BRPI0721180A2 - Derivados de isoquinolina substituídos com cicloalquilamina - Google Patents

Info

Publication number

BRPI0721180A2

BRPI0721180A2 BRPI0721180-5A BRPI0721180A BRPI0721180A2 BR PI0721180 A2 BRPI0721180 A2 BR PI0721180A2 BR PI0721180 A BRPI0721180 A BR PI0721180A BR PI0721180 A2 BRPI0721180 A2 BR PI0721180A2

Authority

BR

Brazil

Prior art keywords

alkyl

alkylene

heterocyclyl

halogen

compound according

Prior art date

2006-12-27

Links

• Espacenet
• Global Dossier
• Discuss

• 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title description 13
• -1 6-substituted isoquinoline Chemical class 0.000 claims abstract description 172
• 150000001875 compounds Chemical class 0.000 claims abstract description 139
• 238000011282 treatment Methods 0.000 claims abstract description 15
• 125000000217 alkyl group Chemical group 0.000 claims description 134
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 121
• 125000000623 heterocyclic group Chemical group 0.000 claims description 95
• 229910052736 halogen Inorganic materials 0.000 claims description 94
• 150000002367 halogens Chemical class 0.000 claims description 94
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 63
• 125000003118 aryl group Chemical group 0.000 claims description 55
• 239000000460 chlorine Substances 0.000 claims description 36
• 150000003839 salts Chemical class 0.000 claims description 36
• 125000002947 alkylene group Chemical group 0.000 claims description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 18
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 15
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 14
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical group NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 14
• 125000004432 carbon atom Chemical group C* 0.000 claims description 13
• 238000011161 development Methods 0.000 claims description 12
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
• 229910052731 fluorine Inorganic materials 0.000 claims description 11
• 206010020772 Hypertension Diseases 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 10
• 229910052801 chlorine Inorganic materials 0.000 claims description 9
• 239000011737 fluorine Substances 0.000 claims description 9
• 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 claims description 9
• 201000010260 leiomyoma Diseases 0.000 claims description 9
• 125000001544 thienyl group Chemical group 0.000 claims description 9
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
• 229910052794 bromium Inorganic materials 0.000 claims description 8
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• 125000004076 pyridyl group Chemical group 0.000 claims description 8
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
• 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 7
• 125000000896 monocarboxylic acid group Chemical group 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
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 6
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
• 206010019280 Heart failures Diseases 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 6
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
• 206010012601 diabetes mellitus Diseases 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
• 201000001320 Atherosclerosis Diseases 0.000 claims description 5
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
• 239000005977 Ethylene Substances 0.000 claims description 5
• 208000006011 Stroke Diseases 0.000 claims description 5
• 201000011510 cancer Diseases 0.000 claims description 5
• 208000017169 kidney disease Diseases 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 4
• 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
• 201000006474 Brain Ischemia Diseases 0.000 claims description 4
• 206010008120 Cerebral ischaemia Diseases 0.000 claims description 4
• 208000002249 Diabetes Complications Diseases 0.000 claims description 4
• 208000010228 Erectile Dysfunction Diseases 0.000 claims description 4
• 206010020880 Hypertrophy Diseases 0.000 claims description 4
• 206010061218 Inflammation Diseases 0.000 claims description 4
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 4
• 208000002193 Pain Diseases 0.000 claims description 4
• 208000017442 Retinal disease 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
• 239000004480 active ingredient Substances 0.000 claims description 4
• 239000000654 additive Substances 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 208000006673 asthma Diseases 0.000 claims description 4
• 239000007844 bleaching agent Substances 0.000 claims description 4
• 206010008118 cerebral infarction Diseases 0.000 claims description 4
• 208000029078 coronary artery disease Diseases 0.000 claims description 4
• 230000004064 dysfunction Effects 0.000 claims description 4
• 230000002124 endocrine Effects 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
• 210000004072 lung Anatomy 0.000 claims description 4
• 230000004770 neurodegeneration Effects 0.000 claims description 4
• 210000000056 organ Anatomy 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 230000002093 peripheral effect Effects 0.000 claims description 4
