HUE034829T2 - Heterocyclic derivatives - Google Patents

Info

Publication number

HUE034829T2

HUE034829T2 HUE14727034A HUE14727034A HUE034829T2 HU E034829 T2 HUE034829 T2 HU E034829T2 HU E14727034 A HUE14727034 A HU E14727034A HU E14727034 A HUE14727034 A HU E14727034A HU E034829 T2 HUE034829 T2 HU E034829T2

Authority

HU

Hungary

Prior art keywords

ylmethyl

methyl

pyrazole

carboxylic acid

benzyl

Prior art date

2013-05-23

Links

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• Global Dossier
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• 125000000623 heterocyclic group Chemical group 0.000 title description 13
• 125000000217 alkyl group Chemical group 0.000 claims description 210
• 125000003545 alkoxy group Chemical group 0.000 claims description 148
• 150000001875 compounds Chemical class 0.000 claims description 146
• 125000003118 aryl group Chemical group 0.000 claims description 81
• 125000005843 halogen group Chemical group 0.000 claims description 51
• 229910052757 nitrogen Inorganic materials 0.000 claims description 49
• 229910052801 chlorine Inorganic materials 0.000 claims description 45
• 229910052731 fluorine Inorganic materials 0.000 claims description 44
• 229910052799 carbon Inorganic materials 0.000 claims description 31
• 239000002253 acid Substances 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
• 150000001412 amines Chemical class 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 12
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 206010061218 Inflammation Diseases 0.000 claims description 9
• 230000004054 inflammatory process Effects 0.000 claims description 9
• 125000004429 atom Chemical group 0.000 claims description 8
• 238000002360 preparation method Methods 0.000 claims description 8
• 239000007788 liquid Substances 0.000 claims description 7
• 208000001953 Hypotension Diseases 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 5
• 201000011510 cancer Diseases 0.000 claims description 5
• 206010040070 Septic Shock Diseases 0.000 claims description 4
• 230000002378 acidificating effect Effects 0.000 claims description 4
• 230000036303 septic shock Effects 0.000 claims description 4
• 239000000126 substance Substances 0.000 claims description 4
• 230000004304 visual acuity Effects 0.000 claims description 4
• 229910052727 yttrium Inorganic materials 0.000 claims description 4
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 3
• 230000000241 respiratory effect Effects 0.000 claims description 3
• 230000015271 coagulation Effects 0.000 claims description 2
• 238000005345 coagulation Methods 0.000 claims description 2
• 229910052740 iodine Inorganic materials 0.000 claims description 2
• BQMDWLHBHLILMV-HVTWWXFQSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCSC)C(O)=O BQMDWLHBHLILMV-HVTWWXFQSA-N 0.000 claims 4
• 108010036387 trimethionine Proteins 0.000 claims 3
• 239000000654 additive Substances 0.000 claims 2
• 230000000996 additive effect Effects 0.000 claims 2
• 150000001408 amides Chemical class 0.000 claims 2
• 239000013256 coordination polymer Substances 0.000 claims 2
• 230000002792 vascular Effects 0.000 claims 2
• YPFNIPKMNMDDDB-UHFFFAOYSA-K 2-[2-[bis(carboxylatomethyl)amino]ethyl-(2-hydroxyethyl)amino]acetate;iron(3+) Chemical compound [Fe+3].OCCN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O YPFNIPKMNMDDDB-UHFFFAOYSA-K 0.000 claims 1
• 241000219495 Betulaceae Species 0.000 claims 1
• 206010052770 Coma states Diseases 0.000 claims 1
• 208000010201 Exanthema Diseases 0.000 claims 1
• 208000008589 Obesity Diseases 0.000 claims 1
• 235000008753 Papaver somniferum Nutrition 0.000 claims 1
• 240000001090 Papaver somniferum Species 0.000 claims 1
• 241000555745 Sciuridae Species 0.000 claims 1
• 206010003230 arteritis Diseases 0.000 claims 1
• 229910052789 astatine Inorganic materials 0.000 claims 1
• 206010008129 cerebral palsy Diseases 0.000 claims 1
• 239000003610 charcoal Substances 0.000 claims 1
• 239000003245 coal Substances 0.000 claims 1
• 239000003086 colorant Substances 0.000 claims 1
• 239000002131 composite material Substances 0.000 claims 1
• 201000005884 exanthem Diseases 0.000 claims 1
• 238000010304 firing Methods 0.000 claims 1
• 230000004927 fusion Effects 0.000 claims 1
• 239000003292 glue Substances 0.000 claims 1
• 230000000423 heterosexual effect Effects 0.000 claims 1
• 210000001144 hymen Anatomy 0.000 claims 1
• 239000002054 inoculum Substances 0.000 claims 1
• 208000012866 low blood pressure Diseases 0.000 claims 1
• 235000012054 meals Nutrition 0.000 claims 1
• 239000002184 metal Substances 0.000 claims 1
• 229910052751 metal Inorganic materials 0.000 claims 1
• 239000000178 monomer Substances 0.000 claims 1
• 235000015097 nutrients Nutrition 0.000 claims 1
• 235000020824 obesity Nutrition 0.000 claims 1
• 229910052698 phosphorus Inorganic materials 0.000 claims 1
• 206010037844 rash Diseases 0.000 claims 1
• 230000000306 recurrent effect Effects 0.000 claims 1
• 239000011435 rock Substances 0.000 claims 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims 1
• 229960001860 salicylate Drugs 0.000 claims 1
• 210000002784 stomach Anatomy 0.000 claims 1
• 239000004575 stone Substances 0.000 claims 1
• 235000013616 tea Nutrition 0.000 claims 1
• 210000002435 tendon Anatomy 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 272
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 225
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 181
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 130
• 235000019439 ethyl acetate Nutrition 0.000 description 125
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 120
• 239000000203 mixture Substances 0.000 description 108
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 107
• 239000007787 solid Substances 0.000 description 100
• 239000011541 reaction mixture Substances 0.000 description 86
• 239000000243 solution Substances 0.000 description 84
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 77
• 239000012267 brine Substances 0.000 description 75
• 125000001424 substituent group Chemical group 0.000 description 75
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 67
• 239000000377 silicon dioxide Substances 0.000 description 64
• 125000001072 heteroaryl group Chemical group 0.000 description 63
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
• -1 indole amides Chemical class 0.000 description 53
• 238000006243 chemical reaction Methods 0.000 description 51
• WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 49
• 108090000113 Plasma Kallikrein Proteins 0.000 description 47
• 102000003827 Plasma Kallikrein Human genes 0.000 description 45
• 239000002904 solvent Substances 0.000 description 42
• 238000003818 flash chromatography Methods 0.000 description 40
• 238000005160 1H NMR spectroscopy Methods 0.000 description 36
• 238000004587 chromatography analysis Methods 0.000 description 36
• 150000003839 salts Chemical class 0.000 description 36
• 239000010410 layer Substances 0.000 description 35
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 31
• 239000000047 product Substances 0.000 description 31
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 30
• 239000003921 oil Substances 0.000 description 29
• 235000019198 oils Nutrition 0.000 description 29
• 239000003480 eluent Substances 0.000 description 27
• 238000003756 stirring Methods 0.000 description 27
• 239000012044 organic layer Substances 0.000 description 26
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 25
• 239000012453 solvate Substances 0.000 description 25
• 238000000034 method Methods 0.000 description 24
• 229920006395 saturated elastomer Polymers 0.000 description 24
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 23
• 125000004432 carbon atom Chemical group C* 0.000 description 23
• 229910052760 oxygen Inorganic materials 0.000 description 23
• 229910052717 sulfur Inorganic materials 0.000 description 23
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 22
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 22
• 125000005842 heteroatom Chemical group 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• MVXVYAKCVDQRLW-UHFFFAOYSA-N azain Natural products C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
• 230000002829 reductive effect Effects 0.000 description 21
• 125000004043 oxo group Chemical group O=* 0.000 description 20
• 238000011282 treatment Methods 0.000 description 19
• 239000003112 inhibitor Substances 0.000 description 18
• 125000002757 morpholinyl group Chemical group 0.000 description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
• 125000003386 piperidinyl group Chemical group 0.000 description 17
• 125000006239 protecting group Chemical group 0.000 description 17
• 239000000725 suspension Substances 0.000 description 17
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
• SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 16
• 239000003814 drug Substances 0.000 description 16
• 229910000027 potassium carbonate Inorganic materials 0.000 description 16
• 239000007821 HATU Substances 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 239000012043 crude product Substances 0.000 description 15
• 125000004093 cyano group Chemical group *C#N 0.000 description 15
• 230000000694 effects Effects 0.000 description 15
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• 125000004433 nitrogen atom Chemical group N* 0.000 description 15
• 239000000843 powder Substances 0.000 description 15
• 238000010992 reflux Methods 0.000 description 15
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
• 229940086542 triethylamine Drugs 0.000 description 15
• LWDVTRXNUGVQES-UHFFFAOYSA-N 6-(aminomethyl)isoquinolin-1-amine Chemical compound NC1=NC=CC2=CC(CN)=CC=C21 LWDVTRXNUGVQES-UHFFFAOYSA-N 0.000 description 14
• 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 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
• 206010012601 diabetes mellitus Diseases 0.000 description 13
• 238000009472 formulation Methods 0.000 description 13
• YUHZIUAREWNXJT-UHFFFAOYSA-N (2-fluoropyridin-3-yl)boronic acid Chemical class OB(O)C1=CC=CN=C1F YUHZIUAREWNXJT-UHFFFAOYSA-N 0.000 description 12
• 150000005258 1H-pyrrolo(2,3-b)pyridines Chemical class 0.000 description 12
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 12
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 12
• 229910052721 tungsten Inorganic materials 0.000 description 12
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• 206010012688 Diabetic retinal oedema Diseases 0.000 description 11
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• VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 11
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• 239000002244 precipitate Substances 0.000 description 11
• 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 11
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 10
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 10
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
• 229910052739 hydrogen Inorganic materials 0.000 description 10
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 10
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 10
• UVUGVZJMKMGPPT-UHFFFAOYSA-N 1-[[4-[(2-oxopyridin-1-yl)methyl]phenyl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound OC(=O)c1cn(Cc2ccc(Cn3ccccc3=O)cc2)nc1C(F)(F)F UVUGVZJMKMGPPT-UHFFFAOYSA-N 0.000 description 9
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 9
• 206010012689 Diabetic retinopathy Diseases 0.000 description 9
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• 239000013058 crude material Substances 0.000 description 9
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• AKICKQUUHMJAPD-UHFFFAOYSA-N 1-[[4-(chloromethyl)phenyl]methyl]-4-methylpyrazole Chemical compound Cc1cnn(Cc2ccc(CCl)cc2)c1 AKICKQUUHMJAPD-UHFFFAOYSA-N 0.000 description 8
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
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• 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
• 235000019341 magnesium sulphate Nutrition 0.000 description 8
• MCLBVPPTLFLLSH-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[4-[(4-methylpyrazol-1-yl)methyl]phenyl]methyl]imidazole-4-carboxamide Chemical compound C1=C(C)C=NN1CC(C=C1)=CC=C1CN1C=C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)N=C1 MCLBVPPTLFLLSH-UHFFFAOYSA-N 0.000 description 8
• RAUIBWGXUJDXBK-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-ethyl-4-methyl-5-[[4-[(2-oxopyridin-1-yl)methyl]phenyl]methyl]pyrrole-2-carboxamide Chemical compound CCN1C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=CC(C)=C1CC(C=C1)=CC=C1CN1C=CC=CC1=O RAUIBWGXUJDXBK-UHFFFAOYSA-N 0.000 description 8
• 125000001624 naphthyl group Chemical group 0.000 description 8
• 239000000546 pharmaceutical excipient Substances 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• MJCHTYLRKNLUNO-UHFFFAOYSA-N 2,5-dimethyl-1-[(2-phenyl-1,3-thiazol-4-yl)methyl]pyrrole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=C(C)N1CC1=CSC(C=2C=CC=CC=2)=N1 MJCHTYLRKNLUNO-UHFFFAOYSA-N 0.000 description 7
• 206010019860 Hereditary angioedema Diseases 0.000 description 7
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• 239000003795 chemical substances by application Substances 0.000 description 7
• SLRCFYCDNOSNHM-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(6-pyrrolidin-1-ylpyridin-3-yl)methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C=1C=C2C(N)=NC=CC2=CC=1CNC(=O)C(C(=N1)C(F)(F)F)=CN1CC(C=N1)=CC=C1N1CCCC1 SLRCFYCDNOSNHM-UHFFFAOYSA-N 0.000 description 7
• DWHBFTOTOHZYPK-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[4-[(4-methylpyrazol-1-yl)methyl]phenyl]methyl]-3-morpholin-4-ylpyrazole-4-carboxamide Chemical compound C1=C(C)C=NN1CC(C=C1)=CC=C1CN1N=C(N2CCOCC2)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 DWHBFTOTOHZYPK-UHFFFAOYSA-N 0.000 description 7
• KEVAPGHQGBLBGH-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-3-cyclopropyl-1-[[4-[(4-methylpyrazol-1-yl)methyl]phenyl]methyl]pyrazole-4-carboxamide Chemical compound C1=C(C)C=NN1CC(C=C1)=CC=C1CN1N=C(C2CC2)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 KEVAPGHQGBLBGH-UHFFFAOYSA-N 0.000 description 7
• 229940126155 plasma kallikrein inhibitor Drugs 0.000 description 7
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 6
• LAXWAYHNIVBBPC-UHFFFAOYSA-N 6-(aminomethyl)isoquinolin-1-amine;dihydrochloride Chemical compound Cl.Cl.NC1=NC=CC2=CC(CN)=CC=C21 LAXWAYHNIVBBPC-UHFFFAOYSA-N 0.000 description 6
• 208000031229 Cardiomyopathies Diseases 0.000 description 6
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
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• HSHMTRLVTQNRRC-UHFFFAOYSA-N [4-[(4-methylpyrazol-1-yl)methyl]phenyl]methanol Chemical compound C1=C(C)C=NN1CC1=CC=C(CO)C=C1 HSHMTRLVTQNRRC-UHFFFAOYSA-N 0.000 description 6
• 125000003277 amino group Chemical group 0.000 description 6
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• 125000001153 fluoro group Chemical group F* 0.000 description 6
• 238000004128 high performance liquid chromatography Methods 0.000 description 6
• 150000002473 indoazoles Chemical class 0.000 description 6
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