CH436297A - Process for the preparation of 11-basic substituted dibenz (b, f) - (1,4) oxazepine - Google Patents

Process for the preparation of 11-basic substituted dibenz (b, f) - (1,4) oxazepine

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Publication number
CH436297A
CH436297A CH676263A CH676263A CH436297A CH 436297 A CH436297 A CH 436297A CH 676263 A CH676263 A CH 676263A CH 676263 A CH676263 A CH 676263A CH 436297 A CH436297 A CH 436297A
Authority
CH
Switzerland
Prior art keywords
sep
formula
base
oxazepine
dibenz
Prior art date
Application number
CH676263A
Other languages
German (de)
Inventor
Jean Dr Schmutz
Fritz Dr Hunziker
Martin Kuenzle Frans
Original Assignee
Wander Ag Dr A
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
Priority to CH1646466A priority Critical patent/CH450426A/en
Priority to CH1646266A priority patent/CH450424A/en
Priority to CH1646366A priority patent/CH450425A/en
Priority to FR974433A priority patent/FR3485M/en
Priority to GB21056/64A priority patent/GB1045903A/en
Priority to SE12185/65A priority patent/SE317382B/xx
Priority to DE1470426A priority patent/DE1470426C3/en
Priority to AT973765A priority patent/AT252925B/en
Priority to AT455864A priority patent/AT258912B/en
Priority to FR975816A priority patent/FR3488M/en
Priority to CH676263A priority patent/CH436297A/en
Priority to ES300317A priority patent/ES300317A1/en
Application filed by Wander Ag Dr A filed Critical Wander Ag Dr A
Priority to NO153434A priority patent/NO115657B/no
Priority to FI1159/64A priority patent/FI42214B/fi
Priority to NL646406089A priority patent/NL140242B/en
Priority to DK269464AA priority patent/DK107552C/en
Priority to DK145665AA priority patent/DK107481C/en
Priority to DK145765AA priority patent/DK107482C/en
Priority to BE648683A priority patent/BE648683A/xx
Priority to DK145865AA priority patent/DK118463B/en
Priority to AT973665A priority patent/AT250975B/en
Priority to SE12187/65A priority patent/SE300111B/xx
Publication of CH436297A publication Critical patent/CH436297A/en
Priority to US797281A priority patent/US3546226A/en
Priority to US29279A priority patent/US3683034A/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D267/02—Seven-membered rings
    • C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
    • C07D267/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D267/16—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with two six-membered rings
    • C07D267/20—[b, f]-condensed
    • 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

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (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)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

  

  



  Verfahren zur Herstellung 11-basisch substituierter   Dibenzlb, fl-l1,    4] oxazepine
Die Erfindung betrifft ein Verfahren von gegebenenfalls in den Benzolkernen durch Halogenatome, Trifluormethylgruppen oder 1 bis 3 C-Atome enthaltende Alkyl-, Alkoxy-oder Alkylmercaptogruppen ein-oder mehrfach substituierten   llbasisch    substituierten Dibenz [b, f]   [1,    4] oxazepinen der Formel :
EMI1.1     
   worinRt einWasserstoffatom    oder eine   1    bis 3 C-Atome enthaltende Alkyl-, Alkoxyalkyl-oder Hydroxyalkylgruppe, welch letztere auch acyliert sein kann, darstellt, sowie von   Säure-Additionssalzen    davon.



   Die gewünschten Produkte   (I)    werden erfindungsgemäss erhalten, wenn man in den Benzolkernen gegebenenfalls entsprechend substituierte Verbindungen der Formel :
EMI1.2     
 mit reaktionsfähigen Estern von Alkoholen der Formel   Ri-OH,    worin   Ri    die genannte Bedeutung hat, umsetzt, wobei die Reaktionsprodukte in Form der freien Basen oder von Säureadditionssalzen gewonnen werden. Als reaktionsfähige Ester von Alkoholen der Formel   RI-OH    kommen insbesondere   Halogenwasserstoffsäureester    in Betracht. Die Umsetzung erfolgt vorzugsweise in einem inerten Lösungsmittel, z. B. Benzol, durch Erwärmen auf Rückflusstemperatur.



