KR20160017139A - 항섬유증 제제의 할로겐화 유사체 - Google Patents
항섬유증 제제의 할로겐화 유사체 Download PDFInfo
- Publication number
- KR20160017139A KR20160017139A KR1020167002802A KR20167002802A KR20160017139A KR 20160017139 A KR20160017139 A KR 20160017139A KR 1020167002802 A KR1020167002802 A KR 1020167002802A KR 20167002802 A KR20167002802 A KR 20167002802A KR 20160017139 A KR20160017139 A KR 20160017139A
- Authority
- KR
- South Korea
- Prior art keywords
- optionally substituted
- group
- heterocycloalkyl
- alkyl
- cycloalkenyl
- 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.)
- Ceased
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- 230000003510 anti-fibrotic effect Effects 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 76
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 125000001072 heteroaryl group Chemical group 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 38
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 37
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 32
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 31
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 29
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims description 27
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000005843 halogen group Chemical group 0.000 claims description 22
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 22
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 19
- 125000003282 alkyl amino group Chemical group 0.000 claims description 17
- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 15
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 14
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- -1 alkoxyheteroaryl Chemical group 0.000 description 99
- 239000000243 solution Substances 0.000 description 50
- 150000003839 salts Chemical class 0.000 description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 30
- 239000000725 suspension Substances 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- 125000005647 linker group Chemical group 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 26
- 239000007787 solid Substances 0.000 description 25
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 229940002612 prodrug Drugs 0.000 description 17
- 239000000651 prodrug Substances 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
- 206010057190 Respiratory tract infections Diseases 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- ZDSSCYCDBASEJQ-UHFFFAOYSA-N N-malonylanthranilic acid Chemical class OC(=O)CC(=O)NC1=CC=CC=C1C(O)=O ZDSSCYCDBASEJQ-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- 125000006239 protecting group Chemical group 0.000 description 13
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 12
- 239000005711 Benzoic acid Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 235000010233 benzoic acid Nutrition 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 12
- NZHGWWWHIYHZNX-CSKARUKUSA-N tranilast Chemical class C1=C(OC)C(OC)=CC=C1\C=C\C(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-CSKARUKUSA-N 0.000 description 12
- 229960005342 tranilast Drugs 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- IPHURZAZBKLMQJ-UHFFFAOYSA-N 3,4-bis(difluoromethoxy)benzaldehyde Chemical compound FC(F)OC1=CC=C(C=O)C=C1OC(F)F IPHURZAZBKLMQJ-UHFFFAOYSA-N 0.000 description 8
- 125000003710 aryl alkyl group Chemical group 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 125000004442 acylamino group Chemical group 0.000 description 6
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 5
- 125000001931 aliphatic group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
- 150000001851 cinnamic acid derivatives Chemical class 0.000 description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 235000005985 organic acids Nutrition 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 125000004465 cycloalkenyloxy group Chemical group 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 230000004761 fibrosis Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical class NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 3
- ZWJZCGIQTJXAIP-UHFFFAOYSA-N 3-(difluoromethoxy)-2-phenylprop-2-enoic acid Chemical compound FC(OC=C(C(=O)O)C1=CC=CC=C1)F ZWJZCGIQTJXAIP-UHFFFAOYSA-N 0.000 description 3
- YMIMKAHNQCJSPZ-UHFFFAOYSA-N 3-but-2-ynoxy-4-(difluoromethoxy)benzaldehyde Chemical compound CC#CCOC1=CC(C=O)=CC=C1OC(F)F YMIMKAHNQCJSPZ-UHFFFAOYSA-N 0.000 description 3
- ZLIKNROJGXXNJG-UHFFFAOYSA-N 4-(difluoromethoxy)-3-hydroxybenzaldehyde Chemical compound OC1=CC(C=O)=CC=C1OC(F)F ZLIKNROJGXXNJG-UHFFFAOYSA-N 0.000 description 3
- ZLAIHVWDSXIUJU-UHFFFAOYSA-N 5-bromo-2-[(2-carboxyacetyl)amino]benzoic acid Chemical compound OC(=O)CC(=O)NC1=CC=C(Br)C=C1C(O)=O ZLAIHVWDSXIUJU-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 101710148271 UDP-glucose:glycoprotein glucosyltransferase 1 Proteins 0.000 description 3
- 102100029151 UDP-glucuronosyltransferase 1A10 Human genes 0.000 description 3
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 230000001028 anti-proliverative effect Effects 0.000 description 3
- 125000005018 aryl alkenyl group Chemical group 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 208000027119 bilirubin metabolic disease Diseases 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- ZOJRTXAFHQRALF-SOFGYWHQSA-N ethyl (e)-3-[3,4-bis(difluoromethoxy)phenyl]but-2-enoate Chemical compound CCOC(=O)\C=C(/C)C1=CC=C(OC(F)F)C(OC(F)F)=C1 ZOJRTXAFHQRALF-SOFGYWHQSA-N 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 208000036796 hyperbilirubinemia Diseases 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- AWUPLMYXZJKHEG-UHFFFAOYSA-N methyl 2-chloro-2,2-difluoroacetate Chemical compound COC(=O)C(F)(F)Cl AWUPLMYXZJKHEG-UHFFFAOYSA-N 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
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- JVUFLOPCFNFKJP-UHFFFAOYSA-N n-(3-phenylprop-2-enoyl)benzamide Chemical class C=1C=CC=CC=1C=CC(=O)NC(=O)C1=CC=CC=C1 JVUFLOPCFNFKJP-UHFFFAOYSA-N 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 2
- DFRRVNQWKPJQCO-FNORWQNLSA-N (e)-3-[3-but-2-ynoxy-4-(difluoromethoxy)phenyl]prop-2-enoic acid Chemical compound CC#CCOC1=CC(\C=C\C(O)=O)=CC=C1OC(F)F DFRRVNQWKPJQCO-FNORWQNLSA-N 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical class NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 2
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- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- SHOFEQJWALLTLQ-UHFFFAOYSA-N 2-amino-5-chloro-n-methylbenzamide Chemical compound CNC(=O)C1=CC(Cl)=CC=C1N SHOFEQJWALLTLQ-UHFFFAOYSA-N 0.000 description 2
