KR20100044225A - 5-피리디논 치환된 인다졸 - Google Patents

Info

Publication number

KR20100044225A

KR20100044225A KR1020107003768A KR20107003768A KR20100044225A KR 20100044225 A KR20100044225 A KR 20100044225A KR 1020107003768 A KR1020107003768 A KR 1020107003768A KR 20107003768 A KR20107003768 A KR 20107003768A KR 20100044225 A KR20100044225 A KR 20100044225A

Authority

KR

South Korea

Prior art keywords

compound

mmol

indazol

phenyl

formula

Prior art date

2007-07-21

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Withdrawn

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• ADEKJVNFIQUGRR-UHFFFAOYSA-N 4h-pyridin-3-one Chemical group O=C1CC=CN=C1 ADEKJVNFIQUGRR-UHFFFAOYSA-N 0.000 title abstract description 3
• 150000002473 indoazoles Chemical class 0.000 title abstract description 3
• 238000000034 method Methods 0.000 claims abstract description 171
• 150000001875 compounds Chemical class 0.000 claims description 332
• -1 3-hydroxypyrrolidin-1-yl Chemical group 0.000 claims description 206
• 125000000217 alkyl group Chemical group 0.000 claims description 31
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
• 150000003839 salts Chemical class 0.000 claims description 20
• 238000011282 treatment Methods 0.000 claims description 20
• 125000003118 aryl group Chemical group 0.000 claims description 14
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 13
• 125000001072 heteroaryl group Chemical group 0.000 claims description 12
• 208000008589 Obesity Diseases 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 235000020824 obesity Nutrition 0.000 claims description 11
• 125000005842 heteroatom Chemical group 0.000 claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
• SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 6
• SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 5
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 4
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
• 208000019901 Anxiety disease Diseases 0.000 claims description 3
• 230000036506 anxiety Effects 0.000 claims description 3
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
• 201000010099 disease Diseases 0.000 claims description 3
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 2
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
• 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 2
• 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
• 150000002475 indoles Chemical class 0.000 claims description 2
• 125000001041 indolyl group Chemical group 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
• 150000004892 pyridazines Chemical class 0.000 claims description 2
• 125000004260 quinazolin-2-yl group Chemical group [H]C1=NC(*)=NC2=C1C([H])=C([H])C([H])=C2[H] 0.000 claims description 2
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical group N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 2
• 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 claims description 2
• 229940075993 receptor modulator Drugs 0.000 claims description 2
• 125000005843 halogen group Chemical group 0.000 claims 1
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
• 239000000203 mixture Substances 0.000 description 103
• 238000005481 NMR spectroscopy Methods 0.000 description 97
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 82
• 239000007787 solid Substances 0.000 description 78
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 76
• 239000000126 substance Substances 0.000 description 70
• 238000002360 preparation method Methods 0.000 description 68
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 64
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 62
• 239000000460 chlorine Substances 0.000 description 56
• 238000009472 formulation Methods 0.000 description 54
• 239000000243 solution Substances 0.000 description 51
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
• 238000006243 chemical reaction Methods 0.000 description 43
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
• 239000011734 sodium Substances 0.000 description 33
• 239000000741 silica gel Substances 0.000 description 30
• 229910002027 silica gel Inorganic materials 0.000 description 30
• 239000002585 base Substances 0.000 description 29
• 238000003818 flash chromatography Methods 0.000 description 29
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 28
• 235000019439 ethyl acetate Nutrition 0.000 description 28
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
• 239000000843 powder Substances 0.000 description 27
• 239000012267 brine Substances 0.000 description 23
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
• 238000000746 purification Methods 0.000 description 21
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 18
• 229910000024 caesium carbonate Inorganic materials 0.000 description 18
• 239000011541 reaction mixture Substances 0.000 description 18
• 239000000725 suspension Substances 0.000 description 18
• 229910000027 potassium carbonate Inorganic materials 0.000 description 17
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
• 239000002904 solvent Substances 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 239000000284 extract Substances 0.000 description 13
• 229910052736 halogen Inorganic materials 0.000 description 13
• 150000002367 halogens Chemical class 0.000 description 13
