US3833559A - Dibenzocycloheptenyl lactamimides - Google Patents

Dibenzocycloheptenyl lactamimides Download PDF

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Publication number
US3833559A
US3833559A US00321288A US32128873A US3833559A US 3833559 A US3833559 A US 3833559A US 00321288 A US00321288 A US 00321288A US 32128873 A US32128873 A US 32128873A US 3833559 A US3833559 A US 3833559A
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US
United States
Prior art keywords
dibenzo
dihydro
cycloheptan
imino
compounds
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
US00321288A
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English (en)
Inventor
M Grisar
Kenzie R Mac
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.)
Richardson Vicks Inc
Original Assignee
Richardson Merrell Inc
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 Richardson Merrell Inc filed Critical Richardson Merrell Inc
Priority to US00321288A priority Critical patent/US3833559A/en
Priority to ZA00738703A priority patent/ZA738703B/xx
Priority to AU62514/73A priority patent/AU476386B2/en
Priority to CA186,440A priority patent/CA1003826A/en
Priority to IL43703A priority patent/IL43703A/en
Priority to GB5521273A priority patent/GB1421058A/en
Priority to DE2361929A priority patent/DE2361929A1/de
Priority to JP48144809A priority patent/JPS604168B2/ja
Priority to FR7400316A priority patent/FR2213064B1/fr
Application granted granted Critical
Publication of US3833559A publication Critical patent/US3833559A/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
    • C07D227/00—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00
    • C07D227/02—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D227/06—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D227/10—Nitrogen atoms not forming part of a nitro radical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics

Definitions

  • n represents an integer of from 3 to 11.
  • This invention relates to novel dibenzocycloheptenyl lactamimide derivatives and pharmaceutically acceptable salts useful as diuretic agents, antiinflammatory agents, and anticoagulants.
  • novel compounds of this invention are dibenzocycloheptenyllactamimides as represented by the following general Formula I and pharmaccutically acceptable acid addition salts thereof.
  • n is an integer of from 3 to 11.
  • the compounds of Formula I have pharmacological activities as diuretic agents, antiinflammatory agents, ,or anticoagulants.
  • Pharmaceutical compositions containing the novel compounds of Formula -I and the administration of said compounds, either alone or in the form of a pharmaceutical composition, to a host for their biological activity are also included within the scope of the invention.v
  • Preferred compounds of this invention are those of Formulas I to III wherein n is an integer of from 3 to 7.
  • Pharmaceutically acceptable acid addition salts of the base compounds of this invention are those of any suitable inorganic or organic acids.
  • Suitable inorganic acids are, for example, hydrochloric, hydrobromic, sulfuric or phosphoric acids and the like.
  • Suitable organic acids are, for example, carboxylic acids such as acetic, propionic, glycolic, lactic, pyruvic, malonic, succinic, fumaric, malic, tartaric, citric, ascorbic, maleic, hydroxy-maleic, benzoic, hydroxybenzoic, phenylacetic, cinnamic, salicylic, 2- phenoxybenzoic and the like, or sulfonic acids such as methane sulfonic, 2-hydroxyethane sulfonic acid and the like.
  • novel compounds of this invention and pharmaceutically acceptable acid addition salts thereof are useful as diuretic agents, antiinflammatory agents and anticoagulants and can be administered to warm blooded animals and mammals, either alone or in the form of pharmaceutical preparations which contain the compounds suitable for oral or parenteral administration.
  • Pharmaceutical preparations containing compounds of this invention and conventional pharmaceutical carriers can be employed in unit dosage forms such as solids, for example, tablets and capsules, or liquid solutions, suspensions or elixirs for oral administration, or liquid solution, suspensions, emulsions, and the like for parenteral use.
  • the quantity of compound administered can vary over a wide range to provide from about 0.1 mg./kg. (milligrarns'per kilogram) to about 50 mg./ kg.
  • Unit doses of these compounds can contain from about 5 to-250 mg. of the compound and may be administered, for example, from 1 to 4 times daily.
  • Illustrative examples of pharmaceutical preparation containing novel compounds of this invention suitable for administration may be found in Examples 5 to 7 of this specification.-
  • n is an integer of from 3 to 11 and lower alkyl may be methyl, ethyl or the like, with 10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5-amine in a manner like that reported by R. E. Benson and T. L.
  • the reaction may be carried out either in the presence or absence of a solvent.
  • a solvent such as, methanol, ethanol or the like he used; however; other hydrocarbon solvents such as benzene, toluene and the like may be used.
  • a basic or acidic catalyst such as tertiary amine or hydrogen chloride may be added to the reaction mixture.
  • the hydrochloride salt of the amine be used in the reaction.
  • the temperature of the reaction can vary from 40 C. to 180 C., and the preferred temperature is about to about C.
  • the reaction time varies from about 1 hour to hours being dependent upon the temperature of the reaction and the reactant primary amine.
  • lactim ethers which find use in this reaction may be prepared from commercially available corresponding lactams by methods known in the art. For example, by
  • the compounds of this invention may also be prepared using a complex of an appropriate lactam with phosphorous oxychloride, phosgene, boronitri-fluoride etherate, dimethyl sulfate, hydrogen halide or a combination of two or more such reagents. This reaction has been studied by H. Bredereck in a series of articles in Chem.
  • a portion of the wheat starch is used to make a granulated starch paste which together with the remainder of the wheat starch and the lactose is granulated, screened and mixed with the active ingredient, that is, (a), and the magnesium stearate.
  • the mixture is compressed into tablets Weighing 150 mg. each.
  • the composition is prepared by dissolving the active ingredient, that is (a), and sufl'icient sodium chloride in Water for injection to render the solution isotonic.
  • the composition may be dispensed in a single ampule containing 100 mg. of the active ingredient for multiple dosage or in 20 ampules for single dosage.
  • EXAMPLE 7 An illustrative composition for hard gelatin capsules is as follows:
  • n is an integer of from 3 to 7.
  • a compound of claim 2 which is 2-[(10,11-dihydro- 5H dibenzo[a,d]cycloheptan 5 yl)imino]hexahydroazepine or a pharmaceutically acceptable acid addition salt thereof.
  • a compound of claim 2 which is 2-[(10,l1-dihydro- 5H dibenzo[a,d]cycloheptan 5 yl)imino]piperidine or a pharmaceutically acceptable acid addition salt thereof.
  • a compound of claim 2 which is 2-[(10,11-dihydro- 5H dibenzo[a,d]cycloheptan 5 yl)imino]octahydroazocine or a pharmaceutically acceptable acid addition salt thereof.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pyrrole Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
US00321288A 1973-01-05 1973-01-05 Dibenzocycloheptenyl lactamimides Expired - Lifetime US3833559A (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
US00321288A US3833559A (en) 1973-01-05 1973-01-05 Dibenzocycloheptenyl lactamimides
ZA00738703A ZA738703B (en) 1973-01-05 1973-11-13 Dibenzocycloheptenyl lactamimides
AU62514/73A AU476386B2 (en) 1973-01-05 1973-11-15 Dibenzocycloheptenyl lactamimides
CA186,440A CA1003826A (en) 1973-01-05 1973-11-22 Dibenzocycloheptenyl lactamimides
IL43703A IL43703A (en) 1973-01-05 1973-11-26 Divenzocyclohepthenyl lactamimides
GB5521273A GB1421058A (en) 1973-01-05 1973-11-28 Dibenzocycloheptenyl lactamimides
DE2361929A DE2361929A1 (de) 1973-01-05 1973-12-13 Dibenzocycloheptenyl-lactamimide und diese enthaltende pharmazeutische zusammensetzungen
JP48144809A JPS604168B2 (ja) 1973-01-05 1973-12-28 ジベンゾシクロヘプテニルラクタムイミド
FR7400316A FR2213064B1 (enrdf_load_stackoverflow) 1973-01-05 1974-01-04