- IBGBGRVKPALMCQ-UHFFFAOYSA-N 3,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1O IBGBGRVKPALMCQ-UHFFFAOYSA-N 0.000 description 2
- CDASCEKDGKTDOL-UHFFFAOYSA-N 4-(difluoromethoxy)-3,5-dimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1OC(F)F CDASCEKDGKTDOL-UHFFFAOYSA-N 0.000 description 2
- KGPOVKAYCXTCQS-UHFFFAOYSA-N 4-(difluoromethoxy)-3-methoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1OC(F)F KGPOVKAYCXTCQS-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
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- 101800000733 Angiotensin-2 Proteins 0.000 description 2
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- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
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- LLQPHQFNMLZJMP-UHFFFAOYSA-N Fentrazamide Chemical compound N1=NN(C=2C(=CC=CC=2)Cl)C(=O)N1C(=O)N(CC)C1CCCCC1 LLQPHQFNMLZJMP-UHFFFAOYSA-N 0.000 description 2
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- 150000001204 N-oxides Chemical class 0.000 description 2
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- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
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- 229910052700 potassium Inorganic materials 0.000 description 1
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
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- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
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- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/004—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with organometalhalides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/38—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
- C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
- C07C47/575—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
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|---|---|---|---|
| US1613407P | 2007-12-21 | 2007-12-21 | |
| US61/016,134 | 2007-12-21 | ||
| PCT/AU2008/001868 WO2009079692A1 (en) | 2007-12-21 | 2008-12-19 | Halogenated analogues of anti-fibrotic agents |
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| KR1020107011284A Division KR101593708B1 (ko) | 2007-12-21 | 2008-12-19 | 항섬유증 제제의 할로겐화 유사체 |
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| KR20160017139A true KR20160017139A (ko) | 2016-02-15 |
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| KR1020107011284A Active KR101593708B1 (ko) | 2007-12-21 | 2008-12-19 | 항섬유증 제제의 할로겐화 유사체 |
| KR1020167002802A Ceased KR20160017139A (ko) | 2007-12-21 | 2008-12-19 | 항섬유증 제제의 할로겐화 유사체 |
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| KR1020107011284A Active KR101593708B1 (ko) | 2007-12-21 | 2008-12-19 | 항섬유증 제제의 할로겐화 유사체 |
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| EP (2) | EP3045170B1 (enExample) |
| JP (2) | JP5730578B2 (enExample) |
| KR (2) | KR101593708B1 (enExample) |
| CN (2) | CN107162928B (enExample) |
| AU (1) | AU2008341010B2 (enExample) |
| CA (1) | CA2709937C (enExample) |
| MX (2) | MX337320B (enExample) |
| NZ (1) | NZ584613A (enExample) |
| SG (1) | SG10201506526QA (enExample) |
