SG174205A1 - Substituted azoanthracene derivatives, pharmaceutical compositions, and methods of use thereof - Google Patents

Info

Publication number

SG174205A1

SG174205A1 SG2011063112A SG2011063112A SG174205A1 SG 174205 A1 SG174205 A1 SG 174205A1 SG 2011063112 A SG2011063112 A SG 2011063112A SG 2011063112 A SG2011063112 A SG 2011063112A SG 174205 A1 SG174205 A1 SG 174205A1

Authority

SG

Singapore

Prior art keywords

independently selected

optionally substituted

phenyl

substituents independently

heteroaryl

Prior art date

2009-03-30

Links

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• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 28
• 238000000034 method Methods 0.000 title claims description 119
• 150000001875 compounds Chemical class 0.000 claims abstract description 395
• 239000000203 mixture Substances 0.000 claims abstract description 155
• 150000003839 salts Chemical class 0.000 claims abstract description 34
• 101001015516 Homo sapiens Glucagon-like peptide 1 receptor Proteins 0.000 claims abstract description 8
• 230000009286 beneficial effect Effects 0.000 claims abstract description 8
• 201000000083 maturity-onset diabetes of the young type 1 Diseases 0.000 claims abstract description 7
• -1 heterocyclylene Chemical group 0.000 claims description 542
• 125000001424 substituent group Chemical group 0.000 claims description 290
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 253
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 222
• 125000000217 alkyl group Chemical group 0.000 claims description 122
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 103
• 125000000623 heterocyclic group Chemical group 0.000 claims description 87
• 125000001072 heteroaryl group Chemical group 0.000 claims description 82
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 76
• 229910052757 nitrogen Inorganic materials 0.000 claims description 72
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 69
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 68
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 65
• 229910052736 halogen Inorganic materials 0.000 claims description 58
• 229910052739 hydrogen Inorganic materials 0.000 claims description 57
• 239000001257 hydrogen Substances 0.000 claims description 50
• 125000003118 aryl group Chemical group 0.000 claims description 48
• 150000002367 halogens Chemical class 0.000 claims description 47
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 43
• 125000000304 alkynyl group Chemical group 0.000 claims description 38
• 125000003342 alkenyl group Chemical group 0.000 claims description 37
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
• 238000006467 substitution reaction Methods 0.000 claims description 32
• 125000002947 alkylene group Chemical group 0.000 claims description 30
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 26
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 25
• 125000004419 alkynylene group Chemical group 0.000 claims description 17
• 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 17
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
• 125000004429 atom Chemical group 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 16
• 125000004367 cycloalkylaryl group Chemical group 0.000 claims description 15
• 125000005215 cycloalkylheteroaryl group Chemical group 0.000 claims description 15
• 125000005842 heteroatom Chemical group 0.000 claims description 15
• 125000002971 oxazolyl group Chemical group 0.000 claims description 15
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 13
• 125000004450 alkenylene group Chemical group 0.000 claims description 13
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
• 125000005218 alkyleneheteroaryl group Chemical group 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 239000011593 sulfur Chemical group 0.000 claims description 12
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
• 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 claims description 11
• 239000002253 acid Substances 0.000 claims description 11
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 11
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 10
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
• 239000001301 oxygen Substances 0.000 claims description 10
• 229920000728 polyester Polymers 0.000 claims description 10
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
• 125000005275 alkylenearyl group Chemical group 0.000 claims description 8
• 150000002431 hydrogen Chemical class 0.000 claims description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
• 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 claims description 7
• 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 7
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 7
• 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
• 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
• 208000002705 Glucose Intolerance Diseases 0.000 claims description 6
• 125000000732 arylene group Chemical group 0.000 claims description 6
• 125000005549 heteroarylene group Chemical group 0.000 claims description 6
• 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 claims description 6
• 230000004913 activation Effects 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 5
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
• 239000004480 active ingredient Substances 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• 239000008103 glucose Substances 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 201000009104 prediabetes syndrome Diseases 0.000 claims description 4
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 3
• 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 claims description 3
• 206010022489 Insulin Resistance Diseases 0.000 claims description 3
