GB1584378A - (pyrazol-1-yl)-phenylacetic acids processes for their preparation and medicaments containing them - Google Patents
(pyrazol-1-yl)-phenylacetic acids processes for their preparation and medicaments containing them Download PDFInfo
- Publication number
- GB1584378A GB1584378A GB42440/77A GB4244077A GB1584378A GB 1584378 A GB1584378 A GB 1584378A GB 42440/77 A GB42440/77 A GB 42440/77A GB 4244077 A GB4244077 A GB 4244077A GB 1584378 A GB1584378 A GB 1584378A
- Authority
- GB
- United Kingdom
- Prior art keywords
- acid
- chloro
- pyrazol
- phenyll
- chloropyrazol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 87
- 230000008569 process Effects 0.000 title claims description 75
- 238000002360 preparation method Methods 0.000 title claims description 30
- 239000003814 drug Substances 0.000 title claims description 19
- AMAPMVWSJNXHCG-UHFFFAOYSA-N 2-phenyl-2-pyrazol-1-ylacetic acid Chemical class C1=CC=NN1C(C(=O)O)C1=CC=CC=C1 AMAPMVWSJNXHCG-UHFFFAOYSA-N 0.000 title 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 239
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 204
- 150000003839 salts Chemical class 0.000 claims description 170
- IJPFBRONCJOTTA-UHFFFAOYSA-N 5-chloro-1h-pyrazole Chemical compound ClC1=CC=NN1 IJPFBRONCJOTTA-UHFFFAOYSA-N 0.000 claims description 147
- WLJVXDMOQOGPHL-UHFFFAOYSA-N benzyl-alpha-carboxylic acid Natural products OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 147
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 139
- 239000002253 acid Substances 0.000 claims description 130
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 106
- -1 pyrazol 1 yl phenylacetic acid Chemical compound 0.000 claims description 103
- 239000000243 solution Substances 0.000 claims description 100
- 235000019260 propionic acid Nutrition 0.000 claims description 99
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 98
- 238000006243 chemical reaction Methods 0.000 claims description 90
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 86
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 85
- 229910052740 iodine Inorganic materials 0.000 claims description 76
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 74
- 150000001875 compounds Chemical class 0.000 claims description 73
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 70
- XHZWFUVEKDDQPF-UHFFFAOYSA-N 5-bromo-1h-pyrazole Chemical compound BrC1=CC=NN1 XHZWFUVEKDDQPF-UHFFFAOYSA-N 0.000 claims description 55
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 53
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 52
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 150000007513 acids Chemical class 0.000 claims description 42
- 229960003424 phenylacetic acid Drugs 0.000 claims description 42
- 239000003279 phenylacetic acid Substances 0.000 claims description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
- 125000005843 halogen group Chemical group 0.000 claims description 37
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims description 36
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 34
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 34
- 125000001246 bromo group Chemical group Br* 0.000 claims description 33
- 239000007858 starting material Substances 0.000 claims description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 30
- 229910052801 chlorine Inorganic materials 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 29
- 239000002904 solvent Substances 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 229960000583 acetic acid Drugs 0.000 claims description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 23
- 238000010438 heat treatment Methods 0.000 claims description 23
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 claims description 22
- 150000007530 organic bases Chemical class 0.000 claims description 22
- 230000009467 reduction Effects 0.000 claims description 22
- 239000012362 glacial acetic acid Substances 0.000 claims description 21
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 21
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 claims description 20
- DULCUDSUACXJJC-UHFFFAOYSA-N Ethyl phenylacetate Chemical compound CCOC(=O)CC1=CC=CC=C1 DULCUDSUACXJJC-UHFFFAOYSA-N 0.000 claims description 20
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 20
- 239000000460 chlorine Substances 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 20
- 150000007529 inorganic bases Chemical class 0.000 claims description 20
- 150000002825 nitriles Chemical class 0.000 claims description 20
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 239000003921 oil Substances 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 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 claims description 17
- 150000001408 amides Chemical class 0.000 claims description 17
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 17
- 229940080818 propionamide Drugs 0.000 claims description 17
- 239000011734 sodium Substances 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- 229910052783 alkali metal Inorganic materials 0.000 claims description 15
- 229910052794 bromium Inorganic materials 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 229910052708 sodium Inorganic materials 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 239000013543 active substance Substances 0.000 claims description 13
- 238000009835 boiling Methods 0.000 claims description 13
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- FZOOXGZQJUAYHH-UHFFFAOYSA-N 2-hydrazinyl-2-phenylacetic acid Chemical compound NNC(C(O)=O)C1=CC=CC=C1 FZOOXGZQJUAYHH-UHFFFAOYSA-N 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 11
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 11
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 230000020477 pH reduction Effects 0.000 claims description 11
- 239000012071 phase Substances 0.000 claims description 11
- KVJHGPAAOUGYJX-UHFFFAOYSA-N 1,1,3,3-tetraethoxypropane Chemical compound CCOC(OCC)CC(OCC)OCC KVJHGPAAOUGYJX-UHFFFAOYSA-N 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- 150000001298 alcohols Chemical class 0.000 claims description 10
- 125000005907 alkyl ester group Chemical group 0.000 claims description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 10
- 230000003301 hydrolyzing effect Effects 0.000 claims description 10
- 239000012429 reaction media Substances 0.000 claims description 10
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 8
- 239000002168 alkylating agent Substances 0.000 claims description 8
- 229940100198 alkylating agent Drugs 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
- OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical compound CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 claims description 8
- 230000002140 halogenating effect Effects 0.000 claims description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 claims description 8
- 235000011149 sulphuric acid Nutrition 0.000 claims description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- 150000001340 alkali metals Chemical class 0.000 claims description 7
- 238000009833 condensation Methods 0.000 claims description 7
- 230000005494 condensation Effects 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000004494 ethyl ester group Chemical group 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- 239000000543 intermediate Substances 0.000 claims description 6
- 239000013067 intermediate product Substances 0.000 claims description 6
- 239000002609 medium Substances 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 6
- 150000003217 pyrazoles Chemical class 0.000 claims description 6
- KEQTWHPMSVAFDA-UHFFFAOYSA-N 2,3-dihydro-1h-pyrazole Chemical compound C1NNC=C1 KEQTWHPMSVAFDA-UHFFFAOYSA-N 0.000 claims description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 5
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 5
- 150000001299 aldehydes Chemical class 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 230000029936 alkylation Effects 0.000 claims description 5
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 239000000470 constituent Substances 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 5
- 239000004289 sodium hydrogen sulphite Substances 0.000 claims description 5
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- SURMYNZXHKLDFO-UHFFFAOYSA-N 2-bromopropanedial Chemical compound O=CC(Br)C=O SURMYNZXHKLDFO-UHFFFAOYSA-N 0.000 claims description 4
- SEFXKMQMTKOMHI-UHFFFAOYSA-N 2-phenyl-2-(1h-pyrazol-5-yl)acetic acid Chemical class C=1C=CC=CC=1C(C(=O)O)C=1C=CNN=1 SEFXKMQMTKOMHI-UHFFFAOYSA-N 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products 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 claims description 4
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 claims description 4
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims description 4
- 229910021626 Tin(II) chloride Inorganic materials 0.000 claims description 4
- 235000011054 acetic acid Nutrition 0.000 claims description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 4
- 239000012670 alkaline solution Substances 0.000 claims description 4
- 239000012736 aqueous medium Substances 0.000 claims description 4
- 150000001649 bromium compounds Chemical class 0.000 claims description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims description 4
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 claims description 4
- 150000007857 hydrazones Chemical class 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 239000011630 iodine Substances 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 4
- 235000011150 stannous chloride Nutrition 0.000 claims description 4
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 4
- 239000000829 suppository Substances 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 claims description 4
- 229940086542 triethylamine Drugs 0.000 claims description 4
- OLNQXLSMGCYOIM-UHFFFAOYSA-N 2-(4-hydrazinylphenyl)acetic acid Chemical compound NNC1=CC=C(CC(O)=O)C=C1 OLNQXLSMGCYOIM-UHFFFAOYSA-N 0.000 claims description 3
- VHOMAPWVLKRQAZ-UHFFFAOYSA-N Benzyl propionate Chemical compound CCC(=O)OCC1=CC=CC=C1 VHOMAPWVLKRQAZ-UHFFFAOYSA-N 0.000 claims description 3
- 229920002261 Corn starch Polymers 0.000 claims description 3
- 235000019759 Maize starch Nutrition 0.000 claims description 3
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 claims description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 150000001805 chlorine compounds Chemical class 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 238000000354 decomposition reaction Methods 0.000 claims description 3
- 238000006356 dehydrogenation reaction Methods 0.000 claims description 3
- 150000001989 diazonium salts Chemical class 0.000 claims description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- 150000004679 hydroxides Chemical class 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 229960005205 prednisolone Drugs 0.000 claims description 3
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- IJNJLGFTSIAHEA-UHFFFAOYSA-N prop-2-ynal Chemical compound O=CC#C IJNJLGFTSIAHEA-UHFFFAOYSA-N 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 239000000454 talc Substances 0.000 claims description 3
- 229910052623 talc Inorganic materials 0.000 claims description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 2
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- LGUKTYAEODCQMW-UHFFFAOYSA-N 2-(4-amino-3-bromophenyl)acetic acid Chemical compound NC1=CC=C(CC(O)=O)C=C1Br LGUKTYAEODCQMW-UHFFFAOYSA-N 0.000 claims 2
- RNPFHSPLVUBKAU-UHFFFAOYSA-N 2-(4-amino-3-chlorophenyl)acetic acid Chemical compound NC1=CC=C(CC(O)=O)C=C1Cl RNPFHSPLVUBKAU-UHFFFAOYSA-N 0.000 claims 2
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- QWHYRTWHSGITBL-UHFFFAOYSA-N 2-[4-(4-chloropyrazol-1-yl)phenyl]-2-oxoacetic acid Chemical compound C1=CC(C(=O)C(=O)O)=CC=C1N1N=CC(Cl)=C1 QWHYRTWHSGITBL-UHFFFAOYSA-N 0.000 claims 2
- CEAIBRZKLBUDQF-UHFFFAOYSA-N 2-azaniumyl-2-(2,6-dichlorophenyl)acetate Chemical compound OC(=O)C(N)C1=C(Cl)C=CC=C1Cl CEAIBRZKLBUDQF-UHFFFAOYSA-N 0.000 claims 2
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- QIQVQGQTATZQAL-UHFFFAOYSA-N 2-hydroxy-2-phenyl-2-(1h-pyrazol-5-yl)acetic acid Chemical class C=1C=CC=CC=1C(O)(C(=O)O)C=1C=CNN=1 QIQVQGQTATZQAL-UHFFFAOYSA-N 0.000 claims 2
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- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 2
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims 2
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- 239000011591 potassium Substances 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- JIQXKYSNGXUDJU-UHFFFAOYSA-N propan-2-ylidenehydrazine Chemical class CC(C)=NN JIQXKYSNGXUDJU-UHFFFAOYSA-N 0.000 description 1
- DXGIRFAFSFKYCF-UHFFFAOYSA-N propanehydrazide Chemical compound CCC(=O)NN DXGIRFAFSFKYCF-UHFFFAOYSA-N 0.000 description 1
- LZFIOSVZIQOVFW-UHFFFAOYSA-N propyl 2-hydroxybenzoate Chemical class CCCOC(=O)C1=CC=CC=C1O LZFIOSVZIQOVFW-UHFFFAOYSA-N 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- 150000004892 pyridazines Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 229940058287 salicylic acid derivative anticestodals Drugs 0.000 description 1
- 150000003872 salicylic acid derivatives Chemical class 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical class OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 150000003549 thiazolines Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- RYVBINGWVJJDPU-UHFFFAOYSA-M tributyl(hexadecyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC RYVBINGWVJJDPU-UHFFFAOYSA-M 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 229940045999 vitamin b 12 Drugs 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/16—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1313876 | 1976-10-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1584378A true GB1584378A (en) | 1981-02-11 |
Family
ID=4389651
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB42440/77A Expired GB1584378A (en) | 1976-10-14 | 1977-10-12 | (pyrazol-1-yl)-phenylacetic acids processes for their preparation and medicaments containing them |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US4239901A (enExample) |
| JP (1) | JPS5350161A (enExample) |
| AT (1) | AT364354B (enExample) |
| AU (1) | AU521207B2 (enExample) |
| BE (1) | BE859781A (enExample) |
| CA (1) | CA1097661A (enExample) |
| DE (1) | DE2746067A1 (enExample) |
| DK (1) | DK455877A (enExample) |
| ES (1) | ES463240A1 (enExample) |
| FR (1) | FR2367750A1 (enExample) |
| GB (1) | GB1584378A (enExample) |
| GR (1) | GR61620B (enExample) |
| IE (1) | IE45624B1 (enExample) |
| LU (1) | LU78310A1 (enExample) |
| NL (1) | NL7711262A (enExample) |
| NZ (1) | NZ185426A (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3029160A1 (de) | 1980-08-01 | 1982-03-04 | Basf Ag, 6700 Ludwigshafen | Verfahren zur herstellung von pyrazolen |
| US4581463A (en) * | 1981-10-16 | 1986-04-08 | Ethyl Corporation | Nucleophilic substitution process combined with additional reaction steps |
| US4710581A (en) * | 1981-10-16 | 1987-12-01 | Ethyl Corporation | Nucleophilic substitution process |
| US4502995A (en) * | 1981-11-02 | 1985-03-05 | Ethyl Corporation | Nucleophilic substitution process |
| US4503056A (en) * | 1982-03-02 | 1985-03-05 | Abbott Laboratories | 1-(Pyridazinyl)pyrazoline derivatives |
| US4540795A (en) * | 1983-02-25 | 1985-09-10 | Ethyl Corporation | Fluoronitroaralkyloxazolines, derivatives thereof, and nucleophilic substitution processes for preparing them |
| US5633399A (en) * | 1991-10-31 | 1997-05-27 | Abbott Laboratories | Process for the preparation of fluorinated benzoic acids |
| IS4164A (is) * | 1993-06-11 | 1994-12-12 | Ab Astra | Efnasambönd sem hindra flæði magasýru |
| US5556863A (en) * | 1993-06-11 | 1996-09-17 | Astra Aktiebolag | Compound for gastric acid secretion inhibition |
| US5665756A (en) * | 1994-08-03 | 1997-09-09 | Hoechst Marion Roussel, Inc. | Aminoalkyloximes useful in the treatment of depression and obsessive compulsive disorders |
| US5510361A (en) * | 1994-10-20 | 1996-04-23 | The Procter & Gamble Company | Di-tert-butylphenol compounds with heterocyclic moiety, useful as anti-inflammatory agents |
| US5811605A (en) * | 1997-02-19 | 1998-09-22 | Ppg Industries, Inc. | Preparation of 1,2,3,3-tetrachloropropene |
| DE19808261A1 (de) * | 1998-02-27 | 1999-10-28 | Bayer Ag | Arylphenylsubstituierte cyclische Ketoenole |
| US6723348B2 (en) * | 2001-11-16 | 2004-04-20 | Ethypharm | Orodispersible tablets containing fexofenadine |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2858314A (en) * | 1954-06-07 | 1958-10-28 | Georgian Vlasios | Hydrocarbazolenines |
| CH448121A (de) * | 1963-03-13 | 1967-12-15 | Hoffmann La Roche | Verfahren zur Herstellung substituierter Hydrazinverbindungen |
| US3526653A (en) * | 1964-06-15 | 1970-09-01 | Merck & Co Inc | Phenylacetamides |
| BR6574940D0 (pt) * | 1964-11-27 | 1973-08-07 | Merck & Co Inc | Processo para fazer acidos fenil-aceticos |
| US3766260A (en) * | 1968-03-27 | 1973-10-16 | Ciba Geigy Corp | Tertiary aminoacids |
| US3867452A (en) * | 1970-12-30 | 1975-02-18 | Merrill Wilcox | 2-Nitrophenylhydrazines |
| FR2137211B1 (enExample) * | 1971-05-17 | 1974-08-02 | Bouchara Emile | |
| GB1484413A (en) * | 1974-04-18 | 1977-09-01 | Kissei Pharmaceutical | Aromatic amidocarboxylic acid derivatives |
-
1977
- 1977-10-12 GB GB42440/77A patent/GB1584378A/en not_active Expired
- 1977-10-12 AT AT0729077A patent/AT364354B/de not_active IP Right Cessation
- 1977-10-12 US US05/841,382 patent/US4239901A/en not_active Expired - Lifetime
- 1977-10-12 GR GR54562A patent/GR61620B/el unknown
- 1977-10-12 FR FR7730644A patent/FR2367750A1/fr active Granted
- 1977-10-13 LU LU7778310A patent/LU78310A1/xx unknown
- 1977-10-13 CA CA288,666A patent/CA1097661A/en not_active Expired
- 1977-10-13 IE IE2091/77A patent/IE45624B1/en unknown
- 1977-10-13 NZ NZ185426A patent/NZ185426A/xx unknown
- 1977-10-13 DE DE19772746067 patent/DE2746067A1/de not_active Withdrawn
- 1977-10-13 JP JP12196477A patent/JPS5350161A/ja active Pending
- 1977-10-13 NL NL7711262A patent/NL7711262A/xx not_active Application Discontinuation
- 1977-10-13 AU AU29631/77A patent/AU521207B2/en not_active Expired
- 1977-10-13 DK DK455877A patent/DK455877A/da unknown
- 1977-10-14 BE BE6046180A patent/BE859781A/xx unknown
- 1977-10-14 ES ES463240A patent/ES463240A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| IE45624B1 (en) | 1982-10-06 |
| BE859781A (fr) | 1978-04-14 |
| GR61620B (en) | 1978-12-04 |
| FR2367750A1 (fr) | 1978-05-12 |
| ES463240A1 (es) | 1978-09-01 |
| AU521207B2 (en) | 1982-03-25 |
| NL7711262A (nl) | 1978-04-18 |
| AT364354B (de) | 1981-10-12 |
| CA1097661A (en) | 1981-03-17 |
| ATA729077A (de) | 1981-03-15 |
| AU2963177A (en) | 1979-04-26 |
| IE45624L (en) | 1978-04-14 |
| DE2746067A1 (de) | 1978-04-20 |
| DK455877A (da) | 1978-04-15 |
| FR2367750B1 (enExample) | 1981-11-27 |
| LU78310A1 (enExample) | 1979-02-02 |
| US4239901A (en) | 1980-12-16 |
| NZ185426A (en) | 1979-12-11 |
| JPS5350161A (en) | 1978-05-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| PCNP | Patent ceased through non-payment of renewal fee |