CA2380786A1 - 3(5)-ureido-pyrazole derivatives, process for their preparation and their use as antitumor agents - Google Patents
3(5)-ureido-pyrazole derivatives, process for their preparation and their use as antitumor agents Download PDFInfo
- Publication number
- CA2380786A1 CA2380786A1 CA002380786A CA2380786A CA2380786A1 CA 2380786 A1 CA2380786 A1 CA 2380786A1 CA 002380786 A CA002380786 A CA 002380786A CA 2380786 A CA2380786 A CA 2380786A CA 2380786 A1 CA2380786 A1 CA 2380786A1
- Authority
- CA
- Canada
- Prior art keywords
- pyrazol
- cyclopropyl
- urea
- amino
- phenethyl
- Prior art date
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims description 37
- 230000008569 process Effects 0.000 title description 13
- 239000002246 antineoplastic agent Substances 0.000 title description 10
- 238000002360 preparation method Methods 0.000 title description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- XAEGRAIWWBXIRR-UHFFFAOYSA-N 1h-pyrazol-5-ylurea Chemical class NC(=O)NC=1C=CNN=1 XAEGRAIWWBXIRR-UHFFFAOYSA-N 0.000 claims abstract description 23
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 201000011510 cancer Diseases 0.000 claims abstract description 11
- 208000035475 disorder Diseases 0.000 claims abstract description 11
- 230000002062 proliferating effect Effects 0.000 claims abstract description 11
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 4
- 208000036142 Viral infection Diseases 0.000 claims abstract description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 4
- 230000009385 viral infection Effects 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 175
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 74
- -1 carboxy, amino Chemical group 0.000 claims description 54
- 239000004202 carbamide Substances 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 15
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 13
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 230000005764 inhibitory process Effects 0.000 claims description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims description 13
- 102000016736 Cyclin Human genes 0.000 claims description 12
- 108050006400 Cyclin Proteins 0.000 claims description 12
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 12
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 12
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 12
- 125000005014 aminoalkynyl group Chemical group 0.000 claims description 12
- 125000001769 aryl amino group Chemical group 0.000 claims description 12
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 12
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 12
- 125000005110 aryl thio group Chemical group 0.000 claims description 12
- 125000004104 aryloxy group Chemical group 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 108091000080 Phosphotransferase Proteins 0.000 claims description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 102000020233 phosphotransferase Human genes 0.000 claims description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 230000003301 hydrolyzing effect Effects 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 229920000642 polymer Polymers 0.000 claims description 8
