JP5405303B2 - 置換されたスルホンアミド誘導体 - Google Patents

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Publication number

JP5405303B2

JP5405303B2 JP2009529606A JP2009529606A JP5405303B2 JP 5405303 B2 JP5405303 B2 JP 5405303B2 JP 2009529606 A JP2009529606 A JP 2009529606A JP 2009529606 A JP2009529606 A JP 2009529606A JP 5405303 B2 JP5405303 B2 JP 5405303B2

Authority

JP

Japan

Prior art keywords

group

alkyl

substituted

mmol

solution

Prior art date

2006-09-29

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.)

Expired - Fee Related

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• 229940124530 sulfonamide Drugs 0.000 title claims description 33
• 150000003456 sulfonamides Chemical class 0.000 title claims description 33
• 239000000203 mixture Substances 0.000 claims description 104
• 239000011734 sodium Substances 0.000 claims description 101
• 125000003118 aryl group Chemical group 0.000 claims description 92
• -1 benzyloxy, phenoxy, phenyl Chemical group 0.000 claims description 71
• 229920006395 saturated elastomer Polymers 0.000 claims description 70
• 125000000623 heterocyclic group Chemical group 0.000 claims description 51
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 51
• 229910052739 hydrogen Inorganic materials 0.000 claims description 48
• 239000002253 acid Substances 0.000 claims description 47
• 125000001072 heteroaryl group Chemical group 0.000 claims description 42
• 229910052799 carbon Inorganic materials 0.000 claims description 41
• 125000005842 heteroatom Chemical group 0.000 claims description 41
• 229910052757 nitrogen Inorganic materials 0.000 claims description 37
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
• 238000004519 manufacturing process Methods 0.000 claims description 30
• HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical class O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 claims description 29
• 239000003960 organic solvent Substances 0.000 claims description 28
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 27
• 125000000217 alkyl group Chemical group 0.000 claims description 26
• 229910052740 iodine Inorganic materials 0.000 claims description 24
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 22
• 125000004076 pyridyl group Chemical group 0.000 claims description 20
• 125000004122 cyclic group Chemical group 0.000 claims description 19
• 239000003814 drug Substances 0.000 claims description 19
• 208000002193 Pain Diseases 0.000 claims description 18
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
• 125000001624 naphthyl group Chemical group 0.000 claims description 16
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 15
• 125000002757 morpholinyl group Chemical group 0.000 claims description 15
• 229910052760 oxygen Inorganic materials 0.000 claims description 15
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
• 229910052938 sodium sulfate Inorganic materials 0.000 claims description 14
• 235000011152 sodium sulphate Nutrition 0.000 claims description 14
• 125000001424 substituent group Chemical group 0.000 claims description 14
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 claims description 12
• 150000007530 organic bases Chemical class 0.000 claims description 12
• 150000003839 salts Chemical class 0.000 claims description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 11
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
• 125000003386 piperidinyl group Chemical group 0.000 claims description 10
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 8
• 125000003107 substituted aryl group Chemical group 0.000 claims description 8
• 239000013543 active substance Substances 0.000 claims description 7
• 229910002091 carbon monoxide Inorganic materials 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
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
• 125000002950 monocyclic group Chemical group 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
• PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 6
• 238000010640 amide synthesis reaction Methods 0.000 claims description 6
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
• 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 6
• 201000010099 disease Diseases 0.000 claims description 6
• 125000002541 furyl group Chemical group 0.000 claims description 6
• 125000005936 piperidyl group Chemical group 0.000 claims description 6
• 125000003367 polycyclic group Chemical group 0.000 claims description 6
• 208000000094 Chronic Pain Diseases 0.000 claims description 5
• 208000005298 acute pain Diseases 0.000 claims description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
• 239000003795 chemical substances by application Substances 0.000 claims description 4
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 4
• 235000019341 magnesium sulphate Nutrition 0.000 claims description 4
• 201000004624 Dermatitis Diseases 0.000 claims description 3
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
• 208000019695 Migraine disease Diseases 0.000 claims description 3
• 208000012902 Nervous system disease Diseases 0.000 claims description 3
• 208000008589 Obesity Diseases 0.000 claims description 3
• 206010040070 Septic Shock Diseases 0.000 claims description 3
• 150000007513 acids Chemical class 0.000 claims description 3
• 229940121369 angiogenesis inhibitor Drugs 0.000 claims description 3
• 239000004037 angiogenesis inhibitor Substances 0.000 claims description 3
• 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 claims description 3
• 235000020824 obesity Nutrition 0.000 claims description 3
• 230000010410 reperfusion Effects 0.000 claims description 3
• 208000023504 respiratory system disease Diseases 0.000 claims description 3
• 150000003335 secondary amines Chemical class 0.000 claims description 3
• 230000036303 septic shock Effects 0.000 claims description 3
• 208000011580 syndromic disease Diseases 0.000 claims description 3
• 208000009935 visceral pain Diseases 0.000 claims description 3
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
• 125000005418 aryl aryl group Chemical group 0.000 claims description 2
• 206010012601 diabetes mellitus Diseases 0.000 claims description 2
• BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 2
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
• 206010027599 migraine Diseases 0.000 claims description 2
• 150000003141 primary amines Chemical class 0.000 claims description 2
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
• 125000004434 sulfur atom Chemical group 0.000 claims description 2
• 150000001735 carboxylic acids Chemical class 0.000 claims 1
• 125000004430 oxygen atom Chemical group O* 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 448
• 239000000243 solution Substances 0.000 description 331
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 315
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 259
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 222
