US3821227A - 4,7 dioxo 12h-cyclopenta (2, 1-8:3,4 g')diquinoline 2,9 dicarboxylic acid derivatives - Google Patents

4,7 dioxo 12h-cyclopenta (2, 1-8:3,4 g')diquinoline 2,9 dicarboxylic acid derivatives Download PDF

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US3821227A
US3821227A US00308035A US30803572A US3821227A US 3821227 A US3821227 A US 3821227A US 00308035 A US00308035 A US 00308035A US 30803572 A US30803572 A US 30803572A US 3821227 A US3821227 A US 3821227A
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diquinoline
cyclopenta
tetrahydro
dicarboxylic acid
dioxo
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C Hall
H Johnson
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Pharmacia and Upjohn Co
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Upjohn Co
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Priority to GB4510573A priority patent/GB1404284A/en
Priority to JP48120076A priority patent/JPS4981400A/ja
Priority to DE2356830A priority patent/DE2356830A1/de
Priority to FR7341082A priority patent/FR2206945B1/fr
Priority to BE137947A priority patent/BE807548A/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
    • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
    • C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
    • C07C2603/18—Fluorenes; Hydrogenated fluorenes

Definitions

  • compositions are useful in the prophylactic treatment of sensitized humans and mammals for allergy and all anaphylactic reactions of a reagin or non-reagin mediated nature.
  • the compounds of Formula 1, above are represented by the structural formulae la and lb, below, which are its tautomeric forms. It is to be understood that the compounds of this invention are likely to be mixtures of all tautomeric forms, the percentages of each tautomer being dependent on the nature of R and Z and the physical environment of the compound.
  • Z is selected from the group consisting of hydrogen, phenyl, and lower alkyl of 1 through 3 carbon atoms;
  • A is selected from the group Quit i wherein R' and R are selected from the group consisting of hydrogen-and lower alkyl of 1 through 6 carbon atoms.
  • alkali metals include lithium, sodium and potassium.
  • lower alkyl of from 1 through 3 carbon atoms include methyl, ethyl, propyl and isopropyl.
  • lower alkyl of 4 through 6 carbon atoms include butyl, pentyl and hexyl and the isomeric forms thereof
  • alkyl amine include monoethylamine, monomethylamine, mono- .propylamine, monoisopropylamine, diethylamine, di-
  • amine cation examples include all ymethyl)-aminomethane,
  • PROCESS A The compounds of the formula A 13i ROOC l [j wooon ki wherein A has the same meaning as above and R has the same meaning as above except hydrogen, are prepared by the steps comprising l. mixing a corresponding compound of the formula QOOCC E CCOOQ wherein Q is lower alkyl of 1 through 3 carbon atoms or phenyl with a corresponding compound of the formula A HQN- NH2 .2 a. H. V A wherein A has the same meaning as above, to yield a corresponding compound of the formula A QOOOC/ ooooo ooorrl J liHooo wherein A and Q have the same meaning as above;
  • a third step is required for preparing the compounds of thefor n l H H Hoes-@Ofi ooH 3 wherein A has the same meaning as above, namely, hydrolyzing a corresponding compound produced in the manner described in step (2) immediately above and having the formula wherein A and Q have the same meaning as above, e.g.,
  • the first step of Process A' comprises mixing a dialkylacetylene dicarboxylate (IV) with a compound of Formula [11, e.g., a 2,7-diaminofluorene, in a molar ratio of approximately 2 of the former (IV) to l of the latter (Ill) reactants, to yield a corresponding diadduct, a tetraalkyl 2,2'-[(fluorene-2,7-diyl)diimino]dibutendioate (ll).
  • Molar ratios in excess of 2:1 e.g., 3:1 to 5:1 are also satisfactory.
  • Appropriate solvents for the reaction are alkanols of from ,l through 6 carbon atoms, preferably of from 1 through 3 carbon atoms, benzene, diethylether, dioxane, tetrahydrofuran, or any other solvent which puts both reactants (IV and III) into solution and allows formation of the desired compound (ll).
  • the reaction proceeds readily at room temperature and can be accelerated by increasing the temperature to about 100C.
  • step (2) ring closure of a diadduct (ll) produced in step (1) and formation of the desired corresponding dialkyl l ,4,7, l -tetrahydro-4,7-dioxo-12H- cyclopenta[2, l -g:3,4 g'1diquinoline-2,9-dicarboxylate (l) is accomplished by heating said diadduct (ll) at a relatively high temperature.
