især antihistaminvirkninger og orexigene virkninger, som gør dem værdifulde i terapien.
Det følgende eksempel anføres for at illustrere fremgangsmåden ifølge opfindelsen nærmere.
3 14398A
Eksempel.
a) Fremstil liner af udgangsmateriale 5-chlor-pyrido[2,3-b]benzothiazenin-(1,5).
3
Til en blanding af 200 cm phosphoroxychlorid og 71 g phosphorpenta= chlorid sætter man 40 g 5,6-dihydro-5-oxo-pyrido[2,3-b]benzothiazepin- (1,5), opvarmer reaktionsblandingen under tilbagesvaling i 4 timer og fjerner derefter overskud af phosphoroxychlorid ved destillation. Rema- 3 nensen optages så i 300 cm kold chloroform. Den organiske opløsning vaskes flere gange med isvand og tørres så på magniumsulfat. Opløsningsmidlerne fjernes ved destillation i vakuum ved omgivelsernes temperatur. Remanensen optages i vandfri ether og vaskes så flere gange med kold ether. Efter tørring i vakuum fås 37 g 5-chlor-pyrido[2,3-b]benzothia= zepin-(l,5), som smelter ved 134-135°C.
b) Fremstilling af slutprodukt 5-(11-methyl-4'-piperazinyl)-pyrido[2,3-b]benzothiazepin-(1,5) (Formel I, R^H^)
Til en opløsning af 10 g N-methylpiperazin i 75 cm"^ vandfri toluen sættes på én gang 12,4 g 5-chlor-pyrido[2,3-b]benzothiazepin-(1,5) fremstillet ifølge a). Man opvarmer progressivt til tilbagesvaling, og derefter holdes ved tilbagesvaling i 2 1/2 time. Man hælder reaktionsblandingen i syrnet vand og lader den henstå under omrøring i 1/2 time. Den vandige fase vaskes så med ether, gøres alkalisk med ammoniak til pH 8 og ekstraheres med chloroform. Den organiske fase tørres på magniumsulfat. Efter afdampning af chloroformen i vakuum fås en pastaagtig remanens, som udfælder i ether. Dette produkt (8 g) omkrystalli- 3 3 seres af en blanding af 50 cm acetone og 40 cm vand og giver 5,7 g af det forventede produkt, som smelter ved 137° C.
De farmakologiske egenskaber af det omhandlede produkt illustreres i det følgende.
I Antihistaminvirkning
Bronchoconstrictor virkning af histaminaerosol.
Metode.
Grupper på 6 marsvin på 200 til 250 g udsættes i et lukket rum i 5 4 143984 minutter for en aerosol af 0,2% histamin i vandig opløsning.
Der anvendes to aerosoler med 4 timers mellemrum. Det afprøvede produkt administreres ad intraperitoneal vej (I.P.) 30 minutter før tilførsel af den anden aerosol.
Nedenstående tabel I viser den procentmængde beskyttede dyr, som ikke får en apnøtisk krise på 5 minutter.
Tabel I
Produkt fra eksemplet % beskyttelse mg/kg I.P.
0,062 17 0,125 33 0,250 50 0,500 100 DE50 mg/kg I.P. 0,155
Virkning overfor DL^qq histamin Metode.
Trefarvede hanmarsvin, der vejer 400-5Q0 g, modtager det undersøgte produkt ad intraperitoneal vej. Tredive minutter senere injicerer man ad intravenøs vej 800 γ/kg histamin, d.v.s. DL1Q0 i fysiologisk opløsning .
Dyrene holdes under observation i en time.
Nedenstående tabel II viser den procentiske beskyttelse overfor dødeligheden fremkaldt med histamin.
5 143984
Tabel II
Produkt fra eksemplet % beskyttelse mg/kg I.P.
0,062 0 0,125 60 0,250 100 DE50 mg/kg I.P. 0,120 II Orexigenvirkning Næringsindtagelse hos kat.