   Die in der beschriebenen Weise erhaltenen Basen sind in den meisten Fällen kristallisierbar, sonst im Hochvakuum unzersetzt destillierbar, und bilden mit anorganischen und organischen Säuren, beispielsweise Salzsäure, Bromwasserstoffsäure, SchwefelsÏure, Sal  petersäure,    Phosphorsäure, Essigsäure Oxalsäure, Weinsäure, Toluolsulfonsäure und dergleichen, in Wasser beständige Additionssalze, in welcher Form die Produkte ebenfalls verwendet werden können.



   Die in der beschriebenen Weise erhaltenen Basen und ihre Säure-Additionssalze sind neue Verbindungen, die als Wirkstoffe in Arzneimitteln oder als Zwischenprodukte zur Herstellung von solchen Verwendung finden. Insbesondere fallen die Produkte als Neuroplegika, Neuroleptika und Analgetika in Betracht. Einzelne davon eignen sich zur Behandlung psychotischer Zustände. Diese Wirksamkeit äussert sich pharmakologisch in starker   Motilitätsdämpfung    bei Mäusen, die mit kataleptischer Wirkung einhergehen kann. Die   Motilitätsdämpfung    wird durch Messung der   Laufaktivität    nach der Methode von Caviezel und Baillod [Pharm. Acta Helv. 33, 469 (1958)] erfasst.



  Die   Laufaktivitätswerte    einiger erfindungsgemässer Produkte sowie deren Toxizität werden in der folgenden Tabelle I mit den entsprechenden Zahlen für Chlorpromazin verglichen.



      Tabelle I    Wirkstoff ToxizitÏt Maus LaufaktivitÏt Maus
LD50 mg/kg p.o. ED50 mg/kg p.o.



  Chlorpromazin 135 3, 5   11- (4-Methyl-1-piperazinyl)-    dibenz [b, f]   [1,      4]-oxazepin    230 2, 7 2-Chlor-11- (4-methyl-1-piperazinyl) dibenz [b, f] [1,   4]-oxazepin    47 0, 05   2-Brom-11- (4-methyl-1-piperazinyl)-       dibenz [b,    f]   [1,    4]-oxazepin 95 0, 05 2-Fluor-11- (4-methyl-1-piperazinyl) dibenz [b, f]   [1,      4]-oxazepin    120 0, 13 4-Chlor-11-(4-methyl-1-piperazinyl) dibenz [b, f]   [1,      4]-oxazepin    800 5, 4   8-Chlor-11- (4-methyl-1-piperazinyl)-    dibenz [b, f]   [1,      4]-oxazepin    410 10, 5
Beispiel 1
Zu einer auf 60  C erwärmten Lösung von 6,

   26 g 2-Chlor-ll- (l-piperazinyl)-dibenz [b, f]   [1,    4] oxazepin in 50 ml Benzol wird eine Lösung von 1, 42 g Methyliodid in 30 ml Benzol getropft. Das Gemisch wird während 30 Minuten unter Rückfluss erwärmt. Nach dem Abkühlen nutscht man das Hydroiodid des Ausgangsmaterials ab und dampft das Filtrat im Vakuum zur Trockne ein. Der Rückstand wird aus   Aceton/Petroläther    kristallisiert, wobei man 2,7 g 2-Chlor-11-(4-methyl-1piperazinyl)-dibenz[b,f][l,4]oxazepin vom Schmelzpunkt 109-110¯C erhÏlt.



   In analoger Weise wie im vorerwähnten Beispiel erhalt man aus entsprechenden Ausgangsstoffen die in der nachfolgenden Tabelle II genannten Produkte. In der rechten Kolonne bedeutet Ac Aceton, Ae Ather, Ch Chloroform und Pe   Petroläther.   



