CA1311486C - Acide 2,3,4,9-tetrahydro-1h-carbazole-1-acetique substitue - Google Patents

Acide 2,3,4,9-tetrahydro-1h-carbazole-1-acetique substitue

Info

Publication number: CA1311486C
Authority: CA; Canada
Prior art keywords: compounds; pharmaceutically acceptable; hydrogen; acetic acid; ethyl
Prior art date: 1987-10-08
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 - Fee Related

Application number

CA000548886A

Other languages

English (en)

Inventor

Philip F. Hughes

Christopher A. Demerson

Leslie G. Humber

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.)

Wyeth LLC

Original Assignee

American Home Products Corp

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.)

1987-10-08

Filing date

1987-10-08

Publication date

1992-12-15

1987-10-08 Application filed by American Home Products Corp filed Critical American Home Products Corp

1987-10-08 Priority to CA000548886A priority Critical patent/CA1311486C/fr

1992-12-15 Application granted granted Critical

1992-12-15 Publication of CA1311486C publication Critical patent/CA1311486C/fr

2009-12-15 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

AZZZVAUBRCDMFI-UHFFFAOYSA-N 2-(2,3,4,9-tetrahydro-1h-carbazol-1-yl)acetic acid Chemical class N1C2=CC=CC=C2C2=C1C(CC(=O)O)CCC2 AZZZVAUBRCDMFI-UHFFFAOYSA-N 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 47
150000003839 salts Chemical class 0.000 claims abstract description 26
239000001257 hydrogen Substances 0.000 claims abstract description 15
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 14
125000000217 alkyl group Chemical group 0.000 claims abstract description 11
238000000034 method Methods 0.000 claims abstract description 11
230000000202 analgesic effect Effects 0.000 claims abstract description 9
239000000730 antalgic agent Substances 0.000 claims abstract description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 23
-1 8-ethynyl-1-ethyl-2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid Chemical compound 0.000 claims description 17
239000002253 acid Substances 0.000 claims description 16
150000002148 esters Chemical class 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
150000002431 hydrogen Chemical group 0.000 claims description 6
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 5
229910052802 copper Chemical group 0.000 claims description 5
239000010949 copper Chemical group 0.000 claims description 5
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 4
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 4
150000007513 acids Chemical class 0.000 claims description 4
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims description 4
150000007857 hydrazones Chemical class 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 3
229940035676 analgesics Drugs 0.000 claims description 3
230000002757 inflammatory effect Effects 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
229940127240 opiate Drugs 0.000 claims description 3
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 2
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 claims description 2
229960001138 acetylsalicylic acid Drugs 0.000 claims description 2
150000001735 carboxylic acids Chemical class 0.000 claims description 2
239000003054 catalyst Substances 0.000 claims description 2
229960004126 codeine Drugs 0.000 claims description 2
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 claims description 2
125000002534 ethynyl group Chemical class [H]C#C* 0.000 claims description 2
OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims description 2
229960001680 ibuprofen Drugs 0.000 claims description 2
150000002576 ketones Chemical class 0.000 claims description 2
229910052744 lithium Inorganic materials 0.000 claims description 2
229960005181 morphine Drugs 0.000 claims description 2
229960002085 oxycodone Drugs 0.000 claims description 2
229960005489 paracetamol Drugs 0.000 claims description 2
230000008569 process Effects 0.000 claims description 2
WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 claims 2
239000003937 drug carrier Substances 0.000 claims 2
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims 2
239000008194 pharmaceutical composition Substances 0.000 claims 2
230000003301 hydrolyzing effect Effects 0.000 claims 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims 1
238000002360 preparation method Methods 0.000 abstract description 12
239000002260 anti-inflammatory agent Substances 0.000 abstract description 3
229940121363 anti-inflammatory agent Drugs 0.000 abstract description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
238000012360 testing method Methods 0.000 description 15
239000000243 solution Substances 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
229940079593 drug Drugs 0.000 description 12
239000003814 drug Substances 0.000 description 12
239000000203 mixture Substances 0.000 description 12
239000003208 petroleum Substances 0.000 description 12
239000000047 product Substances 0.000 description 12
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
229960000583 acetic acid Drugs 0.000 description 11
229940093499 ethyl acetate Drugs 0.000 description 11
235000019439 ethyl acetate Nutrition 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
241000699670 Mus sp. Species 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
230000007062 hydrolysis Effects 0.000 description 8
238000006460 hydrolysis reaction Methods 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
229960001866 silicon dioxide Drugs 0.000 description 8
239000007787 solid Substances 0.000 description 8
239000002671 adjuvant Substances 0.000 description 7
230000003110 anti-inflammatory effect Effects 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
206010030113 Oedema Diseases 0.000 description 6
239000002904 solvent Substances 0.000 description 6
230000000694 effects Effects 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
