JPWO2020077123A5 - - Google Patents
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- JPWO2020077123A5 JPWO2020077123A5 JP2021519726A JP2021519726A JPWO2020077123A5 JP WO2020077123 A5 JPWO2020077123 A5 JP WO2020077123A5 JP 2021519726 A JP2021519726 A JP 2021519726A JP 2021519726 A JP2021519726 A JP 2021519726A JP WO2020077123 A5 JPWO2020077123 A5 JP WO2020077123A5
- Authority
- JP
- Japan
- Prior art keywords
- compound
- oxo
- methyl
- dione
- triazine
- 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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- 125000005843 halogen group Chemical group 0.000 claims 27
- 150000001875 compounds Chemical class 0.000 claims 24
- 150000003839 salts Chemical class 0.000 claims 20
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 18
- 125000001424 substituent group Chemical group 0.000 claims 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 5
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- -1 2-(6-(3,5-dichloro-4-((5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy)phenyl)-3,5-dioxo-4,5- dihydro-1,2,4-triazin-2(3H)-yl)ethyl acetate Chemical compound 0.000 claims 2
- WHBKMGQKMZNMET-UHFFFAOYSA-N 6-[3,5-dichloro-4-(1-methyl-6-oxo-5-propan-2-ylpyridazin-3-yl)oxyphenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NN(C(C(=C1)C(C)C)=O)C)Cl)C=1C(NC(N(N=1)C)=O)=O WHBKMGQKMZNMET-UHFFFAOYSA-N 0.000 claims 2
- URKIICBSOSXJCC-UHFFFAOYSA-N 6-[3,5-dichloro-4-(6-oxo-5-propan-2-yl-1H-pyridazine-3-carbonyl)phenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1C(=O)C1=NNC(C(=C1)C(C)C)=O)Cl)C=1C(NC(NN=1)=O)=O URKIICBSOSXJCC-UHFFFAOYSA-N 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 2
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 claims 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims 1
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 claims 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 claims 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 claims 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 claims 1
- RTDAJOPROCTICA-UHFFFAOYSA-N 2-[6-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1H-pyridazin-3-yl)oxy]phenyl]-3,5-dioxo-1,2,4-triazin-2-yl]acetonitrile Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(C)C)=O)Cl)C=1C(NC(N(N=1)CC#N)=O)=O RTDAJOPROCTICA-UHFFFAOYSA-N 0.000 claims 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 claims 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 claims 1
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 claims 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 claims 1
- HPVSVRNZHXKFME-UHFFFAOYSA-N 6-[3,5-dichloro-2-fluoro-4-(1-methyl-6-oxo-5-propan-2-ylpyridazin-3-yl)oxyphenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound ClC=1C(=C(C=C(C=1OC1=NN(C(C(=C1)C(C)C)=O)C)Cl)C=1C(NC(NN=1)=O)=O)F HPVSVRNZHXKFME-UHFFFAOYSA-N 0.000 claims 1
