MXPA05001724A - Derivados de urea como inhibidores de quinasa. - Google Patents
Derivados de urea como inhibidores de quinasa.Info
- Publication number
- MXPA05001724A MXPA05001724A MXPA05001724A MXPA05001724A MXPA05001724A MX PA05001724 A MXPA05001724 A MX PA05001724A MX PA05001724 A MXPA05001724 A MX PA05001724A MX PA05001724 A MXPA05001724 A MX PA05001724A MX PA05001724 A MXPA05001724 A MX PA05001724A
- Authority
- MX
- Mexico
- Prior art keywords
- cyano
- urea
- pyrazinyl
- phenyl
- chloro
- Prior art date
Links
- 229940043355 kinase inhibitor Drugs 0.000 title description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
- 150000003672 ureas Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 153
- 238000000034 method Methods 0.000 claims abstract description 27
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 69
- -1 amino, carboxy Chemical group 0.000 claims description 59
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 239000004202 carbamide Substances 0.000 claims description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 20
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 230000001225 therapeutic effect Effects 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 16
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000004686 alkyl sulfanyl alkyl group Chemical group 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 5
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- PVAQILHDQHGVSP-UHFFFAOYSA-N 1-(5-chloro-2-cyclohex-2-en-1-yloxyphenyl)-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OC1CCCC=C1 PVAQILHDQHGVSP-UHFFFAOYSA-N 0.000 claims description 2
- BMZFLFKIZNBUFB-UHFFFAOYSA-N 1-(5-chloro-2-phenacyloxyphenyl)-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OCC(=O)C1=CC=CC=C1 BMZFLFKIZNBUFB-UHFFFAOYSA-N 0.000 claims description 2
- ULABCUBILRGHSL-UHFFFAOYSA-N 1-[2-[bis(2-methoxyethyl)amino]-5-cyanophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCCN(CCOC)C1=CC=C(C#N)C=C1NC(=O)NC1=CN=C(C#N)C=N1 ULABCUBILRGHSL-UHFFFAOYSA-N 0.000 claims description 2
- YFTMNKQWOWZYPP-UHFFFAOYSA-N 1-[5-bromo-2-[(2-hydroxy-2-phenylethyl)-methylamino]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1C=C(Br)C=C(NC(=O)NC=2N=CC(=NC=2)C#N)C=1N(C)CC(O)C1=CC=CC=C1 YFTMNKQWOWZYPP-UHFFFAOYSA-N 0.000 claims description 2
- SECWPIJSHYOZKM-UHFFFAOYSA-N 1-[5-chloro-2-(1-ethoxypropan-2-yloxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CCOCC(C)OC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 SECWPIJSHYOZKM-UHFFFAOYSA-N 0.000 claims description 2
- FHKIBVIDIBQHBF-UHFFFAOYSA-N 1-[5-chloro-2-(1-methoxypropan-2-yloxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCC(C)OC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 FHKIBVIDIBQHBF-UHFFFAOYSA-N 0.000 claims description 2
- MWFYFELKCFAENX-UHFFFAOYSA-N 1-[5-chloro-2-(2-methoxyethoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 MWFYFELKCFAENX-UHFFFAOYSA-N 0.000 claims description 2
- NHLKQOYABMYRNX-UHFFFAOYSA-N 1-[5-chloro-2-(3-methoxy-3-methylbutoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COC(C)(C)CCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 NHLKQOYABMYRNX-UHFFFAOYSA-N 0.000 claims description 2
- GBSMMFHITBMOIH-UHFFFAOYSA-N 1-[5-chloro-2-[3-(dimethylamino)propoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CN(C)CCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 GBSMMFHITBMOIH-UHFFFAOYSA-N 0.000 claims description 2
- 125000005336 allyloxy group Chemical group 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 3
- SECYNSPYZHCPIK-UHFFFAOYSA-N 1-(5-chloro-2-cyclopent-3-en-1-yloxyphenyl)-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OC1CC=CC1 SECYNSPYZHCPIK-UHFFFAOYSA-N 0.000 claims 1
- XYCSIMKFHRSWBS-UHFFFAOYSA-N 1-[2-[2-(4-bromophenoxy)ethoxy]-5-chlorophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OCCOC1=CC=C(Br)C=C1 XYCSIMKFHRSWBS-UHFFFAOYSA-N 0.000 claims 1
- NSHVATFCXCSIAN-UHFFFAOYSA-N 1-[2-[benzyl(2-hydroxyethyl)amino]-5-chlorophenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1C=C(Cl)C=C(NC(=O)NC=2N=CC(=NC=2)C#N)C=1N(CCO)CC1=CC=CC=C1 NSHVATFCXCSIAN-UHFFFAOYSA-N 0.000 claims 1
