TWI591067B - 吡唑并吡啶及吡唑并嘧啶 - Google Patents

Info

Publication number

TWI591067B

TWI591067B TW104115312A TW104115312A TWI591067B TW I591067 B TWI591067 B TW I591067B TW 104115312 A TW104115312 A TW 104115312A TW 104115312 A TW104115312 A TW 104115312A TW I591067 B TWI591067 B TW I591067B

Authority

TW

Taiwan

Prior art keywords

amino

methyl

phenyl

fluoro

pyrazolo

Prior art date

2014-05-14

Links

• Espacenet
• Global Dossier
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• APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 title description 3
• 150000005229 pyrazolopyridines Chemical class 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 353
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 289
• 238000002360 preparation method Methods 0.000 claims description 248
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 187
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 159
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 148
• -1 C 1 -C 6 alkoxy Chemical group 0.000 claims description 141
• 125000000623 heterocyclic group Chemical group 0.000 claims description 140
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 133
• 125000005843 halogen group Chemical group 0.000 claims description 111
• 229910052799 carbon Inorganic materials 0.000 claims description 87
• 125000001072 heteroaryl group Chemical group 0.000 claims description 84
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 78
• 150000003839 salts Chemical class 0.000 claims description 75
• 229910052739 hydrogen Inorganic materials 0.000 claims description 70
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 69
• 125000001624 naphthyl group Chemical group 0.000 claims description 68
• 229910052757 nitrogen Inorganic materials 0.000 claims description 67
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 66
• 125000000217 alkyl group Chemical group 0.000 claims description 62
• 150000001412 amines Chemical class 0.000 claims description 55
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 51
• 229910052760 oxygen Inorganic materials 0.000 claims description 51
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 51
• 125000001424 substituent group Chemical group 0.000 claims description 50
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 46
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
• 125000004434 sulfur atom Chemical group 0.000 claims description 36
• 229920006395 saturated elastomer Polymers 0.000 claims description 33
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 32
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 28
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 25
• 125000003277 amino group Chemical group 0.000 claims description 24
• 208000006673 asthma Diseases 0.000 claims description 23
• 235000005152 nicotinamide Nutrition 0.000 claims description 23
• 239000011570 nicotinamide Substances 0.000 claims description 23
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 22
• 239000002253 acid Substances 0.000 claims description 20
• 239000003814 drug Substances 0.000 claims description 20
• 125000002950 monocyclic group Chemical group 0.000 claims description 20
• 238000011282 treatment Methods 0.000 claims description 20
• 125000005842 heteroatom Chemical group 0.000 claims description 19
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 18
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
• 239000001257 hydrogen Substances 0.000 claims description 18
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 17
• 125000004104 aryloxy group Chemical group 0.000 claims description 17
• 125000001153 fluoro group Chemical group F* 0.000 claims description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 16
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 16
• 125000003545 alkoxy group Chemical group 0.000 claims description 15
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
• 125000003118 aryl group Chemical group 0.000 claims description 13
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 13
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
• 239000004202 carbamide Substances 0.000 claims description 11
• 229960003742 phenol Drugs 0.000 claims description 11
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 10
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 8
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 8
