KR20090094338A - 치환된 이소퀴놀린 및 이소퀴놀리논 유도체 - Google Patents
치환된 이소퀴놀린 및 이소퀴놀리논 유도체Info
- Publication number
- KR20090094338A KR20090094338A KR1020097013517A KR20097013517A KR20090094338A KR 20090094338 A KR20090094338 A KR 20090094338A KR 1020097013517 A KR1020097013517 A KR 1020097013517A KR 20097013517 A KR20097013517 A KR 20097013517A KR 20090094338 A KR20090094338 A KR 20090094338A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- alkylene
- aryl
- compound
- heterocyclyl
- 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.)
- Abandoned
Links
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 title abstract description 16
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 title description 18
- 150000002537 isoquinolines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 162
- -1 6-substituted isoquinolines Chemical class 0.000 claims abstract description 57
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 285
- 125000000623 heterocyclic group Chemical group 0.000 claims description 97
- 229910052736 halogen Inorganic materials 0.000 claims description 87
- 150000002367 halogens Chemical class 0.000 claims description 87
- 238000000034 method Methods 0.000 claims description 79
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 65
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 47
- 150000003839 salts Chemical class 0.000 claims description 42
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 37
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000002947 alkylene group Chemical group 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 206010020772 Hypertension Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 9
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 7
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 7
- 229920002554 vinyl polymer Polymers 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 208000017169 kidney disease Diseases 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 5
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 201000006370 kidney failure Diseases 0.000 claims description 5
- 230000002093 peripheral effect Effects 0.000 claims description 5
- 208000030507 AIDS Diseases 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 206010002383 Angina Pectoris 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
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 4
- 206010059109 Cerebral vasoconstriction Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 208000002249 Diabetes Complications 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
- 206010030043 Ocular hypertension 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
- 239000000654 additive Substances 0.000 claims description 4
- 208000021328 arterial occlusion Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 206010008118 cerebral infarction Diseases 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 230000004064 dysfunction Effects 0.000 claims description 4
- 230000002124 endocrine Effects 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 210000001035 gastrointestinal tract Anatomy 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
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 230000004770 neurodegeneration Effects 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
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- 208000020084 Bone disease Diseases 0.000 claims description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
- 125000000172 C5-C10 aryl 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
- 206010035664 Pneumonia Diseases 0.000 claims description 3
- 208000005107 Premature Birth Diseases 0.000 claims description 3
- 206010036590 Premature baby Diseases 0.000 claims description 3
- 208000013616 Respiratory Distress Syndrome 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
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 208000019425 cirrhosis of liver 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
- 208000007903 liver failure Diseases 0.000 claims description 3
- 231100000835 liver failure Toxicity 0.000 claims description 3
- 238000004519 manufacturing process Methods 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
- 238000011321 prophylaxis Methods 0.000 claims description 3
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
- 206010020880 Hypertrophy Diseases 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 206010023421 Kidney fibrosis Diseases 0.000 claims 1
- 230000001363 autoimmune Effects 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 206010020718 hyperplasia Diseases 0.000 claims 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 16
- 108010041788 rho-Associated Kinases Proteins 0.000 abstract description 15
- 102000000568 rho-Associated Kinases Human genes 0.000 abstract description 15
- 230000026731 phosphorylation Effects 0.000 abstract description 6
- 238000006366 phosphorylation reaction Methods 0.000 abstract description 6
- 102000011131 Myosin-Light-Chain Phosphatase Human genes 0.000 abstract description 5
- 108010037801 Myosin-Light-Chain Phosphatase Proteins 0.000 abstract description 5
- 230000001404 mediated effect Effects 0.000 abstract description 5
- 230000006806 disease prevention Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 239000000243 solution Substances 0.000 description 34
- 239000002904 solvent Substances 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 125000001424 substituent group Chemical group 0.000 description 19
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 239000000651 prodrug Substances 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 238000002953 preparative HPLC Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- ZTEATMVVGQUULZ-UHFFFAOYSA-N 6-bromoisoquinoline Chemical compound C1=NC=CC2=CC(Br)=CC=C21 ZTEATMVVGQUULZ-UHFFFAOYSA-N 0.000 description 8
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
- BCZPUVXMWIBIRE-UHFFFAOYSA-N 7-chloro-6-fluoroisoquinoline Chemical compound C1=NC=C2C=C(Cl)C(F)=CC2=C1 BCZPUVXMWIBIRE-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 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 6
- BTUPJEUTBPAUHV-UHFFFAOYSA-N 6-bromo-2-[(4-methoxyphenyl)methyl]isoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(Br)C=C2C=C1 BTUPJEUTBPAUHV-UHFFFAOYSA-N 0.000 description 6
- ZDYXSEQHOVSTPA-UHFFFAOYSA-N 6-bromo-2h-isoquinolin-1-one Chemical compound C1=CNC(=O)C=2C1=CC(Br)=CC=2 ZDYXSEQHOVSTPA-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
- 150000001204 N-oxides Chemical class 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 238000004108 freeze drying Methods 0.000 description 6
- 230000008570 general process Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- LIOVBCSJACUZOR-UHFFFAOYSA-N tert-butyl 4-(7-chloroisoquinolin-6-yl)sulfanylpiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1SC1=CC2=CC=NC=C2C=C1Cl LIOVBCSJACUZOR-UHFFFAOYSA-N 0.000 description 6
- 239000003039 volatile agent Substances 0.000 description 6
- QNNTUJSIGVWFAS-UHFFFAOYSA-N 6-bromo-2-oxidoisoquinolin-2-ium Chemical compound C1=C(Br)C=CC2=C[N+]([O-])=CC=C21 QNNTUJSIGVWFAS-UHFFFAOYSA-N 0.000 description 5
- 230000005526 G1 to G0 transition Effects 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 239000012876 carrier material Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- MNLWRVRXGBORJM-UHFFFAOYSA-N n-[(4-bromophenyl)methyl]-n-(2,2-dimethoxyethyl)-4-methylbenzenesulfonamide Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(CC(OC)OC)CC1=CC=C(Br)C=C1 MNLWRVRXGBORJM-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 4
- MDVYTGOMIMUNHS-UHFFFAOYSA-N 6-bromo-7-chloroisoquinoline Chemical compound N1=CC=C2C=C(Br)C(Cl)=CC2=C1 MDVYTGOMIMUNHS-UHFFFAOYSA-N 0.000 description 4
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 4
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 229960001456 adenosine triphosphate Drugs 0.000 description 4
- 150000001299 aldehydes Chemical group 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000001631 hypertensive effect Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- LYGKCOQTIFILER-UHFFFAOYSA-N tert-butyl 4-[7-chloro-2-[(4-methoxyphenyl)methyl]-1-oxoisoquinolin-6-yl]sulfinylpiperidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC(Cl)=C(S(=O)C3CCN(CC3)C(=O)OC(C)(C)C)C=C2C=C1 LYGKCOQTIFILER-UHFFFAOYSA-N 0.000 description 4
- DBFRMDJLBVKKDT-UHFFFAOYSA-N tert-butyl 4-[7-chloro-2-[(4-methoxyphenyl)methyl]-1-oxoisoquinolin-6-yl]sulfonylpiperidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC(Cl)=C(S(=O)(=O)C3CCN(CC3)C(=O)OC(C)(C)C)C=C2C=C1 DBFRMDJLBVKKDT-UHFFFAOYSA-N 0.000 description 4
- USYCVFFWCMHPPG-UHFFFAOYSA-N tert-butyl 4-sulfanylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(S)CC1 USYCVFFWCMHPPG-UHFFFAOYSA-N 0.000 description 4
- MSQCQINLJMEVNJ-UHFFFAOYSA-N 1-chloroisoquinoline Chemical class C1=CC=C2C(Cl)=NC=CC2=C1 MSQCQINLJMEVNJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- IHINXRIGMFDMCV-UHFFFAOYSA-N 6-bromo-1,7-dichloroisoquinoline Chemical compound N1=CC=C2C=C(Br)C(Cl)=CC2=C1Cl IHINXRIGMFDMCV-UHFFFAOYSA-N 0.000 description 3
- VOAHGGQULSSGQW-UHFFFAOYSA-N 6-bromo-1-chloroisoquinoline Chemical compound BrC1=CC=C2C(Cl)=NC=CC2=C1 VOAHGGQULSSGQW-UHFFFAOYSA-N 0.000 description 3
- YBOSZRTYHKSTRI-UHFFFAOYSA-N 6-bromo-7-chloro-2-oxidoisoquinolin-2-ium Chemical compound C1=C(Br)C(Cl)=CC2=C[N+]([O-])=CC=C21 YBOSZRTYHKSTRI-UHFFFAOYSA-N 0.000 description 3
- ABZAYLFRWGIRDU-UHFFFAOYSA-N 7-bromo-6-fluoroisoquinoline Chemical compound C1=NC=C2C=C(Br)C(F)=CC2=C1 ABZAYLFRWGIRDU-UHFFFAOYSA-N 0.000 description 3
- QXUFUCCRXUMGFQ-MERQFXBCSA-N 7-chloro-6-[(3s)-pyrrolidin-3-yl]sulfanylisoquinoline;hydrochloride Chemical compound Cl.ClC1=CC2=CN=CC=C2C=C1S[C@H]1CCNC1 QXUFUCCRXUMGFQ-MERQFXBCSA-N 0.000 description 3
- XOHMOYAJUKHIJD-UHFFFAOYSA-N 7-chloro-6-piperidin-4-ylsulfanyl-2h-isoquinolin-1-one Chemical compound ClC1=CC(C(NC=C2)=O)=C2C=C1SC1CCNCC1 XOHMOYAJUKHIJD-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 208000001132 Osteoporosis Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 101710088493 Rho-associated protein kinase 2 Proteins 0.000 description 3
- 102100039314 Rho-associated protein kinase 2 Human genes 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 150000001499 aryl bromides Chemical class 0.000 description 3
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- MHERTDRSZJXPSK-UHFFFAOYSA-N n-(1-ethylpiperidin-4-yl)isoquinolin-6-amine Chemical compound C1CN(CC)CCC1NC1=CC=C(C=NC=C2)C2=C1 MHERTDRSZJXPSK-UHFFFAOYSA-N 0.000 description 3
- IWHCBWVHESFUSD-UHFFFAOYSA-N n-(azetidin-3-yl)isoquinolin-6-amine Chemical compound C1NCC1NC1=CC=C(C=NC=C2)C2=C1 IWHCBWVHESFUSD-UHFFFAOYSA-N 0.000 description 3
- WDGHULPTPUSTQP-ZDUSSCGKSA-N n-[(3s)-pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C1NCC[C@@H]1NC1=CC=C(C=NC=C2)C2=C1 WDGHULPTPUSTQP-ZDUSSCGKSA-N 0.000 description 3
- IEMKXFLENZAFAZ-UHFFFAOYSA-N n-[(4-bromophenyl)methyl]-2,2-dimethoxyethanamine Chemical compound COC(OC)CNCC1=CC=C(Br)C=C1 IEMKXFLENZAFAZ-UHFFFAOYSA-N 0.000 description 3
- UMSLQMFEKLYKNI-UHFFFAOYSA-N n-piperidin-4-ylisoquinolin-6-amine Chemical compound C1CNCCC1NC1=CC=C(C=NC=C2)C2=C1 UMSLQMFEKLYKNI-UHFFFAOYSA-N 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 238000006268 reductive amination reaction Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- FXONDUNRLLHJAB-AWEZNQCLSA-N tert-butyl (3s)-3-(7-chloroisoquinolin-6-yl)sulfanylpyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1SC1=CC2=CC=NC=C2C=C1Cl FXONDUNRLLHJAB-AWEZNQCLSA-N 0.000 description 3
- KYLJPUGKGHFDOL-VIFPVBQESA-N tert-butyl (3s)-3-acetylsulfanylpyrrolidine-1-carboxylate Chemical compound CC(=O)S[C@H]1CCN(C(=O)OC(C)(C)C)C1 KYLJPUGKGHFDOL-VIFPVBQESA-N 0.000 description 3
- SJAKIGKVIJINMY-UHFFFAOYSA-N tert-butyl 4-acetylsulfanylpiperidine-1-carboxylate Chemical compound CC(=O)SC1CCN(C(=O)OC(C)(C)C)CC1 SJAKIGKVIJINMY-UHFFFAOYSA-N 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- DALCSUIFEAPBJG-FSRHSHDFSA-N 2-[(4-methoxyphenyl)methyl]-6-[[(3r)-piperidin-3-yl]amino]isoquinolin-1-one;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(N[C@H]3CNCCC3)C=C2C=C1 DALCSUIFEAPBJG-FSRHSHDFSA-N 0.000 description 2
- UVERWHDUVILVDB-FERBBOLQSA-N 2-[(4-methoxyphenyl)methyl]-6-[[(3s)-pyrrolidin-3-yl]amino]isoquinolin-1-one;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CN1C(=O)C2=CC=C(N[C@@H]3CNCC3)C=C2C=C1 UVERWHDUVILVDB-FERBBOLQSA-N 0.000 description 2
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- DVGJFFBVFHRJEC-UHFFFAOYSA-N 3-(bromomethyl)piperidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC(CBr)C1 DVGJFFBVFHRJEC-UHFFFAOYSA-N 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- RFVKAFQMHHUEAZ-UHFFFAOYSA-N 6,7-dichloroisoquinoline Chemical compound C1=NC=C2C=C(Cl)C(Cl)=CC2=C1 RFVKAFQMHHUEAZ-UHFFFAOYSA-N 0.000 description 2
- AEAVFEJWLZNEGE-UHFFFAOYSA-N 6-(1-benzylpiperidin-3-yl)sulfanyl-7-chloroisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC(C1)CCCN1CC1=CC=CC=C1 AEAVFEJWLZNEGE-UHFFFAOYSA-N 0.000 description 2
- WVSPFSJKDBTPIQ-UHFFFAOYSA-N 6-(azepan-4-ylamino)-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NC=CC2=CC=1NC1CCCNCC1 WVSPFSJKDBTPIQ-UHFFFAOYSA-N 0.000 description 2