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• 238000003756 stirring Methods 0.000 description 12
• 239000007788 liquid Substances 0.000 description 11
• 108020003175 receptors Proteins 0.000 description 11
• 102000005962 receptors Human genes 0.000 description 11
• 229910000104 sodium hydride Inorganic materials 0.000 description 11
• YWNJQQNBJQUKME-UHFFFAOYSA-N 2-bromo-5-methylpyridine Chemical compound CC1=CC=C(Br)N=C1 YWNJQQNBJQUKME-UHFFFAOYSA-N 0.000 description 10
• LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 10
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• 238000004440 column chromatography Methods 0.000 description 10
• 239000013078 crystal Substances 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 125000006239 protecting group Chemical group 0.000 description 10
• 239000012312 sodium hydride Substances 0.000 description 10
• 239000000443 aerosol Substances 0.000 description 9
• 239000003054 catalyst Substances 0.000 description 9
• 229910052757 nitrogen Inorganic materials 0.000 description 9
• WKDQLIHUYYRQJE-UHFFFAOYSA-N 1-(1h-indazol-5-yl)-4-[4-(trifluoromethyl)phenyl]pyridin-2-one Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC(=O)N(C=2C=C3C=NNC3=CC=2)C=C1 WKDQLIHUYYRQJE-UHFFFAOYSA-N 0.000 description 8
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
• XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 8
• 229910021529 ammonia Inorganic materials 0.000 description 8
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 8
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 125000003545 alkoxy group Chemical group 0.000 description 7
• 229910052801 chlorine Inorganic materials 0.000 description 7
• 239000003814 drug Substances 0.000 description 7
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
• 239000004615 ingredient Substances 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 239000012299 nitrogen atmosphere Substances 0.000 description 7
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 7
• NRGKFNDKBDBBGY-UHFFFAOYSA-N 1h-pyridin-2-one;hydrochloride Chemical compound Cl.O=C1C=CC=CN1 NRGKFNDKBDBBGY-UHFFFAOYSA-N 0.000 description 6
• 239000005725 8-Hydroxyquinoline Substances 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 229960003540 oxyquinoline Drugs 0.000 description 6
• 239000002245 particle Substances 0.000 description 6
• MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 6
• 239000002287 radioligand Substances 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 5
• IQEYGQYCDAWICE-UHFFFAOYSA-N 1-[1-(2-morpholin-4-ylethyl)indazol-5-yl]-4-[4-(trifluoromethyl)phenyl]pyridin-2-one Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC(=O)N(C=2C=C3C=NN(CCN4CCOCC4)C3=CC=2)C=C1 IQEYGQYCDAWICE-UHFFFAOYSA-N 0.000 description 5
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 239000002502 liposome Substances 0.000 description 5
• 210000004072 lung Anatomy 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 229910052760 oxygen Inorganic materials 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• KJOSHMJIMSORSW-UHFFFAOYSA-N 1-[1-(3-chloropropyl)indazol-5-yl]-4-[4-(trifluoromethyl)phenyl]pyridin-2-one Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC(=O)N(C=2C=C3C=NN(CCCCl)C3=CC=2)C=C1 KJOSHMJIMSORSW-UHFFFAOYSA-N 0.000 description 4
• STVHMYNPQCLUNJ-UHFFFAOYSA-N 5-bromo-1h-indazole Chemical compound BrC1=CC=C2NN=CC2=C1 STVHMYNPQCLUNJ-UHFFFAOYSA-N 0.000 description 4
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
• MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 4
• 229910013684 LiClO 4 Inorganic materials 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• 229960000583 acetic acid Drugs 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 239000012190 activator Substances 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 229910052786 argon Inorganic materials 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 230000027455 binding Effects 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• 239000003795 chemical substances by application Substances 0.000 description 4
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 4
• 238000000354 decomposition reaction Methods 0.000 description 4
• 238000010511 deprotection reaction Methods 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 239000011737 fluorine Substances 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 229940088597 hormone Drugs 0.000 description 4
• 239000005556 hormone Substances 0.000 description 4
• 150000003840 hydrochlorides Chemical class 0.000 description 4
• 239000001257 hydrogen Substances 0.000 description 4
• 229910052739 hydrogen Inorganic materials 0.000 description 4
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 4
• 239000003446 ligand Substances 0.000 description 4
• 239000000314 lubricant Substances 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• QHXLIQMGIGEHJP-UHFFFAOYSA-N picoline - borane complex Substances [B].CC1=CC=CC=N1 QHXLIQMGIGEHJP-UHFFFAOYSA-N 0.000 description 4
• 229910000160 potassium phosphate Inorganic materials 0.000 description 4
• 235000011009 potassium phosphates Nutrition 0.000 description 4
• 230000002265 prevention Effects 0.000 description 4
• 230000009870 specific binding Effects 0.000 description 4
• 0 *c1ccc2[n]ncc2c1 Chemical compound *c1ccc2[n]ncc2c1 0.000 description 3
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