   Tabelle   11   
Substituenten Beispiel Ri in den Benzol-Physikalische Konstanten kernen    2-CH3    H Smp. der Base :   97-98     C (aus Pe)    3-CH3    7-Cl Smp. der Base : 147-148¯ C (aus Pe)    4-CHs    2, 8-Dichlor Smp. der Base : 130-131¯ C (aus   Ae/Pe)   
5 -CH3 4, 8-Dichlor Smp. der Base : 134-135¯ C (aus Ae/Pe)    6-CH3 4-CH3    Smp. der Base :   179-182  C    (aus Ac/Pe)    7-CH3 2-CH3    Smp. der Base : 130-131¯ C (aus   Ae/Pe)       8-CH3      4-Cl    Smp. der Base : 173-174¯ C (aus   Ac/Pe)       9-CH3 6-Cl    Smp. der Base :

     83-87       C    (aus Pe)    10 ZI3 3-CH3    Smp. der Base :   103-105  C    (aus Ae/Pe)    11 CH3 2-Br    Smp. der Base :   95-99     C (aus Pe) 
Substituenten Beispiel Ri in den Benzol-Physikalische Konstanten kernen
EMI3.1     


<tb> 12-CH3 <SEP> 3, <SEP> 4-Dimethyl, <SEP> Smp. <SEP> der <SEP> Base <SEP> : <SEP> 167-168  <SEP> C <SEP> (aus <SEP> Ac/Pe)
<tb> 13-CH3 <SEP> 2-F <SEP> Smp. <SEP> der <SEP> Base <SEP> : <SEP> 81-86  <SEP> C <SEP> (aus <SEP> Pe)
<tb> 14-CH3 <SEP> 1, <SEP> 4-Dimethyl <SEP> Smp. <SEP> der <SEP> Base <SEP> : <SEP> 143-144  <SEP> C <SEP> (aus <SEP> Ae/Pe)
<tb> 15-CH3 <SEP> 3-Cl <SEP> Smp. <SEP> der <SEP> Base <SEP> :

   <SEP> 122-124  <SEP> C <SEP> (aus <SEP> Ae/Pe)
<tb> 16- <SEP> (CH2) <SEP> 2-OH <SEP> 2-Cl <SEP> Smp. <SEP> des <SEP> Dihydrochlorids <SEP> : <SEP> 197-237 C <SEP> (aus <SEP> Me/Ae)
<tb> 17-CH3 <SEP> 4-CH3 <SEP> ; <SEP> 8-Cl <SEP> Smp. <SEP> der <SEP> Base <SEP> : <SEP> 151-152  <SEP> C <SEP> (aus <SEP> Ae/Pe)
<tb> 18-CH3 <SEP> 2-OGH3 <SEP> Smp. <SEP> der <SEP> Base <SEP> : <SEP> 107-108  <SEP> C <SEP> (aus <SEP> Ae/Pe)
<tb> 19 <SEP> CEI3 <SEP> 4-C2H5 <SEP> Smp. <SEP> der <SEP> Base <SEP> : <SEP> 128-130  <SEP> C <SEP> (aus <SEP> Ae/Pe)
<tb> 20-CH3 <SEP> 2, <SEP> 4-Dichlor <SEP> Smp. <SEP> der <SEP> Base <SEP> : <SEP> 135-138  <SEP> C <SEP> (aus <SEP> Ac/Pe)
<tb> 21-CH3 <SEP> 4-CH3 <SEP> ; <SEP> 7-Cl <SEP> Smp. <SEP> der <SEP> Base <SEP> : <SEP> 167-168  <SEP> C <SEP> (aus <SEP> Ac/Ae)
<tb>  <SEP> O <SEP> 2-Cl <SEP> Smp. <SEP> des <SEP> Dihydrochlorids <SEP> :

   <SEP> 155-160  <SEP> C
<tb>  <SEP> ll <SEP> (aus <SEP> Essigester/Me/Ae)
<tb> 22-CH2CH20-C-CH3
<tb>



  



  Process for the preparation of 11-base substituted dibenzlb, fl-l1, 4] oxazepines
The invention relates to a process for dibenz [b, f] [1, 4] oxazepines of the formula optionally substituted one or more times in the benzene nuclei by halogen atoms, trifluoromethyl groups or alkyl, alkoxy or alkyl mercapto groups containing 1 or 3 carbon atoms :
EMI1.1
   wherein Rt represents a hydrogen atom or an alkyl, alkoxyalkyl or hydroxyalkyl group containing 1 to 3 C atoms, which latter can also be acylated, as well as acid addition salts thereof.



