CA2580497A1 - Substituted n-alkylpyrimidinones - Google Patents
Substituted n-alkylpyrimidinones Download PDFInfo
- Publication number
- CA2580497A1 CA2580497A1 CA002580497A CA2580497A CA2580497A1 CA 2580497 A1 CA2580497 A1 CA 2580497A1 CA 002580497 A CA002580497 A CA 002580497A CA 2580497 A CA2580497 A CA 2580497A CA 2580497 A1 CA2580497 A1 CA 2580497A1
- Authority
- CA
- Canada
- Prior art keywords
- oxy
- difluorobenzyl
- isopropyl
- bromo
- oxo
- 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
- 150000001875 compounds Chemical class 0.000 claims abstract description 184
- 238000000034 method Methods 0.000 claims abstract description 56
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- -1 carboxydialkylamino Chemical group 0.000 claims description 154
- 125000006507 2,4-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(F)C(=C1[H])C([H])([H])* 0.000 claims description 124
- 239000001257 hydrogen Substances 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 150000003839 salts Chemical class 0.000 claims description 40
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 208000006673 asthma Diseases 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- VBNRICRDJAQAJA-UHFFFAOYSA-N n-[3-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]propyl]acetamide Chemical compound O=C1N(C(C)C)C(NCCCNC(C)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br VBNRICRDJAQAJA-UHFFFAOYSA-N 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 208000027866 inflammatory disease Diseases 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- UEJKJMYZYNSSCL-UHFFFAOYSA-N n-[3-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]propyl]-2-hydroxy-2-methylpropanamide Chemical compound O=C1N(C(C)C)C(NCCCNC(=O)C(C)(C)O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br UEJKJMYZYNSSCL-UHFFFAOYSA-N 0.000 claims description 12
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 11
- 125000005026 carboxyaryl group Chemical group 0.000 claims description 11
- BKSNXASLMVFGBR-UHFFFAOYSA-N n-[3-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]propyl]-2-hydroxyacetamide Chemical compound O=C1N(C(C)C)C(NCCCNC(=O)CO)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br BKSNXASLMVFGBR-UHFFFAOYSA-N 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- ZYQZKGORNWSTRT-UHFFFAOYSA-N n-[3-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]propyl]methanesulfonamide Chemical compound O=C1N(C(C)C)C(NCCCNS(C)(=O)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br ZYQZKGORNWSTRT-UHFFFAOYSA-N 0.000 claims description 9
- NTKIJIDIFGRONI-UHFFFAOYSA-N 2-(2-aminoethylamino)-5-bromo-6-[(2,4-difluorophenyl)methoxy]-3-propan-2-ylpyrimidin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1N(C(C)C)C(NCCN)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br NTKIJIDIFGRONI-UHFFFAOYSA-N 0.000 claims description 8
- SSNDZPVOOJSQLK-UHFFFAOYSA-N 2-[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]oxyethylurea Chemical compound O=C1N(C(C)C)C(OCCNC(N)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br SSNDZPVOOJSQLK-UHFFFAOYSA-N 0.000 claims description 7
- WAONXWIUTLWDCQ-UHFFFAOYSA-N 2-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]ethylurea Chemical compound O=C1N(C(C)C)C(NCCNC(N)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br WAONXWIUTLWDCQ-UHFFFAOYSA-N 0.000 claims description 7
- LLTODSASWXALDV-UHFFFAOYSA-N 2-but-3-enyl-5-chloro-6-[(2,4-difluorophenyl)methoxy]-3-propan-2-ylpyrimidin-4-one Chemical compound O=C1N(C(C)C)C(CCC=C)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl LLTODSASWXALDV-UHFFFAOYSA-N 0.000 claims description 7
