DK2413693T3 - Substituted azoanthracenderivater, pharmaceutical compositions and methods for use thereof - Google Patents

Info

Publication number

DK2413693T3

DK2413693T3 DK10779665.8T DK10779665T DK2413693T3 DK 2413693 T3 DK2413693 T3 DK 2413693T3 DK 10779665 T DK10779665 T DK 10779665T DK 2413693 T3 DK2413693 T3 DK 2413693T3

Authority

DK

Denmark

Prior art keywords

phenyl

benzyloxy

amino

dichloro

propionic acid

Prior art date

2009-03-30

Links

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• 238000000034 method Methods 0.000 title claims description 347
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 13
• 150000001875 compounds Chemical class 0.000 claims description 256
• -1 benzothiopheneyl Chemical group 0.000 claims description 205
• 239000000203 mixture Substances 0.000 claims description 195
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 158
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 69
• 125000000217 alkyl group Chemical group 0.000 claims description 55
• 125000001424 substituent group Chemical group 0.000 claims description 55
• 229910052757 nitrogen Chemical group 0.000 claims description 52
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 38
• 125000003118 aryl group Chemical group 0.000 claims description 36
• 239000001257 hydrogen Substances 0.000 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
• 150000003839 salts Chemical class 0.000 claims description 35
• 125000000623 heterocyclic group Chemical group 0.000 claims description 33
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
• 125000001072 heteroaryl group Chemical group 0.000 claims description 30
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 30
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
• 125000000304 alkynyl group Chemical group 0.000 claims description 22
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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 20
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 19
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
• 229910052736 halogen Inorganic materials 0.000 claims description 18
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
• 239000003795 chemical substances by application Substances 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 17
• 125000003342 alkenyl group Chemical group 0.000 claims description 16
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• 150000002367 halogens Chemical class 0.000 claims description 14
• 125000004429 atom Chemical group 0.000 claims description 13
• 229910052799 carbon Inorganic materials 0.000 claims description 13
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
• 125000002947 alkylene group Chemical group 0.000 claims description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
• 239000011593 sulfur Chemical group 0.000 claims description 9
• 125000004419 alkynylene group Chemical group 0.000 claims description 8
• 125000001153 fluoro group Chemical group F* 0.000 claims description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 150000002431 hydrogen Chemical class 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 239000001301 oxygen Substances 0.000 claims description 7
• 208000002705 Glucose Intolerance Diseases 0.000 claims description 6
• 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 5
• 239000000556 agonist Substances 0.000 claims description 5
• 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 206010012601 diabetes mellitus Diseases 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
• 239000004480 active ingredient Substances 0.000 claims description 4
• 125000005275 alkylenearyl group Chemical group 0.000 claims description 4
• 239000003472 antidiabetic agent Substances 0.000 claims description 4
• 125000002541 furyl group Chemical group 0.000 claims description 4
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 4
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
• 201000000083 maturity-onset diabetes of the young type 1 Diseases 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000002971 oxazolyl group Chemical group 0.000 claims description 4
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 201000009104 prediabetes syndrome Diseases 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 125000000335 thiazolyl group Chemical group 0.000 claims description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 3
• 206010022489 Insulin Resistance Diseases 0.000 claims description 3
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 201000001421 hyperglycemia Diseases 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 230000002265 prevention Effects 0.000 claims description 3
• 208000011580 syndromic disease Diseases 0.000 claims description 3
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 2
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
• 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 2
• 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 2
• 208000031226 Hyperlipidaemia Diseases 0.000 claims description 2
• 102000004877 Insulin Human genes 0.000 claims description 2
• 108090001061 Insulin Proteins 0.000 claims description 2
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
• 208000008589 Obesity Diseases 0.000 claims description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
• 125000005218 alkyleneheteroaryl group Chemical group 0.000 claims description 2
• 229940125708 antidiabetic agent Drugs 0.000 claims description 2
• 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
• 208000006575 hypertriglyceridemia Diseases 0.000 claims description 2
• 230000001771 impaired effect Effects 0.000 claims description 2
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
• 239000004615 ingredient Substances 0.000 claims description 2
• 229940125396 insulin Drugs 0.000 claims description 2
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 2
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• 235000020824 obesity Nutrition 0.000 claims description 2
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
• 230000029663 wound healing Effects 0.000 claims description 2
• 239000003112 inhibitor Substances 0.000 claims 3
• HPYNZHMRTTWQTB-UHFFFAOYSA-N 2,3-dimethylpyridine Chemical compound CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 claims 2
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims 2
• 229940123208 Biguanide Drugs 0.000 claims 2
• 102000023984 PPAR alpha Human genes 0.000 claims 2
• 108010028924 PPAR alpha Proteins 0.000 claims 2
• 230000003178 anti-diabetic effect Effects 0.000 claims 2
• 125000004803 chlorobenzyl group Chemical group 0.000 claims 2
• 125000000068 chlorophenyl group Chemical group 0.000 claims 2
• 125000002946 cyanobenzyl group Chemical group 0.000 claims 2
• 125000004175 fluorobenzyl group Chemical group 0.000 claims 2
• 125000001207 fluorophenyl group Chemical group 0.000 claims 2
• 125000004344 phenylpropyl group Chemical group 0.000 claims 2
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
• ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims 1
• ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 claims 1
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
• SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims 1
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
• 208000023275 Autoimmune disease Diseases 0.000 claims 1
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
• 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 claims 1
• 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims 1
• 102000030914 Fatty Acid-Binding Human genes 0.000 claims 1
• 102000004366 Glucosidases Human genes 0.000 claims 1
• 108010056771 Glucosidases Proteins 0.000 claims 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims 1
• 102000000536 PPAR gamma Human genes 0.000 claims 1
• 108010016731 PPAR gamma Proteins 0.000 claims 1
• 206010036049 Polycystic ovaries Diseases 0.000 claims 1
• 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 claims 1
• 229940100389 Sulfonylurea Drugs 0.000 claims 1
• 229940123464 Thiazolidinedione Drugs 0.000 claims 1
• 239000003242 anti bacterial agent Substances 0.000 claims 1
• 230000000879 anti-atherosclerotic effect Effects 0.000 claims 1
• 230000003262 anti-osteoporosis Effects 0.000 claims 1
• 230000002785 anti-thrombosis Effects 0.000 claims 1