• 208000037803 restenosis Diseases 0.000 claims description 4
• 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 3
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
• 208000023275 Autoimmune disease Diseases 0.000 claims description 3
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
• 208000020084 Bone disease Diseases 0.000 claims description 3
• 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 3
• 208000006029 Cardiomegaly Diseases 0.000 claims description 3
• 208000010412 Glaucoma Diseases 0.000 claims description 3
• 206010019663 Hepatic failure Diseases 0.000 claims description 3
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 3
• 206010030043 Ocular hypertension Diseases 0.000 claims description 3
• 208000005107 Premature Birth Diseases 0.000 claims description 3
• 206010036590 Premature baby Diseases 0.000 claims description 3
• 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
• 206010040047 Sepsis Diseases 0.000 claims description 3
• 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
• 210000004204 blood vessel Anatomy 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
• 208000001286 intracranial vasospasm Diseases 0.000 claims description 3
• 208000023589 ischemic disease Diseases 0.000 claims description 3
• 210000003734 kidney Anatomy 0.000 claims description 3
• 201000006370 kidney failure Diseases 0.000 claims description 3
• 210000004185 liver Anatomy 0.000 claims description 3
• 208000007903 liver failure Diseases 0.000 claims description 3
• 231100000835 liver failure Toxicity 0.000 claims description 3
• 230000002265 prevention Effects 0.000 claims description 3
• 201000004240 prostatic hypertrophy Diseases 0.000 claims description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
• 206010053159 Organ failure Diseases 0.000 claims description 2
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
• 229910006069 SO3H Inorganic materials 0.000 claims description 2
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 2
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
• 125000001153 fluoro group Chemical group F* 0.000 claims description 2
• 230000000302 ischemic effect Effects 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 2
• 230000006378 damage Effects 0.000 claims 2
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 1
• 241000894006 Bacteria Species 0.000 claims 1
• 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims 1
• 229910018828 PO3H2 Inorganic materials 0.000 claims 1
• 208000027418 Wounds and injury Diseases 0.000 claims 1
• 125000005275 alkylenearyl group Chemical group 0.000 claims 1
• 239000000969 carrier Substances 0.000 claims 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
• 208000014674 injury Diseases 0.000 claims 1
• 150000002825 nitriles Chemical class 0.000 claims 1
• 210000000278 spinal cord Anatomy 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 35
• 102000000568 rho-Associated Kinases Human genes 0.000 abstract description 13
• 108010041788 rho-Associated Kinases Proteins 0.000 abstract description 13
• 230000001404 mediated effect Effects 0.000 abstract description 5
• 230000026731 phosphorylation Effects 0.000 abstract description 5
• 238000006366 phosphorylation reaction Methods 0.000 abstract description 5
• 102000011131 Myosin-Light-Chain Phosphatase Human genes 0.000 abstract description 3
• 108010037801 Myosin-Light-Chain Phosphatase Proteins 0.000 abstract description 3
• 230000006806 disease prevention Effects 0.000 abstract description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 82
• 238000000034 method Methods 0.000 description 72
• 239000000243 solution Substances 0.000 description 49
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
• 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 43
• 238000006243 chemical reaction Methods 0.000 description 35
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• 239000002904 solvent Substances 0.000 description 32
• 239000000047 product Substances 0.000 description 31
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
• 150000001412 amines Chemical class 0.000 description 30
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 25
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 238000002953 preparative HPLC Methods 0.000 description 20
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 125000001424 substituent group Chemical group 0.000 description 18
• 239000012043 crude product Substances 0.000 description 17
• AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 17
• 239000012044 organic layer Substances 0.000 description 17
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
• 238000003756 stirring Methods 0.000 description 15
• 239000000126 substance Substances 0.000 description 15
• ALLJCJZVQMDEHE-UHFFFAOYSA-N 6-fluoroisoquinoline Chemical class C1=NC=CC2=CC(F)=CC=C21 ALLJCJZVQMDEHE-UHFFFAOYSA-N 0.000 description 13
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 13
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• 235000019341 magnesium sulphate Nutrition 0.000 description 13
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
• ALTPGTZNQQAMJI-UHFFFAOYSA-N 5-chloroisoquinolin-6-ol Chemical compound C1=NC=CC2=C(Cl)C(O)=CC=C21 ALTPGTZNQQAMJI-UHFFFAOYSA-N 0.000 description 12
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 12
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
• 239000002244 precipitate Substances 0.000 description 12
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 11
• 238000000746 purification Methods 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
• 239000000651 prodrug Substances 0.000 description 10
• 229940002612 prodrug Drugs 0.000 description 10
• 239000011541 reaction mixture Substances 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• 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 10
• BCZPUVXMWIBIRE-UHFFFAOYSA-N 7-chloro-6-fluoroisoquinoline Chemical compound C1=NC=C2C=C(Cl)C(F)=CC2=C1 BCZPUVXMWIBIRE-UHFFFAOYSA-N 0.000 description 9
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 239000007787 solid Substances 0.000 description 9
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• 150000003840 hydrochlorides Chemical class 0.000 description 8
• 239000000825 pharmaceutical preparation Substances 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 7
• UAKCWZYJYLLDBJ-UHFFFAOYSA-N 5-bromoisoquinolin-6-ol Chemical compound C1=NC=CC2=C(Br)C(O)=CC=C21 UAKCWZYJYLLDBJ-UHFFFAOYSA-N 0.000 description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• KXHZVAKJNQKBFQ-UHFFFAOYSA-N n-(2,2-dimethoxyethyl)-n-[(4-fluorophenyl)methyl]-4-methylbenzenesulfonamide Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(CC(OC)OC)CC1=CC=C(F)C=C1 KXHZVAKJNQKBFQ-UHFFFAOYSA-N 0.000 description 7
• 229940086542 triethylamine Drugs 0.000 description 7
• XZNUJESLPUNSNO-UHFFFAOYSA-N 6-methoxyisoquinoline Chemical compound C1=NC=CC2=CC(OC)=CC=C21 XZNUJESLPUNSNO-UHFFFAOYSA-N 0.000 description 6
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
• 150000002431 hydrogen Chemical class 0.000 description 6
• RAVIPCWMLZMENX-UHFFFAOYSA-N 5-chloro-6-fluoroisoquinoline Chemical compound C1=NC=CC2=C(Cl)C(F)=CC=C21 RAVIPCWMLZMENX-UHFFFAOYSA-N 0.000 description 5
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
• 230000004913 activation Effects 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 238000001704 evaporation Methods 0.000 description 5
• 230000008020 evaporation Effects 0.000 description 5
• 208000015181 infectious disease Diseases 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 125000004551 isoquinolin-3-yl group Chemical group C1=NC(=CC2=CC=CC=C12)* 0.000 description 5
• GPVPDRHTRGTSIH-UHFFFAOYSA-N isoquinolin-6-ol Chemical compound C1=NC=CC2=CC(O)=CC=C21 GPVPDRHTRGTSIH-UHFFFAOYSA-N 0.000 description 5
• KLSMOPWFVBTUHA-UHFFFAOYSA-N n-(2,2-dimethoxyethyl)-4-methyl-n-[(3,4,5-trifluorophenyl)methyl]benzenesulfonamide Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(CC(OC)OC)CC1=CC(F)=C(F)C(F)=C1 KLSMOPWFVBTUHA-UHFFFAOYSA-N 0.000 description 5
• 229910052757 nitrogen Inorganic materials 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 238000010898 silica gel chromatography Methods 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• DQARDWKWPIRJEH-UHFFFAOYSA-N tert-butyl n-(4-hydroxycyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(O)CC1 DQARDWKWPIRJEH-UHFFFAOYSA-N 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
• PUGBDHNZMLRNIX-UHFFFAOYSA-N 4-(5-chloroisoquinolin-6-yl)oxycyclohexan-1-one Chemical compound C1=CC2=CN=CC=C2C(Cl)=C1OC1CCC(=O)CC1 PUGBDHNZMLRNIX-UHFFFAOYSA-N 0.000 description 4
• UORWTZYYTNAMNF-UHFFFAOYSA-N 4-chloro-6-fluoroisoquinoline Chemical compound C1=NC=C(Cl)C2=CC(F)=CC=C21 UORWTZYYTNAMNF-UHFFFAOYSA-N 0.000 description 4
• CUDYASREPDKSDX-UHFFFAOYSA-N 4-ethyl-6-methoxyisoquinoline Chemical compound C1=C(OC)C=C2C(CC)=CN=CC2=C1 CUDYASREPDKSDX-UHFFFAOYSA-N 0.000 description 4
• WAKOKPIOTSYDIB-UHFFFAOYSA-N 5,6,7-trifluoroisoquinoline Chemical compound N1=CC=C2C(F)=C(F)C(F)=CC2=C1 WAKOKPIOTSYDIB-UHFFFAOYSA-N 0.000 description 4
• IUGDGTHETHKRLX-UHFFFAOYSA-N 5,7-dichloro-6-fluoroisoquinoline Chemical compound C1=NC=CC2=C(Cl)C(F)=C(Cl)C=C21 IUGDGTHETHKRLX-UHFFFAOYSA-N 0.000 description 4
• MRIVGGHLXJGDIQ-UHFFFAOYSA-N 5-chloro-6-(1,4-dioxaspiro[4.5]decan-8-yloxy)isoquinoline Chemical compound C1=CC2=CN=CC=C2C(Cl)=C1OC(CC1)CCC21OCCO2 MRIVGGHLXJGDIQ-UHFFFAOYSA-N 0.000 description 4
• UKSBEGUPFICXCI-UHFFFAOYSA-N 6-fluoro-7-methoxyisoquinoline Chemical compound N1=CC=C2C=C(F)C(OC)=CC2=C1 UKSBEGUPFICXCI-UHFFFAOYSA-N 0.000 description 4
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• FSAKYYJOUJJNAG-BGYRXZFFSA-N C1=C(Cl)C(S(=O)(=O)N=CN(C)C)=CC(CN[C@@H]2CC[C@@H](CC2)OC=2C(=C3C=CN=CC3=CC=2)Cl)=C1 Chemical compound C1=C(Cl)C(S(=O)(=O)N=CN(C)C)=CC(CN[C@@H]2CC[C@@H](CC2)OC=2C(=C3C=CN=CC3=CC=2)Cl)=C1 FSAKYYJOUJJNAG-BGYRXZFFSA-N 0.000 description 4
• YLHCMDNAKVPTIO-MGCOHNPYSA-N C1C[C@@H](O)CC[C@@H]1N1C(=O)C2=CC=CC=C2C1=O Chemical compound C1C[C@@H](O)CC[C@@H]1N1C(=O)C2=CC=CC=C2C1=O YLHCMDNAKVPTIO-MGCOHNPYSA-N 0.000 description 4
• 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 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
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