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 claims description 7
- RRGJIRNODFCZTR-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(1h-indol-6-yl)urea Chemical compound C=1C=C2C=CNC2=CC=1NC(=O)NC(NN=1)=CC=1C1CC1 RRGJIRNODFCZTR-UHFFFAOYSA-N 0.000 claims description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 230000022131 cell cycle Effects 0.000 claims description 5
- 230000004663 cell proliferation Effects 0.000 claims description 5
- 230000001419 dependent effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- JNERJKKRDPVUEX-UHFFFAOYSA-N 1-(2-phenylethyl)-3-[5-(2-phenylethyl)-1h-pyrazol-3-yl]urea Chemical compound C=1C(CCC=2C=CC=CC=2)=NNC=1NC(=O)NCCC1=CC=CC=C1 JNERJKKRDPVUEX-UHFFFAOYSA-N 0.000 claims description 4
- LPAQWHHDOXAKNP-UHFFFAOYSA-N 1-(5-cyclopentyl-1h-pyrazol-3-yl)-3-(2-phenylethyl)urea Chemical compound C=1C(C2CCCC2)=NNC=1NC(=O)NCCC1=CC=CC=C1 LPAQWHHDOXAKNP-UHFFFAOYSA-N 0.000 claims description 4
- XHHMORVGUBZUCC-UHFFFAOYSA-N 1-(5-cyclopentyl-1h-pyrazol-3-yl)-3-[2-(3,4-dimethoxyphenyl)ethyl]urea Chemical compound C1=C(OC)C(OC)=CC=C1CCNC(=O)NC1=CC(C2CCCC2)=NN1 XHHMORVGUBZUCC-UHFFFAOYSA-N 0.000 claims description 4
- FPXSIHNCQOGEIE-UHFFFAOYSA-N 1-(5-cyclopentyl-1h-pyrazol-3-yl)-3-propylurea Chemical compound N1C(NC(=O)NCCC)=CC(C2CCCC2)=N1 FPXSIHNCQOGEIE-UHFFFAOYSA-N 0.000 claims description 4
- OJRWHECJGITDRU-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(2-piperidin-1-ylethyl)urea Chemical compound C=1C(C2CC2)=NNC=1NC(=O)NCCN1CCCCC1 OJRWHECJGITDRU-UHFFFAOYSA-N 0.000 claims description 4
- WTENIFDFISCSNB-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(2-pyridin-2-ylethyl)urea Chemical compound C=1C(C2CC2)=NNC=1NC(=O)NCCC1=CC=CC=N1 WTENIFDFISCSNB-UHFFFAOYSA-N 0.000 claims description 4
- VIEMSIQIDUUAPS-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[(1-ethylpyrrolidin-2-yl)methyl]urea Chemical compound CCN1CCCC1CNC(=O)NC1=CC(C2CC2)=NN1 VIEMSIQIDUUAPS-UHFFFAOYSA-N 0.000 claims description 4
- VVKLIMBQAJSOGP-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[(2,4-dichlorophenyl)methyl]urea Chemical compound ClC1=CC(Cl)=CC=C1CNC(=O)NC1=CC(C2CC2)=NN1 VVKLIMBQAJSOGP-UHFFFAOYSA-N 0.000 claims description 4
- MLJRGKUBYURCTM-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[(3,4-dichlorophenyl)methyl]urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CNC(=O)NC1=CC(C2CC2)=NN1 MLJRGKUBYURCTM-UHFFFAOYSA-N 0.000 claims description 4
- RQGKFXBYCVIDLR-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[(4-fluorophenyl)methyl]urea Chemical compound C1=CC(F)=CC=C1CNC(=O)NC1=CC(C2CC2)=NN1 RQGKFXBYCVIDLR-UHFFFAOYSA-N 0.000 claims description 4
- ALKIPBUKIYZEEG-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[(4-methylphenyl)methyl]urea Chemical compound C1=CC(C)=CC=C1CNC(=O)NC1=CC(C2CC2)=NN1 ALKIPBUKIYZEEG-UHFFFAOYSA-N 0.000 claims description 4