• 229940088710 antibiotic agent Drugs 0.000 claims 1
• 239000002220 antihypertensive agent Substances 0.000 claims 1
• 229940030600 antihypertensive agent Drugs 0.000 claims 1
• 239000003524 antilipemic agent Substances 0.000 claims 1
• 239000000164 antipsychotic agent Substances 0.000 claims 1
• 229940005529 antipsychotics Drugs 0.000 claims 1
• 229960004676 antithrombotic agent Drugs 0.000 claims 1
• 206010003246 arthritis Diseases 0.000 claims 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
• 230000001684 chronic effect Effects 0.000 claims 1
• 125000004802 cyanophenyl group Chemical group 0.000 claims 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 208000033679 diabetic kidney disease Diseases 0.000 claims 1
• 230000009977 dual effect Effects 0.000 claims 1
• 108091022862 fatty acid binding Proteins 0.000 claims 1
• 229960004580 glibenclamide Drugs 0.000 claims 1
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 claims 1
• 208000037824 growth disorder Diseases 0.000 claims 1
• 230000002519 immonomodulatory effect Effects 0.000 claims 1
• 208000000509 infertility Diseases 0.000 claims 1
• 230000036512 infertility Effects 0.000 claims 1
• 231100000535 infertility Toxicity 0.000 claims 1
• 229950004994 meglitinide Drugs 0.000 claims 1
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical group CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims 1
• 229960003105 metformin Drugs 0.000 claims 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
• 201000010065 polycystic ovary syndrome Diseases 0.000 claims 1
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 504
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 287
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 241
• 235000019439 ethyl acetate Nutrition 0.000 description 211
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 203
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 201
• 239000000243 solution Substances 0.000 description 154
• 229940095574 propionic acid Drugs 0.000 description 151
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 127
• 239000000047 product Substances 0.000 description 119
• 239000011541 reaction mixture Substances 0.000 description 114
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 112
• 238000006243 chemical reaction Methods 0.000 description 109
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 96
• 239000012267 brine Substances 0.000 description 93
• 239000012044 organic layer Substances 0.000 description 89
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 77
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 75
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 70
• 238000003818 flash chromatography Methods 0.000 description 67
• 239000000741 silica gel Substances 0.000 description 60
• 229910002027 silica gel Inorganic materials 0.000 description 60
• 229960001866 silicon dioxide Drugs 0.000 description 60
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
• 230000002829 reductive effect Effects 0.000 description 56
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 53
• 239000002904 solvent Substances 0.000 description 53
• 238000005160 1H NMR spectroscopy Methods 0.000 description 49
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 48
• 229910052938 sodium sulfate Inorganic materials 0.000 description 48
• 235000011152 sodium sulphate Nutrition 0.000 description 48
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
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• 238000002360 preparation method Methods 0.000 description 42
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• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 40
• 239000010410 layer Substances 0.000 description 39
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 32
• 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 32
• 150000001412 amines Chemical class 0.000 description 30
• 238000006467 substitution reaction Methods 0.000 description 30
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 29
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• 125000004432 carbon atom Chemical group C* 0.000 description 23
• 150000002148 esters Chemical class 0.000 description 23
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• 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 22
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• 239000002253 acid Substances 0.000 description 21
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
• 238000004440 column chromatography Methods 0.000 description 20
• 239000000284 extract Substances 0.000 description 20
• GARVSVCVQCGHLY-UHFFFAOYSA-N isoquinoline-7,8-dicarboxylic acid Chemical compound C1=CN=CC2=C(C(O)=O)C(C(=O)O)=CC=C21 GARVSVCVQCGHLY-UHFFFAOYSA-N 0.000 description 19
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• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 17
• 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 16
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• OGZJASWLLYAZIA-INIZCTEOSA-N methyl (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate Chemical compound C1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1B1OC(C)(C)C(C)(C)O1 OGZJASWLLYAZIA-INIZCTEOSA-N 0.000 description 3
• AEYXEFACMZSBHG-TUYUPMGOSA-N methyl (2s)-2-amino-3-[(2r)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]propanoate;hydrochloride Chemical compound Cl.C1=CC([C@H]2OC3=CC=C(C=C3OC2)C[C@H](N)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 AEYXEFACMZSBHG-TUYUPMGOSA-N 0.000 description 3
• CBZDDKMGJLYWRG-HNNXBMFYSA-N methyl (2s)-2-amino-3-[4-(2,3-dimethylpyridin-4-yl)oxyphenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC1=CC=NC(C)=C1C CBZDDKMGJLYWRG-HNNXBMFYSA-N 0.000 description 3
• JJJKCAAPLWARHE-CKUXDGONSA-N methyl (2s)-2-amino-3-[4-(2,3-dimethylpyridin-4-yl)oxyphenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC1=CC=NC(C)=C1C JJJKCAAPLWARHE-CKUXDGONSA-N 0.000 description 3
• FDFQRJWLHKSHPZ-LBPRGKRZSA-N methyl (2s)-3-(4-bromophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=C(Br)C=C1 FDFQRJWLHKSHPZ-LBPRGKRZSA-N 0.000 description 3
• LXOYICPHPKAIRO-SIKLNZKXSA-N methyl (2s)-3-[(2s)-2-(4-acetyloxyphenyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1([C@@H]2OC3=CC=C(C=C3OC2)C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C(OC(C)=O)C=C1 LXOYICPHPKAIRO-SIKLNZKXSA-N 0.000 description 3
• UBXVBIYYOUTSRO-WIOPSUGQSA-N methyl (2s)-3-[(2s)-2-(4-acetyloxyphenyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(4-nitrophenyl)sulfonylamino]propanoate Chemical compound C1([C@@H]2OC3=CC=C(C=C3OC2)C[C@@H](C(=O)OC)NS(=O)(=O)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C(OC(C)=O)C=C1 UBXVBIYYOUTSRO-WIOPSUGQSA-N 0.000 description 3
• UWOYWBGELCFGKB-FXAWDEMLSA-N methyl (2s)-3-[(2s)-2-(4-hydroxyphenyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1([C@@H]2OC3=CC=C(C=C3OC2)C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C(O)C=C1 UWOYWBGELCFGKB-FXAWDEMLSA-N 0.000 description 3
• ITULJIQPZPCOBS-BHBYDHKZSA-N methyl (2s)-3-[(2s)-2-[3-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(4-nitrophenyl)sulfonylamino]propanoate Chemical compound C=1C([C@@H]2OC3=CC=C(C=C3OC2)C[C@@H](C(=O)OC)NS(=O)(=O)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=CC=1OCC1=CC=C(Cl)C(Cl)=C1 ITULJIQPZPCOBS-BHBYDHKZSA-N 0.000 description 3
• RJJDDNNLUJAHLC-WSZLSEGOSA-N methyl (2s)-3-[(2s)-2-[3-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[[(1s)-1-phenylpropyl]amino]propanoate Chemical compound C=1C([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N[C@@H](CC)C=2C=CC=CC=2)C(=O)OC)=CC=CC=1OCC1=CC=C(Cl)C(Cl)=C1 RJJDDNNLUJAHLC-WSZLSEGOSA-N 0.000 description 3
• CPHKMDBOUKBUGH-NDOUHODOSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)OC)NC(=O)[C@H]1NCC2=CC=3O[C@@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 CPHKMDBOUKBUGH-NDOUHODOSA-N 0.000 description 3
• JVKJKADJNQEXEA-QMMMGPOBSA-N methyl (3s)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate Chemical compound OC1=C(O)C=C2CN[C@H](C(=O)OC)CC2=C1 JVKJKADJNQEXEA-QMMMGPOBSA-N 0.000 description 3
• DYKLPYKFQICXER-ODTVBPJYSA-N methyl (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylate Chemical compound C1=CC([C@@H]2OC=3C=C4CN([C@@H](CC4=CC=3OC2)C(=O)OC)[C@@H](CC)C=2C=CC=CC=2)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 DYKLPYKFQICXER-ODTVBPJYSA-N 0.000 description 3
• LJHAPRKTPAREGO-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical compound COC(=O)C(P(=O)(OC)OC)NC(=O)OC(C)(C)C LJHAPRKTPAREGO-UHFFFAOYSA-N 0.000 description 3
• KSKRPHSHPQTWJK-MHZLTWQESA-N methyl 3-[(2r)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]prop-2-enoate Chemical compound C1=CC([C@H]2OC3=CC=C(C=C3OC2)C=C(NC(=O)OC(C)(C)C)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 KSKRPHSHPQTWJK-MHZLTWQESA-N 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 150000002828 nitro derivatives Chemical class 0.000 description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• 238000006268 reductive amination reaction Methods 0.000 description 3
• 150000003335 secondary amines Chemical class 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• 235000010288 sodium nitrite Nutrition 0.000 description 3
• 239000012265 solid product Substances 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 150000003456 sulfonamides Chemical class 0.000 description 3
• QHUVTWQYVYYCIH-UITVWODBSA-N tert-butyl (3s)-8-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1,2,3,6,8,9-hexahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](CNC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 QHUVTWQYVYYCIH-UITVWODBSA-N 0.000 description 3
• WBMGIEPKPCDHAD-IWJNXRQDSA-N tert-butyl (3s,8s)-3-[4-(cyclohexylmethoxy)phenyl]-8-[[(2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC2CCCCC2)=CC=1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=NC(C)=C1C WBMGIEPKPCDHAD-IWJNXRQDSA-N 0.000 description 3
• YZPVIRDQSFKCJS-IWJNXRQDSA-N tert-butyl (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-8-[[(2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=NC(C)=C1C YZPVIRDQSFKCJS-IWJNXRQDSA-N 0.000 description 3
• RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 description 2
• CMUGKDLRHYPCSS-QFIPXVFZSA-N (2r)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxine-6-carbonitrile Chemical compound C1=C(Cl)C(Cl)=CC=C1COC1=CC=C([C@H]2OC3=CC=C(C=C3OC2)C#N)C=C1 CMUGKDLRHYPCSS-QFIPXVFZSA-N 0.000 description 2
• YDECNSWOIFUDLC-JOCHJYFZSA-N (2s)-2-[3-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde Chemical compound C1=C(Cl)C(Cl)=CC=C1COC1=CC=CC([C@@H]2OC3=CC=C(C=O)C=C3OC2)=C1 YDECNSWOIFUDLC-JOCHJYFZSA-N 0.000 description 2
• BUDRXDXIUACVTR-JOCHJYFZSA-N (2s)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde Chemical compound C1=C(Cl)C(Cl)=CC=C1COC1=CC=C([C@@H]2OC3=CC=C(C=O)C=C3OC2)C=C1 BUDRXDXIUACVTR-JOCHJYFZSA-N 0.000 description 2
• CMUGKDLRHYPCSS-JOCHJYFZSA-N (2s)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxine-6-carbonitrile Chemical compound C1=C(Cl)C(Cl)=CC=C1COC1=CC=C([C@@H]2OC3=CC=C(C=C3OC2)C#N)C=C1 CMUGKDLRHYPCSS-JOCHJYFZSA-N 0.000 description 2
• UUZSXAUGISGKMS-SIORXBAWSA-N (2s)-2-[[(3s)-7-(benzenesulfonyl)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)S(=O)(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 UUZSXAUGISGKMS-SIORXBAWSA-N 0.000 description 2
• DTGFQIGGGWYXHC-DHUDCZEASA-N (2s)-2-[[(3s)-7-(tert-butylcarbamoyl)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)C1CC2=CC=3OC[C@@H](OC=3C=C2CN1C(=O)NC(C)(C)C)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 DTGFQIGGGWYXHC-DHUDCZEASA-N 0.000 description 2
• OXEHLWBZPWIUMM-MHWJKXMPSA-N (2s)-2-[[(3s)-7-[(2-amino-4-methyl-1,3-thiazol-5-yl)sulfonyl]-3-(4-ethoxyphenyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C1=CC(OCC)=CC=C1[C@@H]1OC2=CC(CN(C(C3)C(=O)N[C@@H](CC=4C=CC(=CC=4)C=4C=CC(=CC=4)C#N)C(O)=O)S(=O)(=O)C4=C(N=C(N)S4)C)=C3C=C2OC1 OXEHLWBZPWIUMM-MHWJKXMPSA-N 0.000 description 2
• JHVBEGBKQNSPAI-KNGBNFTKSA-N (2s)-2-[[(3s)-7-[(2-amino-4-methyl-1,3-thiazol-5-yl)sulfonyl]-3-(4-phenylmethoxyphenyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound N1=C(N)SC(S(=O)(=O)N2C(CC3=CC=4OC[C@@H](OC=4C=C3C2)C=2C=CC(OCC=3C=CC=CC=3)=CC=2)C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)C(O)=O)=C1C JHVBEGBKQNSPAI-KNGBNFTKSA-N 0.000 description 2
• UJFMGHIFBOGDJZ-YUTPAWSZSA-N (2s)-2-[[(3s)-7-[(2-amino-4-methyl-1,3-thiazol-5-yl)sulfonyl]-3-[4-(cyclopentylmethoxy)phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound N1=C(N)SC(S(=O)(=O)N2C(CC3=CC=4OC[C@@H](OC=4C=C3C2)C=2C=CC(OCC3CCCC3)=CC=2)C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)C(O)=O)=C1C UJFMGHIFBOGDJZ-YUTPAWSZSA-N 0.000 description 2
• NMJVMRQXELZJEU-SIORXBAWSA-N (2s)-2-[[(3s)-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 NMJVMRQXELZJEU-SIORXBAWSA-N 0.000 description 2
• PYIGYZMESCXTLC-DSMKTCEVSA-N (2s)-2-[[(3s,8s)-3-[4-(cyclopentylmethoxy)phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC2CCCC2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C PYIGYZMESCXTLC-DSMKTCEVSA-N 0.000 description 2
• DQDQVAWHSSGEPH-AMNOJZCUSA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(2-methylpentan-3-yl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1C(C(C)C)CC)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C DQDQVAWHSSGEPH-AMNOJZCUSA-N 0.000 description 2
• UOZPOZDOXYJXIJ-TVAVRQBESA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(pyridin-2-ylmethyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound CC1=NC=CC(C=2C=CC(C[C@H](NC(=O)[C@H]3N(CC4=CC=5O[C@H](COC=5C=C4C3)C=3C=CC(OCC=4C=C(Cl)C(Cl)=CC=4)=CC=3)CC=3N=CC=CC=3)C(O)=O)=CC=2)=C1C UOZPOZDOXYJXIJ-TVAVRQBESA-N 0.000 description 2
• YIKYLHBXYYFCEZ-WWKIHPBISA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-(4-pyridin-4-ylphenyl)propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC=C1 YIKYLHBXYYFCEZ-WWKIHPBISA-N 0.000 description 2
• DEDPYBWOUXWMOX-ZTAAISNPSA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C DEDPYBWOUXWMOX-ZTAAISNPSA-N 0.000 description 2
• GLSFNHSIUULLSS-ZTAAISNPSA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-methylphenyl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=C(C)C=C1 GLSFNHSIUULLSS-ZTAAISNPSA-N 0.000 description 2
• YDEJWKQAAPBIMZ-DSMKTCEVSA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-[2-(fluoromethyl)pyridin-4-yl]phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(CF)=C1 YDEJWKQAAPBIMZ-DSMKTCEVSA-N 0.000 description 2
• GFHHVMCDGJQWKC-ZTAAISNPSA-N (2s)-2-[[(3s,8s)-3-[4-[(3-chlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C GFHHVMCDGJQWKC-ZTAAISNPSA-N 0.000 description 2
• VDVOMHPLPSQTPY-IFMZLZCVSA-N (2s)-2-[[(3s,8s)-7-acetyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1C(=O)C)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C VDVOMHPLPSQTPY-IFMZLZCVSA-N 0.000 description 2
• JUPRHEXJQLPHQL-WRUZSIFFSA-N (2s)-2-[[(3s,8s)-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2-methylpyridin-4-yl)oxyphenyl]propanoic acid Chemical compound C1=NC(C)=CC(OC=2C=CC(C[C@H](NC(=O)[C@H]3N(CC4=CC=5O[C@H](COC=5C=C4C3)C=3C=CC(OCC=4C=C(Cl)C(Cl)=CC=4)=CC=3)C(=O)C=3C=CC=CC=3)C(O)=O)=CC=2)=C1 JUPRHEXJQLPHQL-WRUZSIFFSA-N 0.000 description 2
• TYZJBCBRUMLMRT-DSMKTCEVSA-N (2s)-3-[4-(4-chlorophenyl)phenyl]-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 TYZJBCBRUMLMRT-DSMKTCEVSA-N 0.000 description 2
• MJFQCGFYARRZQR-PPCQQBJASA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(5-methyl-1,2-oxazol-4-yl)methyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound O1N=CC(CN2C(CC3=CC=4OC[C@@H](OC=4C=C3C2)C=2C=CC(OCC=3C=C(Cl)C(Cl)=CC=3)=CC=2)C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)C(O)=O)=C1C MJFQCGFYARRZQR-PPCQQBJASA-N 0.000 description 2
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• 150000004657 carbamic acid derivatives Chemical class 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 2
• 239000000470 constituent Substances 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 229940076286 cupric acetate Drugs 0.000 description 2
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
• 125000004956 cyclohexylene group Chemical group 0.000 description 2
• 125000004980 cyclopropylene group Chemical group 0.000 description 2
• 238000007872 degassing Methods 0.000 description 2
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 238000010931 ester hydrolysis Methods 0.000 description 2
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 2
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 229960001519 exenatide Drugs 0.000 description 2
• 230000037406 food intake Effects 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 230000002641 glycemic effect Effects 0.000 description 2
• 125000004438 haloalkoxy group Chemical group 0.000 description 2
• 125000005549 heteroarylene group Chemical group 0.000 description 2