229910052740 iodine Inorganic materials 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
239000012153 distilled water Substances 0.000 description 4
150000007529 inorganic bases Chemical class 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
239000007858 starting material Substances 0.000 description 4
RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
101150041968 CDC13 gene Proteins 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
150000001242 acetic acid derivatives Chemical class 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
210000000548 hind-foot Anatomy 0.000 description 3
239000000463 material Substances 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
229920000053 polysorbate 80 Polymers 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
238000012216 screening Methods 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000000725 suspension Substances 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
DLLUKLKKUJXLNY-UHFFFAOYSA-N (2-iodophenyl)hydrazine;hydrochloride Chemical compound [Cl-].[NH3+]NC1=CC=CC=C1I DLLUKLKKUJXLNY-UHFFFAOYSA-N 0.000 description 2
HCQVOEBHAJXJSJ-UHFFFAOYSA-N 2-(4-methylmorpholin-4-ium-4-yl)ethanol Chemical compound OCC[N+]1(C)CCOCC1 HCQVOEBHAJXJSJ-UHFFFAOYSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
WKYYYUWKFPFVEY-UHFFFAOYSA-N 2-ethylcyclohexan-1-one Chemical compound CCC1CCCCC1=O WKYYYUWKFPFVEY-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
229940124599 anti-inflammatory drug Drugs 0.000 description 2
239000002585 base Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
150000001768 cations Chemical class 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
229910001873 dinitrogen Inorganic materials 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
239000005457 ice water Substances 0.000 description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
239000012071 phase Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
125000001453 quaternary ammonium group Chemical group 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
241000894007 species Species 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
TVAGMFLSZWFEJN-UHFFFAOYSA-N 1,3,4,9-tetrahydrothiopyrano[3,4-b]indole Chemical class N1C2=CC=CC=C2C2=C1CSCC2 TVAGMFLSZWFEJN-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
XKLNOVWDVMWTOB-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1h-carbazole Chemical class N1C2=CC=CC=C2C2=C1CCCC2 XKLNOVWDVMWTOB-UHFFFAOYSA-N 0.000 description 1
KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical compound OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 description 1
SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
UBPDKIDWEADHPP-UHFFFAOYSA-N 2-iodoaniline Chemical compound NC1=CC=CC=C1I UBPDKIDWEADHPP-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
VAJZCFLYJRMBFN-UHFFFAOYSA-N 4,4-dimethylmorpholin-4-ium Chemical compound C[N+]1(C)CCOCC1 VAJZCFLYJRMBFN-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
BURCBXFLMTZETR-UHFFFAOYSA-N C(#CC)[Li].C#CC.[Cu+] Chemical compound C(#CC)[Li].C#CC.[Cu+] BURCBXFLMTZETR-UHFFFAOYSA-N 0.000 description 1
CVONLNDIAJPRPY-UHFFFAOYSA-N C(C)C1C(CCCC1)O.C(C)C1C(CCCC1)=O Chemical compound C(C)C1C(CCCC1)O.C(C)C1C(CCCC1)=O CVONLNDIAJPRPY-UHFFFAOYSA-N 0.000 description 1
KCODCRVKLNQAPI-UHFFFAOYSA-N CC#C[Cu] Chemical compound CC#C[Cu] KCODCRVKLNQAPI-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
239000003810 Jones reagent Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000186359 Mycobacterium Species 0.000 description 1
PQBAWAQIRZIWIV-UHFFFAOYSA-N N-methylpyridinium Chemical compound C[N+]1=CC=CC=C1 PQBAWAQIRZIWIV-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
230000003187 abdominal effect Effects 0.000 description 1
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
238000011047 acute toxicity test Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
125000005263 alkylenediamine group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000001754 anti-pyretic effect Effects 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
229940097320 beta blocking agent Drugs 0.000 description 1
239000012267 brine Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
229960001948 caffeine Drugs 0.000 description 1
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000000496 cardiotonic agent Substances 0.000 description 1
230000003177 cardiotonic effect Effects 0.000 description 1
239000002561 chemical irritant Substances 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
MYTMXVHNEWBFAL-UHFFFAOYSA-L dipotassium;carbonate;hydrate Chemical compound O.[K+].[K+].[O-]C([O-])=O MYTMXVHNEWBFAL-UHFFFAOYSA-L 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
230000000857 drug effect Effects 0.000 description 1
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
229960005293 etodolac Drugs 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
239000007789 gas Substances 0.000 description 1
238000003304 gavage Methods 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
150000002475 indoles Chemical class 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
YUKWZENWOLVMKD-UHFFFAOYSA-N methyl 2-(1-ethyl-2-oxocyclohexyl)acetate Chemical compound COC(=O)CC1(CC)CCCCC1=O YUKWZENWOLVMKD-UHFFFAOYSA-N 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
230000003040 nociceptive effect Effects 0.000 description 1
239000002674 ointment Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
KVNYFPKFSJIPBJ-UHFFFAOYSA-N ortho-diethylbenzene Natural products CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000013641 positive control Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000004044 response Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000000526 short-path distillation Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
LALRXNPLTWZJIJ-UHFFFAOYSA-N triethylborane Chemical compound CCB(CC)CC LALRXNPLTWZJIJ-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000003643 water by type Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)

CA000548886A 1987-10-08 1987-10-08 Acide 2,3,4,9-tetrahydro-1h-carbazole-1-acetique substitue Expired - Fee Related CA1311486C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000548886A CA1311486C (fr)	1987-10-08	1987-10-08	Acide 2,3,4,9-tetrahydro-1h-carbazole-1-acetique substitue

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA000548886A CA1311486C (fr)	1987-10-08	1987-10-08	Acide 2,3,4,9-tetrahydro-1h-carbazole-1-acetique substitue

Publications (1)

Publication Number	Publication Date
CA1311486C true CA1311486C (fr)	1992-12-15

Family

ID=4136611

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000548886A Expired - Fee Related CA1311486C (fr)	1987-10-08	1987-10-08	Acide 2,3,4,9-tetrahydro-1h-carbazole-1-acetique substitue

Country Status (1)

Country	Link
CA (1)	CA1311486C (fr)

1987
- 1987-10-08 CA CA000548886A patent/CA1311486C/fr not_active Expired - Fee Related

Legal Events

Date	Code	Title	Description
2001-12-17	MKLA	Lapsed

Publication	Publication Date	Title
US4810699A (en)	1989-03-07	Substituted 1,3,4,9-tetrahydropyrano[3,4,-b]indole-1-acetic acids, pharmaceutical compositions containing them, and methods for treating inflammatory conditions and for analgesic purposes using them
EP0200391B1 (fr)	1989-08-09	Dérivés substitués de l'acide 2,3,4,9-Tétrahydro-1H-carbazole-1-acétique
US4782076A (en)	1988-11-01	Substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid derivatives, composition and use
KR940009788B1 (ko)	1994-10-17	치환된 1,3,4,9-테트라하이드로피라노[3,4-b]인돌-1-아세트산의 제조방법
US4578398A (en)	1986-03-25	Substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid, compositions and use
CA1311486C (fr)	1992-12-15	Acide 2,3,4,9-tetrahydro-1h-carbazole-1-acetique substitue
US4584312A (en)	1986-04-22	Substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid, compositions and use
US4855445A (en)	1989-08-08	Substituted-8-alkenyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acids
JP2733490B2 (ja)	1998-03-30	置換１，３，４，９‐テトラヒドロピラノ［３，４‐ｂ］インドール‐１‐酢酸
EP0008446B1 (fr)	1982-09-22	Procédé de préparation de carbazoles, et les dérivés de carbazole utilisés pour ce procédé
US4927842A (en)	1990-05-22	2,3,4,9-tetrahydro-1H-carbazole acetic acid derivatives, composition and use as anti-inflammatories
US4960902A (en)	1990-10-02	Trifluoromethoxy substituted 1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acids
US4709048A (en)	1987-11-24	Production of substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid derivatives
EP0238226B1 (fr)	1990-12-05	1,3,4,9-Tétrahydropyrano[3,4-b]indole -1-acétates substitués
CA1311484C (fr)	1992-12-15	Acide 2,3,4,9-tetrahydro-1h-carbazole-1-acetique substitue
CA1311485C (fr)	1992-12-15	Acide 2,3,4,9-tetrahydro-1h-carbazole-1-acetique substitue
US5128363A (en)	1992-07-07	Trifluoromethoxy substituted 1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acids
US4886886A (en)	1989-12-12	Substituted 1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acids
US4775690A (en)	1988-10-04	Substituted 1,3,4,9-tetrahydropyrano(3,4-b)indole-1-acetic acids
US5055590A (en)	1991-10-08	Preparation of 2,3,4,9-tetrahydro-1H-carbazole acetic acid derivatives
US4971960A (en)	1990-11-20	Substituted 1,3,4,9-tetrahydropyrano(3,4-b)indole-1-acetic acids
US4826994A (en)	1989-05-02	Production of substituted 1,3,4,9-tetrahydropyrano(3,4-B)indole-1-acetic acids
US4687860A (en)	1987-08-18	Substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid
US4847389A (en)	1989-07-11	Production of substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid derivatives
US4701533A (en)	1987-10-20	Process for preparing substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid