CN1638761A - 作为ccr-3受体拮抗剂的氮杂环丁烷衍生物 - Google Patents
作为ccr-3受体拮抗剂的氮杂环丁烷衍生物 Download PDFInfo
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- CN1638761A CN1638761A CNA038056488A CN03805648A CN1638761A CN 1638761 A CN1638761 A CN 1638761A CN A038056488 A CNA038056488 A CN A038056488A CN 03805648 A CN03805648 A CN 03805648A CN 1638761 A CN1638761 A CN 1638761A
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- China
- Prior art keywords
- alkyl
- group
- substituted
- phenyl
- phenoxy
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- 108010017316 CCR3 Receptors Proteins 0.000 title description 4
- 102000004499 CCR3 Receptors Human genes 0.000 title description 4
- 229940044551 receptor antagonist Drugs 0.000 title description 3
- 239000002464 receptor antagonist Substances 0.000 title description 3
- 150000001539 azetidines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 250
- 238000000034 method Methods 0.000 claims abstract description 67
- 150000003839 salts Chemical group 0.000 claims abstract description 37
- 230000008569 process Effects 0.000 claims abstract description 22
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 claims abstract description 11
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 230000001404 mediated effect Effects 0.000 claims abstract description 3
- -1 cyano, hydroxy Chemical group 0.000 claims description 173
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 108
- 239000001257 hydrogen Substances 0.000 claims description 90
- 229910052739 hydrogen Inorganic materials 0.000 claims description 90
- 125000001424 substituent group Chemical group 0.000 claims description 86
- 150000002367 halogens Chemical class 0.000 claims description 64
- 229910052757 nitrogen Inorganic materials 0.000 claims description 64
- 229910052736 halogen Inorganic materials 0.000 claims description 61
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 58
- 229910052760 oxygen Inorganic materials 0.000 claims description 46
- 125000000623 heterocyclic group Chemical group 0.000 claims description 45
- 239000001301 oxygen Substances 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 43
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 41
- 238000002360 preparation method Methods 0.000 claims description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 33
- 125000005842 heteroatom Chemical group 0.000 claims description 33
- 125000006413 ring segment Chemical group 0.000 claims description 33
- 229910052717 sulfur Chemical group 0.000 claims description 31
- 238000011282 treatment Methods 0.000 claims description 31
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 29
- 239000011593 sulfur Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 125000001624 naphthyl group Chemical group 0.000 claims description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 24
- 239000000460 chlorine Substances 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 20
- 125000004423 acyloxy group Chemical group 0.000 claims description 19
- 239000011737 fluorine Substances 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 18
- 125000000524 functional group Chemical group 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
- 230000002757 inflammatory effect Effects 0.000 claims description 17
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 16
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 15
- 125000002252 acyl group Chemical group 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000005605 benzo group Chemical group 0.000 claims description 14
- 208000027866 inflammatory disease Diseases 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 229910052740 iodine Inorganic materials 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 10
- 208000027771 Obstructive airways disease Diseases 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 6
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000000962 organic group Chemical group 0.000 claims description 6
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 4
- 208000026935 allergic disease Diseases 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 3
- 239000000739 antihistaminic agent Substances 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 230000001387 anti-histamine Effects 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 229940124630 bronchodilator Drugs 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 240
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 187
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 108
- 239000000243 solution Substances 0.000 description 104
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- 239000011541 reaction mixture Substances 0.000 description 68
- 235000019439 ethyl acetate Nutrition 0.000 description 62
- 150000003254 radicals Chemical class 0.000 description 55
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 54
