DK143981B - Analogifremgangsmaade til fremstilling af 2-(2-pyridyl)-3-(p-chlorphenyl)-propylaminer - Google Patents

Analogifremgangsmaade til fremstilling af 2-(2-pyridyl)-3-(p-chlorphenyl)-propylaminer Download PDF

Info

Publication number
DK143981B
DK143981B DK534473AA DK534473A DK143981B DK 143981 B DK143981 B DK 143981B DK 534473A A DK534473A A DK 534473AA DK 534473 A DK534473 A DK 534473A DK 143981 B DK143981 B DK 143981B
Authority
DK
Denmark
Prior art keywords
pyridyl
propylamines
chlorphenyl
preparing
chlorophenyl
Prior art date
Application number
DK534473AA
Other languages
English (en)
Other versions
DK143981C (da
Inventor
W J Welstead
B T Merriman
Original Assignee
Robins Co Inc A H
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.)
Filing date
Publication date
Application filed by Robins Co Inc A H filed Critical Robins Co Inc A H
Publication of DK143981B publication Critical patent/DK143981B/da
Application granted granted Critical
Publication of DK143981C publication Critical patent/DK143981C/da

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/26—Radicals substituted by halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/57—Nitriles

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pyridine Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

(19) DANMARK (φ * yRa,
Wj (12) FREMLÆGGELSESSKRIFT od 143981 B
DIREKTORATET FOR PATENT- OG VAREMÆRKEVÆSENET
(21) Ansøgning nr. 55^V75 (51) lnt.CI.* C 07 D 213/38 (22) Indleveringsdag 1 · okt. 1 975 (24) Løbedag 1 · okt. 1975 (41) Aim. tilgængelig 5· apr. 197^· (44) Fremlagt 9 · nov · 1 9^1 (86) International ansøgning nr. - (86) International indleveringsdag - (85) Videreførelsesdag - (62) Stamansøgning nr. -
(30) Prioritet 2. okt. 1972, 29586?, US
(71) Ansøger A.H. ROBINS COMPANY INCORPORATED, Richmond, US.
(72) Opfinder William John Welstead Jr., US: Burt Trosey Merriman
Jr., US.
(74) Fuldmægtig Ingeniørfirmaet Budde, Schou & Co.
(54) Analogifremgangsmåde til fremF
stilling af 2-(2-pyridyl)-3-(p-chlor= phenyl)-propylaminer.
Den foreliggende opfindelse angår en analogifremgangsmåde til fremstilling af hidtil ukendte 2-(2-pyridyl)-3-(p-chlorphenyl)--propylaminer med formlen
O
OD /=\ 1 i r- C1\_J—CH— CH-CH2-Am
00 'V—V
^ hvori Am er en aminogruppe eller en dialkylaminogruppe med 1-6 carbon- atomer i hver alkyldel, eller farmaceutisk acceptable syreadditionssalte deraf, hvilken fremgangsmåde er ejendommelig ved, at man tt
O
2 143931 (a) omsætter 2-(2-p-chlorphenylethyl)-pyridin med formlen ci'G>’cH2’cH2'^ (ii) med en sekundær amin med formlen Am-H, hvori Am er som defineret ovenfor, og parafomaldehyd, eller (b) til dannelse af forbindelser for hvilke Am = NE^, omsætter a-p-chlorbenzyl-2-pyridylacetonitril med formlen O-™™ CH„ φ
Cl med lithiumaluminiumhydrid, hvorefter om ønsket en ved a) eller b) dannet forbindelse med formel I omdannes til et farmaceutisk acceptabelt syreadditionssalt.
De i dialkylaminogruppen indgående alkyldele har lige eller forgrenede kæder med 1 til 6 carbonatomer, med fortrinsvis ikke mere end 4 carbonatomer hver, og eksemplificeres ved sådanne grupper som methyl, ethyl, propyl, isopropyl, butyl, sek.butyl, tert.butyl, amyl, isoamyl og hexyl.
De farmaceutiske acceptable syreadditionssalte af baserne med formlen I dannes med ikke-toksiske organiske og uorganiske syrer. Eksempler på sådanne organiske salte er de med maleinsyre, fu-marsyre, vinsyre, og ravsyre dannede. Eksempler på sådanne uorganiske salte er de med saltsyre, hydrobromidsyre og phosphorsyre dannede.
De ved fremgangsmåden ifølge opfindelsen foretagne reaktionssekvenser kan gengives ved følgende reaktionsskema:
_ π o P
(a) —CH2-CH2“kv. ) + CH2° + ~v'l\_/“CH2-CH-CH2Ain 11 3 143981 ί^Ί __ (b) l^Njl-CHCN + LiAlHj- C1’\_y~tCH2 CH~CH2-NH2 CH_ I *· III 1
Cl hvori Am har den ovenfor anførte betydning.
Almen metode til fremstilling af 2-(2-pyridyl)-3-(p-chlorphenyl)-propylaminer (a) En lavere alkanol-vand-opløsning indeholdende 2—(2—p— -chlorphenyl[ethyl])-pyridin, en sekundær amin og paraformaldehyd koges under tilbagesvaling i et langvarigt tidsrum fra ea. 40 timer til ca. 100 timer, eller indtil alikvot^analyser af reaktionsblandingen ved hensigtsmæssige foranstaltninger som f.eks. gaschromatografi indicerer, at der er dannet et væsentligt udbytte af slutprodukt. Produktet isoleres fra reaktionsblandingen ved en passende fremgangsmåde såsom syre-base-ekstraktion, chromatoqrafi af olieresten på en magnesiumsilikatsøjle eller omdannelse af basen til et syreadditionssalt, som renses yderligere ved omkrystallisation fra et passende opløsningsmiddel.
(b) En omrørt tør etherblanding af lithiumaluminiumhy-drid og aluminiumchlorid behandles med en tør etheropløsning af a--p-chlorbenzyl-2-pyridylacetonitril. Efter omrøring i et tidsrum fra ca. 1 time til ca. 5 timer sønderdeles reaktionsblandingen forsigtigt ved tilsætning af vand, lagene adskilles, og produktet isoleres fra det organiske lag ved syre-base-ekstraktion. Produktet omdannes til et hensigtsmæssigt syreadditionssalt, som renses yderligere ved omkrystallisation fra et hensigtsmæssigt opløsningsmiddel.
Fra Chem. Abstr. bd. 52, nr. 1 (januar 1958), 378 c-e, kendes kondensation af a-(p-chlorphenyl)-a-(2-pyridyl)-acetonitril og bromacetonediethylacetal i nærværelse af NaNH2 efterfulgt af forsæbning og decarboxylering til dannelse af 1-p-chlorphenyl-l-(2-pyridyl)--3-oxobutan, der ved Leuckartreaktion giver 1-p-chlorphenyl-l-(2-py-ridyl)-3-dimethylaminobutan. Intet er anført om disse forbindelsers eventuelle farmakologiske aktivitet.
4 143981
Fra britisk patentskrift nr. 771.814 kendes propylaminer såsom 3-(p-chlorphenyl)-3-(2'-pyridyl)-dimethylaminopropan, der har antihistaminvirkning og anvendes til at behandle forskellige allergier.
Forbindelserne fremstillet ifølge opfindelsen udviser derimod god antisekretorisk virkning således som bestemt ved sænkning af rumfanget af mavesekretioner hos rotter ved fremgangsmåden med underbinding af mavemunden (Shays standardmetode). Herved er konstateret ED5Q-værdier på 14,0 mg/kg for forbindelsen fremstillet ifølge nedenstående eks. 2, medens ED^q er 21,0 mg/kg legemsvægt for forbindelsen i eks. 3.
Anvendelige midler indeholdende mindst én af forbindelserne ifølge opfindelsen i tilknytning til en farmaceutisk bærer eller et passende strækkemiddel kan fremstilles i overensstemmelse med konventionel teknik og præparationer.
Midlerne kan præpareres som dosisenheder, idet hver enhed er tilpasset eller indrettet til at tilvejebringe en fast dosis af aktiv bestanddel. Tabletter, kapsler og overtrukne tabletter er blot eksempler på foretrukne dosisenheder ifølge opfindelsen. Enhedsdoser kan være på 5 mg eller derover og ligger fortrinsvis på 25, 50 og 100 mg.
Midlet kan indgives til pattedyr for at undertrykke deres sekreteringsaktivitet, og den indgivende dosis vil afhænge af tilfældets alvorlighed og de almene betingelser såvel.’.som legemsvægten hos pattedyr, der er under behandling.
Udgangsmaterialer til fremstilling af de hidtil ukendte forbindelser ifølge opfindelsen er forbindelserne med ovenstående formler II og III. De er enten kommercielt tilgængelige, eller de kan fremstilles ved de umiddelbart nedenfor anførte fremgangsmåder til udgangsmaterialernes tilvejebringelse.
Fremstilling af udgangsmaterialer
Fremstilling 1 q-(p-Chlorbenzyliden)-2-pyridylacetonitril
En blanding af 20,0 g (0,17 mol) 2-pyridylacetonitril, g (0,25^ mol) p-ehlorbenzaldehyd, 13,S g ^0,03½ mol) 10/'s natriumhydroxidopløsning og 100 ml ethanol opvarmes til 50°C i 1,0 time. a-(p-chlorbenzyliden)-2-pyridylacetonitril fås i 66/'s udbytte efter opsamling fra den afkølede reaktionsblanding og krystallisation fra ethanol-vandblandingen.
5 143981
Analyse:
Beregnet for C^HgNgCl : C - 69,86% H = 2,77#, N = 11,64#,
Pundet : C *= 6g,84#, H = 3,81#, N = 11,69#.
Fremstilling 2 a- (p-chlorbenzyl)-2-pyridylacetonitril En opløsning af 34,7 g (0,145 mol) g-(p-chlorbenzyliden)--2-pyridylacetonitril i 150 ml methanol behandles med 10% palladium på trækul, og blandingen rystes ved 3 atmosfæres tryk i nitrogen ved stuetemperatur i 2 timer, i løbet af hvilket tidsrum der sker et trykfald på 0,7 atmosfære. Den filtrerede opløsning koncentreres ved nedsat tryk, hvilket giver 31,7 g remanens, som efter tyndtlagschromatografi viser tilstedeværelsen af to forbindelser. Chromatografering af remanensen på magnesiumsilicat giver 29,6 g (70,5%) a-(p-chlorbenzyl)-2-pyridylacetonitril.
Analyse:
Beregnet for C^H-^lS^Cl: C = 69,28%, H = 4,57%, N = 11,54%
Fundet: C = 69,78%, H = 4,64%, N = 11,61%.
Fremstilling 3 2-(p-Chlorphenethyl)-pyridin
En omrørt opløsning af 13,9 g (0,15 mol) 2-picolin i 90 ml tetrahydrofuran behandles med 105 ml butyllithium i hexan (15,14% bedømt ved forsøg svarende til 0,168 mol) ved -40°C. Efter 1,0 time indicerer alikvotanalyser 50%'s omsætning. Der tilsættes yderligere 40 ml (0,064 mol) butyllithium i hexan, og efter yderligere 1,0 times reaktionsperiode tilsættes 24,2 g (0,15 mol) p-chlorben-zylchlorid ved -45°C. Reaktionsblandingen holdes under -35°C i tre timer, hvorefter den tillades at nå op på stuetemperatur. Efter omrøring natten over hældes reaktionsblandingen op i vand, det organiske lag skilles fra, vaskes med vand, tørres (over magnesiumsulfat) og inddampes ved nedsat tryk, hvilket giver en remanens på 39,3 g. Destillation af remanensen ved 0,10 mm Hg giver tre fraktioner, der destillerer ved 115-120°C, 120-125°C og 130--135°C. De tre fraktioners vægt er 26,3 g (81,1%). Kernemagnetre-sonansspektret for fraktionerne 1 og 2 er helt i overensstemmelse med strukturen for 2-(p-chlorphenethyl)-pyridin.
6 143981
Fremgangsmåden ifølge opfindelsen Eksempel 1 3-(p-Chlorphenyl)-2-(2-pyridyl)-N,N-dimethylpropyl-amin-dlmaleat.
En omrørt blanding af 25,1 g (0,11 mol) 2-[2-(p-chlor-phenyl)ethyl]pyridin, 16,9 g (0,56 mol) paraformaldehyd, 75 g (0,92 mol) dimethylamin-hydrochlorid, 50 ml vand og 145 ml 95%'s ethanol koges under tilbagesvaling i 44 timer. Efter 17 timer er 50 ml methanol afdestilleret. Efter afslutningen af de 44 timer viser gaschromatografi af en alikvotdel, at 10-15% af udgangsmaterialet er tilbage. Den afkølede reaktionsblanding behandles med 200 ml 1 normal saltsyre og ekstraheres med 6 portioner chloroform på hver 100 ml. Den sure opløsning behandles med 5 normal natriumhydroxidopløsning, og det i base uopløselige produkt ekstraheres over i chloroform. De kombinerede chloroformekstrakter vaskes med vand, tørres (over magnesiumsulfat), og koncentreres under nedsat tryk til en olie (28,5 g). Olien (25,4 g) i isopropa-nol omdannes til dimaleat-saltet. Omkrystallisation af saltet fra ethylacetat giver 23 g (40%) af dimaleatsaltet, som smelter ved 86-88°C.
Analyse:
Beregnet for : C = 56,86%, H = 5,37%, N = 5,53%
Fundet : C = 56,92%, H = 5,43%, N = 5,56%.
Eksempel 2 3-(p-Chlorphenyl)-2-(2-pyridyl)-propylamin-fumarat
En omrørt opløsning af 1,27 g (0,03 mol) lithiumalu-miniumhydrid i 75 ml tør ether behandles med en suspension af 4,4 g (0,03 mol) aluminiumchlorid i 75 ml tør ether. Efter 5 minutter behandles den heterogene blanding dråbevis med en opløsning af 8,1 g (0,03 mol) a-(p-chlorbenzyl)-2-pyridylacetonitril i 100 ml tør ether. Reaktionsblandingen omrøres i 1 time, efter at tilsætningen er tilendebragt. Overskuddet af lithiumaluminiumhydrid sønderdeles med vand, og blandingen behandles med 42 ml svovlsyre og 33 ml vand. Etherlaget skilles fra, og det vandige sure lag ekstraheres flere gange med ether. Det sure lag gøres basisk med kaliumhydroxidopløsning til pH 11, og det basiske produkt ekstraheres med ether. De kombinerede etherekstrakter tørres (over magnesiumsulfat) og koncentreres under nedsat tryk til en olie (8,2 g).
7 143981
Den rå olie (7,5 g) omdannes til fumaratsaltet i isopropanol. Omkrystallisation af saltet fr alsopropanol-vand giver 8,5 g (70%) rent monofumaratsalt, der smelter ved 169-173°C. Den analytiske prøve (isopropanol-vand) smelter ved 172-174°C.
Analyse:
Beregnet for C28Hi9ClN2°4: C = 59,59%, H = 5,28%, N = 7,72%,
Fundet ( C = 59,51%, H = 5,30%, N = 7,59%.
DK534473A 1972-10-02 1973-10-01 Analogifremgangsmaade til fremstilling af 2-(2-pyridyl)-3-(p-chlorphenyl)-propylaminer DK143981C (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US29386372 1972-10-02
US00293863A US3819641A (en) 1972-10-02 1972-10-02 2-(2-pyridyl)-omega-phenylalkylamines

Publications (2)

Publication Number Publication Date
DK143981B true DK143981B (da) 1981-11-09
DK143981C DK143981C (da) 1982-04-26

Family

ID=23130909

Family Applications (1)

Application Number Title Priority Date Filing Date
DK534473A DK143981C (da) 1972-10-02 1973-10-01 Analogifremgangsmaade til fremstilling af 2-(2-pyridyl)-3-(p-chlorphenyl)-propylaminer

Country Status (19)

Country Link
US (1) US3819641A (da)
JP (1) JPS614832B2 (da)
AT (1) AT329558B (da)
AU (1) AU6067373A (da)
BE (1) BE805529A (da)
CA (1) CA1018169A (da)
CH (1) CH583704A5 (da)
DE (1) DE2349493A1 (da)
DK (1) DK143981C (da)
FI (1) FI56966C (da)
FR (1) FR2201099B1 (da)
GB (1) GB1440777A (da)
IE (1) IE40373B1 (da)
IL (1) IL43335A0 (da)
NL (1) NL178787C (da)
NO (1) NO140186C (da)
PH (1) PH10660A (da)
SE (1) SE394431B (da)
ZA (1) ZA737710B (da)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3923988A (en) * 1972-10-02 1975-12-02 Robins Co Inc A H 2-(2-pyridyl)-{107 -phenylalkylamines
US4562258A (en) * 1982-02-04 1985-12-31 Findlay John W A 6-[3-Amino-1-(4-tolyl)prop-1E-enyl]pyridine-2-carboxylic acid derivatives having antihistaminic activity
US4584382A (en) * 1983-02-01 1986-04-22 Findlay John W A Pyridyl acrylate compound
US4621094A (en) * 1983-03-10 1986-11-04 Findlay John W A Anti-histaminic pyridyl compounds
JPH0434982Y2 (da) * 1986-11-21 1992-08-19
US5430044A (en) * 1987-02-06 1995-07-04 Fisons Corporation Arylalkyl-amines and -amides having anticonvulsant and neuroprotective properties
CN108314631A (zh) * 2018-04-19 2018-07-24 中国科学院昆明植物研究所 二芳基乙烯类化合物及其药物组合物和其应用

