US3652567A - Quinazolinone derivative and process for the production thereof - Google Patents

Quinazolinone derivative and process for the production thereof Download PDF

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Publication number
US3652567A
US3652567A US866719A US3652567DA US3652567A US 3652567 A US3652567 A US 3652567A US 866719 A US866719 A US 866719A US 3652567D A US3652567D A US 3652567DA US 3652567 A US3652567 A US 3652567A
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US
United States
Prior art keywords
methyl
quinazoline
hydroxypropyl
phenylpiperazine
compound
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
US866719A
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English (en)
Inventor
Karl-Heinz Boltze
Dietrich Lorenz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Troponwerke Dinklage and Co
Original Assignee
Troponwerke Dinklage and Co
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 Troponwerke Dinklage and Co filed Critical Troponwerke Dinklage and Co
Application granted granted Critical
Publication of US3652567A publication Critical patent/US3652567A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F27/00—Details of transformers or inductances, in general

Definitions

  • This invention relates to a new quinazolinone derivative and to a process for the production thereof.
  • the invention provides as a new chemical compound 2-methy1-3- ⁇ 3-[4-phenylpiperazinyl-(1)] 2 hydroxypropyl ⁇ -quinazoline-4-one (hereinafter referred to as I) having the following formula:
  • the LD values with the mouse are very high, being mg./kg. intravenously and 710 mg./kg. per os; 500 mg./ kg. per os are tolerated without reaction by the rabbit. This shows a very low toxicity of the compound I.
  • the compound according to the invention may be prepared by the condensation of l-phenylpiperazine with 2- methyl-3-[3-bromo-2-hydroxypropyl] quinazoline-4-one or by the addition to it of 2-methyl-3- [2,3-epoxypropyl1- quinazoline-4-one or by condensing 2-methylquinazoline- 4-one with epichlorhydrin and then adding to it l-phenylpiperazine preferably without isolation of the intermediate.
  • the invention therefore also provides a process for the preparation of the 2-methyl-3- ⁇ 3 [4 phenylpiperazinyl- (1) ]-2-hydroxypropyl ⁇ -quinazo1ine-4-one in which (a) l-phenylpiperazine is condensed with 2-methyl-3- [3-bromo-2-hydroxypropyl]-quinazoline-4-one or (b) 2 methyl-3-[2,3-epoxypropyl]-quinazoline-4-one is reacted with l-phenylpiperazine; or
  • the reactions can be carried out in the absence of solvents at temperatures above C. and also in the presence of organic solvents, such as ethyl alcohol, at room temperature or higher temperature.
  • the compound according to the invention may be formulated with a pharmaceutical carrier to provide formulations adapted for the particular route of administration in particular the oral route, for example in the form of a syrup, elixir or the like or as a tablet or capsule.
  • EXAMPLE 2 10.8 g. of 2-methyl-3-(2,3-epoxypropyl)-quinazoline-4- one and 8.1 g. of l-phenylpiperazine are boiled for 4 hours in 70 ml. of absolute ethanol and the solution is kept for several hours at room temperature and then in the cold. The substance which precipitates is filtered 01?, the contents of the filter are washed-with ether and then crystallised from ethanol. 14.2 g. of 2-methyl-3- ⁇ 3-[4- phenylpiperazinyl 1 ]-2-hydroxypropyl ⁇ -quinazoline-4- one are formed, corresponding to 75% of the theoretical.
  • EXAMPLE 3 29.2 g. of 2-methylquinazoline-4-one and 70 m1. 82.5 g.) of epichlorhydrin are dissolved in methanol and then an equimolar quantity of sodium methylate in methanol is added. After standing for 12 hours at room temperature, the viscous mass which forms (39.6 g.) is filtered off, removed from the filter and maintained with 44.5 g. of l-phenylpiperazine for 30 minutes in an oil bath at 110 C. The mass (84 g. crude yield) is then worked up as previously described.
  • wa 2-methyl-3- ⁇ 3-[4-phenylpiperaziny1-(1) ]-2-hydroxypropyl ⁇ quinazolin-4-one.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Power Engineering (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (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)
  • Plural Heterocyclic Compounds (AREA)
US866719A 1968-10-16 1969-10-15 Quinazolinone derivative and process for the production thereof Expired - Lifetime US3652567A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19681803210 DE1803210A1 (de) 1968-10-16 1968-10-16 2-Methyl-3-(3-[4-phenylpiperazinyl-(1)]-2-hydroxypropyl)-chinazolinon-(4) und Verfahren zu seiner Herstellung

Publications (1)

Publication Number Publication Date
US3652567A true US3652567A (en) 1972-03-28

Family

ID=5710568

Family Applications (1)

Application Number Title Priority Date Filing Date
US866719A Expired - Lifetime US3652567A (en) 1968-10-16 1969-10-15 Quinazolinone derivative and process for the production thereof

Country Status (7)

Country Link
US (1) US3652567A (de)
CH (1) CH531524A (de)
DE (1) DE1803210A1 (de)
FI (1) FI52725C (de)
FR (1) FR2020814B1 (de)
GB (1) GB1245316A (de)
SE (1) SE378422B (de)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3879393A (en) * 1973-06-18 1975-04-22 Miles Lab Derivatives of 1,3-disubstituted 2,4(1h,3h)-quinazolinediones
DE4203050A1 (de) * 1992-02-04 1992-12-10 Heiko Delecate Kombinierter niederspannungs-solarstrom-druckluftmotor fuer beliebig hohe abtriebsleistung und mehreren grossen abtriebsdrehmomenten
WO2005123694A3 (en) * 2004-06-17 2006-04-13 Novartis Ag Quinazolinone compounds for the treatment of cough
US8552015B2 (en) 2002-02-06 2013-10-08 Novartis Ag Quinazolinone derivatives and their use as CB agonists

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1936588A1 (de) * 1969-07-18 1971-02-18 Troponwerke Dinklage & Co Pharmakologisch wirksame Chinazolinon-Verbindung,ihre Verwendung in pharmakologischen Zubereitungen und Verfahren zu ihrer Herstellung

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3231572A (en) * 1963-08-05 1966-01-25 Miles Lab 3-substituted-4-quinazolones

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3879393A (en) * 1973-06-18 1975-04-22 Miles Lab Derivatives of 1,3-disubstituted 2,4(1h,3h)-quinazolinediones
DE4203050A1 (de) * 1992-02-04 1992-12-10 Heiko Delecate Kombinierter niederspannungs-solarstrom-druckluftmotor fuer beliebig hohe abtriebsleistung und mehreren grossen abtriebsdrehmomenten
US8552015B2 (en) 2002-02-06 2013-10-08 Novartis Ag Quinazolinone derivatives and their use as CB agonists
WO2005123694A3 (en) * 2004-06-17 2006-04-13 Novartis Ag Quinazolinone compounds for the treatment of cough
US20080004296A1 (en) * 2004-06-17 2008-01-03 Christine Charman Organic Compounds

Also Published As

Publication number Publication date
FR2020814B1 (de) 1974-02-01
DE1803210A1 (de) 1970-05-14
FI52725B (de) 1977-08-01
GB1245316A (en) 1971-09-08
CH531524A (de) 1972-12-15
SE378422B (de) 1975-09-01
FR2020814A1 (de) 1970-07-17
FI52725C (fi) 1977-11-10

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