- TYDDEJOCGWLJDZ-UHFFFAOYSA-N 6-[3,5-dichloro-2-methyl-4-(1-methyl-6-oxo-5-propan-2-ylpyridazin-3-yl)oxyphenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound ClC=1C(=C(C=C(C=1OC1=NN(C(C(=C1)C(C)C)=O)C)Cl)C=1C(NC(NN=1)=O)=O)C TYDDEJOCGWLJDZ-UHFFFAOYSA-N 0.000 claims 1
- SSKGZHIFMAXRFN-UHFFFAOYSA-N 6-[3,5-dichloro-4-(1-methyl-6-oxo-5-propan-2-ylpyridazin-3-yl)oxyphenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NN(C(C(=C1)C(C)C)=O)C)Cl)C=1C(NC(NN=1)=O)=O SSKGZHIFMAXRFN-UHFFFAOYSA-N 0.000 claims 1
- KUXBZWUVZSOSHV-UHFFFAOYSA-N 6-[3,5-dichloro-4-(1-methyl-6-oxo-5-propan-2-ylpyridazine-3-carbonyl)phenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1C(=O)C1=NN(C(C(=C1)C(C)C)=O)C)Cl)C=1C(NC(N(N=1)C)=O)=O KUXBZWUVZSOSHV-UHFFFAOYSA-N 0.000 claims 1
- LBFQIZMJDQPECD-UHFFFAOYSA-N 6-[3,5-dichloro-4-(5-cyclopropyl-1-methyl-6-oxopyridazin-3-yl)oxyphenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NN(C(C(=C1)C1CC1)=O)C)Cl)C=1C(NC(N(N=1)C)=O)=O LBFQIZMJDQPECD-UHFFFAOYSA-N 0.000 claims 1
- MHPYWCOWVCIOIP-UHFFFAOYSA-N 6-[3,5-dichloro-4-(5-cyclopropyl-1-methyl-6-oxopyridazin-3-yl)oxyphenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NN(C(C(=C1)C1CC1)=O)C)Cl)C=1C(NC(NN=1)=O)=O MHPYWCOWVCIOIP-UHFFFAOYSA-N 0.000 claims 1
- REGUHCOVNGSBRF-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(1-methyl-6-oxo-5-propan-2-ylpyridazin-3-yl)methyl]phenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1CC1=NN(C(C(=C1)C(C)C)=O)C)Cl)C=1C(NC(N(N=1)C)=O)=O REGUHCOVNGSBRF-UHFFFAOYSA-N 0.000 claims 1
- ADGHRZPNZJIEJX-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(1-methyl-6-oxo-5-propan-2-ylpyridazin-3-yl)methyl]phenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1CC1=NN(C(C(=C1)C(C)C)=O)C)Cl)C=1C(NC(NN=1)=O)=O ADGHRZPNZJIEJX-UHFFFAOYSA-N 0.000 claims 1
- NDVXEJLLJOREQG-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(5-cyclopropyl-6-oxo-1H-pyridazin-3-yl)oxy]phenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C1CC1)=O)Cl)C=1C(NC(N(N=1)C)=O)=O NDVXEJLLJOREQG-UHFFFAOYSA-N 0.000 claims 1
- RTIOKJDBMLZLCZ-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(5-ethyl-6-oxo-1H-pyridazin-3-yl)oxy]phenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)CC)=O)Cl)C=1C(NC(N(N=1)C)=O)=O RTIOKJDBMLZLCZ-UHFFFAOYSA-N 0.000 claims 1
- GGIBMTAXDNTITM-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(6-oxo-5-pentan-3-yl-1H-pyridazin-3-yl)oxy]phenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(CC)CC)=O)Cl)C=1C(NC(N(N=1)C)=O)=O GGIBMTAXDNTITM-UHFFFAOYSA-N 0.000 claims 1
- CLXLSCFRNUWYKU-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1H-pyridazin-3-yl)methyl]phenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1CC1=NNC(C(=C1)C(C)C)=O)Cl)C=1C(NC(N(N=1)C)=O)=O CLXLSCFRNUWYKU-UHFFFAOYSA-N 0.000 claims 1
- KQPPTHXSJLQESC-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1H-pyridazin-3-yl)methyl]phenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1CC1=NNC(C(=C1)C(C)C)=O)Cl)C=1C(NC(NN=1)=O)=O KQPPTHXSJLQESC-UHFFFAOYSA-N 0.000 claims 1
- STPFJPOIOASPOG-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1H-pyridazin-3-yl)oxy]phenyl]-2-(2,2,2-trifluoroethyl)-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(C)C)=O)Cl)C=1C(NC(N(N=1)CC(F)(F)F)=O)=O STPFJPOIOASPOG-UHFFFAOYSA-N 0.000 claims 1
- WSJSJDWITRLQPD-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1H-pyridazin-3-yl)oxy]phenyl]-2-(2,2-difluoroethyl)-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(C)C)=O)Cl)C=1C(NC(N(N=1)CC(F)F)=O)=O WSJSJDWITRLQPD-UHFFFAOYSA-N 0.000 claims 1
- PDIVOLYTJVBNPZ-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1H-pyridazin-3-yl)oxy]phenyl]-2-ethyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(C)C)=O)Cl)C=1C(NC(N(N=1)CC)=O)=O PDIVOLYTJVBNPZ-UHFFFAOYSA-N 0.000 claims 1
- HDDBATPGMROKJI-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1H-pyridazin-3-yl)oxy]phenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(C)C)=O)Cl)C=1C(NC(N(N=1)C)=O)=O HDDBATPGMROKJI-UHFFFAOYSA-N 0.000 claims 1
- IYWDMJWLEDEUDS-UHFFFAOYSA-N 6-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1H-pyridazin-3-yl)oxy]phenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(C)C)=O)Cl)C=1C(NC(NN=1)=O)=O IYWDMJWLEDEUDS-UHFFFAOYSA-N 0.000 claims 1
- DVPVATAJTXYFDC-UHFFFAOYSA-N 6-[3,5-dichloro-4-[[5-(1-hydroxyethyl)-6-oxo-1H-pyridazin-3-yl]oxy]phenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(C)O)=O)Cl)C=1C(NC(N(N=1)C)=O)=O DVPVATAJTXYFDC-UHFFFAOYSA-N 0.000 claims 1
- HCXSKJHQNQJXMT-UHFFFAOYSA-N 6-[3,5-dichloro-4-[[5-(1-hydroxyethyl)-6-oxo-1H-pyridazin-3-yl]oxy]phenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(C)O)=O)Cl)C=1C(NC(NN=1)=O)=O HCXSKJHQNQJXMT-UHFFFAOYSA-N 0.000 claims 1
- PJFYIHRNTTYZBS-UHFFFAOYSA-N 6-[3,5-dichloro-4-[[5-(1-hydroxypropan-2-yl)-6-oxo-1H-pyridazin-3-yl]oxy]phenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(CO)C)=O)Cl)C=1C(NC(N(N=1)C)=O)=O PJFYIHRNTTYZBS-UHFFFAOYSA-N 0.000 claims 1
- CEJGHUDAFOSYFR-UHFFFAOYSA-N 6-[3,5-dichloro-4-[[5-(1-hydroxypropyl)-6-oxo-1H-pyridazin-3-yl]oxy]phenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C(CC)O)=O)Cl)C=1C(NC(N(N=1)C)=O)=O CEJGHUDAFOSYFR-UHFFFAOYSA-N 0.000 claims 1
- HRSJYDJVXRIJNS-UHFFFAOYSA-N 6-[4-(5-acetyl-1-methyl-6-oxopyridazin-3-yl)oxy-3,5-dichlorophenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound C(C)(=O)C1=CC(=NN(C1=O)C)OC1=C(C=C(C=C1Cl)C=1C(NC(NN=1)=O)=O)Cl HRSJYDJVXRIJNS-UHFFFAOYSA-N 0.000 claims 1
- HXFZWUMQFRTWBH-UHFFFAOYSA-N 6-[4-[(5-butan-2-yl-6-oxo-1H-pyridazin-3-yl)oxy]-3,5-dichlorophenyl]-2-methyl-1,2,4-triazine-3,5-dione Chemical compound C(C)(CC)C1=CC(=NNC1=O)OC1=C(C=C(C=C1Cl)C=1C(NC(N(N=1)C)=O)=O)Cl HXFZWUMQFRTWBH-UHFFFAOYSA-N 0.000 claims 1
- SIFPVSSBEUBNGD-SSDOTTSWSA-N 6-[4-[[5-[(2R)-butan-2-yl]-6-oxo-1H-pyridazin-3-yl]oxy]-3,5-dichlorophenyl]-2H-1,2,4-triazine-3,5-dione Chemical compound CC[C@@H](C)C1=CC(=NNC1=O)OC2=C(C=C(C=C2Cl)C3=NNC(=O)NC3=O)Cl SIFPVSSBEUBNGD-SSDOTTSWSA-N 0.000 claims 1
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- 229940126657 Compound 17 Drugs 0.000 claims 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 claims 1
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- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 claims 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 claims 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 claims 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 claims 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 229940125904 compound 1 Drugs 0.000 claims 1
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- 229940125797 compound 12 Drugs 0.000 claims 1
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- 229940125782 compound 2 Drugs 0.000 claims 1
- 229940125810 compound 20 Drugs 0.000 claims 1
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- 229940125833 compound 23 Drugs 0.000 claims 1
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- 229940125851 compound 27 Drugs 0.000 claims 1
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- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
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| CN111320609A (zh) | 2018-12-13 | 2020-06-23 | 拓臻股份有限公司 | 一种THRβ受体激动剂化合物及其制备方法和用途 |
| GEP20247637B (en) | 2019-05-08 | 2024-06-25 | Aligos Therapeutics Inc | Modulators of thr-b and methods of use thereof |
| AU2020336272A1 (en) | 2019-08-23 | 2022-04-14 | Terns Pharmaceuticals, Inc. | Thyroid hormone receptor beta agonist compounds |
| CN114375193B (zh) | 2019-09-12 | 2024-05-14 | 拓臻制药公司 | 甲状腺激素受体β激动剂化合物 |
| CN113278013B (zh) * | 2020-02-20 | 2022-09-23 | 昆药集团股份有限公司 | 2,6-二取代的1,2,4-三嗪-3,5-二酮化合物及其制备方法和应用 |
| US20230257367A1 (en) * | 2020-06-02 | 2023-08-17 | Chengdu Kanghong Pharmaceutical Co., Ltd. | Novel thyroid hormone beta receptor agonist |
| WO2022053028A1 (zh) * | 2020-09-10 | 2022-03-17 | 南京明德新药研发有限公司 | 1,2,4-三嗪-3,5(2h,4h)-二酮类化合物及其应用 |
| CN112645936B (zh) * | 2020-12-17 | 2022-03-01 | 山东第一医科大学(山东省医学科学院) | 取代的哒嗪酮类化合物及其用途 |
| CA3212130A1 (en) * | 2021-03-03 | 2022-09-09 | Terns Pharmaceuticals, Inc. | Thyroid hormone receptor beta agonist compounds |
| US20240398794A1 (en) | 2023-04-07 | 2024-12-05 | Terns Pharmaceuticals, Inc. | COMBINATIONS OF GLP-1R AND THRß AGONISTS AND METHODS OF USE THEREOF |
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| US6787652B1 (en) | 1999-09-30 | 2004-09-07 | Pfizer, Inc. | 6-Azauracil derivatives as thyroid receptor ligands |
| EP1088819B1 (en) | 1999-09-30 | 2005-06-15 | Pfizer Products Inc. | 6-azauracil derivatives as thyroid receptor ligands |
| US7230031B2 (en) | 2002-01-30 | 2007-06-12 | Kissei Pharmaceutical Co., Ltd. | Thyroid hormone receptor ligand, medicinal compositions containing the same and use thereof |
| WO2003094845A2 (en) | 2002-05-08 | 2003-11-20 | Bristol-Myers Squibb Company | Pyridine-based thyroid receptor ligands |
| US7572799B2 (en) | 2003-11-24 | 2009-08-11 | Pfizer Inc | Pyrazolo[4,3-d]pyrimidines as Phosphodiesterase Inhibitors |
| FR2882750B1 (fr) * | 2005-03-03 | 2007-05-11 | Pierre Fabre Medicament Sa | Derives de 1,2,4-triazines, leur preparation et leur application en therapeutique humaine |
| GB0513692D0 (en) | 2005-07-04 | 2005-08-10 | Karobio Ab | Novel pharmaceutical compositions |
| PL1919878T3 (pl) * | 2005-07-21 | 2011-03-31 | Hoffmann La Roche | Pochodne pirydazynonu jako agoniści receptora hormonu tarczycy |
| FR2933979B1 (fr) | 2008-07-15 | 2012-08-24 | Pf Medicament | Derives de triazines et uraciles, leur preparation et leur application en therapeutique humaine |
| TWI534144B (zh) | 2009-04-20 | 2016-05-21 | 田邊三菱製藥股份有限公司 | 甲狀腺荷爾蒙β受體作動藥 |
| WO2011038207A1 (en) | 2009-09-25 | 2011-03-31 | Metabasis Therapeutics, Inc. | Phosphorus-containing thyroid hormone receptor agonists and methods of use |
| EP2780338B1 (en) * | 2011-11-14 | 2016-11-09 | Ignyta, Inc. | Uracil derivatives as axl and c-met kinase inhibitors |
| CN103130723B (zh) | 2011-11-30 | 2015-01-14 | 成都地奥制药集团有限公司 | 一种多聚(adp-核糖)聚合酶抑制剂 |
| EP3189046B1 (en) * | 2014-09-05 | 2020-08-26 | Genentech, Inc. | Therapeutic compounds and uses thereof |
| IL266054B2 (en) | 2016-10-18 | 2023-10-01 | Madrigal Pharmaceuticals Inc | Methods for treating liver disorders or lipid disorders using a THR-BETA agonist |
| CN109574995B (zh) | 2018-01-23 | 2020-07-24 | 深圳市塔吉瑞生物医药有限公司 | 取代的哒嗪酮化合物 |
| CN111801324B (zh) | 2018-06-12 | 2021-10-22 | 四川海思科制药有限公司 | 甲状腺激素受体激动剂及其用途 |
| CA3110520A1 (en) | 2018-08-24 | 2020-02-27 | Terns, Inc. | Thyroid hormone receptor beta agonist compounds |
| US12391677B2 (en) | 2018-10-12 | 2025-08-19 | InventisBio Co., Ltd. | Thyroid hormone receptor agonists |
| CN111320609A (zh) | 2018-12-13 | 2020-06-23 | 拓臻股份有限公司 | 一种THRβ受体激动剂化合物及其制备方法和用途 |
| CN111484481A (zh) | 2019-01-26 | 2020-08-04 | 察略盛医药科技(上海)有限公司 | 哒嗪酮类衍生物、其制备方法及其在医药上的用途 |
| US12338206B2 (en) | 2019-02-21 | 2025-06-24 | Nanjing Ruijie Pharma Co., Ltd. | Compounds and their uses as thyroid hormone receptor agonists |
| CN114174282A (zh) | 2019-05-29 | 2022-03-11 | 南京明德新药研发有限公司 | 作为甲状腺素受体-β激动剂的哒嗪酮类衍生物及其应用 |
-
2019
- 2019-10-09 TW TW108136747A patent/TWI840423B/zh active
- 2019-10-09 TW TW113111231A patent/TWI884745B/zh active
- 2019-10-10 CN CN201980067301.7A patent/CN112839655B/zh active Active
- 2019-10-10 US US16/598,978 patent/US11203587B2/en active Active
- 2019-10-10 MA MA053868A patent/MA53868A/fr unknown
- 2019-10-10 JP JP2021519726A patent/JP7595004B2/ja active Active
- 2019-10-10 EP EP19870196.3A patent/EP3863635A4/en active Pending
- 2019-10-10 AU AU2019357618A patent/AU2019357618B2/en active Active
- 2019-10-10 CA CA3114015A patent/CA3114015A1/en active Pending
- 2019-10-10 WO PCT/US2019/055689 patent/WO2020077123A1/en not_active Ceased
- 2019-10-11 AR ARP190102912A patent/AR116694A1/es unknown
-
2022
- 2022-06-30 US US17/855,672 patent/US20220348561A1/en not_active Abandoned
-
2024
- 2024-11-25 JP JP2024204381A patent/JP2025041602A/ja active Pending
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