- SSSIXPWCPBDBDK-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[2-(2h-imidazol-4-yl)ethyl]urea Chemical compound C=1C(C2CC2)=NNC=1NC(=O)NCCC1=NCN=C1 SSSIXPWCPBDBDK-UHFFFAOYSA-N 0.000 claims description 4
- CAHHXBJGROIOFC-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[[3-(trifluoromethyl)phenyl]methyl]urea Chemical compound FC(F)(F)C1=CC=CC(CNC(=O)NC=2NN=C(C=2)C2CC2)=C1 CAHHXBJGROIOFC-UHFFFAOYSA-N 0.000 claims description 4
- OUAPTOAHWNWJFF-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-phenylurea Chemical compound C=1C=CC=CC=1NC(=O)NC(NN=1)=CC=1C1CC1 OUAPTOAHWNWJFF-UHFFFAOYSA-N 0.000 claims description 4
- GLKUJDRNEWGWED-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound ClC1=CC=CC=C1CNC(=O)NC1=CC(C2CC2)=NN1 GLKUJDRNEWGWED-UHFFFAOYSA-N 0.000 claims description 4
- YIPVUYPVWMTONF-UHFFFAOYSA-N 1-[2-(3-chlorophenyl)ethyl]-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound ClC1=CC=CC(CCNC(=O)NC=2NN=C(C=2)C2CC2)=C1 YIPVUYPVWMTONF-UHFFFAOYSA-N 0.000 claims description 4
- MEFQJYDWUSDIGD-UHFFFAOYSA-N 1-[2-(4-hydroxyphenyl)ethyl]-3-[5-(2-phenylethyl)-1h-pyrazol-3-yl]urea Chemical compound C1=CC(O)=CC=C1CCNC(=O)NC1=CC(CCC=2C=CC=CC=2)=NN1 MEFQJYDWUSDIGD-UHFFFAOYSA-N 0.000 claims description 4
- NTMDAPLYMTYWFT-UHFFFAOYSA-N 1-butyl-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound N1C(NC(=O)NCCCC)=CC(C2CC2)=N1 NTMDAPLYMTYWFT-UHFFFAOYSA-N 0.000 claims description 4
- NXJOUUPOIKRHKE-UHFFFAOYSA-N 4-(aminomethyl)-n-(5-cyclopentyl-1h-pyrazol-3-yl)piperidine-1-carboxamide Chemical compound C1CC(CN)CCN1C(=O)NC1=CC(C2CCCC2)=NN1 NXJOUUPOIKRHKE-UHFFFAOYSA-N 0.000 claims description 4
- YLUKNHHMAPJELC-UHFFFAOYSA-N 4-(aminomethyl)-n-[5-(2-phenylethyl)-1h-pyrazol-3-yl]piperidine-1-carboxamide Chemical compound C1CC(CN)CCN1C(=O)NC1=CC(CCC=2C=CC=CC=2)=NN1 YLUKNHHMAPJELC-UHFFFAOYSA-N 0.000 claims description 4
- HPEUFTOMXSOAMP-UHFFFAOYSA-N 4-[2-nitro-4-(trifluoromethyl)phenyl]-n-[5-(2-phenylethyl)-1h-pyrazol-3-yl]piperazine-1-carboxamide Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1N1CCN(C(=O)NC=2NN=C(CCC=3C=CC=CC=3)C=2)CC1 HPEUFTOMXSOAMP-UHFFFAOYSA-N 0.000 claims description 4
- UFPLCCLBXJKWPZ-UHFFFAOYSA-N 4-benzyl-n-(5-cyclopentyl-1h-pyrazol-3-yl)piperazine-1-carboxamide Chemical compound C1CN(CC=2C=CC=CC=2)CCN1C(=O)NC(NN=1)=CC=1C1CCCC1 UFPLCCLBXJKWPZ-UHFFFAOYSA-N 0.000 claims description 4
- DTZHLGKCUSWJAU-UHFFFAOYSA-N 4-benzyl-n-[5-(2-phenylethyl)-1h-pyrazol-3-yl]piperazine-1-carboxamide Chemical compound C1CN(CC=2C=CC=CC=2)CCN1C(=O)NC(NN=1)=CC=1CCC1=CC=CC=C1 DTZHLGKCUSWJAU-UHFFFAOYSA-N 0.000 claims description 4
- CCKDCFIPKHSBLP-UHFFFAOYSA-N 4-methyl-n-[5-(2-phenylethyl)-1h-pyrazol-3-yl]piperazine-1-carboxamide Chemical compound C1CN(C)CCN1C(=O)NC1=CC(CCC=2C=CC=CC=2)=NN1 CCKDCFIPKHSBLP-UHFFFAOYSA-N 0.000 claims description 4
