TWI415839B - 作為ｐｇｄｓ抑制劑之嘧啶醯胺化合物 - Google Patents

Info

Publication number

TWI415839B

TWI415839B TW095136806A TW95136806A TWI415839B TW I415839 B TWI415839 B TW I415839B TW 095136806 A TW095136806 A TW 095136806A TW 95136806 A TW95136806 A TW 95136806A TW I415839 B TWI415839 B TW I415839B

Authority

TW

Taiwan

Prior art keywords

carboxylic acid

decylamine

group

pyrimidine

fluorophenyl

Prior art date

2005-10-04

Links

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• Global Dossier
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• 239000003112 inhibitor Substances 0.000 title description 7
• 101150020741 Hpgds gene Proteins 0.000 title description 2
• FUXJMHXHGDAHPD-UHFFFAOYSA-N pyrimidine-2-carboxamide Chemical class NC(=O)C1=NC=CC=N1 FUXJMHXHGDAHPD-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 114
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 26
• 206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 10
• 201000010105 allergic rhinitis Diseases 0.000 claims abstract description 10
• 208000006673 asthma Diseases 0.000 claims abstract description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
• 201000009961 allergic asthma Diseases 0.000 claims abstract description 6
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 4
• -1 benzo[c]isothiazolyl Chemical group 0.000 claims description 415
• XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 203
• DYPNEVXAPRDVCM-UHFFFAOYSA-N 2-(3-fluorophenyl)pyrimidine-5-carboxylic acid Chemical compound N1=CC(C(=O)O)=CN=C1C1=CC=CC(F)=C1 DYPNEVXAPRDVCM-UHFFFAOYSA-N 0.000 claims description 121
• BOAIYSRFGWBZCF-UHFFFAOYSA-N 2-phenylpyrimidine-5-carboxylic acid Chemical compound N1=CC(C(=O)O)=CN=C1C1=CC=CC=C1 BOAIYSRFGWBZCF-UHFFFAOYSA-N 0.000 claims description 109
• 229910052739 hydrogen Inorganic materials 0.000 claims description 79
• 150000003839 salts Chemical class 0.000 claims description 73
• 125000000217 alkyl group Chemical group 0.000 claims description 58
• 229910052736 halogen Inorganic materials 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 48
• 150000002367 halogens Chemical class 0.000 claims description 47
• 150000001204 N-oxides Chemical class 0.000 claims description 46
• 150000001412 amines Chemical class 0.000 claims description 43
• GBPSQUKBRZGSBG-UHFFFAOYSA-N C1=CC=C(C=C1)CNCCCCCCCCCC=S(=O)=O Chemical compound C1=CC=C(C=C1)CNCCCCCCCCCC=S(=O)=O GBPSQUKBRZGSBG-UHFFFAOYSA-N 0.000 claims description 38
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 36
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 30
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
• 239000001257 hydrogen Substances 0.000 claims description 22
• LZMNSJCIRQSESL-UHFFFAOYSA-N 2-(3-fluorophenyl)-4-methylpyrimidine-5-carboxylic acid Chemical compound C1=C(C(O)=O)C(C)=NC(C=2C=C(F)C=CC=2)=N1 LZMNSJCIRQSESL-UHFFFAOYSA-N 0.000 claims description 20
• 125000004076 pyridyl group Chemical group 0.000 claims description 20
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 18
• 125000005843 halogen group Chemical group 0.000 claims description 18
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• 125000002883 imidazolyl group Chemical group 0.000 claims description 14
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 14
• 238000011282 treatment Methods 0.000 claims description 14
• 239000002253 acid Substances 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 13
• 125000000468 ketone group Chemical group 0.000 claims description 12
• 125000000335 thiazolyl group Chemical group 0.000 claims description 12
• 125000003386 piperidinyl group Chemical group 0.000 claims description 11
• 125000003277 amino group Chemical group 0.000 claims description 9
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
• 239000000126 substance Substances 0.000 claims description 9
• IOFQQZZRBFKEIF-UHFFFAOYSA-N 2-(5-methyl-1,2,4-oxadiazol-3-yl)pyrimidine-5-carboxylic acid Chemical compound O1C(C)=NC(C=2N=CC(=CN=2)C(O)=O)=N1 IOFQQZZRBFKEIF-UHFFFAOYSA-N 0.000 claims description 8
• MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 150000003180 prostaglandins Chemical class 0.000 claims description 8
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
• FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 claims description 7
• MORKTPRONBOIJR-UHFFFAOYSA-N 2-pyridin-3-ylpyrimidine-5-carboxylic acid Chemical compound N1=CC(C(=O)O)=CN=C1C1=CC=CN=C1 MORKTPRONBOIJR-UHFFFAOYSA-N 0.000 claims description 7
• 201000010099 disease Diseases 0.000 claims description 7
• 150000002431 hydrogen Chemical class 0.000 claims description 7
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 7
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
• KVOLJYNCWUOVPC-UHFFFAOYSA-N 2-(4-fluorophenyl)pyrimidine-5-carboxylic acid Chemical compound N1=CC(C(=O)O)=CN=C1C1=CC=C(F)C=C1 KVOLJYNCWUOVPC-UHFFFAOYSA-N 0.000 claims description 6
• 102000003960 Ligases Human genes 0.000 claims description 6
• 108090000364 Ligases Proteins 0.000 claims description 6
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
• 125000002971 oxazolyl group Chemical group 0.000 claims description 6
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 5
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 5
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 5
• DBPZPSJZEOLWJP-UHFFFAOYSA-N 2-(2,5-difluorophenyl)pyrimidine-5-carboxylic acid Chemical compound N1=CC(C(=O)O)=CN=C1C1=CC(F)=CC=C1F DBPZPSJZEOLWJP-UHFFFAOYSA-N 0.000 claims description 5
• PGHKQASEGLDCRU-UHFFFAOYSA-N 2-pyridin-2-ylpyrimidine-5-carboxylic acid Chemical compound N1=CC(C(=O)O)=CN=C1C1=CC=CC=N1 PGHKQASEGLDCRU-UHFFFAOYSA-N 0.000 claims description 5
• BDZAKJITXGLLPO-UHFFFAOYSA-N 4-methyl-2-[(2-phenylpyrimidine-5-carbonyl)amino]-1,3-thiazole-5-carboxylic acid Chemical compound S1C(C(O)=O)=C(C)N=C1NC(=O)C1=CN=C(C=2C=CC=CC=2)N=C1 BDZAKJITXGLLPO-UHFFFAOYSA-N 0.000 claims description 5
• LMEVZGZYIQYYNG-UHFFFAOYSA-N 2-pyrazol-1-ylpyrimidine-5-carboxylic acid Chemical compound N1=CC(C(=O)O)=CN=C1N1N=CC=C1 LMEVZGZYIQYYNG-UHFFFAOYSA-N 0.000 claims description 4
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
• CFYPDUCBWGTJMP-UHFFFAOYSA-N 4-methyl-2-pyridin-2-ylpyrimidine-5-carboxylic acid Chemical compound C1=C(C(O)=O)C(C)=NC(C=2N=CC=CC=2)=N1 CFYPDUCBWGTJMP-UHFFFAOYSA-N 0.000 claims description 4
• LWBPSVFSYUOCOS-UHFFFAOYSA-N 4-methyl-2-pyridin-3-ylpyrimidine-5-carboxylic acid Chemical compound C1=C(C(O)=O)C(C)=NC(C=2C=NC=CC=2)=N1 LWBPSVFSYUOCOS-UHFFFAOYSA-N 0.000 claims description 4
• SBMKVOMWVWBYCZ-UHFFFAOYSA-N 6-[(2-phenylpyrimidine-5-carbonyl)amino]-1h-benzimidazole-2-carboxylic acid Chemical compound C1=C2NC(C(=O)O)=NC2=CC=C1NC(=O)C(C=N1)=CN=C1C1=CC=CC=C1 SBMKVOMWVWBYCZ-UHFFFAOYSA-N 0.000 claims description 4
• UYOIZJOTTGKXKG-UHFFFAOYSA-N C1=CC=C(C=C1)NCCCCCCCCCC=S(=O)=O Chemical compound C1=CC=C(C=C1)NCCCCCCCCCC=S(=O)=O UYOIZJOTTGKXKG-UHFFFAOYSA-N 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000004501 isothiazol-5-yl group Chemical group S1N=CC=C1* 0.000 claims description 4
• 125000002757 morpholinyl group Chemical group 0.000 claims description 4
• RBYGKKADXIDWNE-UHFFFAOYSA-N n-[diethoxyphosphoryl(phenyl)methyl]-2-phenylpyrimidine-5-carboxamide Chemical compound C=1C=CC=CC=1C(P(=O)(OCC)OCC)NC(=O)C(C=N1)=CN=C1C1=CC=CC=C1 RBYGKKADXIDWNE-UHFFFAOYSA-N 0.000 claims description 4
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 3
• UHLFFWBONYSGAB-UHFFFAOYSA-N 2-(2-methyl-1,3-thiazol-4-yl)pyrimidine-5-carboxylic acid Chemical compound S1C(C)=NC(C=2N=CC(=CN=2)C(O)=O)=C1 UHLFFWBONYSGAB-UHFFFAOYSA-N 0.000 claims description 3
• RWMORAFKNKQOES-UHFFFAOYSA-N 2-[2-[(2-phenylpyrimidine-5-carbonyl)amino]-1,3-thiazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CSC(NC(=O)C=2C=NC(=NC=2)C=2C=CC=CC=2)=N1 RWMORAFKNKQOES-UHFFFAOYSA-N 0.000 claims description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
