ZA200502836B - Hydroxy alkyl substituted 1,3,8-triazaspiroÄ4.5.Üdecan-4-one derivatives usefel for the treatment of ORL-1 receptor mediated disoreders - Google Patents
Hydroxy alkyl substituted 1,3,8-triazaspiroÄ4.5.Üdecan-4-one derivatives usefel for the treatment of ORL-1 receptor mediated disoreders Download PDFInfo
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- ZA200502836B ZA200502836B ZA200502836A ZA200502836A ZA200502836B ZA 200502836 B ZA200502836 B ZA 200502836B ZA 200502836 A ZA200502836 A ZA 200502836A ZA 200502836 A ZA200502836 A ZA 200502836A ZA 200502836 B ZA200502836 B ZA 200502836B
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- South Africa
- Prior art keywords
- group
- hydroxy
- methyl
- phenyl
- heteroaryl
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- 108010020615 nociceptin receptor Proteins 0.000 title claims description 26
- 230000001404 mediated effect Effects 0.000 title claims description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 title description 3
- -1 hydroxy, carboxy Chemical group 0.000 claims description 668
- 150000001875 compounds Chemical class 0.000 claims description 162
- 125000001424 substituent group Chemical group 0.000 claims description 129
- 125000001072 heteroaryl group Chemical group 0.000 claims description 128
- 125000003118 aryl group Chemical group 0.000 claims description 113
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 80
- 229910052739 hydrogen Inorganic materials 0.000 claims description 74
- 239000001257 hydrogen Substances 0.000 claims description 72
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 70
- 229910052736 halogen Inorganic materials 0.000 claims description 68
- 150000002367 halogens Chemical class 0.000 claims description 68
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 68
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 64
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 60
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 56
- 150000002431 hydrogen Chemical group 0.000 claims description 54
- 229910052757 nitrogen Inorganic materials 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 50
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 47
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 47
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
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- 150000003839 salts Chemical class 0.000 claims description 29
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- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 21
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 208000035475 disorder Diseases 0.000 claims description 18
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 230000008569 process Effects 0.000 claims description 17
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- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 12
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- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 11
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- 125000006509 3,4-difluorobenzyl group Chemical group [H]C1=C(F)C(F)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 10
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- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 9
- 125000006279 3-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Br)=C1[H])C([H])([H])* 0.000 claims description 9
- 125000006482 3-iodobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(I)=C1[H])C([H])([H])* 0.000 claims description 9
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 9
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 9
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 9
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 9
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 9
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 9
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000006494 2-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 claims description 8
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 8
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 8
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 8
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 8
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000006495 3-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 claims description 8
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 8
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims description 8
- 125000000173 4-trifluoromethoxy benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC(F)(F)F)C([H])([H])* 0.000 claims description 8
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 8
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
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- 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 7
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000005806 3,4,5-trimethoxybenzyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1C([H])([H])* 0.000 claims description 7
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 7
- 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 claims description 7
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 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 6
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- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 6
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- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims description 5
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- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
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- 125000001847 2-phenylcyclopropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- JOPKRKHMGGOVME-AKOCCIFCSA-N 3-[(2s)-3-amino-2-hydroxypropyl]-2-(1,2-dihydroacenaphthylen-1-yl)-1-(4-fluorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CNCCC21C(=O)N(C[C@@H](O)CN)C(C1C=3C=CC=C4C=CC=C(C=34)C1)N2C1=CC=C(F)C=C1 JOPKRKHMGGOVME-AKOCCIFCSA-N 0.000 claims description 2
- 102100031613 Hypermethylated in cancer 2 protein Human genes 0.000 claims description 2
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- IMGQPABKFUXCTN-GDLZYMKVSA-N 1-(4-fluorophenyl)-3-[(2r)-2-hydroxy-3-[3-(methylamino)propylamino]propyl]-8-[(8-methylnaphthalen-1-yl)methyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CN(CC=2C3=C(C)C=CC=C3C=CC=2)CCC21C(=O)N(C[C@H](O)CNCCCNC)CN2C1=CC=C(F)C=C1 IMGQPABKFUXCTN-GDLZYMKVSA-N 0.000 claims 1
- ALXBWOVLKSYZNY-RUZDIDTESA-N 3-[(2r)-3-amino-2-hydroxypropyl]-1-(4-fluorophenyl)-8-[(8-methylnaphthalen-1-yl)methyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C=12C(C)=CC=CC2=CC=CC=1CN(CC1)CCC1(C(N(C[C@H](O)CN)C1)=O)N1C1=CC=C(F)C=C1 ALXBWOVLKSYZNY-RUZDIDTESA-N 0.000 claims 1
- NNFWJRYNXMYWJE-JOCHJYFZSA-N 3-[(2r)-3-amino-2-hydroxypropyl]-8-cyclooctyl-1-(4-fluorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CN(C2CCCCCCC2)CCC21C(=O)N(C[C@H](O)CN)CN2C1=CC=C(F)C=C1 NNFWJRYNXMYWJE-JOCHJYFZSA-N 0.000 claims 1
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Classifications
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- 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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Landscapes
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- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40913402P | 2002-09-09 | 2002-09-09 |
Publications (1)
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|---|---|
| ZA200502836B true ZA200502836B (en) | 2006-06-28 |
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| ZA200502836A ZA200502836B (en) | 2002-09-09 | 2005-04-07 | Hydroxy alkyl substituted 1,3,8-triazaspiroÄ4.5.Üdecan-4-one derivatives usefel for the treatment of ORL-1 receptor mediated disoreders |
Country Status (19)
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| EP (1) | EP1601674B1 (es) |
| JP (1) | JP4712384B2 (es) |
| KR (1) | KR20050043935A (es) |
| CN (1) | CN100402529C (es) |
| AR (1) | AR041205A1 (es) |
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| CA (1) | CA2498275C (es) |
| CL (1) | CL2003001814A1 (es) |
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| NO (1) | NO20051743L (es) |
| NZ (1) | NZ538307A (es) |
| PL (1) | PL377047A1 (es) |
| RS (1) | RS20050208A (es) |
| TW (1) | TWI296627B (es) |
| WO (1) | WO2004022558A2 (es) |
| ZA (1) | ZA200502836B (es) |
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2003
- 2003-09-05 AU AU2003268512A patent/AU2003268512A1/en not_active Abandoned
- 2003-09-05 EP EP03749479A patent/EP1601674B1/en not_active Expired - Lifetime
- 2003-09-05 EA EA200500331A patent/EA009369B1/ru not_active IP Right Cessation
- 2003-09-05 KR KR1020057003938A patent/KR20050043935A/ko not_active Application Discontinuation
- 2003-09-05 CA CA2498275A patent/CA2498275C/en not_active Expired - Fee Related
- 2003-09-05 WO PCT/US2003/027956 patent/WO2004022558A2/en active Application Filing
- 2003-09-05 RS YUP-2005/0208A patent/RS20050208A/sr unknown
- 2003-09-05 PL PL377047A patent/PL377047A1/pl not_active Application Discontinuation
- 2003-09-05 NZ NZ538307A patent/NZ538307A/en unknown
- 2003-09-05 CN CNB038249901A patent/CN100402529C/zh not_active Expired - Fee Related
- 2003-09-05 US US10/656,934 patent/US7081463B2/en not_active Expired - Lifetime
- 2003-09-05 MX MXPA05002622A patent/MXPA05002622A/es active IP Right Grant
- 2003-09-05 BR BR0306309-7A patent/BR0306309A/pt not_active IP Right Cessation
- 2003-09-05 JP JP2004534697A patent/JP4712384B2/ja not_active Expired - Fee Related
- 2003-09-08 AR ARP030103248A patent/AR041205A1/es unknown
- 2003-09-08 TW TW092124686A patent/TWI296627B/zh not_active IP Right Cessation
- 2003-09-09 CL CL200301814A patent/CL2003001814A1/es unknown
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2005
- 2005-04-07 ZA ZA200502836A patent/ZA200502836B/en unknown
- 2005-04-08 NO NO20051743A patent/NO20051743L/no not_active Application Discontinuation
- 2005-10-04 US US11/242,654 patent/US7582649B2/en active Active
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2008
- 2008-12-03 US US12/327,437 patent/US8778956B2/en not_active Expired - Lifetime
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| PL377047A1 (pl) | 2006-01-23 |
| WO2004022558A3 (en) | 2004-05-21 |
| US8778956B2 (en) | 2014-07-15 |
| TWI296627B (en) | 2008-05-11 |
| US20040142955A1 (en) | 2004-07-22 |
| CN100402529C (zh) | 2008-07-16 |
| KR20050043935A (ko) | 2005-05-11 |
| US20090124614A1 (en) | 2009-05-14 |
| RS20050208A (en) | 2007-08-03 |
| NZ538307A (en) | 2008-04-30 |
| CL2003001814A1 (es) | 2005-02-11 |
| US7081463B2 (en) | 2006-07-25 |
| AR041205A1 (es) | 2005-05-11 |
| EA009369B1 (ru) | 2007-12-28 |
| CN1694883A (zh) | 2005-11-09 |
| JP2006500393A (ja) | 2006-01-05 |
| US7582649B2 (en) | 2009-09-01 |
| CA2498275A1 (en) | 2004-03-18 |
| JP4712384B2 (ja) | 2011-06-29 |
| TW200418857A (en) | 2004-10-01 |
| AU2003268512A1 (en) | 2004-03-29 |
| WO2004022558A2 (en) | 2004-03-18 |
| NO20051743L (no) | 2005-05-18 |
| EA200500331A1 (ru) | 2005-08-25 |
| EP1601674A2 (en) | 2005-12-07 |
| US20060030577A1 (en) | 2006-02-09 |
| BR0306309A (pt) | 2004-10-19 |
| CA2498275C (en) | 2011-07-12 |
| EP1601674B1 (en) | 2012-08-08 |
| MXPA05002622A (es) | 2005-09-08 |
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