TWI435723B - 經取代之異喹啉及異喹啉酮衍生物 - Google Patents
經取代之異喹啉及異喹啉酮衍生物 Download PDFInfo
- Publication number
- TWI435723B TWI435723B TW096149805A TW96149805A TWI435723B TW I435723 B TWI435723 B TW I435723B TW 096149805 A TW096149805 A TW 096149805A TW 96149805 A TW96149805 A TW 96149805A TW I435723 B TWI435723 B TW I435723B
- Authority
- TW
- Taiwan
- Prior art keywords
- alkyl
- compound
- yloxy
- isoquinolin
- halogen
- Prior art date
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- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 title description 17
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 title description 12
- 150000002537 isoquinolines Chemical class 0.000 title 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 227
- 150000001875 compounds Chemical class 0.000 claims description 133
- 125000000623 heterocyclic group Chemical group 0.000 claims description 98
- 229910052736 halogen Inorganic materials 0.000 claims description 90
- 150000002367 halogens Chemical class 0.000 claims description 90
- -1 NH 2 Chemical group 0.000 claims description 64
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 45
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 35
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 125000002947 alkylene group Chemical group 0.000 claims description 15
- 102000000568 rho-Associated Kinases Human genes 0.000 claims description 15
- 108010041788 rho-Associated Kinases Proteins 0.000 claims description 15
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000006720 (C1-C6) alkyl (C6-C10) aryl group Chemical group 0.000 claims description 11
- 206010020772 Hypertension Diseases 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 230000003176 fibrotic effect Effects 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 206010020880 Hypertrophy Diseases 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 6
- 230000026731 phosphorylation Effects 0.000 claims description 6
- 238000006366 phosphorylation reaction Methods 0.000 claims description 6
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000011161 development Methods 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- RNEDMLYPHADAJP-UHFFFAOYSA-N 2-[4-[(7-chloro-1-oxo-2h-isoquinolin-6-yl)oxy]piperidin-1-yl]acetic acid Chemical compound C1CN(CC(=O)O)CCC1OC(C(=C1)Cl)=CC2=C1C(=O)NC=C2 RNEDMLYPHADAJP-UHFFFAOYSA-N 0.000 claims description 4
- 208000030507 AIDS Diseases 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000035143 Bacterial infection Diseases 0.000 claims description 4
- 201000006474 Brain Ischemia Diseases 0.000 claims description 4
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 4
- 208000006029 Cardiomegaly Diseases 0.000 claims description 4
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 4
- 102000011131 Myosin-Light-Chain Phosphatase Human genes 0.000 claims description 4
- 108010037801 Myosin-Light-Chain Phosphatase Proteins 0.000 claims description 4
- 206010030043 Ocular hypertension Diseases 0.000 claims description 4
- 208000002193 Pain Diseases 0.000 claims description 4
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 4
- 208000017442 Retinal disease Diseases 0.000 claims description 4
- 206010038923 Retinopathy Diseases 0.000 claims description 4
- 208000007536 Thrombosis Diseases 0.000 claims description 4
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 4
- 230000004064 dysfunction Effects 0.000 claims description 4
- 230000002124 endocrine Effects 0.000 claims description 4