| WO (1) | WO2009079692A1 (enExample) |
| ZA (1) | ZA201003376B (enExample) |
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|---|---|---|---|---|
| PT2799427T (pt) | 2006-07-05 | 2018-10-16 | Fibrotech Therapeutics Pty Ltd | Compostos terapêuticos |
| KR101593708B1 (ko) | 2007-12-21 | 2016-02-12 | 피브로테크 세라퓨틱 피티와이 엘티디 | 항섬유증 제제의 할로겐화 유사체 |
| EP2491030B1 (en) | 2009-10-22 | 2015-07-15 | Fibrotech Therapeutics PTY LTD | Fused ring analogues of anti-fibrotic agents |
| PL2642989T3 (pl) * | 2010-11-24 | 2019-07-31 | Occurx Pty Ltd | Sposoby leczenia chorób oczu związanych z zapaleniem i proliferacją naczyniową |
| KR102268883B1 (ko) * | 2013-03-15 | 2021-06-28 | 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 | 누트린-3a 및 펩티드에 의한 폐 섬유증의 저해 |
| US9908915B2 (en) * | 2013-11-26 | 2018-03-06 | Yale University | Cell-penetrating compositions and methods using same |
| JP6533997B2 (ja) * | 2014-12-26 | 2019-06-26 | 株式会社ヤクルト本社 | Ｚｎｆ１４３阻害活性を有する化合物およびその利用 |
| CA3052036A1 (en) | 2017-02-03 | 2018-08-09 | Certa Therapeutics Pty Ltd. | Anti-fibrotic compounds |
| 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 |
| IL305480A (en) * | 2021-03-17 | 2023-10-01 | Occurx Pty Ltd | Compounds for the treatment of disorders and their salts and polymorphs |
| CN116730977A (zh) * | 2022-03-04 | 2023-09-12 | 华东理工大学 | 新型芳基杂环类化合物及其制备方法和用途 |
Family Cites Families (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5640710B2 (enExample) | 1973-01-18 | 1981-09-22 | ||
| JPS5830302B2 (ja) * | 1974-04-16 | 1983-06-28 | キツセイヤクヒンコウギヨウ カブシキガイシヤ | シンキホウコウゾクカルボンサンアミドユウドウタイ ノ セイゾウホウホウ |
| GB1484413A (en) * | 1974-04-18 | 1977-09-01 | Kissei Pharmaceutical | Aromatic amidocarboxylic acid derivatives |
| JPS511440A (ja) | 1974-04-18 | 1976-01-08 | Kissei Pharmaceutical | Shinkihokozokukarubonsanjudotai no seizohoho |
| JPS5848545B2 (ja) | 1974-04-18 | 1983-10-28 | キツセイヤクヒンコウギヨウ カブシキガイシヤ | シンキホウコウゾクカルボンサンアミドユウドウタイ ノ セイゾウホウホウ |
| JPS5576852A (en) | 1978-12-01 | 1980-06-10 | Hisamitsu Pharmaceut Co Inc | Novel derivative of anthranilic acid |
| JPS5817186B2 (ja) | 1981-01-23 | 1983-04-05 | キツセイ薬品工業株式会社 | 新規芳香族カルボン酸誘導体の製造方法 |
| JPS5838244A (ja) * | 1981-09-01 | 1983-03-05 | Kissei Pharmaceut Co Ltd | 核置換シンナモイルアントラニル酸塩およびその製造方法 |
| US4587356A (en) * | 1981-09-01 | 1986-05-06 | Kissei Pharmaceutical Co., Ltd. | Process for the production of nuclear substituted cinnamoylanthranilic acid derivatives |
| JPS6019754A (ja) | 1983-07-14 | 1985-01-31 | Kissei Pharmaceut Co Ltd | 芳香族カルボン酸アミド誘導体の製造方法 |
| JPS60152454A (ja) | 1984-01-18 | 1985-08-10 | Terumo Corp | アミド誘導体およびこれを有効成分として含有する５−リポキシゲナ−ゼ作用阻害剤 |
| JPH07116029B2 (ja) * | 1989-04-04 | 1995-12-13 | キッセイ薬品工業株式会社 | トラニラスト水溶液製剤 |
| ATE153655T1 (de) * | 1990-02-08 | 1997-06-15 | Eisai Co Ltd | Benzensulfonamidderivat |
| US5248825A (en) * | 1990-09-20 | 1993-09-28 | Merrell Dow Pharmaceuticals Inc. | Calcium uptake inhibitors |
| ATE167181T1 (de) * | 1993-12-09 | 1998-06-15 | Ono Pharmaceutical Co | Naphthylessigsäurederivate als pgez agonisten und antagonisten |
| NZ331339A (en) | 1996-02-15 | 2001-02-23 | Kissei Pharmaceutical | Neovascularization inhibitor comprising N-(3, 4-dimethoxycinnamoyl)anthranilic acid |
| JPH09278653A (ja) | 1996-04-05 | 1997-10-28 | Santen Pharmaceut Co Ltd | 網膜疾患治療剤 |