• POAYTBQJGDPYTN-UHFFFAOYSA-N ethyl 4-methyl-2-[(2-phenylpyrimidine-5-carbonyl)amino]-1,3-thiazole-5-carboxylate Chemical compound CC1=C(C(=O)OCC)SC(NC(=O)C=2C=NC(=NC=2)C=2C=CC=CC=2)=N1 POAYTBQJGDPYTN-UHFFFAOYSA-N 0.000 claims description 3
• 239000011737 fluorine Substances 0.000 claims description 3
• 229910052731 fluorine Inorganic materials 0.000 claims description 3
• 230000005764 inhibitory process Effects 0.000 claims description 3
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
• IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 claims description 2
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 8
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 4
• 125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 claims 3
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims 3
• VPUAYOJTHRDUTK-UHFFFAOYSA-N 1-ethylpyrrole Chemical compound CCN1C=CC=C1 VPUAYOJTHRDUTK-UHFFFAOYSA-N 0.000 claims 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims 1
• 241000534944 Thia Species 0.000 claims 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 1
• 125000003943 azolyl group Chemical group 0.000 claims 1
• 150000001555 benzenes Chemical group 0.000 claims 1
• FPVJHDMFGIXROX-UHFFFAOYSA-N n-[3-(aminomethyl)phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(CN)=C1 FPVJHDMFGIXROX-UHFFFAOYSA-N 0.000 claims 1
• VTHOTOFWYDBNID-UHFFFAOYSA-N n-decylaniline Chemical compound CCCCCCCCCCNC1=CC=CC=C1 VTHOTOFWYDBNID-UHFFFAOYSA-N 0.000 claims 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
• 125000001113 thiadiazolyl group Chemical group 0.000 claims 1
• 230000000172 allergic effect Effects 0.000 abstract description 3
• 208000027866 inflammatory disease Diseases 0.000 abstract description 3
• 208000010668 atopic eczema Diseases 0.000 abstract description 2
• 238000001819 mass spectrum Methods 0.000 description 147
• 238000000034 method Methods 0.000 description 119
• 239000012265 solid product Substances 0.000 description 116
• 239000000203 mixture Substances 0.000 description 106
• 238000005481 NMR spectroscopy Methods 0.000 description 104
• 235000019439 ethyl acetate Nutrition 0.000 description 99
• 239000000243 solution Substances 0.000 description 87
• 125000001072 heteroaryl group Chemical group 0.000 description 76
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 73
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
• 229910052757 nitrogen Inorganic materials 0.000 description 71
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 70
• 125000003118 aryl group Chemical group 0.000 description 53
• 125000006413 ring segment Chemical group 0.000 description 48
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 42
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 38
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
• 125000000623 heterocyclic group Chemical group 0.000 description 35
• 229910052717 sulfur Inorganic materials 0.000 description 34
• 125000003545 alkoxy group Chemical group 0.000 description 33
• 239000012453 solvate Substances 0.000 description 33
• 125000000753 cycloalkyl group Chemical group 0.000 description 30
• 239000011734 sodium Substances 0.000 description 30
• 125000004434 sulfur atom Chemical group 0.000 description 29
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
• 125000004432 carbon atom Chemical group C* 0.000 description 26
• 239000007787 solid Substances 0.000 description 24
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 23
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
• 229910052760 oxygen Inorganic materials 0.000 description 21
• 239000001301 oxygen Substances 0.000 description 21
• 239000004480 active ingredient Substances 0.000 description 20
• 238000006243 chemical reaction Methods 0.000 description 19