- BVEIFHBHLLITHU-UHFFFAOYSA-N 6-(azetidin-3-ylamino)-2h-isoquinolin-1-one;hydrochloride Chemical compound Cl.C=1C=C2C(=O)NC=CC2=CC=1NC1CNC1 BVEIFHBHLLITHU-UHFFFAOYSA-N 0.000 description 2
- NSWBKBQTZAJPIV-UHFFFAOYSA-N 6-bromo-7-chloro-2-[(4-methoxyphenyl)methyl]isoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC(Cl)=C(Br)C=C2C=C1 NSWBKBQTZAJPIV-UHFFFAOYSA-N 0.000 description 2
- UFPAXXQUNCNMLO-UHFFFAOYSA-N 6-piperidin-4-ylsulfanyl-7-propylisoquinoline;hydrochloride Chemical compound Cl.CCCC1=CC2=CN=CC=C2C=C1SC1CCNCC1 UFPAXXQUNCNMLO-UHFFFAOYSA-N 0.000 description 2
- PYHTZAAWAIERKG-UHFFFAOYSA-N 7-bromo-6-(piperidin-3-ylmethylsulfanyl)isoquinoline Chemical compound BrC1=CC2=CN=CC=C2C=C1SCC1CCCNC1 PYHTZAAWAIERKG-UHFFFAOYSA-N 0.000 description 2
- IBDPGOXCTLZQGV-UHFFFAOYSA-N 7-bromo-6-(pyrrolidin-3-ylmethylsulfanyl)isoquinoline Chemical compound BrC1=CC2=CN=CC=C2C=C1SCC1CCNC1 IBDPGOXCTLZQGV-UHFFFAOYSA-N 0.000 description 2
- KZOSCZXUHGBLMP-UHFFFAOYSA-N 7-bromo-6-chloroisoquinoline Chemical compound C1=NC=C2C=C(Br)C(Cl)=CC2=C1 KZOSCZXUHGBLMP-UHFFFAOYSA-N 0.000 description 2
- DUJOGJALZSEARZ-UHFFFAOYSA-N 7-bromo-6-piperidin-4-ylsulfanylisoquinoline;hydrochloride Chemical compound Cl.BrC1=CC2=CN=CC=C2C=C1SC1CCNCC1 DUJOGJALZSEARZ-UHFFFAOYSA-N 0.000 description 2
- PQAGNKVFHQWOCU-UHFFFAOYSA-N 7-chloro-6-(piperidin-3-ylmethylsulfanyl)isoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SCC1CCCNC1 PQAGNKVFHQWOCU-UHFFFAOYSA-N 0.000 description 2
- ZKPMXASJOMIEJR-UHFFFAOYSA-N 7-chloro-6-(piperidin-4-ylmethylsulfanyl)isoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SCC1CCNCC1 ZKPMXASJOMIEJR-UHFFFAOYSA-N 0.000 description 2
- PYNDYFLFRZXXJP-UHFFFAOYSA-N 7-chloro-6-(pyrrolidin-2-ylmethylsulfanyl)isoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SCC1CCCN1 PYNDYFLFRZXXJP-UHFFFAOYSA-N 0.000 description 2
- NEUNIDWMMGPNMS-UHFFFAOYSA-N 7-chloro-6-(pyrrolidin-3-ylmethylsulfanyl)isoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SCC1CCNC1 NEUNIDWMMGPNMS-UHFFFAOYSA-N 0.000 description 2
- FEWODNUFCQFNIE-ZDUSSCGKSA-N 7-chloro-6-[(3s)-1-ethylpyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1N(CC)CC[C@@H]1SC1=CC2=CC=NC=C2C=C1Cl FEWODNUFCQFNIE-ZDUSSCGKSA-N 0.000 description 2
- RTGKLYWJASSVFC-UHFFFAOYSA-N 7-chloro-6-[1-(pyridin-3-ylmethyl)piperidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC(C1)CCCN1CC1=CC=CN=C1 RTGKLYWJASSVFC-UHFFFAOYSA-N 0.000 description 2
- RJDZNRMXDWFXOV-UHFFFAOYSA-N 7-chloro-6-[1-(pyridin-4-ylmethyl)piperidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC(C1)CCCN1CC1=CC=NC=C1 RJDZNRMXDWFXOV-UHFFFAOYSA-N 0.000 description 2
- CCZXHNOABBLUFE-UHFFFAOYSA-N 7-chloro-6-[1-[(2-chlorophenyl)methyl]piperidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC=CC=C1CN1CC(SC=2C(=CC3=CN=CC=C3C=2)Cl)CCC1 CCZXHNOABBLUFE-UHFFFAOYSA-N 0.000 description 2
- SKJMWZKXUVAAJP-UHFFFAOYSA-N 7-chloro-6-[1-[(3,5-dichlorophenyl)methyl]piperidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC(Cl)=CC(CN2CC(CCC2)SC=2C(=CC3=CN=CC=C3C=2)Cl)=C1 SKJMWZKXUVAAJP-UHFFFAOYSA-N 0.000 description 2
- IMIUHPLXCMUPEF-UHFFFAOYSA-N 7-chloro-6-[1-[(3-chlorophenyl)methyl]piperidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC=CC(CN2CC(CCC2)SC=2C(=CC3=CN=CC=C3C=2)Cl)=C1 IMIUHPLXCMUPEF-UHFFFAOYSA-N 0.000 description 2
- UVZPWUGLNAXECG-UHFFFAOYSA-N 7-chloro-6-[1-[(4-chlorophenyl)methyl]piperidin-3-yl]sulfanylisoquinoline Chemical compound C1=CC(Cl)=CC=C1CN1CC(SC=2C(=CC3=CN=CC=C3C=2)Cl)CCC1 UVZPWUGLNAXECG-UHFFFAOYSA-N 0.000 description 2
- OMDJEMAZYVHWOK-UHFFFAOYSA-N 7-chloro-6-[1-[(4-methylphenyl)methyl]piperidin-3-yl]sulfanylisoquinoline Chemical compound C1=CC(C)=CC=C1CN1CC(SC=2C(=CC3=CN=CC=C3C=2)Cl)CCC1 OMDJEMAZYVHWOK-UHFFFAOYSA-N 0.000 description 2
- WCBIDOUPUKKYAA-UHFFFAOYSA-N 7-chloro-6-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-3-yl]sulfanylisoquinoline Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1CC(SC=2C(=CC3=CN=CC=C3C=2)Cl)CCC1 WCBIDOUPUKKYAA-UHFFFAOYSA-N 0.000 description 2
- WBRZDMQMZUTNSB-UHFFFAOYSA-N 7-chloro-6-piperidin-4-ylsulfinyl-2h-isoquinolin-1-one Chemical compound ClC1=CC(C(NC=C2)=O)=C2C=C1S(=O)C1CCNCC1 WBRZDMQMZUTNSB-UHFFFAOYSA-N 0.000 description 2
- UXLWSEAYUKYERO-UHFFFAOYSA-N 7-chloro-6-piperidin-4-ylsulfonyl-2h-isoquinolin-1-one Chemical compound ClC1=CC(C(NC=C2)=O)=C2C=C1S(=O)(=O)C1CCNCC1 UXLWSEAYUKYERO-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 2
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102000004257 Potassium Channel Human genes 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 101150111584 RHOA gene Proteins 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N anhydrous trimethylamine Natural products CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 229940125400 channel inhibitor Drugs 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229940113088 dimethylacetamide Drugs 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000004310 lactic acid Chemical class 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- BZUMFZRRPOIERE-OGLMXYFKSA-N n'-[3-[[3-(7-chloroisoquinolin-6-yl)sulfanylpiperidin-1-yl]methyl]-4-methoxyphenyl]sulfonyl-n,n-dimethylmethanimidamide Chemical compound COC1=CC=C(S(=O)(=O)\N=C\N(C)C)C=C1CN1CC(SC=2C(=CC3=CN=CC=C3C=2)Cl)CCC1 BZUMFZRRPOIERE-OGLMXYFKSA-N 0.000 description 2
- VERPQXNZIKPZSN-UHFFFAOYSA-N n-piperidin-4-ylisoquinolin-6-amine;hydrochloride Chemical compound Cl.C1CNCCC1NC1=CC=C(C=NC=C2)C2=C1 VERPQXNZIKPZSN-UHFFFAOYSA-N 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 125000000160 oxazolidinyl group Chemical group 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 230000003836 peripheral circulation Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 108020001213 potassium channel Proteins 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 201000002793 renal fibrosis Diseases 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 239000003590 rho kinase inhibitor Substances 0.000 description 2
- 239000011435 rock Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- WPGLRFGDZJSQGI-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(N)C1 WPGLRFGDZJSQGI-UHFFFAOYSA-N 0.000 description 2
- STRHKPXYYZDKFJ-UHFFFAOYSA-N tert-butyl 4-(7-propylisoquinolin-6-yl)sulfanylpiperidine-1-carboxylate Chemical compound CCCC1=CC2=CN=CC=C2C=C1SC1CCN(C(=O)OC(C)(C)C)CC1 STRHKPXYYZDKFJ-UHFFFAOYSA-N 0.000 description 2
- TUDOJUSCXDCAPH-UHFFFAOYSA-N tert-butyl 4-(7-propylisoquinolin-6-yl)sulfanylpiperidine-1-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCCC1=CC2=CN=CC=C2C=C1SC1CCN(C(=O)OC(C)(C)C)CC1 TUDOJUSCXDCAPH-UHFFFAOYSA-N 0.000 description 2
- SRDSJYNZSNVSGS-UHFFFAOYSA-N tert-butyl 4-(ethylamino)piperidine-1-carboxylate Chemical compound CCNC1CCN(C(=O)OC(C)(C)C)CC1 SRDSJYNZSNVSGS-UHFFFAOYSA-N 0.000 description 2
- URZILZASFPGYMQ-UHFFFAOYSA-N tert-butyl 4-(isoquinolin-6-ylamino)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=CC=C(C=NC=C2)C2=C1 URZILZASFPGYMQ-UHFFFAOYSA-N 0.000 description 2
- KUUIZUUSRWBGAG-UHFFFAOYSA-N tert-butyl 4-(isoquinolin-6-ylamino)piperidine-1-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CN(C(=O)OC(C)(C)C)CCC1NC1=CC=C(C=NC=C2)C2=C1 KUUIZUUSRWBGAG-UHFFFAOYSA-N 0.000 description 2
- LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 2
- CRFSWDBNKHNGGA-UHFFFAOYSA-N tert-butyl 4-hydroxyazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(O)CC1 CRFSWDBNKHNGGA-UHFFFAOYSA-N 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 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 2
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
- JIDDDPVQQUHACU-YFKPBYRVSA-N (2s)-pyrrolidine-2-carbaldehyde Chemical group O=C[C@@H]1CCCN1 JIDDDPVQQUHACU-YFKPBYRVSA-N 0.000 description 1
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
- PVRSIFAEUCUJPK-UHFFFAOYSA-N (4-methoxyphenyl)hydrazine Chemical compound COC1=CC=C(NN)C=C1 PVRSIFAEUCUJPK-UHFFFAOYSA-N 0.000 description 1
- 125000001272 (C1-C4)-alkylene-phenyl group Chemical group 0.000 description 1
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- 125000005955 1H-indazolyl group Chemical group 0.000 description 1
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- LYIIBVSRGJSHAV-UHFFFAOYSA-N 2-aminoacetaldehyde Chemical compound NCC=O LYIIBVSRGJSHAV-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- AGTWPNVLBGFBEM-UHFFFAOYSA-N 3-(bromomethyl)pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCC(CBr)C1 AGTWPNVLBGFBEM-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FAHZIKXYYRGSHF-UHFFFAOYSA-N 3-bromo-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1Br FAHZIKXYYRGSHF-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical class C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- GVORVQPNNSASDM-UHFFFAOYSA-N 3-chloro-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1Cl GVORVQPNNSASDM-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- GRFYHMYJGCPLFJ-UHFFFAOYSA-N 4-(bromomethyl)piperidine-1-carboxylic acid Chemical compound OC(=O)N1CCC(CBr)CC1 GRFYHMYJGCPLFJ-UHFFFAOYSA-N 0.000 description 1
- LDYVDYZLCRUOTM-UHFFFAOYSA-N 4-bromo-3-chlorobenzaldehyde Chemical compound ClC1=CC(C=O)=CC=C1Br LDYVDYZLCRUOTM-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 1
- 125000006043 5-hexenyl group Chemical group 0.000 description 1
- ZKHRBNPTXHEKTA-UHFFFAOYSA-N 6-(1-benzylpiperidin-4-yl)sulfanyl-7-bromoisoquinoline Chemical compound BrC1=CC2=CN=CC=C2C=C1SC(CC1)CCN1CC1=CC=CC=C1 ZKHRBNPTXHEKTA-UHFFFAOYSA-N 0.000 description 1
- HUXDKPSFNCTGIB-UHFFFAOYSA-N 6-(1-butylpiperidin-3-yl)sulfanyl-7-chloroisoquinoline Chemical compound C1N(CCCC)CCCC1SC1=CC2=CC=NC=C2C=C1Cl HUXDKPSFNCTGIB-UHFFFAOYSA-N 0.000 description 1
- WGNADEYRZOUGQF-UHFFFAOYSA-N 6-(1-butylpiperidin-4-yl)sulfanyl-7-chloroisoquinoline Chemical compound C1CN(CCCC)CCC1SC1=CC2=CC=NC=C2C=C1Cl WGNADEYRZOUGQF-UHFFFAOYSA-N 0.000 description 1
- AHCIFLGRWIIPQR-UHFFFAOYSA-N 6-(azepan-4-ylsulfanyl)-7-bromoisoquinoline Chemical compound BrC1=CC2=CN=CC=C2C=C1SC1CCCNCC1 AHCIFLGRWIIPQR-UHFFFAOYSA-N 0.000 description 1
- FXPIVNXNKBMTKO-UHFFFAOYSA-N 6-(azepan-4-ylsulfanyl)-7-bromoisoquinoline;hydrochloride Chemical compound Cl.BrC1=CC2=CN=CC=C2C=C1SC1CCCNCC1 FXPIVNXNKBMTKO-UHFFFAOYSA-N 0.000 description 1
- IABJYPUYUTXEKT-UHFFFAOYSA-N 6-(azepan-4-ylsulfanyl)-7-chloroisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC1CCCNCC1 IABJYPUYUTXEKT-UHFFFAOYSA-N 0.000 description 1
- NVUXXWQLCOLJAO-UHFFFAOYSA-N 6-(azepan-4-ylsulfanyl)-7-chloroisoquinoline;hydrochloride Chemical compound Cl.ClC1=CC2=CN=CC=C2C=C1SC1CCCNCC1 NVUXXWQLCOLJAO-UHFFFAOYSA-N 0.000 description 1
- GJKDZRLSDSTPRZ-UHFFFAOYSA-N 6-(azetidin-3-ylamino)-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NC=CC2=CC=1NC1CNC1 GJKDZRLSDSTPRZ-UHFFFAOYSA-N 0.000 description 1
- RHILRJAKKIKUSE-UHFFFAOYSA-N 6-(piperidin-3-ylmethylamino)-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NC=CC2=CC=1NCC1CCCNC1 RHILRJAKKIKUSE-UHFFFAOYSA-N 0.000 description 1
- JLDWMAYTMARMLB-UHFFFAOYSA-N 6-(piperidin-4-ylamino)-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NC=CC2=CC=1NC1CCNCC1 JLDWMAYTMARMLB-UHFFFAOYSA-N 0.000 description 1
- PGECPDPEXVMRBI-UHFFFAOYSA-N 6-(pyrrolidin-2-ylmethylamino)-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NC=CC2=CC=1NCC1CCCN1 PGECPDPEXVMRBI-UHFFFAOYSA-N 0.000 description 1
- QUNPKGURAXKGCP-UHFFFAOYSA-N 6-[(1-benzylazetidin-3-yl)amino]-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NC=CC2=CC=1NC(C1)CN1CC1=CC=CC=C1 QUNPKGURAXKGCP-UHFFFAOYSA-N 0.000 description 1
- QRXAAANYPGDHDT-UHFFFAOYSA-N 6-[(1-benzylpiperidin-4-yl)amino]-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NC=CC2=CC=1NC(CC1)CCN1CC1=CC=CC=C1 QRXAAANYPGDHDT-UHFFFAOYSA-N 0.000 description 1
- RYHFAWLLIQEDDP-UHFFFAOYSA-N 6-[(1-cyclohexylazetidin-3-yl)amino]-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NC=CC2=CC=1NC(C1)CN1C1CCCCC1 RYHFAWLLIQEDDP-UHFFFAOYSA-N 0.000 description 1
- WJRWLQKTSKGTFT-UHFFFAOYSA-N 6-[(1-ethylpiperidin-3-yl)amino]-2h-isoquinolin-1-one Chemical compound C1N(CC)CCCC1NC1=CC=C2C(=O)NC=CC2=C1 WJRWLQKTSKGTFT-UHFFFAOYSA-N 0.000 description 1
- MZETXHNBVLISRX-UHFFFAOYSA-N 6-[(1-pentan-3-ylazetidin-3-yl)amino]-2h-isoquinolin-1-one Chemical compound C1N(C(CC)CC)CC1NC1=CC=C2C(=O)NC=CC2=C1 MZETXHNBVLISRX-UHFFFAOYSA-N 0.000 description 1
- XKJBNBDOSHZVLN-UHFFFAOYSA-N 6-[(1-propan-2-ylazetidin-3-yl)amino]-2h-isoquinolin-1-one Chemical compound C1N(C(C)C)CC1NC1=CC=C2C(=O)NC=CC2=C1 XKJBNBDOSHZVLN-UHFFFAOYSA-N 0.000 description 1
- VSCNZHWGTWQNIM-SFHVURJKSA-N 6-[(3s)-1-benzylpyrrolidin-3-yl]sulfanyl-7-chloroisoquinoline Chemical compound C([C@@H](C1)SC2=CC3=CC=NC=C3C=C2Cl)CN1CC1=CC=CC=C1 VSCNZHWGTWQNIM-SFHVURJKSA-N 0.000 description 1
- CKYQVHDXWRESJH-HNNXBMFYSA-N 6-[(3s)-1-butylpyrrolidin-3-yl]sulfanyl-7-chloroisoquinoline Chemical compound C1N(CCCC)CC[C@@H]1SC1=CC2=CC=NC=C2C=C1Cl CKYQVHDXWRESJH-HNNXBMFYSA-N 0.000 description 1
- VSQDBDWBRJREOU-MRXNPFEDSA-N 6-[[(3r)-1-(2-methylpropyl)piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(CC(C)C)CCC[C@H]1NC1=CC=C2C(=O)NC=CC2=C1 VSQDBDWBRJREOU-MRXNPFEDSA-N 0.000 description 1
- NIMBFLKMMGLEPQ-CQSZACIVSA-N 6-[[(3r)-1-(3,3,3-trifluoropropyl)piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(CCC(F)(F)F)CCC[C@H]1NC1=CC=C2C(=O)NC=CC2=C1 NIMBFLKMMGLEPQ-CQSZACIVSA-N 0.000 description 1
- HHWVOXYWEMARDB-QGZVFWFLSA-N 6-[[(3r)-1-(3-methylbutyl)piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(CCC(C)C)CCC[C@H]1NC1=CC=C2C(=O)NC=CC2=C1 HHWVOXYWEMARDB-QGZVFWFLSA-N 0.000 description 1
- OUTCAXOGJWZMCQ-LJQANCHMSA-N 6-[[(3r)-1-(cyclohexylmethyl)piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CCN1CC1CCCCC1 OUTCAXOGJWZMCQ-LJQANCHMSA-N 0.000 description 1
- WPPQONKBJNWWGR-MRXNPFEDSA-N 6-[[(3r)-1-(cyclopropylmethyl)piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CCN1CC1CC1 WPPQONKBJNWWGR-MRXNPFEDSA-N 0.000 description 1
- ZSBDOLYNOZIZQM-HSZRJFAPSA-N 6-[[(3r)-1-(naphthalen-2-ylmethyl)piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC=CC2=CC(CN3CCC[C@H](C3)NC=3C=C4C=CNC(C4=CC=3)=O)=CC=C21 ZSBDOLYNOZIZQM-HSZRJFAPSA-N 0.000 description 1
- DXESJZCIOILEMP-GOSISDBHSA-N 6-[[(3r)-1-(pyridin-2-ylmethyl)piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CCN1CC1=CC=CC=N1 DXESJZCIOILEMP-GOSISDBHSA-N 0.000 description 1
- RPKCSORPYRFNSB-GOSISDBHSA-N 6-[[(3r)-1-(pyridin-3-ylmethyl)piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CCN1CC1=CC=CN=C1 RPKCSORPYRFNSB-GOSISDBHSA-N 0.000 description 1
- YYUDQEGYYMEVDY-GOSISDBHSA-N 6-[[(3r)-1-(pyridin-4-ylmethyl)piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CCN1CC1=CC=NC=C1 YYUDQEGYYMEVDY-GOSISDBHSA-N 0.000 description 1
- ICSAHKNAYXAYMQ-QGZVFWFLSA-N 6-[[(3r)-1-[(2,3,5-trifluorophenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound FC1=CC(F)=C(F)C(CN2C[C@@H](CCC2)NC=2C=C3C(C(NC=C3)=O)=CC=2)=C1 ICSAHKNAYXAYMQ-QGZVFWFLSA-N 0.000 description 1
- NHGGYLFFSRPSLW-GOSISDBHSA-N 6-[[(3r)-1-[(2,3-difluoro-4-methylphenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound FC1=C(F)C(C)=CC=C1CN1C[C@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CCC1 NHGGYLFFSRPSLW-GOSISDBHSA-N 0.000 description 1
- ZQZPUURGPVPVKF-GOSISDBHSA-N 6-[[(3r)-1-[(2,4-dichlorophenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound ClC1=CC(Cl)=CC=C1CN1C[C@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CCC1 ZQZPUURGPVPVKF-GOSISDBHSA-N 0.000 description 1
- PCRHXXBVJMQZLD-GOSISDBHSA-N 6-[[(3r)-1-[(2-chlorophenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound ClC1=CC=CC=C1CN1C[C@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CCC1 PCRHXXBVJMQZLD-GOSISDBHSA-N 0.000 description 1
- GNJWMOMUMZPVPW-LJQANCHMSA-N 6-[[(3r)-1-[(3,5-dichlorophenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound ClC1=CC(Cl)=CC(CN2C[C@@H](CCC2)NC=2C=C3C(C(NC=C3)=O)=CC=2)=C1 GNJWMOMUMZPVPW-LJQANCHMSA-N 0.000 description 1
- UHJVSBRIMLMWNC-QGZVFWFLSA-N 6-[[(3r)-1-[(3-chloro-2-fluorophenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound FC1=C(Cl)C=CC=C1CN1C[C@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CCC1 UHJVSBRIMLMWNC-QGZVFWFLSA-N 0.000 description 1
- KEBZWRCREUTGSD-LJQANCHMSA-N 6-[[(3r)-1-[(3-chlorophenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound ClC1=CC=CC(CN2C[C@@H](CCC2)NC=2C=C3C(C(NC=C3)=O)=CC=2)=C1 KEBZWRCREUTGSD-LJQANCHMSA-N 0.000 description 1
- JVYKJLYGVYEPCI-LJQANCHMSA-N 6-[[(3r)-1-[(4-chlorophenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC(Cl)=CC=C1CN1C[C@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CCC1 JVYKJLYGVYEPCI-LJQANCHMSA-N 0.000 description 1
- XYQSOLWEWPYKKC-HXUWFJFHSA-N 6-[[(3r)-1-[(4-methylphenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC(C)=CC=C1CN1C[C@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CCC1 XYQSOLWEWPYKKC-HXUWFJFHSA-N 0.000 description 1
- HUKYFMVKTMGNCD-LJQANCHMSA-N 6-[[(3r)-1-[(4-methylsulfonylphenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1C[C@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CCC1 HUKYFMVKTMGNCD-LJQANCHMSA-N 0.000 description 1
- BRWLLTTWDNZPCT-LJQANCHMSA-N 6-[[(3r)-1-[(5-fluoro-2-methylsulfonylphenyl)methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound CS(=O)(=O)C1=CC=C(F)C=C1CN1C[C@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CCC1 BRWLLTTWDNZPCT-LJQANCHMSA-N 0.000 description 1
- HWUPUKJWSUDHHP-LJQANCHMSA-N 6-[[(3r)-1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1C[C@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CCC1 HWUPUKJWSUDHHP-LJQANCHMSA-N 0.000 description 1
- GAUVWDCIOADOMU-LJQANCHMSA-N 6-[[(3r)-1-benzylpiperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CCN1CC1=CC=CC=C1 GAUVWDCIOADOMU-LJQANCHMSA-N 0.000 description 1
- RGYMTQXWLQOOLF-GOSISDBHSA-N 6-[[(3r)-1-benzylpyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1CC1=CC=CC=C1 RGYMTQXWLQOOLF-GOSISDBHSA-N 0.000 description 1
- BKPBPHNIPPYSQK-MRXNPFEDSA-N 6-[[(3r)-1-butylpiperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(CCCC)CCC[C@H]1NC1=CC=C2C(=O)NC=CC2=C1 BKPBPHNIPPYSQK-MRXNPFEDSA-N 0.000 description 1
- SJIXIHURUUYNLN-QGZVFWFLSA-N 6-[[(3r)-1-cyclohexylpiperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CCN1C1CCCCC1 SJIXIHURUUYNLN-QGZVFWFLSA-N 0.000 description 1
- PPTFMHZSLAXBJU-OAHLLOKOSA-N 6-[[(3r)-1-propylpiperidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(CCC)CCC[C@H]1NC1=CC=C2C(=O)NC=CC2=C1 PPTFMHZSLAXBJU-OAHLLOKOSA-N 0.000 description 1
- FMEBKYMISKDMAJ-HNNXBMFYSA-N 6-[[(3s)-1-(2-methylpropyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(CC(C)C)CC[C@@H]1NC1=CC=C2C(=O)NC=CC2=C1 FMEBKYMISKDMAJ-HNNXBMFYSA-N 0.000 description 1
- WWCMKFZGPGDODB-INIZCTEOSA-N 6-[[(3s)-1-(3-methylbutyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(CCC(C)C)CC[C@@H]1NC1=CC=C2C(=O)NC=CC2=C1 WWCMKFZGPGDODB-INIZCTEOSA-N 0.000 description 1
- DGOCREFWVBIYDZ-SFHVURJKSA-N 6-[[(3s)-1-(cyclohexylmethyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1CC1CCCCC1 DGOCREFWVBIYDZ-SFHVURJKSA-N 0.000 description 1
- QRAGSCCYFLULLS-HNNXBMFYSA-N 6-[[(3s)-1-(cyclopropylmethyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1CC1CC1 QRAGSCCYFLULLS-HNNXBMFYSA-N 0.000 description 1
- WGHXXYDTGIFESP-NRFANRHFSA-N 6-[[(3s)-1-(naphthalen-1-ylmethyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC=C2C(CN3CC[C@@H](C3)NC=3C=C4C=CNC(C4=CC=3)=O)=CC=CC2=C1 WGHXXYDTGIFESP-NRFANRHFSA-N 0.000 description 1
- DMJMBACWGLJVIJ-QFIPXVFZSA-N 6-[[(3s)-1-(naphthalen-2-ylmethyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC=CC2=CC(CN3CC[C@@H](C3)NC=3C=C4C=CNC(C4=CC=3)=O)=CC=C21 DMJMBACWGLJVIJ-QFIPXVFZSA-N 0.000 description 1
- QNHFXLGRHNOIME-JRZJBTRGSA-N 6-[[(3s)-1-(piperidin-3-ylmethyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1CC1CCCNC1 QNHFXLGRHNOIME-JRZJBTRGSA-N 0.000 description 1
- ILBXPSPINJBUMX-KRWDZBQOSA-N 6-[[(3s)-1-(pyridin-2-ylmethyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1CC1=CC=CC=N1 ILBXPSPINJBUMX-KRWDZBQOSA-N 0.000 description 1
- BKYQWGDBJRCOJC-KRWDZBQOSA-N 6-[[(3s)-1-(pyridin-3-ylmethyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1CC1=CC=CN=C1 BKYQWGDBJRCOJC-KRWDZBQOSA-N 0.000 description 1
- XPANIWXLTKQBIR-KRWDZBQOSA-N 6-[[(3s)-1-(pyridin-4-ylmethyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1CC1=CC=NC=C1 XPANIWXLTKQBIR-KRWDZBQOSA-N 0.000 description 1
- GABGBOHGFGUQOP-VYIIXAMBSA-N 6-[[(3s)-1-(pyrrolidin-3-ylmethyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1CC1CCNC1 GABGBOHGFGUQOP-VYIIXAMBSA-N 0.000 description 1
- FVRMZNQNPIRWMF-INIZCTEOSA-N 6-[[(3s)-1-(thiophen-3-ylmethyl)pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1CC=1C=CSC=1 FVRMZNQNPIRWMF-INIZCTEOSA-N 0.000 description 1
- IZEVEHNTKOXTRO-INIZCTEOSA-N 6-[[(3s)-1-[(1-methylpyrazol-4-yl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=NN(C)C=C1CN1C[C@@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CC1 IZEVEHNTKOXTRO-INIZCTEOSA-N 0.000 description 1
- VOHMAHUIQDBVDS-INIZCTEOSA-N 6-[[(3s)-1-[(2,3,5-trifluorophenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound FC1=CC(F)=C(F)C(CN2C[C@H](CC2)NC=2C=C3C(C(NC=C3)=O)=CC=2)=C1 VOHMAHUIQDBVDS-INIZCTEOSA-N 0.000 description 1
- JIJWUJUKPCEGJK-KRWDZBQOSA-N 6-[[(3s)-1-[(2,3-difluoro-4-methylphenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound FC1=C(F)C(C)=CC=C1CN1C[C@@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CC1 JIJWUJUKPCEGJK-KRWDZBQOSA-N 0.000 description 1
- SCGTWFVOSMZRCO-KRWDZBQOSA-N 6-[[(3s)-1-[(2,4-dichlorophenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound ClC1=CC(Cl)=CC=C1CN1C[C@@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CC1 SCGTWFVOSMZRCO-KRWDZBQOSA-N 0.000 description 1
- WYCRJLHOZXPXPY-KRWDZBQOSA-N 6-[[(3s)-1-[(2-chlorophenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound ClC1=CC=CC=C1CN1C[C@@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CC1 WYCRJLHOZXPXPY-KRWDZBQOSA-N 0.000 description 1
- FVGACGKOBRAIDY-SFHVURJKSA-N 6-[[(3s)-1-[(3,5-dichlorophenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound ClC1=CC(Cl)=CC(CN2C[C@H](CC2)NC=2C=C3C(C(NC=C3)=O)=CC=2)=C1 FVGACGKOBRAIDY-SFHVURJKSA-N 0.000 description 1
- FUCKVBWSHXHPRC-INIZCTEOSA-N 6-[[(3s)-1-[(3-chloro-2-fluorophenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound FC1=C(Cl)C=CC=C1CN1C[C@@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CC1 FUCKVBWSHXHPRC-INIZCTEOSA-N 0.000 description 1
- UZAWVKFZJPTZGB-SFHVURJKSA-N 6-[[(3s)-1-[(3-chlorophenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound ClC1=CC=CC(CN2C[C@H](CC2)NC=2C=C3C(C(NC=C3)=O)=CC=2)=C1 UZAWVKFZJPTZGB-SFHVURJKSA-N 0.000 description 1
- LIJLGRJMIOBKSV-SFHVURJKSA-N 6-[[(3s)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC(Cl)=CC=C1CN1C[C@@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CC1 LIJLGRJMIOBKSV-SFHVURJKSA-N 0.000 description 1
- FSFLVTPODJEKDY-IBGZPJMESA-N 6-[[(3s)-1-[(4-methylphenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC(C)=CC=C1CN1C[C@@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CC1 FSFLVTPODJEKDY-IBGZPJMESA-N 0.000 description 1
- XMEKBZZJMMPOOV-SFHVURJKSA-N 6-[[(3s)-1-[(4-methylsulfonylphenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1C[C@@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CC1 XMEKBZZJMMPOOV-SFHVURJKSA-N 0.000 description 1
- OEDWXMZHJGWYOO-SFHVURJKSA-N 6-[[(3s)-1-[(5-fluoro-2-methylsulfonylphenyl)methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound CS(=O)(=O)C1=CC=C(F)C=C1CN1C[C@@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CC1 OEDWXMZHJGWYOO-SFHVURJKSA-N 0.000 description 1
- WFIAQYYWWQNYAC-SFHVURJKSA-N 6-[[(3s)-1-[[4-(trifluoromethyl)phenyl]methyl]pyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1C[C@@H](NC=2C=C3C(C(NC=C3)=O)=CC=2)CC1 WFIAQYYWWQNYAC-SFHVURJKSA-N 0.000 description 1
- RGYMTQXWLQOOLF-SFHVURJKSA-N 6-[[(3s)-1-benzylpyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1CC1=CC=CC=C1 RGYMTQXWLQOOLF-SFHVURJKSA-N 0.000 description 1
- CDSDCXVCPMGPKE-HNNXBMFYSA-N 6-[[(3s)-1-butylpyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(CCCC)CC[C@@H]1NC1=CC=C2C(=O)NC=CC2=C1 CDSDCXVCPMGPKE-HNNXBMFYSA-N 0.000 description 1
- KIHBMXLPCMVZHW-INIZCTEOSA-N 6-[[(3s)-1-cyclohexylpyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C([C@@H](C1)NC=2C=C3C=CNC(C3=CC=2)=O)CN1C1CCCCC1 KIHBMXLPCMVZHW-INIZCTEOSA-N 0.000 description 1
- YGGOBDSDUWIUJL-HNNXBMFYSA-N 6-[[(3s)-1-pentan-3-ylpyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(C(CC)CC)CC[C@@H]1NC1=CC=C2C(=O)NC=CC2=C1 YGGOBDSDUWIUJL-HNNXBMFYSA-N 0.000 description 1
- QEJJEXHMSLDQRC-AWEZNQCLSA-N 6-[[(3s)-1-propan-2-ylpyrrolidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(C(C)C)CC[C@@H]1NC1=CC=C2C(=O)NC=CC2=C1 QEJJEXHMSLDQRC-AWEZNQCLSA-N 0.000 description 1
- RXMDPFCIKCSPIJ-UHFFFAOYSA-N 6-[[1-(3-methylbutyl)azetidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1N(CCC(C)C)CC1NC1=CC=C2C(=O)NC=CC2=C1 RXMDPFCIKCSPIJ-UHFFFAOYSA-N 0.000 description 1
- NJMANOQAOBJHGH-UHFFFAOYSA-N 6-[[1-(cyclohexylmethyl)azetidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NC=CC2=CC=1NC(C1)CN1CC1CCCCC1 NJMANOQAOBJHGH-UHFFFAOYSA-N 0.000 description 1
- UWDSIMRYITVGMK-UHFFFAOYSA-N 6-[[1-(cyclopropylmethyl)azetidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C=1C=C2C(=O)NC=CC2=CC=1NC(C1)CN1CC1CC1 UWDSIMRYITVGMK-UHFFFAOYSA-N 0.000 description 1
- OYAUENXKCKEMIN-UHFFFAOYSA-N 6-[[1-[(2,3-difluoro-4-methylphenyl)methyl]azetidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound FC1=C(F)C(C)=CC=C1CN1CC(NC=2C=C3C(C(NC=C3)=O)=CC=2)C1 OYAUENXKCKEMIN-UHFFFAOYSA-N 0.000 description 1
- GQYVDPMQURDTCN-UHFFFAOYSA-N 6-[[1-[(2-chlorophenyl)methyl]azetidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound ClC1=CC=CC=C1CN1CC(NC=2C=C3C(C(NC=C3)=O)=CC=2)C1 GQYVDPMQURDTCN-UHFFFAOYSA-N 0.000 description 1
- SXEKVOHQZWXSEN-UHFFFAOYSA-N 6-[[1-[(3-chloro-2-fluorophenyl)methyl]azetidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound FC1=C(Cl)C=CC=C1CN1CC(NC=2C=C3C(C(NC=C3)=O)=CC=2)C1 SXEKVOHQZWXSEN-UHFFFAOYSA-N 0.000 description 1
- BMOWPDCGJKAWFF-UHFFFAOYSA-N 6-[[1-[(3-chlorophenyl)methyl]azetidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound ClC1=CC=CC(CN2CC(C2)NC=2C=C3C(C(NC=C3)=O)=CC=2)=C1 BMOWPDCGJKAWFF-UHFFFAOYSA-N 0.000 description 1
- DXAVRRPCDQLUTP-UHFFFAOYSA-N 6-[[1-[(4-chlorophenyl)methyl]azetidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC(Cl)=CC=C1CN1CC(NC=2C=C3C(C(NC=C3)=O)=CC=2)C1 DXAVRRPCDQLUTP-UHFFFAOYSA-N 0.000 description 1