- JBNRXWLOFSXQPH-UHFFFAOYSA-N 1-[5-chloro-2-(2-cyclohexylethoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound C=1N=C(C#N)C=NC=1NC(=O)NC1=CC(Cl)=CC=C1OCCC1CCCCC1 JBNRXWLOFSXQPH-UHFFFAOYSA-N 0.000 claims 1
- LXKNXVQJYTVJID-UHFFFAOYSA-N 1-[5-chloro-2-(2-ethoxyethoxy)phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CCOCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 LXKNXVQJYTVJID-UHFFFAOYSA-N 0.000 claims 1
- WZDAKTSKZFOPJB-UHFFFAOYSA-N 1-[5-chloro-2-[(2-methylcyclopropyl)methoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound CC1CC1COC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 WZDAKTSKZFOPJB-UHFFFAOYSA-N 0.000 claims 1
- RRIUNYNGHUZZFO-UHFFFAOYSA-N 1-[5-chloro-2-[2-(2-methoxyethoxy)ethoxy]phenyl]-3-(5-cyanopyrazin-2-yl)urea Chemical compound COCCOCCOC1=CC=C(Cl)C=C1NC(=O)NC1=CN=C(C#N)C=N1 RRIUNYNGHUZZFO-UHFFFAOYSA-N 0.000 claims 1
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 31
- 102000001253 Protein Kinase Human genes 0.000 abstract description 7
- 108060006633 protein kinase Proteins 0.000 abstract description 7
- 239000000047 product Substances 0.000 description 75
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 74
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- PQANGXXSEABURG-UHFFFAOYSA-N cyclohex-2-en-1-ol Chemical compound OC1CCCC=C1 PQANGXXSEABURG-UHFFFAOYSA-N 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000012141 concentrate Substances 0.000 description 17
- 235000008504 concentrate Nutrition 0.000 description 17
- 235000013877 carbamide Nutrition 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 150000002431 hydrogen Chemical group 0.000 description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 125000005843 halogen group Chemical group 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 9
- 125000002950 monocyclic group Chemical group 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 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 8
- IBZKBSXREAQDTO-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)ethanamine Chemical compound COCCNCCOC IBZKBSXREAQDTO-UHFFFAOYSA-N 0.000 description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 7
- 125000004414 alkyl thio group Chemical group 0.000 description 7
- 125000002619 bicyclic group Chemical group 0.000 description 7
- 125000001188 haloalkyl group Chemical group 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 101150113535 chek1 gene Proteins 0.000 description 6
- 125000004966 cyanoalkyl group Chemical group 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 125000004971 nitroalkyl group Chemical group 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000004438 haloalkoxy group Chemical group 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 125000004043 oxo group Chemical group O=* 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 125000005129 aryl carbonyl group Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000005909 Kieselgur Substances 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- ZCTYHONEGJTYQV-UHFFFAOYSA-N N-methylphenylethanolamine Chemical compound CNCC(O)C1=CC=CC=C1 ZCTYHONEGJTYQV-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 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 3
- 201000010099 disease Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
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- 239000012065 filter cake Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- ARXJGSRGQADJSQ-UHFFFAOYSA-N 1-methoxypropan-2-ol Chemical compound COCC(C)O ARXJGSRGQADJSQ-UHFFFAOYSA-N 0.000 description 2
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 2
- XNIOWJUQPMKCIJ-UHFFFAOYSA-N 2-(benzylamino)ethanol Chemical compound OCCNCC1=CC=CC=C1 XNIOWJUQPMKCIJ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000005083 alkoxyalkoxy group Chemical group 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