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 8
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 7
• 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 7
• 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 7
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 6
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 6
• 206010040070 Septic Shock Diseases 0.000 claims description 6
• 201000008937 atopic dermatitis Diseases 0.000 claims description 6
• 206010061218 Inflammation Diseases 0.000 claims description 5
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 5
• 206010003246 arthritis Diseases 0.000 claims description 5
• 208000010668 atopic eczema Diseases 0.000 claims description 5
• 230000001684 chronic effect Effects 0.000 claims description 5
• 230000004054 inflammatory process Effects 0.000 claims description 5
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
• 208000024827 Alzheimer disease Diseases 0.000 claims description 4
• 208000035143 Bacterial infection Diseases 0.000 claims description 4
• 206010014561 Emphysema Diseases 0.000 claims description 4
• 206010028735 Nasal congestion Diseases 0.000 claims description 4
• 201000004681 Psoriasis Diseases 0.000 claims description 4
• 208000011191 Pulmonary vascular disease Diseases 0.000 claims description 4
• 230000001154 acute effect Effects 0.000 claims description 4
• 125000004429 atom Chemical group 0.000 claims description 4
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
• SXLQVQAYOSDJEP-UHFFFAOYSA-N 4-[[2-[ethyl(methylsulfonyl)amino]-5-fluorophenyl]methylamino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)N(S(=O)(=O)C)C1=C(CNC2=NC(=CC3=C2C(=NN3)C(=O)N)C3=C(C=C(C(=C3)F)O)CC(F)(F)F)C=C(C=C1)F SXLQVQAYOSDJEP-UHFFFAOYSA-N 0.000 claims description 3
• GTGNVCWEJRBFQX-AWEZNQCLSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[[(1S)-1-[2-[methyl(methylsulfonyl)amino]phenyl]ethyl]amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)N[C@@H](C)C1=C(C=CC=C1)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC GTGNVCWEJRBFQX-AWEZNQCLSA-N 0.000 claims description 3
• WZBOJPGRAWGCAD-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C)C)C(=NN2)C(=O)N)CC(F)(F)F)O WZBOJPGRAWGCAD-UHFFFAOYSA-N 0.000 claims description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
• 208000000884 Airway Obstruction Diseases 0.000 claims description 3
• 201000001320 Atherosclerosis Diseases 0.000 claims description 3
• 206010048962 Brain oedema Diseases 0.000 claims description 3
• 206010006458 Bronchitis chronic Diseases 0.000 claims description 3
• 206010006482 Bronchospasm Diseases 0.000 claims description 3
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
• 208000031229 Cardiomyopathies Diseases 0.000 claims description 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
• 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 3
• 208000011231 Crohn disease Diseases 0.000 claims description 3
• 201000004624 Dermatitis Diseases 0.000 claims description 3
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
• 206010013935 Dysmenorrhoea Diseases 0.000 claims description 3
• 201000009273 Endometriosis Diseases 0.000 claims description 3
• 206010016654 Fibrosis Diseases 0.000 claims description 3
• 208000010412 Glaucoma Diseases 0.000 claims description 3
• 201000005569 Gout Diseases 0.000 claims description 3
• 206010018634 Gouty Arthritis Diseases 0.000 claims description 3
• 206010019280 Heart failures Diseases 0.000 claims description 3
• 208000016300 Idiopathic chronic eosinophilic pneumonia Diseases 0.000 claims description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
• 208000000112 Myalgia Diseases 0.000 claims description 3
• 208000007201 Myocardial reperfusion injury Diseases 0.000 claims description 3
• OCHNNQQTHRHVOJ-UHFFFAOYSA-N N-[2-[[[6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridin-4-yl]-methylamino]methyl]phenyl]-N-methylmethanesulfonamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)N(C)CC1=C(C=CC=C1)N(S(=O)(=O)C)C)C=NN2)CC(F)(F)F)O OCHNNQQTHRHVOJ-UHFFFAOYSA-N 0.000 claims description 3
• 206010028741 Nasal inflammation Diseases 0.000 claims description 3
• 206010028980 Neoplasm Diseases 0.000 claims description 3
• 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 3
• 208000008589 Obesity Diseases 0.000 claims description 3
• 208000001132 Osteoporosis Diseases 0.000 claims description 3