Metode.
Grupper på 3 hankatte, der vejer mellem 2 og 3 kg gøres betinget af at indtage deres daglige næring i et enkelt måltid mellem kl. 10 og 12. Vand gives ad libitum. Produktet som skal undersøges, administreres ad intraperitoneal vej 30 minutter før måltidet. Den Indtatgne mængde næring beregnes.
Med doser på 1 og 4 mg pr. kg. (I.P.) forøger produktet fra eksemplet den indtagne mængde næring 20 til 50% afhængig af kattene.
III Virkning overfor en passiv hudoverfølsomhedsreaktion.
Metode.
Den anvendte metode er beskrevet af MOTA I i Immunology, 1964, 7, side 681. Denne metode består i at sensibilisere rotter med fire intradermale injektioner af 0,1 ml rotteantiserum.
Antiserumet fås af dyr behandlet med en blanding af ovalbumin og Bor-detella pertussis. 72 timer efter sensibilisering administrerer man til dyrene ad intravenøs eller intraperitoneal vej produktet,som skal undersøges, og 1 ml pr. rotte (I.V.) af en 0,02% opløsning af Evansblåt + 5 mg ovalbumin pr. ml i en isotonisk vandig opløsning af 9 o/oo na= 6 143984 triumchlorid. Tredive minutter efter denne sidste injektion aflives dyrene, og man måler overfladen af hver blå plet, svarende til punktet for injektion af antiserum.
Resultaterne udtrykkes som procentvis formindskelse af den farvede overflade.
Resultater
Resultaterne er anført i nedenstående tabel III, hvori der som sammenligning er anført resultaterne fremkommet med dinatriumchromoglycat (indgivet intravenøst).
Tabel III
Produkt Administra- Doser Gennemsnits-2 % hæm- Statis- DE™ tionsvej overflade mrn -ning tisk _____jSiSrmg/kg 0 % 66,7 - 2,62 0.125 54,4 ί 3,26 18 xx
Eksempel I.P. 0 90'8 ^92 " °'57 0,5 46,3 - 3,78 49 xxx 0 66,7 ± 2,'62 1 25,1 - 3,45 62 xxx 0 31,77 - 3,16 0,15 27,86 - 3,82 12 ns 0,31 30,5 ~ 2,59 4 ns -----0,64
Dinatri= I.V. 0 72,46-4,37 umchrom= 0,625 35,42 - 5,02 51 xxx glycat ' 0 31,77 - 3,16 1,25 2,30 - l,o7 93 xxx 2,5 0,23 - 0,23 99 xxx XX 99% signifikant xxx 99,9% signifikant ns ikke signifikant
Sammenfattende kan siges, at forbindelsen fra eksemplet har antihistaminegenskaber, orexigene egenskaber og især antianaphylaxiegenskaber.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB14692/77A GB1587128A (en) | 1977-04-07 | 1977-04-07 | Benzothiazepine derivatives |
| GB1469277 | 1977-04-07 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK153478A DK153478A (da) | 1978-10-08 |
| DK143984B true DK143984B (da) | 1981-11-09 |
| DK143984C DK143984C (da) | 1982-04-19 |
Family
ID=10045866
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK153478A DK143984C (da) | 1977-04-07 | 1978-04-06 | Analogifremgangsmaade til fremstilling af derivater af pyrido(2,3-b)benzothiazepin-(1,5) |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US4163785A (da) |
| JP (1) | JPS5416498A (da) |
| AR (1) | AR217291A1 (da) |
| AT (1) | AT360028B (da) |
| AU (1) | AU514413B2 (da) |
| BE (1) | BE865735A (da) |
| CA (1) | CA1072550A (da) |
| CH (1) | CH630638A5 (da) |
| CS (1) | CS200543B2 (da) |
| DD (1) | DD135727A5 (da) |
| DE (1) | DE2815088C2 (da) |
| DK (1) | DK143984C (da) |
| ES (1) | ES468547A1 (da) |
| FR (1) | FR2386547A1 (da) |
| GB (1) | GB1587128A (da) |
| GR (1) | GR62852B (da) |
| HU (1) | HU178008B (da) |
| MX (1) | MX5046E (da) |
| NL (1) | NL7803720A (da) |
| NO (1) | NO781185L (da) |
| PT (1) | PT67839B (da) |
| SE (1) | SE427355B (da) |
| SU (1) | SU668609A3 (da) |
| ZA (1) | ZA781849B (da) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4391808A (en) * | 1980-06-12 | 1983-07-05 | Ciba-Geigy Corporation | 5(1-Piperazinyl(imidazo[2,1-b][1,3,5]benzothiadiazepines |
| FR2511683A1 (fr) * | 1981-08-20 | 1983-02-25 | Hexachimie | Nouveaux derives de la pyrido (2,3-b) benzothiazepine(1,5) substituee en 5 par une carboxypiperazine, leur procede de preparation, leur application en therapeutique |
| FR2511684A1 (fr) * | 1981-08-20 | 1983-02-25 | Hexachimie | Nouveaux derives de la pyrido (2,3-b) benzothiazepine-(1,5), leur preparation, leur action antiallergique et antihistaminique |
| CA2024071C (en) * | 1989-08-29 | 2002-06-04 | Karl D. Hargrave | Pyrido [2, 3-b] [1,5]benzoxazepin (and thiazepin)-5 (6h)-ones and-thiones and their use in prevention or treatment of hiv infection |
| KR0166964B1 (ko) * | 1989-08-29 | 1999-01-15 | 데이비드 이. 프랭크호우서 | 피리도[2,3-b][1,5]벤즈옥사제핀(및 티아제핀)-5(6H)-온 및 -티온 |
| US5075440A (en) * | 1990-05-03 | 1991-12-24 | Ortho Pharmaceutical Corporation | Novel pyrido[2,3-f](1,4)thiazepines and pyrido[3,2-b](1,5)benzothiazepines |
| BE1004596A4 (fr) | 1990-09-26 | 1992-12-22 | Therabel Res S A N V | Derives de methylpiperazinoazepine, leur preparation et leur utilisation. |
| GB9109557D0 (en) * | 1991-05-02 | 1991-06-26 | Wellcome Found | Chemical compounds |
| US5393752A (en) * | 1992-05-26 | 1995-02-28 | Therabel Research S.A./N.V. | Methylpiperazinoazepine compounds, preparation and use thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR5315E (fr) * | 1905-08-08 | 1906-03-06 | Bellanger Nee Marie Ernestine | Stérilisateur perfectionné pour le desséchement des objets stérilisés par évacuation et condensation successives de la vapeur d'eau qu'ils contiennent et pour leur conservation à l'état stérile acquis jusqu'à l'ouverture de leur contenant |
| DE1620703B2 (de) * | 1960-08-16 | 1976-11-25 | Ausscheidung aus: 12 80 879 Dr. A. Wander AG, Bern | 11-basisch substituierte dibenzo eckige klammer auf b,f eckige klammer zu-eckige klammer auf 1,4 eckige klammer zu-thiazepine |
| GB1156781A (en) * | 1965-04-07 | 1969-07-02 | Lab U P S A | New Heterocyclic Compounds |
| US3412193A (en) * | 1965-12-13 | 1968-11-19 | American Cyanamid Co | 11-(4-methyl-1-piperazinyl)dibenz[b, f][1, 4]oxazepines or thiazepines for controlling fertility |