  • the neat diadduct (ll) can be heated directly, but it is preferable to put it into a solvent that can function as a heat transfer medium.
  • any high boiling inert solvent such as a mineral oil, hexamethylphosphoric triamide, diphenyl ether, or Dowtherm A (a commercial mixture of diphenyl and diphenyl ether), is suitable.
  • the ring cyclization step is preferably carried out at temperatures of from about 220C. to about 280C, although lower or higher temperatures can be employed, if desired.
  • Particularly preferred solvents are Dowtherm A or diphenyl ether, which boil at about 250C, thus enabling the ring cyclization to occur during reflux. (At this point of the process, different esters'can be prepared at the R position of the carboxy group, e.g., by a standard transesterification reaction.)
  • An advantage of the elevated temperature during the ring cyclization step is that any adduct fonned in the preceding step which is not in a position to cyclize, since it is trans to the benzene ring, is isomerized to the cis configuration during the heating, thereby allowing substantial yields of the desired compound to be produced.
  • This trans adduct preparation occurs more frequently when an aprotic solvent and a dialkylacetylene dicarboxylate are used in the adduct formation step.
  • a 2,9-dicarboxylate ester (l) resulting from step (2) is converted to its corresponding 2,9-dicarboxylic acid (I) by treatment with a base (e.g., by heating the former with an aqueous so-.
  • a thus produceddicarboxylic acid (I) can be readily converted to acorresponding amine salt or alkali'metal derivative by contacting the former with two' equivalents of thc dcsired amine or alkali metal and heating in a sufficient amount of water to effect solubilization.
  • the crystalline salts can be precipitated by the addition of methanol.
  • PROCESS B The compounds of the formula 1. mixing, in the presence of an acid catalyst, a corresponding compound of the formula wherein Q and Z have the same meaning as above, with a corresponding compound of the formula A mN-@ @NH;
  • A has the same meaning as above, yield a corresponding compound of the formula wherein A, Q and Z have the same meaning as above; 2. heating a thus producedcorresponding compound resulting from step (1) to yield a corresponding compound of Formula I, above
  • a third step is required for preparing the compounds of the formula H /A )Tooon L v p I III E N aooo wherein A and Z have the same meaning as above, namely, hydrolyzing a corresponding compound produced in the manner described in step (2) immediately above and having the formula wherein A, Q and Z havethe same meaning as above, e.g., with an .alkali metal hydroxide and then adding thereto a strong acid.
  • the first step of Process B comprises mixing an alkali metal salt of a di(alkyl or phenyl) oxalacylate (IV') with a 2,7-diaminofluorene (III), in a molar ratio of at least 2 of the fonner (IV) to l of the latter (III) reactants, in the presence. of an acid catalyst, to yield a corresponding diadduct, a tetraalkyl 2,2'-[(9-oxofluorene- 2,6-diyl)diimino] bis 3-alkyl(or phenyl) butenedioate] (ll).
  • Molar ratios in excess of 2:l e.g., 3: l; to
  • oxaloacylate reagent (IV') When using the oxaloacylate reagent (IV') to form the diadduct, there should be a sufficient amount of acid present to-protonate the oxaloacylate carbon and catalyze the removal of the keto grouping as water.
  • the acid can also serve as a solvent for the two reagents as well.
  • glacial acetic acid, propionic acid, p-toluene sulfonic acid, and butyric acid are acids which can be used.
  • benzene, toluene, diethyl ether, dioxane, tetrahydrofuran, or alcohols from one to about four carbon atoms can be employed.
  • the length of time for the formation of the diadduct is temperature dependent. At room temperature the reaction proceeds rather slowly, but as the temperature is raised, reaction time is decreased. Acceptable reaction times are achieved at temperatures ranging from about 40 to about 70C., although reaction temperatures can be above 100C. if desired.
  • Additional purification of the products can be accomplished by conventional means, for example, by elution chromatography from an adsorbent column with a suitable solvent such as acetone, ethyl acetate, ether, methylene chloride and Skellysolve B (hexanes), mixtures and combinations of these solvents; also be gradient elution chromatography from an adsorbent column with a suitable mixtureof solvents, such as, methylene chloride- Skellysolve B, acetone-Skellysolve B, and the like.