- 201000001881 impotence Diseases 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 208000001286 intracranial vasospasm Diseases 0.000 claims description 4
- 201000006370 kidney failure Diseases 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 208000020431 spinal cord injury Diseases 0.000 claims description 4
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 208000031104 Arterial Occlusive disease Diseases 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 206010019663 Hepatic failure Diseases 0.000 claims description 3
- 206010053159 Organ failure Diseases 0.000 claims description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
- 239000000654 additive Substances 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
- 208000029078 coronary artery disease Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 206010061989 glomerulosclerosis Diseases 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 208000023589 ischemic disease Diseases 0.000 claims description 3
- 230000000302 ischemic effect Effects 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 208000007903 liver failure Diseases 0.000 claims description 3
- 231100000835 liver failure Toxicity 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 230000008816 organ damage Effects 0.000 claims description 3
- 230000003836 peripheral circulation Effects 0.000 claims description 3
- 230000002093 peripheral effect Effects 0.000 claims description 3
- UINNXXOTDJHRNZ-UHFFFAOYSA-N 2-[4-[(7-chloro-1-oxo-2h-isoquinolin-6-yl)oxy]piperidin-1-yl]-n-propylacetamide Chemical compound C1CN(CC(=O)NCCC)CCC1OC(C(=C1)Cl)=CC2=C1C(=O)NC=C2 UINNXXOTDJHRNZ-UHFFFAOYSA-N 0.000 claims description 2
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000002792 vascular Effects 0.000 claims description 2
- NAXXPRDTNHGANA-UHFFFAOYSA-N 6-[1-(1-aminocyclopropanecarbonyl)piperidin-4-yl]oxy-7-chloro-2h-isoquinolin-1-one Chemical compound C1CC(OC=2C(=CC=3C(=O)NC=CC=3C=2)Cl)CCN1C(=O)C1(N)CC1 NAXXPRDTNHGANA-UHFFFAOYSA-N 0.000 claims 1
- AVIDWLIDJBAKSI-UHFFFAOYSA-N 6-[1-(2-aminopropanoyl)piperidin-4-yl]oxy-7-chloro-2h-isoquinolin-1-one Chemical compound C1CN(C(=O)C(N)C)CCC1OC(C(=C1)Cl)=CC2=C1C(=O)NC=C2 AVIDWLIDJBAKSI-UHFFFAOYSA-N 0.000 claims 1
- WTTZLNANAWUAIT-QGZVFWFLSA-N 6-[1-[(2s)-2-amino-3,3-dimethylbutanoyl]piperidin-4-yl]oxy-2h-isoquinolin-1-one Chemical compound C1CN(C(=O)[C@@H](N)C(C)(C)C)CCC1OC1=CC=C2C(=O)NC=CC2=C1 WTTZLNANAWUAIT-QGZVFWFLSA-N 0.000 claims 1
- YAPQBSNGCNKDLW-INIZCTEOSA-N 7-chloro-6-[1-[(2s)-pyrrolidine-2-carbonyl]piperidin-4-yl]oxy-2h-isoquinolin-1-one Chemical compound ClC1=CC(C(NC=C2)=O)=C2C=C1OC(CC1)CCN1C(=O)[C@@H]1CCCN1 YAPQBSNGCNKDLW-INIZCTEOSA-N 0.000 claims 1
- 206010061728 Bone lesion Diseases 0.000 claims 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical group CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 claims 1
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 claims 1
- 206010036595 Premature delivery Diseases 0.000 claims 1
- 201000005008 bacterial sepsis Diseases 0.000 claims 1
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 230000000762 glandular Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 238000000034 method Methods 0.000 description 47
- 239000000243 solution Substances 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 29
- 239000002585 base Substances 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 238000001514 detection method Methods 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- 125000001424 substituent group Chemical group 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