- 235000019341 magnesium sulphate Nutrition 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- 239000012043 crude product Substances 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- 239000012074 organic phase Substances 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 33
- 238000003818 flash chromatography Methods 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 32
- 229910002027 silica gel Inorganic materials 0.000 description 32
- 239000003480 eluent Substances 0.000 description 30
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
- 208000006673 asthma Diseases 0.000 description 25
- 239000012267 brine Substances 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 239000012071 phase Substances 0.000 description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 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 14
- 239000000047 product Substances 0.000 description 13
- XGMBEBOZDVVNJD-NSHDSACASA-N (2s)-2-amino-4-[3-(4-chlorophenoxy)azetidin-1-yl]butan-1-ol Chemical compound C1N(CC[C@@H](CO)N)CC1OC1=CC=C(Cl)C=C1 XGMBEBOZDVVNJD-NSHDSACASA-N 0.000 description 11
- 239000004202 carbamide Substances 0.000 description 11
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- 229920006395 saturated elastomer Polymers 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 239000012131 assay buffer Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
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- 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 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- ZVHMJDWHTKULHY-ZDUSSCGKSA-N 1-[(2s)-4-[3-(4-chlorophenoxy)azetidin-1-yl]-1-hydroxybutan-2-yl]-3-(5-ethyl-1,3,4-thiadiazol-2-yl)urea Chemical compound S1C(CC)=NN=C1NC(=O)N[C@H](CO)CCN1CC(OC=2C=CC(Cl)=CC=2)C1 ZVHMJDWHTKULHY-ZDUSSCGKSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 210000003979 eosinophil Anatomy 0.000 description 8
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 8
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 8
- FFAJBRIJPGOECU-INIZCTEOSA-N 1-[(2s)-4-[3-(4-chlorophenoxy)azetidin-1-yl]-1-hydroxybutan-2-yl]-3-(5-cyclopropyl-2-methylpyrazol-3-yl)urea Chemical compound C([C@@H](CO)NC(=O)NC1=CC(=NN1C)C1CC1)CN(C1)CC1OC1=CC=C(Cl)C=C1 FFAJBRIJPGOECU-INIZCTEOSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
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- 125000005843 halogen group Chemical group 0.000 description 7
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- 239000002244 precipitate Substances 0.000 description 7
- MSTOPLWRMNGDRS-INIZCTEOSA-N 1-[(2s)-4-[3-(4-chlorophenoxy)azetidin-1-yl]-1-hydroxybutan-2-yl]-3-(5-ethyl-2-methylpyrazol-3-yl)urea Chemical compound CN1N=C(CC)C=C1NC(=O)N[C@H](CO)CCN1CC(OC=2C=CC(Cl)=CC=2)C1 MSTOPLWRMNGDRS-INIZCTEOSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 6
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
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- 239000000872 buffer Substances 0.000 description 6
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- 239000007858 starting material Substances 0.000 description 6
- TZYLGSCNERZEPK-UHFFFAOYSA-N 3-[3-(4-fluorophenoxy)azetidin-1-yl]propan-1-amine Chemical compound C1N(CCCN)CC1OC1=CC=C(F)C=C1 TZYLGSCNERZEPK-UHFFFAOYSA-N 0.000 description 5
- AKWMZTHDHYASMI-UHFFFAOYSA-N 3-[3-[(4-chlorophenyl)methyl]azetidin-1-yl]propan-1-amine Chemical compound C1N(CCCN)CC1CC1=CC=C(Cl)C=C1 AKWMZTHDHYASMI-UHFFFAOYSA-N 0.000 description 5
- QVNYNCBHNRXHTB-UHFFFAOYSA-N 5-ethyl-2-methylpyrazol-3-amine Chemical compound CCC=1C=C(N)N(C)N=1 QVNYNCBHNRXHTB-UHFFFAOYSA-N 0.000 description 5
- 101000978392 Homo sapiens Eotaxin Proteins 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
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- 238000010992 reflux Methods 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 5
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- WMNNQAMLIXEEAA-UHFFFAOYSA-N 3-(4-fluorophenoxy)azetidine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1OC1CNC1 WMNNQAMLIXEEAA-UHFFFAOYSA-N 0.000 description 4
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 4
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- 125000002837 carbocyclic group Chemical group 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 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 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
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- BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical class NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 4
- AQVSVNPMMUQBOB-UHFFFAOYSA-N phenyl n-(5-ethyl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound S1C(CC)=NN=C1NC(=O)OC1=CC=CC=C1 AQVSVNPMMUQBOB-UHFFFAOYSA-N 0.000 description 4
- OCPYUGLLMXUVGB-UHFFFAOYSA-N phenyl n-(5-ethyl-2-methylpyrazol-3-yl)carbamate Chemical compound CN1N=C(CC)C=C1NC(=O)OC1=CC=CC=C1 OCPYUGLLMXUVGB-UHFFFAOYSA-N 0.000 description 4