• 125000001041 indolyl group Chemical group 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• DUMSKQUKLVSSII-UHFFFAOYSA-N iodomethylcyclopentane Chemical compound ICC1CCCC1 DUMSKQUKLVSSII-UHFFFAOYSA-N 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
• 125000001786 isothiazolyl group Chemical group 0.000 description 2
• 238000005304 joining Methods 0.000 description 2
• 208000030159 metabolic disease Diseases 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• IVDOIYGHPJPXFO-PKLMIRHRSA-N methyl (2r)-2-amino-3-[4-(4-cyanophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@@H](N)C(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 IVDOIYGHPJPXFO-PKLMIRHRSA-N 0.000 description 2
• GTPSYWNNEXIAGW-HKGQQODZSA-N methyl (2s)-2-[[(3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1NCC2=CC=3O[C@@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=NC(C)=C1C GTPSYWNNEXIAGW-HKGQQODZSA-N 0.000 description 2
• MQZCTAVTLPFULC-VEBFQCSLSA-N methyl (2s)-2-[[(3s)-1-acetyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydropyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](CN(C=3C=C2C1)C(C)=O)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 MQZCTAVTLPFULC-VEBFQCSLSA-N 0.000 description 2
• IUWQRTYGNBILBK-KXIZWUBZSA-N methyl (2s)-2-[[(3s)-3-[4-[(3-chloro-4-methylphenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(C)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 IUWQRTYGNBILBK-KXIZWUBZSA-N 0.000 description 2
• VICBVLZLISVDCT-VHYZKNOSSA-N methyl (2s)-2-[[(3s,8s)-3-[4-(3-chlorophenoxy)phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OC=2C=C(Cl)C=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=NC(C)=C1C VICBVLZLISVDCT-VHYZKNOSSA-N 0.000 description 2
• XWNBUFPRJYNESG-VHYZKNOSSA-N methyl (2s)-2-[[(3s,8s)-3-[4-(3-chlorophenyl)phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(=CC=1)C=1C=C(Cl)C=CC=1)C(C=C1)=CC=C1C1=CC=NC(C)=C1C XWNBUFPRJYNESG-VHYZKNOSSA-N 0.000 description 2
• BRUKMUWDWWPPBM-IIRRWZJPSA-N methyl (2s)-2-[[(3s,8s)-3-[4-(cyclohexylmethoxy)phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)oxyphenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC2CCCCC2)=CC=1)C(C=C1)=CC=C1OC1=CC=NC(C)=C1C BRUKMUWDWWPPBM-IIRRWZJPSA-N 0.000 description 2
• RIPOSSZLZQIYOB-YLJLHNITSA-N methyl (2s)-2-[[(3s,8s)-3-[4-(cyclohexylmethoxy)phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC2CCCCC2)=CC=1)C(C=C1)=CC=C1C1=CC=NC(C)=C1C RIPOSSZLZQIYOB-YLJLHNITSA-N 0.000 description 2
• HMKJGFLHCXAJFP-CKUXDGONSA-N methyl (2s)-2-amino-3-[4-(2-methylpyridin-4-yl)oxyphenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC1=CC=NC(C)=C1 HMKJGFLHCXAJFP-CKUXDGONSA-N 0.000 description 2
• QWJMMNXUOBFQLN-RSAXXLAASA-N methyl (2s)-2-amino-3-[4-(4-chlorophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(Cl)C=C1 QWJMMNXUOBFQLN-RSAXXLAASA-N 0.000 description 2
• ZPGYXIVFYCKLQK-SFHVURJKSA-N methyl (2s)-2-amino-3-[4-(4-cyanophenyl)phenyl]-2-methylpropanoate Chemical compound C1=CC(C[C@](C)(N)C(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 ZPGYXIVFYCKLQK-SFHVURJKSA-N 0.000 description 2
• VRRRLQSVWDNHDW-RSAXXLAASA-N methyl (2s)-2-amino-3-[4-(4-fluorophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(F)C=C1 VRRRLQSVWDNHDW-RSAXXLAASA-N 0.000 description 2
• ZLCHSICIKWGTID-CKUXDGONSA-N methyl (2s)-2-amino-3-[4-[2-(fluoromethyl)pyridin-4-yl]phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC(CF)=C1 ZLCHSICIKWGTID-CKUXDGONSA-N 0.000 description 2
• JMUQVEFMAXSRQF-ZOWNYOTGSA-N methyl (2s)-2-amino-3-[5-(4-cyanophenyl)thiophen-2-yl]propanoate;hydrochloride Chemical compound Cl.S1C(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 JMUQVEFMAXSRQF-ZOWNYOTGSA-N 0.000 description 2
• NQIFXJSLCUJHBB-LBPRGKRZSA-N methyl (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=C(O)C=C1 NQIFXJSLCUJHBB-LBPRGKRZSA-N 0.000 description 2
• AGWKPQQUZAALHO-IBGZPJMESA-N methyl (2s)-3-(4-hydroxyphenyl)-2-methyl-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C([C@@](C)(C(=O)OC)NC(=O)OCC=1C=CC=CC=1)C1=CC=C(O)C=C1 AGWKPQQUZAALHO-IBGZPJMESA-N 0.000 description 2
• JQPPZFDAUFVJIL-VIFPVBQESA-N methyl (2s)-3-(5-bromothiophen-2-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=C(Br)S1 JQPPZFDAUFVJIL-VIFPVBQESA-N 0.000 description 2
• DNAFOSMJBHMVEX-IGKIAQTJSA-N methyl (2s)-3-[(2r)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC([C@H]2OC3=CC=C(C=C3OC2)C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 DNAFOSMJBHMVEX-IGKIAQTJSA-N 0.000 description 2
• FHUMOBVHYICPOI-FIBWVYCGSA-N methyl (2s)-3-[(2r)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(4-nitrophenyl)sulfonylamino]propanoate Chemical compound C1=CC([C@H]2OC3=CC=C(C=C3OC2)C[C@@H](C(=O)OC)NS(=O)(=O)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 FHUMOBVHYICPOI-FIBWVYCGSA-N 0.000 description 2
• PPAPOWBYYFKEST-NGCAANIMSA-N methyl (2s)-3-[(2r)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[[(1s)-1-phenylpropyl]amino]propanoate Chemical compound C1=CC([C@H]2OC3=CC=C(C=C3OC2)C[C@H](N[C@@H](CC)C=2C=CC=CC=2)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 PPAPOWBYYFKEST-NGCAANIMSA-N 0.000 description 2
• OGDLZKANMRDWRF-PNIUZAESSA-N methyl (2s)-3-[(2s)-2-(4-acetyloxyphenyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[[(1s)-1-phenylpropyl]amino]propanoate Chemical compound C1([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N[C@@H](CC)C=2C=CC=CC=2)C(=O)OC)=CC=C(OC(C)=O)C=C1 OGDLZKANMRDWRF-PNIUZAESSA-N 0.000 description 2
• XMDDUGULQPUMIB-JCYRPKCISA-N methyl (2s)-3-[(2s)-2-(4-hydroxyphenyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[[(1s)-1-phenylpropyl]amino]propanoate Chemical compound C1([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N[C@@H](CC)C=2C=CC=CC=2)C(=O)OC)=CC=C(O)C=C1 XMDDUGULQPUMIB-JCYRPKCISA-N 0.000 description 2
• FVLLSXQHLDNFST-VHYZKNOSSA-N methyl (2s)-3-[(2s)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(4-nitrophenyl)sulfonyl-[(1s)-1-phenylpropyl]amino]propanoate Chemical compound C1=CC([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N([C@@H](CC)C=2C=CC=CC=2)S(=O)(=O)C=2C=CC(=CC=2)[N+]([O-])=O)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 FVLLSXQHLDNFST-VHYZKNOSSA-N 0.000 description 2
• FHUMOBVHYICPOI-BHBYDHKZSA-N methyl (2s)-3-[(2s)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(4-nitrophenyl)sulfonylamino]propanoate Chemical compound C1=CC([C@@H]2OC3=CC=C(C=C3OC2)C[C@@H](C(=O)OC)NS(=O)(=O)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 FHUMOBVHYICPOI-BHBYDHKZSA-N 0.000 description 2
• PPAPOWBYYFKEST-YLJHYDRVSA-N methyl (2s)-3-[(2s)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[[(1r)-1-phenylpropyl]amino]propanoate Chemical compound C1=CC([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N[C@H](CC)C=2C=CC=CC=2)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 PPAPOWBYYFKEST-YLJHYDRVSA-N 0.000 description 2
• LXOYICPHPKAIRO-YDNXMHBPSA-N methyl (2s)-3-[2-(4-acetyloxyphenyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1OC2=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C2OC1C1=CC=C(OC(C)=O)C=C1 LXOYICPHPKAIRO-YDNXMHBPSA-N 0.000 description 2
• YLBJCHJGSFAUQU-UCFFOFKASA-N methyl (2s)-3-[2-(4-acetyloxyphenyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2-aminopropanoate Chemical compound C1OC2=CC(C[C@H](N)C(=O)OC)=CC=C2OC1C1=CC=C(OC(C)=O)C=C1 YLBJCHJGSFAUQU-UCFFOFKASA-N 0.000 description 2
• DNAFOSMJBHMVEX-BXXZMZEQSA-N methyl (2s)-3-[2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1OC2=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C2OC1C(C=C1)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 DNAFOSMJBHMVEX-BXXZMZEQSA-N 0.000 description 2
• OSUIIODYUWFPJK-PVCWFJFTSA-N methyl (2s)-3-[3-bromo-4-[1-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-hydroxyethoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound BrC1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1OC(CO)C(C=C1)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 OSUIIODYUWFPJK-PVCWFJFTSA-N 0.000 description 2
• CXDVNMQGZJJDLH-UJGAEZNTSA-N methyl (2s)-3-[3-bromo-4-[2-[tert-butyl(diphenyl)silyl]oxy-1-[4-[(3,4-dichlorophenyl)methoxy]phenyl]ethoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound BrC1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1OC(C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)CO[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 CXDVNMQGZJJDLH-UJGAEZNTSA-N 0.000 description 2
• MCSRCZOMLYENHO-IBGZPJMESA-N methyl (2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1C1=CC=NC(C)=C1C MCSRCZOMLYENHO-IBGZPJMESA-N 0.000 description 2
• GOUWLKGRUODXDV-IBGZPJMESA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1C1=CC=C(C#N)C=C1 GOUWLKGRUODXDV-IBGZPJMESA-N 0.000 description 2
• COEKCZCWLCNZBB-HKGQQODZSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1NCC2=CC=3O[C@@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 COEKCZCWLCNZBB-HKGQQODZSA-N 0.000 description 2
• SBRJJILRBNATLO-TXSBWBSASA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2,3,6,7,8,9-hexahydropyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](CN(C)C=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 SBRJJILRBNATLO-TXSBWBSASA-N 0.000 description 2
• CSFRLQBHXIFSIG-VEBFQCSLSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dimethylphenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(C)C(C)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 CSFRLQBHXIFSIG-VEBFQCSLSA-N 0.000 description 2
• OGBLFWFWYDAKSZ-INIZCTEOSA-N methyl (2s)-3-[5-(4-cyanophenyl)thiophen-2-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound S1C(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1C1=CC=C(C#N)C=C1 OGBLFWFWYDAKSZ-INIZCTEOSA-N 0.000 description 2
• AVDQGIMBHNKULH-NLJOTIRTSA-N methyl (3s,8s)-3-(4-hydroxyphenyl)-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylate Chemical compound C1([C@@H]2OC=3C=C4CN([C@@H](CC4=CC=3OC2)C(=O)OC)[C@@H](CC)C=2C=CC=CC=2)=CC=C(O)C=C1 AVDQGIMBHNKULH-NLJOTIRTSA-N 0.000 description 2
• ZQZFFJHCMLLJGF-HHHXNRCGSA-N methyl 3-[(2s)-2-[3-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]prop-2-enoate Chemical compound C=1C([C@@H]2OC3=CC=C(C=C3OC2)C=C(NC(=O)OC(C)(C)C)C(=O)OC)=CC=CC=1OCC1=CC=C(Cl)C(Cl)=C1 ZQZFFJHCMLLJGF-HHHXNRCGSA-N 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• IVBVDGOVRUPPAU-UHFFFAOYSA-N n,6-dimethyl-5-nitropyridin-2-amine Chemical compound CNC1=CC=C([N+]([O-])=O)C(C)=N1 IVBVDGOVRUPPAU-UHFFFAOYSA-N 0.000 description 2
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
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• 239000012299 nitrogen atmosphere Substances 0.000 description 2
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• YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
• 125000003367 polycyclic group Chemical group 0.000 description 2
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• 125000003226 pyrazolyl group Chemical group 0.000 description 2
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• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 2
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• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
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• VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
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• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
• YZPVIRDQSFKCJS-RNMNAOLMSA-N tert-butyl (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-8-[[(2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1N(CC2=CC=3O[C@@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=NC(C)=C1C YZPVIRDQSFKCJS-RNMNAOLMSA-N 0.000 description 2
• VWTNSISTYUPFBH-IWJNXRQDSA-N tert-butyl (3s,8s)-3-[3-[(3,4-dichlorophenyl)methoxy]phenyl]-8-[[(2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=C(OCC=2C=C(Cl)C(Cl)=CC=2)C=CC=1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=NC(C)=C1C VWTNSISTYUPFBH-IWJNXRQDSA-N 0.000 description 2
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 2
• XMXIFYUQKOMUJR-UHFFFAOYSA-N tert-butyl n-[5-(bromomethyl)-4-methyl-1,3-thiazol-2-yl]carbamate Chemical compound CC=1N=C(NC(=O)OC(C)(C)C)SC=1CBr XMXIFYUQKOMUJR-UHFFFAOYSA-N 0.000 description 2
• JKBGHFXEMZZLFY-UHFFFAOYSA-N tert-butyl n-[5-(bromomethyl)pyridin-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(CBr)C=N1 JKBGHFXEMZZLFY-UHFFFAOYSA-N 0.000 description 2
• IUKJGZQDJHHXDK-UHFFFAOYSA-N tert-butyl n-[5-(hydroxymethyl)-4-methyl-1,3-thiazol-2-yl]carbamate Chemical compound CC=1N=C(NC(=O)OC(C)(C)C)SC=1CO IUKJGZQDJHHXDK-UHFFFAOYSA-N 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 150000003573 thiols Chemical class 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
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• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• HQRWWHIETAKIMO-SNVBAGLBSA-N (1r)-1-phenylbutan-1-ol Chemical compound CCC[C@@H](O)C1=CC=CC=C1 HQRWWHIETAKIMO-SNVBAGLBSA-N 0.000 description 1
• BUDRXDXIUACVTR-QFIPXVFZSA-N (2r)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde Chemical compound C1=C(Cl)C(Cl)=CC=C1COC1=CC=C([C@H]2OC3=CC=C(C=O)C=C3OC2)C=C1 BUDRXDXIUACVTR-QFIPXVFZSA-N 0.000 description 1
• ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 1
• SQECZMJJIUCWKE-WRKASMAWSA-N (2s)-2-[[(3s)-1-acetyl-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)C1N(CC=2C=C3O[C@H](CN(C3=CC=2C1)C(=O)C)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C=1C=CC=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 SQECZMJJIUCWKE-WRKASMAWSA-N 0.000 description 1
• YRVXPRAJBJCWNM-SIORXBAWSA-N (2s)-2-[[(3s)-7-(2-chlorobenzoyl)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C=1C(=CC=CC=1)Cl)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 YRVXPRAJBJCWNM-SIORXBAWSA-N 0.000 description 1
• UMWOCGDGIRGQRL-NRDMTTIESA-N (2s)-2-[[(3s)-7-(4-acetamidophenyl)sulfonyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C1=CC(NC(=O)C)=CC=C1S(=O)(=O)N1C(C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)C(O)=O)CC2=CC(OC[C@@H](O3)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)=C3C=C2C1 UMWOCGDGIRGQRL-NRDMTTIESA-N 0.000 description 1
• ANSZCEZIDJYVLD-YUTPAWSZSA-N (2s)-2-[[(3s)-7-[(2-amino-1,3-thiazol-5-yl)sulfonyl]-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound S1C(N)=NC=C1S(=O)(=O)N1C(C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)C(O)=O)CC2=CC(OC[C@@H](O3)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)=C3C=C2C1 ANSZCEZIDJYVLD-YUTPAWSZSA-N 0.000 description 1
• IJJGULDXVBWFMH-LLSVSLFMSA-N (2s)-2-[[(3s)-7-[(2-chloro-6-fluorophenyl)methyl]-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)CC=1C(=CC=CC=1F)Cl)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 IJJGULDXVBWFMH-LLSVSLFMSA-N 0.000 description 1
• BMHMWUGFHPAUBO-LLSVSLFMSA-N (2s)-2-[[(3s)-7-[(2-chlorophenyl)methyl]-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)CC=1C(=CC=CC=1)Cl)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 BMHMWUGFHPAUBO-LLSVSLFMSA-N 0.000 description 1
• DMWQFXVWOFZMDC-NRDMTTIESA-N (2s)-2-[[(3s)-7-[(2-cyanophenyl)methyl]-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)CC=1C(=CC=CC=1)C#N)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 DMWQFXVWOFZMDC-NRDMTTIESA-N 0.000 description 1
• BWHBEKAUPGCKNA-LLSVSLFMSA-N (2s)-2-[[(3s)-7-benzyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)CC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 BWHBEKAUPGCKNA-LLSVSLFMSA-N 0.000 description 1
• KVVGVRCAGXLJRL-XSBWBPONSA-N (2s)-2-[[(3s)-7-but-2-ynoxycarbonyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)C1CC2=CC=3OC[C@@H](OC=3C=C2CN1C(=O)OCC#CC)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 KVVGVRCAGXLJRL-XSBWBPONSA-N 0.000 description 1
• ORVIXSAPJXWSAV-DSMKTCEVSA-N (2s)-2-[[(3s,8s)-3-(4-cyclohexyloxyphenyl)-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OC2CCCCC2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C ORVIXSAPJXWSAV-DSMKTCEVSA-N 0.000 description 1
• LIRITKFHAYJRMK-WWKIHPBISA-N (2s)-2-[[(3s,8s)-3-(4-cyclopentyloxyphenyl)-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OC2CCCC2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C LIRITKFHAYJRMK-WWKIHPBISA-N 0.000 description 1
• UDIWNRGEFHPODU-VQRUSENYSA-N (2s)-2-[[(3s,8s)-3-[4-(3-chlorophenoxy)phenyl]-7-(2,5-dimethyl-1,3-oxazole-4-carbonyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound O1C(C)=NC(C(=O)N2[C@@H](CC3=CC=4OC[C@@H](OC=4C=C3C2)C=2C=CC(OC=3C=C(Cl)C=CC=3)=CC=2)C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C(=C(C)N=CC=2)C)C(O)=O)=C1C UDIWNRGEFHPODU-VQRUSENYSA-N 0.000 description 1
• TZOOEQWPQASMBH-VQRUSENYSA-N (2s)-2-[[(3s,8s)-3-[4-(3-chlorophenyl)phenyl]-7-(2,5-dimethyl-1,3-oxazole-4-carbonyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound O1C(C)=NC(C(=O)N2[C@@H](CC3=CC=4OC[C@@H](OC=4C=C3C2)C=2C=CC(=CC=2)C=2C=C(Cl)C=CC=2)C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C(=C(C)N=CC=2)C)C(O)=O)=C1C TZOOEQWPQASMBH-VQRUSENYSA-N 0.000 description 1
• BNUFTAKJIDKGNT-ZTAAISNPSA-N (2s)-2-[[(3s,8s)-3-[4-(cyclohexylmethoxy)phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC2CCCCC2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C BNUFTAKJIDKGNT-ZTAAISNPSA-N 0.000 description 1
• KRTUZUQQOGGJLI-IWJNXRQDSA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(2,5-dimethyl-1,3-oxazole-4-carbonyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound O1C(C)=NC(C(=O)N2[C@@H](CC3=CC=4OC[C@@H](OC=4C=C3C2)C=2C=CC(OCC=3C=C(Cl)C(Cl)=CC=3)=CC=2)C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C(=C(C)N=CC=2)C)C(O)=O)=C1C KRTUZUQQOGGJLI-IWJNXRQDSA-N 0.000 description 1
• GLDWINJLFVTQNO-VQRUSENYSA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(2-methylpropanoyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1C(=O)C(C)C)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C GLDWINJLFVTQNO-VQRUSENYSA-N 0.000 description 1
• XXXHGAXRCNAYKZ-UWFQYGBDSA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(2-phenylacetyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound CC1=NC=CC(C=2C=CC(C[C@H](NC(=O)[C@H]3N(CC4=CC=5O[C@H](COC=5C=C4C3)C=3C=CC(OCC=4C=C(Cl)C(Cl)=CC=4)=CC=3)C(=O)CC=3C=CC=CC=3)C(O)=O)=CC=2)=C1C XXXHGAXRCNAYKZ-UWFQYGBDSA-N 0.000 description 1
• ITRIHRNIJPFRBN-YSBVQXAESA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-(4-pyridazin-4-ylphenyl)propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NN=C1 ITRIHRNIJPFRBN-YSBVQXAESA-N 0.000 description 1
• DSGPZERMCHZOFC-WWKIHPBISA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-(4-pyridin-3-yloxyphenyl)propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1OC1=CC=CN=C1 DSGPZERMCHZOFC-WWKIHPBISA-N 0.000 description 1
• UWHLJNJTFATDEI-WWKIHPBISA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-(4-pyridin-3-ylphenyl)propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=CN=C1 UWHLJNJTFATDEI-WWKIHPBISA-N 0.000 description 1
• AFWCGPRDQKWXQQ-WWKIHPBISA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-(4-pyridin-4-yloxyphenyl)propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1OC1=CC=NC=C1 AFWCGPRDQKWXQQ-WWKIHPBISA-N 0.000 description 1
• SWYCKRUNRBYFCY-YSBVQXAESA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-(4-pyrimidin-4-ylphenyl)propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC=N1 SWYCKRUNRBYFCY-YSBVQXAESA-N 0.000 description 1
• PWHKSISUWOVVCU-BPLXVOGRSA-N (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-(4-quinolin-4-ylphenyl)propanoic acid Chemical compound C1=CC([C@@H]2OC=3C=C4CN([C@@H](CC4=CC=3OC2)C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C3=CC=CC=C3N=CC=2)C(O)=O)[C@@H](CC)C=2C=CC=CC=2)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 PWHKSISUWOVVCU-BPLXVOGRSA-N 0.000 description 1
• MWIHKJOXPIXUHD-KYUGQUBOSA-N (2s)-2-[[(3s,8s)-7-benzoyl-3-(4-hydroxyphenyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound CC1=NC=CC(C=2C=CC(C[C@H](NC(=O)[C@H]3N(CC4=CC=5O[C@H](COC=5C=C4C3)C=3C=CC(O)=CC=3)C(=O)C=3C=CC=CC=3)C(O)=O)=CC=2)=C1C MWIHKJOXPIXUHD-KYUGQUBOSA-N 0.000 description 1
• BUEWJCQCDQRXON-TVAVRQBESA-N (2s)-2-[[(3s,8s)-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid Chemical compound CC1=NC=CC(C=2C=CC(C[C@H](NC(=O)[C@H]3N(CC4=CC=5O[C@H](COC=5C=C4C3)C=3C=CC(OCC=4C=C(Cl)C(Cl)=CC=4)=CC=3)C(=O)C=3C=CC=CC=3)C(O)=O)=CC=2)=C1C BUEWJCQCDQRXON-TVAVRQBESA-N 0.000 description 1
• ULNOXUAEIPUJMK-NSHDSACASA-N (2s)-3-(4-bromophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(Br)C=C1 ULNOXUAEIPUJMK-NSHDSACASA-N 0.000 description 1
• HHNNFRCLMQFXBA-QMMMGPOBSA-N (2s)-3-(5-bromothiophen-2-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(Br)S1 HHNNFRCLMQFXBA-QMMMGPOBSA-N 0.000 description 1
• FMKRVVVDUOECNS-FNFZQODSSA-N (2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-2-[[(3s,8s)-3-(4-ethoxyphenyl)-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C1=CC(OCC)=CC=C1[C@@H]1OC2=CC(CN([C@@H](C3)C(=O)N[C@@H](CC=4C=CC(=CC=4)C=4C(=C(C)N=CC=4)C)C(O)=O)[C@@H](CC)C=4C=CC=CC=4)=C3C=C2OC1 FMKRVVVDUOECNS-FNFZQODSSA-N 0.000 description 1
• RWORUGWZTDSQLW-IGVZRYHESA-N (2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-2-[[(3s,8s)-3-(4-hydroxyphenyl)-7-[(2-methylpropan-2-yl)oxycarbonyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound CC1=NC=CC(C=2C=CC(C[C@H](NC(=O)[C@H]3N(CC4=CC=5O[C@H](COC=5C=C4C3)C=3C=CC(O)=CC=3)C(=O)OC(C)(C)C)C(O)=O)=CC=2)=C1C RWORUGWZTDSQLW-IGVZRYHESA-N 0.000 description 1
• WQLZRHZSUWMMJQ-CNZZUQSYSA-N (2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-2-[[(3s,8s)-3-(4-methoxyphenyl)-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OC)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C WQLZRHZSUWMMJQ-CNZZUQSYSA-N 0.000 description 1
• BDXOBUMPXLYNSC-WWKIHPBISA-N (2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-2-[[(3s,8s)-3-(4-pentan-3-yloxyphenyl)-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C1=CC(OC(CC)CC)=CC=C1[C@@H]1OC2=CC(CN([C@@H](C3)C(=O)N[C@@H](CC=4C=CC(=CC=4)C=4C(=C(C)N=CC=4)C)C(O)=O)[C@@H](CC)C=4C=CC=CC=4)=C3C=C2OC1 BDXOBUMPXLYNSC-WWKIHPBISA-N 0.000 description 1
• MPENUVICSRASOD-ZTAAISNPSA-N (2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-2-[[(3s,8s)-3-(4-phenylmethoxyphenyl)-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=CC=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C MPENUVICSRASOD-ZTAAISNPSA-N 0.000 description 1
• GDQZHFMIDYNLGM-YSBVQXAESA-N (2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-2-[[(3s,8s)-3-[4-(2-methylpropoxy)phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC(C)C)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C GDQZHFMIDYNLGM-YSBVQXAESA-N 0.000 description 1
• KXNBQVBTARYAPT-NMGHVLOISA-N (2s)-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]-2-[[(3s,8s)-7-[(1s)-1-phenylpropyl]-3-(4-propan-2-yloxyphenyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3OC[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OC(C)C)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=NC(C)=C1C KXNBQVBTARYAPT-NMGHVLOISA-N 0.000 description 1
• PBYKFQUJDVHITJ-SIORXBAWSA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(2-methylsulfonylbenzoyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(=O)N1C(C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)C(O)=O)CC2=CC(OC[C@@H](O3)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)=C3C=C2C1 PBYKFQUJDVHITJ-SIORXBAWSA-N 0.000 description 1
• NSUBDOAQQLVIMH-XSBWBPONSA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(3-methylbutanoyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@H](NC(=O)C1CC2=CC=3OC[C@@H](OC=3C=C2CN1C(=O)CC(C)C)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 NSUBDOAQQLVIMH-XSBWBPONSA-N 0.000 description 1
• FUEWTSQUZDUBBJ-NRDMTTIESA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(3-phenylprop-2-ynoyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C#CC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 FUEWTSQUZDUBBJ-NRDMTTIESA-N 0.000 description 1
• JLKOPQBMIMTEQZ-SIORXBAWSA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(oxan-4-ylmethyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)CC1CCOCC1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 JLKOPQBMIMTEQZ-SIORXBAWSA-N 0.000 description 1
• PBOSJJXRTSTDIL-JYGRHXHISA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(oxolane-2-carbonyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C1OCCC1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 PBOSJJXRTSTDIL-JYGRHXHISA-N 0.000 description 1
• PDAGVQSSSILNAO-HBRKMURKSA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(oxolane-3-carbonyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C1COCC1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 PDAGVQSSSILNAO-HBRKMURKSA-N 0.000 description 1
• UGQKNWAOBDBGEC-AZHBUCKTSA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(pyrazine-2-carbonyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C=1N=CC=NC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 UGQKNWAOBDBGEC-AZHBUCKTSA-N 0.000 description 1
• YMLGANKWCDSYDT-DHUDCZEASA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(thiophene-2-carbonyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C=1SC=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 YMLGANKWCDSYDT-DHUDCZEASA-N 0.000 description 1
• ASDKMUIOKAYBEX-PPCQQBJASA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1-methylpyrazol-3-yl)methyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound CN1C=CC(CN2C(CC3=CC=4OC[C@@H](OC=4C=C3C2)C=2C=CC(OCC=3C=C(Cl)C(Cl)=CC=3)=CC=2)C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)C(O)=O)=N1 ASDKMUIOKAYBEX-PPCQQBJASA-N 0.000 description 1
• DUEOZWMHVORFFB-WLESTYKDSA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(2-fluoro-6-methoxyphenyl)methyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound COC1=CC=CC(F)=C1CN1C(C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)C(O)=O)CC2=CC(OC[C@@H](O3)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)=C3C=C2C1 DUEOZWMHVORFFB-WLESTYKDSA-N 0.000 description 1
• YYEVCNKQVKZUTH-SIORXBAWSA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[2-(trifluoromethyl)benzoyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C=1C(=CC=CC=1)C(F)(F)F)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 YYEVCNKQVKZUTH-SIORXBAWSA-N 0.000 description 1
• VVIYBXRUKGBNOM-CCAUFTTCSA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[[(1s)-1-phenylethyl]carbamoyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@H](NC(=O)C1CC2=CC=3OC[C@@H](OC=3C=C2CN1C(=O)N[C@@H](C)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 VVIYBXRUKGBNOM-CCAUFTTCSA-N 0.000 description 1
• KHULCJBLCDFJMU-KNGBNFTKSA-N (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-ethyl-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoic acid Chemical compound C([C@H](NC(=O)C1CC2=CC=3OC[C@@H](OC=3C=C2CN1CC)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 KHULCJBLCDFJMU-KNGBNFTKSA-N 0.000 description 1
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• AXGHPDQOHHPZPQ-SQKCAUCHSA-N methyl (2S)-2-amino-3-[4-(6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)phenyl]propanoate dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC2=C1CCC2 AXGHPDQOHHPZPQ-SQKCAUCHSA-N 0.000 description 1
• CPHKMDBOUKBUGH-LJQBVWCNSA-N methyl (2r)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoate;hydrochloride Chemical compound Cl.C([C@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 CPHKMDBOUKBUGH-LJQBVWCNSA-N 0.000 description 1
• DHTOBCRRDQQFDF-CUOYHRFUSA-N methyl (2s)-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-(4-phenylphenyl)propanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 DHTOBCRRDQQFDF-CUOYHRFUSA-N 0.000 description 1
• IKJYXHJKOWUBIE-YLJLHNITSA-N methyl (2s)-2-[[(3s,8s)-3-[3-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=C(OCC=2C=C(Cl)C(Cl)=CC=2)C=CC=1)C(C=C1)=CC=C1C1=CC=NC(C)=C1C IKJYXHJKOWUBIE-YLJLHNITSA-N 0.000 description 1
• ONIFDNPOWHWTKN-IIRRWZJPSA-N methyl (2s)-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)oxyphenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1OC1=CC=NC(C)=C1C ONIFDNPOWHWTKN-IIRRWZJPSA-N 0.000 description 1
• QESUUXXYIDFJBN-VHYZKNOSSA-N methyl (2s)-2-[[(3s,8s)-7-benzoyl-3-(4-hydroxyphenyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(O)=CC=1)C(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=NC(C)=C1C QESUUXXYIDFJBN-VHYZKNOSSA-N 0.000 description 1
• OOVDEPZODSXAMU-MERQFXBCSA-N methyl (2s)-2-amino-3-(4-hydroxyphenyl)-2-methylpropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@](C)(N)CC1=CC=C(O)C=C1 OOVDEPZODSXAMU-MERQFXBCSA-N 0.000 description 1
• ZABGKWGFGXZMDE-HNNXBMFYSA-N methyl (2s)-2-amino-3-(4-phenylphenyl)propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=CC=C1 ZABGKWGFGXZMDE-HNNXBMFYSA-N 0.000 description 1
• WCDKVWFWDPQMCU-GXKRWWSZSA-N methyl (2s)-2-amino-3-(4-pyridazin-4-ylphenyl)propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NN=C1 WCDKVWFWDPQMCU-GXKRWWSZSA-N 0.000 description 1
• JVESDFDDVMRUSG-UTLKBRERSA-N methyl (2s)-2-amino-3-(4-pyridin-3-yloxyphenyl)propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC1=CC=CN=C1 JVESDFDDVMRUSG-UTLKBRERSA-N 0.000 description 1
• YNTJMRFPJOFPBB-UTLKBRERSA-N methyl (2s)-2-amino-3-(4-pyridin-3-ylphenyl)propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=CN=C1 YNTJMRFPJOFPBB-UTLKBRERSA-N 0.000 description 1
• GLGPKPQQVWBNHT-UTLKBRERSA-N methyl (2s)-2-amino-3-(4-pyridin-4-yloxyphenyl)propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC1=CC=NC=C1 GLGPKPQQVWBNHT-UTLKBRERSA-N 0.000 description 1
• KUYHWWRTSRRQBZ-AWEZNQCLSA-N methyl (2s)-2-amino-3-(4-pyridin-4-ylphenyl)propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC=C1 KUYHWWRTSRRQBZ-AWEZNQCLSA-N 0.000 description 1
• QZJVXDVJAKAXBA-UQKRIMTDSA-N methyl (2s)-2-amino-3-(4-pyridin-4-ylphenyl)propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC=C1 QZJVXDVJAKAXBA-UQKRIMTDSA-N 0.000 description 1
• PIUNBHWGWRIUQG-LTCKWSDVSA-N methyl (2s)-2-amino-3-(4-pyrimidin-4-ylphenyl)propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC=N1 PIUNBHWGWRIUQG-LTCKWSDVSA-N 0.000 description 1
• LDJINKGMHULDDJ-RMRYJAPISA-N methyl (2s)-2-amino-3-(4-quinolin-4-ylphenyl)propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC2=CC=CC=C12 LDJINKGMHULDDJ-RMRYJAPISA-N 0.000 description 1
• QKUJYEXCHKMXCJ-NXCGSPNESA-N methyl (2s)-2-amino-3-[(2s)-2-[3-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]propanoate;hydrochloride Chemical compound Cl.C=1C([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N)C(=O)OC)=CC=CC=1OCC1=CC=C(Cl)C(Cl)=C1 QKUJYEXCHKMXCJ-NXCGSPNESA-N 0.000 description 1
• QQPJRKNRJFFDGM-XUZZJYLKSA-N methyl (2s)-2-amino-3-[(2s)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]propanoate Chemical compound C1=CC([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 QQPJRKNRJFFDGM-XUZZJYLKSA-N 0.000 description 1
• AEYXEFACMZSBHG-CHXZROHQSA-N methyl (2s)-2-amino-3-[2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]propanoate;hydrochloride Chemical compound Cl.C1OC2=CC(C[C@H](N)C(=O)OC)=CC=C2OC1C(C=C1)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 AEYXEFACMZSBHG-CHXZROHQSA-N 0.000 description 1
• WZQQREOQRMDGBG-GXKRWWSZSA-N methyl (2s)-2-amino-3-[4-(1-methylpyrazol-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CN(C)N=C1 WZQQREOQRMDGBG-GXKRWWSZSA-N 0.000 description 1
• BOFVVYUFGLYKPK-ZOWNYOTGSA-N methyl (2s)-2-amino-3-[4-(2,5-dimethylpyrazol-3-yl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC(C)=NN1C BOFVVYUFGLYKPK-ZOWNYOTGSA-N 0.000 description 1
• KZJUKZLKCIDTJH-SQKCAUCHSA-N methyl (2s)-2-amino-3-[4-(2,5-dimethylpyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC(C)=NC=C1C KZJUKZLKCIDTJH-SQKCAUCHSA-N 0.000 description 1
• ADUBVOOKGZJCOK-LTCKWSDVSA-N methyl (2s)-2-amino-3-[4-(2,6-difluoropyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC(F)=NC(F)=C1 ADUBVOOKGZJCOK-LTCKWSDVSA-N 0.000 description 1
• WFIWHWIZKZQLQS-SQKCAUCHSA-N methyl (2s)-2-amino-3-[4-(2,6-dimethylpyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC(C)=NC(C)=C1 WFIWHWIZKZQLQS-SQKCAUCHSA-N 0.000 description 1
• ZOXHCJRTMIFOOK-GXKRWWSZSA-N methyl (2s)-2-amino-3-[4-(2-aminopyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC(N)=C1 ZOXHCJRTMIFOOK-GXKRWWSZSA-N 0.000 description 1
• MMRUERBYEIBSEU-LTCKWSDVSA-N methyl (2s)-2-amino-3-[4-(2-aminopyrimidin-5-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CN=C(N)N=C1 MMRUERBYEIBSEU-LTCKWSDVSA-N 0.000 description 1
• FXKGJSZSGGMWLG-SQKCAUCHSA-N methyl (2s)-2-amino-3-[4-(2-ethylpyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=NC(CC)=CC(C=2C=CC(C[C@H](N)C(=O)OC)=CC=2)=C1 FXKGJSZSGGMWLG-SQKCAUCHSA-N 0.000 description 1
• HTKCBDIOOBGMHO-GXKRWWSZSA-N methyl (2s)-2-amino-3-[4-(2-fluoropyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC(F)=C1 HTKCBDIOOBGMHO-GXKRWWSZSA-N 0.000 description 1
• VEEWDEKPXLEUIK-UTLKBRERSA-N methyl (2s)-2-amino-3-[4-(2-methoxypyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC(OC)=C1 VEEWDEKPXLEUIK-UTLKBRERSA-N 0.000 description 1
• HBIVMGDVKRRTDK-LTCKWSDVSA-N methyl (2s)-2-amino-3-[4-(2-methylpyrazol-3-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NN1C HBIVMGDVKRRTDK-LTCKWSDVSA-N 0.000 description 1
• QLEXCAHRRZTNCN-CKUXDGONSA-N methyl (2s)-2-amino-3-[4-(2-methylpyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC(C)=C1 QLEXCAHRRZTNCN-CKUXDGONSA-N 0.000 description 1
• KDBKOPUMAFHOPX-SQKCAUCHSA-N methyl (2s)-2-amino-3-[4-(2-propan-2-ylpyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC(C(C)C)=C1 KDBKOPUMAFHOPX-SQKCAUCHSA-N 0.000 description 1
• SCYCMIXUYFJDKF-RMRYJAPISA-N methyl (2s)-2-amino-3-[4-(2-propylpyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=NC(CCC)=CC(C=2C=CC(C[C@H](N)C(=O)OC)=CC=2)=C1 SCYCMIXUYFJDKF-RMRYJAPISA-N 0.000 description 1
