DK145820B - Analogifremgangsmaade til fremstilling af d-2-(6-methoxy-2-naphthyl)-propanal - Google Patents
Analogifremgangsmaade til fremstilling af d-2-(6-methoxy-2-naphthyl)-propanal Download PDFInfo
- Publication number
- DK145820B DK145820B DK186170AA DK186170A DK145820B DK 145820 B DK145820 B DK 145820B DK 186170A A DK186170A A DK 186170AA DK 186170 A DK186170 A DK 186170A DK 145820 B DK145820 B DK 145820B
- Authority
- DK
- Denmark
- Prior art keywords
- naphthyl
- methoxy
- propanal
- preparing
- analogy procedure
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 210000000548 hind-foot Anatomy 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 230000027950 fever generation Effects 0.000 description 2
- 210000002683 foot Anatomy 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 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
- 208000010392 Bone Fractures Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 1
- 210000002346 musculoskeletal system Anatomy 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/41—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrogenolysis or reduction of carboxylic groups or functional derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
(19) DANMARK
|p (12) FREML/EGGELSESSKRIFT ου 145820 B
DIREKTORATET FOR PATENT- OG VAREMÆRKEVÆSENET
(21) Ansøgning nr. 18β1 /ΥΟ (51) |nt.CI.3 C 07 C 47/277 (22) Indleveringsdag 1 ^ 1970 (24) Løbedag 14. apr. 1970 (41) Aim. tilgængelig 10. apr. 1971 (44) Fremlagt 1 ^ · niar. 1985 (86) International ansøgning nr. - (86) International indleveringsdag - (85) Videreførelsesdag - (62) Stamansøgning nr. -
(30) Prioritet 9* okt. 1969* 865216, US
(71) Ansøger SYNTEX CORPORATION, Panama, PA.
(72) Opfinder John Hans Pried, US: Ian Thomas Harrison, US.
(74) Fuldmægtig Firmaet Chas. Hude.
(54) Analogifremgangsmåde til fremstil= ling af d-2- (6-methoxy-2-naph.th.yl) -propanal.
Den foreliggende opfindelse angår en analogifremgangsmåde til fremstilling af d-2-(6-methoxy-2-naphthyl)-propanal.
Det er kendt, at d,1-2-(6-methoxy-2-naphthyl)-propanal har antiinflammatorisk virkning, jvf. dansk patentansøgning nr. 3638/69.
ffi Det har nu vist sig, at d-2-(6-methoxy-2-naphthyl) -propanal ^ har en stærkere antiinflammatorisk virkning end den racemiske
CvJ
00 forbindelse, hvilket blev konstateret ved prøven med car- ^ rageenininduceret poteinflammation hos rotter, der udføres -*3' t— som følger: * Q Der anvendes hunrotter, som vejer 80-90 g. Forsøgsmaterialer ne indgives til tidspunktet 0 ved tvangsfodring i 1 ml vandig bærer. Efter 1 time injiceres 0,05 ml af en 1%'ig 2 145820 opløsning (i 0,9% NaCl) af carrageenin i den højre bagpote. Denne injektion forårsager inflammation af poten. Rotterne dræbes 3 timer efter injektionen, og begge bagpoter fjernes og vejes separat, og man beregner den procen-5 tiske forøgelse af potestørrelsen som følger: Vægt af højre bagpote - Vægt af venstre bagpote χ Vægt af venstre bagpote
Resultaterne af disse forsøg er vist i følgende tabel:
Forbindelse Oral antiinflammatorisk virkning d,1-2-(6-methoxy-2- naphthyl)-propanal 1 d-2- (6-methoxy-2- naphthyl)-propanal 1 3
Den ifølge opfindelsen fremstillede forbindelse er med andre 10 ord mindst 3 gange så aktiv som den racemiske forbindelse.
d-2-(6-methoxy-2-naphthyl)-propanal udviser foruden anti-inflammatorisk også analgetisk og antipyretisk virkning. Forbindelsen kan derfor anvendes til behandling og mildnelse af betændelse, smerte og pyrexia hos pattedyr, 15 Forbindelsen er særlig nyttig til behandling af betændelse såsom betændelsestilstande i muskelskeletsysternet, skelets led og andre væv. Forbindelsen er derfor nyttig til behandling af tilstande, der karakteriseres ved betændelse, såsom rheumatisme, kvæstelse, sønderrivelse, arthritis, knog-20 lefrakturer, posttraumatiske tilstande og gigt. I de tilfælde , hvori de ovennævnte tilstande indbefatter smerte og pyrexia sammen med betændelse, er forbindelsen nyttig til mildnelse af disse tilstande og af betændelsen.
145820 3
Den foretrukne administrationsmåde er oral administration, som anvender en bekvem daglig dosering, der kan indstilles i overensstemmelse med graden af ydelsen. I almindelighed anvendes en daglig dosis fra 0,1 mg til 60 mg aktiv for-5 bindelse pr. kg legemsvægt af pattedyret. De fleste til stande reagerer overfor behandling, der omfatter et doseringsniveau af størrelsesordenen 0,5 til 5 mg.
Fremgangsmåden ifølge opfindelsen er ejendommelig ved, at a) 1-2-(6-methoxy-2-naphthyl)-1-propanol oxideres, eller 10 b) d-2-(6-methoxy-2-naphthyl)-propionsyre reduceres.
Opfindelsen illustreres nærmere af følgende eksempler.
Eksempel 1.
En opløsning af 23 g d-2-(6-methoxy-2-naphthyl)-propionsyre (kendt fra sydafrikansk patent nr. 67/7597) i 100 ml benzol 15 og 20 ml thionylchlorid opvarmes under tilbagesvaling i 2 timer. Reaktionsblandingen inddampes så i vakuum til dannelse af det tilsvarende syrechlorid. En opløsning af remanensen i 300 ml tetrahydrofuran afkøles til -80°C og behandles med 47 g lithiumaluminiumtritertiær-butoxyhydrid 20 (2 molære ækvivalenter). Efter omrøring af reaktionsbland ingen ved denne temperatur i 1 time får blandingen lov at opvarmes til stuetemperatur og hældes i vand.
Blandingen ekstraheres så med benzol, og den organiske fase inddampes i vakuum til dannelse af d-2-(6-methoxy-2-25 naphthyl)-propanal, der omkrystalliseres af en blanding af dichlormethan og hexan.
Eksempel 2.
En opløsning af 58Q mg 1-2-(6-methoxy-2-naphthyl)-l-pro= panol (kendt fra dansk patent nr. 141.165) i 25 ml di=
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86521669A | 1969-10-09 | 1969-10-09 | |
| US86521669 | 1969-10-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK145820B true DK145820B (da) | 1983-03-14 |
| DK145820C DK145820C (da) | 1983-09-05 |
Family
ID=25344966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK186170A DK145820C (da) | 1969-10-09 | 1970-04-14 | Analogifremgangsmaade til fremstilling af d-2-(6-methoxy-2-naphthyl)-propanal |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS54908B1 (da) |
| BE (1) | BE747925A (da) |
| BR (1) | BR6915468D0 (da) |
| CA (1) | CA921492A (da) |
| CH (2) | CH546724A (da) |
| DE (2) | DE2043048C3 (da) |
| DK (1) | DK145820C (da) |
| ES (2) | ES383496A1 (da) |
| FI (1) | FI50521C (da) |
| FR (1) | FR2068541B1 (da) |
| GB (1) | GB1297306A (da) |
| IL (1) | IL33947A (da) |
| NL (1) | NL7004198A (da) |
| NO (1) | NO131593C (da) |
| SE (1) | SE362066B (da) |
| ZA (1) | ZA701177B (da) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK156642B (da) * | 1973-09-11 | 1989-09-18 | Beecham Group Ltd | Analogifremgangsmaade til fremstilling af napthalenderivater |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4912248A (en) * | 1987-05-18 | 1990-03-27 | The Procter & Gamble Company | Novel anti-inflammatory agents, pharmaceutical compositions and methods for reducing inflammation |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3562336A (en) * | 1968-07-24 | 1971-02-09 | Syntex Corp | Synthesis of naphthalene derivatives |
| US3637767A (en) * | 1968-07-30 | 1972-01-25 | Syntex Corp | 2-(6'-methoxynaphth-2'-yl)propylene oxide and 5'-halo derivatives |
-
1969
- 1969-12-19 BR BR215468/69A patent/BR6915468D0/pt unknown
-
1970
- 1970-02-23 ZA ZA701177A patent/ZA701177B/xx unknown
- 1970-02-23 CA CA075524A patent/CA921492A/en not_active Expired
- 1970-02-23 IL IL33947A patent/IL33947A/en unknown
- 1970-03-05 FI FI700605A patent/FI50521C/fi active
- 1970-03-10 GB GB1297306D patent/GB1297306A/en not_active Expired
- 1970-03-20 NO NO1043/70A patent/NO131593C/no unknown
- 1970-03-24 JP JP2479570A patent/JPS54908B1/ja active Pending
- 1970-03-24 NL NL7004198A patent/NL7004198A/xx unknown
- 1970-03-25 BE BE747925D patent/BE747925A/xx not_active IP Right Cessation
- 1970-04-14 DK DK186170A patent/DK145820C/da not_active IP Right Cessation
- 1970-04-20 FR FR707014295A patent/FR2068541B1/fr not_active Expired
- 1970-08-10 SE SE10932/70A patent/SE362066B/xx unknown
- 1970-08-27 CH CH149873A patent/CH546724A/xx not_active IP Right Cessation
- 1970-08-27 CH CH1286570A patent/CH549547A/xx not_active IP Right Cessation
- 1970-08-31 DE DE2043048A patent/DE2043048C3/de not_active Expired
- 1970-08-31 DE DE2065420A patent/DE2065420C2/de not_active Expired
- 1970-09-09 ES ES70383496A patent/ES383496A1/es not_active Expired
-
1973
- 1973-04-02 ES ES413265A patent/ES413265A1/es not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK156642B (da) * | 1973-09-11 | 1989-09-18 | Beecham Group Ltd | Analogifremgangsmaade til fremstilling af napthalenderivater |
Also Published As
| Publication number | Publication date |
|---|---|
| SE362066B (da) | 1973-11-26 |
| DK145820C (da) | 1983-09-05 |
| IL33947A (en) | 1973-06-29 |
| FR2068541A1 (da) | 1971-08-27 |
| GB1297306A (da) | 1972-11-22 |
| FI50521C (fi) | 1976-04-12 |
| DE2043048A1 (de) | 1971-04-22 |
| CH546724A (de) | 1974-03-15 |
| BE747925A (fr) | 1970-08-31 |
| NO131593B (da) | 1975-03-17 |
| IL33947A0 (en) | 1970-04-20 |
| NO131593C (da) | 1975-07-02 |
| BR6915468D0 (pt) | 1973-03-13 |
| ES383496A1 (es) | 1973-07-01 |
| CH549547A (de) | 1974-05-31 |
| DE2043048B2 (de) | 1973-11-15 |
| NL7004198A (da) | 1971-04-14 |
| CA921492A (en) | 1973-02-20 |
| ES413265A1 (es) | 1976-06-16 |
| ZA701177B (en) | 1971-09-29 |
| JPS54908B1 (da) | 1979-01-18 |
| DE2065420A1 (de) | 1973-07-05 |
| DE2043048C3 (de) | 1974-06-27 |
| DE2065420C2 (de) | 1982-07-22 |
| FI50521B (da) | 1975-12-31 |
| FR2068541B1 (da) | 1973-04-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU678063B2 (en) | Nitric esters having anti-inflammatory and/or analgesic activity and process for their preparation | |
| Beltrami et al. | Some Methylhydrazonium Salts; An Improved Synthesis of Tetramethylhydrazine1 | |
| IL22818A (en) | 4-Alcohol Acetic Acetic Acids and their History, Processes for Preparation and Pharmaceutical Preparations Containing Them | |
| EP0000200B1 (en) | New n-amidino-3,5-diamino-6-substituted-2-pyrazinecarboxamides and process for preparing same | |
| NO122370B (da) | ||
| DK145820B (da) | Analogifremgangsmaade til fremstilling af d-2-(6-methoxy-2-naphthyl)-propanal | |
| JPH0222059B2 (da) | ||
| US3976673A (en) | 4-Cyclopropylmethyleneoxy-3-chlorophenylacetic acid and salts thereof | |
| US3565943A (en) | 1-indancarboxylic acids and derivatives | |
| PT75581B (fr) | Procede de preparation de 1-azaxantone | |
| Brown et al. | Products of the Oxidation of Nitrolutidine and Nitrocollidine | |
| Jones et al. | Pyrazolines. VII. The Stereochemistry of the Thermal Decomposition of 5-Phenyl-1-pyrazolines1 | |
| JP3358069B2 (ja) | 三環性複素環類、その製造法及び剤 | |
| IL29707A (en) | Phenthiazine derivatives | |
| US2413656A (en) | Alpha-(meta-hydroxyphenyl)-beta-methylaminoethanol para-aminobenzoate | |
| US3275685A (en) | [(1-alkenylsulfonyl)phenoxy] alkanoic acids | |
| US4094988A (en) | Method of treating gastric ulcers using 5,6-dihydro-1,4-dithiinoxides | |
| DE1620308A1 (de) | Verfahren zur Herstellung von neuen heterocyclischen Verbindungen | |
| US3539585A (en) | 4-hydroxy-2-thiazoline-5-alkanoic acids | |
| Barger et al. | 140. Constitution of carpaine. Part III | |
| US2543187A (en) | Pharmaceutical intermediates | |
| SU386931A1 (ru) | Способ получения амидов 2,2-диметил-з- ацетиламиноциклобутилуксусной кислоты | |
| IE47335B1 (en) | Oxime derivatives of 7-amino-thiazolyl-acetamidocephalosporanic | |
| Dunn | Preparation of D and L Forms of Glycl-β-2-thienylalanine | |
| SU535273A1 (ru) | Способ получени 5,6,11,12-тетрахлортетрацена |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUP | Patent expired |