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- MXUCWQSQDZOHNY-SNVBAGLBSA-N (2r)-4-[3-(4-chlorophenoxy)azetidin-1-yl]butan-2-amine Chemical compound C1N(CC[C@H](N)C)CC1OC1=CC=C(Cl)C=C1 MXUCWQSQDZOHNY-SNVBAGLBSA-N 0.000 description 3
- SPTUDKYSCLWPRA-LBPRGKRZSA-N (2s)-4-[3-(4-chlorophenoxy)azetidin-1-yl]-1-methoxybutan-2-amine Chemical compound C1N(CC[C@H](N)COC)CC1OC1=CC=C(Cl)C=C1 SPTUDKYSCLWPRA-LBPRGKRZSA-N 0.000 description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 3
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Classifications
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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GB0206218.0 | 2002-03-15 | ||
GB0206218A GB0206218D0 (en) | 2002-03-15 | 2002-03-15 | Organic compounds |
GB0229627A GB0229627D0 (en) | 2002-12-19 | 2002-12-19 | Organic compounds |
GB0229627.5 | 2002-12-19 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN110498750A (zh) * | 2019-09-02 | 2019-11-26 | 南通大学 | 一种(r)-4-羟基-1-甲氧基丁-2-基氨基甲酸叔丁酯的合成方法 |
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EP1608319A4 (en) | 2003-04-03 | 2007-02-28 | Univ California | IMPROVED HEMMER FOR SOLUBLE EPOXY HYDROLASE |
EP1638939A2 (en) * | 2003-06-24 | 2006-03-29 | Neurosearch A/S | Aza-ring derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
US20070043013A1 (en) * | 2003-09-15 | 2007-02-22 | Le Grand Darren M | 1,3 Disubstituted azetidine derivatives for use as ccr-3 receptor antagonists in the treatment of inflammatory and allergic diseases |
GB0402101D0 (en) | 2004-01-30 | 2004-03-03 | Novartis Ag | Organic compounds |
JP2007532484A (ja) | 2004-03-16 | 2007-11-15 | ザ・レジェンツ・オブ・ザ・ユニバーシティ・オブ・カリフォルニア | 可溶性エポキシド加水分解酵素の阻害剤およびエポキシエイコサノイドを用いて腎症を緩和する方法 |
GB0417801D0 (en) * | 2004-08-10 | 2004-09-15 | Novartis Ag | Organic compounds |
CA2584342C (en) * | 2004-10-20 | 2013-04-30 | The Regents Of The University Of California | Improved inhibitors for the soluble epoxide hydrolase |
GB0607196D0 (en) * | 2006-04-11 | 2006-05-17 | Prosidion Ltd | G-protein coupled receptor agonists |
GB0720390D0 (en) * | 2007-10-18 | 2007-11-28 | Prosidion Ltd | G-Protein coupled receptor agonists |
GB0720389D0 (en) * | 2007-10-18 | 2008-11-12 | Prosidion Ltd | G-Protein Coupled Receptor Agonists |
WO2010129351A1 (en) | 2009-04-28 | 2010-11-11 | Schepens Eye Research Institute | Method to identify and treat age-related macular degeneration |
MX371290B (es) | 2011-01-07 | 2020-01-24 | Novartis Ag | Formulaciones inmunosupresoras. |
EP3050574B1 (en) | 2015-01-28 | 2019-10-09 | Universite De Bordeaux | Use of plerixafor for treating and/or preventing acute exacerbations of chronic obstructive pulmonary disease |
WO2019147862A1 (en) | 2018-01-26 | 2019-08-01 | Flx Bio, Inc. | Chemokine receptor modulators and uses thereof |
TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗tslp抗體治療炎性或阻塞性氣道疾病之方法 |
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GB2093456B (en) | 1980-10-08 | 1984-12-05 | Robins Co Inc A H | 1-r1-3-phenozyazetidines |
US5095014A (en) * | 1990-12-07 | 1992-03-10 | A. H. Robins Company, Incorporated | 3-(2-chloro-4-(trifluoromethyl)phenoxy)-1-azetidine carboxamides having anticonvulsant activity |
AU8576098A (en) | 1997-07-25 | 1999-02-16 | Merck & Co., Inc. | Cyclic amine modulators of chemokine receptor activity |
IL125658A0 (en) * | 1997-08-18 | 1999-04-11 | Hoffmann La Roche | Ccr-3 receptor antagonists |
PE20001420A1 (es) * | 1998-12-23 | 2000-12-18 | Pfizer | Moduladores de ccr5 |
GB0019006D0 (en) * | 2000-08-04 | 2000-09-20 | Astrazeneca Ab | Novel compounds |
GB0117387D0 (en) | 2001-07-17 | 2001-09-05 | Novartis Ag | Organic compounds |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110498750A (zh) * | 2019-09-02 | 2019-11-26 | 南通大学 | 一种(r)-4-羟基-1-甲氧基丁-2-基氨基甲酸叔丁酯的合成方法 |
CN110498750B (zh) * | 2019-09-02 | 2021-10-15 | 南通大学 | 一种(r)-4-羟基-1-甲氧基丁-2-基氨基甲酸叔丁酯的合成方法 |
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CO5611125A2 (es) | 2006-02-28 |
KR20040091690A (ko) | 2004-10-28 |
US20050222118A1 (en) | 2005-10-06 |
AU2003227072A1 (en) | 2003-09-29 |
JP2009102325A (ja) | 2009-05-14 |
IL164016A0 (en) | 2005-12-18 |
KR100706270B1 (ko) | 2007-04-11 |
EP1487435A1 (en) | 2004-12-22 |
MXPA04009057A (es) | 2005-01-25 |
JP4332433B2 (ja) | 2009-09-16 |
CA2479266A1 (en) | 2003-09-25 |
RU2314292C2 (ru) | 2008-01-10 |
NO20044373L (no) | 2004-10-14 |
NZ535082A (en) | 2006-08-31 |
AU2003227072B2 (en) | 2006-08-10 |
JP2005526773A (ja) | 2005-09-08 |
WO2003077907A1 (en) | 2003-09-25 |
TW200305395A (en) | 2003-11-01 |
TW200800167A (en) | 2008-01-01 |
BR0308419A (pt) | 2005-01-18 |
AR041786A1 (es) | 2005-06-01 |
PL371055A1 (en) | 2005-06-13 |
RU2004130487A (ru) | 2005-07-10 |
US7288537B2 (en) | 2007-10-30 |
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