Also Published As

Publication number Publication date
NL7313472A (da) 1974-04-04
CH583704A5 (da) 1977-01-14
FI56966C (fi) 1980-05-12
IL43335A0 (en) 1973-11-28
GB1440777A (en) 1976-06-23
ZA737710B (da) 1974-08-28
IE40373L (en) 1974-04-02
NO140186C (no) 1979-07-18
DE2349493A1 (de) 1974-04-18
DK143981C (da) 1982-04-26
US3819641A (en) 1974-06-25
FR2201099A1 (da) 1974-04-26
AU6067373A (en) 1975-03-27
AT329558B (de) 1976-05-25
FI56966B (fi) 1980-01-31
PH10660A (en) 1977-07-27
FR2201099B1 (da) 1977-01-28
JPS49132077A (da) 1974-12-18
NL178787B (nl) 1985-12-16
SE394431B (sv) 1977-06-27
BE805529A (fr) 1974-02-01
JPS614832B2 (da) 1986-02-13
NO140186B (no) 1979-04-09
ATA843073A (de) 1975-08-15
IE40373B1 (en) 1979-05-23
CA1018169A (en) 1977-09-27
NL178787C (nl) 1986-05-16

Similar Documents

Publication Publication Date Title
US8906943B2 (en) Synthetic compounds and methods to decrease nicotine self-administration
EP0310950B1 (en) Quinoline intermediates for the synthesis of 1H-imidazo[4,5-c]quinolines and 1H-imidazo[4,5-c]quinolin-4-amimes
KR100274104B1 (ko) 포스포디에스테라제 억제제로서의 피리도[2,3-d]피리미딘 유도체, 이의 제조방법 및 이를 함유하는 약제학적 조성물
EP0241006B1 (en) 3,3-disubstituted indolines
US20060247439A1 (en) Mchir antagonists
US6900232B2 (en) Cycloalkyl alkanoic acids as integrin receptor antagonists
NO760993L (da)
EP0311010A2 (en) Alpha,Alpha-disubstituted aromatics and heteroaromatics as cognition enhancers
TW200401776A (en) Novel quinuclidine carbamate derivatives and medicinal compositions containing the same
DK143981B (da) Analogifremgangsmaade til fremstilling af 2-(2-pyridyl)-3-(p-chlorphenyl)-propylaminer
US4297359A (en) Anti-ulcer compositions containing certain pyridyl oxime ethers
WO1989008653A1 (en) 1H/3H-[4-(N,N-DICYCLOALKYL/BRANCHED-ALKYLCARBOXAMIDO)-BENZYL]IMIDAZO[4,5-c]PYRIDINES AS PAF ANTAGONISTS
FI89492C (fi) Foerfarande foer framstaellning av farmakologiskt vaerdefulla tetrahydro-6h-tiazolo/5,4-d/azepiner
US4327213A (en) Alpha-hydrocarbonoxyimino-pyrazineacetonitriles
EP0222474B1 (en) Gamma-carbolines
EP0244201B1 (en) 3-hydroxypyridines
FI75560C (fi) Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 4-(hydroxialkyltiometyl)pyridiner.
US7456192B2 (en) 3β-amino azabicyclooctane heteroaromatic amid derivatives preparation method and therapeutic uses thereof
US7091357B2 (en) Chain-modified pyridino-N substituted nicotine compounds for use in the treatment of CNS pathologies
US4751228A (en) 1,6-naphthyridine derivatives
EP0035820B1 (en) Novel quinoline derivatives, pharmaceutical compositions containing such compounds, and method for the preparation of these compounds
IL36400A (en) Process for the manufacture of quinoline derivatives and intermediates therefor
SK287098B6 (sk) Deriváty fenyl- a pyridyl-tetrahydropyridínu, spôsob ich prípravy a farmaceutická kompozícia, ktorá ich obsahuje, a použitie
KR100302216B1 (ko) 새로운니코틴산에스테르화합물및그제조방법
DK150158B (da) Analogifremgangsmaade til fremstilling af 4-phenylthieno-(2,3-c)piperidiner eller fysiologisk acceptable syreadditionssalte deraf