   The desired products (I) are obtained according to the invention if, if appropriate, correspondingly substituted compounds of the formula are used in the benzene nuclei:
EMI1.2
 with reactive esters of alcohols of the formula Ri-OH, in which Ri has the meaning mentioned, the reaction products being obtained in the form of the free bases or of acid addition salts. Particularly suitable reactive esters of alcohols of the formula RI-OH are hydrohalic acid esters. The reaction is preferably carried out in an inert solvent, e.g. B. benzene, by heating to reflux temperature.



   The bases obtained in the manner described are in most cases crystallizable, otherwise they can be distilled without decomposition in a high vacuum, and form with inorganic and organic acids, for example hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, oxalic acid, tartaric acid, toluenesulfonic acid and the like in Water-resistant addition salts, in which form the products can also be used.



   The bases obtained in the manner described and their acid addition salts are new compounds which are used as active ingredients in medicaments or as intermediates for the preparation of such use. In particular, the products come into consideration as neuroplegics, neuroleptics and analgesics. Some of them are suitable for the treatment of psychotic states. This efficacy manifests itself pharmacologically in a strong reduction in motility in mice, which can be associated with cataleptic effects. The motility damping is determined by measuring the running activity according to the method of Caviezel and Baillod [Pharm. Acta Helv. 33, 469 (1958)].



  The running activity values of some products according to the invention and their toxicity are compared in Table I below with the corresponding figures for chlorpromazine.



      Table I active substance toxicity mouse running activity mouse
LD50 mg / kg p.o. ED50 mg / kg p.o.



  Chlorpromazine 135 3, 5 11- (4-methyl-1-piperazinyl) -dibenz [b, f] [1,4] -oxazepine 230 2, 7 2-chloro-11- (4-methyl-1-piperazinyl) dibenz [b, f] [1,4] -oxazepine 47 0.05 2-Bromo-11- (4-methyl-1-piperazinyl) -dibenz [b, f] [1,4] -oxazepine 95 0.05 2 -Fluoro-11- (4-methyl-1-piperazinyl) dibenz [b, f] [1, 4] -oxazepine 120 0.13 4-chloro-11- (4-methyl-1-piperazinyl) dibenz [b, f] [1, 4] -oxazepine 800 5, 4 8-chloro-11- (4-methyl-1-piperazinyl) -dibenz [b, f] [1, 4] -oxazepine 410 10, 5
example 1
To a solution of 6 heated to 60 C,

   A solution of 1.42 g of methyl iodide in 30 ml of benzene is added dropwise to 26 g of 2-chloro-II- (l-piperazinyl) -dibenz [b, f] [1, 4] oxazepine in 50 ml of benzene. The mixture is refluxed for 30 minutes. After cooling, the hydroiodide of the starting material is suction filtered and the filtrate is evaporated to dryness in vacuo. The residue is crystallized from acetone / petroleum ether, 2.7 g of 2-chloro-11- (4-methyl-1piperazinyl) -dibenz [b, f] [l, 4] oxazepine having a melting point of 109-110 ° C.



   In a manner analogous to that in the aforementioned example, the products listed in Table II below are obtained from appropriate starting materials. In the right column, acetone means acetone, Ae means ether, Ch means chloroform and Pe means petroleum ether.