- NUHPXWLXOFUHMG-UHFFFAOYSA-N 4-phenyl-n-[5-(2-phenylethyl)-1h-pyrazol-3-yl]piperazine-1-carboxamide Chemical compound C1CN(C=2C=CC=CC=2)CCN1C(=O)NC(NN=1)=CC=1CCC1=CC=CC=C1 NUHPXWLXOFUHMG-UHFFFAOYSA-N 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 201000009030 Carcinoma Diseases 0.000 claims description 4
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- 239000003085 diluting agent Substances 0.000 claims description 4
- 201000005787 hematologic cancer Diseases 0.000 claims description 4
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 4
- ZWUDNZGGEODYHA-UHFFFAOYSA-N n-(5-cyclopentyl-1h-pyrazol-3-yl)-4-[2-nitro-4-(trifluoromethyl)phenyl]piperazine-1-carboxamide Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1N1CCN(C(=O)NC=2NN=C(C=2)C2CCCC2)CC1 ZWUDNZGGEODYHA-UHFFFAOYSA-N 0.000 claims description 4
- AHFFUFRQYKJGJO-UHFFFAOYSA-N n-(5-cyclopentyl-1h-pyrazol-3-yl)-4-methylpiperazine-1-carboxamide Chemical compound C1CN(C)CCN1C(=O)NC1=CC(C2CCCC2)=NN1 AHFFUFRQYKJGJO-UHFFFAOYSA-N 0.000 claims description 4
- ZAOJKSRSJWRKMB-UHFFFAOYSA-N n-(5-cyclopentyl-1h-pyrazol-3-yl)-4-phenylpiperazine-1-carboxamide Chemical compound C1CN(C=2C=CC=CC=2)CCN1C(=O)NC(NN=1)=CC=1C1CCCC1 ZAOJKSRSJWRKMB-UHFFFAOYSA-N 0.000 claims description 4
- QTOIYFFZKXQIAT-UHFFFAOYSA-N n-(5-cyclopentyl-1h-pyrazol-3-yl)morpholine-4-carboxamide Chemical compound C1COCCN1C(=O)NC(NN=1)=CC=1C1CCCC1 QTOIYFFZKXQIAT-UHFFFAOYSA-N 0.000 claims description 4
- LUHBNVCYMYNIDQ-UHFFFAOYSA-N n-(5-cyclopentyl-1h-pyrazol-3-yl)piperazine-1-carboxamide Chemical compound C1CNCCN1C(=O)NC(NN=1)=CC=1C1CCCC1 LUHBNVCYMYNIDQ-UHFFFAOYSA-N 0.000 claims description 4
- BPBJODNQCKQQKF-UHFFFAOYSA-N n-(5-cyclopentyl-1h-pyrazol-3-yl)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)NC(NN=1)=CC=1C1CCCC1 BPBJODNQCKQQKF-UHFFFAOYSA-N 0.000 claims description 4
- ZRXIDGLJJYNNPC-UHFFFAOYSA-N n-[5-(2-phenylethyl)-1h-pyrazol-3-yl]piperazine-1-carboxamide Chemical compound C1CNCCN1C(=O)NC(NN=1)=CC=1CCC1=CC=CC=C1 ZRXIDGLJJYNNPC-UHFFFAOYSA-N 0.000 claims description 4
- AMQRDSWZYLWQFB-UHFFFAOYSA-N n-[5-(2-phenylethyl)-1h-pyrazol-3-yl]piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)NC(NN=1)=CC=1CCC1=CC=CC=C1 AMQRDSWZYLWQFB-UHFFFAOYSA-N 0.000 claims description 4
- SMJLZWKZTCCUDX-UHFFFAOYSA-N n-[5-(2-phenylethyl)-1h-pyrazol-3-yl]pyrrolidine-1-carboxamide Chemical compound C1CCCN1C(=O)NC(NN=1)=CC=1CCC1=CC=CC=C1 SMJLZWKZTCCUDX-UHFFFAOYSA-N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
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- 210000001685 thyroid gland Anatomy 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- NBIVABITAGSCNR-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-ylmethyl)-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound C=1C=C2OCOC2=CC=1CNC(=O)NC(NN=1)=CC=1C1CC1 NBIVABITAGSCNR-UHFFFAOYSA-N 0.000 claims description 3
- FUUVDMXWFLVEAL-UHFFFAOYSA-N 1-(1-benzylpiperidin-4-yl)-3-(5-cyclopentyl-1h-pyrazol-3-yl)urea Chemical compound C=1C(C2CCCC2)=NNC=1NC(=O)NC(CC1)CCN1CC1=CC=CC=C1 FUUVDMXWFLVEAL-UHFFFAOYSA-N 0.000 claims description 3
- LJWNEBAMSQLONR-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NC=2NN=C(C=2)C2CC2)=C1 LJWNEBAMSQLONR-UHFFFAOYSA-N 0.000 claims description 3
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- RPOPBLOLIWMNIR-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(2,5-dimethylpyrazol-3-yl)urea Chemical compound CN1N=C(C)C=C1NC(=O)NC1=CC(C2CC2)=NN1 RPOPBLOLIWMNIR-UHFFFAOYSA-N 0.000 claims description 3
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- YWIJHJCJXNMHLF-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(2-pyrrolidin-1-ylethyl)urea Chemical compound C=1C(C2CC2)=NNC=1NC(=O)NCCN1CCCC1 YWIJHJCJXNMHLF-UHFFFAOYSA-N 0.000 claims description 3
- SBZFKIXGUOMWGU-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(3,4-dimethoxyphenyl)urea Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)NC1=CC(C2CC2)=NN1 SBZFKIXGUOMWGU-UHFFFAOYSA-N 0.000 claims description 3
- IRDDJYLPWTWDKU-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(3,5-dimethylphenyl)urea Chemical compound CC1=CC(C)=CC(NC(=O)NC=2NN=C(C=2)C2CC2)=C1 IRDDJYLPWTWDKU-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or 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
- C07D231/38—Nitrogen atoms
- C07D231/40—Acylated on said nitrogen atom
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- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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- A61K31/5375—1,4-Oxazines, e.g. morpholine
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US09/372,833 US6387900B1 (en) | 1999-08-12 | 1999-08-12 | 3(5)-ureido-pyrazole derivatives process for their preparation and their use as antitumor agents |
US09/372,833 | 1999-08-12 | ||
PCT/US2000/017878 WO2001012188A1 (en) | 1999-08-12 | 2000-08-11 | 3(5)-ureido-pyrazole derivatives, process for their preparation and their use as antitumor agents |
Publications (1)
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CA2380786A1 true CA2380786A1 (en) | 2001-02-22 |
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CA002380786A Abandoned CA2380786A1 (en) | 1999-08-12 | 2000-08-11 | 3(5)-ureido-pyrazole derivatives, process for their preparation and their use as antitumor agents |
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Families Citing this family (75)
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US20070244120A1 (en) * | 2000-08-18 | 2007-10-18 | Jacques Dumas | Inhibition of raf kinase using substituted heterocyclic ureas |
ES2377847T3 (es) | 1999-01-13 | 2012-04-02 | Bayer Healthcare Llc | Difenil ureas sustituidas con omega-carboxi arilo como agentes inhibidores de la cinasa p38 |
US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
CA2699568C (en) | 1999-12-24 | 2013-03-12 | Aventis Pharma Limited | Azaindoles |
AU2972701A (en) * | 2000-02-07 | 2001-08-14 | Bristol Myers Squibb Co | 3-aminopyrazole inhibitors of cyclin dependent kinases |
JP2004507455A (ja) | 2000-04-25 | 2004-03-11 | ブリストル−マイヤーズ スクイブ カンパニー | サイクリン依存性キナーゼ阻害剤としての、5−チオ−、スルフィニル−およびスルホニルピラゾロ[3,4−b]−ピリジンの用途 |
AU2001280009A1 (en) * | 2000-08-31 | 2002-03-13 | Pfizer Products Inc. | Pyrazole derivatives and their use as protein kinase inhibitors |
AU2002215053A1 (en) * | 2000-11-27 | 2002-06-24 | Pharmacia Italia S.P.A. | Phenylacetamido- pyrazole derivatives and their use as antitumor agents |
GB0115109D0 (en) | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
PT2305255E (pt) † | 2001-12-03 | 2012-09-04 | Bayer Healthcare Llc | Compostos de arilureia em combinação com outros agentes citostáticos ou citotóxicos para tratamento de cancros humanos |
US20050113283A1 (en) * | 2002-01-18 | 2005-05-26 | David Solow-Cordero | Methods of treating conditions associated with an EDG-4 receptor |
SI1478358T1 (sl) | 2002-02-11 | 2013-09-30 | Bayer Healthcare Llc | Sorafenib tozilat za zdravljenje bolezni, značilnih po abnormalni angiogenezi |
KR20030071029A (ko) * | 2002-02-27 | 2003-09-03 | 주식회사 팜제니아 | 항암제 및 방사선 치료 증진제로서 유용한 조성물 |
US20030225089A1 (en) * | 2002-04-10 | 2003-12-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and p38 kinase inhibitors |
DE10221052A1 (de) * | 2002-05-10 | 2003-12-04 | Transmit Technologietransfer | Wirkstoffe zu Therapie, Diagnostik und Prophylaxe von Erkrankungen, bei denen abnorme Proteinstrukturen auftreten |
MXPA04011417A (es) * | 2002-05-17 | 2005-02-14 | Pharmacia Italia Spa | Derivados de aminoindazol activos como inhibidores de cinasa, procedimiento para su preparacion y composiciones farmaceuticas que los comprenden. |
ATE548354T1 (de) | 2002-07-24 | 2012-03-15 | Ptc Therapeutics Inc | Ureido-substituierte benzoesäureverbindungen und ihre verwendung für die nonsense-suppression und behandlung von erkrankungen |
MXPA05002493A (es) * | 2002-09-05 | 2005-05-27 | Neurosearch As | Derivados de diarilurea y su uso como bloqueadores del canal del cloro. |
CA2501799C (en) * | 2002-10-09 | 2008-06-17 | Pfizer Products Inc. | Pyrazole compounds for treatment of neurodegenerative disorders |
UA81790C2 (uk) | 2002-12-19 | 2008-02-11 | Фармация Италия С.П.А. | Заміщені піролопіразольні похідні як інгібітори кінази |
US7557129B2 (en) | 2003-02-28 | 2009-07-07 | Bayer Healthcare Llc | Cyanopyridine derivatives useful in the treatment of cancer and other disorders |
GB0305426D0 (en) * | 2003-03-08 | 2003-04-16 | Glaxo Group Ltd | Novel compounds |
DK1626714T3 (da) | 2003-05-20 | 2007-10-15 | Bayer Pharmaceuticals Corp | Dirarylurinstoffer mod sygdomme medieret af PDGFR |
GEP20094664B (en) | 2003-05-22 | 2009-04-10 | Nerviano Medical Sciences Srl | Pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors |
US7141568B2 (en) | 2003-07-09 | 2006-11-28 | Pfizer Italia S.R.L. | Pyrrolo[3,4-c]pyrazole derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
RS52625B (en) | 2003-07-23 | 2013-06-28 | Bayer Healthcare Llc | FLUORO SUBSTITUTED OMEGA-CARBOXYARYL DIPHENYL UREA FOR TREATMENT AND PREVENTION OF DISEASES AND DISEASES |
TW200526204A (en) | 2004-02-03 | 2005-08-16 | Pharmacia Italia Spa | 1h-thieno[2,3-c]pyrazole derivatives useful as kinase inhibitors |