• YHERHCNWQURTLQ-UTLKBRERSA-N methyl (2s)-2-amino-3-[4-(3-fluoropyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC=C1F YHERHCNWQURTLQ-UTLKBRERSA-N 0.000 description 1
• GSOMWHZFPZNEMX-UTLKBRERSA-N methyl (2s)-2-amino-3-[4-(3-methoxypyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC=C1OC GSOMWHZFPZNEMX-UTLKBRERSA-N 0.000 description 1
• JTPMAMGFSDCWSW-SQKCAUCHSA-N methyl (2s)-2-amino-3-[4-(3-methylphenyl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=CC(C)=C1 JTPMAMGFSDCWSW-SQKCAUCHSA-N 0.000 description 1
• QGCPUNGQJSRSQM-NTISSMGPSA-N methyl (2s)-2-amino-3-[4-(4-cyano-3-fluorophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C#N)C(F)=C1 QGCPUNGQJSRSQM-NTISSMGPSA-N 0.000 description 1
• NMCROLOVMHXPSL-HNNXBMFYSA-N methyl (2s)-2-amino-3-[4-(4-fluorophenyl)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(F)C=C1 NMCROLOVMHXPSL-HNNXBMFYSA-N 0.000 description 1
• HNAUTRSQBWZHGJ-NTISSMGPSA-N methyl (2s)-2-amino-3-[4-(4-methoxyphenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(OC)C=C1 HNAUTRSQBWZHGJ-NTISSMGPSA-N 0.000 description 1
• BOZVHPFMZPKTRE-INIZCTEOSA-N methyl (2s)-2-amino-3-[4-(4-methylphenyl)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C)C=C1 BOZVHPFMZPKTRE-INIZCTEOSA-N 0.000 description 1
• NCIPTOKUHQWFBY-NTISSMGPSA-N methyl (2s)-2-amino-3-[4-(4-methylphenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C)C=C1 NCIPTOKUHQWFBY-NTISSMGPSA-N 0.000 description 1
• FWBUCIPBENKDCL-GXKRWWSZSA-N methyl (2s)-2-amino-3-[4-(6-aminopyridin-3-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(N)N=C1 FWBUCIPBENKDCL-GXKRWWSZSA-N 0.000 description 1
• SNRYGKFTMWDHME-CKUXDGONSA-N methyl (2s)-2-amino-3-[4-(6-cyanopyridin-3-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C#N)N=C1 SNRYGKFTMWDHME-CKUXDGONSA-N 0.000 description 1
• UZQNTNOCMBHTHJ-CKUXDGONSA-N methyl (2s)-2-amino-3-[4-(6-methylpyridin-3-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C)N=C1 UZQNTNOCMBHTHJ-CKUXDGONSA-N 0.000 description 1
• MLILKESKEVNHKE-CKUXDGONSA-N methyl (2s)-2-amino-3-[4-[2-(hydroxymethyl)pyridin-4-yl]phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC(CO)=C1 MLILKESKEVNHKE-CKUXDGONSA-N 0.000 description 1
• WNBCFEWMVAWWRM-GXKRWWSZSA-N methyl (2s)-2-amino-3-[4-[2-(trifluoromethyl)pyridin-4-yl]phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC(C(F)(F)F)=C1 WNBCFEWMVAWWRM-GXKRWWSZSA-N 0.000 description 1
• HRJQWRTUPVHRBT-RSAXXLAASA-N methyl (2s)-2-amino-3-[4-[4-(trifluoromethyl)phenyl]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C(F)(F)F)C=C1 HRJQWRTUPVHRBT-RSAXXLAASA-N 0.000 description 1
• GJKXBQRPEONFLG-CKUXDGONSA-N methyl (2s)-2-amino-3-[4-[6-(dimethylamino)pyridin-3-yl]phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(N(C)C)N=C1 GJKXBQRPEONFLG-CKUXDGONSA-N 0.000 description 1
• HTGCHTIDQKPGIA-CKUXDGONSA-N methyl (2s)-2-amino-3-[4-[6-(hydroxymethyl)pyridin-3-yl]phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(CO)N=C1 HTGCHTIDQKPGIA-CKUXDGONSA-N 0.000 description 1
• OLODBSAKHNXKPY-NSHDSACASA-N methyl (2s)-3-(3-bromo-4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=C(O)C(Br)=C1 OLODBSAKHNXKPY-NSHDSACASA-N 0.000 description 1
• ZOSBOGJFIOVFCW-ODTVBPJYSA-N methyl (2s)-3-[(2s)-2-(4-acetyloxyphenyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(4-nitrophenyl)sulfonyl-[(1s)-1-phenylpropyl]amino]propanoate Chemical compound C1([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N([C@@H](CC)C=2C=CC=CC=2)S(=O)(=O)C=2C=CC(=CC=2)[N+]([O-])=O)C(=O)OC)=CC=C(OC(C)=O)C=C1 ZOSBOGJFIOVFCW-ODTVBPJYSA-N 0.000 description 1
• YLBJCHJGSFAUQU-QFBILLFUSA-N methyl (2s)-3-[(2s)-2-(4-acetyloxyphenyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2-aminopropanoate Chemical compound C1([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N)C(=O)OC)=CC=C(OC(C)=O)C=C1 YLBJCHJGSFAUQU-QFBILLFUSA-N 0.000 description 1
• XVWMHDVHFPHVOB-RPLLCQBOSA-N methyl (2s)-3-[(2s)-2-[3-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C=1C([C@@H]2OC3=CC=C(C=C3OC2)C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=CC=1OCC1=CC=C(Cl)C(Cl)=C1 XVWMHDVHFPHVOB-RPLLCQBOSA-N 0.000 description 1
• WGXVUDWIBURIEX-VHYZKNOSSA-N methyl (2s)-3-[(2s)-2-[3-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[(4-nitrophenyl)sulfonyl-[(1s)-1-phenylpropyl]amino]propanoate Chemical compound C=1C([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N([C@@H](CC)C=2C=CC=CC=2)S(=O)(=O)C=2C=CC(=CC=2)[N+]([O-])=O)C(=O)OC)=CC=CC=1OCC1=CC=C(Cl)C(Cl)=C1 WGXVUDWIBURIEX-VHYZKNOSSA-N 0.000 description 1
• PPAPOWBYYFKEST-WSZLSEGOSA-N methyl (2s)-3-[(2s)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-[[(1s)-1-phenylpropyl]amino]propanoate Chemical compound C1=CC([C@@H]2OC3=CC=C(C=C3OC2)C[C@H](N[C@@H](CC)C=2C=CC=CC=2)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 PPAPOWBYYFKEST-WSZLSEGOSA-N 0.000 description 1
• HEDULFULVLLAHM-BXXZMZEQSA-N methyl (2s)-3-[2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3-dihydro-1,4-benzodioxin-6-yl]-2-(propan-2-ylamino)propanoate Chemical compound C1OC2=CC(C[C@@H](C(=O)OC)NC(C)C)=CC=C2OC1C(C=C1)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 HEDULFULVLLAHM-BXXZMZEQSA-N 0.000 description 1
• WVANWKCNVUQWKC-CUOYHRFUSA-N methyl (2s)-3-[4-(4-chlorophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 WVANWKCNVUQWKC-CUOYHRFUSA-N 0.000 description 1
• HSASQFQFOHAJFQ-XBEPADRLSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-(4-ethoxyphenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoate;hydrochloride Chemical compound Cl.C1=CC(OCC)=CC=C1[C@@H]1OC2=CC(CNC(C3)C(=O)N[C@@H](CC=4C=CC(=CC=4)C=4C=CC(=CC=4)C#N)C(=O)OC)=C3C=C2OC1 HSASQFQFOHAJFQ-XBEPADRLSA-N 0.000 description 1
• KQGKFGPLFWMQGN-CUOYHRFUSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorobenzoyl)amino]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(NC(=O)C=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 KQGKFGPLFWMQGN-CUOYHRFUSA-N 0.000 description 1
• YQCZOZPZVSCMDE-NVJPACMSSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-2-methylpropanoate;hydrochloride Chemical compound Cl.C([C@@](C)(C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 YQCZOZPZVSCMDE-NVJPACMSSA-N 0.000 description 1
• XELNJDJVFFLKMR-LLSVSLFMSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(pyridin-2-ylmethyl)-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)CC=1N=CC=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 XELNJDJVFFLKMR-LLSVSLFMSA-N 0.000 description 1
• CPHKMDBOUKBUGH-ROYBKCIRSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]propanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)OC)NC(=O)[C@H]1NCC2=CC=3O[C@H](COC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 CPHKMDBOUKBUGH-ROYBKCIRSA-N 0.000 description 1
• SFBFOJAPSYMOEM-SANMLTNESA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-methyl-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C([C@@](C)(C(=O)OC)NC(=O)OCC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 SFBFOJAPSYMOEM-SANMLTNESA-N 0.000 description 1
• FXRUEMUFUNIGQC-SFHVURJKSA-N methyl (2s)-3-[4-[2-(hydroxymethyl)pyridin-4-yl]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1C1=CC=NC(CO)=C1 FXRUEMUFUNIGQC-SFHVURJKSA-N 0.000 description 1
• DYKLPYKFQICXER-JHFJJOSTSA-N methyl (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylate Chemical compound C1=CC([C@H]2OC=3C=C4CN([C@@H](CC4=CC=3OC2)C(=O)OC)[C@@H](CC)C=2C=CC=CC=2)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 DYKLPYKFQICXER-JHFJJOSTSA-N 0.000 description 1
• FZOKCBXIRHOWQE-MPSNESSQSA-N methyl (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-propan-2-yl-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylate Chemical compound C1=CC([C@H]2COC=3C=C4CC(N(CC4=CC=3O2)C(C)C)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 FZOKCBXIRHOWQE-MPSNESSQSA-N 0.000 description 1
• LPDXYVVKLAIOTG-QRPNPIFTSA-N methyl (3s)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate;hydrochloride Chemical compound Cl.OC1=C(O)C=C2CN[C@H](C(=O)OC)CC2=C1 LPDXYVVKLAIOTG-QRPNPIFTSA-N 0.000 description 1
• AWICHGXVMPHEBI-QXTIUPHPSA-N methyl (3s,8s)-3-(4-acetyloxyphenyl)-7-[(1s)-1-phenylpropyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylate Chemical compound C1([C@@H]2OC=3C=C4CN([C@@H](CC4=CC=3OC2)C(=O)OC)[C@@H](CC)C=2C=CC=CC=2)=CC=C(OC(C)=O)C=C1 AWICHGXVMPHEBI-QXTIUPHPSA-N 0.000 description 1
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