  • a suitable solvent such as acetone, ethyl acetate, ether, methylene chloride and Skellysolve B (hexanes), mixtures and combinations of these solvents
  • a suitable mixtureof solvents such as, methylene chloride- Skellysolve B, acetone-Skellysolve B, and the like.
  • novel compounds (I) of this invention have antiallergic (especially anti-asthmatic) activity, inhibiting a positive Passive Cutaneous Anaphylactic (PCA) test induced by the rat immunochemical counterpart of human IgE (regain), and is considered indicative of inhibiting human allergic activity. This activity is apparent when these compounds are tested for their inhibition of the rat PCA reaction.
  • PCA assay is described by I. Mota in Immunology 5111 (1962).
  • ethylfluorene (III) (obtained as in Preparation 3) is treated with an excess 1.6 ml. in hexane) of butyl lithium. Methyl iodide is added to the reaction mixture,
  • EXAMPLE 1 1,4,7, 1 O-tetrahydro-4,7, l2-trioxol 2H-cyclopenta- [2,1-g:3,4-g]diquinoline-2,9-dicarboxylic acid
  • PART A Tetramethyl 2,2'-[(9-oxofluorene-2,7-diyl)diiminol-dibutendioate
  • PART B Dimethyl 1,4,7,10-tetrahydro-4,7,12-trioxo-l2H- cyclopenta[2,1-g:3,4-g']diquinoline-2,9-dicarboxylate 2 g. of the compound (II) obtained in Part A, above,
  • EXAMPLE 5 1 ,4,7, 1 0-Tetrahydro-4,7-dioxo-12-01-12H- cyclopenta[2,1-g:3,4-g]diquinoline-2,9-dicarboxylic acid (1) Following the procedure of Example 1 but substituting diisopropylacetylene dicarboxylate (1V) [prepared as in J. Chem. Soc. 678 (1948)] and 2,7-diaminofluoren-9-ol (lll) (prepared as in Ann. Chim.
  • EXAMPLE 7 1 ,4,7, l 0-Tetrahydro-4,7-dioxo'- l 2-ethyl- 1 2-01- 1 2H- cyclopenta[ 2, l -g:3 ,4-g' ]diquinoline-2,9-dicarboxylic acid (1) Following the procedure of Example 1 but substituting 2,7-diaminofluoren-9-ethyl-9-ol ([11) (obtained as in Preparation 1,-above) for 2,7-diaminofluoren-9-one (111) in Part A thereof, yields l,4,7,l0-tetrahydro-4,7-
  • EXAMPLE 8 1 ,4,7,10-Tetrahydro-4,7 dioxo-12-ethylidene-l 2H- cyclopenta[ 2, l -g: 3,4g]diquinoline-2,9-dicarboxylic acid (1)) Following the procedure of Example 1 but substituting 2,7-diamino-9-ethylidenefluorene (111) (obtained as in Preparation 2, above)'for 2,7-diaminofluoren-9-one (III) in Part A thereof, yields 1,4,7,10-tetrahydro-4,7- dioxo-l 2-ethylidene-12H-cyclopenta[2, l-g:3,4- g]diquinoline-Z,9-dicarboxylic acid (1).
  • EXAMPLE 10 1,4,7, 1 0-Tetrahydro-4,7-dioxol 2-ethyll 2-methyll 2H-cyclopenta[2, 1-g:3,4-g' ]diquinoline-2,9- dicarboxylic acid (1)
  • EXAMPLE 1 Di(tris-hydroxymethyl)methylammonium l ,4,7,10-tetrahydr0-4,7,12-trioxo-12H- cyclopenta[2,1-g:3,4-g']diquinoline-2,9-dicarboxylic acid (1) To 10ml of water, 1 g.
  • g]diquinolinc-2,9-dicarboxylic acid (1) is precipitated by the addition of methanol to the mixture.
  • an amine such as methylamine, dimethylamine, trimethylamineethylamine, diethylamine, triethylamine, propylamine, dipropylamine, tripropylamine, isopropylamine, diisopropylamine, triisopropylamine, ethanolamine, D-threo-2-amino-l-(p-nitrophenyl )-l ,3-propanediol, N,N-bis(hydroxyethyl)- piperazine, 2-amino-2-methyl-l-propanol, 2-amino-2- methyl-1,3-propanediol or 2,2-bis(hydroxymethyl)- 2,2,2"-nitrilotriethanol, yields the corresponding di- (substituted ammonium) salt of
  • compositions of the present invention are presented for administration to humans an animals in unit dosage forms, such as tablets, capsules, pills, suppositories, powders, granules, sterile parenteral solutions or suspensions, and oral solutions or suspensions, and oilin-water and water-in-oil emulsions containing suitable quantities of the compound of Formula la.