   Table 11
Substituents Example Ri in the benzene-physical constants nuclei 2-CH3 H mp. Of the base: 97-98 C (from Pe) 3-CH3 7-Cl. Mp. Of the base: 147-148¯ C (from Pe) 4-CHs 2,8-dichloro mp. Of the base: 130-131¯ C (from Ae / Pe)
5 -CH3 4, 8-dichloro M.p. of the base: 134-135¯ C (from Ae / Pe) 6-CH3 4-CH3 M.p. of the base: 179-182 C (from Ac / Pe) 7-CH3 2- CH3 melting point of the base: 130-131¯ C (from Ae / Pe) 8-CH3 4-Cl melting point of the base: 173-174¯ C (from Ac / Pe) 9-CH3 6-Cl melting point of the base:

     83-87 C (from Pe) 10 ZI3 3-CH3 mp. Of the base: 103-105 C (from Ae / Pe) 11 CH3 2-Br. Mp. Of the base: 95-99 C (from Pe)
Substituents example Ri in the benzene-physical constants nuclei
EMI3.1


<tb> 12-CH3 <SEP> 3, <SEP> 4-dimethyl, <SEP> Smp. <SEP> of the <SEP> base <SEP>: <SEP> 167-168 <SEP> C <SEP> (from <SEP> Ac / Pe)
<tb> 13-CH3 <SEP> 2-F <SEP> Smp. <SEP> of the <SEP> Base <SEP>: <SEP> 81-86 <SEP> C <SEP> (from <SEP> Pe)
<tb> 14-CH3 <SEP> 1, <SEP> 4-dimethyl <SEP> Smp. <SEP> of the <SEP> base <SEP>: <SEP> 143-144 <SEP> C <SEP> (from < SEP> Ae / Pe)
<tb> 15-CH3 <SEP> 3-Cl <SEP> Smp. <SEP> of the <SEP> Base <SEP>:

   <SEP> 122-124 <SEP> C <SEP> (from <SEP> Ae / Pe)
<tb> 16- <SEP> (CH2) <SEP> 2-OH <SEP> 2-Cl <SEP> m.p. <SEP> of the <SEP> dihydrochloride <SEP>: <SEP> 197-237 C <SEP> (from <SEP> Me / Ae)
<tb> 17-CH3 <SEP> 4-CH3 <SEP>; <SEP> 8-Cl <SEP> Smp. <SEP> of the <SEP> Base <SEP>: <SEP> 151-152 <SEP> C <SEP> (from <SEP> Ae / Pe)
<tb> 18-CH3 <SEP> 2-OGH3 <SEP> Smp. <SEP> of the <SEP> Base <SEP>: <SEP> 107-108 <SEP> C <SEP> (from <SEP> Ae / Pe )
<tb> 19 <SEP> CEI3 <SEP> 4-C2H5 <SEP> Smp. <SEP> of the <SEP> Base <SEP>: <SEP> 128-130 <SEP> C <SEP> (from <SEP> Ae / Pe)
<tb> 20-CH3 <SEP> 2, <SEP> 4-dichloro <SEP> Smp. <SEP> of the <SEP> base <SEP>: <SEP> 135-138 <SEP> C <SEP> (from < SEP> Ac / Pe)
<tb> 21-CH3 <SEP> 4-CH3 <SEP>; <SEP> 7-Cl <SEP> Smp. <SEP> of the <SEP> Base <SEP>: <SEP> 167-168 <SEP> C <SEP> (from <SEP> Ac / Ae)
<tb> <SEP> O <SEP> 2-Cl <SEP> Smp. <SEP> of the <SEP> dihydrochloride <SEP>:

   <SEP> 155-160 <SEP> C
<tb> <SEP> ll <SEP> (from <SEP> ethyl acetate / Me / Ae)
<tb> 22-CH2CH20-C-CH3
<tb>

Claims (1)

PATENTANSPRUCH Verfahren zur Herstellung von gegebenenfalls in den Benzolkernen durch Halogenatome, Trifluormethylgruppen oder 1 bis 3 C-Atome enthaltende Alkyl-, Alkoxy-oder Alkylmercaptogruppen ein-oder mehrfach substituierten llbasisch substituierten Dibenz [b, f] [1, 4] oxazepinen der Formel : EMI3.2 worin Ri eine 1 bis 3 C-Atome enthaltende Alkyl-, Alkoxyalkyl-oder Hydroxyalkylgruppe, welch letztere auch acyliert sein kann, darstellt, sowie von Säure Additionssalzen davon, dadurch gekennzeichnet, dass man in den Benzolkernen gegebenenfalls entsprechend substituierte Verbindungen der Formel : PATENT CLAIM Process for the preparation of optionally substituted basic substituted dibenz [b, f] [1, 4] oxazepines with halogen atoms, trifluoromethyl groups or 1 to 3 carbon atoms containing alkyl, alkoxy or alkyl mercapto groups in the benzene nuclei of the formula: EMI3.2 wherein Ri is an alkyl, alkoxyalkyl or hydroxyalkyl group containing 1 to 3 carbon atoms, which latter can also be acylated, and acid addition salts thereof, characterized in that optionally correspondingly substituted compounds of the formula: EMI3.3 mit reaktionsfähigen Estern von Alkoholen der Formel Ri-OH, worin Ri die genannte Bedeutung hat, umsetzt, wobei die Reaktionsprodukte in Form der freien Basen oder von Säure-Additionssalzen gewonnen werden. EMI3.3 with reactive esters of alcohols of the formula Ri-OH, in which Ri has the meaning mentioned, the reaction products being obtained in the form of the free bases or of acid addition salts. Anmerkung des Eidg. Amtes für geistiges Eigentum : Sollten Teile der Beschreibung mit der im Patentanspruch gegebenen Definition der Erfindung nicht in Einklang stehen, so sei daran erinnert, dass gemäss Art. 51 des Patentgesetzes der Patentanspruch für den sachlichen Geltungsbereich des Patentes massgebend ist. Note from the Federal Office for Intellectual Property: If parts of the description are not in accordance with the definition of the invention given in the patent claim, it should be remembered that according to Art. 51 of the Patent Act, the patent claim is decisive for the material scope of the patent.
CH676263A 1963-03-01 1964-05-27 Process for the preparation of 11-basic substituted dibenz (b, f) - (1,4) oxazepine CH436297A (en)

Priority Applications (24)

Application Number Priority Date Filing Date Title
CH1646466A CH450426A (en) 1963-03-01 1963-09-27 Process for the preparation of 11-basic substituted dibenz (b, f) (1,4) oxazepine
CH1646266A CH450424A (en) 1963-03-01 1963-09-27 Process for the preparation of 11-basic substituted dibenz (b, f) (1,4) oxazepine
CH1646366A CH450425A (en) 1963-03-01 1963-09-27 Process for the preparation of 11-basic substituted dibenz (b, f) (1,4) oxazepine
FR974433A FR3485M (en) 1963-03-01 1964-05-14 5-nitro-2-furylthioamide.
GB21056/64A GB1045903A (en) 1963-09-27 1964-05-21 Dibenzoxazepines
SE12185/65A SE317382B (en) 1963-09-27 1964-05-22
DE1470426A DE1470426C3 (en) 1963-09-27 1964-05-25 Dibenz [bfl [1,4] oxazepine derivatives and process for their preparation
AT455864A AT258912B (en) 1964-05-27 1964-05-26 Process for the production of new 11-basic substituted dibenz [b, f] [1,4] oxazepines
FR975816A FR3488M (en) 1963-09-27 1964-05-26 Dibenz [b, f] [1,4] oxazepines substituted with basic groups at position 11, useful as neuroplegic, neuroleptic and analgesic agents.
AT973765A AT252925B (en) 1964-05-27 1964-05-26 Process for the production of new 11-basic substituted dibenz [b, f] [1,4] oxazepines
ES300317A ES300317A1 (en) 1963-09-27 1964-05-27 Procedure for the obtaining of 11-basic replacements dibenzo [b'f] [1,4] oxacepinas (Machine-translation by Google Translate, not legally binding)
CH676263A CH436297A (en) 1964-05-27 1964-05-27 Process for the preparation of 11-basic substituted dibenz (b, f) - (1,4) oxazepine
NO153434A NO115657B (en) 1963-09-27 1964-05-28
FI1159/64A FI42214B (en) 1963-09-27 1964-05-28
DK145665AA DK107481C (en) 1963-09-27 1964-05-29 Process for the preparation of dibenz (b, f) (1,4) oxazepines or acid addition salts thereof basicly substituted in the 11-position.
DK269464AA DK107552C (en) 1963-09-27 1964-05-29 Process for the preparation of dibenz (b, f) (1,4) oxazepines or acid addition salts thereof basicly substituted in the 11-position.
NL646406089A NL140242B (en) 1963-03-01 1964-05-29 METHOD FOR PREPARING THE 11-PLACE SUBSTITUTED DIBENZ (B.F.) (1.4) OXAZEPINES BY A BASIC GROUP.
DK145765AA DK107482C (en) 1963-09-27 1964-05-29 Process for the preparation of dibenz (b, f) (1,4) oxazepines or acid addition salts thereof basicly substituted in the 11-position.
BE648683A BE648683A (en) 1963-09-27 1964-12-01
DK145865AA DK118463B (en) 1963-09-27 1965-03-22 Analogous process for the preparation of dibenz (b, f) (1,4) oxazepines or acid addition salts thereof basicly substituted in the 11-position.
AT973665A AT250975B (en) 1964-05-27 1965-05-26 Process for the production of new 11-basic substituted dibenz [b, f] [1, 4] oxazepines
SE12187/65A SE300111B (en) 1963-09-27 1965-09-20
US797281A US3546226A (en) 1963-03-01 1969-02-06 11-basic-substituted dibenzoxazepines
US29279A US3683034A (en) 1963-09-27 1970-04-16 Process for the preparation of substituted hydroquinones

