US3895034A - 1 OR 2-Mono and dialkyl substituted thienobenzopyrans - Google Patents

1 OR 2-Mono and dialkyl substituted thienobenzopyrans Download PDF

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US3895034A
US3895034A US392636A US39263673A US3895034A US 3895034 A US3895034 A US 3895034A US 392636 A US392636 A US 392636A US 39263673 A US39263673 A US 39263673A US 3895034 A US3895034 A US 3895034A
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Prior art keywords
methyl
thieno
dihydro
hydroxy
benzopyran
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Martin Winn
Raj Kumar Razdan
Haldean Cloyce Dalzell
Joyce Ruth Krei
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Sharps Associates
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Sharps Associates
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Priority to US392636A priority Critical patent/US3895034A/en
Priority to AU71746/74A priority patent/AU481685B2/en
Priority to GB3748174A priority patent/GB1473117A/en
Priority to DE2441206A priority patent/DE2441206A1/de
Priority to FR7429450A priority patent/FR2242090B1/fr
Priority to JP49098460A priority patent/JPS5050398A/ja
Priority to CA208,086A priority patent/CA1029023A/en
Priority to US05/524,626 priority patent/US3946111A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups

Definitions

  • R is a lower alkyl group having 1 to 5 carbons
  • R is hydrogen or a lower alkyl group having 1 to 5 carbons
  • R is a lower alkyl group
  • R is an alkyl group having 1 to 20 carbon atoms, a phenyllower alkyl group or a cycloalkyl-lower alkyl group.
  • the compounds have analgesic, antihypertensive, antidepressant, anticonvulsant, antianxiety, sedativehypnotic and/or tranquilization activity.
  • novel l,2-dihydro-4H-thieno[2,3- c][ l] benzopyrans of the fomiula wherein R is a lower alkyl group having 1 to carbon atoms and R, is hydrogen or a lower alkyl group having 1 to 5 carbon atoms, and when R and R, are both lower alkyl such groups can be on the same or different carbon atoms in the thieno ring, R is a lower alkyl group and R is an alkyl group having 1 to 20 carbon atoms, a phenyl-lower alkyl group or a cycloalkyl-lower alkyl group, and novel intermediates useful in making such compounds.
  • R and R When R and R are both in the l-position on the thieno ring, generally only one of such groups will be alkyl and the other will be hydrogen.
  • the compounds where R is an alkyl having 5 to carbons are particularly useful as are the compounds when R, R and R are lower alkyl groups having 1 to 3 carbon atoms, and especially methyl.
  • lower-alkyl means saturated, monovalent aliphatic-radicals, including straight and branched-chain radicals of from 1 to 6 carbon atoms, as illustrated by, but not limited to methyl, ethyl, propyl, isopropyl, butyl, see-butyl, amyl, hexyl and the like.
  • alkyl means saturated, monovalent aliphatic radicals, including straight and branched chain radicals of from 1 to 20 carbon atoms, as illustrated by, but not limited to methyl, n-amyl, nhexyl, Z-heptyl, n-heptyl, 3-methyl-2-octyl, n-octyl, 2- nonyl, Z-tetradecyl, n-hexadecyl, 2-eicosanyl, and the like.
  • cycloalkyl means cyclic, saturated aliphatic-radicals of from three to eight carbon atoms, as illustrated by, but not limited to cyclopropyl, cyclobutyl, 2-methylcyclobutyl, cyclohexyl, 4- methylcyclohexyl, cyclooctyl, and the like.
  • phenyl-lower alkyl means a monovalent radical consisting of a phenyl nucleus bonded to the rest of the molecule, respectively, through a divalent lower-alkylene radical of from 1 to '6 carbon atoms as illustrated by, but not limited to methylene, l',l-ethylene, 1,2-ethylene, 1,3-propylene, 1,2-propylene. 1,4-butylene, and the like.
  • benzene or phenyl ring can bear any number and kind of substituents such as would occur to the person skilled in organic chemistry.
  • substituents include lower-alkyl, lower-alkoxy, halo (chloro. bromo, iodo orfluoro), nitro, lower-alkylmercapto. and the like.
  • the compounds of Formula 1 can be prepared by re acting a S-substituted resorcinol of Formula 2 Formula 2 wherein R has the previously assigned significance, with a 3-oxo-tetrahydrothiophene-Z-carboxylate of Formula 3 COOR4 S wherein R represents a lower alkyl group, to produce a 1,2-dihydro-4-oxo-4H-thieno-[2,3-c]1 l lbenzopyran of Formula 4 Formula 3 R R g 1 0H 0 0 R Formula 4 which can then be reacted with a lower alkyl magnesium halide to produce a compound of Formula 5 which is then reacted with an acid such as hydrochloric acid or p-toluene sulfonic acid to dehydrate it to produce a 4,4-dialkyll ,2-dihydro-9-hydroXy-7-R -4H- thieno-[2,3- c][ l lbenzopyran
  • 5-,substituted resorcinols whichcan ,be used in the processare 5-(3-methyl-2-octyl)resorcinol, S-n-pentylresorcinol, .5-benzylresorcinol, 1;:5-(3- phenylpropyl) resorcinol, 5-[2-(p-fluorophenyl)ethy l] resorcinol, S-cyclopentylmethyl resorcinol and 5-(3- cyclohexylpropyl) resorcinol.
  • the resorcinol starting materials are disclosed in the chemical literature and many are commercially available.
  • the 3-oxo-tetrahydrothiophene-Z-carboxylates, and others within the scope of Formula 3, which can be used in the invention can be produced by the known Dieckmann cyclization of a di-lower alkyl 4 or 5-R 4 or 5 R -3-thiahexanedioate. This can be illustrated by the cyclization of dimethyl 5-methyl-3- thiahexanedioate to methyl 4-methyl-3-oxotetrahydrothiophene-2-carboxylate according to the following reaction:
  • the process in which the 5-substituted resorcinol is reacted with a 3-oxo-tetrahydrothiophene-Z- carboxylate of Formula 3 to produce a compound of Formula 4 is readily effected by bringing the reactants together in a suitable liquid reaction medium in the presence of an acid catalyst. Hydrochloric acid dissolved in ethanol is suitable for conducting the reaction.
  • the reaction can be carried out also in a mixture of concentrated sulfuric acid and phosphorous oxychloride, or in phosphorus oxychloride either alone or in an organic solvent, for example benzene or toluene.
  • the product can be recovered from the reaction mixture by conventional means.
  • the compounds of Formula 4 can be converted to the compounds of Formula 5 by reacting a compound of Formula 4 with an alkyl magnesium halide such as methyl magnesium chloride, ethyl magnesium iodide or propyl magnesium chloride.
  • the reaction can be effected by bringing the reactants together in a suitable inert liquid reaction medium such as diethyl ether, dibutyl ether, tetrahydrofuran, anisole and pyridine.
  • the reaction proceeds rapidly at reflux temperature.
  • the desired product of Formula 5 can be isolated from the reaction mixture by standard methods after the reaction is terminated, it is generally not advantageous to isolate the triol. Instead, the trio] of Formula 5 can be treated, without isolation, with an acid to convert it to a compound of Formula 1.
  • the compounds of this invention have antihypertensive, antidepressant, analgesic, anticonvulsant and/or antianxiety activity in animals and such activities indicates potential human use for the compounds as drugs.
  • the pharmacological activity for the compounds having the nuclear alkyl substituents in the c-ring of this invention is surprisingly different from the activity of the prior art related compound l,2-dihydro-4,4- dimethyl-9-hydroxy-7-( 3 -methyl-2-octyl )-4H-thieno- [2,3-c][1]benzopyran (SP-6) disclosed in Nature, Vol. 226, June 27, 1970, pp. 1265-67 which does not have an alkyl group in the c-ring.
  • Audiogenic seizure test for anticonvulsant activity Poltnikoff, N.P., J. Pharmacol, Exp. Therap. 119, 294 (1957).
  • SP-6 at an oral dose of 1.0 mg./kg. caused an increase of 30 minutes in total sleep time in EEG sleep (sedative-hypnotic) studies in cats. This increase was a result of an increase of 49 minutes in the slow wave stage of sleep, a decrease of 19 minutes in the spindle stage, and no change in the rapid eye movement (REM) stage.
  • REM rapid eye movement
  • SP-6 caused an increase of 31 minutes in total sleep time.
  • SP-6 by these tests has antihypertensive, antidepressant, anticonvulsant, sedafive-hypnotic and anti-anxiety or tranquilization activity.
  • SP-l47 caused a 62% reduction in fighting behavior in the mouse fighting test.
  • SP-l47 had very potent activity in the hot plate (ED 1.4 mg./kg. p.o.), writhing (ED 4.7 mg./kg., p.o.), and rat tail flick (ED 1.4 mg./kg. p.o.) analgesic tests.
  • SP-147 at an oral dose of 0.1 mg./kg. caused an increase of 21 minutes in total sleep time in EEG sleep (sedativehypnotic) studies in cats.
  • SPA-l6 at an oral dose of 30 mg./kg., protected 20% of the mice from the convulsions. At an oral dose of 10 mg./kg., SPA- l 6 caused a 40% reduction in fighting behavior in the mouse fighting test. SPA-16 had no analgesic activity at the doses employed. Activity in these tests indicates SPA-16 is useful as an antidepressant agent.
  • SPA- 19 1,2-dihydro-9-hydroxy-7-( 3-methyl-2-octyl)-2,2,4,4- tetramethyI-4I-I-thieno-[2,3-c][ l ]benzopyran (SPA- 19) administered orally in a dose of 10 mg./kg., showed no reduction in the systolic blood pressure of geneti-' cally hypertensive rats. In an oral dose of 20 mg./kg., it showed marked activity in the mouse modified DOPA potentiation test. In the audiogenic seizure test, SPA-19 in an oral dose of 30 mg./kg., protected 20% of the mice from the convulsions.
  • SPA- 19 caused a 36% reduction in fighting behavior in the mouse fighting test. SPA-19 had no analgesic activity at the doses employed. Activity in these tests indicates SPA-19 is useful as an antidepressant agent.
  • SPA-24 1,2-dihydro-2,2-dimethyl-9-hydroxy-7-n-pentyl-4- oxo-4l-I-thieno-[2,3-c][ l ]benzopyran (SPA-24) administered orally in a dose of 10 mg./kg., showed no reduction in the systolic blood pressure of genetically hypertensive rats. In an oral dose of 5 mg./kg., it showed moderate activity in the mouse modified DOPA potentiation test. In the audiogenic seizure test, SPA-24 at an oral dose of 30 mg./kg., afforded no protection to the mice from the convulsions. At an oral dose of 10 mg./kg., SPA-24 caused a 28% reduction in fighting behavior in the mouse fighting test. SPA-24 had no analgesic activity at the doses employed. SPA-24 is useful as an antidepressant agent.
  • SPA-38 1 ,2-'dihydro-9-hydroxy-2,2,4,4-tetramethyl-7-npenty1-4I-I-thieno-[ 2,3-c][ 1]benzopyran (SPA-38) administered orally in a dose of 10 mg./kg., showed no reduction in the systolic blood pressure of genetically hypertensive rats. In an oral dose of 20 mg./kg., it showed moderate activity in the mouse modified DOPA potentiationtest. In the audiogenic seizure test, SPA-38 at an oral dose of 30 mg./kg., afforded no protection to the mice from the convulsions. At an oral dose of 10 mg./kg., SPA-38 caused a 36% reduction in fighting behavior in the mouse fighting test. SPA-38 had no analgesic activity at the doses employed. SPA-38 is useful as an antidepressant agent.
  • SPA-41 administered orally in a dose of 10 mg./kg., showed no reduction in the systolic blood pressure of genetically hypertensive rats. At an oral dose of 10 mg./kg., it showed moderate activity in the mouse modified DOPA potentiation test.
  • SPA-41 in an oral dose of 30 mg./kg., afforded no protection to the mice from the convulsions. At an oral dose of 10 mg./kg., SPA-41 caused a 31% reduction in fighting behavior in the mouse fighting test. SPA-41 had no analgesic activity at the doses employed.
  • SPA-41 is useful as an antidepressant agent.
  • SPA-46 1,2-dihydro-2,4,4-trimethyl-9-hydroxy-7-(3-methy1- 2-octyl)-4H-thieno-[2,3-c][ 1 ]benzopyran (SPA-46) administered orally in a dose of 10 mg./kg.; showed no reduction in the systolic blood pressure of genetically hypertensive rats. At an oral dose of -mg./kg., it showed marked activity in the mouse modified DOPA potentiation test. In the audiogenic seizure test, SPA- 46in oral doses of 10 and 30 mg./kg., protected 20 and 60% of the mice, respectively, from the convulsions.
  • SPA-46 caused a 43% reduction in fighting behavior in the mouse fighting test.
  • SPA-46 had moderate activity in the acetic acid induced writhing test in mice (ED 34 mg./kg., p.o.).
  • SPA-46 is useful as an antidepressant, anticonvulsant, or analgesic agent.
  • SP-147 is approximately comparable in potency to SP-6 as both an anticonvulsant and an anti-anxiety agent.
  • SP-l47 is much more potent than SP-6 as a sedative-hypnotic and analgesic agent, and is less potent than SP-6 as an antidepressant.
  • SPA-16, SPA-19, SPA-24, SPA-38 and SPA-41 are somewhat less potent than SP-6 as antidepressants, but the antihypertensive, anticonvulsant, anti-anxiety, and analgesic properties have been greatly reduced or lost altogether. These compounds thus have a much more selective activity than SP-6 thus indicating a usefulness where the broad spectrum of activities of SP-6 would be contra indicated. There do not appear to be large differences in potency among these five compounds (excluding SP-6) in the various tests.
  • the potency of SPA-42 is also selective to induce ment of mild anti-anxiety activity.
  • SPA-46 is more potent as an analgesic agent than SP-6. SPA-46 is somewhat less potent than SP-6 as an antidepressant, and comparable in potency as an anticonvulsant.
  • the amount of active ingredient administered may be varied; however, it is necessary thatthe amount of active ingredient be such that a suitable dosage is given.
  • the selected dosage depends upon the desired therapeutic effect, on the route of administration and on the duration of treatment. Dosages of from 0.1 to mg./kg. of body weight daily, preferably individed doses, i.e., three to four times daily, can be administered.
  • the active agents of this invention can be administered to animals, including humans, as pure com: pounds. It is advisable, however, tofirst combine ,one or more of the compounds with a suitable'pharmaceutical carrier to attain a satisfactory size to dosage relationship and thereby obtain-a pharmaceuti'calcomposition. 1 3..
  • Solid carriers such as starch, sugantalcand the like can be used to form powders.
  • the powders can be used for direct administration or they may be used to make tablets or to fill gelatin capsules.
  • Suitable lubricants like magnesium stearate, binders such as gelatin,
  • disintegrating agents like sodium carbonate in combination with citric acid can be used to form tablets.
  • Sweetening and flavoring agents can also be included.
  • Unit dosage forms such as tablets and capsules can contain any suitable predetermined amount of one or more of the active agents,'and they may be administered one or more at a time at regular intervals. Such unit dosage forms, however, should generally contain a concentration of 0.1 to 50 percent by weight of one or moreof the active compounds. Unit dosage forms, such as tablets and capsules, can contain about 2 to 300 mg. of active agent.
  • a typical tablet can have the composition:
  • the compounds of Formula 1 exhibit both oral and parenteral activity and accordingly can be formulated in dosage forms for either oral or parenteral administration to a patient.
  • Solid dosage forms for oral administration include capsules, tablets, pills, powders, granules and the like.
  • Liquid dosage forms for oral administration include emulsions, solutions, suspensions, syrups andthe like, containing diluents commonly used in the art such as water. Besides inert diluents, such preparations can also include adjuvants such as wetting agents,emu1sifying and suspending agents and sweetening, flavoring and perfurning agents. I
  • Preparations for "parenteral administration include sterile aqueous or non-aqueous solutions.
  • non-aqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils such as olive oil and i'nject'able organic esters such as ethyl oleate.
  • the parenteral preparations are sterilized by conventional methods.
  • the excess Grignard reagent was decomposed by the addition of a saturated solution of ammonium sulfate followed by additional water and dilute hydrochloric acid.
  • the organic layer was separated, washed to neutrality with water, dried, and evaporated in a rotary evaporator.
  • the residue was dissolved in 30 ml. of warm methanol and was dehydrated by the addition of 2 drops of concentrated hydrochloric acid and warming.
  • the reaction mixture was added to water and the product was extracted into ethyl ether.
  • the ether solution was washed free of acid, dried, and concentrated in a rotary evaporator, leaving 5.2 g. of a brown oil.
  • the oil was purified by column chromatography (silica gel, graded ethyl ether/petroleum ether), yielding 4.3 g. (90%) of product as a cloudy, pale yellow oil from the fractions eluted by 1:99 and 2:98 ethyl ether/- petroleum ether.
  • the material showed a single spot on thin layer chromatography (silica gel, 1:4 ethyl acetate/hexane) and the nuclear magnetic resonance and infrared spectra agreed with the assigned structure.
  • reaction mixture was extracted with dilute aqueous sodium chloride and hydrochloric acid and then twice with aqueous sodium bicarbonate solution.
  • the reaction mixture was dried over magnesium sulfate and then distilled to give 128 g. of diethyl 4.4-dimethyl-3- thiahexanedioate, b.p. 9095C./0.5 mm.
  • R is a lower alkyl group having 1 to 5 carbons
  • R is hydrogen or a lower alkyl group having 1 to 5 carbons
  • R is a lower alkyl group and R is an alkyl group having 1 to carbon atoms
  • R is an alkyl having 5 to 10 carbon atoms.
  • a compound according to claim 1 having the name 1,2-dihydro-9-hydroxyl -methyl-7-( 3-methyl-2-octyl)- 4-oxo-4H-thieno-[2,3-c][ l ]benzopyran.
  • a compound according to claim 1 having the name l,2-dihydro-2,2-dimethyl-9-hydroxy-7-( 3-methyl-2- octyl)-4-oxo-4l-l-thieno-[2,3-c][ 1 ]benzopyran.
  • a compound according to claim 1 having the name 1,2-dihydro-2,2-dimethyl-9-hydroxy-7-n-pentyl-4-oxo- 4H-thieno-[ 2,3-c 1 ]benzopyran.
  • a compound according to claim 1 having the name 1 ,2-dihydro-9-hydroxy-2-methyl-7-( 3-methyl-2-octyl)- 4-oxo-4H-thieno-[ 2,3-c 1 ]benzopyran.
  • a compound according to claim 1 having the name 1 ,2-dihydro-9-hydroxy-2-methyl-7-n-pentyl-4-oxo-4l-lthieno-[2,3-c][ l ]benzopyran.
  • a compound according to claim 1 having the name 1 ,2-dihydrol ,4,4-trimethyl-9-hydroxy-7-( 3-methyl-2- octyl)-4l-l-thieno-[2,3-c][ l ]benzopyran.
  • a compound according to claim 1 having the name 1 ,2-dihydro-9-hydroxy-7-( 3-methyl-2-octyl )-2,2,4,4- tetramethyl-4l-l-thieno-[2,3-c] l ]benzopyran.
  • a compound according to claim 1 having the name l,2-dihydro-9-hydroxy-2,2,4,4-tetramethyl-7-npentyl-4H-thieno-I 2,3-c][ l ]benzopyran.
  • a compound according to claim 1 having the name 1 ,2-dihydro-2,4,4-trimethyl-9-hydroxy-7-( 3- methyl-2-octyl)-4ll-thieno-[2,3-c][ l ]benzopyran.
  • a compound according to claim 1 having the name 1 ,2-dihydro-9-hydroxy-7-n-pentyl-2,4,4- trimethyl-4l-l-thieno-[ 2,3-c][ 1 ]beniopyran.
  • alkyl group in which the cycloalkyl group contains 3 to is UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. 3,895,034 'DATED July 15, 1975 INVENTORrfSl Martin Winn et al.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
US392636A 1973-08-29 1973-08-29 1 OR 2-Mono and dialkyl substituted thienobenzopyrans Expired - Lifetime US3895034A (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
US392636A US3895034A (en) 1973-08-29 1973-08-29 1 OR 2-Mono and dialkyl substituted thienobenzopyrans
AU71746/74A AU481685B2 (en) 1973-08-29 1974-07-29 1 or 2 mono and dialkyl substituted thienobenzopyrans
GB3748174A GB1473117A (en, 2012) 1973-08-29 1974-08-27
FR7429450A FR2242090B1 (en, 2012) 1973-08-29 1974-08-28
DE2441206A DE2441206A1 (de) 1973-08-29 1974-08-28 1- oder 2-mono- und -dialkylsubstituierte thienobenzopyrane
JP49098460A JPS5050398A (en, 2012) 1973-08-29 1974-08-29
CA208,086A CA1029023A (en) 1973-08-29 1974-08-29 1 or 2 - mono and dialkyl substituted thienobenzopyrans
US05/524,626 US3946111A (en) 1973-08-29 1974-11-18 Pharmaceutical compositions containing 1 or 2-mono and dialkyl substituted thienobenzopyrans and pharmacological uses thereof

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US392636A US3895034A (en) 1973-08-29 1973-08-29 1 OR 2-Mono and dialkyl substituted thienobenzopyrans

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US05/524,626 Division US3946111A (en) 1973-08-29 1974-11-18 Pharmaceutical compositions containing 1 or 2-mono and dialkyl substituted thienobenzopyrans and pharmacological uses thereof

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JP (1) JPS5050398A (en, 2012)
CA (1) CA1029023A (en, 2012)
DE (1) DE2441206A1 (en, 2012)
FR (1) FR2242090B1 (en, 2012)
GB (1) GB1473117A (en, 2012)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3972880A (en) * 1974-03-05 1976-08-03 Sharps Associates Morpholine containing esters of thienobenzopyrans and thiopyranobenzopyrans
US4021451A (en) * 1972-05-16 1977-05-03 American Home Products Corporation Process for preparing polycyclic heterocycles having a pyran ring
US4025640A (en) * 1975-08-26 1977-05-24 American Hoechst Corporation Oxothienobenzoxepin-acetic acids, precursors and derivatives thereof
US4287192A (en) * 1978-10-02 1981-09-01 Abbott Laboratories Antiglaucoma agents
US4974609A (en) * 1986-08-18 1990-12-04 Philip Morris Incorporated Tobacco flavorants

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3639427A (en) * 1970-01-08 1972-02-01 Little Inc A Novel 1 2 3 4-tetrahydro - (and 1 2 3 4 12 13-hexahydro) cyclopenta(c)(1)benzopyrans
US3639426A (en) * 1970-01-08 1972-02-01 Little Inc A 4-oxo-9-hydroxy-7-(3-methyl-2-octyl)-1 2 3 4-tetrahydrocyclopenta(c)(1)benzopyran
US3656906A (en) * 1970-04-13 1972-04-18 Little Inc A Method for detecting and quantitating the presence of cannabinoids and analogs thereof in biological materials and resulting products
US3801597A (en) * 1971-05-31 1974-04-02 Y Makisumi 2,3-dihydro-4h-thieno(3,2-c)(1)benzopyran-4-ones

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3639427A (en) * 1970-01-08 1972-02-01 Little Inc A Novel 1 2 3 4-tetrahydro - (and 1 2 3 4 12 13-hexahydro) cyclopenta(c)(1)benzopyrans
US3639426A (en) * 1970-01-08 1972-02-01 Little Inc A 4-oxo-9-hydroxy-7-(3-methyl-2-octyl)-1 2 3 4-tetrahydrocyclopenta(c)(1)benzopyran
US3656906A (en) * 1970-04-13 1972-04-18 Little Inc A Method for detecting and quantitating the presence of cannabinoids and analogs thereof in biological materials and resulting products
US3801597A (en) * 1971-05-31 1974-04-02 Y Makisumi 2,3-dihydro-4h-thieno(3,2-c)(1)benzopyran-4-ones

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4021451A (en) * 1972-05-16 1977-05-03 American Home Products Corporation Process for preparing polycyclic heterocycles having a pyran ring
US3972880A (en) * 1974-03-05 1976-08-03 Sharps Associates Morpholine containing esters of thienobenzopyrans and thiopyranobenzopyrans
US4025640A (en) * 1975-08-26 1977-05-24 American Hoechst Corporation Oxothienobenzoxepin-acetic acids, precursors and derivatives thereof
US4287192A (en) * 1978-10-02 1981-09-01 Abbott Laboratories Antiglaucoma agents
US4974609A (en) * 1986-08-18 1990-12-04 Philip Morris Incorporated Tobacco flavorants

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AU7174674A (en) 1976-01-29
GB1473117A (en, 2012) 1977-05-11
FR2242090A1 (en, 2012) 1975-03-28
CA1029023A (en) 1978-04-04
DE2441206A1 (de) 1975-03-27
JPS5050398A (en, 2012) 1975-05-06
FR2242090B1 (en, 2012) 1978-07-21

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