• 208000002193 Pain Diseases 0.000 claims description 3
• 206010037660 Pyrexia Diseases 0.000 claims description 3
• 206010063837 Reperfusion injury Diseases 0.000 claims description 3
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
• 208000017442 Retinal disease Diseases 0.000 claims description 3
• 206010038910 Retinitis Diseases 0.000 claims description 3
• 206010038923 Retinopathy Diseases 0.000 claims description 3
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
• 206010039094 Rhinitis perennial Diseases 0.000 claims description 3
• 201000010001 Silicosis Diseases 0.000 claims description 3
• 208000006045 Spondylarthropathies Diseases 0.000 claims description 3
• 208000006011 Stroke Diseases 0.000 claims description 3
• 206010042496 Sunburn Diseases 0.000 claims description 3
• 208000007536 Thrombosis Diseases 0.000 claims description 3
• 206010044248 Toxic shock syndrome Diseases 0.000 claims description 3
• 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 3
• 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
• 206010046914 Vaginal infection Diseases 0.000 claims description 3
• 201000008100 Vaginitis Diseases 0.000 claims description 3
• 208000036142 Viral infection Diseases 0.000 claims description 3
• 206010069351 acute lung injury Diseases 0.000 claims description 3
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 3
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
• 208000002205 allergic conjunctivitis Diseases 0.000 claims description 3
• 201000010105 allergic rhinitis Diseases 0.000 claims description 3
• 208000024998 atopic conjunctivitis Diseases 0.000 claims description 3
• 208000006752 brain edema Diseases 0.000 claims description 3
• 201000009267 bronchiectasis Diseases 0.000 claims description 3
• 206010006451 bronchitis Diseases 0.000 claims description 3
• 230000007885 bronchoconstriction Effects 0.000 claims description 3
• 201000011510 cancer Diseases 0.000 claims description 3
• 208000007451 chronic bronchitis Diseases 0.000 claims description 3
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• 230000004761 fibrosis Effects 0.000 claims description 3
• 238000011010 flushing procedure Methods 0.000 claims description 3
• 230000035874 hyperreactivity Effects 0.000 claims description 3
• 208000028867 ischemia Diseases 0.000 claims description 3
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
• 208000019423 liver disease Diseases 0.000 claims description 3
• 208000002780 macular degeneration Diseases 0.000 claims description 3
• 229930182817 methionine Natural products 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
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• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
• 208000005987 polymyositis Diseases 0.000 claims description 3
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• JCWGFKMAGZQXMM-UHFFFAOYSA-N 2-[4-amino-2-[[2-[benzenesulfonyl(methyl)amino]-5-hydroxyphenyl]methylamino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]pyridin-3-yl]-2-iminoacetamide Chemical compound CN(C1=CC=C(O)C=C1CNC1=C(C(=N)C(N)=O)C(N)=CC(=N1)C1=CC(F)=C(O)C=C1CC(F)(F)F)S(=O)(=O)C1=CC=CC=C1 JCWGFKMAGZQXMM-UHFFFAOYSA-N 0.000 claims description 2
• FBOHXIKPCPPBCA-UHFFFAOYSA-N 2-[4-amino-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-2-[[2-[methyl(pyridin-3-ylsulfonyl)amino]phenyl]methylamino]pyridin-3-yl]-2-iminoacetamide Chemical compound CN(C1=CC=CC=C1CNC1=C(C(=N)C(N)=O)C(N)=CC(=N1)C1=CC(F)=C(O)C=C1CC(F)(F)F)S(=O)(=O)C1=CC=CN=C1 FBOHXIKPCPPBCA-UHFFFAOYSA-N 0.000 claims description 2
• WBJKFNOYTALWJK-UHFFFAOYSA-N 3-ethyl-4-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol Chemical compound CCC1=CC(O)=CC=C1C1=NC(N2CCC3=CC(F)=CC=C3C2)=C2C=NNC2=C1 WBJKFNOYTALWJK-UHFFFAOYSA-N 0.000 claims description 2
• COIIDULXTXBYHQ-UHFFFAOYSA-N 3-ethyl-4-[4-(6-methoxy-7-phenylmethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol Chemical compound CCC1=CC(O)=CC=C1C1=NC(N2CCC3=C(C2)C=C(OCC2=CC=CC=C2)C(OC)=C3)=C2C=NNC2=C1 COIIDULXTXBYHQ-UHFFFAOYSA-N 0.000 claims description 2
• SIIZUOGQMGVPBG-UHFFFAOYSA-N 3-ethyl-4-[4-[6-(4-methylimidazol-1-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol Chemical compound CCC1=CC(O)=CC=C1C1=NC(N2CCC3=CC(=CC=C3C2)N2C=NC(C)=C2)=C2C=NNC2=C1 SIIZUOGQMGVPBG-UHFFFAOYSA-N 0.000 claims description 2
• YDHPBDFTCLQXLO-UHFFFAOYSA-N 4-(cyclopentylmethylamino)-6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C1(CCCC1)CNC1=NC(=CC2=C1C(=NN2)C(=O)NC)C2=C(C=C(C(=C2)F)O)CC YDHPBDFTCLQXLO-UHFFFAOYSA-N 0.000 claims description 2
• FRFUERGTAKOJMH-UHFFFAOYSA-N 4-(cyclopentylmethylamino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C1(CCCC1)CNC1=NC(=CC2=C1C(=NN2)C(=O)NC)C2=C(C=C(C(=C2)F)O)CC(F)(F)F FRFUERGTAKOJMH-UHFFFAOYSA-N 0.000 claims description 2
• FTSYURCNSVPOMF-UHFFFAOYSA-N 4-[4-(2-cyclopropylethylamino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-2-fluoro-5-(2,2,2-trifluoroethyl)phenol Chemical compound C1(CC1)CCNC1=C2C(=NC(=N1)C1=CC(=C(C=C1CC(F)(F)F)O)F)NN=C2 FTSYURCNSVPOMF-UHFFFAOYSA-N 0.000 claims description 2
• FHHZSTXNBSIOAQ-UHFFFAOYSA-N 4-[4-(butylamino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-2-fluoro-5-(2,2,2-trifluoroethyl)phenol Chemical compound C(CCC)NC1=C2C(=NC(=N1)C1=CC(=C(C=C1CC(F)(F)F)O)F)NN=C2 FHHZSTXNBSIOAQ-UHFFFAOYSA-N 0.000 claims description 2
• VDOZUOGOAFISEB-UHFFFAOYSA-N 4-[4-(cyclopropylmethylamino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-2-fluoro-5-(2,2,2-trifluoroethyl)phenol Chemical compound C1(CC1)CNC1=C2C(=NC(=N1)C1=CC(=C(C=C1CC(F)(F)F)O)F)NN=C2 VDOZUOGOAFISEB-UHFFFAOYSA-N 0.000 claims description 2
• ZUSBJVMMJXWILX-UHFFFAOYSA-N 4-[[2-[benzenesulfonyl(methyl)amino]phenyl]methylamino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C1=CC=CC=C1)C)C(=NN2)C(=O)N)CC(F)(F)F)O ZUSBJVMMJXWILX-UHFFFAOYSA-N 0.000 claims description 2
• RYQQIWSTVBYSJY-UHFFFAOYSA-N 4-[[2-[dimethylsulfamoyl(methyl)amino]phenyl]methylamino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound CNC(=O)c1n[nH]c2cc(nc(NCc3ccccc3N(C)S(=O)(=O)N(C)C)c12)-c1cc(F)c(O)cc1CC(F)(F)F RYQQIWSTVBYSJY-UHFFFAOYSA-N 0.000 claims description 2
• BPDPCRMNEGZLFA-UHFFFAOYSA-N 4-[[2-[ethyl(ethylsulfonyl)amino]phenyl]methylamino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)N(C1=C(CNC2=NC(=CC3=C2C(=NN3)C(=O)NC)C3=C(C=C(C(=C3)F)O)CC(F)(F)F)C=CC=C1)S(=O)(=O)CC BPDPCRMNEGZLFA-UHFFFAOYSA-N 0.000 claims description 2
• KYZUYGBVLZMXTB-UHFFFAOYSA-N 4-[[5-chloro-2-[methyl(methylsulfonyl)amino]pyridin-3-yl]methylamino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound ClC=1C=C(C(=NC1)N(S(=O)(=O)C)C)CNC1=NC(=CC2=C1C(=NN2)C(=O)N)C2=C(C=C(C(=C2)F)O)CC(F)(F)F KYZUYGBVLZMXTB-UHFFFAOYSA-N 0.000 claims description 2
• GTGNVCWEJRBFQX-CQSZACIVSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[[(1R)-1-[2-[methyl(methylsulfonyl)amino]phenyl]ethyl]amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)N[C@H](C)C1=C(C=CC=C1)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC GTGNVCWEJRBFQX-CQSZACIVSA-N 0.000 claims description 2
• VEWTZPFUPWZJAM-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-2H-pyrazolo[3,4-d]pyrimidine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=NC(=C2C(=N1)NN=C2C(=O)N)NCC2=C(C=CC=C2)N(S(=O)(=O)C)C)CC(F)(F)F)O VEWTZPFUPWZJAM-UHFFFAOYSA-N 0.000 claims description 2
• RGWGGKUGOBJLKL-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[2-[methyl(methylsulfonyl)amino]pyridin-3-yl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC=1C(=NC=CC1)N(S(=O)(=O)C)C)C(=NN2)C(=O)N)CC(F)(F)F)O RGWGGKUGOBJLKL-UHFFFAOYSA-N 0.000 claims description 2
• SVRYJVCODHDAJL-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-(2-methylpropylamino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC(C)C)C(=NN2)C(=O)NC)CC(F)(F)F)O SVRYJVCODHDAJL-UHFFFAOYSA-N 0.000 claims description 2
• 241000222122 Candida albicans Species 0.000 claims description 2
• 206010007134 Candida infections Diseases 0.000 claims description 2
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 2
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• JABQPZDKQDXGKV-UHFFFAOYSA-N [1-[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]-3-methylazetidin-3-yl] formate Chemical compound C(=O)OC1(CN(C1)C1=NC(=CC2=C1C=NN2)C2=C(C=C(C=C2)O)CC)C JABQPZDKQDXGKV-UHFFFAOYSA-N 0.000 claims description 2
• GDTSORVEXWKOID-UHFFFAOYSA-N [4-[4-(7,8-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-ethylphenyl] formate Chemical compound C(=O)OC1=CC(=C(C=C1)C1=CC2=C(C(=N1)N1CC3=C(C(=CC=C3CC1)OC)OC)C=NN2)CC GDTSORVEXWKOID-UHFFFAOYSA-N 0.000 claims description 2
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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
• 150000003751 zinc Chemical class 0.000 description 1
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
• XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1