- UMBNETZTFSLMMR-UHFFFAOYSA-N 3-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]propylurea Chemical compound O=C1N(C(C)C)C(NCCCNC(N)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br UMBNETZTFSLMMR-UHFFFAOYSA-N 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 206010003246 arthritis Diseases 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- VITRCFXLUXTZEN-UHFFFAOYSA-N n-[2-[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]oxyethyl]methanesulfonamide Chemical compound O=C1N(C(C)C)C(OCCNS(C)(=O)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br VITRCFXLUXTZEN-UHFFFAOYSA-N 0.000 claims description 7
- HLRYPLKYKRLCJO-UHFFFAOYSA-N n-[2-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]ethyl]methanesulfonamide Chemical compound O=C1N(C(C)C)C(NCCNS(C)(=O)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br HLRYPLKYKRLCJO-UHFFFAOYSA-N 0.000 claims description 7
- GSTRDNSSNNCLJV-UHFFFAOYSA-N 2-(3-aminopyrrolidin-1-yl)-5-bromo-6-[(2,4-difluorophenyl)methoxy]-3-propan-2-ylpyrimidin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.BrC=1C(=O)N(C(C)C)C(N2CC(N)CC2)=NC=1OCC1=CC=C(F)C=C1F GSTRDNSSNNCLJV-UHFFFAOYSA-N 0.000 claims description 6
- DISCBTTXKOZWIO-UHFFFAOYSA-N 2-[5-chloro-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]oxyethylurea Chemical compound O=C1N(C(C)C)C(OCCNC(N)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl DISCBTTXKOZWIO-UHFFFAOYSA-N 0.000 claims description 6
- PAFHRDGJYIXJIG-UHFFFAOYSA-N 2-[[5-chloro-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]ethylurea Chemical compound O=C1N(C(C)C)C(NCCNC(N)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl PAFHRDGJYIXJIG-UHFFFAOYSA-N 0.000 claims description 6
- JUNVPYLLMPVFJS-UHFFFAOYSA-N 5-bromo-6-[(2,4-difluorophenyl)methoxy]-2-phenyl-3-propan-2-ylpyrimidin-4-one Chemical compound BrC=1C(=O)N(C(C)C)C(C=2C=CC=CC=2)=NC=1OCC1=CC=C(F)C=C1F JUNVPYLLMPVFJS-UHFFFAOYSA-N 0.000 claims description 6
- 125000006550 alkoxycarbonyl aryl group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- NOHMREPTHCGWPY-UHFFFAOYSA-N 4-[5-chloro-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]oxybutanamide Chemical compound O=C1N(C(C)C)C(OCCCC(N)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl NOHMREPTHCGWPY-UHFFFAOYSA-N 0.000 claims description 5
- SBBTWBLLBGENSR-UHFFFAOYSA-N 5-bromo-6-[(2,4-difluorophenyl)methoxy]-2-[(4-fluorophenyl)methylamino]-3-propan-2-ylpyrimidin-4-one Chemical compound N=1C(OCC=2C(=CC(F)=CC=2)F)=C(Br)C(=O)N(C(C)C)C=1NCC1=CC=C(F)C=C1 SBBTWBLLBGENSR-UHFFFAOYSA-N 0.000 claims description 5
- QEQSKWBHCFOANW-GFCCVEGCSA-N 5-bromo-6-[(2,4-difluorophenyl)methoxy]-2-[[(2r)-2,3-dihydroxypropyl]amino]-3-propan-2-ylpyrimidin-4-one Chemical compound O=C1N(C(C)C)C(NC[C@@H](O)CO)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br QEQSKWBHCFOANW-GFCCVEGCSA-N 0.000 claims description 5
- QEQSKWBHCFOANW-LBPRGKRZSA-N 5-bromo-6-[(2,4-difluorophenyl)methoxy]-2-[[(2s)-2,3-dihydroxypropyl]amino]-3-propan-2-ylpyrimidin-4-one Chemical compound O=C1N(C(C)C)C(NC[C@H](O)CO)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br QEQSKWBHCFOANW-LBPRGKRZSA-N 0.000 claims description 5
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000005094 alkyl carbonyl amino alkyl group Chemical group 0.000 claims description 5
- 125000005154 alkyl sulfonyl amino alkyl group Chemical group 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 5
- 125000005122 aminoalkylamino group Chemical group 0.000 claims description 5
- 125000005121 aminocarbonylalkoxy group Chemical group 0.000 claims description 5
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 5
- 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 5
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 5