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- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- XDJCYKMWJCYQJM-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCO XDJCYKMWJCYQJM-UHFFFAOYSA-N 0.000 description 1
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 239000006208 topical dosage form Substances 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 230000001573 trophoblastic effect Effects 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 210000003741 urothelium Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 201000010653 vesiculitis Diseases 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 235000014692 zinc oxide Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/218,121 US20040034038A1 (en) | 2002-08-13 | 2002-08-13 | Urea kinase inhibitors |
| PCT/US2003/024474 WO2004014876A1 (en) | 2002-08-13 | 2003-08-05 | Urea derivatives as kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA05001724A true MXPA05001724A (es) | 2005-05-27 |
Family
ID=31714498
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA05001724A MXPA05001724A (es) | 2002-08-13 | 2003-08-05 | Derivados de urea como inhibidores de quinasa. |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20040034038A1 (https=) |
| EP (1) | EP1534692A1 (https=) |
| JP (1) | JP2006500353A (https=) |
| CA (1) | CA2494848A1 (https=) |
| MX (1) | MXPA05001724A (https=) |
| WO (1) | WO2004014876A1 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005072733A1 (en) * | 2004-01-20 | 2005-08-11 | Millennium Pharmaceuticals, Inc. | Dyarylurea compounds as chk-1 inhibitors |
| GB0512324D0 (en) * | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
| MX2007000265A (es) * | 2004-07-02 | 2007-07-20 | Icos Corp | Compuestos utiles para inhibir chk1. |
| HRP20100678T1 (hr) | 2005-03-29 | 2011-02-28 | Icos Corporation | Derivati heteroariluree korisni kao inhibitori chk1 |
| GEP20105074B (en) * | 2005-12-21 | 2010-09-10 | Novartis Ag | Pyrimidinyl aryl urea derivatives being fgf inhibitors |
| HU227696B1 (en) * | 2006-04-13 | 2011-12-28 | Egyt Gyogyszervegyeszeti Gyar | Zinc salt of rosuvastatin, process for its preparation and pharmaceutical compositions containing it |
| JP2010510222A (ja) * | 2006-11-17 | 2010-04-02 | シェーリング コーポレイション | 増殖性障害に対する併用療法 |
| US8314108B2 (en) | 2008-12-17 | 2012-11-20 | Eli Lilly And Company | 5-(5-(2-(3-aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-ylamino)pyrazine-2-carbonitrile, pharmaceutically acceptable salts thereof, or solvate of salts |
| PA8850801A1 (es) | 2008-12-17 | 2010-07-27 | Lilly Co Eli | Compuestos útiles para inhibir chk1 |
| GB201008005D0 (en) | 2010-05-13 | 2010-06-30 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| EP2970114B1 (en) * | 2013-03-15 | 2019-05-15 | Bristol-Myers Squibb Company | Ido inhibitors |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1213022C (zh) * | 1997-12-22 | 2005-08-03 | 拜尔有限公司 | 用对称和不对称的取代二苯脲抑制raf激酶 |
| EP1140840B1 (en) * | 1999-01-13 | 2006-03-22 | Bayer Pharmaceuticals Corp. | -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| KR20020084116A (ko) * | 2000-02-07 | 2002-11-04 | 애보트 게엠베하 운트 콤파니 카게 | 2-벤조티아졸릴 우레아 유도체 및 이의 단백질 키나제억제제로서의 용도 |
| UA76977C2 (en) * | 2001-03-02 | 2006-10-16 | Icos Corp | Aryl- and heteroaryl substituted chk1 inhibitors and their use as radiosensitizers and chemosensitizers |
-
2002
- 2002-08-13 US US10/218,121 patent/US20040034038A1/en not_active Abandoned
-
2003
- 2003-08-05 MX MXPA05001724A patent/MXPA05001724A/es unknown
- 2003-08-05 EP EP03784917A patent/EP1534692A1/en not_active Withdrawn
- 2003-08-05 WO PCT/US2003/024474 patent/WO2004014876A1/en not_active Ceased
- 2003-08-05 CA CA002494848A patent/CA2494848A1/en not_active Abandoned
- 2003-08-05 JP JP2004527753A patent/JP2006500353A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004014876A1 (en) | 2004-02-19 |
| JP2006500353A (ja) | 2006-01-05 |
| US20040034038A1 (en) | 2004-02-19 |
| CA2494848A1 (en) | 2004-02-19 |
| EP1534692A1 (en) | 2005-06-01 |
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