- 239000000203 mixture Substances 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 239000012312 sodium hydride Substances 0.000 description 14
- 229910000104 sodium hydride Inorganic materials 0.000 description 14
- 238000003756 stirring Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 12
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 229940113088 dimethylacetamide Drugs 0.000 description 11
- 125000003277 amino group Chemical group 0.000 description 10
- 239000000651 prodrug Substances 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 239000000825 pharmaceutical preparation Substances 0.000 description 8
- 238000002953 preparative HPLC Methods 0.000 description 8
- 125000004076 pyridyl group Chemical group 0.000 description 8
- TYKCTIFMODKQPO-UHFFFAOYSA-N 1,7-dichloro-6-fluoroisoquinoline Chemical compound C1=NC(Cl)=C2C=C(Cl)C(F)=CC2=C1 TYKCTIFMODKQPO-UHFFFAOYSA-N 0.000 description 7
- PGMJNARLMAJWSA-UHFFFAOYSA-N 6-fluoro-2-[(4-methoxyphenyl)methyl]-7-methylisoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC(C)=C(F)C=C2C=C1 PGMJNARLMAJWSA-UHFFFAOYSA-N 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 150000001204 N-oxides Chemical class 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 230000003068 static effect Effects 0.000 description 6
- 125000001544 thienyl group Chemical group 0.000 description 6
- VCCTUCDRIAEXLU-UHFFFAOYSA-N 6-fluoro-2h-isoquinolin-1-one Chemical compound C1=CNC(=O)C=2C1=CC(F)=CC=2 VCCTUCDRIAEXLU-UHFFFAOYSA-N 0.000 description 5
- UYGSZFXAPFKVLQ-LLVKDONJSA-N 7-methyl-6-[[(3r)-pyrrolidin-3-yl]methoxy]-2h-isoquinolin-1-one Chemical compound CC1=CC(C(NC=C2)=O)=C2C=C1OC[C@@H]1CCNC1 UYGSZFXAPFKVLQ-LLVKDONJSA-N 0.000 description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000012876 carrier material Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 150000003840 hydrochlorides Chemical class 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 5
- WNWMWOLCNSZQIQ-UHFFFAOYSA-N 2-[4-[(7-chloro-1-oxo-2h-isoquinolin-6-yl)oxy]piperidin-1-yl]acetamide Chemical compound C1CN(CC(=O)N)CCC1OC(C(=C1)Cl)=CC2=C1C(=O)NC=C2 WNWMWOLCNSZQIQ-UHFFFAOYSA-N 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- CWTXLDUQCRTOSP-UHFFFAOYSA-N 5,6-difluoro-2-[(4-methoxyphenyl)methyl]-4-methylisoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(F)C(F)=C2C(C)=C1 CWTXLDUQCRTOSP-UHFFFAOYSA-N 0.000 description 4
- OMHXDAMUVZERGT-INIZCTEOSA-N 6-[(3s)-1-benzylpyrrolidin-3-yl]oxy-7-chloro-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)OC2=CC3=C(C(NC=C3)=O)C=C2Cl)CN1CC1=CC=CC=C1 OMHXDAMUVZERGT-INIZCTEOSA-N 0.000 description 4
- KFDMDJDJRCKKTR-UHFFFAOYSA-N 6-fluoro-2-[(4-methoxyphenyl)methyl]-4,7-dimethylisoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC(C)=C(F)C=C2C(C)=C1 KFDMDJDJRCKKTR-UHFFFAOYSA-N 0.000 description 4
- CUUMQWIQWBZTOL-UHFFFAOYSA-N 6-fluoro-2-[(4-methoxyphenyl)methyl]isoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(F)C=C2C=C1 CUUMQWIQWBZTOL-UHFFFAOYSA-N 0.000 description 4
- OQMBJKGORSBEHX-UHFFFAOYSA-N 7-chloro-6-fluoro-2-oxidoisoquinolin-2-ium Chemical compound C1=C(F)C(Cl)=CC2=C[N+]([O-])=CC=C21 OQMBJKGORSBEHX-UHFFFAOYSA-N 0.000 description 4
- BCZPUVXMWIBIRE-UHFFFAOYSA-N 7-chloro-6-fluoroisoquinoline Chemical compound C1=NC=C2C=C(Cl)C(F)=CC2=C1 BCZPUVXMWIBIRE-UHFFFAOYSA-N 0.000 description 4
- CQQYUDKSGYFTGD-NSHDSACASA-N 7-methyl-6-[(3s)-pyrrolidin-3-yl]oxy-2h-isoquinolin-1-one Chemical compound CC1=CC(C(NC=C2)=O)=C2C=C1O[C@H]1CCNC1 CQQYUDKSGYFTGD-NSHDSACASA-N 0.000 description 4
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2009
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