- RWCNJFWOBIDFKZ-UHFFFAOYSA-N 6-[[1-[(4-methylphenyl)methyl]azetidin-3-yl]amino]-2h-isoquinolin-1-one Chemical compound C1=CC(C)=CC=C1CN1CC(NC=2C=C3C(C(NC=C3)=O)=CC=2)C1 RWCNJFWOBIDFKZ-UHFFFAOYSA-N 0.000 description 1
- JFDDZMNLWUMVDO-UHFFFAOYSA-N 6-[ethyl(piperidin-4-yl)amino]-2h-isoquinolin-1-one Chemical compound C=1C=C(C(NC=C2)=O)C2=CC=1N(CC)C1CCNCC1 JFDDZMNLWUMVDO-UHFFFAOYSA-N 0.000 description 1
- GNBZRDRERAMROO-UHFFFAOYSA-N 6-[methyl(piperidin-4-yl)amino]-2h-isoquinolin-1-one Chemical compound C=1C=C(C(NC=C2)=O)C2=CC=1N(C)C1CCNCC1 GNBZRDRERAMROO-UHFFFAOYSA-N 0.000 description 1
- BBMIIVVHLNQHEJ-UHFFFAOYSA-N 6-[piperidin-4-yl(propyl)amino]-2h-isoquinolin-1-one Chemical compound C=1C=C(C(NC=C2)=O)C2=CC=1N(CCC)C1CCNCC1 BBMIIVVHLNQHEJ-UHFFFAOYSA-N 0.000 description 1
- SEQPOMQDFFDHAA-UHFFFAOYSA-N 6-bromo-1-phenylmethoxyisoquinoline Chemical compound N=1C=CC2=CC(Br)=CC=C2C=1OCC1=CC=CC=C1 SEQPOMQDFFDHAA-UHFFFAOYSA-N 0.000 description 1
- GHVZZWBJRRTGHT-UHFFFAOYSA-N 6-bromo-7-chloro-2h-isoquinolin-1-one Chemical compound C1=C(Br)C(Cl)=CC2=C1C=CNC2=O GHVZZWBJRRTGHT-UHFFFAOYSA-N 0.000 description 1
- PRDJZATVNLRSER-UHFFFAOYSA-N 6-chloro-7-(pyrrolidin-2-ylmethylsulfanyl)isoquinoline Chemical compound ClC1=CC2=CC=NC=C2C=C1SCC1CCCN1 PRDJZATVNLRSER-UHFFFAOYSA-N 0.000 description 1
- 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 1
- LHLQIHUBGJFCAG-UHFFFAOYSA-N 6-phenylmethoxyisoquinoline Chemical compound C=1C=C2C=NC=CC2=CC=1OCC1=CC=CC=C1 LHLQIHUBGJFCAG-UHFFFAOYSA-N 0.000 description 1
- IXKZRJOJEGJMIM-UHFFFAOYSA-N 6-piperidin-4-ylsulfanyl-7-propylisoquinoline Chemical compound CCCC1=CC2=CN=CC=C2C=C1SC1CCNCC1 IXKZRJOJEGJMIM-UHFFFAOYSA-N 0.000 description 1
- DKFBVFJDVNRKPE-UHFFFAOYSA-N 7-bromo-6-(1-butylpiperidin-4-yl)sulfanylisoquinoline Chemical compound C1CN(CCCC)CCC1SC1=CC2=CC=NC=C2C=C1Br DKFBVFJDVNRKPE-UHFFFAOYSA-N 0.000 description 1
- XRNGWEXBLBLLTH-UHFFFAOYSA-N 7-bromo-6-(1-cyclohexylpiperidin-4-yl)sulfanylisoquinoline Chemical compound BrC1=CC2=CN=CC=C2C=C1SC(CC1)CCN1C1CCCCC1 XRNGWEXBLBLLTH-UHFFFAOYSA-N 0.000 description 1
- BACRLKZQBSKGDS-UHFFFAOYSA-N 7-bromo-6-(1-ethylpiperidin-4-yl)sulfanylisoquinoline Chemical compound C1CN(CC)CCC1SC1=CC2=CC=NC=C2C=C1Br BACRLKZQBSKGDS-UHFFFAOYSA-N 0.000 description 1
- OUESCYPCHGEOEN-UHFFFAOYSA-N 7-bromo-6-(1-propan-2-ylpiperidin-4-yl)sulfanylisoquinoline Chemical compound C1CN(C(C)C)CCC1SC1=CC2=CC=NC=C2C=C1Br OUESCYPCHGEOEN-UHFFFAOYSA-N 0.000 description 1
- WXRNVWWNAUWEBU-UHFFFAOYSA-N 7-bromo-6-(1-propylpiperidin-4-yl)sulfanylisoquinoline Chemical compound C1CN(CCC)CCC1SC1=CC2=CC=NC=C2C=C1Br WXRNVWWNAUWEBU-UHFFFAOYSA-N 0.000 description 1
- USPWUGKOGWPBHQ-UHFFFAOYSA-N 7-bromo-6-(piperidin-3-ylmethylsulfanyl)isoquinoline;hydrochloride Chemical compound Cl.BrC1=CC2=CN=CC=C2C=C1SCC1CCCNC1 USPWUGKOGWPBHQ-UHFFFAOYSA-N 0.000 description 1
- BDBUHJMATNKZDM-UHFFFAOYSA-N 7-bromo-6-(pyrrolidin-3-ylmethylsulfanyl)isoquinoline;hydrochloride Chemical compound Cl.BrC1=CC2=CN=CC=C2C=C1SCC1CCNC1 BDBUHJMATNKZDM-UHFFFAOYSA-N 0.000 description 1
- ROJYXIAICXTOOU-UHFFFAOYSA-N 7-bromo-6-[1-(2-methylpropyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound C1CN(CC(C)C)CCC1SC1=CC2=CC=NC=C2C=C1Br ROJYXIAICXTOOU-UHFFFAOYSA-N 0.000 description 1
- YCAUCPOSTVZUEW-UHFFFAOYSA-N 7-bromo-6-[1-(3,3,3-trifluoropropyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound C1CN(CCC(F)(F)F)CCC1SC1=CC2=CC=NC=C2C=C1Br YCAUCPOSTVZUEW-UHFFFAOYSA-N 0.000 description 1
- XEJCELOOFBMZDZ-UHFFFAOYSA-N 7-bromo-6-[1-(3-methylbutyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound C1CN(CCC(C)C)CCC1SC1=CC2=CC=NC=C2C=C1Br XEJCELOOFBMZDZ-UHFFFAOYSA-N 0.000 description 1
- RAWNBIUYVJSDLR-UHFFFAOYSA-N 7-bromo-6-[1-(cyclohexylmethyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound BrC1=CC2=CN=CC=C2C=C1SC(CC1)CCN1CC1CCCCC1 RAWNBIUYVJSDLR-UHFFFAOYSA-N 0.000 description 1
- ITYORPDLMDCPJR-UHFFFAOYSA-N 7-bromo-6-[1-(cyclopropylmethyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound BrC1=CC2=CN=CC=C2C=C1SC(CC1)CCN1CC1CC1 ITYORPDLMDCPJR-UHFFFAOYSA-N 0.000 description 1
- UKZVLNHBSAIXLV-UHFFFAOYSA-N 7-bromo-6-[1-(naphthalen-1-ylmethyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound C1=CC=C2C(CN3CCC(CC3)SC3=CC4=CC=NC=C4C=C3Br)=CC=CC2=C1 UKZVLNHBSAIXLV-UHFFFAOYSA-N 0.000 description 1
- PTAVRNRCQQRUHS-UHFFFAOYSA-N 7-bromo-6-[1-(naphthalen-2-ylmethyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound C1=CC=CC2=CC(CN3CCC(CC3)SC3=CC4=CC=NC=C4C=C3Br)=CC=C21 PTAVRNRCQQRUHS-UHFFFAOYSA-N 0.000 description 1
- QXDWCKNINGYQSY-UHFFFAOYSA-N 7-bromo-6-[1-(pyridin-2-ylmethyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound BrC1=CC2=CN=CC=C2C=C1SC(CC1)CCN1CC1=CC=CC=N1 QXDWCKNINGYQSY-UHFFFAOYSA-N 0.000 description 1
- XZMXAFYYDMKWTG-UHFFFAOYSA-N 7-bromo-6-[1-[(1-methylpyrazol-4-yl)methyl]piperidin-4-yl]sulfanylisoquinoline Chemical compound C1=NN(C)C=C1CN1CCC(SC=2C(=CC3=CN=CC=C3C=2)Br)CC1 XZMXAFYYDMKWTG-UHFFFAOYSA-N 0.000 description 1
- GGVCNDWYEDMCLG-UHFFFAOYSA-N 7-bromo-6-[1-[(1-methylpyrrol-3-yl)methyl]piperidin-4-yl]sulfanylisoquinoline Chemical compound CN1C=CC(CN2CCC(CC2)SC=2C(=CC3=CN=CC=C3C=2)Br)=C1 GGVCNDWYEDMCLG-UHFFFAOYSA-N 0.000 description 1
- FMYNKOWRBYCREZ-UHFFFAOYSA-N 7-bromo-6-[1-[(2,4-dichlorophenyl)methyl]piperidin-4-yl]sulfanylisoquinoline Chemical compound ClC1=CC(Cl)=CC=C1CN1CCC(SC=2C(=CC3=CN=CC=C3C=2)Br)CC1 FMYNKOWRBYCREZ-UHFFFAOYSA-N 0.000 description 1
- JDWNNQDZNGLEGI-UHFFFAOYSA-N 7-bromo-6-[1-[(2-chlorophenyl)methyl]piperidin-4-yl]sulfanylisoquinoline Chemical compound ClC1=CC=CC=C1CN1CCC(SC=2C(=CC3=CN=CC=C3C=2)Br)CC1 JDWNNQDZNGLEGI-UHFFFAOYSA-N 0.000 description 1
- LVZSCRKWRSNDPU-UHFFFAOYSA-N 7-bromo-6-[1-[(3,5-dichlorophenyl)methyl]piperidin-4-yl]sulfanylisoquinoline Chemical compound ClC1=CC(Cl)=CC(CN2CCC(CC2)SC=2C(=CC3=CN=CC=C3C=2)Br)=C1 LVZSCRKWRSNDPU-UHFFFAOYSA-N 0.000 description 1
- WSLYTUUQSOYASJ-UHFFFAOYSA-N 7-bromo-6-[1-[(3-chlorophenyl)methyl]piperidin-4-yl]sulfanylisoquinoline Chemical compound ClC1=CC=CC(CN2CCC(CC2)SC=2C(=CC3=CN=CC=C3C=2)Br)=C1 WSLYTUUQSOYASJ-UHFFFAOYSA-N 0.000 description 1
- KPVRKMZVEWVXEA-UHFFFAOYSA-N 7-bromo-6-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]sulfanylisoquinoline Chemical compound C1=CC(Cl)=CC=C1CN1CCC(SC=2C(=CC3=CN=CC=C3C=2)Br)CC1 KPVRKMZVEWVXEA-UHFFFAOYSA-N 0.000 description 1
- VOEBEAVBZCPHQX-UHFFFAOYSA-N 7-bromo-6-[1-[(5-fluoro-2-methylsulfonylphenyl)methyl]piperidin-4-yl]sulfanylisoquinoline Chemical compound CS(=O)(=O)C1=CC=C(F)C=C1CN1CCC(SC=2C(=CC3=CN=CC=C3C=2)Br)CC1 VOEBEAVBZCPHQX-UHFFFAOYSA-N 0.000 description 1
- LVDMWUJATAQKCV-UHFFFAOYSA-N 7-bromo-6-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]sulfanylisoquinoline Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1CCC(SC=2C(=CC3=CN=CC=C3C=2)Br)CC1 LVDMWUJATAQKCV-UHFFFAOYSA-N 0.000 description 1
- YUWAFAQSAYEICV-UHFFFAOYSA-N 7-bromo-6-[1-[[4-(trifluoromethylsulfonyl)phenyl]methyl]piperidin-4-yl]sulfanylisoquinoline Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1CN1CCC(SC=2C(=CC3=CN=CC=C3C=2)Br)CC1 YUWAFAQSAYEICV-UHFFFAOYSA-N 0.000 description 1
- DOPIZHVRVATNNS-UHFFFAOYSA-N 7-bromo-6-piperidin-4-ylsulfanylisoquinoline Chemical compound BrC1=CC2=CN=CC=C2C=C1SC1CCNCC1 DOPIZHVRVATNNS-UHFFFAOYSA-N 0.000 description 1
- QCMHFSGOBOHYCP-UHFFFAOYSA-N 7-chloro-6-(1-cyclohexylpiperidin-3-yl)sulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC(C1)CCCN1C1CCCCC1 QCMHFSGOBOHYCP-UHFFFAOYSA-N 0.000 description 1
- OIMUZGVKQWPRDF-UHFFFAOYSA-N 7-chloro-6-(1-cyclohexylpiperidin-4-yl)sulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC(CC1)CCN1C1CCCCC1 OIMUZGVKQWPRDF-UHFFFAOYSA-N 0.000 description 1
- FJQVOCSQVKHQJM-UHFFFAOYSA-N 7-chloro-6-(1-ethylpiperidin-3-yl)sulfanylisoquinoline Chemical compound C1N(CC)CCCC1SC1=CC2=CC=NC=C2C=C1Cl FJQVOCSQVKHQJM-UHFFFAOYSA-N 0.000 description 1
- JUYRLPWJGHSDTO-UHFFFAOYSA-N 7-chloro-6-(1-ethylpiperidin-4-yl)sulfanylisoquinoline Chemical compound C1CN(CC)CCC1SC1=CC2=CC=NC=C2C=C1Cl JUYRLPWJGHSDTO-UHFFFAOYSA-N 0.000 description 1
- VCNDOAJZXICVKX-UHFFFAOYSA-N 7-chloro-6-(1-propan-2-ylpiperidin-3-yl)sulfanylisoquinoline Chemical compound C1N(C(C)C)CCCC1SC1=CC2=CC=NC=C2C=C1Cl VCNDOAJZXICVKX-UHFFFAOYSA-N 0.000 description 1
- DICAJTUUMPPDOK-UHFFFAOYSA-N 7-chloro-6-(1-propan-2-ylpiperidin-4-yl)sulfanylisoquinoline Chemical compound C1CN(C(C)C)CCC1SC1=CC2=CC=NC=C2C=C1Cl DICAJTUUMPPDOK-UHFFFAOYSA-N 0.000 description 1
- OQMNGDSYRRKVAP-UHFFFAOYSA-N 7-chloro-6-(1-propylpiperidin-3-yl)sulfanylisoquinoline Chemical compound C1N(CCC)CCCC1SC1=CC2=CC=NC=C2C=C1Cl OQMNGDSYRRKVAP-UHFFFAOYSA-N 0.000 description 1
- APUYMVJBYOXQEU-UHFFFAOYSA-N 7-chloro-6-(1-propylpiperidin-4-yl)sulfanylisoquinoline Chemical compound C1CN(CCC)CCC1SC1=CC2=CC=NC=C2C=C1Cl APUYMVJBYOXQEU-UHFFFAOYSA-N 0.000 description 1
- UHUAEJZBPADZOH-UHFFFAOYSA-N 7-chloro-6-(piperidin-3-ylmethylsulfanyl)isoquinoline;hydrochloride Chemical compound Cl.ClC1=CC2=CN=CC=C2C=C1SCC1CCCNC1 UHUAEJZBPADZOH-UHFFFAOYSA-N 0.000 description 1
- IGLSIAPPYSIVKP-UHFFFAOYSA-N 7-chloro-6-(piperidin-4-ylamino)-2h-isoquinolin-1-one Chemical compound ClC1=CC(C(NC=C2)=O)=C2C=C1NC1CCNCC1 IGLSIAPPYSIVKP-UHFFFAOYSA-N 0.000 description 1
- QBKRVNVBQASYJE-UHFFFAOYSA-N 7-chloro-6-(piperidin-4-ylmethylsulfanyl)isoquinoline;hydrochloride Chemical compound Cl.ClC1=CC2=CN=CC=C2C=C1SCC1CCNCC1 QBKRVNVBQASYJE-UHFFFAOYSA-N 0.000 description 1
- PTBYQARGDHMSOL-UHFFFAOYSA-N 7-chloro-6-(pyrrolidin-2-ylmethylsulfanyl)isoquinoline;hydrochloride Chemical compound Cl.ClC1=CC2=CN=CC=C2C=C1SCC1CCCN1 PTBYQARGDHMSOL-UHFFFAOYSA-N 0.000 description 1
- RXIPSAQMDKMOBL-UHFFFAOYSA-N 7-chloro-6-(pyrrolidin-3-ylmethylsulfanyl)isoquinoline;hydrochloride Chemical compound Cl.ClC1=CC2=CN=CC=C2C=C1SCC1CCNC1 RXIPSAQMDKMOBL-UHFFFAOYSA-N 0.000 description 1
- COBPFSZBCSWTRR-CHPOKUKFSA-N 7-chloro-6-[(2S)-1-cyclopropyl-2-methylpyrrolidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=C(C=C2C=CN=CC2=C1)SC1[C@@H](N(CC1)C1CC1)C COBPFSZBCSWTRR-CHPOKUKFSA-N 0.000 description 1
- MYTYLCWLCVYKQF-HNNXBMFYSA-N 7-chloro-6-[(3s)-1-(2-methylpropyl)pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1N(CC(C)C)CC[C@@H]1SC1=CC2=CC=NC=C2C=C1Cl MYTYLCWLCVYKQF-HNNXBMFYSA-N 0.000 description 1
- YDYYBBAWGBSOJD-ZDUSSCGKSA-N 7-chloro-6-[(3s)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1N(CCC(F)(F)F)CC[C@@H]1SC1=CC2=CC=NC=C2C=C1Cl YDYYBBAWGBSOJD-ZDUSSCGKSA-N 0.000 description 1
- NMHHSXOUWUFQBR-INIZCTEOSA-N 7-chloro-6-[(3s)-1-(3-methylbutyl)pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1N(CCC(C)C)CC[C@@H]1SC1=CC2=CC=NC=C2C=C1Cl NMHHSXOUWUFQBR-INIZCTEOSA-N 0.000 description 1
- FAZRXLBINDKGOX-SFHVURJKSA-N 7-chloro-6-[(3s)-1-(cyclohexylmethyl)pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C([C@@H](C1)SC2=CC3=CC=NC=C3C=C2Cl)CN1CC1CCCCC1 FAZRXLBINDKGOX-SFHVURJKSA-N 0.000 description 1
- UEECQCMHSYQZMG-QFIPXVFZSA-N 7-chloro-6-[(3s)-1-(naphthalen-2-ylmethyl)pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1=CC=CC2=CC(CN3CC[C@@H](C3)SC3=CC4=CC=NC=C4C=C3Cl)=CC=C21 UEECQCMHSYQZMG-QFIPXVFZSA-N 0.000 description 1
- QRSBKJJRXPOKRB-KRWDZBQOSA-N 7-chloro-6-[(3s)-1-(pyridin-2-ylmethyl)pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C([C@@H](C1)SC2=CC3=CC=NC=C3C=C2Cl)CN1CC1=CC=CC=N1 QRSBKJJRXPOKRB-KRWDZBQOSA-N 0.000 description 1
- NCIFBTOOSNHUHZ-KRWDZBQOSA-N 7-chloro-6-[(3s)-1-(pyridin-3-ylmethyl)pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C([C@@H](C1)SC2=CC3=CC=NC=C3C=C2Cl)CN1CC1=CC=CN=C1 NCIFBTOOSNHUHZ-KRWDZBQOSA-N 0.000 description 1
- ZPJMAWKQCKTFKT-KRWDZBQOSA-N 7-chloro-6-[(3s)-1-(pyridin-4-ylmethyl)pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C([C@@H](C1)SC2=CC3=CC=NC=C3C=C2Cl)CN1CC1=CC=NC=C1 ZPJMAWKQCKTFKT-KRWDZBQOSA-N 0.000 description 1
- VFLPUGDUSAEJGZ-KRWDZBQOSA-N 7-chloro-6-[(3s)-1-[(2,4-dichlorophenyl)methyl]pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC(Cl)=CC=C1CN1C[C@@H](SC=2C(=CC3=CN=CC=C3C=2)Cl)CC1 VFLPUGDUSAEJGZ-KRWDZBQOSA-N 0.000 description 1
- YHJDKKSUXCHSOF-KRWDZBQOSA-N 7-chloro-6-[(3s)-1-[(2-chlorophenyl)methyl]pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC=CC=C1CN1C[C@@H](SC=2C(=CC3=CN=CC=C3C=2)Cl)CC1 YHJDKKSUXCHSOF-KRWDZBQOSA-N 0.000 description 1
- YZSVLCQNFRDUAJ-SFHVURJKSA-N 7-chloro-6-[(3s)-1-[(3,5-dichlorophenyl)methyl]pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC(Cl)=CC(CN2C[C@H](CC2)SC=2C(=CC3=CN=CC=C3C=2)Cl)=C1 YZSVLCQNFRDUAJ-SFHVURJKSA-N 0.000 description 1
- DYRJWEVPDHXUDL-SFHVURJKSA-N 7-chloro-6-[(3s)-1-[(3-chlorophenyl)methyl]pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC=CC(CN2C[C@H](CC2)SC=2C(=CC3=CN=CC=C3C=2)Cl)=C1 DYRJWEVPDHXUDL-SFHVURJKSA-N 0.000 description 1
- YVOGIKZJBXGREI-SFHVURJKSA-N 7-chloro-6-[(3s)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1=CC(Cl)=CC=C1CN1C[C@@H](SC=2C(=CC3=CN=CC=C3C=2)Cl)CC1 YVOGIKZJBXGREI-SFHVURJKSA-N 0.000 description 1
- ILYXZZFDZPFRBY-IBGZPJMESA-N 7-chloro-6-[(3s)-1-[(4-methylphenyl)methyl]pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1=CC(C)=CC=C1CN1C[C@@H](SC=2C(=CC3=CN=CC=C3C=2)Cl)CC1 ILYXZZFDZPFRBY-IBGZPJMESA-N 0.000 description 1
- IHAIDRVFFACESS-SFHVURJKSA-N 7-chloro-6-[(3s)-1-[(4-methylsulfonylphenyl)methyl]pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1C[C@@H](SC=2C(=CC3=CN=CC=C3C=2)Cl)CC1 IHAIDRVFFACESS-SFHVURJKSA-N 0.000 description 1
- PSBZNJIDUAWAKH-SFHVURJKSA-N 7-chloro-6-[(3s)-1-[(5-fluoro-2-methylsulfonylphenyl)methyl]pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound CS(=O)(=O)C1=CC=C(F)C=C1CN1C[C@@H](SC=2C(=CC3=CN=CC=C3C=2)Cl)CC1 PSBZNJIDUAWAKH-SFHVURJKSA-N 0.000 description 1
- NVOPRIXKTLKTDX-SFHVURJKSA-N 7-chloro-6-[(3s)-1-[[4-(trifluoromethyl)phenyl]methyl]pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1C[C@@H](SC=2C(=CC3=CN=CC=C3C=2)Cl)CC1 NVOPRIXKTLKTDX-SFHVURJKSA-N 0.000 description 1
- YYSUUJUSKLWOCG-KRWDZBQOSA-N 7-chloro-6-[(3s)-1-[[4-(trifluoromethylsulfonyl)phenyl]methyl]pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1CN1C[C@@H](SC=2C(=CC3=CN=CC=C3C=2)Cl)CC1 YYSUUJUSKLWOCG-KRWDZBQOSA-N 0.000 description 1
- SJJBPUBSEAQSPV-KRWDZBQOSA-N 7-chloro-6-[(3s)-1-cyclohexylpyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C([C@@H](C1)SC2=CC3=CC=NC=C3C=C2Cl)CN1C1CCCCC1 SJJBPUBSEAQSPV-KRWDZBQOSA-N 0.000 description 1
- QRNJQPOCHQPNIM-ZOWNYOTGSA-N 7-chloro-6-[(3s)-1-ethylpyrrolidin-3-yl]sulfanylisoquinoline;hydrochloride Chemical compound Cl.C1N(CC)CC[C@@H]1SC1=CC2=CC=NC=C2C=C1Cl QRNJQPOCHQPNIM-ZOWNYOTGSA-N 0.000 description 1
- KDDUEHARCATUSX-AWEZNQCLSA-N 7-chloro-6-[(3s)-1-propan-2-ylpyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1N(C(C)C)CC[C@@H]1SC1=CC2=CC=NC=C2C=C1Cl KDDUEHARCATUSX-AWEZNQCLSA-N 0.000 description 1
- PZCRDBMSWSHPNH-AWEZNQCLSA-N 7-chloro-6-[(3s)-1-propylpyrrolidin-3-yl]sulfanylisoquinoline Chemical compound C1N(CCC)CC[C@@H]1SC1=CC2=CC=NC=C2C=C1Cl PZCRDBMSWSHPNH-AWEZNQCLSA-N 0.000 description 1
- VZSPDUHUWQGLPA-NSHDSACASA-N 7-chloro-6-[(3s)-pyrrolidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1S[C@H]1CCNC1 VZSPDUHUWQGLPA-NSHDSACASA-N 0.000 description 1
- HEOJIYXDQUMQKZ-UHFFFAOYSA-N 7-chloro-6-[1-(2-methylpropyl)piperidin-3-yl]sulfanylisoquinoline Chemical compound C1N(CC(C)C)CCCC1SC1=CC2=CC=NC=C2C=C1Cl HEOJIYXDQUMQKZ-UHFFFAOYSA-N 0.000 description 1
- PVWXZUDVLSXPRO-UHFFFAOYSA-N 7-chloro-6-[1-(2-methylpropyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound C1CN(CC(C)C)CCC1SC1=CC2=CC=NC=C2C=C1Cl PVWXZUDVLSXPRO-UHFFFAOYSA-N 0.000 description 1
- MOGOFVCHUOPWQU-UHFFFAOYSA-N 7-chloro-6-[1-(3,3,3-trifluoropropyl)piperidin-3-yl]sulfanylisoquinoline Chemical compound C1N(CCC(F)(F)F)CCCC1SC1=CC2=CC=NC=C2C=C1Cl MOGOFVCHUOPWQU-UHFFFAOYSA-N 0.000 description 1
- ZQQYRVHMFNKIDF-UHFFFAOYSA-N 7-chloro-6-[1-(3,3,3-trifluoropropyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound C1CN(CCC(F)(F)F)CCC1SC1=CC2=CC=NC=C2C=C1Cl ZQQYRVHMFNKIDF-UHFFFAOYSA-N 0.000 description 1
- SVXKZJMOQWZBJG-UHFFFAOYSA-N 7-chloro-6-[1-(3-methylbutyl)piperidin-3-yl]sulfanylisoquinoline Chemical compound C1N(CCC(C)C)CCCC1SC1=CC2=CC=NC=C2C=C1Cl SVXKZJMOQWZBJG-UHFFFAOYSA-N 0.000 description 1
- WAIUFLJLUMTIJO-UHFFFAOYSA-N 7-chloro-6-[1-(3-methylbutyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound C1CN(CCC(C)C)CCC1SC1=CC2=CC=NC=C2C=C1Cl WAIUFLJLUMTIJO-UHFFFAOYSA-N 0.000 description 1
- HMDRVIWJNBQIBH-UHFFFAOYSA-N 7-chloro-6-[1-(cyclohexylmethyl)piperidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC(C1)CCCN1CC1CCCCC1 HMDRVIWJNBQIBH-UHFFFAOYSA-N 0.000 description 1
- WQDPQJYRDLKMOB-UHFFFAOYSA-N 7-chloro-6-[1-(cyclohexylmethyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC(CC1)CCN1CC1CCCCC1 WQDPQJYRDLKMOB-UHFFFAOYSA-N 0.000 description 1
- BZMKLEKNIGNMDR-UHFFFAOYSA-N 7-chloro-6-[1-(cyclopropylmethyl)piperidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC(C1)CCCN1CC1CC1 BZMKLEKNIGNMDR-UHFFFAOYSA-N 0.000 description 1
- ZAQHBOYFVWOCCE-UHFFFAOYSA-N 7-chloro-6-[1-(cyclopropylmethyl)piperidin-4-yl]sulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC(CC1)CCN1CC1CC1 ZAQHBOYFVWOCCE-UHFFFAOYSA-N 0.000 description 1
- SNQYYDFRAFFONU-UHFFFAOYSA-N 7-chloro-6-[1-(pyridin-2-ylmethyl)piperidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC(C1)CCCN1CC1=CC=CC=N1 SNQYYDFRAFFONU-UHFFFAOYSA-N 0.000 description 1
- HCOCDPWAEMALCH-UHFFFAOYSA-N 7-chloro-6-[1-[(2,4-dichlorophenyl)methyl]piperidin-3-yl]sulfanylisoquinoline Chemical compound ClC1=CC(Cl)=CC=C1CN1CC(SC=2C(=CC3=CN=CC=C3C=2)Cl)CCC1 HCOCDPWAEMALCH-UHFFFAOYSA-N 0.000 description 1
- PTKVNYJGJSGOCB-UHFFFAOYSA-N 7-chloro-6-fluoro-2-[(4-methoxyphenyl)methyl]isoquinolin-1-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC(Cl)=C(F)C=C2C=C1 PTKVNYJGJSGOCB-UHFFFAOYSA-N 0.000 description 1
- IKMSNGBBBMWXQZ-UHFFFAOYSA-N 7-chloro-6-piperidin-3-ylsulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC1CCCNC1 IKMSNGBBBMWXQZ-UHFFFAOYSA-N 0.000 description 1
- ZDXRNDIJPXYZDD-UHFFFAOYSA-N 7-chloro-6-piperidin-3-ylsulfanylisoquinoline;hydrochloride Chemical compound Cl.ClC1=CC2=CN=CC=C2C=C1SC1CCCNC1 ZDXRNDIJPXYZDD-UHFFFAOYSA-N 0.000 description 1
- VSCDGTIWXMJPQG-UHFFFAOYSA-N 7-chloro-6-piperidin-4-ylsulfanyl-2h-isoquinolin-1-one;hydrochloride Chemical compound Cl.ClC1=CC(C(NC=C2)=O)=C2C=C1SC1CCNCC1 VSCDGTIWXMJPQG-UHFFFAOYSA-N 0.000 description 1
- ZQWJIYVFIQKYGA-UHFFFAOYSA-N 7-chloro-6-piperidin-4-ylsulfanylisoquinoline Chemical compound ClC1=CC2=CN=CC=C2C=C1SC1CCNCC1 ZQWJIYVFIQKYGA-UHFFFAOYSA-N 0.000 description 1
- QGUBXDQNODQAJN-UHFFFAOYSA-N 7-chloro-6-piperidin-4-ylsulfanylisoquinoline;hydrochloride Chemical compound Cl.ClC1=CC2=CN=CC=C2C=C1SC1CCNCC1 QGUBXDQNODQAJN-UHFFFAOYSA-N 0.000 description 1
- NYEAQCGMMWEZCY-UHFFFAOYSA-N 7-chloro-6-piperidin-4-ylsulfinyl-2h-isoquinolin-1-one;hydrochloride Chemical compound Cl.ClC1=CC(C(NC=C2)=O)=C2C=C1S(=O)C1CCNCC1 NYEAQCGMMWEZCY-UHFFFAOYSA-N 0.000 description 1
- IORHBHHHYBJUBO-UHFFFAOYSA-N 7-chloro-6-piperidin-4-ylsulfonyl-2h-isoquinolin-1-one;hydrochloride Chemical compound Cl.ClC1=CC(C(NC=C2)=O)=C2C=C1S(=O)(=O)C1CCNCC1 IORHBHHHYBJUBO-UHFFFAOYSA-N 0.000 description 1
- QUIOIYXUVFOHQJ-UHFFFAOYSA-N 7-chloro-n-(1-methylpiperidin-4-yl)isoquinolin-6-amine Chemical compound C1CN(C)CCC1NC1=CC2=CC=NC=C2C=C1Cl QUIOIYXUVFOHQJ-UHFFFAOYSA-N 0.000 description 1
- AYBMWZHNAWJZMK-UHFFFAOYSA-N 7-chloro-n-piperidin-4-ylisoquinolin-6-amine Chemical compound ClC1=CC2=CN=CC=C2C=C1NC1CCNCC1 AYBMWZHNAWJZMK-UHFFFAOYSA-N 0.000 description 1
- PVFOHMXILQEIHX-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-bromophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Br PVFOHMXILQEIHX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical class OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 238000007125 Buchwald synthesis reaction Methods 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Chemical class OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 206010048554 Endothelial dysfunction Diseases 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 101000669921 Homo sapiens Rho-associated protein kinase 2 Proteins 0.000 description 1
- 206010055171 Hypertensive nephropathy Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 206010027458 Metastases to lung Diseases 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 102000016349 Myosin Light Chains Human genes 0.000 description 1
- 108010067385 Myosin Light Chains Proteins 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 1
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000005275 alkylenearyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000005512 benztetrazolyl group Chemical group 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000004623 carbolinyl group Chemical group 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 229960002303 citric acid monohydrate Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125936 compound 42 Drugs 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical compound C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- WDUDHEOUGWAKFD-UHFFFAOYSA-N ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+) Chemical compound [Fe+2].CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1.CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1 WDUDHEOUGWAKFD-UHFFFAOYSA-N 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000008694 endothelial dysfunction Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical class CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- NGOGFTYYXHNFQH-UHFFFAOYSA-N fasudil Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 NGOGFTYYXHNFQH-UHFFFAOYSA-N 0.000 description 1
- 229960002435 fasudil Drugs 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 150000008423 fluorobenzenes Chemical class 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000000174 gluconic acid Chemical class 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- CANNEYRNFLETNI-UHFFFAOYSA-N iron(3+) propan-2-one Chemical compound [Fe+3].CC(=O)C CANNEYRNFLETNI-UHFFFAOYSA-N 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 150000004272 isoquinoline-5-sulfonamides Chemical class 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- RYEXTBOQKFUPOE-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].CC[CH2-] RYEXTBOQKFUPOE-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000001114 myogenic effect Effects 0.000 description 1
- YTDSGDDBHRQOBQ-UJUJBVAOSA-N n'-[2-chloro-5-[[(3r)-3-(isoquinolin-6-ylamino)piperidin-1-yl]methyl]phenyl]sulfonyl-n,n-dimethylmethanimidamide Chemical compound C1=C(Cl)C(S(=O)(=O)/N=C/N(C)C)=CC(CN2C[C@@H](CCC2)NC=2C=C3C=CN=CC3=CC=2)=C1 YTDSGDDBHRQOBQ-UJUJBVAOSA-N 0.000 description 1
- YVMWWHMRAYOKFE-QZLJHNFXSA-N n'-[2-chloro-5-[[(3r)-3-(isoquinolin-6-ylamino)pyrrolidin-1-yl]methyl]phenyl]sulfonyl-n,n-dimethylmethanimidamide Chemical compound C1=C(Cl)C(S(=O)(=O)/N=C/N(C)C)=CC(CN2C[C@@H](CC2)NC=2C=C3C=CN=CC3=CC=2)=C1 YVMWWHMRAYOKFE-QZLJHNFXSA-N 0.000 description 1
- WYDLWXZZXJBJAB-CSWGWEJPSA-N n'-[2-chloro-5-[[(3r)-3-[(1-oxo-2h-isoquinolin-6-yl)amino]piperidin-1-yl]methyl]phenyl]sulfonyl-n,n-dimethylmethanimidamide Chemical compound C1=C(Cl)C(S(=O)(=O)/N=C/N(C)C)=CC(CN2C[C@@H](CCC2)NC=2C=C3C(C(NC=C3)=O)=CC=2)=C1 WYDLWXZZXJBJAB-CSWGWEJPSA-N 0.000 description 1
- PBPKTYNQIFAIAT-CRXVIZHGSA-N n'-[2-chloro-5-[[(3s)-3-[(1-oxo-2h-isoquinolin-6-yl)amino]pyrrolidin-1-yl]methyl]phenyl]sulfonyl-n,n-dimethylmethanimidamide Chemical compound C1=C(Cl)C(S(=O)(=O)/N=C/N(C)C)=CC(CN2C[C@H](CC2)NC=2C=C3C(C(NC=C3)=O)=CC=2)=C1 PBPKTYNQIFAIAT-CRXVIZHGSA-N 0.000 description 1
- VWKZYKSTXKPXLU-MFKUBSTISA-N n'-[2-chloro-5-[[3-(isoquinolin-6-ylamino)azetidin-1-yl]methyl]phenyl]sulfonyl-n,n-dimethylmethanimidamide Chemical compound C1=C(Cl)C(S(=O)(=O)/N=C/N(C)C)=CC(CN2CC(C2)NC=2C=C3C=CN=CC3=CC=2)=C1 VWKZYKSTXKPXLU-MFKUBSTISA-N 0.000 description 1
- VQAJHEINCRCXNT-MORQCWLFSA-N n'-[3-[[(3r)-3-(isoquinolin-6-ylamino)piperidin-1-yl]methyl]-4-methoxyphenyl]sulfonyl-n,n-dimethylmethanimidamide Chemical compound COC1=CC=C(S(=O)(=O)\N=C\N(C)C)C=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CCC1 VQAJHEINCRCXNT-MORQCWLFSA-N 0.000 description 1
- NKVSSQFWVFTXJY-XBIXJXDHSA-N n'-[3-[[(3r)-3-(isoquinolin-6-ylamino)pyrrolidin-1-yl]methyl]-4-methoxyphenyl]sulfonyl-n,n-dimethylmethanimidamide Chemical compound COC1=CC=C(S(=O)(=O)\N=C\N(C)C)C=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CC1 NKVSSQFWVFTXJY-XBIXJXDHSA-N 0.000 description 1
- PXOHIMNNBBNYCW-OVVQPSECSA-N n'-[3-[[4-(isoquinolin-6-ylamino)piperidin-1-yl]methyl]-4-methoxyphenyl]sulfonyl-n,n-dimethylmethanimidamide Chemical compound COC1=CC=C(S(=O)(=O)\N=C\N(C)C)C=C1CN1CCC(NC=2C=C3C=CN=CC3=CC=2)CC1 PXOHIMNNBBNYCW-OVVQPSECSA-N 0.000 description 1
- YVBWVKRFBKAFGQ-LQKURTRISA-N n'-[5-[[4-(7-bromoisoquinolin-6-yl)sulfanylpiperidin-1-yl]methyl]-2-chlorophenyl]sulfonyl-n,n-dimethylmethanimidamide Chemical compound C1=C(Cl)C(S(=O)(=O)/N=C/N(C)C)=CC(CN2CCC(CC2)SC=2C(=CC3=CN=CC=C3C=2)Br)=C1 YVBWVKRFBKAFGQ-LQKURTRISA-N 0.000 description 1
- CHYBLEJVKVQGRY-UHFFFAOYSA-N n-(1-benzylazetidin-3-yl)isoquinolin-6-amine Chemical compound C1C(NC=2C=C3C=CN=CC3=CC=2)CN1CC1=CC=CC=C1 CHYBLEJVKVQGRY-UHFFFAOYSA-N 0.000 description 1
- HVQAZWACKCMMJH-UHFFFAOYSA-N n-(1-benzylpiperidin-4-yl)isoquinolin-6-amine Chemical compound C1CC(NC=2C=C3C=CN=CC3=CC=2)CCN1CC1=CC=CC=C1 HVQAZWACKCMMJH-UHFFFAOYSA-N 0.000 description 1
- QMTFLOWPFVJJMI-UHFFFAOYSA-N n-(1-butylazetidin-3-yl)isoquinolin-6-amine Chemical compound C1N(CCCC)CC1NC1=CC=C(C=NC=C2)C2=C1 QMTFLOWPFVJJMI-UHFFFAOYSA-N 0.000 description 1
- LJAXUNWQUXKIRP-UHFFFAOYSA-N n-(1-butylpiperidin-4-yl)-n-methylisoquinolin-6-amine Chemical compound C1CN(CCCC)CCC1N(C)C1=CC=C(C=NC=C2)C2=C1 LJAXUNWQUXKIRP-UHFFFAOYSA-N 0.000 description 1
- BALGDSCKYCDBJJ-UHFFFAOYSA-N n-(1-butylpiperidin-4-yl)isoquinolin-6-amine Chemical compound C1CN(CCCC)CCC1NC1=CC=C(C=NC=C2)C2=C1 BALGDSCKYCDBJJ-UHFFFAOYSA-N 0.000 description 1
- KPZFSIIVBMIRFO-UHFFFAOYSA-N n-(1-cyclohexylazetidin-3-yl)isoquinolin-6-amine Chemical compound C1C(NC=2C=C3C=CN=CC3=CC=2)CN1C1CCCCC1 KPZFSIIVBMIRFO-UHFFFAOYSA-N 0.000 description 1
- KZCULAXWTDHIPU-UHFFFAOYSA-N n-(1-cyclohexylpiperidin-4-yl)isoquinolin-6-amine Chemical compound C1CCCCC1N1CCC(NC=2C=C3C=CN=CC3=CC=2)CC1 KZCULAXWTDHIPU-UHFFFAOYSA-N 0.000 description 1
- SZFKMJKXSKUZIX-UHFFFAOYSA-N n-(1-ethylazetidin-3-yl)isoquinolin-6-amine Chemical compound C1N(CC)CC1NC1=CC=C(C=NC=C2)C2=C1 SZFKMJKXSKUZIX-UHFFFAOYSA-N 0.000 description 1