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 201000001421 hyperglycemia Diseases 0.000 claims description 3
• 208000030159 metabolic disease Diseases 0.000 claims description 3
• 125000004434 sulfur atom 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
• 201000001320 Atherosclerosis Diseases 0.000 claims description 2
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 claims description 2
• 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 2
• 102000051325 Glucagon Human genes 0.000 claims description 2
• 108060003199 Glucagon Proteins 0.000 claims description 2
• 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 2
• 208000031226 Hyperlipidaemia Diseases 0.000 claims description 2
• 206010020772 Hypertension Diseases 0.000 claims description 2
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
• 208000008589 Obesity Diseases 0.000 claims description 2
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
• 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
• 239000008280 blood Substances 0.000 claims description 2
• 210000004369 blood Anatomy 0.000 claims description 2
• 230000001419 dependent effect Effects 0.000 claims description 2
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=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](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)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(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 2
• 229960004666 glucagon Drugs 0.000 claims description 2
• 208000006575 hypertriglyceridemia Diseases 0.000 claims description 2
• 230000001771 impaired effect Effects 0.000 claims description 2
• 230000003914 insulin secretion Effects 0.000 claims description 2
• 235000020824 obesity Nutrition 0.000 claims description 2
• 208000011580 syndromic disease Diseases 0.000 claims description 2
• 230000029663 wound healing Effects 0.000 claims description 2
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims 1
• 206010012689 Diabetic retinopathy Diseases 0.000 claims 1
• 208000030814 Eating disease Diseases 0.000 claims 1
• 208000019454 Feeding and Eating disease Diseases 0.000 claims 1
• 208000033679 diabetic kidney disease Diseases 0.000 claims 1
• 235000014632 disordered eating Nutrition 0.000 claims 1
• 230000030136 gastric emptying Effects 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
• 230000028327 secretion Effects 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 33
• 201000010099 disease Diseases 0.000 abstract description 17
• 208000035475 disorder Diseases 0.000 abstract description 16
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 337
• 239000000460 chlorine Substances 0.000 description 270
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 227
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 150
• 235000019439 ethyl acetate Nutrition 0.000 description 143
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
• 239000000243 solution Substances 0.000 description 106
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 99
• 238000006243 chemical reaction Methods 0.000 description 94
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 94
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 92
• 239000000047 product Substances 0.000 description 80
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 76
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 76
• 239000012267 brine Substances 0.000 description 73
• 239000012044 organic layer Substances 0.000 description 71
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
• 239000011541 reaction mixture Substances 0.000 description 68
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 64
• 238000003818 flash chromatography Methods 0.000 description 58
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
• 239000000741 silica gel Substances 0.000 description 51
• 229910002027 silica gel Inorganic materials 0.000 description 51
• 229960001866 silicon dioxide Drugs 0.000 description 51
• 238000005481 NMR spectroscopy Methods 0.000 description 47
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 45
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 44
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 42
• 239000007787 solid Substances 0.000 description 42
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
• 238000003756 stirring Methods 0.000 description 38
• 239000010410 layer Substances 0.000 description 37
• 239000002904 solvent Substances 0.000 description 35
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
• 230000002829 reductive effect Effects 0.000 description 33
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 30
• 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 30
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 27
• 239000011734 sodium Substances 0.000 description 27
• 229910052938 sodium sulfate Inorganic materials 0.000 description 27
• 235000011152 sodium sulphate Nutrition 0.000 description 27
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
• JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 24
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 23
• 125000004432 carbon atom Chemical group C* 0.000 description 23
• 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 23
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 22
• 238000001035 drying Methods 0.000 description 21
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 21
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 21
• 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 21
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
• 239000003921 oil Substances 0.000 description 19
• 235000019198 oils Nutrition 0.000 description 19
• 150000001412 amines Chemical class 0.000 description 18
• 239000000284 extract Substances 0.000 description 17
• 229930040373 Paraformaldehyde Natural products 0.000 description 16
• 229920002866 paraformaldehyde Polymers 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 16
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 238000004440 column chromatography Methods 0.000 description 14
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
• 238000002360 preparation method Methods 0.000 description 13
• 238000000746 purification Methods 0.000 description 13
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• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 11
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 11
• 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 11
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 10
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 10
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 10
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• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 10
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 10
• 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 description 10
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• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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• CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 10
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• 239000012043 crude product Substances 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
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• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 9
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 9
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 9
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• 238000010992 reflux Methods 0.000 description 9
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• 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 9
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 8
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• 125000001786 isothiazolyl group Chemical group 0.000 description 2
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• GTPSYWNNEXIAGW-YLJLHNITSA-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)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-YLJLHNITSA-N 0.000 description 2
• 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 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
• 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 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
• 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 2
• 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 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
• 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
• 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
• KSKRPHSHPQTWJK-HHHXNRCGSA-N methyl 3-[(2S)-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-HHHXNRCGSA-N 0.000 description 2
• 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 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
• 150000004702 methyl esters Chemical class 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
• RXLYNDDWAMZCDD-UHFFFAOYSA-N n-(4-methyl-5-nitropyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC(C)=C([N+]([O-])=O)C=N1 RXLYNDDWAMZCDD-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
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 102000004164 orphan nuclear receptors Human genes 0.000 description 2
• 108090000629 orphan nuclear receptors Proteins 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
• 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
• 229920002223 polystyrene Polymers 0.000 description 2
• 229940095574 propionic acid Drugs 0.000 description 2
• MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical group CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 238000006268 reductive amination reaction Methods 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 229940124530 sulfonamide Drugs 0.000 description 2
• 150000003456 sulfonamides Chemical class 0.000 description 2
• 238000006277 sulfonation reaction Methods 0.000 description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
• XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 2
• 229910052815 sulfur oxide Inorganic materials 0.000 description 2
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
• 238000003786 synthesis reaction Methods 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
• 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
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 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
• 150000003672 ureas Chemical class 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• 229920002554 vinyl polymer Polymers 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• NPLZNDDFVCGRAG-UHFFFAOYSA-N (2-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1C#N NPLZNDDFVCGRAG-UHFFFAOYSA-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
• GVVCHDNSTMEUCS-MUGJNUQGSA-N (2s,5s)-1-[2-[(2s,5s)-2,5-diethylphospholan-1-yl]phenyl]-2,5-diethylphospholane Chemical compound CC[C@H]1CC[C@H](CC)P1C1=CC=CC=C1P1[C@@H](CC)CC[C@@H]1CC GVVCHDNSTMEUCS-MUGJNUQGSA-N 0.000 description 1
• GFUZTXDPFFUWSH-IGKIAQTJSA-N (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(2-methylpropan-2-yl)oxycarbonyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid Chemical compound C1=CC([C@H]2OC=3C=C4CN([C@@H](CC4=CC=3OC2)C(O)=O)C(=O)OC(C)(C)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 GFUZTXDPFFUWSH-IGKIAQTJSA-N 0.000 description 1
• GFUZTXDPFFUWSH-LFHRXCRSSA-N (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(2-methylpropan-2-yl)oxycarbonyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid Chemical compound C1=CC([C@@H]2OC=3C=C4CN(C(CC4=CC=3OC2)C(O)=O)C(=O)OC(C)(C)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 GFUZTXDPFFUWSH-LFHRXCRSSA-N 0.000 description 1
