CA3104465A1 - Composes heterocycliques utiles dans le traitement d'une maladie - Google Patents
Composes heterocycliques utiles dans le traitement d'une maladie Download PDFInfo
- Publication number
- CA3104465A1 CA3104465A1 CA3104465A CA3104465A CA3104465A1 CA 3104465 A1 CA3104465 A1 CA 3104465A1 CA 3104465 A CA3104465 A CA 3104465A CA 3104465 A CA3104465 A CA 3104465A CA 3104465 A1 CA3104465 A1 CA 3104465A1
- Authority
- CA
- Canada
- Prior art keywords
- pyrazol
- biphenyl
- fluoro
- chloro
- carbonyl
- 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.)
- Pending
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 61
- 201000010099 disease Diseases 0.000 title claims abstract description 55
- 238000011282 treatment Methods 0.000 title abstract description 7
- 150000002391 heterocyclic compounds Chemical class 0.000 title abstract description 4
- 230000001419 dependent effect Effects 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims description 258
- -1 (R)-1-(2-chloro-4'-(5-(((1-(2-chlorophenyl)ethoxy)carbonyl)amino)-4-fluoro-1H-pyrazol-1-yl)-[1,1'-biphenyl]-yl)cyclopropane-1-carboxylic acid Chemical compound 0.000 claims description 198
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 132
- 238000000034 method Methods 0.000 claims description 123
- 239000004305 biphenyl Substances 0.000 claims description 116
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 94
- 125000000217 alkyl group Chemical group 0.000 claims description 93
- 125000004432 carbon atom Chemical group C* 0.000 claims description 87
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 81
- 229910052799 carbon Inorganic materials 0.000 claims description 79
- 125000001424 substituent group Chemical group 0.000 claims description 68
- 235000010290 biphenyl Nutrition 0.000 claims description 66
- WRGQSWVCFNIUNZ-GDCKJWNLSA-N 1-oleoyl-sn-glycerol 3-phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)(O)=O WRGQSWVCFNIUNZ-GDCKJWNLSA-N 0.000 claims description 53
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims description 53
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims description 30
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 23
- 125000006627 ethoxycarbonylamino group Chemical group 0.000 claims description 22
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 16
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 13
- XDMDPYZKKFPYAC-MRXNPFEDSA-N 1-[4-[5-[4-chloro-5-[[(1R)-1-(2-chlorophenyl)ethoxy]carbonylamino]pyrazol-1-yl]pyridin-2-yl]phenyl]cyclopropane-1-carboxylic acid Chemical compound ClC=1C=NN(C=1NC(=O)O[C@H](C)C1=C(C=CC=C1)Cl)C=1C=CC(=NC=1)C1=CC=C(C=C1)C1(CC1)C(=O)O XDMDPYZKKFPYAC-MRXNPFEDSA-N 0.000 claims description 11
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical class CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 9
- ZDIJGIHMESWCFF-MRXNPFEDSA-N 1-[4-[5-[5-[[(1R)-1-(2-chlorophenyl)ethoxy]carbonylamino]-4-fluoropyrazol-1-yl]pyridin-2-yl]phenyl]cyclopropane-1-carboxylic acid Chemical compound ClC1=C(C=CC=C1)[C@@H](C)OC(=O)NC1=C(C=NN1C=1C=CC(=NC=1)C1=CC=C(C=C1)C1(CC1)C(=O)O)F ZDIJGIHMESWCFF-MRXNPFEDSA-N 0.000 claims description 8
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 8
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 8
- 229940002612 prodrug Drugs 0.000 claims description 8
- 239000000651 prodrug Substances 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 2
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- MFFBTZGSWIPPND-LJQANCHMSA-N 1-[4-[4-[4-fluoro-5-[[(1R)-1-phenylethoxy]carbonylamino]pyrazol-1-yl]phenyl]-3-methylphenyl]cyclopropane-1-carboxylic acid Chemical compound FC=1C=NN(C=1NC(=O)O[C@H](C)C1=CC=CC=C1)C1=CC=C(C=C1)C1=C(C=C(C=C1)C1(CC1)C(=O)O)C MFFBTZGSWIPPND-LJQANCHMSA-N 0.000 claims 2
- LMSCJYHFCZUSNG-LJQANCHMSA-N [(1R)-1-phenylethyl] N-[4-chloro-2-[4-[4-[1-(methylsulfonylcarbamoyl)cyclopropyl]phenyl]phenyl]pyrazol-3-yl]carbamate Chemical compound C[C@H](C1=CC=CC=C1)OC(=O)NC2=C(C=NN2C3=CC=C(C=C3)C4=CC=C(C=C4)C5(CC5)C(=O)NS(=O)(=O)C)Cl LMSCJYHFCZUSNG-LJQANCHMSA-N 0.000 claims 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
- FIEYNBQUIDBZII-QGZVFWFLSA-N 1-[3-fluoro-4-[4-[4-fluoro-5-[[(1R)-1-phenylethoxy]carbonylamino]pyrazol-1-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound FC1=C(C=CC(=C1)C1(CC1)C(=O)O)C1=CC=C(C=C1)N1N=CC(=C1NC(=O)O[C@H](C)C1=CC=CC=C1)F FIEYNBQUIDBZII-QGZVFWFLSA-N 0.000 claims 1
- BYBREJDTMCSPBO-QGZVFWFLSA-N 1-[4-[4-[4-chloro-5-[[(1R)-1-phenylethoxy]carbonylamino]pyrazol-1-yl]phenyl]-2-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound ClC=1C=NN(C=1NC(=O)O[C@H](C)C1=CC=CC=C1)C1=CC=C(C=C1)C1=CC(=C(C=C1)C1(CC1)C(=O)O)F BYBREJDTMCSPBO-QGZVFWFLSA-N 0.000 claims 1
- PSRAUDUUUYAQQW-QGZVFWFLSA-N 1-[4-[4-[4-chloro-5-[[(1R)-1-phenylethoxy]carbonylamino]pyrazol-1-yl]phenyl]-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound ClC=1C=NN(C=1NC(=O)O[C@H](C)C1=CC=CC=C1)C1=CC=C(C=C1)C1=C(C=C(C=C1)C1(CC1)C(=O)O)F PSRAUDUUUYAQQW-QGZVFWFLSA-N 0.000 claims 1
- KGMFHQGWBBOGMX-LJQANCHMSA-N 1-[4-[4-[4-chloro-5-[[(1R)-1-phenylethoxy]carbonylamino]pyrazol-1-yl]phenyl]-3-methylphenyl]cyclopropane-1-carboxylic acid Chemical compound ClC=1C=NN(C=1NC(=O)O[C@H](C)C1=CC=CC=C1)C1=CC=C(C=C1)C1=C(C=C(C=C1)C1(CC1)C(=O)O)C KGMFHQGWBBOGMX-LJQANCHMSA-N 0.000 claims 1
- QUCZGUDNUFQGRB-QGZVFWFLSA-N [(1R)-1-(2-chlorophenyl)ethyl] N-[2-[4-[4-[1-(cyanocarbamoyl)cyclopropyl]-2-fluorophenyl]phenyl]-4-fluoropyrazol-3-yl]carbamate Chemical compound C(#N)NC(=O)C1(CC1)C1=CC(=C(C=C1)C1=CC=C(C=C1)N1N=CC(=C1NC(O[C@H](C)C1=C(C=CC=C1)Cl)=O)F)F QUCZGUDNUFQGRB-QGZVFWFLSA-N 0.000 claims 1
- VWOYOAMZHQUJGA-GOSISDBHSA-N [(1R)-1-(2-chlorophenyl)ethyl] N-[4-chloro-2-[4-[4-[1-(cyanocarbamoyl)cyclopropyl]phenyl]phenyl]pyrazol-3-yl]carbamate Chemical compound ClC=1C=NN(C=1NC(O[C@H](C)C1=C(C=CC=C1)Cl)=O)C1=CC=C(C=C1)C1=CC=C(C=C1)C1(CC1)C(NC#N)=O VWOYOAMZHQUJGA-GOSISDBHSA-N 0.000 claims 1
- NVCRVUNLHMUTRJ-QGZVFWFLSA-N [(1R)-1-(2-chlorophenyl)ethyl] N-[4-fluoro-2-[4-[2-fluoro-4-[1-(methylsulfonylcarbamoyl)cyclopropyl]phenyl]phenyl]pyrazol-3-yl]carbamate Chemical compound FC=1C=NN(C=1NC(O[C@H](C)C1=C(C=CC=C1)Cl)=O)C1=CC=C(C=C1)C1=C(C=C(C=C1)C1(CC1)C(NS(=O)(=O)C)=O)F NVCRVUNLHMUTRJ-QGZVFWFLSA-N 0.000 claims 1
- OOYCWKBRJWALRS-GOSISDBHSA-N [(1R)-1-(2-chlorophenyl)ethyl] N-[4-fluoro-2-[4-[4-[1-(methylsulfonylcarbamoyl)cyclopropyl]phenyl]phenyl]pyrazol-3-yl]carbamate Chemical compound FC=1C=NN(C=1NC(O[C@H](C)C1=C(C=CC=C1)Cl)=O)C1=CC=C(C=C1)C1=CC=C(C=C1)C1(CC1)C(NS(=O)(=O)C)=O OOYCWKBRJWALRS-GOSISDBHSA-N 0.000 claims 1
- ZPHJHGIDTNNEBZ-GOSISDBHSA-N [(1R)-1-phenylethyl] N-[4-chloro-2-[4-[4-[1-(2H-tetrazol-5-yl)cyclopropyl]phenyl]phenyl]pyrazol-3-yl]carbamate Chemical compound N1N=NN=C1C1(CC1)C1=CC=C(C=C1)C1=CC=C(C=C1)N1N=CC(=C1NC(O[C@H](C)C1=CC=CC=C1)=O)Cl ZPHJHGIDTNNEBZ-GOSISDBHSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 102000004137 Lysophosphatidic Acid Receptors Human genes 0.000 abstract description 14
- 108090000642 Lysophosphatidic Acid Receptors Proteins 0.000 abstract description 14
- 239000003446 ligand Substances 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 246
- 239000000203 mixture Substances 0.000 description 211
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 129
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 91
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 86
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 83
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 74
- 239000000047 product Substances 0.000 description 65
- 238000006243 chemical reaction Methods 0.000 description 57
- 239000012044 organic layer Substances 0.000 description 53
- 239000011541 reaction mixture Substances 0.000 description 50
- 239000007787 solid Substances 0.000 description 47
- 125000003118 aryl group Chemical group 0.000 description 44
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 43
- 235000019341 magnesium sulphate Nutrition 0.000 description 43
- 239000000243 solution Substances 0.000 description 43
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 239000007864 aqueous solution Substances 0.000 description 41
- 239000012267 brine Substances 0.000 description 41
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 41
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 39
- 238000003756 stirring Methods 0.000 description 37
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 238000012746 preparative thin layer chromatography Methods 0.000 description 32
- 125000001072 heteroaryl group Chemical group 0.000 description 30
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 238000009472 formulation Methods 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
- 125000004122 cyclic group Chemical group 0.000 description 25
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 25
- 125000003342 alkenyl group Chemical group 0.000 description 24
- 125000004429 atom Chemical group 0.000 description 24
- 239000012043 crude product Substances 0.000 description 22
- 230000001404 mediated effect Effects 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 125000005842 heteroatom Chemical group 0.000 description 20
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 19
- 102100040607 Lysophosphatidic acid receptor 1 Human genes 0.000 description 19
- 101710149745 Lysophosphatidic acid receptor 1 Proteins 0.000 description 19
- 238000003556 assay Methods 0.000 description 19
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 19
- 229910000029 sodium carbonate Inorganic materials 0.000 description 18
- 235000017550 sodium carbonate Nutrition 0.000 description 18
- 125000000304 alkynyl group Chemical group 0.000 description 17
- 229910052796 boron Inorganic materials 0.000 description 17
- 238000010898 silica gel chromatography Methods 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- 206010028980 Neoplasm Diseases 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 125000000547 substituted alkyl group Chemical group 0.000 description 14
- 229910052717 sulfur Inorganic materials 0.000 description 14
- 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 13
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 13
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- 238000004809 thin layer chromatography Methods 0.000 description 12
- 239000000556 agonist Substances 0.000 description 11
- 125000003545 alkoxy group Chemical group 0.000 description 11
- 239000005557 antagonist Substances 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 125000002877 alkyl aryl group Chemical group 0.000 description 9
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
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- 239000001301 oxygen Substances 0.000 description 9
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 9
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
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- 102000005962 receptors Human genes 0.000 description 8
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- 125000003710 aryl alkyl group Chemical group 0.000 description 7
- YMGUBTXCNDTFJI-UHFFFAOYSA-M cyclopropanecarboxylate Chemical compound [O-]C(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-M 0.000 description 7
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- 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 group 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 description 5
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 206010064930 age-related macular degeneration Diseases 0.000 description 5
- HVCKDQIAOZNULM-UHFFFAOYSA-N ethyl 2-(4-bromophenyl)pyrazole-3-carboxylate Chemical compound CCOC(=O)C1=CC=NN1C1=CC=C(Br)C=C1 HVCKDQIAOZNULM-UHFFFAOYSA-N 0.000 description 5
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- 125000004430 oxygen atom Chemical group O* 0.000 description 5
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- 125000000168 pyrrolyl group Chemical group 0.000 description 5
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- MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical compound C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 description 1
- 229960005332 zileuton Drugs 0.000 description 1
- 229950009268 zinostatin Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/14—Nitrogen atoms
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
- C07D231/52—Oxygen atom in position 3 and nitrogen atom in position 5, or vice versa
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/48—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
L'invention concerne des composés hétérocycliques qui sont des ligands du récepteur de l'acide lysophosphatidique utiles dans le traitement de maladies et d'états dépendant du récepteur de l'acide lysophosphatidique.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16/010,755 | 2018-06-18 | ||
US16/010,755 US10526298B2 (en) | 2013-03-15 | 2018-06-18 | Heterocyclic compounds useful in the treatment of disease |
PCT/US2019/037749 WO2019246109A1 (fr) | 2018-06-18 | 2019-06-18 | Composés hétérocycliques utiles dans le traitement d'une maladie |
Publications (1)
Publication Number | Publication Date |
---|---|
CA3104465A1 true CA3104465A1 (fr) | 2019-12-26 |
Family
ID=68985801
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA3104465A Pending CA3104465A1 (fr) | 2018-06-18 | 2019-06-18 | Composes heterocycliques utiles dans le traitement d'une maladie |
CA3046894A Abandoned CA3046894A1 (fr) | 2018-06-18 | 2019-06-18 | Composes heterocycliques utiles dans le traitement de maladies |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA3046894A Abandoned CA3046894A1 (fr) | 2018-06-18 | 2019-06-18 | Composes heterocycliques utiles dans le traitement de maladies |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP3807254A4 (fr) |
JP (1) | JP7467361B2 (fr) |
KR (1) | KR20210010635A (fr) |
CA (2) | CA3104465A1 (fr) |
WO (1) | WO2019246109A1 (fr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW202342017A (zh) * | 2022-02-25 | 2023-11-01 | 美商洛子峰生物有限公司 | 用於治療與lpa受體活性相關的病狀的化合物及組合物 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001060819A1 (fr) * | 2000-02-18 | 2001-08-23 | Kirin Beer Kabushiki Kaisha | Nouveaux composes d'isoxazole et de thiazole et leur utilisation en tant que medicaments |
US20040063738A1 (en) | 2001-12-05 | 2004-04-01 | Lahm George Philip | Substituted heterocyclic phthalic acid diamide arthropodicides |
US7846960B2 (en) | 2006-05-24 | 2010-12-07 | Eli Lilly And Company | FXR agonists |
GB2470833B (en) * | 2009-06-03 | 2011-06-01 | Amira Pharmaceuticals Inc | Polycyclic antagonists of lysophosphatidic acid receptors |
GB2474120B (en) * | 2009-10-01 | 2011-12-21 | Amira Pharmaceuticals Inc | Compounds as Lysophosphatidic acid receptor antagonists |
WO2012138648A1 (fr) * | 2011-04-06 | 2012-10-11 | Irm Llc | Compositions et procédés pour la modulation de récepteurs au lpa |
KR20140067048A (ko) * | 2011-08-15 | 2014-06-03 | 인터뮨, 인크. | 라이소포스파티드산 수용체 길항제 |
KR102090231B1 (ko) * | 2013-03-15 | 2020-03-17 | 에피젠 바이오싸이언시즈, 아이엔씨. | 질환의 치료에 유용한 헤테로환식 화합물 |
-
2019
- 2019-06-18 WO PCT/US2019/037749 patent/WO2019246109A1/fr unknown
- 2019-06-18 EP EP19821626.9A patent/EP3807254A4/fr active Pending
- 2019-06-18 CA CA3104465A patent/CA3104465A1/fr active Pending
- 2019-06-18 JP JP2020570145A patent/JP7467361B2/ja active Active
- 2019-06-18 CA CA3046894A patent/CA3046894A1/fr not_active Abandoned
- 2019-06-18 KR KR1020217001002A patent/KR20210010635A/ko active Search and Examination
Also Published As
Publication number | Publication date |
---|---|
EP3807254A1 (fr) | 2021-04-21 |
EP3807254A4 (fr) | 2022-03-23 |
JP2021529733A (ja) | 2021-11-04 |
CA3046894A1 (fr) | 2019-12-18 |
WO2019246109A1 (fr) | 2019-12-26 |
KR20210010635A (ko) | 2021-01-27 |
JP7467361B2 (ja) | 2024-04-15 |
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