  • the preferred method of administration is by inhalation into the lung by means of an aerosol or powder for insufila- Mon.
  • either solid or fluid unit dosage forms can be prepared.
  • the compound of Formula la is mixed with conventional ingredients such as talc, magnesium stearate, dicalcium phosphate, magnesium aluminum silicate, calcium sulfate, starch, lactose, acacia, methylcellulose, and functionally similar materials as pharmaceutical diluents or carriers.
  • Capsules are prepared by mixing the compound with an inert pharmaceutical diluent and filling the mixture into a hard gelatin capsule of appropriate size.
  • Soft gelatin capsules are prepared by machine encapsulation of a slurry of the compound with an acceptable vegetable oil, light liquid petrolatum or other inert oil.
  • Fluid unit dosage forms for oral administration such as syrups, elixirs, and suspensions can be prepared.
  • the water-soluble forms can be dissolved in an aqueous vehicle together with sugar, aromatic flavoring agents and preservatives to form a symp.
  • An elixir is prepared by using a hydro-alcoholic (ethanol) vehicle with suitable sweeteners such as sugar and saccharin, together with an aromatic flavoring agent.
  • Suspensions can be prepared with a syrup vehicle with the aid of a suspending agent such as acacia, tragacanth, methylcellulose and the like.
  • fluid unit dosage forms are prepared utilizing the compound and a sterile vehicle, water being preferred.
  • the compound depending on the vehicle and concentration used, can be either suspended or dissolved in the vehicle.
  • the compound can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampul and sealing.
  • adjuvants such as a local anesthetic, preservative and buffering agents can be dissolved in the vehicle.
  • the composition can be frozen after filling into the vial and the water removed under vacuum. The dry lyophilized powder is then sealed in the vial and an accompanying vial of water for injection is supplied to reconstitute the liquid prior to use.
  • Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilization cannot be accomplished by filtration.
  • the compound can be sterilized by exposure to ethylene oxide before suspending in the sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound.
  • compositions are those adapted for inhalation into the lung and containing a water soluble form of a compound of the Formula la.
  • compositions for inhalation are of three basic types: l a powder mixture preferably micro-pulverized; (2) an aqueous solution to be sprayed with a neublizer; (3) an aerosol with volatile propellant in a pressurized container.
  • the powders are quite simply prepared by mixing a compound of the formula with a solid base which is compatible with lung tissue, preferably lactose.
  • the powders are packaged in a device adapted to emit a measured amount of powder when inhaled through the mouth.
  • Aqueous solutions are prepared by dissolving the compound of the Formula la in water and adding salt to provide as isotonic solution and buffering to a pH compatible with inhalation.
  • the solutions are dispersed in a spray device or nebulizer and sprayed into the mouth while inhaling.
  • Aerosols are prepared by dissolving a compound of the Formula I in water or ethanol and mixing with a volatile propellant and placing in a pressurized container having a metering valve to release a predetermined amount of material.
  • the liquefied propellant employed is one which has a boiling point below 65F. at atmospheric pressure.
  • the liquefied propellant should be non-toxic.
  • the suitable liquefied propellants which may be employed are the lower alkanes contain ing up to five carbon atoms, such as butane and pentane, or a lower alkyl chloride, such as methyl, ethyl, or propyl chlorides.
  • the most suitable liquefied propellants are the fluorinated and fluorochlorinated lower alkanes such as are sold underthe trademarks Freon and Genetron. Mixtures of the above-mentioned propellants may suitably be employed.
  • Examples of these propellants are dichlorodifluoromethane (Freon l2), dichlorotetrafluoroethane (Freon 1 l4), trichloromonofluoromethane (Freon l 1), dichloromonofluormethane (Freon 21 monochlorodifluormethane (Freon 22), trichlorotrifluoroethane (Freon 113), difluoroethane (Genetron l42-A) and monochlorotrifluoromethane (Freon 13).
  • unit dosage form as used .in the specifiuse in humans an animals, as disclosed in detail in this specification, these being features of the present invention.
  • suitable unit dosage forms in accord with this invention are tablets, capsules, pills, suppositories, powder packets, granules, wafers, cachets, teaspoonfuls, tablespoonfuls, dropperfuls, ampuls, vials, aerosols with metered discharges, segregated multiples of any of the foregoing, and other forms as herein described.
  • the dosage of the compound for treatment depends on the route of administration and the potency of the specific compound.
  • a .dosage schedule of from about 0.01 to 50 mg. embraces the effective range for preventing allergic attack for which the compositions are effective.
  • the dosage to be administered can be repeated up to 4 timesdaily.
  • a preferred dosage schedule reduces the secondary treatment dosage to from about 0.5% to about of the above dosages, more specifically, from about 1 to about 20% of the above dosages. In this manner a state of allergy prophylaxis can be maintained.
  • the reduced dosage is taken until that dosage no longer provides effective protection. At that T time the larger dosage is repeated, followed by the reduced dosage.
  • An example of such a dosage schedule is the following: An asthmatic insufflates 0.5 mg. of 1,4-
  • the oral dose is from about 0.1 to about 500 mg. in a single dose.
  • compositions of the present invention to humans an animals provides a method for the prophylactic treatment of allergy or all anaphylactic reactions of a reagin or non-reagin mediated nature. That is to say, these compositions when administered to a sensitized individual prior to the time that the individual comes into contact with substances (anti gens), to which he is allergic, will prevent the allergic reaction which would otherwise occur.
  • the process can be used for prophylactic treatment of such chronic conditions as bronchial asthma, allergic conjunctivitis, allergic rhinitis, food allergy, hay fever, urticaria, and auto-immune diseases.
  • EXAMPLE l2 A lot of 10,000 tablets, each containing 0.1 mg. of l,4,7,l0-tetrahydro-4,7,l2-trioxo-l2l-lcyclopenta[ 2, l-g:3,4-g' ]diquinoline-2,9-dicarboxylic acid (I) is prepared from the following types and amounts of ingredients:
  • These tablets are useful in preventing hay feverattacks at a dose of 1 tablet every four hours.
  • EXAMPLE 13 One thousand two-piece hard gelatin capsules, each containing mg. of l,4,7,'l0-tetrahydro-4,7,l2- trioxol 2H-cyclopenta[ 2, l-g:3,4-g' ]diquinoline-2,9- dicarboxylic acid (I) are prepared from the following types and amounts of ingredients:
  • the ingredients are mixed well and filled into capsules of the proper size.
  • EXAMPLE 14 One thousand tablets, each containing 500 mg. of 1,- 4,7, 1 0-tetrahydro-4,7, l2-trioxo-1 2H-cyclopenta[2, lg:3,4-g']diquinoline-2,9-dicarboxylic acid (I) are made from the following types and amounts of ingredients:
  • the ingredients are screened and blended together and pressed into 640 mg. tablets.
  • the tablets are useful to protect against food allergy at a dose of 1 tablet before meals.
  • EXAMPLE A sterile preparation suitable for intramuscular injec- One milliliter of this sterile preparation is injected for prophylactic treatment of allergic rhinitis.
  • EXAMPLE l6 Aqueous Solution 600 ml. of an aqueous solution containing 0.1 mg. of the tris(hydroxymethyl)aminomethane salt of 1,4,7,10- tetrahydro-4,7,12-trioxo-l2H-cyclopenta[2,1-g:3,4- g]diquinoline-2,9-dicarboxylic acid (1) per ml. is pre- 5 pared as follows:
  • the THAM salt and sodium chloride and dissolved in 55 sufficient water to make 600 ml. and sterile filtered.
  • the solution is placed in nebulizers designed to deliver 0.25 ml. of solution per spray.
  • the solution is sprayed into the lungs every four hours for prevention of asthmatic attacks.
  • EXAMPLE l7 Powder for lnsufflation A powder mixture consisting of mg. of tris(hydr- 6 4,7,12-trioxo-12H-cyc1openta[2,1-g:3,4- 5
  • Aerosol Twelve of an aerosol composition is prepared from the following ingredients:
  • the THAM salt is dissolved in the ethanol and chilled to -30C. and added to the chilled Freons.
  • the 12 grams of composition is added to a 13 cc. plastic coated bottle and capped with a metering valve.
  • the metering valve releases 8 mg. of composition in an aerosol.
  • the aerosol is inhaled every six hours for prevention of asthmatic attacks.
  • dicarboxylate (I), 1 ,4,7,10-tetrahydro-4,7-dioxo-1211- cyc1openta[2,1-g:3,4-g]diquino1ine-2,9-dicarbxylic acid (I), diisopropyl 1 ,4,7,10-tetrahydro-4,7-dioxo- 12- ethylidene-121-1-cyclopenta[2, l-g:3,4-g ]diquinoline- 2,9-dicarboxylate (I), disodium l,4,7,l-tetrahydro- 4,7-dioxol 2-ethylidenel 2H-cyclopenta[ 2, l -g:3 ,4 g ]diquinoline-2,9-dicarboxylate (I), 1,4,7, 1 O- tetrahydro-4,7dioxol 2-ethylidene- 1 2H- cycl
  • R and R are selected from the group consisting of hydrogen and lower alkyl of I through 6 carbon atoms 2.
  • R and Z are hydrogen and A is namely, 1 ,4,7,l0-tetrahydro-4,7,l2-trioxo-12H- cyclopenta[2,l-g:3,4-g]diquinoline-2,9-dicarboxy1ic acid.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
US00308035A 1972-11-20 1972-11-20 4,7 dioxo 12h-cyclopenta (2, 1-8:3,4 g')diquinoline 2,9 dicarboxylic acid derivatives Expired - Lifetime US3821227A (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
US00308035A US3821227A (en) 1972-11-20 1972-11-20 4,7 dioxo 12h-cyclopenta (2, 1-8:3,4 g')diquinoline 2,9 dicarboxylic acid derivatives
GB4510573A GB1404284A (en) 1972-11-20 1973-09-26 Cyclopenta their preparation
JP48120076A JPS4981400A (fr) 1972-11-20 1973-10-26
DE2356830A DE2356830A1 (de) 1972-11-20 1973-11-14 1,4,7,10-tetrahydro-4,7-dioxo-12hcyclopentadichinolin-2,9-dicarbonsaeurederivate, verfahren zu ihrer herstellung und arzneimittel, die diese verbindungen enthalten
FR7341082A FR2206945B1 (fr) 1972-11-20 1973-11-19
BE137947A BE807548A (fr) 1972-11-20 1973-11-20 Composes du type cyclopentane-diquinoleine et leur preparation

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US00308035A US3821227A (en) 1972-11-20 1972-11-20 4,7 dioxo 12h-cyclopenta (2, 1-8:3,4 g')diquinoline 2,9 dicarboxylic acid derivatives

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JP (1) JPS4981400A (fr)
BE (1) BE807548A (fr)
DE (1) DE2356830A1 (fr)
FR (1) FR2206945B1 (fr)
GB (1) GB1404284A (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3953598A (en) * 1972-09-08 1976-04-27 The Upjohn Company Compounds, compositions and methods of use
WO2020165394A1 (fr) * 2019-02-15 2020-08-20 Merck Patent Gmbh Composés polymérisables et leur utilisation dans des affichages à cristaux liquides

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05118062A (ja) * 1991-10-25 1993-05-14 Inax Corp 浴室用配管ユニツト
CN112778140B (zh) * 2020-12-29 2023-01-03 宁波博雅聚力新材料科技有限公司 一种含芴二胺单体、聚酰亚胺薄膜及其制备方法和用途

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3953598A (en) * 1972-09-08 1976-04-27 The Upjohn Company Compounds, compositions and methods of use
WO2020165394A1 (fr) * 2019-02-15 2020-08-20 Merck Patent Gmbh Composés polymérisables et leur utilisation dans des affichages à cristaux liquides
CN113423802A (zh) * 2019-02-15 2021-09-21 默克专利股份有限公司 可聚合化合物及其于液晶显示器中的用途
US11685863B2 (en) 2019-02-15 2023-06-27 Merck Patent Gmbh Polymerisable compounds and the use thereof in liquid-crystal displays
TWI826647B (zh) * 2019-02-15 2023-12-21 德商馬克專利公司 可聚合化合物及其在液晶顯示器中之用途
CN113423802B (zh) * 2019-02-15 2024-05-28 默克专利股份有限公司 可聚合化合物及其于液晶显示器中的用途

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GB1404284A (en) 1975-08-28
DE2356830A1 (de) 1974-06-06
FR2206945B1 (fr) 1977-11-10
BE807548A (fr) 1974-05-20
JPS4981400A (fr) 1974-08-06
FR2206945A1 (fr) 1974-06-14

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