TW200843765A - 2-aminopyridine analogs as glucokinase activators - Google Patents

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Publication number

TW200843765A

TW200843765A TW097110307A TW97110307A TW200843765A TW 200843765 A TW200843765 A TW 200843765A TW 097110307 A TW097110307 A TW 097110307A TW 97110307 A TW97110307 A TW 97110307A TW 200843765 A TW200843765 A TW 200843765A

Authority

TW

Taiwan

Prior art keywords

compound

alkyl

formula

mmol

group

Prior art date

2007-03-23

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• 108010021582 Glucokinase Proteins 0.000 title claims abstract description 25
• 102000030595 Glucokinase Human genes 0.000 title claims abstract description 20
• 150000003930 2-aminopyridines Chemical class 0.000 title description 6
• 239000012190 activator Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 319
• 238000000034 method Methods 0.000 claims abstract description 122
• 230000000694 effects Effects 0.000 claims abstract description 10
• 125000000217 alkyl group Chemical group 0.000 claims description 203
• -1 compound oxime Chemical class 0.000 claims description 196
• 238000006243 chemical reaction Methods 0.000 claims description 160
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 96
• 229910052794 bromium Inorganic materials 0.000 claims description 48
• 229910052757 nitrogen Inorganic materials 0.000 claims description 47
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
• 125000001424 substituent group Chemical group 0.000 claims description 39
• 125000004429 atom Chemical group 0.000 claims description 36
• 125000003118 aryl group Chemical group 0.000 claims description 34
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 30
• 229910052731 fluorine Inorganic materials 0.000 claims description 27
• 229910052801 chlorine Inorganic materials 0.000 claims description 25
• 239000003054 catalyst Substances 0.000 claims description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
• 201000010099 disease Diseases 0.000 claims description 22
• 150000003512 tertiary amines Chemical class 0.000 claims description 21
• 150000002923 oximes Chemical class 0.000 claims description 20
• 238000012360 testing method Methods 0.000 claims description 20
• 229910052740 iodine Inorganic materials 0.000 claims description 17
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 16
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 13
• 229910052751 metal Inorganic materials 0.000 claims description 13
• 239000002184 metal Substances 0.000 claims description 13
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 12
• 125000000565 sulfonamide group Chemical group 0.000 claims description 10
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 125000000623 heterocyclic group Chemical group 0.000 claims description 9
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
• 239000003153 chemical reaction reagent Substances 0.000 claims description 8
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 8
• 125000001072 heteroaryl group Chemical group 0.000 claims description 8
• 230000004913 activation Effects 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 239000010949 copper Substances 0.000 claims description 7
• 125000005842 heteroatom Chemical group 0.000 claims description 7
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 6
• 229910052802 copper Inorganic materials 0.000 claims description 6
• 125000004122 cyclic group Chemical group 0.000 claims description 6
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 6
• 229910052763 palladium Inorganic materials 0.000 claims description 6
• 238000003776 cleavage reaction Methods 0.000 claims description 5
• 230000008878 coupling Effects 0.000 claims description 5
• 238000010168 coupling process Methods 0.000 claims description 5
• 238000005859 coupling reaction Methods 0.000 claims description 5
• GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 claims description 5
• 230000007017 scission Effects 0.000 claims description 5
• 239000000126 substance Substances 0.000 claims description 5
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
• 239000004593 Epoxy Substances 0.000 claims description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 125000006239 protecting group Chemical group 0.000 claims description 4
• XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims description 3
• 102000004190 Enzymes Human genes 0.000 claims description 3
• 108090000790 Enzymes Proteins 0.000 claims description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
• 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 description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 125000004434 sulfur atom Chemical group 0.000 claims description 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
• 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 2
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 2
• JCFWQBLQYTZMOF-UHFFFAOYSA-N [Cl-].C[NH2+]C.S Chemical compound [Cl-].C[NH2+]C.S JCFWQBLQYTZMOF-UHFFFAOYSA-N 0.000 claims description 2
• 229910052805 deuterium Inorganic materials 0.000 claims description 2
• WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 claims description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
• IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 claims 2
• PXFIAYNRKNWKLV-UHFFFAOYSA-N 2-(dimethylamino)acetonitrile;hydrochloride Chemical compound Cl.CN(C)CC#N PXFIAYNRKNWKLV-UHFFFAOYSA-N 0.000 claims 1
• DTSCZKIBPYQEND-UHFFFAOYSA-L CN(C)[Ru](Cl)Cl Chemical compound CN(C)[Ru](Cl)Cl DTSCZKIBPYQEND-UHFFFAOYSA-L 0.000 claims 1
• XRJWYPZEAXAVPF-UHFFFAOYSA-N S.SNS Chemical compound S.SNS XRJWYPZEAXAVPF-UHFFFAOYSA-N 0.000 claims 1
• 229910006074 SO2NH2 Inorganic materials 0.000 claims 1
• 125000004430 oxygen atom Chemical group O* 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 claims 1
• 206010012601 diabetes mellitus Diseases 0.000 abstract description 11
• 230000001404 mediated effect Effects 0.000 abstract description 5
• 206010011953 Decreased activity Diseases 0.000 abstract 1
• 230000003213 activating effect Effects 0.000 abstract 1
• 230000002950 deficient Effects 0.000 abstract 1
• 230000006806 disease prevention Effects 0.000 abstract 1
• 208000037765 diseases and disorders Diseases 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 267
• 235000019439 ethyl acetate Nutrition 0.000 description 128
• 206010057190 Respiratory tract infections Diseases 0.000 description 90
• 239000000243 solution Substances 0.000 description 90
• 239000000203 mixture Substances 0.000 description 87
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 86
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 81
• 239000007787 solid Substances 0.000 description 81
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 79
• 238000002360 preparation method Methods 0.000 description 78
• 239000002585 base Substances 0.000 description 77
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 73
• FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 69
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 66
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 63
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 63
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 61
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 56
• 238000005481 NMR spectroscopy Methods 0.000 description 54
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 48
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 40
• 238000005160 1H NMR spectroscopy Methods 0.000 description 37
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 36
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 33
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 33
• 239000012044 organic layer Substances 0.000 description 30
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 28
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 27
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 27
• 239000008103 glucose Substances 0.000 description 27
• 229910052938 sodium sulfate Inorganic materials 0.000 description 27
• 235000011152 sodium sulphate Nutrition 0.000 description 27
• 101150041968 CDC13 gene Proteins 0.000 description 25
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
• 239000000460 chlorine Substances 0.000 description 24
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 24
• 239000002904 solvent Substances 0.000 description 24
• 238000003756 stirring Methods 0.000 description 23
• 238000001819 mass spectrum Methods 0.000 description 22
• 229920006395 saturated elastomer Polymers 0.000 description 22
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
• 229910000104 sodium hydride Inorganic materials 0.000 description 20
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
• 239000002253 acid Substances 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 17
• ZVDDJPSHRNMSKV-UHFFFAOYSA-N acetaldehyde;hydrochloride Chemical compound Cl.CC=O ZVDDJPSHRNMSKV-UHFFFAOYSA-N 0.000 description 17
• UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 17
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 16
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 16
• 239000007789 gas Substances 0.000 description 16
• 125000004076 pyridyl group Chemical group 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• 230000015572 biosynthetic process Effects 0.000 description 15
• 238000004949 mass spectrometry Methods 0.000 description 15
• 239000000463 material Substances 0.000 description 15
• 239000011541 reaction mixture Substances 0.000 description 15
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
• 239000000741 silica gel Substances 0.000 description 14
• 229910002027 silica gel Inorganic materials 0.000 description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 13
• 239000001257 hydrogen Substances 0.000 description 13
• 239000000543 intermediate Substances 0.000 description 13
• 238000010992 reflux Methods 0.000 description 13
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 12
• QJAVDKKSRYQDRY-UHFFFAOYSA-N Cl.CCC(=O)CC Chemical compound Cl.CCC(=O)CC QJAVDKKSRYQDRY-UHFFFAOYSA-N 0.000 description 12
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• 239000012312 sodium hydride Substances 0.000 description 12
• 150000001412 amines Chemical class 0.000 description 11
• 150000002576 ketones Chemical class 0.000 description 11
• 239000010410 layer Substances 0.000 description 11
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• 235000017557 sodium bicarbonate Nutrition 0.000 description 10
• DUCOISOCHCDKOU-UHFFFAOYSA-N Cl.Cl.C(C)C(=O)CC Chemical compound Cl.Cl.C(C)C(=O)CC DUCOISOCHCDKOU-UHFFFAOYSA-N 0.000 description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
• 150000003927 aminopyridines Chemical class 0.000 description 9
• 239000012267 brine Substances 0.000 description 9
• 239000003921 oil Substances 0.000 description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
• 239000011734 sodium Substances 0.000 description 9
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
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• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 8
• 239000008280 blood Substances 0.000 description 8
• 210000004369 blood Anatomy 0.000 description 8
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 239000013058 crude material Substances 0.000 description 8
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 7
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
• 238000001514 detection method Methods 0.000 description 7
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• 208000024891 symptom Diseases 0.000 description 7
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• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
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• 239000007864 aqueous solution Substances 0.000 description 6
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• 238000004587 chromatography analysis Methods 0.000 description 6
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• 150000002148 esters Chemical class 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 238000003818 flash chromatography Methods 0.000 description 6
• 150000004820 halides Chemical class 0.000 description 6
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
• 150000002825 nitriles Chemical class 0.000 description 6
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• 229940124597 therapeutic agent Drugs 0.000 description 6
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• 206010036790 Productive cough Diseases 0.000 description 5
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 5
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
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• 229910052736 halogen Inorganic materials 0.000 description 5
• 150000002367 halogens Chemical class 0.000 description 5
• DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 5
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 5
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