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH676263A CH436297A (en) 1964-05-27 1964-05-27 Process for the preparation of 11-basic substituted dibenz (b, f) - (1,4) oxazepine

Publications (1)

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CH436297A true CH436297A (en) 1967-05-31

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CH (1) CH436297A (en)

Cited By (8)

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US6890919B2 (en) 2001-06-26 2005-05-10 Shitij Kapur Atypical antipsychotic agents having low affinity for the D2 receptor
US8288372B2 (en) 2002-11-26 2012-10-16 Alexza Pharmaceuticals, Inc. Method for treating headache with loxapine
WO2004047844A1 (en) * 2002-11-26 2004-06-10 Alexza Pharmaceuticals, Inc. Use of loxapine and amoxapine for the manufacture of a medicament for the treatment of pain
US9370629B2 (en) 2003-05-21 2016-06-21 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US8991387B2 (en) 2003-05-21 2015-03-31 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US8387612B2 (en) 2003-05-21 2013-03-05 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US7550454B2 (en) 2003-12-22 2009-06-23 Acadia Pharmaceuticals, Inc. Amino substituted diaryl[a,d]cycloheptene analogs as muscarinic agonists and methods of treatment of neuropsychiatric disorders
US7622461B2 (en) 2003-12-22 2009-11-24 Acadia Pharmaceuticals Inc. Amino substituted diaryl[a,d]cycloheptene analogs as muscarinic agonists and methods of treatment of neuropsychiatric disorders
US7517871B2 (en) 2003-12-22 2009-04-14 Acadia Pharmaceuticals, Inc. Amino substituted diaryl[a,d]cycloheptene analogs as muscarinic agonists and methods of treatment of neuropsychiatric disorders
US7491715B2 (en) 2003-12-22 2009-02-17 Acadia Pharmaceuticals, Inc. Amino substituted diaryl[a,d]cycloheptene analogs as muscarinic agonists and methods of treatment of neuropsychiatric disorders
US11642473B2 (en) 2007-03-09 2023-05-09 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
US12138383B2 (en) 2007-03-09 2024-11-12 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
US12214118B2 (en) 2018-02-02 2025-02-04 Alexza Pharmaceuticals, Inc. Electrical condensation aerosol device
US12214119B2 (en) 2018-02-02 2025-02-04 Alexza Pharmaceuticals, Inc. Electrical condensation aerosol device
EP4428132A1 (en) * 2023-03-08 2024-09-11 Johann-Wolfgang-Goethe-Universität Frankfurt am Main Slack-activating compounds and their medical use
WO2024184543A1 (en) * 2023-03-08 2024-09-12 Johann Wolfgang Goethe-Universität Frankfurt am Main Slack-activating compounds and their medical use

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