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US00321288A US3833559A (en) 1973-01-05 1973-01-05 Dibenzocycloheptenyl lactamimides

Publications (1)

Publication Number Publication Date
US3833559A true US3833559A (en) 1974-09-03

Family

ID=23249975

Family Applications (1)

Application Number Title Priority Date Filing Date
US00321288A Expired - Lifetime US3833559A (en) 1973-01-05 1973-01-05 Dibenzocycloheptenyl lactamimides

Country Status (9)

Country Link
US (1) US3833559A (enrdf_load_stackoverflow)
JP (1) JPS604168B2 (enrdf_load_stackoverflow)
AU (1) AU476386B2 (enrdf_load_stackoverflow)
CA (1) CA1003826A (enrdf_load_stackoverflow)
DE (1) DE2361929A1 (enrdf_load_stackoverflow)
FR (1) FR2213064B1 (enrdf_load_stackoverflow)
GB (1) GB1421058A (enrdf_load_stackoverflow)
IL (1) IL43703A (enrdf_load_stackoverflow)
ZA (1) ZA738703B (enrdf_load_stackoverflow)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5010072A (en) * 1988-06-28 1991-04-23 Merrell Dow Pharmaceuticals Inc. Lactamimides as calcium antagonists
US5082837A (en) * 1988-06-28 1992-01-21 Merrell Dow Pharmaceuticals Lactamimides as calcium antagonists
US5198433A (en) * 1988-06-28 1993-03-30 Merrell Dow Pharmaceuticals Inc. Lactamimides as calcium antagonists

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA722441B (en) * 1971-05-13 1973-01-31 Richardson Merrell Inc 9-fluorenyl lactamimides

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5010072A (en) * 1988-06-28 1991-04-23 Merrell Dow Pharmaceuticals Inc. Lactamimides as calcium antagonists
US5082837A (en) * 1988-06-28 1992-01-21 Merrell Dow Pharmaceuticals Lactamimides as calcium antagonists
US5198433A (en) * 1988-06-28 1993-03-30 Merrell Dow Pharmaceuticals Inc. Lactamimides as calcium antagonists

Also Published As

Publication number Publication date
AU6251473A (en) 1975-05-15
IL43703A0 (en) 1974-03-14
FR2213064A1 (enrdf_load_stackoverflow) 1974-08-02
IL43703A (en) 1977-07-31
DE2361929A1 (de) 1974-07-18
JPS4995965A (enrdf_load_stackoverflow) 1974-09-11
GB1421058A (en) 1976-01-14
AU476386B2 (en) 1976-09-16
CA1003826A (en) 1977-01-18
FR2213064B1 (enrdf_load_stackoverflow) 1977-06-03
ZA738703B (en) 1975-02-26
JPS604168B2 (ja) 1985-02-01

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