- 125000005280 halo alkyl sulfonyloxy group Chemical group 0.000 claims description 5
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 5
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 5
- JNWNCXLSOFWTJC-UHFFFAOYSA-N n-[2-[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]oxyethyl]acetamide Chemical compound O=C1N(C(C)C)C(OCCNC(C)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br JNWNCXLSOFWTJC-UHFFFAOYSA-N 0.000 claims description 5
- CFVVRMVUSDULGG-UHFFFAOYSA-N n-[2-[5-chloro-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]oxyethyl]acetamide Chemical compound O=C1N(C(C)C)C(OCCNC(C)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl CFVVRMVUSDULGG-UHFFFAOYSA-N 0.000 claims description 5
- CBCVMZGGQYJUIF-UHFFFAOYSA-N n-[2-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]ethyl]-2-hydroxy-2-methylpropanamide Chemical compound O=C1N(C(C)C)C(NCCNC(=O)C(C)(C)O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br CBCVMZGGQYJUIF-UHFFFAOYSA-N 0.000 claims description 5
- ZAJQXLOBSMVLBE-UHFFFAOYSA-N n-[2-[[5-chloro-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]ethyl]acetamide Chemical compound O=C1N(C(C)C)C(NCCNC(C)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl ZAJQXLOBSMVLBE-UHFFFAOYSA-N 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- XGXJJWDDONBHML-AWEZNQCLSA-N (2s)-1-[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]pyrrolidine-2-carboxamide Chemical compound BrC=1C(=O)N(C(C)C)C(N2[C@@H](CCC2)C(N)=O)=NC=1OCC1=CC=C(F)C=C1F XGXJJWDDONBHML-AWEZNQCLSA-N 0.000 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
- GSTRDNSSNNCLJV-BTQNPOSSSA-N 2-[(3r)-3-aminopyrrolidin-1-yl]-5-bromo-6-[(2,4-difluorophenyl)methoxy]-3-propan-2-ylpyrimidin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.BrC=1C(=O)N(C(C)C)C(N2C[C@H](N)CC2)=NC=1OCC1=CC=C(F)C=C1F GSTRDNSSNNCLJV-BTQNPOSSSA-N 0.000 claims description 4
- SGRUMBUUODMHDX-UHFFFAOYSA-N 4-[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]benzamide Chemical compound BrC=1C(=O)N(C(C)C)C(C=2C=CC(=CC=2)C(N)=O)=NC=1OCC1=CC=C(F)C=C1F SGRUMBUUODMHDX-UHFFFAOYSA-N 0.000 claims description 4
- KRTBXIMTCFRNMM-UHFFFAOYSA-N 4-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]butanamide Chemical compound O=C1N(C(C)C)C(NCCCC(N)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br KRTBXIMTCFRNMM-UHFFFAOYSA-N 0.000 claims description 4
- JXIROSMQIFDQTQ-UHFFFAOYSA-N 5-bromo-6-[(2,4-difluorophenyl)methoxy]-2-[(2-hydroxy-2-methylpropyl)amino]-3-propan-2-ylpyrimidin-4-one Chemical compound O=C1N(C(C)C)C(NCC(C)(C)O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br JXIROSMQIFDQTQ-UHFFFAOYSA-N 0.000 claims description 4
- CHSZFCSTKGLBIE-CQSZACIVSA-N 5-bromo-6-[(2,4-difluorophenyl)methoxy]-2-[(3r)-3-(methylamino)pyrrolidin-1-yl]-3-propan-2-ylpyrimidin-4-one Chemical compound C1[C@H](NC)CCN1C1=NC(OCC=2C(=CC(F)=CC=2)F)=C(Br)C(=O)N1C(C)C CHSZFCSTKGLBIE-CQSZACIVSA-N 0.000 claims description 4
- MRHBQYLSGUHBKI-UHFFFAOYSA-N 5-bromo-6-[(2,4-difluorophenyl)methoxy]-3-propan-2-ylpyrimidin-4-one Chemical compound O=C1N(C(C)C)C=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br MRHBQYLSGUHBKI-UHFFFAOYSA-N 0.000 claims description 4
- NCVJOLGPKBVARQ-UHFFFAOYSA-N 5-chloro-6-[(2,4-difluorophenyl)methoxy]-2-(4-hydroxybutoxy)-3-propan-2-ylpyrimidin-4-one Chemical compound O=C1N(C(C)C)C(OCCCCO)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl NCVJOLGPKBVARQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- AASGNNCHVSQMGF-UHFFFAOYSA-N n-[2-[5-chloro-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]oxyethyl]methanesulfonamide Chemical compound O=C1N(C(C)C)C(OCCNS(C)(=O)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl AASGNNCHVSQMGF-UHFFFAOYSA-N 0.000 claims description 4
