JP2012530081A - スフィンゴシン１リン酸１（ｓ１ｐ１）受容体アゴニストとして用いるためのチアゾールまたはチアジアゾール誘導体 - Google Patents

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Publication number

JP2012530081A

JP2012530081A JP2012515319A JP2012515319A JP2012530081A JP 2012530081 A JP2012530081 A JP 2012530081A JP 2012515319 A JP2012515319 A JP 2012515319A JP 2012515319 A JP2012515319 A JP 2012515319A JP 2012530081 A JP2012530081 A JP 2012530081A

Authority

JP

Japan

Prior art keywords

oxy

methylethyl

phenyl

mmol

thiadiazol

Prior art date

2009-06-19

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Withdrawn

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• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 title abstract 2
• 150000004867 thiadiazoles Chemical class 0.000 title abstract 2
• -1 sphingosine monophosphate Chemical class 0.000 title description 44
• 239000000018 receptor agonist Substances 0.000 title description 4
• 229940044601 receptor agonist Drugs 0.000 title description 4
• WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 title description 2
• 150000003839 salts Chemical class 0.000 claims abstract description 57
• 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 claims abstract description 24
• 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 claims abstract description 24
• 238000000034 method Methods 0.000 claims abstract description 17
• 230000001404 mediated effect Effects 0.000 claims abstract description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• 150000001875 compounds Chemical class 0.000 claims description 101
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 24
• 229910052757 nitrogen Inorganic materials 0.000 claims description 24
• 201000010099 disease Diseases 0.000 claims description 17
• 239000001257 hydrogen Substances 0.000 claims description 17
• 229910052739 hydrogen Inorganic materials 0.000 claims description 17
• 125000000217 alkyl group Chemical group 0.000 claims description 16
• 208000035475 disorder Diseases 0.000 claims description 13
• 206010025135 lupus erythematosus Diseases 0.000 claims description 13
• 206010028980 Neoplasm Diseases 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
• 201000004681 Psoriasis Diseases 0.000 claims description 10
• 201000006417 multiple sclerosis Diseases 0.000 claims description 10
• HOZSSWZKSCQQPY-UHFFFAOYSA-N 4-[6-[2-(3-cyano-4-propan-2-yloxyphenyl)-1,3-thiazol-5-yl]-5-ethyl-3,4-dihydro-1h-isoquinolin-2-yl]butanoic acid Chemical compound CCC1=C2CCN(CCCC(O)=O)CC2=CC=C1C(S1)=CN=C1C1=CC=C(OC(C)C)C(C#N)=C1 HOZSSWZKSCQQPY-UHFFFAOYSA-N 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 150000002367 halogens Chemical class 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• BFVYMCYGZXSCQF-UHFFFAOYSA-N 3-[6-[2-(3-cyano-4-propan-2-yloxyphenyl)-1,3-thiazol-5-yl]-5-ethyl-3,4-dihydro-1h-isoquinolin-2-yl]propanoic acid Chemical compound CCC1=C2CCN(CCC(O)=O)CC2=CC=C1C(S1)=CN=C1C1=CC=C(OC(C)C)C(C#N)=C1 BFVYMCYGZXSCQF-UHFFFAOYSA-N 0.000 claims description 7
• 230000033115 angiogenesis Effects 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 238000002054 transplantation Methods 0.000 claims description 7
• HIYZNZOEFYXPOH-UHFFFAOYSA-N 3-[6-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-5-ethyl-3,4-dihydro-1h-isoquinolin-2-yl]propanoic acid Chemical compound CCC1=C2CCN(CCC(O)=O)CC2=CC=C1C(S1)=NN=C1C1=CC=C(OC(C)C)C(Cl)=C1 HIYZNZOEFYXPOH-UHFFFAOYSA-N 0.000 claims description 6
• 208000023275 Autoimmune disease Diseases 0.000 claims description 6
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 6
• 208000011231 Crohn disease Diseases 0.000 claims description 6
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
• 206010027476 Metastases Diseases 0.000 claims description 6
• 208000002193 Pain Diseases 0.000 claims description 6
• 206010063837 Reperfusion injury Diseases 0.000 claims description 6
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 6
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
• 230000001154 acute effect Effects 0.000 claims description 6
• 206010003246 arthritis Diseases 0.000 claims description 6
• 208000006673 asthma Diseases 0.000 claims description 6
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
• 208000037976 chronic inflammation Diseases 0.000 claims description 6
• 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• 230000002757 inflammatory effect Effects 0.000 claims description 6
• 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 6
• 201000001119 neuropathy Diseases 0.000 claims description 6
• 230000007823 neuropathy Effects 0.000 claims description 6
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 6
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
• 208000019553 vascular disease Diseases 0.000 claims description 6
• 230000003612 virological effect Effects 0.000 claims description 6
• GOEKOPDTSMLSRO-UHFFFAOYSA-N 3-[5-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-1,3-dihydroisoindol-2-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(C=2C=C3CN(CCC(O)=O)CC3=CC=2)S1 GOEKOPDTSMLSRO-UHFFFAOYSA-N 0.000 claims description 5
• KJSOQPSUYLGTOQ-UHFFFAOYSA-N 3-[6-[5-[3-cyano-4-(2-methylpropyl)phenyl]-1,3,4-thiadiazol-2-yl]-5-ethyl-3,4-dihydro-1h-isoquinolin-2-yl]propanoic acid Chemical compound CCC1=C2CCN(CCC(O)=O)CC2=CC=C1C(S1)=NN=C1C1=CC=C(CC(C)C)C(C#N)=C1 KJSOQPSUYLGTOQ-UHFFFAOYSA-N 0.000 claims description 5
• 125000004432 carbon atom Chemical group C* 0.000 claims description 5
• PYRDBTPSMUQFPJ-UHFFFAOYSA-N 2-(3-chloro-4-propan-2-yloxyphenyl)-5-(2,3-dihydro-1h-isoindol-5-yl)-1,3,4-thiadiazole;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(C=2C=C3CNCC3=CC=2)S1 PYRDBTPSMUQFPJ-UHFFFAOYSA-N 0.000 claims description 4
• QGWQNVMOEUFEIR-UHFFFAOYSA-N 4-[6-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-5-ethyl-3,4-dihydro-1h-isoquinolin-2-yl]butanoic acid Chemical compound CCC1=C2CCN(CCCC(O)=O)CC2=CC=C1C(S1)=NN=C1C1=CC=C(OC(C)C)C(Cl)=C1 QGWQNVMOEUFEIR-UHFFFAOYSA-N 0.000 claims description 4
• FMNVTIRPVUHEBF-UHFFFAOYSA-N 4-[7-[2-(3-chloro-4-propan-2-yloxyphenyl)-1,3-thiazol-5-yl]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]butanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC=C(C=2C=C3CCN(CCCC(O)=O)CCC3=CC=2)S1 FMNVTIRPVUHEBF-UHFFFAOYSA-N 0.000 claims description 4
• MHJITZGNDJOVPT-UHFFFAOYSA-N 5-(3-chloro-4-propan-2-yloxyphenyl)-2-(2,3,4,5-tetrahydro-1h-3-benzazepin-7-yl)-1,3-thiazole Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=CN=C(C=2C=C3CCNCCC3=CC=2)S1 MHJITZGNDJOVPT-UHFFFAOYSA-N 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• CNWYBOVJIUYVNE-UHFFFAOYSA-N 2-(3-chloro-4-propan-2-yloxyphenyl)-5-(2,3,4,5-tetrahydro-1h-3-benzazepin-7-yl)-1,3-thiazole Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC=C(C=2C=C3CCNCCC3=CC=2)S1 CNWYBOVJIUYVNE-UHFFFAOYSA-N 0.000 claims description 3
• MLDDRIFHQZBWFV-UHFFFAOYSA-N 2-propan-2-yloxy-5-[5-(1,2,3,4-tetrahydroisoquinolin-5-yl)-1,3,4-thiadiazol-2-yl]benzonitrile Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NN=C(C=2C=3CCNCC=3C=CC=2)S1 MLDDRIFHQZBWFV-UHFFFAOYSA-N 0.000 claims description 3
• SAARRMVYKCRBBM-UHFFFAOYSA-N 2-propan-2-yloxy-5-[5-(1,2,3,4-tetrahydroisoquinolin-6-yl)-1,3,4-thiadiazol-2-yl]benzonitrile Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NN=C(C=2C=C3CCNCC3=CC=2)S1 SAARRMVYKCRBBM-UHFFFAOYSA-N 0.000 claims description 3
• AJWBTOCYYQDQMZ-UHFFFAOYSA-N 4-[7-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3-thiazol-2-yl]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]butanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=CN=C(C=2C=C3CCN(CCCC(O)=O)CCC3=CC=2)S1 AJWBTOCYYQDQMZ-UHFFFAOYSA-N 0.000 claims description 3
• MDLAYHHUUJGHJV-UHFFFAOYSA-N 4-[7-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-1,2,4,5-tetrahydro-3-benzazepin-3-yl]butanoic acid;hydrochloride Chemical compound Cl.C1=C(C#N)C(OC(C)C)=CC=C1C1=NN=C(C=2C=C3CCN(CCCC(O)=O)CCC3=CC=2)S1 MDLAYHHUUJGHJV-UHFFFAOYSA-N 0.000 claims description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 229910052731 fluorine Inorganic materials 0.000 claims description 3
• XBSKAZRTIYWPDS-UHFFFAOYSA-N 2-(3-chloro-4-propan-2-yloxyphenyl)-5-(2,3,4,5-tetrahydro-1h-3-benzazepin-7-yl)-1,3,4-thiadiazole Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(C=2C=C3CCNCCC3=CC=2)S1 XBSKAZRTIYWPDS-UHFFFAOYSA-N 0.000 claims description 2
• YYSFXNOSSYJURL-UHFFFAOYSA-N 3-[6-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-5-methyl-3,4-dihydro-1h-isoquinolin-2-yl]propanoic acid Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NN=C(C=2C(=C3CCN(CCC(O)=O)CC3=CC=2)C)S1 YYSFXNOSSYJURL-UHFFFAOYSA-N 0.000 claims description 2
• VSMRHANQUBHRND-UHFFFAOYSA-N 4-[6-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-5-methyl-3,4-dihydro-1h-isoquinolin-2-yl]butanoic acid Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NN=C(C=2C(=C3CCN(CCCC(O)=O)CC3=CC=2)C)S1 VSMRHANQUBHRND-UHFFFAOYSA-N 0.000 claims description 2
• LCDDMTDFELNROZ-UHFFFAOYSA-N 5-[5-(5-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-1,3,4-thiadiazol-2-yl]-2-propan-2-yloxybenzonitrile Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NN=C(C=2C(=C3CCNCC3=CC=2)C)S1 LCDDMTDFELNROZ-UHFFFAOYSA-N 0.000 claims description 2
• 241000124008 Mammalia Species 0.000 claims description 2
• 125000002393 azetidinyl group Chemical group 0.000 claims description 2
• 125000004069 aziridinyl group Chemical group 0.000 claims description 2
• 125000002619 bicyclic group Chemical group 0.000 claims description 2
• 229910052799 carbon Inorganic materials 0.000 claims description 2
• 125000000623 heterocyclic group Chemical group 0.000 claims description 2
• 125000002757 morpholinyl group Chemical group 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• 230000001575 pathological effect Effects 0.000 claims 3
• 230000000144 pharmacologic effect Effects 0.000 abstract description 3
• 230000008569 process Effects 0.000 abstract description 2
• 239000000203 mixture Substances 0.000 description 113
• 238000002360 preparation method Methods 0.000 description 94
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 70
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 67
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 46
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
• 230000014759 maintenance of location Effects 0.000 description 44
• 239000000243 solution Substances 0.000 description 41
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
• VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
• 239000012074 organic phase Substances 0.000 description 34
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• 239000011541 reaction mixture Substances 0.000 description 32
• 239000000741 silica gel Substances 0.000 description 30
• 229910002027 silica gel Inorganic materials 0.000 description 30
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
• 239000007787 solid Substances 0.000 description 25
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
• 238000003818 flash chromatography Methods 0.000 description 23
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 22
• 239000011734 sodium Substances 0.000 description 22
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 19
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 18
• 239000010410 layer Substances 0.000 description 18
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
• 210000004027 cell Anatomy 0.000 description 17
• 238000000746 purification Methods 0.000 description 17
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
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• 238000003556 assay Methods 0.000 description 15
• 239000011780 sodium chloride Substances 0.000 description 15
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
• 239000003921 oil Substances 0.000 description 13
• 235000019198 oils Nutrition 0.000 description 13
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 12
• 238000010992 reflux Methods 0.000 description 12
• 229920006395 saturated elastomer Polymers 0.000 description 12
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 11
• 239000000460 chlorine Substances 0.000 description 11
• 239000012044 organic layer Substances 0.000 description 11
• 102100025750 Sphingosine 1-phosphate receptor 1 Human genes 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
• 101710155454 Sphingosine 1-phosphate receptor 1 Proteins 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• UXRDAJMOOGEIAQ-CKOZHMEPSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-10,13-dimethyl-16-methylidene-3-oxo-1,2,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UXRDAJMOOGEIAQ-CKOZHMEPSA-N 0.000 description 9
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• 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 8
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• 229910021529 ammonia Inorganic materials 0.000 description 8
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• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
• 239000002904 solvent Substances 0.000 description 8
• 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 7
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• 239000000556 agonist Substances 0.000 description 7
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• 238000012360 testing method Methods 0.000 description 7
• UZNDXSJHAVHWFH-UHFFFAOYSA-N 2-bromo-5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazole Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(Br)S1 UZNDXSJHAVHWFH-UHFFFAOYSA-N 0.000 description 6
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