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 18
• 239000000843 powder Substances 0.000 description 18
• BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 description 18
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
• 125000004429 atom Chemical group 0.000 description 17
• 125000004366 heterocycloalkenyl group Chemical group 0.000 description 17
• 238000002360 preparation method Methods 0.000 description 17
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
• 239000012267 brine Substances 0.000 description 16
• 239000003795 chemical substances by application Substances 0.000 description 16
• 238000001914 filtration Methods 0.000 description 16
• BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 description 16
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 16
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 239000002585 base Substances 0.000 description 15
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 14
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 14
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 14
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
• 125000004122 cyclic group Chemical group 0.000 description 14
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
• 239000002904 solvent Substances 0.000 description 14
• 238000003556 assay Methods 0.000 description 13
• 239000000706 filtrate Substances 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• 102000004190 Enzymes Human genes 0.000 description 12
• 108090000790 Enzymes Proteins 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 125000003282 alkyl amino group Chemical group 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
• 125000003342 alkenyl group Chemical group 0.000 description 11
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 11
• 125000000304 alkynyl group Chemical group 0.000 description 11
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 11
• 125000004438 haloalkoxy group Chemical group 0.000 description 11
• 239000002244 precipitate Substances 0.000 description 11
• 229920006395 saturated elastomer Polymers 0.000 description 11
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 10
• 239000000872 buffer Substances 0.000 description 10
• 125000004663 dialkyl amino group Chemical group 0.000 description 10
• RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 10
• 239000007788 liquid Substances 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
• 239000003995 emulsifying agent Substances 0.000 description 9
• 125000001188 haloalkyl group Chemical group 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 239000011535 reaction buffer Substances 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 8
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• 238000004440 column chromatography Methods 0.000 description 8
• 125000005215 cycloalkylheteroaryl group Chemical group 0.000 description 8
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 8
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 8
• 125000005349 heteroarylcycloalkyl group Chemical group 0.000 description 8
• 125000005842 heteroatom Chemical group 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• 229940124530 sulfonamide Drugs 0.000 description 8
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 125000004414 alkyl thio group Chemical group 0.000 description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
• 238000003818 flash chromatography Methods 0.000 description 7
• 210000003630 histaminocyte Anatomy 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• 239000003826 tablet Substances 0.000 description 7
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• AWFZHOCQRKLVCJ-UHFFFAOYSA-N 2-(3-fluorophenyl)pyrimidine Chemical compound FC1=CC=CC(C=2N=CC=CN=2)=C1 AWFZHOCQRKLVCJ-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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