| DE19624155A1 (de) | 1996-06-18 | 1998-01-08 | Hoechst Ag | Substituierte Benzoesäurederivate, Verfahren zu ihrer Herstellung und die Anwendung der Verbindungen zur Behandlung von Krankheiten |
| JPH10259129A (ja) | 1997-01-16 | 1998-09-29 | Kissei Pharmaceut Co Ltd | 血管新生阻害剤 |
| FR2759368B1 (fr) * | 1997-02-10 | 2001-06-01 | Galderma Rech Dermatologique | Composes biaromatiques, compositions les contenant et utilisations |
| JPH10306024A (ja) * | 1997-03-07 | 1998-11-17 | Kissei Pharmaceut Co Ltd | 糸球体疾患の予防および治療剤 |
| JPH10330254A (ja) | 1997-04-01 | 1998-12-15 | Kissei Pharmaceut Co Ltd | 翼状片の進行および術後の再発抑制剤 |
| US6127392A (en) * | 1997-08-05 | 2000-10-03 | American Home Products Corporation | Anthranilic acid analogs |
| DE19935219A1 (de) * | 1999-07-27 | 2001-02-01 | Boehringer Ingelheim Pharma | Carbonsäureamide, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Herstellung |
| KR100850330B1 (ko) * | 2001-02-28 | 2008-08-04 | 템플 유니버시티-오브 더 커먼웰쓰 시스템 오브 하이어 에듀케이션 | Ｎ-(아릴)-2-아릴에텐술폰아미드 및 이를 이용한 약학적 조성물 |
| US7429593B2 (en) * | 2001-09-14 | 2008-09-30 | Shionogi & Co., Ltd. | Utilities of amide compounds |
| JP4851671B2 (ja) | 2001-10-11 | 2012-01-11 | ニチバン株式会社 | トラニラスト経皮吸収貼付剤およびその製造方法 |
| CA2468544A1 (en) | 2001-12-10 | 2003-06-19 | Amgen Inc. | Vanilloid receptor ligands |
| JP2005516941A (ja) * | 2001-12-19 | 2005-06-09 | アセロジエニクス・インコーポレイテツド | カルコン誘導体及び疾患を治療するためのそれらの使用 |
| AU2002359922A1 (en) * | 2001-12-27 | 2003-07-15 | Taisho Pharmaceutical Co., Ltd. | Carboxylic acid derivative |
| US7351719B2 (en) * | 2002-10-31 | 2008-04-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Amide compounds having MCH-antagonistic activity and medicaments comprising these compounds |
| DE10254872A1 (de) | 2002-11-25 | 2004-06-03 | Symrise Gmbh & Co. Kg | Anthranilsäureamide und deren Derivate als kosmetische und pharmazeutische Wirkstoffe |
| US7250444B2 (en) * | 2003-08-11 | 2007-07-31 | Pfizer Inc. | Pyrrole-based HMG-CoA reductase inhibitors |
| GB0319126D0 (en) * | 2003-08-14 | 2003-09-17 | Smithkline Beecham Corp | Chemical compounds |
| DE10346913A1 (de) * | 2003-10-09 | 2005-05-04 | Merck Patent Gmbh | Acylhydrazonderivate |
| US7592373B2 (en) * | 2003-12-23 | 2009-09-22 | Boehringer Ingelheim International Gmbh | Amide compounds with MCH antagonistic activity and medicaments comprising these compounds |
| DE102004030987A1 (de) * | 2004-06-26 | 2006-01-12 | Merck Patent Gmbh | Ortho-substituierte (3-Hydroxyphenyl)-essigsäure-benzyliden-hydrazide |
| US7671077B2 (en) * | 2004-07-19 | 2010-03-02 | Leu-Fen Hou Lin | Neuroprotective small organic molecules, compositions and uses related thereto |
| CN101056635A (zh) * | 2004-11-04 | 2007-10-17 | 默克公司 | 烟酸受体激动剂、含有该化合物的组合物及治疗方法 |
| AU2005306585A1 (en) | 2004-11-17 | 2006-05-26 | Nuon Therapeutics Pty Limited | A method of modulating B cell functioning |
| JP2008520715A (ja) * | 2004-11-23 | 2008-06-19 | メルク エンド カムパニー インコーポレーテッド | ナイアシン受容体アゴニスト、そのような化合物を含む組成物、および治療方法 |
| ITMI20050261A1 (it) * | 2005-02-21 | 2006-08-22 | Carlo Ghisalberti | Analoghi strutturali di avenatramidi loro uso in composizioni utili nel trattamento di disordini dermatologici |
| AU2006226775A1 (en) | 2005-03-24 | 2006-09-28 | Janssen Pharmaceutica, N.V. | Biaryl derived amide modulators of vanilloid VR1 receptor |
| WO2006122353A1 (en) * | 2005-05-16 | 2006-11-23 | Angiogen Pharmaceuticals Pty. Ltd. | Methods and compositions for the treatment of pain |
| WO2006134013A1 (en) | 2005-06-14 | 2006-12-21 | Symrise Gmbh & Co. Kg | Mixtures comprising anthranilic acid amides and cooling agents as cosmetic and pharmaceutical compositions for alleviating itching |
| WO2007015744A1 (en) | 2005-07-21 | 2007-02-08 | Incyte Corporation | Disubstituted thienyl compounds and their use as pharmaceuticals |
| US8911795B2 (en) * | 2005-11-30 | 2014-12-16 | Symrise Ag | Compositions comprising dihydroavenanthramide D and climbazole as cosmetic and pharmaceutical compositions for alleviating itching |
| US20070286892A1 (en) * | 2006-06-13 | 2007-12-13 | Uri Herzberg | Compositions and methods for preventing or reducing postoperative ileus and gastric stasis in mammals |
| ES2462925T3 (es) * | 2006-06-14 | 2014-05-26 | Symrise Ag | Compuestos con efecto antimicrobiano para el tratamiento de fetidez oral |
| PT2799427T (pt) * | 2006-07-05 | 2018-10-16 | Fibrotech Therapeutics Pty Ltd | Compostos terapêuticos |
| KR100832747B1 (ko) | 2006-10-27 | 2008-05-27 | 한국화학연구원 | 아미노피라졸 유도체, 이의 제조 방법 및 이를 함유하는허혈성 질환의 예방 또는 치료용 조성물 |
| EP2089355A2 (en) | 2006-11-01 | 2009-08-19 | Brystol-Myers Squibb Company | Modulators of glucocorticoid receptor, ap-1, and/or nf- kappa b activity and use thereof |
| EP2030617A1 (en) * | 2007-08-17 | 2009-03-04 | Sygnis Bioscience GmbH & Co. KG | Use of tranilast and derivatives thereof for the therapy of neurological conditions |
| US20100292283A1 (en) | 2007-11-28 | 2010-11-18 | Antonio Nardi | Novel phenyl-acetamide and phenyl-propionamide derivatives useful as potassium channel modulators |
| US20090163586A1 (en) | 2007-12-20 | 2009-06-25 | Astrazeneca Ab | Bis-(Sulfonylamino) Derivatives in Therapy 205 |
| KR101593708B1 (ko) | 2007-12-21 | 2016-02-12 | 피브로테크 세라퓨틱 피티와이 엘티디 | 항섬유증 제제의 할로겐화 유사체 |
| EP2179984A1 (en) * | 2008-10-27 | 2010-04-28 | Congenia S.r.l. | Acrylamido derivatives useful as inhibitors of the mitochondrial permeability transition |
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| EP3045170B1 (en) | 2018-07-04 |
| MX372721B (es) | 2020-05-11 |
| CN102164887A (zh) | 2011-08-24 |
| CA2709937A1 (en) | 2009-07-02 |
| CA2709937C (en) | 2016-03-22 |
| EP2220028A4 (en) | 2011-02-16 |
| JP2011506490A (ja) | 2011-03-03 |
| EP3045170A1 (en) | 2016-07-20 |
| MX2010006787A (es) | 2010-10-04 |
| SG10201506526QA (en) | 2015-09-29 |
| NZ584613A (en) | 2011-07-29 |
| CN107162928B (zh) | 2022-03-11 |
| US20110021815A1 (en) | 2011-01-27 |
| KR101593708B1 (ko) | 2016-02-12 |
| JP2015180624A (ja) | 2015-10-15 |
| KR20100099134A (ko) | 2010-09-10 |
| AU2008341010A1 (en) | 2009-07-02 |
| US8624056B2 (en) | 2014-01-07 |
| WO2009079692A1 (en) | 2009-07-02 |
| JP5730578B2 (ja) | 2015-06-10 |
| EP2220028B1 (en) | 2016-03-09 |
| US20120059188A9 (en) | 2012-03-08 |
| ZA201003376B (en) | 2011-02-23 |
| MX337320B (es) | 2016-01-06 |
| JP6063985B2 (ja) | 2017-01-18 |
| AU2008341010B2 (en) | 2013-04-18 |
| CN107162928A (zh) | 2017-09-15 |
| EP2220028A1 (en) | 2010-08-25 |
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