CH617433A5 - - Google Patents
Download PDFInfo
- Publication number
- CH617433A5 CH617433A5 CH1240875A CH1240875A CH617433A5 CH 617433 A5 CH617433 A5 CH 617433A5 CH 1240875 A CH1240875 A CH 1240875A CH 1240875 A CH1240875 A CH 1240875A CH 617433 A5 CH617433 A5 CH 617433A5
- Authority
- CH
- Switzerland
- Prior art keywords
- amino
- mono
- phenylene
- lower alkyl
- radical
- Prior art date
Links
- -1 1,3-oxazolyl Chemical group 0.000 claims description 79
- 239000000460 chlorine Chemical group 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 239000002585 base Substances 0.000 claims description 15
- 125000005237 alkyleneamino group Chemical group 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- KLYCPFXDDDMZNQ-UHFFFAOYSA-N Benzyne Chemical class C1=CC#CC=C1 KLYCPFXDDDMZNQ-UHFFFAOYSA-N 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000000335 thiazolyl group Chemical group 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 7
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 150000002085 enols Chemical class 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 150000002081 enamines Chemical class 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 3
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-O Pyrrolidinium ion Chemical compound C1CC[NH2+]C1 RWRDLPDLKQPQOW-UHFFFAOYSA-O 0.000 claims description 3
- 150000003973 alkyl amines Chemical class 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000004799 bromophenyl group Chemical group 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 150000002084 enol ethers Chemical class 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-O morpholinium Chemical compound [H+].C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-O 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 claims description 3
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- RIPYGTPGAMWYIX-UHFFFAOYSA-N methoxymethyl thiohypofluorite Chemical group COCSF RIPYGTPGAMWYIX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- QZTCVPNHDKJUEQ-UHFFFAOYSA-N (2-hydroxypyrrolidin-1-yl) acetate Chemical group OC1N(CCC1)OC(C)=O QZTCVPNHDKJUEQ-UHFFFAOYSA-N 0.000 claims 1
- OCIPBCQLICPGLC-UHFFFAOYSA-N 2,3-dihydro-1-benzothiepine-4-carboxamide Chemical class S1CCC(C(=O)N)=CC2=CC=CC=C21 OCIPBCQLICPGLC-UHFFFAOYSA-N 0.000 claims 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims 1
- BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 239000000155 melt Substances 0.000 description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 150000008064 anhydrides Chemical class 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical class NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000009386 Experimental Arthritis Diseases 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 102000035092 Neutral proteases Human genes 0.000 description 2
- 108091005507 Neutral proteases Proteins 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 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 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- LWYCDEZUOPMITD-UHFFFAOYSA-N 2,3-dihydro-1-benzothiepine-4-carboxylic acid Chemical compound S1CCC(C(=O)O)=CC2=CC=CC=C21 LWYCDEZUOPMITD-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- IFXJWHXVTSIROY-UHFFFAOYSA-N 7-chloro-2,3-dihydro-1-benzothiepin-5-ol Chemical compound OC1=CCCSC2=CC=C(Cl)C=C12 IFXJWHXVTSIROY-UHFFFAOYSA-N 0.000 description 1
- ODDRVBCWBAHAOR-UHFFFAOYSA-N 7-chloro-n-(4-fluorophenyl)-5-hydroxy-2,3-dihydro-1-benzothiepine-4-carboxamide Chemical compound C1CSC2=CC=C(Cl)C=C2C(O)=C1C(=O)NC1=CC=C(F)C=C1 ODDRVBCWBAHAOR-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical class C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 240000007711 Peperomia pellucida Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 125000004802 cyanophenyl group Chemical group 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001993 dermatopathological effect Effects 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 210000004728 ear cartilage Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical class OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical class OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-O phenylazanium Chemical compound [NH3+]C1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-O 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
- C07D337/02—Seven-membered rings
- C07D337/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D337/08—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- 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]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Rheumatology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50952474A | 1974-09-26 | 1974-09-26 | |
| US58514775A | 1975-06-09 | 1975-06-09 | |
| US74320876A | 1976-11-18 | 1976-11-18 | |
| US05/854,176 US4185109A (en) | 1974-09-26 | 1977-11-23 | 1-Benzothiepin-4-carboxamides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH617433A5 true CH617433A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1980-05-30 |
Family
ID=27504481
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1240875A CH617433A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1974-09-26 | 1975-09-24 | |
| CH919179A CH623581A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1974-09-26 | 1979-10-11 | |
| CH919079A CH623580A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1974-09-26 | 1979-10-11 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH919179A CH623581A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1974-09-26 | 1979-10-11 | |
| CH919079A CH623580A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1974-09-26 | 1979-10-11 |
Country Status (10)
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4242266A (en) * | 1974-09-26 | 1980-12-30 | Ciba-Geigy Corporation | 1-Benzothiepin-4-carboxylic acid derivatives |
| US4277484A (en) * | 1978-09-20 | 1981-07-07 | Ciba-Geigy Corporation | 1-Benzothiepin-4-carboxamides |
| US4582850A (en) * | 1985-02-28 | 1986-04-15 | Ciba-Geigy Corporation | Topical and systemic treatment of psoriasis using 7-chloro-N-(3,4-dichlorophenyl)-2,3-dihydro-5-hydroxy-1-benzothiepin-4-carboxamide 1,1-dioxide and pharmaceutically acceptable salts thereof |
| US4803197A (en) * | 1987-01-12 | 1989-02-07 | Ciba-Geigy Corporation | 2,1-benzothiazepine-2,2-dioxide-5-carboxylic acid derivatives |
| US6262277B1 (en) | 1994-09-13 | 2001-07-17 | G.D. Searle And Company | Intermediates and processes for the preparation of benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake |
| US6642268B2 (en) | 1994-09-13 | 2003-11-04 | G.D. Searle & Co. | Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors |
| US6268392B1 (en) | 1994-09-13 | 2001-07-31 | G. D. Searle & Co. | Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG Co-A reductase inhibitors |
| US6221897B1 (en) * | 1998-06-10 | 2001-04-24 | Aventis Pharma Deutschland Gmbh | Benzothiepine 1,1-dioxide derivatives, a process for their preparation, pharmaceuticals comprising these compounds, and their use |
| ATE242007T1 (de) | 1998-12-23 | 2003-06-15 | Searle Llc | Kombinationen von cholesteryl ester transfer protein inhibitoren und nicotinsäure derivaten für kardiovaskuläre indikationen |
| BR9916564A (pt) * | 1998-12-23 | 2002-01-29 | Searle Llc | Combinações para indicações cardiovasculares |
| AU2157400A (en) | 1998-12-23 | 2000-07-31 | G.D. Searle & Co. | Combinations of cholesteryl ester transfer protein inhibitors and hmg coa reductase inhibitors for cardiovascular indications |
| AU776953B2 (en) * | 1998-12-23 | 2004-09-30 | G.D. Searle Llc | Combinations of ileal bile acid transport inhibitors and bile acid sequestring agents for cardiovascular indications |
| JP2002533412A (ja) | 1998-12-23 | 2002-10-08 | ジー．ディー．サール エルエルシー | 心臓血管に適用するための回腸胆汁酸輸送阻害剤およびコレステリルエステル転送タンパク質阻害剤の組み合わせ |
| DE69908644T2 (de) | 1998-12-23 | 2004-05-13 | G.D. Searle Llc, Chicago | Kombnationen von cholesteryl ester transfer protein inhibitoren und gallensäure sequestriermitteln für kardiovaskuläre indikationen |
| ATE242009T1 (de) | 1998-12-23 | 2003-06-15 | Searle Llc | Kombinationen von cholesteryl ester transfer protein inhibitoren und fibronsäure derivaten für kardiovaskuläre indikationen |
| HK1045114A1 (zh) | 1998-12-23 | 2002-11-15 | G‧D‧瑟尔有限公司 | 适用於心血管疾病的回肠胆汁酸转运抑制剂和贝酸衍生物的组合 |
| US6794544B2 (en) | 2000-03-10 | 2004-09-21 | Pharmacia Corporation | Method for the preparation of tetrahydrobenzothiepines |
| WO2001068096A2 (en) * | 2000-03-10 | 2001-09-20 | Pharmacia Corporation | Combination therapy for the prophylaxis and treatment of hyperlipidemic conditions and disorders |
| US20040077625A1 (en) * | 2001-07-25 | 2004-04-22 | Tremont Samuel J. | Novel 1,4-benzothiazepine and 1,5-benzothiazepine compounds as inhibitors of apical sodium codependent bile acid transport abd taurocholate uptake |
| MXPA04003524A (es) * | 2001-11-02 | 2004-07-23 | Searle Llc | Compuestos de benzotiepina monofluorados y difluorados novedosos como inhibidores de transporte de acido biliar co-dependiente de sodio apical (asbt) y captacion de taurocolato. |
| JP2005521653A (ja) | 2002-01-17 | 2005-07-21 | ファルマシア コーポレイション | 先端ナトリウム同時依存性胆汁酸輸送（ａｓｂｔ）およびタウロコール酸塩取込みの阻害剤としての新規アルキル／アリールヒドロキシまたはケトチエピン化合物 |
| CA2853285C (en) | 2011-10-28 | 2020-05-05 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases |
| KR102051031B1 (ko) | 2011-10-28 | 2019-12-02 | 루메나 파마수티컬즈, 인코포레이티드 | 고담혈증 및 담즙 정체성 간 질환 치료용 담즙산 재순환 억제제 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3287368A (en) * | 1965-06-08 | 1966-11-22 | Mcneilab Inc | Dihydrobenzothiepin-5(2h)-one oximes |
| US3389144A (en) * | 1965-06-08 | 1968-06-18 | Mcneilab Inc | 5-pyridyl-2, 3, 4, 5-tetrahydrobenzothiepin-5-ols |
| US3287370A (en) * | 1965-06-08 | 1966-11-22 | Mcneilab Inc | Tetrahydrobenzothiepins |
| US3444176A (en) * | 1967-04-28 | 1969-05-13 | Mcneilab Inc | Certain 4-diloweralkylamino-lower alkyl - 5 - pyridyl (or phenyl)-2,3-dihydro - 1 - benzothiepins and derivatives thereof |
| US3505355A (en) * | 1968-08-12 | 1970-04-07 | Mcneilab Inc | Certain dihydrobenzo-thiepin-5(2h)-ones |
| DE2264938A1 (de) * | 1971-07-15 | 1975-06-12 | Warner Lambert Co | 3-arylaminocarbonyl-4-hydroxy-benzo eckige klammer auf b eckige klammer zu thiacyclohex(3)en-1,1-dioxide, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| US3826791A (en) * | 1972-04-28 | 1974-07-30 | Warner Lambert Co | Heterocyclic amides of 4-hydroxy-2h-1-benzothiopyran-3-carboxylic acid 1,1-dioxide and process for their production |
| US3769292A (en) * | 1972-04-28 | 1973-10-30 | Warner Lambert Co | N-(pyridyl)2h 1-benzothiopyran-3-carboxamide-4-hydroxy 1,1-dioxides |
| US3828055A (en) * | 1972-04-28 | 1974-08-06 | Warner Lambert Co | Heterocyclic amides of 4-hydroxy-2h-1-benzothiopyran-3-carboxylic acid 1,1-dioxide |
| US3962261A (en) * | 1974-02-04 | 1976-06-08 | Warner-Lambert Company | 2,3,4,5-tetra hydro-5-oxo-1-benzothiepi n-4-carboxamide 1,1-dioxides |
-
1975
- 1975-09-12 SE SE7510196A patent/SE420725B/xx not_active IP Right Cessation
- 1975-09-23 DE DE2542329A patent/DE2542329C2/de not_active Expired
- 1975-09-24 CH CH1240875A patent/CH617433A5/de not_active IP Right Cessation
- 1975-09-24 CA CA236,220A patent/CA1066279A/en not_active Expired
- 1975-09-24 FR FR7529231A patent/FR2285872A1/fr active Granted
- 1975-09-24 AU AU85148/75A patent/AU496764B2/en not_active Expired
- 1975-09-25 NL NL7511316A patent/NL7511316A/xx not_active Application Discontinuation
- 1975-09-25 AT AT734175A patent/AT346338B/de not_active IP Right Cessation
- 1975-09-25 BE BE160345A patent/BE833787A/xx not_active IP Right Cessation
-
1977
- 1977-11-23 US US05/854,176 patent/US4185109A/en not_active Expired - Lifetime
-
1979
- 1979-10-11 CH CH919179A patent/CH623581A5/de not_active IP Right Cessation
- 1979-10-11 CH CH919079A patent/CH623580A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE7510196L (sv) | 1976-03-29 |
| CA1066279A (en) | 1979-11-13 |
| DE2542329C2 (de) | 1984-05-24 |
| FR2285872B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1978-11-10 |
| AU8514875A (en) | 1977-03-31 |
| US4185109A (en) | 1980-01-22 |
| AT346338B (de) | 1978-11-10 |
| SE420725B (sv) | 1981-10-26 |
| CH623581A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1981-06-15 |
| BE833787A (fr) | 1976-03-25 |
| CH623580A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1981-06-15 |
| DE2542329A1 (de) | 1976-04-15 |
| ATA734175A (de) | 1978-03-15 |
| NL7511316A (nl) | 1976-03-30 |
| FR2285872A1 (fr) | 1976-04-23 |
| AU496764B2 (en) | 1978-10-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CH617433A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| EP0658559A1 (de) | Thienothiazinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als 5-dipoxygenase und Cyclooxygenaseinhibitoren | |
| CH624395A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| DE1695556B2 (de) | 3Alkyl-l,2,3,4,4a,9-hexahydropyrazino [1,2-f] morphanthridinderivate | |
| EP0263352A1 (de) | Neue Imidazo-benzoxazinone, ihre Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE3442860A1 (de) | 5-alkyl-1-phenyl-2-piperazinoalkylpyrazolin-3- on-verbindungen sowie verfahren und zwischenprodukte zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| EP0093252A2 (de) | Thiomethylpyridin-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| EP0576906A1 (de) | Neue Thienothiazinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Antiinflammatorium und Analgeticum | |
| DE2832358C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| DE2514334A1 (de) | Neue pyridinderivate, verfahren zu deren herstellung und ihre verwendung in pharmazeutischen zusammensetzungen | |
| EP0110298B1 (de) | Acridanon-Derivate | |
| CH617188A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| EP0211157A1 (de) | Isoxazolderivate, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutischen Präparate | |
| AT346347B (de) | Verfahren zur herstellung von neuen 2,3- dihydro-1-benzo-thiepin-4-carbonsaeureamiden und ihren salzen mit basen | |
| EP0160173A1 (de) | Benzothiazolderivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltendes Arzneimittel | |
| CH639656A5 (de) | Stickstoffhaltige heterocyclische verbindungen und verfahren zu deren herstellung. | |
| CH634315A5 (de) | Verfahren zur herstellung von substituierten 2-vinylchromonen. | |
| DE2356005A1 (de) | Neue 7-amino-imidazo eckige klammer auf 1,2-a eckige klammer zu pyrimidine, diese enthaltende arzneimittel sowie verfahren zu deren herstellung | |
| DE4425647A1 (de) | Heterocyclyl-1-phenyl substituierte Chinoloncarbonsäuren | |
| DD236929A5 (de) | Verfahren zur herstellung von benzazolderivaten | |
| AT400568B (de) | Neue n-heterocyclische thienothiazincarboxamide, verfahren zu ihrer herstellung und ihre verwendung | |
| DE2237502A1 (de) | Neue heterocyclische verbindungen und verfahren zu deren herstellung | |
| AT400437B (de) | Neue n-heterocyclische thienothiazincarboxamide, verfahren zu ihrer herstellung und ihre verwendung | |
| DE2255562C3 (de) | I -Aminoalkyl-piperidin-4-spiro-2'-thiazolidin-4'-on-derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneipräparate | |
| DE2428640A1 (de) | Anthelmintische verbindungen und verfahren zu ihrer herstellung |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |