NO322109B1 - Vitronektinreseporantagonister - Google Patents

Info

Publication number

NO322109B1

NO322109B1 NO20021113A NO20021113A NO322109B1 NO 322109 B1 NO322109 B1 NO 322109B1 NO 20021113 A NO20021113 A NO 20021113A NO 20021113 A NO20021113 A NO 20021113A NO 322109 B1 NO322109 B1 NO 322109B1

Authority

NO

Norway

Prior art keywords

mmol

phenyl

pyridin

mixture

compound

Prior art date

1999-09-07

Links

• Espacenet
• Global Dossier
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• 150000001875 compounds Chemical class 0.000 claims description 178
• 238000002360 preparation method Methods 0.000 claims description 42
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
• 206010028980 Neoplasm Diseases 0.000 claims description 14
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
• 201000010099 disease Diseases 0.000 claims description 14
• 239000002253 acid Substances 0.000 claims description 13
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 12
• 239000002246 antineoplastic agent Substances 0.000 claims description 12
• 229940034982 antineoplastic agent Drugs 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 11
• 208000006386 Bone Resorption Diseases 0.000 claims description 10
• 230000024279 bone resorption Effects 0.000 claims description 10
• 150000003839 salts Chemical class 0.000 claims description 10
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 9
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
• 229940079593 drug Drugs 0.000 claims description 8
• 208000001132 Osteoporosis Diseases 0.000 claims description 7
• 239000003112 inhibitor Substances 0.000 claims description 6
• 208000037803 restenosis Diseases 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• QDXYOYZNHXVNRD-IBGZPJMESA-N (3s)-4-[4-[2-[6-(methylamino)pyridin-2-yl]ethoxy]phenyl]-3-pyridin-3-ylbutanoic acid Chemical compound CNC1=CC=CC(CCOC=2C=CC(C[C@@H](CC(O)=O)C=3C=NC=CC=3)=CC=2)=N1 QDXYOYZNHXVNRD-IBGZPJMESA-N 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 230000004614 tumor growth Effects 0.000 claims description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
• NSDVPNAHPJEOEL-UHFFFAOYSA-N 4-[4-[2-[6-(methylamino)pyridin-2-yl]ethoxy]phenyl]-3-[4-[methyl(phenyl)carbamoyl]-1,3-oxazol-2-yl]butanoic acid Chemical compound CNC1=CC=CC(CCOC=2C=CC(CC(CC(O)=O)C=3OC=C(N=3)C(=O)N(C)C=3C=CC=CC=3)=CC=2)=N1 NSDVPNAHPJEOEL-UHFFFAOYSA-N 0.000 claims description 3
• 206010027476 Metastases Diseases 0.000 claims description 3
• 230000033115 angiogenesis Effects 0.000 claims description 3
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
• 230000009401 metastasis Effects 0.000 claims description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims description 3
• YXKANWFNHFBKSU-UHFFFAOYSA-N 4-[4-[2-[6-(methylamino)pyridin-2-yl]ethoxy]phenyl]-3-(3-methyl-2h-1,3-thiazol-2-yl)butanoic acid Chemical compound CNC1=CC=CC(CCOC=2C=CC(CC(CC(O)=O)C3N(C=CS3)C)=CC=2)=N1 YXKANWFNHFBKSU-UHFFFAOYSA-N 0.000 claims description 2
• VLACXOGZAUIADN-UHFFFAOYSA-N 4-[4-[2-[6-(methylamino)pyridin-2-yl]ethoxy]phenyl]-3-[4-(trifluoromethyl)phenyl]butanoic acid Chemical compound CNC1=CC=CC(CCOC=2C=CC(CC(CC(O)=O)C=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 VLACXOGZAUIADN-UHFFFAOYSA-N 0.000 claims description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
• 230000008485 antagonism Effects 0.000 claims 2
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims 2
• 229960004316 cisplatin Drugs 0.000 claims 2
• 230000002401 inhibitory effect Effects 0.000 claims 2
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical group C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims 2
• 229960000303 topotecan Drugs 0.000 claims 2
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims 1
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 194
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 160
• 239000000203 mixture Substances 0.000 description 131
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 117
• 239000000243 solution Substances 0.000 description 104
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 99
• 235000019439 ethyl acetate Nutrition 0.000 description 80
• 210000004027 cell Anatomy 0.000 description 64
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 61
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
• 239000000741 silica gel Substances 0.000 description 51
• 229910002027 silica gel Inorganic materials 0.000 description 51
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
• 239000007787 solid Substances 0.000 description 45
• 238000005481 NMR spectroscopy Methods 0.000 description 44
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 44
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
• 239000012044 organic layer Substances 0.000 description 37
• -1 N-methyl- N-phenyl-amino Chemical group 0.000 description 35
• 210000002997 osteoclast Anatomy 0.000 description 35
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• 238000000034 method Methods 0.000 description 33
• 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 33
• 238000006243 chemical reaction Methods 0.000 description 32
• 239000003921 oil Substances 0.000 description 32
• 235000019198 oils Nutrition 0.000 description 32
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 27
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 26
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
• 229920006395 saturated elastomer Polymers 0.000 description 22
• 235000002639 sodium chloride Nutrition 0.000 description 22
• 239000011541 reaction mixture Substances 0.000 description 21
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
• 239000000725 suspension Substances 0.000 description 20
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 19
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
• 239000000872 buffer Substances 0.000 description 19
• CLUBWMGIEFXAFU-UHFFFAOYSA-N 1-[6-(methylamino)pyridin-2-yl]ethanol Chemical compound CNC1=CC=CC(C(C)O)=N1 CLUBWMGIEFXAFU-UHFFFAOYSA-N 0.000 description 18
• 102100022337 Integrin alpha-V Human genes 0.000 description 17
• 108010048673 Vitronectin Receptors Proteins 0.000 description 17
• DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 17
• 229910001868 water Inorganic materials 0.000 description 17
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 16
• 238000010992 reflux Methods 0.000 description 16
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
• 239000011324 bead Substances 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 238000000746 purification Methods 0.000 description 14
• 229910000104 sodium hydride Inorganic materials 0.000 description 14
• 238000004519 manufacturing process Methods 0.000 description 13
• 239000000463 material Substances 0.000 description 13
• 239000002609 medium Substances 0.000 description 13
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 13
• 239000005557 antagonist Substances 0.000 description 12
• 238000003556 assay Methods 0.000 description 12
• 229910052763 palladium Inorganic materials 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• 239000002904 solvent Substances 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• 238000005119 centrifugation Methods 0.000 description 11
• 238000001802 infusion Methods 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• 238000000921 elemental analysis Methods 0.000 description 10
• 239000012737 fresh medium Substances 0.000 description 10
• 239000007788 liquid Substances 0.000 description 10
• 125000006239 protecting group Chemical group 0.000 description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
• 230000002829 reductive effect Effects 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 9
• 239000012980 RPMI-1640 medium Substances 0.000 description 9
• 241000700159 Rattus Species 0.000 description 9
• 230000027455 binding Effects 0.000 description 9
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
• 238000003818 flash chromatography Methods 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 239000011780 sodium chloride Substances 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• 210000000988 bone and bone Anatomy 0.000 description 8
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
• KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 8
• 238000011534 incubation Methods 0.000 description 8
• 239000012442 inert solvent Substances 0.000 description 8
• 239000000543 intermediate Substances 0.000 description 8
• 150000002576 ketones Chemical class 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 8
• 102000005962 receptors Human genes 0.000 description 8
• 108020003175 receptors Proteins 0.000 description 8
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
• 210000001519 tissue Anatomy 0.000 description 8
• 238000002965 ELISA Methods 0.000 description 7
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
• 108010031318 Vitronectin Proteins 0.000 description 7
• 102100035140 Vitronectin Human genes 0.000 description 7
• 239000000010 aprotic solvent Substances 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 108010012088 Fibrinogen Receptors Proteins 0.000 description 6
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
• AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• 102000007591 Tartrate-Resistant Acid Phosphatase Human genes 0.000 description 6
• 108010032050 Tartrate-Resistant Acid Phosphatase Proteins 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 6
• 239000006285 cell suspension Substances 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000010494 dissociation reaction Methods 0.000 description 6
• 230000005593 dissociations Effects 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 6
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 6
• 239000011777 magnesium Substances 0.000 description 6
• 210000005087 mononuclear cell Anatomy 0.000 description 6
• 229910052757 nitrogen Inorganic materials 0.000 description 6
• 230000020477 pH reduction Effects 0.000 description 6
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
• 238000005406 washing Methods 0.000 description 6
• WEMUNMQFXOILNO-UHFFFAOYSA-N 2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethanol Chemical compound C1CCNC2=NC(CCO)=CC=C21 WEMUNMQFXOILNO-UHFFFAOYSA-N 0.000 description 5
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 5
• 208000002966 Giant Cell Tumor of Bone Diseases 0.000 description 5
• 239000012979 RPMI medium Substances 0.000 description 5
• 150000001336 alkenes Chemical class 0.000 description 5
• 125000000217 alkyl group Chemical group 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 229940098773 bovine serum albumin Drugs 0.000 description 5
• 239000011575 calcium Substances 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 238000010168 coupling process Methods 0.000 description 5
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
• 238000001035 drying Methods 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• 239000003446 ligand Substances 0.000 description 5
• 230000001404 mediated effect Effects 0.000 description 5
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 5
• 230000007935 neutral effect Effects 0.000 description 5
• 238000007911 parenteral administration Methods 0.000 description 5
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 5
• 239000002953 phosphate buffered saline Substances 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 230000008569 process Effects 0.000 description 5
• 238000010926 purge Methods 0.000 description 5
• 238000004809 thin layer chromatography Methods 0.000 description 5
• COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 5
• HFFWXPIQBUOVFO-UHFFFAOYSA-N (4-bromophenoxy)-tri(propan-2-yl)silane Chemical compound CC(C)[Si](C(C)C)(C(C)C)OC1=CC=C(Br)C=C1 HFFWXPIQBUOVFO-UHFFFAOYSA-N 0.000 description 4
• BLRCPDFGSIPXRC-UHFFFAOYSA-N 1-o-benzyl 4-o-methyl 2-methylidenebutanedioate Chemical compound COC(=O)CC(=C)C(=O)OCC1=CC=CC=C1 BLRCPDFGSIPXRC-UHFFFAOYSA-N 0.000 description 4
• CGSPVYCZBDFPHJ-UHFFFAOYSA-N 2,2-dimethyl-n-pyridin-2-ylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC=CC=N1 CGSPVYCZBDFPHJ-UHFFFAOYSA-N 0.000 description 4
• YYGDNYRUXHYIKG-UHFFFAOYSA-N 2-[4-methoxy-1-[4-[(2-methylpropan-2-yl)oxycarbonyloxy]phenyl]-4-oxobutan-2-yl]-1,3-oxazole-4-carboxylic acid Chemical compound N=1C(C(O)=O)=COC=1C(CC(=O)OC)CC1=CC=C(OC(=O)OC(C)(C)C)C=C1 YYGDNYRUXHYIKG-UHFFFAOYSA-N 0.000 description 4
• NRPFNQUDKRYCNX-UHFFFAOYSA-N 4-methoxyphenylacetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1 NRPFNQUDKRYCNX-UHFFFAOYSA-N 0.000 description 4
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 4
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