| GB1173826A (en) | 1967-10-11 | 1969-12-10 | May & Baker Ltd | Phenanthridine Derivatives |
| CA918659A (en) * | 1969-07-31 | 1973-01-09 | Yoshitomi Pharmaceutical Industries | 11-(4-substituted-1-piperazinyl)-dibenzo (b,f) (1,4) thiazepines |
-
1977
- 1977-04-07 GB GB14692/77A patent/GB1587128A/en not_active Expired
-
1978
- 1978-03-21 GR GR55766A patent/GR62852B/el unknown
- 1978-03-23 FR FR7808554A patent/FR2386547A1/fr active Granted
- 1978-03-29 PT PT67839A patent/PT67839B/pt unknown
- 1978-03-31 ZA ZA00781849A patent/ZA781849B/xx unknown
- 1978-04-03 MX MX786993U patent/MX5046E/es unknown
- 1978-04-03 AR AR271666A patent/AR217291A1/es active
- 1978-04-03 US US05/892,647 patent/US4163785A/en not_active Expired - Lifetime
- 1978-04-04 ES ES468547A patent/ES468547A1/es not_active Expired
- 1978-04-04 NO NO781185A patent/NO781185L/no unknown
- 1978-04-05 CA CA300,478A patent/CA1072550A/en not_active Expired
- 1978-04-05 JP JP4016478A patent/JPS5416498A/ja active Granted
- 1978-04-05 DD DD78204609A patent/DD135727A5/xx unknown
- 1978-04-06 AU AU34850/78A patent/AU514413B2/en not_active Expired
- 1978-04-06 SE SE7803891A patent/SE427355B/sv unknown
- 1978-04-06 CS CS782254A patent/CS200543B2/cs unknown
- 1978-04-06 AT AT242178A patent/AT360028B/de not_active IP Right Cessation
- 1978-04-06 SU SU782599553A patent/SU668609A3/ru active
- 1978-04-06 DK DK153478A patent/DK143984C/da not_active IP Right Cessation
- 1978-04-06 BE BE2056846A patent/BE865735A/xx not_active IP Right Cessation
- 1978-04-06 CH CH372978A patent/CH630638A5/fr not_active IP Right Cessation
- 1978-04-06 HU HU78HE766A patent/HU178008B/hu unknown
- 1978-04-07 DE DE2815088A patent/DE2815088C2/de not_active Expired
- 1978-04-07 NL NL7803720A patent/NL7803720A/xx not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| SU668609A3 (ru) | 1979-06-15 |
| JPS5416498A (en) | 1979-02-07 |
| FR2386547B1 (da) | 1982-05-21 |
| PT67839B (fr) | 1979-09-28 |
| SE427355B (sv) | 1983-03-28 |
| JPS5620315B2 (da) | 1981-05-13 |
| AU514413B2 (en) | 1981-02-05 |
| BE865735A (fr) | 1978-10-06 |
| MX5046E (es) | 1983-03-01 |
| ZA781849B (en) | 1979-03-28 |
| GR62852B (en) | 1979-06-20 |
| CA1072550A (en) | 1980-02-26 |
| DE2815088A1 (de) | 1978-10-19 |
| US4163785A (en) | 1979-08-07 |
| AT360028B (de) | 1980-12-10 |
| DE2815088C2 (de) | 1985-07-18 |
| CH630638A5 (fr) | 1982-06-30 |
| AU3485078A (en) | 1979-10-11 |
| GB1587128A (en) | 1981-04-01 |
| NL7803720A (nl) | 1978-10-10 |
| PT67839A (fr) | 1978-04-01 |
| AR217291A1 (es) | 1980-03-14 |
| ES468547A1 (es) | 1978-12-01 |
| CS200543B2 (en) | 1980-09-15 |
| DK153478A (da) | 1978-10-08 |
| DK143984C (da) | 1982-04-19 |
| NO781185L (no) | 1978-10-10 |
| FR2386547A1 (fr) | 1978-11-03 |
| ATA242178A (de) | 1980-05-15 |
| DD135727A5 (de) | 1979-05-23 |
| HU178008B (en) | 1982-02-28 |
| SE7803891L (sv) | 1978-10-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |