KR20020032537A - 카복실산 아미드, 이를 함유하는 약제, 이의 용도 및 이의제조방법 - Google Patents
카복실산 아미드, 이를 함유하는 약제, 이의 용도 및 이의제조방법 Download PDFInfo
- Publication number
- KR20020032537A KR20020032537A KR1020027001103A KR20027001103A KR20020032537A KR 20020032537 A KR20020032537 A KR 20020032537A KR 1020027001103 A KR1020027001103 A KR 1020027001103A KR 20027001103 A KR20027001103 A KR 20027001103A KR 20020032537 A KR20020032537 A KR 20020032537A
- Authority
- KR
- South Korea
- Prior art keywords
- group
- alkyl
- groups
- phenyl
- substituted
- 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.)
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 title claims abstract description 23
- 150000001875 compounds Chemical class 0.000 title claims description 48
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 239000003814 drug Substances 0.000 title abstract description 4
- 108010017842 Telomerase Proteins 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 19
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- -1 C 1-3 -alkyl Chemical group 0.000 claims description 291
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 167
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 96
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 94
- 229910052731 fluorine Inorganic materials 0.000 claims description 76
- 229910052801 chlorine Inorganic materials 0.000 claims description 74
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 72
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 57
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 57
- 125000001153 fluoro group Chemical group F* 0.000 claims description 56
- 239000000460 chlorine Substances 0.000 claims description 55
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 125000001624 naphthyl group Chemical group 0.000 claims description 43
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 41
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 38
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 36
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 35
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 35
- 229910052794 bromium Inorganic materials 0.000 claims description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
- 239000011737 fluorine Substances 0.000 claims description 34
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 31
- 125000004432 carbon atom Chemical group C* 0.000 claims description 29
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 27
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 26
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 25
- 125000004076 pyridyl group Chemical group 0.000 claims description 24
- 125000004434 sulfur atom Chemical group 0.000 claims description 24
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 23
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 22
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 20
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 238000001727 in vivo Methods 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 16
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 15
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 14
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000003277 amino group Chemical group 0.000 claims description 12
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 12
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 8
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 230000004962 physiological condition Effects 0.000 claims description 7
- 229920002554 vinyl polymer Polymers 0.000 claims description 7
- 125000006603 (C1-C3) alkylaminosulfonyl group Chemical group 0.000 claims description 6
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 claims description 6
- 125000005050 dihydrooxazolyl group Chemical group O1C(NC=C1)* 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 4
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- SEZWJRWTCIPRSV-UHFFFAOYSA-N [N]C(N)=O Chemical group [N]C(N)=O SEZWJRWTCIPRSV-UHFFFAOYSA-N 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 4
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 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 4
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 4
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 3
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 229940002612 prodrug Drugs 0.000 claims description 3
- 239000000651 prodrug Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 239000008280 blood Substances 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 150000003461 sulfonyl halides Chemical class 0.000 claims description 2
- 125000001680 trimethoxyphenyl group Chemical group 0.000 claims description 2
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 claims 9
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 2
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 239000004305 biphenyl Substances 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 908
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 765
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 363
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 351
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 259
- 239000000741 silica gel Substances 0.000 description 259
- 229910002027 silica gel Inorganic materials 0.000 description 259
- 238000001819 mass spectrum Methods 0.000 description 251
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 177
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 156
- 239000000243 solution Substances 0.000 description 136
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 96
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 88
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
- 239000011734 sodium Substances 0.000 description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- FPQMGQZTBWIHDN-UHFFFAOYSA-N 5-fluoroanthranilic acid Chemical compound NC1=CC=C(F)C=C1C(O)=O FPQMGQZTBWIHDN-UHFFFAOYSA-N 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- 239000002904 solvent Substances 0.000 description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- 239000003208 petroleum Substances 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 239000013543 active substance Substances 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 229920002261 Corn starch Polymers 0.000 description 7
- 239000008120 corn starch Substances 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- 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 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- 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 description 5
- VHJLVAABSRFDPM-ZXZARUISSA-N dithioerythritol Chemical compound SC[C@H](O)[C@H](O)CS VHJLVAABSRFDPM-ZXZARUISSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
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- 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
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Classifications
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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| WO2002096903A2 (fr) * | 2001-05-28 | 2002-12-05 | Aventis Pharma S.A. | Derives chimiques et leur application comme agent antitelomerase |
| FR2825090B1 (fr) * | 2001-05-28 | 2003-08-01 | Aventis Pharma Sa | Derives chimiques et leur application comme agent antitelomerase |
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| US8084492B2 (en) * | 2004-11-19 | 2011-12-27 | The New Industry Research Organization | Benzofuran compound and pharmaceutical composition containing the same |
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| NZ601866A (en) | 2007-06-29 | 2013-12-20 | Acucela Inc | Alkynyl phenyl derivative compounds for treating ophthalmic diseases and disorders |
| WO2009014150A1 (ja) | 2007-07-24 | 2009-01-29 | Astellas Pharma Inc. | ベンズイミダゾール誘導体 |
| KR101593708B1 (ko) * | 2007-12-21 | 2016-02-12 | 피브로테크 세라퓨틱 피티와이 엘티디 | 항섬유증 제제의 할로겐화 유사체 |
| US20110054034A1 (en) * | 2008-02-08 | 2011-03-03 | Schroeder Jr William | Methods of using carboxylic amides as antimicrobial agents |
| US20110282066A1 (en) | 2009-01-27 | 2011-11-17 | Takashi Furutani | Screening method for substance useful as agent for treating prostate cancer |
| WO2010144959A1 (en) * | 2009-06-18 | 2010-12-23 | Fibrotech Therapeutics Pty Ltd | Analogues of anti-fibrotic agents |
| EP2491030B1 (en) | 2009-10-22 | 2015-07-15 | Fibrotech Therapeutics PTY LTD | Fused ring analogues of anti-fibrotic agents |
| EP2758041B1 (de) | 2011-09-20 | 2021-01-13 | Basf Se | Niedermolekulare modulatoren des kälte-menthol-rezeptors trpm8 und deren verwendung |
| EP2794569B1 (en) * | 2011-12-21 | 2017-05-10 | Biota Europe Ltd | Heterocyclic urea compounds |
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| CN110357789B (zh) * | 2018-04-11 | 2022-09-30 | 华东理工大学 | 作为dhodh抑制剂的n-取代丙烯酰胺衍生物及其制备和用途 |
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| JPS6097946A (ja) * | 1983-11-01 | 1985-05-31 | Ono Pharmaceut Co Ltd | カルボキサミド誘導体 |
| JPS60139646A (ja) * | 1983-12-27 | 1985-07-24 | Otsuka Pharmaceut Factory Inc | ナフタレン誘導体 |
| JPS60146855A (ja) * | 1984-01-11 | 1985-08-02 | Ono Pharmaceut Co Ltd | アニリン誘導体 |
| JPS61170528A (ja) | 1985-01-22 | 1986-08-01 | Sutaaroi Sangyo Kk | コバルトの剥離回収方法 |
| US5239083A (en) * | 1991-03-11 | 1993-08-24 | Kyowa Hakko Kogyo Co., Ltd. | Indole derivatives which inhibit steroid 5α reductase |
| JPH0578315A (ja) * | 1991-03-11 | 1993-03-30 | Kyowa Hakko Kogyo Co Ltd | インドール誘導体 |
| JPH0672866A (ja) * | 1992-07-02 | 1994-03-15 | Chugoku Igakuka Gakuin Yakubutsu Kenkyusho | 分化誘導剤 |
| IT1276462B1 (it) | 1995-07-03 | 1997-10-31 | Rotta Research Lab | Diamidi aromatiche acide ad attivita' antigastrinica, procedimento per la loro preparazione e loro uso farmaceutico |
| JPH09154575A (ja) * | 1995-10-04 | 1997-06-17 | Soosei:Kk | テロメラーゼ |
| IT1286141B1 (it) | 1996-07-02 | 1998-07-07 | Rotta Research Lab | Derivati diammidici dell'acido antranilico ad attivita' antigastrinica procedimento per la loro preparazione e loro uso farmaceutico. |
| FR2759368B1 (fr) | 1997-02-10 | 2001-06-01 | Galderma Rech Dermatologique | Composes biaromatiques, compositions les contenant et utilisations |
| JPH1149676A (ja) * | 1997-07-31 | 1999-02-23 | Geron Corp | ピリジン系テロメラーゼ阻害剤 |
| EP1003712A1 (en) * | 1997-08-05 | 2000-05-31 | American Home Products Corporation | Anthranilic acid analogs |
| EP1037880B1 (en) | 1997-12-11 | 2004-06-30 | Janssen Pharmaceutica N.V. | Retinoic acid mimetic anilides |
| CA2338804A1 (en) | 1998-07-28 | 2000-02-10 | Smithkline Beecham Corporation | Propenamides as ccr5 modulators |
| AU1707700A (en) | 1998-10-29 | 2000-05-22 | Bristol-Myers Squibb Company | Novel inhibitors of impdh enzyme |
-
1999
- 1999-07-27 DE DE19935219A patent/DE19935219A1/de not_active Withdrawn
-
2000
- 2000-07-18 US US09/618,702 patent/US6362210B1/en not_active Expired - Lifetime
- 2000-07-22 MX MXPA02000822A patent/MXPA02000822A/es unknown
- 2000-07-22 EP EP00951431A patent/EP1261321A2/de not_active Withdrawn
- 2000-07-22 SK SK296-2002A patent/SK2962002A3/sk not_active Application Discontinuation
- 2000-07-22 CN CN00812829A patent/CN1414849A/zh active Pending
- 2000-07-22 EE EEP200200041A patent/EE200200041A/xx unknown
- 2000-07-22 EA EA200200114A patent/EA200200114A1/ru unknown
- 2000-07-22 HU HU0204373A patent/HUP0204373A3/hu unknown
- 2000-07-22 HR HR20020072A patent/HRP20020072A2/hr not_active Application Discontinuation
- 2000-07-22 CA CA002378382A patent/CA2378382C/en not_active Expired - Fee Related
- 2000-07-22 KR KR1020027001103A patent/KR20020032537A/ko not_active Withdrawn
- 2000-07-22 TR TR2002/00226T patent/TR200200226T2/xx unknown
- 2000-07-22 JP JP2001511906A patent/JP5010788B2/ja not_active Expired - Fee Related
- 2000-07-22 BR BR0013184-9A patent/BR0013184A/pt not_active IP Right Cessation
- 2000-07-22 CZ CZ2002313A patent/CZ2002313A3/cs unknown
- 2000-07-22 AU AU64368/00A patent/AU6436800A/en not_active Abandoned
- 2000-07-22 IL IL14770700A patent/IL147707A0/xx unknown
- 2000-07-22 WO PCT/EP2000/007057 patent/WO2001007020A2/de not_active Ceased
- 2000-07-22 PL PL36133500A patent/PL361335A1/xx not_active Application Discontinuation
- 2000-07-22 YU YU5502A patent/YU5502A/sh unknown
- 2000-07-25 UY UY26256A patent/UY26256A1/es not_active Application Discontinuation
- 2000-07-26 AR ARP000103858A patent/AR024944A1/es not_active Application Discontinuation
- 2000-07-27 CO CO00056547A patent/CO5180639A1/es not_active Application Discontinuation
-
2002
- 2002-01-03 US US10/037,555 patent/US6727250B2/en not_active Expired - Lifetime
- 2002-01-23 BG BG106343A patent/BG106343A/xx unknown
- 2002-01-24 NO NO20020374A patent/NO20020374D0/no not_active Application Discontinuation
- 2002-01-25 ZA ZA200200694A patent/ZA200200694B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US6727250B2 (en) | 2004-04-27 |
| HUP0204373A2 (hu) | 2003-03-28 |
| CO5180639A1 (es) | 2002-07-30 |
| JP5010788B2 (ja) | 2012-08-29 |
| ZA200200694B (en) | 2003-09-23 |
| HUP0204373A3 (en) | 2004-12-28 |
| HRP20020072A2 (en) | 2003-10-31 |
| IL147707A0 (en) | 2002-08-14 |
| WO2001007020A2 (de) | 2001-02-01 |
| PL361335A1 (en) | 2004-10-04 |
| CZ2002313A3 (cs) | 2002-06-12 |
| EE200200041A (et) | 2003-04-15 |
| NO20020374L (no) | 2002-01-24 |
| US6362210B1 (en) | 2002-03-26 |
| AR024944A1 (es) | 2002-10-30 |
| MXPA02000822A (es) | 2002-10-23 |
| DE19935219A1 (de) | 2001-02-01 |
| BR0013184A (pt) | 2003-07-01 |
| UY26256A1 (es) | 2001-03-16 |
| CA2378382A1 (en) | 2001-02-01 |
| JP2003518475A (ja) | 2003-06-10 |
| SK2962002A3 (en) | 2002-06-04 |
| CA2378382C (en) | 2008-09-23 |
| NO20020374D0 (no) | 2002-01-24 |
| EA200200114A1 (ru) | 2002-12-26 |
| YU5502A (sh) | 2005-06-10 |
| WO2001007020A3 (de) | 2002-09-19 |
| EP1261321A2 (de) | 2002-12-04 |
| CN1414849A (zh) | 2003-04-30 |
| TR200200226T2 (tr) | 2002-09-23 |
| BG106343A (bg) | 2002-08-30 |
| US20020099089A1 (en) | 2002-07-25 |
| AU6436800A (en) | 2001-02-13 |
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Legal Events
| Date | Code | Title | Description |
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| PA0105 | International application |
Patent event date: 20020125 Patent event code: PA01051R01D Comment text: International Patent Application |
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| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |