CA2592118C - Urea derivatives as enzyme modulators - Google Patents
Urea derivatives as enzyme modulators Download PDFInfo
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- CA2592118C CA2592118C CA2592118A CA2592118A CA2592118C CA 2592118 C CA2592118 C CA 2592118C CA 2592118 A CA2592118 A CA 2592118A CA 2592118 A CA2592118 A CA 2592118A CA 2592118 C CA2592118 C CA 2592118C
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- Prior art keywords
- c6alkyl
- group
- phenyl
- independently
- moieties
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- 102000004190 Enzymes Human genes 0.000 title description 2
- 108090000790 Enzymes Proteins 0.000 title description 2
- 150000003672 ureas Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 340
- -1 hydroxyC1-C6alkyl Chemical group 0.000 claims description 628
- 125000000623 heterocyclic group Chemical group 0.000 claims description 370
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 313
- 125000000217 alkyl group Chemical group 0.000 claims description 187
- 125000001072 heteroaryl group Chemical group 0.000 claims description 150
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 146
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 145
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 145
- 229910052739 hydrogen Inorganic materials 0.000 claims description 138
- 125000002950 monocyclic group Chemical class 0.000 claims description 129
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 111
- 229910052736 halogen Inorganic materials 0.000 claims description 58
- 150000002367 halogens Chemical class 0.000 claims description 58
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 125000002947 alkylene group Chemical group 0.000 claims description 49
- 229910052757 nitrogen Inorganic materials 0.000 claims description 49
- MZAGXDHQGXUDDX-JSRXJHBZSA-N (e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/C(N)=O MZAGXDHQGXUDDX-JSRXJHBZSA-N 0.000 claims description 45
- 125000004076 pyridyl group Chemical class 0.000 claims description 43
- 125000000714 pyrimidinyl group Chemical class 0.000 claims description 43
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
- 125000002619 bicyclic group Chemical group 0.000 claims description 40
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
- 239000000460 chlorine Substances 0.000 claims description 38
- 125000001769 aryl amino group Chemical group 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 31
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 29
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
- 101100134927 Gallus gallus COR8 gene Proteins 0.000 claims description 27
- 101100533890 Hypocrea jecorina (strain QM6a) sor3 gene Proteins 0.000 claims description 22
- 101100533874 Hypocrea jecorina (strain QM6a) sor5 gene Proteins 0.000 claims description 22
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 21
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 21
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 21
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 16
- 125000004043 oxo group Chemical group O=* 0.000 claims description 16
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 239000002671 adjuvant Substances 0.000 claims description 13
- 239000003085 diluting agent Substances 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 3
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- PRJVZQTXWCBLEB-UHFFFAOYSA-N 1-(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)-3-(3-pyridin-3-yloxyphenyl)urea Chemical compound C=1C=C2N=CC=CC2=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=1)=CC=CC=1OC1=CC=CN=C1 PRJVZQTXWCBLEB-UHFFFAOYSA-N 0.000 claims 1
- JSTMGXFAIRZNNU-UHFFFAOYSA-N 1-[5-cyclopentyl-2-(2-oxo-1h-quinolin-6-yl)pyrazol-3-yl]-3-(3-pyridin-3-yloxyphenyl)urea Chemical compound C=1C=CC(OC=2C=NC=CC=2)=CC=1NC(=O)NC(N(N=1)C=2C=C3C=CC(=O)NC3=CC=2)=CC=1C1CCCC1 JSTMGXFAIRZNNU-UHFFFAOYSA-N 0.000 claims 1
- QHLKDZDJCHUMMB-UHFFFAOYSA-N 1-[5-tert-butyl-2-(1,2,3,4-tetrahydroisoquinolin-6-yl)pyrazol-3-yl]-3-(3-pyridin-3-yloxyphenyl)urea Chemical compound C=1C=C2CNCCC2=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=1)=CC=CC=1OC1=CC=CN=C1 QHLKDZDJCHUMMB-UHFFFAOYSA-N 0.000 claims 1
- JANSXXGUCHWUIS-UHFFFAOYSA-N 1-[5-tert-butyl-2-(1,2,3,4-tetrahydroisoquinolin-6-yl)pyrazol-3-yl]-3-[3-(5-chloropyridin-3-yl)oxyphenyl]urea Chemical compound C=1C=C2CNCCC2=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=1)=CC=CC=1OC1=CN=CC(Cl)=C1 JANSXXGUCHWUIS-UHFFFAOYSA-N 0.000 claims 1
- GSEWMSCZKIPBPB-UHFFFAOYSA-N 1-[5-tert-butyl-2-(1h-indol-5-yl)pyrazol-3-yl]-3-(3-pyridin-3-yloxyphenyl)urea Chemical compound C=1C=C2NC=CC2=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=1)=CC=CC=1OC1=CC=CN=C1 GSEWMSCZKIPBPB-UHFFFAOYSA-N 0.000 claims 1
- GNHCFAKSLLCEHE-UHFFFAOYSA-N 1-[5-tert-butyl-2-(2,3-dihydro-1h-indol-5-yl)pyrazol-3-yl]-3-(3-pyridin-3-yloxyphenyl)urea Chemical compound C=1C=C2NCCC2=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=1)=CC=CC=1OC1=CC=CN=C1 GNHCFAKSLLCEHE-UHFFFAOYSA-N 0.000 claims 1
- KNLMSPRYHJGRQE-UHFFFAOYSA-N 1-[5-tert-butyl-2-(2-oxo-1h-quinolin-6-yl)pyrazol-3-yl]-3-(3-pyridin-3-yloxyphenyl)urea Chemical compound C=1C=C2NC(=O)C=CC2=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=1)=CC=CC=1OC1=CC=CN=C1 KNLMSPRYHJGRQE-UHFFFAOYSA-N 0.000 claims 1
- LORYHOYXROXOQP-UHFFFAOYSA-N 4-[3-[[5-tert-butyl-2-(2-oxo-1h-quinolin-6-yl)pyrazol-3-yl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C4C=CC(=O)NC4=CC=3)C=CC=2)=C1 LORYHOYXROXOQP-UHFFFAOYSA-N 0.000 claims 1
- ZSGKSAIECFWDKA-UHFFFAOYSA-N 4-[4-[[2-(2-aminoquinolin-6-yl)-5-tert-butylpyrazol-3-yl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C4C=CC(N)=NC4=CC=3)=CC=2)=C1 ZSGKSAIECFWDKA-UHFFFAOYSA-N 0.000 claims 1
- HILSIKJYKNOSJS-UHFFFAOYSA-N 4-[4-[[2-[2-(2-aminoethylamino)quinolin-6-yl]-5-tert-butylpyrazol-3-yl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C4C=CC(NCCN)=NC4=CC=3)=CC=2)=C1 HILSIKJYKNOSJS-UHFFFAOYSA-N 0.000 claims 1
- UCNWGTVKXTWOOZ-UHFFFAOYSA-N 4-[4-[[5-cyclopentyl-2-(2-oxo-1h-quinolin-6-yl)pyrazol-3-yl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3N(N=C(C=3)C3CCCC3)C=3C=C4C=CC(=O)NC4=CC=3)=CC=2)=C1 UCNWGTVKXTWOOZ-UHFFFAOYSA-N 0.000 claims 1
- HBFBAFUOVPDFID-UHFFFAOYSA-N 4-[4-[[5-tert-butyl-2-(1,2,3,4-tetrahydroisoquinolin-6-yl)pyrazol-3-yl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C4CCNCC4=CC=3)=CC=2)=C1 HBFBAFUOVPDFID-UHFFFAOYSA-N 0.000 claims 1
- RTCIFWDWEJGZDH-UHFFFAOYSA-N 4-[4-[[5-tert-butyl-2-(2-oxo-1h-quinolin-6-yl)pyrazol-3-yl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C4C=CC(=O)NC4=CC=3)=CC=2)=C1 RTCIFWDWEJGZDH-UHFFFAOYSA-N 0.000 claims 1
- LODJEZMLTMCKMF-UHFFFAOYSA-N 4-[4-[[5-tert-butyl-2-(2-piperazin-1-ylquinolin-6-yl)pyrazol-3-yl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C4C=CC(=NC4=CC=3)N3CCNCC3)=CC=2)=C1 LODJEZMLTMCKMF-UHFFFAOYSA-N 0.000 claims 1
- BWAYONKLFMVSOB-UHFFFAOYSA-N 4-[4-[[5-tert-butyl-2-[2-(dimethylamino)quinolin-6-yl]pyrazol-3-yl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C4C=CC(=NC4=CC=3)N(C)C)=CC=2)=C1 BWAYONKLFMVSOB-UHFFFAOYSA-N 0.000 claims 1
- TYHULVNHHVRNQG-UHFFFAOYSA-N 4-[4-[[5-tert-butyl-2-[2-(methylamino)quinolin-6-yl]pyrazol-3-yl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C4C=CC(NC)=NC4=CC=3)=CC=2)=C1 TYHULVNHHVRNQG-UHFFFAOYSA-N 0.000 claims 1
- IFROIINNXMWKGG-AREMUKBSSA-N 4-[4-[[5-tert-butyl-2-[2-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]quinolin-6-yl]pyrazol-3-yl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C4C=CC(=NC4=CC=3)N3C[C@@H](CC3)N(C)C)=CC=2)=C1 IFROIINNXMWKGG-AREMUKBSSA-N 0.000 claims 1
- YHWJGPZSSHVGPJ-UHFFFAOYSA-N 6-[3-tert-butyl-5-[(3-pyridin-3-yloxyphenyl)carbamoylamino]pyrazol-1-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide Chemical compound C=1C=C2CNC(C(N)=O)CC2=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=1)=CC=CC=1OC1=CC=CN=C1 YHWJGPZSSHVGPJ-UHFFFAOYSA-N 0.000 claims 1
- NLRWTOWGPJMZIJ-UHFFFAOYSA-N 6-[3-tert-butyl-5-[(3-pyridin-3-yloxyphenyl)carbamoylamino]pyrazol-1-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C=1C=C2CNC(C(O)=O)CC2=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=1)=CC=CC=1OC1=CC=CN=C1 NLRWTOWGPJMZIJ-UHFFFAOYSA-N 0.000 claims 1
- UYRSCLXWEXJQGI-UHFFFAOYSA-N 6-[3-tert-butyl-5-[(3-pyridin-3-yloxyphenyl)carbamoylamino]pyrazol-1-yl]-n-(2,3-dihydroxypropyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamide Chemical compound C=1C=C2C(C(=O)NCC(O)CO)NCCC2=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=1)=CC=CC=1OC1=CC=CN=C1 UYRSCLXWEXJQGI-UHFFFAOYSA-N 0.000 claims 1
- AFJPJSNLUVVVMN-UHFFFAOYSA-N 6-[3-tert-butyl-5-[(3-pyridin-3-yloxyphenyl)carbamoylamino]pyrazol-1-yl]-n-(2,3-dihydroxypropyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide Chemical compound C=1C=C2CNC(C(=O)NCC(O)CO)CC2=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C=1)=CC=CC=1OC1=CC=CN=C1 AFJPJSNLUVVVMN-UHFFFAOYSA-N 0.000 claims 1
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Applications Claiming Priority (9)
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| US63898604P | 2004-12-23 | 2004-12-23 | |
| US63908704P | 2004-12-23 | 2004-12-23 | |
| US63898704P | 2004-12-23 | 2004-12-23 | |
| US63896804P | 2004-12-23 | 2004-12-23 | |
| US60/638,968 | 2004-12-23 | ||
| US60/638,986 | 2004-12-23 | ||
| US60/639,087 | 2004-12-23 | ||
| US60/638,987 | 2004-12-23 | ||
| PCT/US2005/047270 WO2006071940A2 (en) | 2004-12-23 | 2005-12-23 | Enzyme modulators and treatments |
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| CA2592118A1 CA2592118A1 (en) | 2006-07-06 |
| CA2592118C true CA2592118C (en) | 2015-11-17 |
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| CA2592118A Expired - Fee Related CA2592118C (en) | 2004-12-23 | 2005-12-23 | Urea derivatives as enzyme modulators |
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| US (2) | US20070078121A1 (enExample) |
| EP (2) | EP1835934A4 (enExample) |
| JP (1) | JP5197016B2 (enExample) |
| AU (1) | AU2005321946B2 (enExample) |
| CA (1) | CA2592118C (enExample) |
| HK (1) | HK1217482A1 (enExample) |
| WO (1) | WO2006071940A2 (enExample) |
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-
2005
- 2005-12-23 EP EP05855777A patent/EP1835934A4/en not_active Withdrawn
- 2005-12-23 EP EP15166821.7A patent/EP2942349A1/en not_active Withdrawn
- 2005-12-23 WO PCT/US2005/047270 patent/WO2006071940A2/en not_active Ceased
- 2005-12-23 US US11/318,399 patent/US20070078121A1/en not_active Abandoned
- 2005-12-23 AU AU2005321946A patent/AU2005321946B2/en not_active Ceased
- 2005-12-23 JP JP2007548595A patent/JP5197016B2/ja not_active Expired - Fee Related
- 2005-12-23 CA CA2592118A patent/CA2592118C/en not_active Expired - Fee Related
-
2007
- 2007-12-21 US US11/963,740 patent/US8163756B2/en active Active
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2016
- 2016-05-11 HK HK16105411.2A patent/HK1217482A1/en unknown
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| WO2006071940A3 (en) | 2009-04-23 |
| US20080113967A1 (en) | 2008-05-15 |
| AU2005321946B2 (en) | 2012-08-16 |
| EP1835934A2 (en) | 2007-09-26 |
| CA2592118A1 (en) | 2006-07-06 |
| EP1835934A4 (en) | 2010-07-28 |
| EP2942349A1 (en) | 2015-11-11 |
| US8163756B2 (en) | 2012-04-24 |
| WO2006071940A2 (en) | 2006-07-06 |
| HK1217482A1 (en) | 2017-01-13 |
| JP5197016B2 (ja) | 2013-05-15 |
| US20070078121A1 (en) | 2007-04-05 |
| AU2005321946A1 (en) | 2006-07-06 |
| JP2008525498A (ja) | 2008-07-17 |
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