- GTTDXZTUQIBSIS-UHFFFAOYSA-N n-[2-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]ethyl]-2-hydroxyacetamide Chemical compound O=C1N(C(C)C)C(NCCNC(=O)CO)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br GTTDXZTUQIBSIS-UHFFFAOYSA-N 0.000 claims description 4
- GTPPRMOOOHMINQ-UHFFFAOYSA-N n-[2-[[5-chloro-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]ethyl]-2-hydroxyacetamide Chemical compound O=C1N(C(C)C)C(NCCNC(=O)CO)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl GTPPRMOOOHMINQ-UHFFFAOYSA-N 0.000 claims description 4
- COLFDQSLDGYLLQ-UHFFFAOYSA-N n-[2-[[5-chloro-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]ethyl]methanesulfonamide Chemical compound O=C1N(C(C)C)C(NCCNS(C)(=O)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl COLFDQSLDGYLLQ-UHFFFAOYSA-N 0.000 claims description 4
- IFUUCNSKRFPCLN-UHFFFAOYSA-N n-[[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]methyl]methanesulfonamide Chemical compound O=C1N(C(C)C)C(CNS(C)(=O)=O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br IFUUCNSKRFPCLN-UHFFFAOYSA-N 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- IRPMXMVROZBYIP-UHFFFAOYSA-N 1-[5-bromo-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]piperidine-3-carboxamide Chemical compound BrC=1C(=O)N(C(C)C)C(N2CC(CCC2)C(N)=O)=NC=1OCC1=CC=C(F)C=C1F IRPMXMVROZBYIP-UHFFFAOYSA-N 0.000 claims description 3
- AKAFDTUDVOGBTP-OAHLLOKOSA-N 5-bromo-6-[(2,4-difluorophenyl)methoxy]-2-[(3r)-3-(ethylamino)pyrrolidin-1-yl]-3-propan-2-ylpyrimidin-4-one Chemical compound C1[C@H](NCC)CCN1C1=NC(OCC=2C(=CC(F)=CC=2)F)=C(Br)C(=O)N1C(C)C AKAFDTUDVOGBTP-OAHLLOKOSA-N 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- WVBPVICOMZLWIV-UHFFFAOYSA-N 2-[(1-acetylpiperidin-4-yl)amino]-5-bromo-6-[(2,4-difluorophenyl)methoxy]-3-propan-2-ylpyrimidin-4-one Chemical compound N=1C(OCC=2C(=CC(F)=CC=2)F)=C(Br)C(=O)N(C(C)C)C=1NC1CCN(C(C)=O)CC1 WVBPVICOMZLWIV-UHFFFAOYSA-N 0.000 claims description 2
- QVSLVCNMIQIJSL-UHFFFAOYSA-N 5-bromo-6-[(2,4-difluorophenyl)methoxy]-2-(3,3-dimethylbutylamino)-3-propan-2-ylpyrimidin-4-one Chemical compound O=C1N(C(C)C)C(NCCC(C)(C)C)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Br QVSLVCNMIQIJSL-UHFFFAOYSA-N 0.000 claims description 2
- PKDJSROLEKLVEI-UQKRIMTDSA-N 5-bromo-6-[(2,4-difluorophenyl)methoxy]-2-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]-3-propan-2-ylpyrimidin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.BrC=1C(=O)N(C(C)C)C(N2[C@@H](CCC2)CO)=NC=1OCC1=CC=C(F)C=C1F PKDJSROLEKLVEI-UQKRIMTDSA-N 0.000 claims description 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 2
- SLAHTTLBYXYYQH-UHFFFAOYSA-N n-[2-[[5-chloro-4-[(2,4-difluorophenyl)methoxy]-6-oxo-1-propan-2-ylpyrimidin-2-yl]amino]ethyl]-2-hydroxy-2-methylpropanamide Chemical compound O=C1N(C(C)C)C(NCCNC(=O)C(C)(C)O)=NC(OCC=2C(=CC(F)=CC=2)F)=C1Cl SLAHTTLBYXYYQH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 32
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 18
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 2
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
- CPJJIKBDEHMSIC-UHFFFAOYSA-N 1-[[2-[(5-bromo-2-methyl-6-oxo-1-propan-2-ylpyrimidin-4-yl)oxymethyl]-5-fluorophenyl]methyl]-3-ethylurea Chemical compound CCNC(=O)NCC1=CC(F)=CC=C1COC1=C(Br)C(=O)N(C(C)C)C(C)=N1 CPJJIKBDEHMSIC-UHFFFAOYSA-N 0.000 claims 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 128
- 102100040247 Tumor necrosis factor Human genes 0.000 abstract description 36
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 abstract description 29
- 230000000694 effects Effects 0.000 abstract description 28
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 abstract description 22
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 abstract description 22
- 108010037462 Cyclooxygenase 2 Proteins 0.000 abstract description 17
- 230000001575 pathological effect Effects 0.000 abstract description 17
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 abstract description 12
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 abstract description 4
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 abstract description 3
- 239000000543 intermediate Chemical class 0.000 abstract description 2
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Classifications
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- Neurosurgery (AREA)
- Communicable Diseases (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
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Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US61885604P | 2004-10-13 | 2004-10-13 | |
US60/618,856 | 2004-10-13 | ||
US63794904P | 2004-12-21 | 2004-12-21 | |
US60/637,949 | 2004-12-21 | ||
PCT/IB2005/003063 WO2006040666A1 (en) | 2004-10-13 | 2005-10-03 | Substituted n-alkylpyrimidinones |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2580497A1 true CA2580497A1 (en) | 2006-04-20 |
Family
ID=35717699
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002580497A Abandoned CA2580497A1 (en) | 2004-10-13 | 2005-10-03 | Substituted n-alkylpyrimidinones |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1802590A1 (pt) |
JP (1) | JP2008515964A (pt) |
BR (1) | BRPI0517555A (pt) |
CA (1) | CA2580497A1 (pt) |
MX (1) | MX2007004493A (pt) |
WO (1) | WO2006040666A1 (pt) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2640665A1 (en) * | 2006-02-10 | 2007-08-16 | Pfizer Products Inc. | Pyridinone pyrazole urea and pyrimidinone pyrazole urea derivatives |
EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
WO2013086208A1 (en) * | 2011-12-06 | 2013-06-13 | Confluence Life Sciences, Inc. | Substituted pyrimidinone-phenyl-pyrimidinyl compounds |
CN108503568A (zh) * | 2017-02-27 | 2018-09-07 | 无锡杰西医药股份有限公司 | 一种适用于工业化生产的高纯度异硫氰酸酯类化合物制备方法 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS63112566A (ja) * | 1986-10-28 | 1988-05-17 | Nissan Chem Ind Ltd | ピリミジノン誘導体、その製法および殺虫・殺ダニ・殺菌剤 |
JPH01190670A (ja) * | 1988-01-22 | 1989-07-31 | Nissan Chem Ind Ltd | ピリミジノン誘導体、その製法および殺虫・殺ダニ・殺菌剤 |
EP1470112A1 (en) * | 2002-01-18 | 2004-10-27 | Pharmacia Corporation | Substituted pyridazinones as inhibitors of p38 |
EP1490064B1 (en) * | 2002-02-14 | 2009-11-18 | Pharmacia Corporation | Substituted pyridinones as modulators of p38 map kinase |
US7183287B2 (en) * | 2003-04-03 | 2007-02-27 | Pharmacia Corporation | Substituted pyrimidinones |
CA2533684A1 (en) * | 2003-07-25 | 2005-02-10 | Amgen Inc. | Substituted pyridones and pyrimidinones with antiinflammatory properties |
-
2005
- 2005-10-03 BR BRPI0517555-0A patent/BRPI0517555A/pt not_active Application Discontinuation
- 2005-10-03 WO PCT/IB2005/003063 patent/WO2006040666A1/en active Application Filing
- 2005-10-03 JP JP2007536286A patent/JP2008515964A/ja not_active Withdrawn
- 2005-10-03 CA CA002580497A patent/CA2580497A1/en not_active Abandoned
- 2005-10-03 MX MX2007004493A patent/MX2007004493A/es unknown
- 2005-10-03 EP EP05791810A patent/EP1802590A1/en not_active Withdrawn
Also Published As
Publication number | Publication date |
---|---|
WO2006040666A1 (en) | 2006-04-20 |
JP2008515964A (ja) | 2008-05-15 |
BRPI0517555A (pt) | 2008-10-14 |
MX2007004493A (es) | 2007-05-08 |
EP1802590A1 (en) | 2007-07-04 |
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