• 230000002829 reductive effect Effects 0.000 description 160
• 239000011541 reaction mixture Substances 0.000 description 143
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 140
• 239000012074 organic phase Substances 0.000 description 133
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 128
• 235000019439 ethyl acetate Nutrition 0.000 description 108
• 239000012043 crude product Substances 0.000 description 99
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 99
• 239000002904 solvent Substances 0.000 description 89
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 88
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 87
• 238000006243 chemical reaction Methods 0.000 description 87
• 150000001875 compounds Chemical class 0.000 description 84
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 83
• 238000004440 column chromatography Methods 0.000 description 83
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 77
• 239000000047 product Substances 0.000 description 68
• 238000003756 stirring Methods 0.000 description 67
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
• 238000000034 method Methods 0.000 description 61
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
• 239000008346 aqueous phase Substances 0.000 description 51
• 230000015572 biosynthetic process Effects 0.000 description 50
• 238000003786 synthesis reaction Methods 0.000 description 47
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 46
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
• 150000001412 amines Chemical class 0.000 description 40
• 238000010626 work up procedure Methods 0.000 description 40
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 39
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 39
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
• 239000000758 substrate Substances 0.000 description 36
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 33
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 30
• 239000000741 silica gel Substances 0.000 description 30
• 229910002027 silica gel Inorganic materials 0.000 description 30
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 29
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 27
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 26
• 238000002360 preparation method Methods 0.000 description 25
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
• 239000007864 aqueous solution Substances 0.000 description 24
• 239000007787 solid Substances 0.000 description 24
• 239000000725 suspension Substances 0.000 description 24
• 238000001914 filtration Methods 0.000 description 23
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 22
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 22
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 21
• 235000011114 ammonium hydroxide Nutrition 0.000 description 21
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 20
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 20
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• 241000282414 Homo sapiens Species 0.000 description 18
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 18
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
• 239000000377 silicon dioxide Substances 0.000 description 18
• OHUMKYGINIODOY-UHFFFAOYSA-N 1-(1-methylpiperidin-4-yl)piperazine Chemical compound C1CN(C)CCC1N1CCNCC1 OHUMKYGINIODOY-UHFFFAOYSA-N 0.000 description 17
• 239000011780 sodium chloride Substances 0.000 description 17
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 16
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
• 235000011054 acetic acid Nutrition 0.000 description 15
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 15
• 238000012360 testing method Methods 0.000 description 15
• 238000004809 thin layer chromatography Methods 0.000 description 15
• 210000004027 cell Anatomy 0.000 description 14
• 239000012299 nitrogen atmosphere Substances 0.000 description 14
• 239000002585 base Substances 0.000 description 13
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 13
• 230000008569 process Effects 0.000 description 13
• BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
• 238000001035 drying Methods 0.000 description 12
• 150000007529 inorganic bases Chemical class 0.000 description 12
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 11
• 239000011575 calcium Substances 0.000 description 11
• SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
• NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 11
• JTMCFGGKUMGQHJ-UHFFFAOYSA-N 2-[[1-(4-methoxy-2,6-dimethylphenyl)sulfonylpiperidin-2-yl]methoxy]-1-piperazin-1-ylethanone;hydrochloride Chemical compound Cl.CC1=CC(OC)=CC(C)=C1S(=O)(=O)N1C(COCC(=O)N2CCNCC2)CCCC1 JTMCFGGKUMGQHJ-UHFFFAOYSA-N 0.000 description 10
• MEHPEOSPGDRMKN-UHFFFAOYSA-N 2-[[1-(4-methoxy-2,6-dimethylphenyl)sulfonylpiperidin-2-yl]methoxy]acetic acid Chemical compound CC1=CC(OC)=CC(C)=C1S(=O)(=O)N1C(COCC(O)=O)CCCC1 MEHPEOSPGDRMKN-UHFFFAOYSA-N 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• 241000702421 Dependoparvovirus Species 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
• 239000005557 antagonist Substances 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• 241000580270 Adeno-associated virus - 4 Species 0.000 description 9
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 9
• 108090001005 Interleukin-6 Proteins 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• 150000001299 aldehydes Chemical class 0.000 description 9
• 150000001414 amino alcohols Chemical class 0.000 description 9
• 125000004432 carbon atom Chemical group C* 0.000 description 9
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
• 239000001257 hydrogen Substances 0.000 description 9
• 239000012071 phase Substances 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• 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 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 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
• 241001465754 Metazoa Species 0.000 description 8
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
• 241000700159 Rattus Species 0.000 description 8
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 8
• 229910052786 argon Inorganic materials 0.000 description 8
• 239000012298 atmosphere Substances 0.000 description 8
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 8
• 239000012141 concentrate Substances 0.000 description 8
• 235000008504 concentrate Nutrition 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• 239000012458 free base Substances 0.000 description 8
• 230000005764 inhibitory process Effects 0.000 description 8
• 238000006467 substitution reaction Methods 0.000 description 8
• 0 CC*(CC(C)(C)C(/*=*/*=C)=C(C)C1)N1S(C)C Chemical compound CC*(CC(C)(C)C(/*=*/*=C)=C(C)C1)N1S(C)C 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• 238000003818 flash chromatography Methods 0.000 description 7
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