US7244757B2 (en) | 2004-04-01 | 2007-07-17 | Pfizer Inc | Pyrazole-amine compounds for the treatment of neurodegenerative disorders |
EP1609789A1 (en) * | 2004-06-23 | 2005-12-28 | Eli Lilly And Company | Ureido-pyrazole derivatives and their use as kinase inhibitors |
NZ552868A (en) * | 2004-08-12 | 2009-07-31 | Pfizer | Triazolopyridinylsulfanyl derivatives as P38 MAP kinase inhibitors |
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1999
- 1999-08-12 US US09/372,833 patent/US6387900B1/en not_active Expired - Fee Related
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2000
- 2000-08-03 PE PE2000000771A patent/PE20010482A1/es not_active Application Discontinuation
- 2000-08-10 CO CO00059913A patent/CO5200848A1/es not_active Application Discontinuation
- 2000-08-10 AR ARP000104118A patent/AR035557A1/es unknown
- 2000-08-11 DE DE60034683T patent/DE60034683T2/de not_active Expired - Fee Related
- 2000-08-11 AU AU67470/00A patent/AU6747000A/en not_active Abandoned
- 2000-08-11 EA EA200200249A patent/EA200200249A1/ru unknown
- 2000-08-11 HU HU0301857A patent/HUP0301857A2/hu unknown
- 2000-08-11 AT AT00955241T patent/ATE361070T1/de not_active IP Right Cessation
- 2000-08-11 NZ NZ517238A patent/NZ517238A/en unknown
- 2000-08-11 CN CN00812736A patent/CN1379668A/zh active Pending
- 2000-08-11 SK SK208-2002A patent/SK2082002A3/sk unknown
- 2000-08-11 KR KR1020027001815A patent/KR20020060158A/ko not_active Application Discontinuation
- 2000-08-11 PL PL00354058A patent/PL354058A1/xx not_active Application Discontinuation
- 2000-08-11 BR BR0013277-2A patent/BR0013277A/pt not_active Application Discontinuation
- 2000-08-11 ES ES00955241T patent/ES2284518T3/es not_active Expired - Lifetime
- 2000-08-11 JP JP2001516534A patent/JP2003507328A/ja not_active Withdrawn
- 2000-08-11 MX MXPA02001497A patent/MXPA02001497A/es active IP Right Grant
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- 2000-08-11 WO PCT/US2000/017878 patent/WO2001012188A1/en active IP Right Grant
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US6387900B1 (en) | 2002-05-14 |
ATE361070T1 (de) | 2007-05-15 |
ES2284518T3 (es) | 2007-11-16 |
SK2082002A3 (en) | 2002-09-10 |
WO2001012188A1 (en) | 2001-02-22 |
PL354058A1 (en) | 2003-12-15 |
EP1202734B1 (en) | 2007-05-02 |
HUP0301857A2 (hu) | 2003-09-29 |
CO5200848A1 (es) | 2002-09-27 |
EA200200249A1 (ru) | 2002-08-29 |
EP1202734A1 (en) | 2002-05-08 |
IL147925A0 (en) | 2002-08-14 |
DE60034683T2 (de) | 2008-01-17 |
PE20010482A1 (es) | 2001-04-20 |
EP1202734A4 (en) | 2004-09-01 |
KR20020060158A (ko) | 2002-07-16 |
AR035557A1 (es) | 2004-06-16 |
NO20020687D0 (no) | 2002-02-11 |
NZ517238A (en) | 2004-01-30 |
JP2003507328A (ja) | 2003-02-25 |
CN1379668A (zh) | 2002-11-13 |
HK1049790A1 (zh) | 2003-05-30 |
DE60034683D1 (de) | 2007-06-14 |
NO20020687L (no) | 2002-04-03 |
ZA200201118B (en) | 2003-05-28 |
BR0013277A (pt) | 2002-06-18 |
MXPA02001497A (es) | 2003-07-21 |
AU6747000A (en) | 2001-03-13 |
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