- PUPNBKJFDQFDCQ-UHFFFAOYSA-N n-(1-ethylpiperidin-3-yl)isoquinolin-6-amine Chemical compound C1N(CC)CCCC1NC1=CC=C(C=NC=C2)C2=C1 PUPNBKJFDQFDCQ-UHFFFAOYSA-N 0.000 description 1
- RZQCLKFGRJYSCQ-UHFFFAOYSA-N n-(1-ethylpiperidin-4-yl)isoquinolin-6-amine;hydrochloride Chemical compound Cl.C1CN(CC)CCC1NC1=CC=C(C=NC=C2)C2=C1 RZQCLKFGRJYSCQ-UHFFFAOYSA-N 0.000 description 1
- DETKWTATWJJAPT-UHFFFAOYSA-N n-(1-methylpiperidin-4-yl)isoquinolin-6-amine Chemical compound C1CN(C)CCC1NC1=CC=C(C=NC=C2)C2=C1 DETKWTATWJJAPT-UHFFFAOYSA-N 0.000 description 1
- NPHTWLMNOLOOBK-UHFFFAOYSA-N n-(1-pentan-3-ylazetidin-3-yl)isoquinolin-6-amine Chemical compound C1N(C(CC)CC)CC1NC1=CC=C(C=NC=C2)C2=C1 NPHTWLMNOLOOBK-UHFFFAOYSA-N 0.000 description 1
- QNGNCTPLAJWXFI-UHFFFAOYSA-N n-(1-propan-2-ylazetidin-3-yl)isoquinolin-6-amine Chemical compound C1N(C(C)C)CC1NC1=CC=C(C=NC=C2)C2=C1 QNGNCTPLAJWXFI-UHFFFAOYSA-N 0.000 description 1
- AXCXWNIPJKEYIG-UHFFFAOYSA-N n-(1-propan-2-ylpiperidin-4-yl)isoquinolin-6-amine Chemical compound C1CN(C(C)C)CCC1NC1=CC=C(C=NC=C2)C2=C1 AXCXWNIPJKEYIG-UHFFFAOYSA-N 0.000 description 1
- WCTJQYJVMRNGEI-UHFFFAOYSA-N n-(1-propylazetidin-3-yl)isoquinolin-6-amine Chemical compound C1N(CCC)CC1NC1=CC=C(C=NC=C2)C2=C1 WCTJQYJVMRNGEI-UHFFFAOYSA-N 0.000 description 1
- SWHBQCLGQYPZOY-UHFFFAOYSA-N n-(1-propylpiperidin-4-yl)isoquinolin-6-amine Chemical compound C1CN(CCC)CCC1NC1=CC=C(C=NC=C2)C2=C1 SWHBQCLGQYPZOY-UHFFFAOYSA-N 0.000 description 1
- MULDYOJOHUCESA-UHFFFAOYSA-N n-(azetidin-3-yl)isoquinolin-6-amine;hydrochloride Chemical compound Cl.C1NCC1NC1=CC=C(C=NC=C2)C2=C1 MULDYOJOHUCESA-UHFFFAOYSA-N 0.000 description 1
- LVFMTJNPEXWQNM-UHFFFAOYSA-N n-(piperidin-3-ylmethyl)isoquinolin-6-amine Chemical compound C=1C=C2C=NC=CC2=CC=1NCC1CCCNC1 LVFMTJNPEXWQNM-UHFFFAOYSA-N 0.000 description 1
- PNYWLIWESPPJFX-UHFFFAOYSA-N n-(pyrrolidin-2-ylmethyl)isoquinolin-6-amine Chemical compound C=1C=C2C=NC=CC2=CC=1NCC1CCCN1 PNYWLIWESPPJFX-UHFFFAOYSA-N 0.000 description 1
- ZTATUCSVYRMQJN-UHFFFAOYSA-N n-(pyrrolidin-3-ylmethyl)isoquinolin-6-amine Chemical compound C=1C=C2C=NC=CC2=CC=1NCC1CCNC1 ZTATUCSVYRMQJN-UHFFFAOYSA-N 0.000 description 1
- QWCOSCSFTKBLJD-UHFFFAOYSA-N n-[(1-butylpiperidin-4-yl)methyl]isoquinolin-6-amine Chemical compound C1CN(CCCC)CCC1CNC1=CC=C(C=NC=C2)C2=C1 QWCOSCSFTKBLJD-UHFFFAOYSA-N 0.000 description 1
- YHIPDZDDTVMCGM-MRXNPFEDSA-N n-[(3r)-1-(3,3,3-trifluoropropyl)piperidin-3-yl]isoquinolin-6-amine Chemical compound C1N(CCC(F)(F)F)CCC[C@H]1NC1=CC=C(C=NC=C2)C2=C1 YHIPDZDDTVMCGM-MRXNPFEDSA-N 0.000 description 1
- UZZSUGHZWWGQBQ-OAHLLOKOSA-N n-[(3r)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C1N(CCC(F)(F)F)CC[C@H]1NC1=CC=C(C=NC=C2)C2=C1 UZZSUGHZWWGQBQ-OAHLLOKOSA-N 0.000 description 1
- DNZWNQWKUVXFDH-LJQANCHMSA-N n-[(3r)-1-(3-methylbutyl)piperidin-3-yl]isoquinolin-6-amine Chemical compound C1N(CCC(C)C)CCC[C@H]1NC1=CC=C(C=NC=C2)C2=C1 DNZWNQWKUVXFDH-LJQANCHMSA-N 0.000 description 1
- IQBKYIVPYLMEPV-GOSISDBHSA-N n-[(3r)-1-(3-methylbutyl)pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C1N(CCC(C)C)CC[C@H]1NC1=CC=C(C=NC=C2)C2=C1 IQBKYIVPYLMEPV-GOSISDBHSA-N 0.000 description 1
- UDLYJZVWBQLEMV-XMMPIXPASA-N n-[(3r)-1-(naphthalen-1-ylmethyl)piperidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC=C2C(CN3C[C@@H](CCC3)NC=3C=C4C=CN=CC4=CC=3)=CC=CC2=C1 UDLYJZVWBQLEMV-XMMPIXPASA-N 0.000 description 1
- DBIKTNLOCCUWRX-RUZDIDTESA-N n-[(3r)-1-(naphthalen-2-ylmethyl)piperidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC=CC2=CC(CN3C[C@@H](CCC3)NC=3C=C4C=CN=CC4=CC=3)=CC=C21 DBIKTNLOCCUWRX-RUZDIDTESA-N 0.000 description 1
- JHFKCQJISWXBMR-XMMPIXPASA-N n-[(3r)-1-(naphthalen-2-ylmethyl)pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC=CC2=CC(CN3C[C@@H](CC3)NC=3C=C4C=CN=CC4=CC=3)=CC=C21 JHFKCQJISWXBMR-XMMPIXPASA-N 0.000 description 1
- FXJOCYZFRSDQJA-HXUWFJFHSA-N n-[(3r)-1-(pyridin-2-ylmethyl)piperidin-3-yl]isoquinolin-6-amine Chemical compound C([C@@H](CCC1)NC=2C=C3C=CN=CC3=CC=2)N1CC1=CC=CC=N1 FXJOCYZFRSDQJA-HXUWFJFHSA-N 0.000 description 1
- SPQJFUFADUJZBR-LJQANCHMSA-N n-[(3r)-1-(pyridin-2-ylmethyl)pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C([C@@H](CC1)NC=2C=C3C=CN=CC3=CC=2)N1CC1=CC=CC=N1 SPQJFUFADUJZBR-LJQANCHMSA-N 0.000 description 1
- MYXKTEBTCKEINR-HXUWFJFHSA-N n-[(3r)-1-(pyridin-3-ylmethyl)piperidin-3-yl]isoquinolin-6-amine Chemical compound C([C@@H](CCC1)NC=2C=C3C=CN=CC3=CC=2)N1CC1=CC=CN=C1 MYXKTEBTCKEINR-HXUWFJFHSA-N 0.000 description 1
- SYZOYFXVBSNDSF-LJQANCHMSA-N n-[(3r)-1-(pyridin-3-ylmethyl)pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C([C@@H](CC1)NC=2C=C3C=CN=CC3=CC=2)N1CC1=CC=CN=C1 SYZOYFXVBSNDSF-LJQANCHMSA-N 0.000 description 1
- NIZAIHMRZXSKIA-HXUWFJFHSA-N n-[(3r)-1-(pyridin-4-ylmethyl)piperidin-3-yl]isoquinolin-6-amine Chemical compound C([C@@H](CCC1)NC=2C=C3C=CN=CC3=CC=2)N1CC1=CC=NC=C1 NIZAIHMRZXSKIA-HXUWFJFHSA-N 0.000 description 1
- WSUBTLYOLNEMCY-LJQANCHMSA-N n-[(3r)-1-(pyridin-4-ylmethyl)pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C([C@@H](CC1)NC=2C=C3C=CN=CC3=CC=2)N1CC1=CC=NC=C1 WSUBTLYOLNEMCY-LJQANCHMSA-N 0.000 description 1
- MVKOXHIKWKVMBF-XCWJXAQQSA-N n-[(3r)-1-(pyrrolidin-3-ylmethyl)piperidin-3-yl]isoquinolin-6-amine Chemical compound C([C@@H](CCC1)NC=2C=C3C=CN=CC3=CC=2)N1CC1CCNC1 MVKOXHIKWKVMBF-XCWJXAQQSA-N 0.000 description 1
- OHRXQEGTJYYSFE-LJQANCHMSA-N n-[(3r)-1-[(2,3,5-trifluorophenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound FC1=CC(F)=C(F)C(CN2C[C@@H](CCC2)NC=2C=C3C=CN=CC3=CC=2)=C1 OHRXQEGTJYYSFE-LJQANCHMSA-N 0.000 description 1
- MELNONUIIXLQRJ-GOSISDBHSA-N n-[(3r)-1-[(2,3,5-trifluorophenyl)methyl]pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound FC1=CC(F)=C(F)C(CN2C[C@@H](CC2)NC=2C=C3C=CN=CC3=CC=2)=C1 MELNONUIIXLQRJ-GOSISDBHSA-N 0.000 description 1
- GZHFBGKZTDVGRD-HXUWFJFHSA-N n-[(3r)-1-[(2,3-difluoro-4-methylphenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound FC1=C(F)C(C)=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CCC1 GZHFBGKZTDVGRD-HXUWFJFHSA-N 0.000 description 1
- XLMZLGYIBRUIEZ-HXUWFJFHSA-N n-[(3r)-1-[(2,4-dichlorophenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound ClC1=CC(Cl)=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CCC1 XLMZLGYIBRUIEZ-HXUWFJFHSA-N 0.000 description 1
- YDVZZTPZWCMZQO-HXUWFJFHSA-N n-[(3r)-1-[(2-chlorophenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound ClC1=CC=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CCC1 YDVZZTPZWCMZQO-HXUWFJFHSA-N 0.000 description 1
- OXXQXDKVJAYYPX-SUMWQHHRSA-N n-[(3r)-1-[(2s)-2-aminopropyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound C1N(C[C@@H](N)C)CCC[C@H]1NC1=CC=C(C=NC=C2)C2=C1 OXXQXDKVJAYYPX-SUMWQHHRSA-N 0.000 description 1
- IDMAJNPBRRUWLN-OAQYLSRUSA-N n-[(3r)-1-[(3,5-dichlorophenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound ClC1=CC(Cl)=CC(CN2C[C@@H](CCC2)NC=2C=C3C=CN=CC3=CC=2)=C1 IDMAJNPBRRUWLN-OAQYLSRUSA-N 0.000 description 1
- DEONOFOULVQYDB-HXUWFJFHSA-N n-[(3r)-1-[(3,5-dichlorophenyl)methyl]pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound ClC1=CC(Cl)=CC(CN2C[C@@H](CC2)NC=2C=C3C=CN=CC3=CC=2)=C1 DEONOFOULVQYDB-HXUWFJFHSA-N 0.000 description 1
- DHTFDKUPKARYOA-LJQANCHMSA-N n-[(3r)-1-[(3-chloro-2-fluorophenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound FC1=C(Cl)C=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CCC1 DHTFDKUPKARYOA-LJQANCHMSA-N 0.000 description 1
- VTSBJLPXXRGPMG-OAQYLSRUSA-N n-[(3r)-1-[(3-chlorophenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound ClC1=CC=CC(CN2C[C@@H](CCC2)NC=2C=C3C=CN=CC3=CC=2)=C1 VTSBJLPXXRGPMG-OAQYLSRUSA-N 0.000 description 1
- NWBJKQCEQJQVBS-HXUWFJFHSA-N n-[(3r)-1-[(3-chlorophenyl)methyl]pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound ClC1=CC=CC(CN2C[C@@H](CC2)NC=2C=C3C=CN=CC3=CC=2)=C1 NWBJKQCEQJQVBS-HXUWFJFHSA-N 0.000 description 1
- SPSMOIBQFXBZOT-OAQYLSRUSA-N n-[(3r)-1-[(4-chlorophenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(Cl)=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CCC1 SPSMOIBQFXBZOT-OAQYLSRUSA-N 0.000 description 1
- PKRKONCRXUGQDP-HXUWFJFHSA-N n-[(3r)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(Cl)=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CC1 PKRKONCRXUGQDP-HXUWFJFHSA-N 0.000 description 1
- ZKFCXVMITPUBBS-JOCHJYFZSA-N n-[(3r)-1-[(4-methylphenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(C)=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CCC1 ZKFCXVMITPUBBS-JOCHJYFZSA-N 0.000 description 1
- WFGYRRXENNZCJK-OAQYLSRUSA-N n-[(3r)-1-[(4-methylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(C)=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CC1 WFGYRRXENNZCJK-OAQYLSRUSA-N 0.000 description 1
- VRWMDKUPKSKACW-OAQYLSRUSA-N n-[(3r)-1-[(4-methylsulfonylphenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CCC1 VRWMDKUPKSKACW-OAQYLSRUSA-N 0.000 description 1
- NLJZDNSUGUKUDQ-HXUWFJFHSA-N n-[(3r)-1-[(4-methylsulfonylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CC1 NLJZDNSUGUKUDQ-HXUWFJFHSA-N 0.000 description 1
- MZALHEMGERSJOT-OAQYLSRUSA-N n-[(3r)-1-[(5-fluoro-2-methylsulfonylphenyl)methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound CS(=O)(=O)C1=CC=C(F)C=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CCC1 MZALHEMGERSJOT-OAQYLSRUSA-N 0.000 description 1
- NBEOYJCTMDDULD-HXUWFJFHSA-N n-[(3r)-1-[(5-fluoro-2-methylsulfonylphenyl)methyl]pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound CS(=O)(=O)C1=CC=C(F)C=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CC1 NBEOYJCTMDDULD-HXUWFJFHSA-N 0.000 description 1
- NLLJJXWGEAVUCS-OAQYLSRUSA-N n-[(3r)-1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CCC1 NLLJJXWGEAVUCS-OAQYLSRUSA-N 0.000 description 1
- NHQXMDOYBLKPAI-HXUWFJFHSA-N n-[(3r)-1-[[4-(trifluoromethyl)phenyl]methyl]pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1C[C@H](NC=2C=C3C=CN=CC3=CC=2)CC1 NHQXMDOYBLKPAI-HXUWFJFHSA-N 0.000 description 1
- NYVKZPKXFXMGCS-QGZVFWFLSA-N n-[(3r)-1-pentan-3-ylpyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C1N(C(CC)CC)CC[C@H]1NC1=CC=C(C=NC=C2)C2=C1 NYVKZPKXFXMGCS-QGZVFWFLSA-N 0.000 description 1
- QYWKTXWXYFBQSD-QGZVFWFLSA-N n-[(3r)-1-propylpiperidin-3-yl]isoquinolin-6-amine Chemical compound C1N(CCC)CCC[C@H]1NC1=CC=C(C=NC=C2)C2=C1 QYWKTXWXYFBQSD-QGZVFWFLSA-N 0.000 description 1
- UZGKJBVIAZBGGQ-CQSZACIVSA-N n-[(3r)-piperidin-3-yl]isoquinolin-6-amine Chemical compound C1CCNC[C@@H]1NC1=CC=C(C=NC=C2)C2=C1 UZGKJBVIAZBGGQ-CQSZACIVSA-N 0.000 description 1
- HEWJMGMDVWGEHN-PFEQFJNWSA-N n-[(3r)-piperidin-3-yl]isoquinolin-6-amine;hydrochloride Chemical compound Cl.C1CCNC[C@@H]1NC1=CC=C(C=NC=C2)C2=C1 HEWJMGMDVWGEHN-PFEQFJNWSA-N 0.000 description 1
- WDGHULPTPUSTQP-CYBMUJFWSA-N n-[(3r)-pyrrolidin-3-yl]isoquinolin-6-amine Chemical compound C1NCC[C@H]1NC1=CC=C(C=NC=C2)C2=C1 WDGHULPTPUSTQP-CYBMUJFWSA-N 0.000 description 1
- YVTAUZDCWVHZGB-BTQNPOSSSA-N n-[(3r)-pyrrolidin-3-yl]isoquinolin-6-amine;hydrochloride Chemical compound Cl.C1NCC[C@H]1NC1=CC=C(C=NC=C2)C2=C1 YVTAUZDCWVHZGB-BTQNPOSSSA-N 0.000 description 1
- HTBRFWQEQNOOJZ-UHFFFAOYSA-N n-[(4-bromo-3-chlorophenyl)methyl]-2,2-dimethoxyethanamine Chemical compound COC(OC)CNCC1=CC=C(Br)C(Cl)=C1 HTBRFWQEQNOOJZ-UHFFFAOYSA-N 0.000 description 1
- QHXHQEANVDGNSF-UHFFFAOYSA-N n-[(4-bromo-3-chlorophenyl)methyl]-n-(2,2-dimethoxyethyl)-4-methylbenzenesulfonamide Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(CC(OC)OC)CC1=CC=C(Br)C(Cl)=C1 QHXHQEANVDGNSF-UHFFFAOYSA-N 0.000 description 1
- WJTBEVJBRUFSSV-UHFFFAOYSA-N n-[1-(2-methylpropyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1N(CC(C)C)CC1NC1=CC=C(C=NC=C2)C2=C1 WJTBEVJBRUFSSV-UHFFFAOYSA-N 0.000 description 1
- GDRADUQYCIKRIV-UHFFFAOYSA-N n-[1-(2-methylpropyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1CN(CC(C)C)CCC1NC1=CC=C(C=NC=C2)C2=C1 GDRADUQYCIKRIV-UHFFFAOYSA-N 0.000 description 1
- NGMSUTTXFUZWMQ-UHFFFAOYSA-N n-[1-(3,3,3-trifluoropropyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1N(CCC(F)(F)F)CC1NC1=CC=C(C=NC=C2)C2=C1 NGMSUTTXFUZWMQ-UHFFFAOYSA-N 0.000 description 1
- SVPHFGBEZGRXMN-UHFFFAOYSA-N n-[1-(3,3,3-trifluoropropyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1CN(CCC(F)(F)F)CCC1NC1=CC=C(C=NC=C2)C2=C1 SVPHFGBEZGRXMN-UHFFFAOYSA-N 0.000 description 1
- ZENZVBPFXDMKCK-UHFFFAOYSA-N n-[1-(3-methylbutyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1N(CCC(C)C)CC1NC1=CC=C(C=NC=C2)C2=C1 ZENZVBPFXDMKCK-UHFFFAOYSA-N 0.000 description 1
- IELCCOBYHJANSQ-UHFFFAOYSA-N n-[1-(3-methylbutyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1CN(CCC(C)C)CCC1NC1=CC=C(C=NC=C2)C2=C1 IELCCOBYHJANSQ-UHFFFAOYSA-N 0.000 description 1
- GHKAAOIPQZCETF-UHFFFAOYSA-N n-[1-(cyclohexylmethyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1C(NC=2C=C3C=CN=CC3=CC=2)CN1CC1CCCCC1 GHKAAOIPQZCETF-UHFFFAOYSA-N 0.000 description 1
- LOFFWFQYUQUSCZ-UHFFFAOYSA-N n-[1-(cyclohexylmethyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1CC(NC=2C=C3C=CN=CC3=CC=2)CCN1CC1CCCCC1 LOFFWFQYUQUSCZ-UHFFFAOYSA-N 0.000 description 1
- MTZPROMZDAPVFF-UHFFFAOYSA-N n-[1-(cyclopropylmethyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1C(NC=2C=C3C=CN=CC3=CC=2)CN1CC1CC1 MTZPROMZDAPVFF-UHFFFAOYSA-N 0.000 description 1
- SWISXYXWBMLIDT-UHFFFAOYSA-N n-[1-(cyclopropylmethyl)piperidin-4-yl]-n-methylisoquinolin-6-amine Chemical compound C=1C=C2C=NC=CC2=CC=1N(C)C(CC1)CCN1CC1CC1 SWISXYXWBMLIDT-UHFFFAOYSA-N 0.000 description 1
- IHWHFTBPKUNCIL-UHFFFAOYSA-N n-[1-(cyclopropylmethyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1CC(NC=2C=C3C=CN=CC3=CC=2)CCN1CC1CC1 IHWHFTBPKUNCIL-UHFFFAOYSA-N 0.000 description 1
- ZVDZMAXFETYNHP-UHFFFAOYSA-N n-[1-(naphthalen-1-ylmethyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC=C2C(CN3CC(C3)NC=3C=C4C=CN=CC4=CC=3)=CC=CC2=C1 ZVDZMAXFETYNHP-UHFFFAOYSA-N 0.000 description 1
- KOAXLRKJXROMCN-UHFFFAOYSA-N n-[1-(naphthalen-1-ylmethyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1=CC=C2C(CN3CCC(CC3)NC=3C=C4C=CN=CC4=CC=3)=CC=CC2=C1 KOAXLRKJXROMCN-UHFFFAOYSA-N 0.000 description 1
- BWMKUKLYBYZBOP-UHFFFAOYSA-N n-[1-(naphthalen-2-ylmethyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC=CC2=CC(CN3CC(C3)NC=3C=C4C=CN=CC4=CC=3)=CC=C21 BWMKUKLYBYZBOP-UHFFFAOYSA-N 0.000 description 1
- OLLUBHOBVWCWDR-UHFFFAOYSA-N n-[1-(naphthalen-2-ylmethyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1=CC=CC2=CC(CN3CCC(CC3)NC=3C=C4C=CN=CC4=CC=3)=CC=C21 OLLUBHOBVWCWDR-UHFFFAOYSA-N 0.000 description 1
- WGEAQDUEFQRRJN-UHFFFAOYSA-N n-[1-(pyridin-2-ylmethyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1C(NC=2C=C3C=CN=CC3=CC=2)CN1CC1=CC=CC=N1 WGEAQDUEFQRRJN-UHFFFAOYSA-N 0.000 description 1
- MCVAUCCVCGLZTR-UHFFFAOYSA-N n-[1-(pyridin-2-ylmethyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1CC(NC=2C=C3C=CN=CC3=CC=2)CCN1CC1=CC=CC=N1 MCVAUCCVCGLZTR-UHFFFAOYSA-N 0.000 description 1
- MSXOPFULOWSYPT-UHFFFAOYSA-N n-[1-(pyridin-3-ylmethyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1C(NC=2C=C3C=CN=CC3=CC=2)CN1CC1=CC=CN=C1 MSXOPFULOWSYPT-UHFFFAOYSA-N 0.000 description 1
- BQMSNSGGLTUJIT-UHFFFAOYSA-N n-[1-(pyridin-3-ylmethyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1CC(NC=2C=C3C=CN=CC3=CC=2)CCN1CC1=CC=CN=C1 BQMSNSGGLTUJIT-UHFFFAOYSA-N 0.000 description 1
- ZCXWSEKMVVSUQE-UHFFFAOYSA-N n-[1-(pyridin-4-ylmethyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1C(NC=2C=C3C=CN=CC3=CC=2)CN1CC1=CC=NC=C1 ZCXWSEKMVVSUQE-UHFFFAOYSA-N 0.000 description 1
- WUWPJSVVHIPIIT-UHFFFAOYSA-N n-[1-(pyridin-4-ylmethyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1CC(NC=2C=C3C=CN=CC3=CC=2)CCN1CC1=CC=NC=C1 WUWPJSVVHIPIIT-UHFFFAOYSA-N 0.000 description 1
- HIXNBQWJCVTTNF-UHFFFAOYSA-N n-[1-(pyrrolidin-3-ylmethyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1C(NC=2C=C3C=CN=CC3=CC=2)CN1CC1CCNC1 HIXNBQWJCVTTNF-UHFFFAOYSA-N 0.000 description 1
- CANXPLBZJXZMAT-UHFFFAOYSA-N n-[1-(thiophen-3-ylmethyl)azetidin-3-yl]isoquinolin-6-amine Chemical compound C1C(NC=2C=C3C=CN=CC3=CC=2)CN1CC=1C=CSC=1 CANXPLBZJXZMAT-UHFFFAOYSA-N 0.000 description 1
- UDERGZPWOLTOMV-UHFFFAOYSA-N n-[1-[(1-methylpyrazol-4-yl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound C1=NN(C)C=C1CN1CC(NC=2C=C3C=CN=CC3=CC=2)C1 UDERGZPWOLTOMV-UHFFFAOYSA-N 0.000 description 1
- WLOCLTLNPJKYQF-UHFFFAOYSA-N n-[1-[(2,3,5-trifluorophenyl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound FC1=CC(F)=C(F)C(CN2CC(C2)NC=2C=C3C=CN=CC3=CC=2)=C1 WLOCLTLNPJKYQF-UHFFFAOYSA-N 0.000 description 1
- ZYQMKAPDLSTBIM-UHFFFAOYSA-N n-[1-[(2,3-difluoro-4-methylphenyl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound FC1=C(F)C(C)=CC=C1CN1CC(NC=2C=C3C=CN=CC3=CC=2)C1 ZYQMKAPDLSTBIM-UHFFFAOYSA-N 0.000 description 1
- ZCWGTVHRAHNECT-UHFFFAOYSA-N n-[1-[(2,4-dichlorophenyl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound ClC1=CC(Cl)=CC=C1CN1CC(NC=2C=C3C=CN=CC3=CC=2)C1 ZCWGTVHRAHNECT-UHFFFAOYSA-N 0.000 description 1
- ICLLWXUXUMJHAE-UHFFFAOYSA-N n-[1-[(2,4-dichlorophenyl)methyl]piperidin-4-yl]isoquinolin-6-amine Chemical compound ClC1=CC(Cl)=CC=C1CN1CCC(NC=2C=C3C=CN=CC3=CC=2)CC1 ICLLWXUXUMJHAE-UHFFFAOYSA-N 0.000 description 1
- QCJXXDVBQPRZDB-UHFFFAOYSA-N n-[1-[(2-chlorophenyl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound ClC1=CC=CC=C1CN1CC(NC=2C=C3C=CN=CC3=CC=2)C1 QCJXXDVBQPRZDB-UHFFFAOYSA-N 0.000 description 1
- JHJDKTBZVWHZPZ-UHFFFAOYSA-N n-[1-[(2-chlorophenyl)methyl]piperidin-4-yl]isoquinolin-6-amine Chemical compound ClC1=CC=CC=C1CN1CCC(NC=2C=C3C=CN=CC3=CC=2)CC1 JHJDKTBZVWHZPZ-UHFFFAOYSA-N 0.000 description 1
- VGFUFGKSRRYMRR-NSHDSACASA-N n-[1-[(2s)-2-aminopropyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound C1N(C[C@@H](N)C)CC1NC1=CC=C(C=NC=C2)C2=C1 VGFUFGKSRRYMRR-NSHDSACASA-N 0.000 description 1
- PDKZMFKFVGVGPK-UHFFFAOYSA-N n-[1-[(3-chloro-2-fluorophenyl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound FC1=C(Cl)C=CC=C1CN1CC(NC=2C=C3C=CN=CC3=CC=2)C1 PDKZMFKFVGVGPK-UHFFFAOYSA-N 0.000 description 1
- FTEWDSVBKBFSOR-UHFFFAOYSA-N n-[1-[(3-chlorophenyl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound ClC1=CC=CC(CN2CC(C2)NC=2C=C3C=CN=CC3=CC=2)=C1 FTEWDSVBKBFSOR-UHFFFAOYSA-N 0.000 description 1
- JIQBCEYFKKXCER-UHFFFAOYSA-N n-[1-[(3-chlorophenyl)methyl]piperidin-4-yl]isoquinolin-6-amine Chemical compound ClC1=CC=CC(CN2CCC(CC2)NC=2C=C3C=CN=CC3=CC=2)=C1 JIQBCEYFKKXCER-UHFFFAOYSA-N 0.000 description 1
- WWDADFVIZAVHSL-UHFFFAOYSA-N n-[1-[(4-chlorophenyl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(Cl)=CC=C1CN1CC(NC=2C=C3C=CN=CC3=CC=2)C1 WWDADFVIZAVHSL-UHFFFAOYSA-N 0.000 description 1
- KOGBXFHWJNQDQX-UHFFFAOYSA-N n-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-n-methylisoquinolin-6-amine Chemical compound C=1C=C2C=NC=CC2=CC=1N(C)C(CC1)CCN1CC1=CC=C(Cl)C=C1 KOGBXFHWJNQDQX-UHFFFAOYSA-N 0.000 description 1
- FTQOWDOATBPRGC-UHFFFAOYSA-N n-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]isoquinolin-6-amine Chemical compound C1=CC(Cl)=CC=C1CN1CCC(NC=2C=C3C=CN=CC3=CC=2)CC1 FTQOWDOATBPRGC-UHFFFAOYSA-N 0.000 description 1
- VQPMXOVTZQFCCJ-UHFFFAOYSA-N n-[1-[(4-methylphenyl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(C)=CC=C1CN1CC(NC=2C=C3C=CN=CC3=CC=2)C1 VQPMXOVTZQFCCJ-UHFFFAOYSA-N 0.000 description 1
- GPXOFMQTZYHHJF-UHFFFAOYSA-N n-[1-[(4-methylphenyl)methyl]piperidin-4-yl]isoquinolin-6-amine Chemical compound C1=CC(C)=CC=C1CN1CCC(NC=2C=C3C=CN=CC3=CC=2)CC1 GPXOFMQTZYHHJF-UHFFFAOYSA-N 0.000 description 1
- MQYOIGUVYFCASP-UHFFFAOYSA-N n-[1-[(4-methylsulfonylphenyl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1CC(NC=2C=C3C=CN=CC3=CC=2)C1 MQYOIGUVYFCASP-UHFFFAOYSA-N 0.000 description 1
- BVXSTRUZNSRDKZ-UHFFFAOYSA-N n-[1-[(4-methylsulfonylphenyl)methyl]piperidin-4-yl]isoquinolin-6-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1CCC(NC=2C=C3C=CN=CC3=CC=2)CC1 BVXSTRUZNSRDKZ-UHFFFAOYSA-N 0.000 description 1
- SLOGIZOUVRYPKF-UHFFFAOYSA-N n-[1-[(5-fluoro-2-methylsulfonylphenyl)methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound CS(=O)(=O)C1=CC=C(F)C=C1CN1CC(NC=2C=C3C=CN=CC3=CC=2)C1 SLOGIZOUVRYPKF-UHFFFAOYSA-N 0.000 description 1
- ZVLHQOGJCPFTBN-UHFFFAOYSA-N n-[1-[(5-fluoro-2-methylsulfonylphenyl)methyl]piperidin-4-yl]isoquinolin-6-amine Chemical compound CS(=O)(=O)C1=CC=C(F)C=C1CN1CCC(NC=2C=C3C=CN=CC3=CC=2)CC1 ZVLHQOGJCPFTBN-UHFFFAOYSA-N 0.000 description 1
- DOMAOJDCIHICEZ-UHFFFAOYSA-N n-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]isoquinolin-6-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1CC(NC=2C=C3C=CN=CC3=CC=2)C1 DOMAOJDCIHICEZ-UHFFFAOYSA-N 0.000 description 1
- CYSGIFXPRNZXSF-UHFFFAOYSA-N n-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]isoquinolin-6-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1CCC(NC=2C=C3C=CN=CC3=CC=2)CC1 CYSGIFXPRNZXSF-UHFFFAOYSA-N 0.000 description 1
- KJIXTKXOMJAZRL-UHFFFAOYSA-N n-[1-[[4-(trifluoromethylsulfonyl)phenyl]methyl]piperidin-4-yl]isoquinolin-6-amine Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1CN1CCC(NC=2C=C3C=CN=CC3=CC=2)CC1 KJIXTKXOMJAZRL-UHFFFAOYSA-N 0.000 description 1
- VFNKLPGHAXILOD-UHFFFAOYSA-N n-benzyl-n-piperidin-4-ylisoquinolin-6-amine Chemical compound C=1C=CC=CC=1CN(C=1C=C2C=CN=CC2=CC=1)C1CCNCC1 VFNKLPGHAXILOD-UHFFFAOYSA-N 0.000 description 1
- ZLTDDCYBUWGUJO-UHFFFAOYSA-N n-methyl-n-(1-methylpiperidin-4-yl)isoquinolin-6-amine Chemical compound C=1C=C2C=NC=CC2=CC=1N(C)C1CCN(C)CC1 ZLTDDCYBUWGUJO-UHFFFAOYSA-N 0.000 description 1
- WSAXFLQEZXTUCI-UHFFFAOYSA-N n-methyl-n-(1-propylpiperidin-4-yl)isoquinolin-6-amine Chemical compound C1CN(CCC)CCC1N(C)C1=CC=C(C=NC=C2)C2=C1 WSAXFLQEZXTUCI-UHFFFAOYSA-N 0.000 description 1
- PAHWJJAUWGAUBE-UHFFFAOYSA-N n-methyl-n-[1-(2-methylpropyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1CN(CC(C)C)CCC1N(C)C1=CC=C(C=NC=C2)C2=C1 PAHWJJAUWGAUBE-UHFFFAOYSA-N 0.000 description 1
- JZRROCNJISJERL-UHFFFAOYSA-N n-methyl-n-[1-(3,3,3-trifluoropropyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C=1C=C2C=NC=CC2=CC=1N(C)C1CCN(CCC(F)(F)F)CC1 JZRROCNJISJERL-UHFFFAOYSA-N 0.000 description 1
- MSMPAZFFPMMKRR-UHFFFAOYSA-N n-methyl-n-[1-(3-methylbutyl)piperidin-4-yl]isoquinolin-6-amine Chemical compound C1CN(CCC(C)C)CCC1N(C)C1=CC=C(C=NC=C2)C2=C1 MSMPAZFFPMMKRR-UHFFFAOYSA-N 0.000 description 1
- VMXJELZLLRTFQE-UHFFFAOYSA-N n-methyl-n-piperidin-4-ylisoquinolin-6-amine Chemical compound C=1C=C2C=NC=CC2=CC=1N(C)C1CCNCC1 VMXJELZLLRTFQE-UHFFFAOYSA-N 0.000 description 1
- HGZABYFUGBKALO-UHFFFAOYSA-N n-piperidin-4-yl-n-(pyridin-3-ylmethyl)isoquinolin-6-amine Chemical compound C=1C=CN=CC=1CN(C=1C=C2C=CN=CC2=CC=1)C1CCNCC1 HGZABYFUGBKALO-UHFFFAOYSA-N 0.000 description 1
- KYQSYRNTAJCTBW-UHFFFAOYSA-N n-piperidin-4-yl-n-(pyridin-4-ylmethyl)isoquinolin-6-amine Chemical compound C=1C=NC=CC=1CN(C=1C=C2C=CN=CC2=CC=1)C1CCNCC1 KYQSYRNTAJCTBW-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 208000037921 secondary disease Diseases 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- 102000030938 small GTPase Human genes 0.000 description 1
- 108060007624 small GTPase Proteins 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 210000003518 stress fiber Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- AKQXKEBCONUWCL-MRVPVSSYSA-N tert-butyl (3r)-3-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@@H](N)C1 AKQXKEBCONUWCL-MRVPVSSYSA-N 0.000 description 1
- CMIBWIAICVBURI-SSDOTTSWSA-N tert-butyl (3r)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](N)C1 CMIBWIAICVBURI-SSDOTTSWSA-N 0.000 description 1
- APCBTRDHCDOPNY-SSDOTTSWSA-N tert-butyl (3r)-3-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](O)C1 APCBTRDHCDOPNY-SSDOTTSWSA-N 0.000 description 1
- ZNWLXJDGRAYAGY-UHFFFAOYSA-N tert-butyl 2-[(isoquinolin-6-ylamino)methyl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1CNC1=CC=C(C=NC=C2)C2=C1 ZNWLXJDGRAYAGY-UHFFFAOYSA-N 0.000 description 1
- TUZDRTUHUYQNQP-UHFFFAOYSA-N tert-butyl 3-[(isoquinolin-6-ylamino)methyl]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC1CNC1=CC=C(C=NC=C2)C2=C1 TUZDRTUHUYQNQP-UHFFFAOYSA-N 0.000 description 1
- UIJXHKXIOCDSEB-UHFFFAOYSA-N tert-butyl 3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(O)C1 UIJXHKXIOCDSEB-UHFFFAOYSA-N 0.000 description 1
- ANTLLZTXAVHLAU-UHFFFAOYSA-N tert-butyl 4-(propylamino)piperidine-1-carboxylate Chemical compound CCCNC1CCN(C(=O)OC(C)(C)C)CC1 ANTLLZTXAVHLAU-UHFFFAOYSA-N 0.000 description 1
- KQPWWQHXOJMBMB-UHFFFAOYSA-N tert-butyl 4-[(7-chloroisoquinolin-6-yl)amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=CC2=CC=NC=C2C=C1Cl KQPWWQHXOJMBMB-UHFFFAOYSA-N 0.000 description 1
- VYEMOCKRMRXZMD-UHFFFAOYSA-N tert-butyl 4-[7-chloro-2-[(4-methoxyphenyl)methyl]-1-oxoisoquinolin-6-yl]sulfanylpiperidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC(Cl)=C(SC3CCN(CC3)C(=O)OC(C)(C)C)C=C2C=C1 VYEMOCKRMRXZMD-UHFFFAOYSA-N 0.000 description 1
- MXNOFWNKIBEEDL-UHFFFAOYSA-N tert-butyl 4-[isoquinolin-6-yl(methyl)amino]piperidine-1-carboxylate Chemical compound C=1C=C2C=NC=CC2=CC=1N(C)C1CCN(C(=O)OC(C)(C)C)CC1 MXNOFWNKIBEEDL-UHFFFAOYSA-N 0.000 description 1
- KZBWIYHDNQHMET-UHFFFAOYSA-N tert-butyl 4-bromopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(Br)CC1 KZBWIYHDNQHMET-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- XWNXEWLCHSLQOI-UHFFFAOYSA-K trisodium;triacetate Chemical compound [Na+].[Na+].[Na+].CC([O-])=O.CC([O-])=O.CC([O-])=O XWNXEWLCHSLQOI-UHFFFAOYSA-K 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
-
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Hospice & Palliative Care (AREA)
- Gynecology & Obstetrics (AREA)
- Physical Education & Sports Medicine (AREA)
- Virology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- AIDS & HIV (AREA)
- Emergency Medicine (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06026896.8 | 2006-12-27 | ||
| EP06026896 | 2006-12-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20090094338A true KR20090094338A (ko) | 2009-09-04 |
Family
ID=38001966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020097013517A Abandoned KR20090094338A (ko) | 2006-12-27 | 2007-12-19 | 치환된 이소퀴놀린 및 이소퀴놀리논 유도체 |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US8748614B2 (enExample) |
| EP (1) | EP2114920A1 (enExample) |
| JP (1) | JP5405315B2 (enExample) |
| KR (1) | KR20090094338A (enExample) |
| CN (1) | CN101573353B (enExample) |
| AU (1) | AU2007338408B2 (enExample) |
| BR (1) | BRPI0720986A2 (enExample) |
| CA (1) | CA2673918C (enExample) |
| CO (1) | CO6210826A2 (enExample) |
| CR (1) | CR10814A (enExample) |
| DO (1) | DOP2009000162A (enExample) |
| EC (1) | ECSP099470A (enExample) |
| IL (1) | IL199537A (enExample) |
| MA (1) | MA31022B1 (enExample) |
| MX (1) | MX2009006517A (enExample) |
| MY (1) | MY155279A (enExample) |
| NO (1) | NO20092424L (enExample) |
| RU (1) | RU2009128693A (enExample) |
| SV (1) | SV2009003312A (enExample) |
| TN (1) | TN2009000268A1 (enExample) |
| WO (1) | WO2008077552A1 (enExample) |
| ZA (1) | ZA200903552B (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2580108T3 (es) | 2005-07-11 | 2016-08-19 | Aerie Pharmaceuticals, Inc | Compuestos de isoquinolina |
| ES2729424T3 (es) | 2006-09-20 | 2019-11-04 | Aerie Pharmaceuticals Inc | Inhibidores de Rho cinasa |
| US8455513B2 (en) | 2007-01-10 | 2013-06-04 | Aerie Pharmaceuticals, Inc. | 6-aminoisoquinoline compounds |
| US8455514B2 (en) | 2008-01-17 | 2013-06-04 | Aerie Pharmaceuticals, Inc. | 6-and 7-amino isoquinoline compounds and methods for making and using the same |
| PE20110054A1 (es) * | 2008-06-24 | 2011-02-15 | Sanofi Aventis | Isoquinolinas e isoquinolinonas 6-sustituidas |
| PL2303845T3 (pl) * | 2008-06-24 | 2014-03-31 | Sanofi Sa | Bi- i policykliczne podstawione pochodne izochinoliny i izochinolinonu jako inhibitory kinazy Rho |
| US8541449B2 (en) * | 2008-06-24 | 2013-09-24 | Sanofi | Substituted isoquinolines and isoquinolinones as Rho kinase inhibitors |
| US8299096B2 (en) * | 2008-06-26 | 2012-10-30 | Inspire Pharmaceuticals, Inc. | Method for treating pulmonary diseases using rho kinase inhibitor compounds |
| US8410147B2 (en) | 2008-06-26 | 2013-04-02 | Inspire Pharmaceuticals, Inc. | Method for treating diseases associated with alterations in cellular integrity using Rho kinase inhibitor compounds |
| US8450344B2 (en) | 2008-07-25 | 2013-05-28 | Aerie Pharmaceuticals, Inc. | Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds |
| CA2760562C (en) | 2009-05-01 | 2016-07-19 | Aerie Pharmaceuticals, Inc. | Dual mechanism inhibitors for the treatment of disease |
| PT3811943T (pt) | 2013-03-15 | 2023-03-15 | Aerie Pharmaceuticals Inc | Composto para uso no tratamento de distúrbios oculares |
| WO2015092009A1 (en) | 2013-12-20 | 2015-06-25 | Laboratorios Del Dr. Esteve, S.A. | Piperazine derivatives having multimodal activity against pain |
| FR3017868A1 (fr) | 2014-02-21 | 2015-08-28 | Servier Lab | Derives d'isoquinoleine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CN105085478B (zh) * | 2014-04-28 | 2019-04-12 | 南京明德新药研发股份有限公司 | 异喹啉磺胺衍生物及其药物组合物和制药用途 |
| EP3194403B1 (en) | 2014-09-15 | 2019-02-06 | Rugen Holdings (Cayman) Limited | Pyrrolopyrimidine derivatives as nr2b nmda receptor antagonists |
| US10221182B2 (en) | 2015-02-04 | 2019-03-05 | Rugen Holdings (Cayman) Limited | 3,3-difluoro-piperidine derivatives as NR2B NMDA receptor antagonists |
| US10584127B2 (en) * | 2015-06-01 | 2020-03-10 | Rugen Holdings (Cayman) Limited | 3,3-difluoropiperidine carbamate heterocyclic compounds as NR2B NMDA receptor antagonists |
| CN105237474B (zh) * | 2015-09-30 | 2017-08-29 | 沈阳药科大学 | 6‑羟基‑7‑芳甲酰基喹啉酮类化合物的制备及其应用 |
| US9643927B1 (en) | 2015-11-17 | 2017-05-09 | Aerie Pharmaceuticals, Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
| JP6832946B2 (ja) | 2015-11-17 | 2021-02-24 | アエリエ ファーマシューティカルズ インコーポレイテッド | キナーゼ阻害剤およびその中間体の調製方法 |
| CN109640966A (zh) | 2016-08-31 | 2019-04-16 | 爱瑞制药公司 | 眼用组合物 |
| US11000526B2 (en) | 2016-11-22 | 2021-05-11 | Rugen Holdings (Cayman) Limited | Treatment of autism spectrum disorders, obsessive-compulsive disorder and anxiety disorders |
| SG11201908179UA (en) | 2017-03-31 | 2019-10-30 | Aerie Pharmaceuticals Inc | Aryl cyclopropyl-amino-isoquinolinyl amide compounds |
| WO2020056345A1 (en) | 2018-09-14 | 2020-03-19 | Aerie Pharmaceuticals, Inc. | Aryl cyclopropyl-amino-isoquinolinyl amide compounds |
| CN109180586B (zh) * | 2018-10-10 | 2022-03-08 | 成都理工大学 | 作为Rho激酶抑制剂的六氢氮杂卓-4-基氧基苯甲酰胺类化合物 |
| US11071730B2 (en) | 2018-10-31 | 2021-07-27 | Gilead Sciences, Inc. | Substituted 6-azabenzimidazole compounds |
| PL3873903T3 (pl) | 2018-10-31 | 2024-05-20 | Gilead Sciences, Inc. | Podstawione związki 6-azabenzimidazolu jako inhibitory hpk1 |
| EP3972695A1 (en) | 2019-05-23 | 2022-03-30 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2485537B2 (fr) * | 1977-04-13 | 1986-05-16 | Anvar | Dipyrido(4,3-b)(3,4-f)indoles, procede d'obtention, application therapeutique et compositions pharmaceutiques les contenant |
| EP0541559A1 (en) | 1990-07-31 | 1993-05-19 | E.I. Du Pont De Nemours And Company | Catalytic equilibration of selected halocarbons |
| US5480883A (en) * | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| GB9516709D0 (en) | 1995-08-15 | 1995-10-18 | Zeneca Ltd | Medicament |
| ZA9610741B (en) | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Substituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
| SI0956865T2 (sl) | 1996-08-12 | 2011-04-29 | Mitsubishi Pharma Corp | Zdravila, ki obsegajo inhibitor Rho-kinaze |
| JPH1087629A (ja) | 1996-09-18 | 1998-04-07 | Fujisawa Pharmaceut Co Ltd | 新規イソキノリン誘導体、およびその医薬用途 |
| AU8872198A (en) | 1997-08-29 | 1999-03-22 | Zeneca Limited | Aminometyl oxooxazolidinyl benzene derivatives |
| TW575567B (en) * | 1998-10-23 | 2004-02-11 | Akzo Nobel Nv | Serine protease inhibitor |
| GB9912701D0 (en) | 1999-06-01 | 1999-08-04 | Smithkline Beecham Plc | Novel compounds |
| US6541456B1 (en) | 1999-12-01 | 2003-04-01 | Isis Pharmaceuticals, Inc. | Antimicrobial 2-deoxystreptamine compounds |
| HUP0204496A3 (en) | 2000-01-20 | 2004-07-28 | Eisai Co Ltd | Novel piperidine compounds and pharmaceutical compositions containing the same and process for preparation the same |
| US7217722B2 (en) * | 2000-02-01 | 2007-05-15 | Kirin Beer Kabushiki Kaisha | Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same |
| AU2001239947A1 (en) | 2000-02-29 | 2001-09-12 | Curis, Inc. | Methods and compositions for regulating adipocytes |
| GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| AR033517A1 (es) | 2000-04-08 | 2003-12-26 | Astrazeneca Ab | Derivados de piperidina, proceso para su preparacion y uso de estos derivados en la fabricacion de medicamentos |
| GB0013060D0 (en) | 2000-05-31 | 2000-07-19 | Astrazeneca Ab | Chemical compounds |
| WO2002034712A1 (en) | 2000-10-27 | 2002-05-02 | Takeda Chemical Industries, Ltd. | Process for preparing substituted aromatic compounds and intermediates therefor |
| JP2004520347A (ja) | 2001-01-15 | 2004-07-08 | グラクソ グループ リミテッド | Ｌｄｌ−受容体発現のインデューサーとしてのアリールピペリジンおよびピペラジン誘導体 |
| SE0101038D0 (sv) | 2001-03-23 | 2001-03-23 | Astrazeneca Ab | Novel compounds |
| JP2004534017A (ja) | 2001-04-27 | 2004-11-11 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ｂａｃｅのインヒビター |
| EP1403255A4 (en) | 2001-06-12 | 2005-04-06 | Sumitomo Pharma | RHO KINASE INHIBITORS |
| GB0117899D0 (en) | 2001-07-23 | 2001-09-12 | Astrazeneca Ab | Chemical compounds |
| WO2003024450A1 (en) | 2001-09-20 | 2003-03-27 | Eisai Co., Ltd. | Methods for treating prion diseases |
| SE0104340D0 (sv) | 2001-12-20 | 2001-12-20 | Astrazeneca Ab | New compounds |
| CN100354264C (zh) * | 2002-07-22 | 2007-12-12 | 旭化成制药株式会社 | 5－取代异喹啉衍生物及含有它们的药物 |
| CN100383140C (zh) | 2002-09-12 | 2008-04-23 | 麒麟麦酒株式会社 | 具有激酶抑制活性的异喹啉衍生物和包含异喹啉衍生物的药剂 |
| US20050014783A1 (en) | 2003-05-29 | 2005-01-20 | Schering Aktiengesellschaft | Use of Rho-kinase inhibitors in the treatment of aneurysm and cardiac hypertrophy |
| WO2004113297A2 (en) | 2003-06-24 | 2004-12-29 | Neurosearch A/S | Aza-ring derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| US7691879B2 (en) | 2003-09-23 | 2010-04-06 | Merck Sharp & Dohme Corp. | Isoquinoline potassium channel inhibitors |
| AU2004276236B2 (en) | 2003-09-23 | 2008-01-24 | Merck Sharp & Dohme Corp. | Isoquinolinone potassium channel inhibitors |
| US20050067037A1 (en) | 2003-09-30 | 2005-03-31 | Conocophillips Company | Collapse resistant composite riser |
| JPWO2005035516A1 (ja) | 2003-10-10 | 2006-12-21 | 小野薬品工業株式会社 | 新規縮合複素環化合物およびその用途 |
| US7449477B2 (en) | 2003-11-25 | 2008-11-11 | Eli Lilly And Company | 7-phenyl-isoquinoline-5-sulfonylamino derivatives as inhibitors of akt (protein kinase B) |
| JP2005232175A (ja) * | 2004-01-21 | 2005-09-02 | Asahi Kasei Pharma Kk | ５−置換イソキノリン医薬 |
| WO2005074535A2 (en) | 2004-01-30 | 2005-08-18 | Eisai Co., Ltd. | Cholinesterase inhibitors for spinal cord disorders |
| US20080312189A1 (en) | 2004-03-05 | 2008-12-18 | Eisai Co., Ltd. | Cadasil Treatment with Cholinesterase Inhibitors |
| SE0400850D0 (sv) | 2004-03-30 | 2004-03-31 | Astrazeneca Ab | Novel Compounds |
| US7517991B2 (en) * | 2004-10-12 | 2009-04-14 | Bristol-Myers Squibb Company | N-sulfonylpiperidine cannabinoid receptor 1 antagonists |
| NI200800025A (es) | 2005-07-26 | 2009-03-03 | Derivados de isoquinolona sustituidos con piperidinilo en calidad de inhibidores de rho-quinasa | |
| EP1912949B1 (en) | 2005-07-26 | 2011-08-24 | Sanofi | Cyclohexylamin isoquinolone derivatives as rho-kinase inhibitors |
| TW200745101A (en) | 2005-09-30 | 2007-12-16 | Organon Nv | 9-Azabicyclo[3.3.1]nonane derivatives |
| US7618985B2 (en) * | 2005-12-08 | 2009-11-17 | N.V. Organon | Isoquinoline derivatives |
| TW200738682A (en) * | 2005-12-08 | 2007-10-16 | Organon Nv | Isoquinoline derivatives |
| US7511063B2 (en) * | 2006-08-16 | 2009-03-31 | Schering Corporation | High affinity quinoline-based kinase ligands |
| US7893088B2 (en) | 2006-08-18 | 2011-02-22 | N.V. Organon | 6-substituted isoquinoline derivatives |
| CN101573354B (zh) | 2006-12-27 | 2014-02-12 | 塞诺菲-安万特股份有限公司 | 取代的异喹啉类及其作为Rho-激酶抑制剂的用途 |
| JP5318779B2 (ja) | 2006-12-27 | 2013-10-16 | サノフイ | シクロアルキルアミン置換イソキノリン及びイソキノリノン誘導体 |
-
2007
- 2007-12-19 RU RU2009128693/04A patent/RU2009128693A/ru not_active Application Discontinuation
- 2007-12-19 AU AU2007338408A patent/AU2007338408B2/en not_active Ceased
- 2007-12-19 MX MX2009006517A patent/MX2009006517A/es active IP Right Grant
- 2007-12-19 WO PCT/EP2007/011165 patent/WO2008077552A1/en not_active Ceased
- 2007-12-19 CA CA2673918A patent/CA2673918C/en not_active Expired - Fee Related
- 2007-12-19 CN CN200780048282.0A patent/CN101573353B/zh not_active Expired - Fee Related
- 2007-12-19 KR KR1020097013517A patent/KR20090094338A/ko not_active Abandoned
- 2007-12-19 MY MYPI20092505A patent/MY155279A/en unknown
- 2007-12-19 JP JP2009543373A patent/JP5405315B2/ja not_active Expired - Fee Related
- 2007-12-19 BR BRPI0720986-0A patent/BRPI0720986A2/pt not_active IP Right Cessation
- 2007-12-19 EP EP07856888A patent/EP2114920A1/en not_active Withdrawn
-
2009
- 2009-05-20 CR CR10814A patent/CR10814A/es not_active Application Discontinuation
- 2009-05-22 ZA ZA200903552A patent/ZA200903552B/xx unknown
- 2009-06-16 CO CO09062102A patent/CO6210826A2/es not_active Application Discontinuation
- 2009-06-18 US US12/487,455 patent/US8748614B2/en not_active Expired - Fee Related
- 2009-06-23 SV SV2009003312A patent/SV2009003312A/es unknown
- 2009-06-24 MA MA32037A patent/MA31022B1/fr unknown
- 2009-06-24 IL IL199537A patent/IL199537A/en not_active IP Right Cessation
- 2009-06-25 NO NO20092424A patent/NO20092424L/no not_active Application Discontinuation
- 2009-06-25 TN TNP2009000268A patent/TN2009000268A1/fr unknown
- 2009-06-26 DO DO2009000162A patent/DOP2009000162A/es unknown
- 2009-06-26 EC EC2009009470A patent/ECSP099470A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0720986A2 (pt) | 2014-03-11 |
| NO20092424L (no) | 2009-09-18 |
| US8748614B2 (en) | 2014-06-10 |
| JP2010514717A (ja) | 2010-05-06 |
| CR10814A (es) | 2009-08-12 |
| MX2009006517A (es) | 2009-06-26 |
| RU2009128693A (ru) | 2011-02-10 |
| CA2673918C (en) | 2015-02-17 |
| MA31022B1 (fr) | 2009-12-01 |
| DOP2009000162A (es) | 2009-07-31 |
| TN2009000268A1 (en) | 2010-10-18 |
| MY155279A (en) | 2015-09-30 |
| CO6210826A2 (es) | 2010-10-20 |
| CN101573353A (zh) | 2009-11-04 |
| ECSP099470A (es) | 2009-07-31 |
| US20100105650A1 (en) | 2010-04-29 |
| IL199537A (en) | 2013-11-28 |
| CA2673918A1 (en) | 2008-07-03 |
| AU2007338408A1 (en) | 2008-07-03 |
| IL199537A0 (en) | 2010-03-28 |
| JP5405315B2 (ja) | 2014-02-05 |
| SV2009003312A (es) | 2010-02-05 |
| CN101573353B (zh) | 2014-08-06 |
| EP2114920A1 (en) | 2009-11-11 |
| WO2008077552A1 (en) | 2008-07-03 |
| AU2007338408B2 (en) | 2012-07-26 |
| ZA200903552B (en) | 2010-04-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5405315B2 (ja) | 置換イソキノリン及びイソキノリノン誘導体 | |
| CN101573338B (zh) | 环烷基胺取代的异喹诺酮和异喹啉酮衍生物 | |
| KR101517154B1 (ko) | Ｒｈｏ-키나제의 억제제로서의 치환된 이소퀴놀린 및 이소퀴놀리논 유도체 | |
| US8772492B2 (en) | Substituted isoquinoline and isoquinolinone derivatives | |
| KR101373535B1 (ko) | Ｒｈｏ-키나제 억제제로서의 피페리디닐-치환된 이소퀴놀론유도체 | |
| KR20090102775A (ko) | 사이클로알킬아민 치환된 이소퀴놀론 유도체 | |
| HK1138583B (en) | Cycloalkylamine substituted isoquinolone and isoquinolinone derivatives | |
| HK1140201B (en) | Substituted isoquinoline and isoquinolinone derivatives as inhibitors of rho-kinase | |
| HK1138582A (en) | Substituted isoquinoline and isoquinolinone derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20090626 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20121128 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20140528 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20140929 |
|
| PC1904 | Unpaid initial registration fee |