• ABYPRALCFKJRCP-ZETCQYMHSA-N (3s)-6,7-dihydroxy-3,4-dihydro-1h-isoquinoline-2,3-dicarboxylic acid Chemical compound OC1=C(O)C=C2CN(C(O)=O)[C@H](C(=O)O)CC2=C1 ABYPRALCFKJRCP-ZETCQYMHSA-N 0.000 description 1
• GFUZTXDPFFUWSH-RPLLCQBOSA-N (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(2-methylpropan-2-yl)oxycarbonyl]-3,6,8,9-tetrahydro-2h-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid Chemical compound C1=CC([C@@H]2OC=3C=C4CN([C@@H](CC4=CC=3OC2)C(O)=O)C(=O)OC(C)(C)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 GFUZTXDPFFUWSH-RPLLCQBOSA-N 0.000 description 1
• CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 1
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
• 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 description 1
• 125000001506 1,2,3-triazol-5-yl group Chemical group [H]N1N=NC([H])=C1[*] 0.000 description 1
• 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 1
• 125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• YZIFVWOCPGPNHB-UHFFFAOYSA-N 1,2-dichloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C(Cl)=C1 YZIFVWOCPGPNHB-UHFFFAOYSA-N 0.000 description 1
• 125000004317 1,3,5-triazin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=N1 0.000 description 1
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
• VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
• YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
• WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
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• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• 150000002009 diols Chemical class 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• QGBQGMHXBSLYLZ-UHFFFAOYSA-N ditert-butyl-(1-naphthalen-1-ylnaphthalen-2-yl)phosphane Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3P(C(C)(C)C)C(C)(C)C)=CC=CC2=C1 QGBQGMHXBSLYLZ-UHFFFAOYSA-N 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
• WHQLQYRFIHPMNA-UHFFFAOYSA-N ethyl acetate;oxolane Chemical compound C1CCOC1.CCOC(C)=O WHQLQYRFIHPMNA-UHFFFAOYSA-N 0.000 description 1
• 210000001508 eye Anatomy 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000012631 food intake Nutrition 0.000 description 1
• 239000008098 formaldehyde solution Substances 0.000 description 1
• 125000004281 furazan-3-yl group Chemical group [H]C1=NON=C1* 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 230000004110 gluconeogenesis Effects 0.000 description 1
• 230000004153 glucose metabolism Effects 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
• 201000008980 hyperinsulinism Diseases 0.000 description 1
• 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
• 125000004282 imidazolidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])N([H])C1([H])* 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=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](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)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)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 description 1
• 239000000859 incretin Substances 0.000 description 1
• 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 1
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 229910017053 inorganic salt Inorganic materials 0.000 description 1
• 229940125396 insulin Drugs 0.000 description 1
• 238000012739 integrated shape imaging system Methods 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000004552 isoquinolin-4-yl group Chemical group C1=NC=C(C2=CC=CC=C12)* 0.000 description 1
• QUFUUBBLCOBJPH-UHFFFAOYSA-N isoquinoline-7-carboxylic acid Chemical compound C1=CN=CC2=CC(C(=O)O)=CC=C21 QUFUUBBLCOBJPH-UHFFFAOYSA-N 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 125000004285 isoxazolidin-3-yl group Chemical group [H]N1OC([H])([H])C([H])([H])C1([H])* 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000037356 lipid metabolism Effects 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000009988 metabolic benefit Effects 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 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 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
• 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
• 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
• 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
• 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
• 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 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
• 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
• CHHIPTRCZWLGBL-CKUXDGONSA-N methyl (2s)-2-amino-3-[4-(3-methylpyridin-4-yl)phenyl]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC=C1C CHHIPTRCZWLGBL-CKUXDGONSA-N 0.000 description 1
• SWJBPEXDUCZVHQ-HNNXBMFYSA-N methyl (2s)-2-amino-3-[4-(4-chlorophenyl)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(Cl)C=C1 SWJBPEXDUCZVHQ-HNNXBMFYSA-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
• 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 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
• ZXBQZVMJOHLRPQ-INIZCTEOSA-N methyl (2s)-2-amino-3-[4-(4-methoxyphenyl)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(OC)C=C1 ZXBQZVMJOHLRPQ-INIZCTEOSA-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
• 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
• 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
• 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 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
• 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 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
• 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
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