JP2003507328A - 3(5)−ウレイド−ピラゾール誘導体、その調製方法および抗腫瘍剤としての使用 - Google Patents
3(5)−ウレイド−ピラゾール誘導体、その調製方法および抗腫瘍剤としての使用Info
- Publication number
- JP2003507328A JP2003507328A JP2001516534A JP2001516534A JP2003507328A JP 2003507328 A JP2003507328 A JP 2003507328A JP 2001516534 A JP2001516534 A JP 2001516534A JP 2001516534 A JP2001516534 A JP 2001516534A JP 2003507328 A JP2003507328 A JP 2003507328A
- Authority
- JP
- Japan
- Prior art keywords
- pyrazol
- cyclopropyl
- urea
- amino
- formula
- 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.)
- Withdrawn
Links
- 239000002246 antineoplastic agent Substances 0.000 title description 9
- 238000002360 preparation method Methods 0.000 title description 3
- 239000000126 substance Substances 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- XAEGRAIWWBXIRR-UHFFFAOYSA-N 1h-pyrazol-5-ylurea Chemical class NC(=O)NC=1C=CNN=1 XAEGRAIWWBXIRR-UHFFFAOYSA-N 0.000 claims abstract description 25
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 23
- 201000011510 cancer Diseases 0.000 claims abstract description 11
- 238000011282 treatment Methods 0.000 claims abstract description 10
- 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 178
- -1 carboxy , Amino Chemical group 0.000 claims description 91
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 41
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 37
- 239000004202 carbamide Substances 0.000 claims description 37
- 239000002904 solvent Substances 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 230000005764 inhibitory process Effects 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000004448 alkyl carbonyl 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
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims description 13
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims description 12
- 102000016736 Cyclin Human genes 0.000 claims description 12
- 108050006400 Cyclin Proteins 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 12
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 12
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 108091000080 Phosphotransferase Proteins 0.000 claims description 9
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 102000020233 phosphotransferase Human genes 0.000 claims description 9
- 230000002062 proliferating effect Effects 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- 125000005336 allyloxy group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 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
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 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 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 230000001419 dependent effect Effects 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 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 4
- 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
- UVOYJUDGAPNFLO-UHFFFAOYSA-N 1-(5-cyclopentyl-1h-pyrazol-3-yl)-3-[2-(4-hydroxyphenyl)ethyl]urea Chemical compound C1=CC(O)=CC=C1CCNC(=O)NC1=CC(C2CCCC2)=NN1 UVOYJUDGAPNFLO-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
- 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 4
- DNZMSQNUCPUAEN-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[(2-ethoxyphenyl)methyl]urea Chemical compound CCOC1=CC=CC=C1CNC(=O)NC1=CC(C2CC2)=NN1 DNZMSQNUCPUAEN-UHFFFAOYSA-N 0.000 claims description 4
- JBNQPPUHAZQJRM-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[(3-methoxyphenyl)methyl]urea Chemical compound COC1=CC=CC(CNC(=O)NC=2NN=C(C=2)C2CC2)=C1 JBNQPPUHAZQJRM-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
- 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
- AMFRZCFUWOMRSB-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound C1=CC(Cl)=CC=C1CNC(=O)NC1=CC(C2CC2)=NN1 AMFRZCFUWOMRSB-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
- SSGTWBRHHUEXQF-UHFFFAOYSA-N 1-[5-(2-phenylethyl)-1h-pyrazol-3-yl]-3-propylurea Chemical compound N1C(NC(=O)NCCC)=CC(CCC=2C=CC=CC=2)=N1 SSGTWBRHHUEXQF-UHFFFAOYSA-N 0.000 claims description 4
- URQFBYJGBGJFJB-UHFFFAOYSA-N 1-benzyl-3-(5-cyclopentyl-1h-pyrazol-3-yl)urea Chemical compound C=1C(C2CCCC2)=NNC=1NC(=O)NCC1=CC=CC=C1 URQFBYJGBGJFJB-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
- 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
- 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
- 208000031481 Pathologic Constriction Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
- 230000022131 cell cycle Effects 0.000 claims description 4
- 230000004663 cell proliferation Effects 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 229940127089 cytotoxic agent Drugs 0.000 claims description 4
- 239000003937 drug carrier Substances 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
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 201000008968 osteosarcoma Diseases 0.000 claims description 4
- 230000036262 stenosis Effects 0.000 claims description 4
- 208000037804 stenosis Diseases 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- KBWOXTUACGNTJX-UHFFFAOYSA-N 1-(1,3-benzothiazol-5-yl)-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound C=1C=C2SC=NC2=CC=1NC(=O)NC(NN=1)=CC=1C1CC1 KBWOXTUACGNTJX-UHFFFAOYSA-N 0.000 claims description 3
- HLYWVPZUDNCLTA-UHFFFAOYSA-N 1-(2-chlorophenyl)-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound ClC1=CC=CC=C1NC(=O)NC1=CC(C2CC2)=NN1 HLYWVPZUDNCLTA-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
- LMAUENNWIDTDEI-UHFFFAOYSA-N 1-(3-aminophenyl)-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound NC1=CC=CC(NC(=O)NC=2NN=C(C=2)C2CC2)=C1 LMAUENNWIDTDEI-UHFFFAOYSA-N 0.000 claims description 3
- AIEYGYPQUCKGQD-UHFFFAOYSA-N 1-(3h-benzimidazol-5-yl)-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound C=1C=C2N=CNC2=CC=1NC(=O)NC(NN=1)=CC=1C1CC1 AIEYGYPQUCKGQD-UHFFFAOYSA-N 0.000 claims description 3
- DBJNONLXERNMRY-UHFFFAOYSA-N 1-(4-aminophenyl)-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound C1=CC(N)=CC=C1NC(=O)NC1=CC(C2CC2)=NN1 DBJNONLXERNMRY-UHFFFAOYSA-N 0.000 claims description 3
- UVBKTBFRVPPOKN-UHFFFAOYSA-N 1-(4-cyanophenyl)-3-(5-cyclopropyl-1h-pyrazol-3-yl)urea Chemical compound C=1C=C(C#N)C=CC=1NC(=O)NC(NN=1)=CC=1C1CC1 UVBKTBFRVPPOKN-UHFFFAOYSA-N 0.000 claims description 3
- TUWACJYUEHXZQM-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(1h-indol-5-yl)urea Chemical compound C=1C=C2NC=CC2=CC=1NC(=O)NC(NN=1)=CC=1C1CC1 TUWACJYUEHXZQM-UHFFFAOYSA-N 0.000 claims description 3
- CQAUMHHMFNEAEF-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(2,3-dimethylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC=2NN=C(C=2)C2CC2)=C1C CQAUMHHMFNEAEF-UHFFFAOYSA-N 0.000 claims description 3
- KSTNBJOADDSFJM-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(2,4-dimethylphenyl)urea Chemical compound CC1=CC(C)=CC=C1NC(=O)NC1=CC(C2CC2)=NN1 KSTNBJOADDSFJM-UHFFFAOYSA-N 0.000 claims description 3
- 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
- YHSVZCPQAZCNPZ-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(2,6-dimethylphenyl)urea Chemical compound CC1=CC=CC(C)=C1NC(=O)NC1=CC(C2CC2)=NN1 YHSVZCPQAZCNPZ-UHFFFAOYSA-N 0.000 claims description 3
- NIYXUXSXSVROSP-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(2-hydroxyphenyl)urea Chemical compound OC1=CC=CC=C1NC(=O)NC1=CC(C2CC2)=NN1 NIYXUXSXSVROSP-UHFFFAOYSA-N 0.000 claims description 3
- FBGOFSYQLFPPIH-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(2-methoxyphenyl)urea Chemical compound COC1=CC=CC=C1NC(=O)NC1=CC(C2CC2)=NN1 FBGOFSYQLFPPIH-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
- OWXBILRETZOPMU-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(3-hydroxyphenyl)urea Chemical compound OC1=CC=CC(NC(=O)NC=2NN=C(C=2)C2CC2)=C1 OWXBILRETZOPMU-UHFFFAOYSA-N 0.000 claims description 3
- DGUDRQUMTLNZRN-UHFFFAOYSA-N 1-(5-cyclopropyl-1h-pyrazol-3-yl)-3-(3-methoxyphenyl)urea Chemical compound COC1=CC=CC(NC(=O)NC=2NN=C(C=2)C2CC2)=C1 DGUDRQUMTLNZRN-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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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
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- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- 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 (2)
Publication Number | Publication Date |
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JP2003507328A true JP2003507328A (ja) | 2003-02-25 |
JP2003507328A5 JP2003507328A5 (US20050059668A1-20050317-C00061.png) | 2007-05-24 |
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Family Applications (1)
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JP2001516534A Withdrawn JP2003507328A (ja) | 1999-08-12 | 2000-08-11 | 3(5)−ウレイド−ピラゾール誘導体、その調製方法および抗腫瘍剤としての使用 |
Country Status (25)
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010524898A (ja) * | 2007-04-18 | 2010-07-22 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としての尿素誘導体 |
JP2013063968A (ja) * | 2011-08-31 | 2013-04-11 | Japan Tobacco Inc | ピラゾール化合物及びその医薬用途 |
Families Citing this family (73)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
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CA2699568C (en) | 1999-12-24 | 2013-03-12 | Aventis Pharma Limited | Azaindoles |
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Cited By (2)
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JP2010524898A (ja) * | 2007-04-18 | 2010-07-22 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としての尿素誘導体 |
JP2013063968A (ja) * | 2011-08-31 | 2013-04-11 | Japan Tobacco Inc | ピラゾール化合物及びその医薬用途 |
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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 |
CA2380786A1 (en) | 2001-02-22 |
NZ517238A (en) | 2004-01-30 |
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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