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IL40320A - Tricyclic carbonyl compounds,their preparation and pharmaceutical compositions containing them - Google Patents

Tricyclic carbonyl compounds,their preparation and pharmaceutical compositions containing them

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Publication number
IL40320A
IL40320A IL40320A IL4032072A IL40320A IL 40320 A IL40320 A IL 40320A IL 40320 A IL40320 A IL 40320A IL 4032072 A IL4032072 A IL 4032072A IL 40320 A IL40320 A IL 40320A
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IL
Israel
Prior art keywords
group
alkyl
carbon atoms
composition
salt
Prior art date
Application number
IL40320A
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IL40320A0 (en
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Wellcome Found
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Publication date
Priority claimed from GB860872*[A external-priority patent/GB1414621A/en
Application filed by Wellcome Found filed Critical Wellcome Found
Publication of IL40320A0 publication Critical patent/IL40320A0/en
Publication of IL40320A publication Critical patent/IL40320A/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • C07D311/82—Xanthenes
    • C07D311/84—Xanthenes 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 in position 9
    • C07D311/86—Oxygen atoms, e.g. xanthones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
    • C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C205/58—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/647—Unsaturated compounds containing a keto groups being part of a ring having unsaturation outside the ring
    • C07C49/653—Unsaturated compounds containing a keto groups being part of a ring having unsaturation outside the ring polycyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/41—Preparation of salts of carboxylic acids
    • C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C65/32—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups
    • C07C65/34—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups polycyclic
    • C07C65/36—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups polycyclic containing rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C65/32—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups
    • C07C65/40—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups containing singly bound oxygen-containing groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C66/00—Quinone carboxylic acids
    • C07C66/02—Anthraquinone carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 carbon atoms of the ring system
    • C07D219/06—Oxygen atoms
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Pyrane Compounds (AREA)

Claims (3)

1. 40320/2 What v/e claim is: 1. A pharmaceutical composition comprising a tricyclic compound of the formula pharmaceutically acceptable wherein Z . is a carboxyl group, a /carboxylate salt group, an alkyl carboxylate group wherein the alkyl moiety has 1 to 6 carbon atoms or a carboxamide group optionally - substituted by alkyl having 1 to 6 carbon atoms; represents a bond or is a carbonyl group, an oxygen 1 ' 1 atom or a group NR in which R is a hydrogen atom or 2 an alkyl group having 1 to *-- carbon atoms ; and is 1 a substituent and has the _same_.meaning as Z or is a- 5 1 hydrogen atom or when Z is a bond or is. a group RR as 2 defined above, Z is a nitro group, a cyano group, a halogen atom, an alkanoyl group, an alkyl group or an alkoxy-group wherein- the- alkyl-'r-moiety of each-of - he;- '.: alkanoyl, alkyl and alkoxy groups has.1 to 6 carbon. atoms , in association with a pharmaceutically acceptable carrier therefor.
2. A pharmaceutical composition comprising a tricyclic compound of the formula wherein Z and Z are the same or different and each is selecte from a carboxyl group, a pharmaceutically acceptable carboxylat salt group, an alkyl carboxylate group, having 1 to 6 carbon - 64 - A371 Claims atoms in the 'alkyl' moiety, and a carboxamide group optionally N - substituted by an alkyl group having 1 to 6 carbon atoms, in association _with. a pharmaceutically acceptable carrier therefor.
3. A pharmaceutical composition comprising a tricyclic compound of theformula where ach is selected from a carboxyl group, a pharmaceutically acceptable carboxylate salt group, an alkyl carboxylate group having 1 to 6 carbon atoms in the 'alkyl' moiety, and a carboxamide group optionally N - substituted by an alkyl group having 1 to 6 carbon atoms , in association with a pharmaceutically acceptable carrier therefor. A pharmaceutical composition comprising a tricyclic compound of the formula Λ 2 wherein Z and Z are the same or different and each is selected from a carboxyl group, a pharmaceutically - 65 - 40320/2 acceptable carboxylate salt group, an alkyl carboxylate group having 1 to 6 carbon atoms in the 'alkyl' moiety and a carboxaraide group Optionally. - substituted by' an alkyl group having 1 to 6 carbon atoms, in association with a pharmaceutically acceptable carrier therefor. 5· A pharmaceutical composition comprising, a tricyclic compound of the formula wherein Z is a carboxyl group or a pharmaceutically 2 acceptable carboxylate salt group and Z is halogen,"" nitrile, alkyl having 2 to 4- carbon atoms, or carbox-amide optionally N - substituted by alkyl, having l'-'to 6 carbon atoms, in association with a pharmaceutically acceptable carrier therefor. 6. A pharmaceutical composition comprising a tricyclic compound of the formula wherein Z is a pharmaceutically acceptable carboxylate salt 3 group, Z represents a bond or is an oxygen atom, a carbonyl group or a group. NR"1" wherein R"*" is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and Z2 is a carboxyl - 66 - 40320/2 group, a pharmaceutically acceptable carboxylate salt? group, an alkyl carboxylate group having 1 to 6 carbon atoms in the alkyl moiety, a carboxamide group optionally N - substituted by alkyl having 1 to 6 carbon atoms, or is a hydrogen atom, provided that when Z^ is a group ■ A 2 NR as defined hereinabove or represents a bond, Z is also selected from a cyano ' roup, a halogen atom, a nitro group, an alkyl group, an alkanoyl group, and an alkoxy group wherein the 'alkyl' moiety of each of the alkyl, alkanoyl and alkoxy. groups , has 1 to 6 carbon atoms, in association with a pharmaceutically acceptable carrier therefor. 7. pharmaceutical composition comprising a tricyclic compound of formula e carboxylate ' salt-il 2 . group and Z is a carboxyl group, a pharmaceutically acceptabl carboxylate salt group, an alkyl carboxylate group having 1 to carbon atoms in the alkyl moiety, a carboxamide group optionally N - substituted by alkyl having 1 to 6 carbon atoms, a halogen or hydrogen atom, cyano group, nitro group, an alkyl group, an alkanoyl group or an alkoxy group wherein the 'alkyl' moiety of each of the alkyl , ! alkanoyl and alkoxy groups, -has 1 to 6 carbon atoms, in association with a pharitfaceutical carrier therefor. - 67 - 40320/2 8. Λ pharmaceutical composition comprising a tricyclic compound of the formula v/herein Z is a pharmaceutically acceptable carboxylate salt group, ^ is a bond, a carbonyl group, an oxygen 1 atom or a group NR in which R is a hydrogen atom or an alkyl group having 1 to carbon atoms, and Z is hydrogen or a pharmaceutically acceptable carboxylate salt group in the 6- or 7- position. 9. A composition as claimed in any of claims 1 to 4 and 2 · wherein both Z and Z are pharmaceutically acceptable carboxylate salt groups. 10. A composition as claimed in any of claims 1 to 9 wherein-.the carboxylate salt, is- a potassium sodium^--.··-_ . calcium, magnesium or ammonium salt. 11. A composition as claimed in any of claims 1 to 9 v/herein the carboxylate salt is a salt of an organic base. 12. A composition as claimed in any of claims 1 to 9 wherein the carboxylate salt is a sodium salt. 13. A pharmaceutical composition comprising fluorenone - 7 - dicarboxylic acid or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable carrier therefor. 14·. A pharmaceutical composition comprising disodium - 68 - A371 Claims fluorenone - 2, - dicarboxylate , in association with a pharmaceutically acceptable carrier therefor. 15· A pharmaceutical composition comprising anthraquinone -2, 6 - dicarboxylic acid or a pharmaceutically acceptable salt thereof in association with a pharmaceutically acceptable carrier therefor. 16. A pharmaceutical composition comprising xanthone - 2, 6 - dicarboxylic acid or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable carrier therefor. 17. pharmaceutical composition comprising a tricyclic compound selected from the class: 7 - acetyl flucrenone - 2 - carboxylic acid, 7 - cyano fluorenone - 2 - carboxylic acid, 7 - ethyl fluorenone - 2 - carboxylic acid, 7 - methoxy fluorenone - 2 - carboxylic acid, 7 - nitro fluorenone - 2 - carboxylic acid, 7 - chloro fluorenone - 2 - carboxylic acid, 7 - carboxamide fluorenone - 2 - carboxylic acid, and fluorenone - 2 - carboxylic acid, in association with a pharmaceutically acceptable carrier therefor. 18. A pharmaceutical composition comprising a tricyclic compound selected from the class: acridone - 2, 6 - dicarboxylic acid, N - methylacridone -2, 7 - dicarboxylic acid, acridone - 2 <- carboxylic acid, anthraquinone - 2 - carboxylic acid, and xanthone - 2 - carboxylic acid. 19. composition as claimed in claim 17 or 18 wherein the acids are in the form of a pharmaceutically A571 Claims C1 acceptable salt thereof. 20. A composition as claimed in either of claims 17 or 18 wherein the carboxylic acids are in the form of a salt of a cation selected from potassium, sodium, calcium, magnesium, ammonium and an organic base cation, 21. A composition as claimed in either of claims or 18 wherein the carboxylic acids are in the form of a sodium or potassium salt of the acids. 22. A composition as claimed in any 'of claims 1 to 21 in the form of a powder suitable for pulmonary administration. ' 23. A composition as claimed in claim 22 wherein the carrier includes a surfactant. 24. A composition as claimed in either of claims 22 or 23 wherein the carrier includes a liquid medium. 25· A composition as claimed in claim 24- wherein the tricyclic compound is a suspension in the liquid medium. 26. A composition as claimed in claim 24 wherein the tricyclic compound is in solution in the liquid medium. 27· A composition as claimed in any of claims 1 to 26 wherein the composition is a self-propelling aerosol composition in a sealed container. 28. A composition as claimed in claim 27 wherein the tricyclic compound comprises 0.1 to 20% w/w of the composition. 29. A composition as claimed in claim 27 or 28 wherein the propellent is selected from the class of lower - 70 - 40320/2 • alkyl hydrocarbons and halogenated lower alkyl hydrocarbons . -30. -A composition as claimed in claim 29 wherein the liquid propellant has a boiling point below 19°C at atmospheric pressure and comprises 50 to 99 « 9/¾-w/w of the composition. 31 . A composition as claimed in any of claims 27 to 30 wherein the composition includes 0.01 to 20% w/w of a surfactant. 32. A composition as claimed in any of claims T to 22 wherein the composition is in the form of an inhalation powder, substantially free of liquid carrier. 33 · . A composition as claimed in claim 32 wherein the powder is enclosed in 'a capsule from which the 'powder may be liberated when incorporated in an inhalation devi 3 ·. A composition as claimed in any of claims 27 to 33 wherein the tricyclic compound is in the form of micronised r,..; p :'· „ 35· A composition as claimed in any of claims 27 to 33 wherein 95?^ b number of the solid particles in the composition have a diameter less than n.m« , ' 36. . A composition as claimed in any of claims 27 to 33 wherein 98% by weight of the solid particles in the composrtidn"haver'a diameter greater"~than— 0. 5^m« — 38. A composition as claimed in claim 32 wherein the carrier comprises particles of a sugar. 40320/2 39· A process for preparing a composition as claimed in any of claims 1 to 38 comprising admixture of the . tricyclic compound wi h the carrier therefor. 40. Λ process for preparing a composition as claimed in any of claims 27 to 3 wherein one cools the tricyclic compound, mixes the' cooled liquid propel1ant therewith -in a cooled- container, and seals the container or one admixes the tricyclic compound with the liquid propellant under super-atmospheric pressure in a sealed container. ' , 41. A tricyclic compound of formul wherein Z is a carboxyl group, a carboxylate salt group an alkyl..earb.ox late. group having 1 to ,6 carbon atoms-in the 'alkyl 'moiety, or a carboxamide group optionally - substituted by alkyl having 1 to 6 carbon atoms; · ¾ · 1 Z^ is oxygen or a group NB wherein B is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; and Z is a carboxyl group, a carboxylate salt group, an-alkyl carboxylate group having 1 to 6 carbon atoms in the .'alkyl1 moiety or is a carboxamide optionally N -substituted by alkyl having 1 to 6.carbon atoms; or . 7, 1 - 2 when L'7 is a group Wfi as defined hereinabove Z is . a halogen atom, cyano group, nitro group, alkyl group, - 72 - 40320/2 alkanoyl group or alkoxy group wherein the 'alkyl' moiety of each of the alkyl, alkaonyl and alkoxy groups has 1 to 6 3 2 carbon atoms; or Z is a bond, Z is a cyano group in the 5-, 6-, 7- or 8-position, and Z^" has the same meaning as 3 2 above or Z is a bond, Z is a halogen atom, an alkyl group having 2 to 4 carbon atoms or a carboxamide optionally N-substituted by alkyl having 1 to 6 carbon atoms in the 7-position, and 7?~ is a carboxyl or a carboxylate salt 3 2 group; provided that when Z is an oxygen atom Z is not a 7-carboxyl group, a 7-carboxylate salt, a 7-alkyl carboxylate or a 7-carboxamide optionally N-substituted by alkyl except Jror 6-nitroacridone-2.-carboxylic- acid and-. -' salts thereof and 7-methylacridone-2-carboxylic acid and salts thereof ." . 4-2. »A tricyclic compound of the formula - 73 - 40320/2 wherein Z is a carboxyl group or a carboxylate salt 2 group and Z is a halogen, atom, a cyano group, an alkyl group having 2 to carbon atoms or a carboxamide group optionally N - substituted by alkyl having 1 to 6 carbon atoms. 43. A tricyclic compound of the formula wherein R , i,s- a hydrogen atom or an alkyl group having 1 to 4' carbon atoms, Z is a carboxyl group, a carboxylate salt group,- an alkyl- carboxylate- group having 1 to 6 carbon atoms in the 'alkyl' moiety, or a carboxamide group optionally N - substituted by alkyl 2 having 1 to 6 carbon atoms, and Z is hydrogen or a 1 substituent and has the same meanting as Z or is a nitro group, a cyano group, a halogen atom, an alkanoyl group, an alkyl group, or an alkoxy group wherein the 1 lkyl 1 · moiety of each of the alkanoyl, alkyl and alkoxy groups has A - '2 ■ ' ■·■ 1 to 6 carbon atoms, provided that both R and Z are not hydrogen except for 6-nitroacridone-2-carboxylic acid and salts thereof and 7-methylacridone-2-carboxylic acid and salts thereof. 44.. A tricyclic compound of the formula wherein is a carboxyl group, a. carboxy - 74 - 40320/2 group, an alkyl carboxylase group having 1 to 6 carbon atoms in the alkyl moiety, or a carboxamide group optionally N - substituted by alkyl "having 1 to 'g 2 1 carbon atoms and Z has the same meaning as Z" or is a nitro group, a cyano group, a halogen atom, an alkanoyl group, an alkyl group or an alkoxy group wherein the 'alkyl' moiety of each of the alkanoyl, alkyl and alkoxy groups is an alkyl group having 1. to 6 carbon atoms except for 6-nitroacridone-2-carboxylic acid and salts thereof. 4-5· A tricyclic compound of the formula wherein"' Z-' is a-- substituent- •:carboxyl- :groupv' carbo:¾^late':i-salt group, alkyl carboxylate havin 1 to 6 carbon atoms in the alkyl moiety, or carboxa ide optionally -substituted by alkyl having 1 to 6 carbon atoms and each . Z group is a hydrogen atom or has the same meaning as 1 Z provided that only one of the Z groups is a substituent group as defined above. 4-6. A compound as claimed in any of claims 4-1 to 4-5 when in the form of solid particles. 4-7· compound as claimed in claim 4-6 wherein 95% by number of the particles have a diameter less than 7μπι. 4-8. A compound as claimed in either of claims 4-6 and 4-7 characterised in that 98% by weig t of . the particles 40320/2 have a diameter greater than 1μ, and less than 20μπι. 9. A solid' . crystalline tricyclic compound- of the formula ■ · wherein Z. is a corbox late salt group, ZJ represents a bond or is an oxygen atom, a carbonyl group, or a group- NR1 wherein R1 is a hydrogen atom or an alkyl 2 group having 1 to 4 carbon atoms, and has the same . meaning as Z 1 provided that when Z3 represents a bond or 1 2 . is a group NR as defined hereinabove, Z is also selected from a cyano group, a halogen atom, a nitro group, an alkyl group, an alkanoyl group. or an alkoxy group, wherein the 'alkyl' moiety of the alkyl, alkanoyl and alkoxy groups is an alkyl group having 1 to 6 carbon atoms; or when is a group-IR 1-as defined_abov:e.. Z2. i-s; also' a- hydrogen-- atom.. - 50. Λ compound as claimed in any one of claims 4-1 to 8 wherein the carboxamide group is unsubstituted. 51. compound as claimed in any of claims 41 to 44 and 46 to wherein the halogen atom is chlorine, bromine or fluorine. 5 . A compound as claimed in any- of claims 4 ''and 43 to 49 -wherein Z 1 and Z2 are both carbox lnte salt groups and the tricyclic compound is water soluble. 53· compound as claimed in any of claims 41 to 9 - 76 - A57 Claims wherein the carboxylate salt groups are the sodium carboxylate salt group. "5 . A solid '. salt of fluorenone -2, 7 -dicarboxylic acid other than the barium salt. 55. Solid — disodium fluorenone - 2, 7 -dicarboxylate. 56. Crystalline disodium fluorenone -2, 7 - dicarboxylate. 57. Disodium fluorenone -2, 7 - dicarboxylate monohydrate . 58. ■—— 7 - Carboxyl fluorenone - 2 -carboxylate salts. 59·' 2 - Sodium carboxylate fluorenone - 7 - carboxyl acid. 60. Acridone - 2,6 - dicarboxylic acid and salts the 61. Xanthone -·2, 6 - dicarboxylic acid and salts thereof. 62. 7 - Carboxarnide fluorenone - 2 - carboxylic acid and salts therof. 65· 7 - ChlorcQt'luorenone - 2 - carboxylic acid and salts thereof. 64. Solid crystalline salts of 7 - met oxyfluorenone - 2 - carboxylic acid. 65· Solid crystalline salts of 7 - nitrofluorenone -2 - carboxylic acid. 66. Solid crystalline salts of 7 - acetylfluorenone -2 - carboxylic acid. - 77 - A37 Claims CJ 67. 7 - Ethylfluorenone - 2 - carboxylic acid and salts thereof. -68. 7 - Cyanofluorenone - 2 carhoxylic acid and salts thereof. 69. Salts of a thraquinone - 2, 6 - dicarboxylic acid other than the calcium and disodium A3 1 Claims 70. A process for preparing a solid crystalline of a tricyclic compound of formula ...X wherein Z.' is carboxylate salt group of a cation selected from potassium, sodium, calcium, magnesium or an organic base, Z is an oxygen atom, a carbonyl group or represents a ' bond or is a group NR in which R is hydrogen or alkyl having 1 to carbon atoms 2 and Z is a carboxylate salt group of a said cation or. a carboxyl group provided that Z 1 and Z2 are hot both sodium carboxylate salt groups or together are calcium dicarboxylate when ^ is a carbonyl group 2 and Z is in the 6- position characterised, m that : one: - (a) compo wherein Y- is an alkyl group, an acyl group, a carboxyl group or a group Z as defined hereinabove ; . is a group Ί? as defined hereinabove or a methylene group and is a methylene group or a carbonyl group; or and ' are the same or different and each is selected from CH and CR wherein R is lower alky1, provided that when Y 4. s CH, Y3 may also be N; : - 2 :—: and Y is an alkyl group, an acyl group, 2 a carboxyl group or a group Z ,as defined hereinabove - 79 - ' AJ7 Claims provided that when Y is the same as Z and Y is the 2 4 same as Z , Y is not a carbonyl group r (b)~ hydrolises a compound of formula XXVI wherein Lr J has the same meaning as above; Y is a carboxyl ^roup g ' precursor or carboxyl group; and Y a carboxyl group precursor pra 5 6 carboxyl group provided that ^ and Y are not both a carboxyl group; with an aqueous alkali; or aqueous mineral acid optionally in the presence of an organic acid; (c) heats a compound of formula χιι wherein Z and Z each have the same meaning as above or are each a carboxyl group; Z-' has the same meaning as above and Q is a leaving group, optionally in the presence of a Lev/is acid or a protonic acid; or (d) when Ί? is an oxygen atom, ones cyclises a compound of formula χχνΐΐ - 80 - 40320/2 XXVII . wherein Z and have the same meaning as before and X is. a leaving group, by heating; ;■ and where necessary treats the reaction mixture with a base or salt of the desired cation and isolates a crystalline solid salt of formula X. 71 . process as claimed in claim 70 wherein the reaction is effected in the liquid phase with heating. 72. A process, as .claimed .in either..01 claims-7-0(a-)- .and- 1 wherein the oxidising agent is nitric acid, a dichroinate salt in acetic acid or chromium trioxide. - optionally with acetic acid- or sulphuric acid. 73 · · process as claimed in either --of claims- 70(a) and 71 wherein when neither of Y 1 and Y 2 is an alkyl group, the oxidising agent is also selected from aqueous •solutions of salts of hypochlorous and hypobromous acids in the presence of base. 7;+ . process as claimed in either of claims 70(b) and 71 wherein the carboxyl group precursor is selected from a nitrile group; a trichloromethyl group and a group .COL' wherein L1 is a leaving group. 75 · process as claimed in claim 7^ wherein the leaving group is a nucleophilic atom or group. - 81 - A371 Claims C ' - ' 76. A process as claimed in claim 75 wherein the nucleophilic group is selected from an optionally and ' substituted amino group,j an alkoxy group. 77· . A process as claimed in claim 75 wherein the nucleophilic atom is a halogen atom. 78½ A process as claimed in either of claims 70 (c) and 71 characterised in that Q is a nucleophilic atom or group. 79· process as claimed in claim 78 wherein the ■ nucleophilic atom is a halogen atom. 80. A process as claimed in claim 78 wherein the nucleophilic group is a hydroxy, alkoxy or optionally substituted amino group. 81. A process as claimed in any of claims 70 (c), 71 > and 78 to 80 wherein the reaction is effected in a polar solvent. 82. A process as claimed in any of claims 70 (c), 7 and 78 to 81 wherein cyclisation is effected at a temperature of up to 300°C. 83· A process as claimed in either of claims 70(d) and 71 wherein the leaving group is a nitro group. 84-. A process as claimed in claim 83 characteeised in that the reaction is effected in a dipolar aprotic solvent. - 82 - A371 Claims 85. A process as claimed in claim 84 characterised in tflat the solvent is selected from dimethyl sulfoxide, dimethyl .acetamide, -methyl-2-¾yrr'olidone , sulfolane, hexamethylphosphor- amide, dimethyl formamide and acetonitrile. 86. A process as claimed in either of claims 70 (d) and 71 wherein the leaving group is a nucleophilic group or atom. 87i A process as claimed in claim 86 wherein the group is a hydroxyl group, a p_-toluene sulphonyloxy group 88. A process as claimed in claim 86 wherein the nucleophilic atom is a halogen atom. 89. A process for preparing a tricyclic compound of formula XXVIII XXVIII 'wherein represents a valency bond, Z is a carboxylate 5 group and Z is a hydrogen atom; or Z^ is an oxygen atom or i\ 5 a carbonyl group, Z is a hydrogen atom and is a carboxylate group, M is a cation selected from sodium, potassium, calcium, magnesium, ammonium and an organic base, m and n are each 1 or 2 and their multiplication product is 2, provided I is not calcium when ^ is a carbonyl group, and M is not sodium 5 5 when Z-' is carbonyl and is carboxylate, wherein one isolates from a solution, in a polar solvent, of a mixture of the dicarboxylate anion and the cation, a compound of XXVIII formula j as defined hereinabove, as a crystalline solid. 90. A process as claimed in claim 89 characterised in that isolation is effected by precipitation of the compound of , XXVIII formula j from solution. - 83 - ..40320/2 ' 91. process as claimed in claim 0 wherein precipitation is effected by addition to the solution of a second solvent which is miscible" with the polar solvent and in which the compou of formula XXVIII is less soluble than in the polar solvent. ■ 92. A process, as claimed in claim 91 wherein the second solvent is also a polar solvent. 93··- process as claimed in either of claims 1 and 92 wherein the polar solvent is water and the second solvent is an alkanol having 1 to carbon atoms* » 9+. process as claimed in claim 0 wherein precipitation is effected by addition of the cation to the solution so as to produce a concentration thereof in excess of the molecular equivalent of the cation in the compound of formula XXVIII. 95·- - process as.._claimed in claim 89 wherein_iisolation is effected by removal of the polar solvent. 96.. A process as claimed in claim.95 wherein removal of the .... solvent is effected by its evaporation. 97·- A process as claimed in claim 96 wherein removal of the solvent" is effected^ by freeze"drying-."- 98. A process as claimed in claim 95 wherein removal of the solvent is effected by azeotropic distillation. . .. ■ 99. A tricyclic compound of the formula X or XXVIII defined in any of claims 70 to 98 when prepared by the process defined in the appropriate claim. A371 Claims C5 99· tricyclic compound of the formula defined in any of claims 0 to 98 when prepared by the process defined in the - 85 - A3 1 Claims C6 100. A pharmaceutical composition of a tricyclic compound as defined in formula I of the specification, substantially as hereinbefore described. 101. A pharmaceutical composition of a tricyclic compound as defined in formula I. of the specification substantially as hereinbefore described with particular reference to Examples A to H, 102. A process of preparing a tricyclic compound as defined in formula V in the specification substantially as hereinbefore described with particular reference to Examples 1 to 33. 103. A process of preparing a tricyclic compound which is the end-product of Examples 1 to 33 substantially as hereinbefore described in said Examples.
IL40320A 1971-09-08 1972-09-07 Tricyclic carbonyl compounds,their preparation and pharmaceutical compositions containing them IL40320A (en)

Applications Claiming Priority (7)

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GB4185271 1971-09-08
GB860872*[A GB1414621A (en) 1971-09-08 1972-02-24 Tricyclic compounds having antiallergic properties and pharmaceuti cal compositions thereof
GB861072 1972-02-24
GB860972 1972-02-24
GB1490972 1972-03-29
GB3581872 1972-08-01
GB4007972 1972-08-29

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IL40320A true IL40320A (en) 1976-12-31

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DE (1) DE2243997A1 (en)
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JPS55122785A (en) * 1979-03-15 1980-09-20 Yoshitomi Pharmaceut Ind Ltd Preparation of benzopyranopyridine derivative
FR2464937A1 (en) * 1979-09-13 1981-03-20 Interox PROCESS FOR THE MANUFACTURE OF SUBSTITUTED ANTHRAQUINONES
US4585876A (en) * 1982-11-25 1986-04-29 Ciba-Geigy Corporation Novel xanthones and thioxanthones
JPS59175840A (en) * 1983-03-24 1984-10-04 イカリ消毒株式会社 Extermination of underground small animals
JPS6034901A (en) * 1984-06-04 1985-02-22 Nippon Nohyaku Co Ltd Prevention and extermination of insect pest, etc.
US4714669A (en) * 1985-04-11 1987-12-22 Ciba-Geigy Corporation Radiation-sensitive polycondensates, their preparation, material coated therewith and the use thereof
TW200301698A (en) 2001-12-21 2003-07-16 Bristol Myers Squibb Co Acridone inhibitors of IMPDH enzyme
CN1748675A (en) * 2005-07-11 2006-03-22 丛晓东 Compound of rhein compound and its preparation method and application in treating diabetes

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US1833272A (en) * 1928-06-21 1931-11-24 Gen Aniline Works Inc Beta-anthraquinone-carboxylic acids and the esters thereof and process of preparing them
DE495100C (en) * 1928-06-22 1930-04-07 I G Farbenindustrie Akt Ges Process for the preparation of ª ‰ -Anthraquinone carboxylic acids and their esters
US3642997A (en) * 1969-06-25 1972-02-15 Merck & Co Inc Tricyclic carboxylic acids in the treatment of inflammation
NL7008621A (en) * 1969-06-25 1970-12-29
US3873538A (en) * 1970-08-05 1975-03-25 Allen & Hanburys Ltd Amino-9,10-dihydro-9,10-dioxo-2-anthroic acids

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LU66018A1 (en) 1973-03-12
BE788514A (en) 1973-03-07
CH630885A5 (en) 1982-07-15
IE37007L (en) 1973-03-08
DD114946A5 (en) 1975-09-05
IE37007B1 (en) 1977-04-13
JPS4834865A (en) 1973-05-22
DD106263A5 (en) 1974-06-12
FR2154476B1 (en) 1975-10-17
IL40320A0 (en) 1972-11-28
AR209571A1 (en) 1977-05-13
DE2243997A1 (en) 1973-03-15
AU4640672A (en) 1974-03-14
NL7212174A (en) 1973-03-12

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