CA2743534A1 - Composes azabicycliques fusionnes inhibant le recepteur vanilloide de sous-type 1 (vr1) - Google Patents

Composes azabicycliques fusionnes inhibant le recepteur vanilloide de sous-type 1 (vr1) Download PDF

Info

Publication number: CA2743534A1
Authority: CA; Canada
Prior art keywords: indazol; hydrogen; alkyl; ylurea; urea
Prior art date: 2003-08-05
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

Application number

CA2743534A

Other languages

English (en)

Inventor

Chih-Hung Lee

Erol K. Bayburt

Stanley Didomenico, Jr.

Irene Drizin

Arthur R. Gomtsyan

John R. Koenig

Richard J. Perner

Robert G. Schmidt, Jr.

Sean C. Turner

Tammie K. White

Guo Zhu Zheng

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Abbott Laboratories

Original Assignee

Abbott Laboratories

Priority date (The priority date 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 date listed.)

2003-08-05

Filing date

2004-08-04

Publication date

2005-02-24

2003-08-05 Priority claimed from US10/634,678 external-priority patent/US6933311B2/en

2004-08-04 Application filed by Abbott Laboratories filed Critical Abbott Laboratories

2005-02-24 Publication of CA2743534A1 publication Critical patent/CA2743534A1/fr

Status Abandoned legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 494
102000005962 receptors Human genes 0.000 title claims description 17
108010025083 TRPV1 receptor Proteins 0.000 title claims description 13
102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 title claims description 10
208000004454 Hyperalgesia Diseases 0.000 claims abstract description 7
206010037211 Psychomotor hyperactivity Diseases 0.000 claims abstract description 7
206010046543 Urinary incontinence Diseases 0.000 claims abstract description 7
230000002757 inflammatory effect Effects 0.000 claims abstract description 5
-1 adamantanyl Chemical group 0.000 claims description 411
239000001257 hydrogen Substances 0.000 claims description 175
229910052739 hydrogen Inorganic materials 0.000 claims description 175
125000000217 alkyl group Chemical group 0.000 claims description 167
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 104
125000003118 aryl group Chemical group 0.000 claims description 100
229910052736 halogen Inorganic materials 0.000 claims description 75
150000002367 halogens Chemical group 0.000 claims description 75
125000002947 alkylene group Chemical group 0.000 claims description 53
125000003545 alkoxy group Chemical group 0.000 claims description 50
125000004438 haloalkoxy group Chemical group 0.000 claims description 42
125000004995 haloalkylthio group Chemical group 0.000 claims description 41
125000001188 haloalkyl group Chemical group 0.000 claims description 40
125000004093 cyano group Chemical group *C#N 0.000 claims description 38
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
150000002431 hydrogen Chemical group 0.000 claims description 35
238000011282 treatment Methods 0.000 claims description 32
125000000753 cycloalkyl group Chemical group 0.000 claims description 30
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 29
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 29
150000003839 salts Chemical class 0.000 claims description 28
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 27
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 22
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 22
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 19
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 19
125000003710 aryl alkyl group Chemical group 0.000 claims description 18
125000003342 alkenyl group Chemical group 0.000 claims description 17
125000005243 carbonyl alkyl group Chemical group 0.000 claims description 17
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 15
125000004414 alkyl thio group Chemical group 0.000 claims description 15
125000004181 carboxyalkyl group Chemical group 0.000 claims description 15
125000004966 cyanoalkyl group Chemical group 0.000 claims description 15
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 14
125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 14
125000004967 formylalkyl group Chemical group 0.000 claims description 14
125000005358 mercaptoalkyl group Chemical group 0.000 claims description 14
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 13
241000124008 Mammalia Species 0.000 claims description 12
125000000304 alkynyl group Chemical group 0.000 claims description 12
239000008194 pharmaceutical composition Substances 0.000 claims description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
FWMLXBPKXUWATL-UHFFFAOYSA-N ethyl 2-isoquinolin-5-ylacetate Chemical compound N1=CC=C2C(CC(=O)OCC)=CC=CC2=C1 FWMLXBPKXUWATL-UHFFFAOYSA-N 0.000 claims description 6
KBCVSFMRVWNMGD-UHFFFAOYSA-N ethyl 2-isoquinolin-5-ylpropanoate Chemical compound N1=CC=C2C(C(C)C(=O)OCC)=CC=CC2=C1 KBCVSFMRVWNMGD-UHFFFAOYSA-N 0.000 claims description 6
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical group [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 5
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
239000002671 adjuvant Substances 0.000 claims description 3
125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 3
DGYVDSUKRCQOPQ-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-octylurea Chemical compound N1=CC=C2C(NC(=O)NCCCCCCCC)=CC=CC2=C1 DGYVDSUKRCQOPQ-UHFFFAOYSA-N 0.000 claims description 2
XWNZVHVHHKQZBK-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-pentylurea Chemical compound N1=CC=C2C(NC(=O)NCCCCC)=CC=CC2=C1 XWNZVHVHHKQZBK-UHFFFAOYSA-N 0.000 claims description 2
230000001668 ameliorated effect Effects 0.000 claims description 2
SHOMMGQAMRXRRK-UHFFFAOYSA-N bicyclo[3.1.1]heptane Chemical compound C1C2CC1CCC2 SHOMMGQAMRXRRK-UHFFFAOYSA-N 0.000 claims description 2
ATFAGQOANYDOJT-UHFFFAOYSA-N ethyl 2-isoquinolin-5-yl-2-methylpropanoate Chemical compound N1=CC=C2C(C(C)(C)C(=O)OCC)=CC=CC2=C1 ATFAGQOANYDOJT-UHFFFAOYSA-N 0.000 claims description 2
KOWZKGCOSUVJPN-UHFFFAOYSA-N ethyl 2-isoquinolin-5-ylbutanoate Chemical compound N1=CC=C2C(C(CC)C(=O)OCC)=CC=CC2=C1 KOWZKGCOSUVJPN-UHFFFAOYSA-N 0.000 claims description 2
230000005764 inhibitory process Effects 0.000 claims description 2
IXMKYBCGJGOHMF-UHFFFAOYSA-N 1-[[4-(8-azabicyclo[3.2.1]octan-8-yl)-2-chlorophenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1CCC2CCC1N2C1=CC=C(CNC(=O)NC=2C=3C=NNC=3C=CC=2)C(Cl)=C1 IXMKYBCGJGOHMF-UHFFFAOYSA-N 0.000 claims 2
KDERRLAIYVWAFI-UHFFFAOYSA-N 1-(1-adamantylmethyl)-3-isoquinolin-5-ylurea Chemical compound N1=CC=C2C(NC(NCC34CC5CC(CC(C5)C3)C4)=O)=CC=CC2=C1 KDERRLAIYVWAFI-UHFFFAOYSA-N 0.000 claims 1
KTZBBXRNJDXCSB-UHFFFAOYSA-N 1-(1-methylindazol-4-yl)-3-[[4-(trifluoromethylsulfanyl)phenyl]methyl]urea Chemical compound C1=CC=C2N(C)N=CC2=C1NC(=O)NCC1=CC=C(SC(F)(F)F)C=C1 KTZBBXRNJDXCSB-UHFFFAOYSA-N 0.000 claims 1
XLNUIJMINAERCA-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(3-phenylpropyl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NCCCC1=CC=CC=C1 XLNUIJMINAERCA-UHFFFAOYSA-N 0.000 claims 1
CPLPTJLBXKCJJG-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(naphthalen-1-ylmethyl)urea Chemical compound C=1C=CC2=CC=CC=C2C=1CNC(=O)NC1=CC=CC2=C1C=NN2 CPLPTJLBXKCJJG-UHFFFAOYSA-N 0.000 claims 1
BFVHJBJQHLCWHI-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[(3-phenylphenyl)methyl]urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NCC(C=1)=CC=CC=1C1=CC=CC=C1 BFVHJBJQHLCWHI-UHFFFAOYSA-N 0.000 claims 1
ZKIMTGFZGJXOTI-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[(4-methylphenyl)methyl]urea Chemical compound C1=CC(C)=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2 ZKIMTGFZGJXOTI-UHFFFAOYSA-N 0.000 claims 1
LPCBGXFLQAHZMH-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[2-(4-methylphenyl)ethyl]urea Chemical compound C1=CC(C)=CC=C1CCNC(=O)NC1=CC=CC2=C1C=NN2 LPCBGXFLQAHZMH-UHFFFAOYSA-N 0.000 claims 1
HIGUERZGRYTBFE-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[[3-(trifluoromethoxy)phenyl]methyl]urea Chemical compound FC(F)(F)OC1=CC=CC(CNC(=O)NC=2C=3C=NNC=3C=CC=2)=C1 HIGUERZGRYTBFE-UHFFFAOYSA-N 0.000 claims 1
PBKPKPFSTTWRCP-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[[3-(trifluoromethyl)phenyl]methyl]urea Chemical compound FC(F)(F)C1=CC=CC(CNC(=O)NC=2C=3C=NNC=3C=CC=2)=C1 PBKPKPFSTTWRCP-UHFFFAOYSA-N 0.000 claims 1
RLEYABCYQNSIDK-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[[4-(trifluoromethylsulfanyl)phenyl]methyl]urea Chemical compound C1=CC(SC(F)(F)F)=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2 RLEYABCYQNSIDK-UHFFFAOYSA-N 0.000 claims 1
YXJBIGBSPDMPJT-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[[6-(trifluoromethyl)pyridin-3-yl]methyl]urea Chemical compound C1=NC(C(F)(F)F)=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2 YXJBIGBSPDMPJT-UHFFFAOYSA-N 0.000 claims 1
UXPZXPONKINKIE-UHFFFAOYSA-N 1-(7-methyl-1h-indazol-4-yl)-3-[[4-(trifluoromethyl)phenyl]methyl]urea Chemical compound C1=2C=NNC=2C(C)=CC=C1NC(=O)NCC1=CC=C(C(F)(F)F)C=C1 UXPZXPONKINKIE-UHFFFAOYSA-N 0.000 claims 1
GHJGOYTUQIDGGR-UHFFFAOYSA-N 1-(7-methyl-1h-indazol-4-yl)-3-[[4-(trifluoromethylsulfanyl)phenyl]methyl]urea Chemical compound C1=2C=NNC=2C(C)=CC=C1NC(=O)NCC1=CC=C(SC(F)(F)F)C=C1 GHJGOYTUQIDGGR-UHFFFAOYSA-N 0.000 claims 1
RTXWGCGAWJQJPH-UHFFFAOYSA-N 1-(cyclohexylmethyl)-3-isoquinolin-5-ylurea Chemical compound C=1C=CC2=CN=CC=C2C=1NC(=O)NCC1CCCCC1 RTXWGCGAWJQJPH-UHFFFAOYSA-N 0.000 claims 1
OAJJISIESWYITC-JTQLQIEISA-N 1-[(1s)-1-(4-bromophenyl)ethyl]-3-(1h-indazol-4-yl)urea Chemical compound C1([C@@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)C)=CC=C(Br)C=C1 OAJJISIESWYITC-JTQLQIEISA-N 0.000 claims 1
UPVIXCWADWMJAR-UHFFFAOYSA-N 1-[(2,3-dichlorophenyl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound ClC1=CC=CC(CNC(=O)NC=2C=3C=NNC=3C=CC=2)=C1Cl UPVIXCWADWMJAR-UHFFFAOYSA-N 0.000 claims 1
YIJCGEUXXHWOMZ-UHFFFAOYSA-N 1-[(2,4-dichlorophenyl)methyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1=CC=C2N(C)N=CC2=C1NC(=O)NCC1=CC=C(Cl)C=C1Cl YIJCGEUXXHWOMZ-UHFFFAOYSA-N 0.000 claims 1
ISTXEYHIIUKJJQ-UHFFFAOYSA-N 1-[(2,4-dimethylphenyl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound CC1=CC(C)=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2 ISTXEYHIIUKJJQ-UHFFFAOYSA-N 0.000 claims 1
DQHJAXPNUPLOIM-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1=CC=C2N(C)N=CC2=C1NC(=O)NCC1=CC=CC=C1Cl DQHJAXPNUPLOIM-UHFFFAOYSA-N 0.000 claims 1
BYBAMVDEGFEQOG-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound ClC1=CC=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2 BYBAMVDEGFEQOG-UHFFFAOYSA-N 0.000 claims 1
GBAYWBKTRQWXNF-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1=CC=C2N(C)N=CC2=C1NC(=O)NCC1=CC=CC=C1F GBAYWBKTRQWXNF-UHFFFAOYSA-N 0.000 claims 1
SGLLXSSYLJXWFO-UHFFFAOYSA-N 1-[(3,4-dichlorophenyl)methyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1=CC=C2N(C)N=CC2=C1NC(=O)NCC1=CC=C(Cl)C(Cl)=C1 SGLLXSSYLJXWFO-UHFFFAOYSA-N 0.000 claims 1
GUYKDZRBMAKFNS-UHFFFAOYSA-N 1-[(3,4-dimethylphenyl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1=C(C)C(C)=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2 GUYKDZRBMAKFNS-UHFFFAOYSA-N 0.000 claims 1
HAXVGGUXPLREJB-UHFFFAOYSA-N 1-[(3-bromo-4-fluorophenyl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1=C(Br)C(F)=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2 HAXVGGUXPLREJB-UHFFFAOYSA-N 0.000 claims 1
HQWPERDKXOCVCJ-UHFFFAOYSA-N 1-[(3-chloro-4-fluorophenyl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1=C(Cl)C(F)=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2 HQWPERDKXOCVCJ-UHFFFAOYSA-N 0.000 claims 1
NBUJIWUAQKWHNI-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1=CC=C2N(C)N=CC2=C1NC(=O)NCC1=CC=C(Cl)C=C1 NBUJIWUAQKWHNI-UHFFFAOYSA-N 0.000 claims 1
QIXBPDJPNDOGRJ-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1=CC(Cl)=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2 QIXBPDJPNDOGRJ-UHFFFAOYSA-N 0.000 claims 1
WUXIXKACQGWCHD-UHFFFAOYSA-N 1-[(4-ethylphenyl)methyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1=CC(CC)=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2C WUXIXKACQGWCHD-UHFFFAOYSA-N 0.000 claims 1
XBOFJTZIVVZPCE-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1=CC=C2N(C)N=CC2=C1NC(=O)NCC1=CC=C(F)C=C1 XBOFJTZIVVZPCE-UHFFFAOYSA-N 0.000 claims 1
WWNBHQMSCKQTIM-UHFFFAOYSA-N 1-[(4-tert-butylcyclohexyl)methyl]-3-isoquinolin-5-ylurea Chemical compound C1CC(C(C)(C)C)CCC1CNC(=O)NC1=CC=CC2=CN=CC=C12 WWNBHQMSCKQTIM-UHFFFAOYSA-N 0.000 claims 1
IHYJOKYZXURJBO-UHFFFAOYSA-N 1-[(4-tert-butylphenyl)methyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1=CC=C2N(C)N=CC2=C1NC(=O)NCC1=CC=C(C(C)(C)C)C=C1 IHYJOKYZXURJBO-UHFFFAOYSA-N 0.000 claims 1
FLANCTWCDAIQGM-UHFFFAOYSA-N 1-[(4-tert-butylphenyl)methyl]-3-(7-methyl-1h-indazol-4-yl)urea Chemical compound C1=2C=NNC=2C(C)=CC=C1NC(=O)NCC1=CC=C(C(C)(C)C)C=C1 FLANCTWCDAIQGM-UHFFFAOYSA-N 0.000 claims 1
GUJOGOUNYTTYFZ-UHFFFAOYSA-N 1-[(6,6-dimethyl-4-bicyclo[3.1.1]heptanyl)methyl]-3-isoquinolin-5-ylurea Chemical compound N1=CC=C2C(NC(=O)NCC3C4CC(CC3)C4(C)C)=CC=CC2=C1 GUJOGOUNYTTYFZ-UHFFFAOYSA-N 0.000 claims 1
FMUQBEMGRSSKCD-UHFFFAOYSA-N 1-[1-(4-bromophenyl)ethyl]-3-(1-methylindazol-4-yl)urea Chemical compound C=1C=CC=2N(C)N=CC=2C=1NC(=O)NC(C)C1=CC=C(Br)C=C1 FMUQBEMGRSSKCD-UHFFFAOYSA-N 0.000 claims 1
ROOAIKVMIHUXGL-UHFFFAOYSA-N 1-[2-(2,4-dimethylphenyl)ethyl]-3-(1h-indazol-4-yl)urea Chemical compound CC1=CC(C)=CC=C1CCNC(=O)NC1=CC=CC2=C1C=NN2 ROOAIKVMIHUXGL-UHFFFAOYSA-N 0.000 claims 1
FJMXKWUCXAIYQJ-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenyl)ethyl]-3-(1h-indazol-4-yl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CCNC(=O)NC1=CC=CC2=C1C=NN2 FJMXKWUCXAIYQJ-UHFFFAOYSA-N 0.000 claims 1
NDCBEUYUWVZYMZ-UHFFFAOYSA-N 1-[[2-fluoro-5-(trifluoromethyl)phenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1CNC(=O)NC1=CC=CC2=C1C=NN2 NDCBEUYUWVZYMZ-UHFFFAOYSA-N 0.000 claims 1
WYKQJCVKBYSZOO-UHFFFAOYSA-N 1-[[3-fluoro-4-(trifluoromethyl)phenyl]methyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1=CC=C2N(C)N=CC2=C1NC(=O)NCC1=CC=C(C(F)(F)F)C(F)=C1 WYKQJCVKBYSZOO-UHFFFAOYSA-N 0.000 claims 1
TYTGHPXWAYOTEG-UHFFFAOYSA-N 1-[[3-fluoro-4-(trifluoromethyl)phenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1=C(C(F)(F)F)C(F)=CC(CNC(=O)NC=2C=3C=NNC=3C=CC=2)=C1 TYTGHPXWAYOTEG-UHFFFAOYSA-N 0.000 claims 1
XHQNKWJFNXHGJK-UHFFFAOYSA-N 1-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound FC(F)(F)C1=CC(F)=CC(CNC(=O)NC=2C=3C=NNC=3C=CC=2)=C1 XHQNKWJFNXHGJK-UHFFFAOYSA-N 0.000 claims 1
UJWLRLODSPVCTG-UHFFFAOYSA-N 1-[[4-(3-azabicyclo[2.2.1]heptan-3-yl)-2-(trifluoromethyl)phenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound FC(F)(F)C1=CC(N2C3CCC(C3)C2)=CC=C1CNC(=O)NC1=CC=CC2=C1C=NN2 UJWLRLODSPVCTG-UHFFFAOYSA-N 0.000 claims 1
HGOIAAUCCRMOEG-UHFFFAOYSA-N 1-[[4-(8-azabicyclo[3.2.1]octan-8-yl)-2-(trifluoromethyl)phenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1CCC2CCC1N2C1=CC=C(CNC(=O)NC=2C=3C=NNC=3C=CC=2)C(C(F)(F)F)=C1 HGOIAAUCCRMOEG-UHFFFAOYSA-N 0.000 claims 1
FPQHPUDYHCLCTO-UHFFFAOYSA-N 1-[[4-(8-azabicyclo[3.2.1]octan-8-yl)-3,5-difluorophenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1CCC2CCC1N2C1=C(F)C=C(CNC(=O)NC=2C=3C=NNC=3C=CC=2)C=C1F FPQHPUDYHCLCTO-UHFFFAOYSA-N 0.000 claims 1
DCSZKXVLNDMKDL-UHFFFAOYSA-N 1-[[4-(8-azabicyclo[3.2.1]octan-8-yl)-3-(trifluoromethyl)phenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1CCC2CCC1N2C1=CC=C(CNC(=O)NC=2C=3C=NNC=3C=CC=2)C=C1C(F)(F)F DCSZKXVLNDMKDL-UHFFFAOYSA-N 0.000 claims 1
ZDTTUYJJORJBME-UHFFFAOYSA-N 1-[[4-(8-azabicyclo[3.2.1]octan-8-yl)-3-chlorophenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1CCC2CCC1N2C1=CC=C(CNC(=O)NC=2C=3C=NNC=3C=CC=2)C=C1Cl ZDTTUYJJORJBME-UHFFFAOYSA-N 0.000 claims 1
ZDSNVUVKDYMAEI-UHFFFAOYSA-N 1-[[4-(8-azabicyclo[3.2.1]octan-8-yl)-3-fluorophenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound C1CCC2CCC1N2C1=CC=C(CNC(=O)NC=2C=3C=NNC=3C=CC=2)C=C1F ZDSNVUVKDYMAEI-UHFFFAOYSA-N 0.000 claims 1
SIFSOERBJAQEEF-UHFFFAOYSA-N 1-[[4-(8-azabicyclo[3.2.1]octan-8-yl)phenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound C=1C=C(N2C3CCC2CCC3)C=CC=1CNC(=O)NC1=CC=CC2=C1C=NN2 SIFSOERBJAQEEF-UHFFFAOYSA-N 0.000 claims 1
LWRBKRYFALJNHP-UHFFFAOYSA-N 1-[[4-(azepan-1-yl)-2-(trifluoromethyl)phenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound C=1C=C(CNC(=O)NC=2C=3C=NNC=3C=CC=2)C(C(F)(F)F)=CC=1N1CCCCCC1 LWRBKRYFALJNHP-UHFFFAOYSA-N 0.000 claims 1
FLNHGCZGIIRXLR-UHFFFAOYSA-N 1-[[4-(azepan-1-yl)-2-chlorophenyl]methyl]-3-(1h-indazol-4-yl)urea Chemical compound C=1C=C(CNC(=O)NC=2C=3C=NNC=3C=CC=2)C(Cl)=CC=1N1CCCCCC1 FLNHGCZGIIRXLR-UHFFFAOYSA-N 0.000 claims 1
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STZCRXQWRGQSJD-UHFFFAOYSA-M sodium;4-[[4-(dimethylamino)phenyl]diazenyl]benzenesulfonate Chemical compound [Na+].C1=CC(N(C)C)=CC=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-UHFFFAOYSA-M 0.000 description 1
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210000000278 spinal cord Anatomy 0.000 description 1
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239000007921 spray Substances 0.000 description 1
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238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
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239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
KCFDHICKAVJCIQ-UHFFFAOYSA-N tert-butyl 4-[[4-(8-azabicyclo[3.2.1]octan-8-yl)-2-chlorophenyl]methylcarbamoylamino]indazole-1-carboxylate Chemical compound C1CCC2CCC1N2C(C=C1Cl)=CC=C1CNC(=O)NC1=C2C=NN(C(=O)OC(C)(C)C)C2=CC=C1 KCFDHICKAVJCIQ-UHFFFAOYSA-N 0.000 description 1
WPQMBEYGZQAJEF-UHFFFAOYSA-N tert-butyl 4-[[4-(8-azabicyclo[3.2.1]octan-8-yl)-3-(trifluoromethyl)phenyl]methylcarbamoylamino]indazole-1-carboxylate Chemical compound C1CCC2CCC1N2C(C(=C1)C(F)(F)F)=CC=C1CNC(=O)NC1=C2C=NN(C(=O)OC(C)(C)C)C2=CC=C1 WPQMBEYGZQAJEF-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
XAMAFLWCELXNAY-UHFFFAOYSA-N tert-butyl n-[(4-cyanophenyl)methyl]-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)CC1=CC=C(C#N)C=C1 XAMAFLWCELXNAY-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000012360 testing method Methods 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
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125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000002769 thiazolinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
238000005809 transesterification reaction Methods 0.000 description 1
238000001890 transfection Methods 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
125000005455 trithianyl group Chemical group 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
238000005303 weighing Methods 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA2743534A 2003-08-05 2004-08-04 Composes azabicycliques fusionnes inhibant le recepteur vanilloide de sous-type 1 (vr1) Abandoned CA2743534A1 (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US10/634,678 US6933311B2 (en)	2003-02-11	2003-08-05	Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
US10/634,678		2003-08-05
CA002534542A CA2534542A1 (fr)	2003-02-11	2004-08-04	Composes azabicycliques fusionnes inhibant le recepteur vanilloide de sous-type 1 (vr1)

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002534542A Division CA2534542A1 (fr)	2003-02-11	2004-08-04	Composes azabicycliques fusionnes inhibant le recepteur vanilloide de sous-type 1 (vr1)

Publications (1)

Publication Number	Publication Date
CA2743534A1 true CA2743534A1 (fr)	2005-02-24

Family

ID=42331820

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2743534A Abandoned CA2743534A1 (fr)	2003-08-05	2004-08-04	Composes azabicycliques fusionnes inhibant le recepteur vanilloide de sous-type 1 (vr1)

Country Status (4)

Country	Link
JP (1)	JP2012072145A (fr)
CA (1)	CA2743534A1 (fr)
IL (1)	IL173515A0 (fr)
TW (1)	TW200524909A (fr)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MXPA04008073A (es) *	2002-02-20	2004-11-26	Abbott Lab	Compuestos azabiciclicos fusionados que inhiben el receptor de subtipo 1 (vr1) del receptor de vainilloide.

2004
- 2004-08-04 TW TW93123414A patent/TW200524909A/zh unknown
- 2004-08-04 CA CA2743534A patent/CA2743534A1/fr not_active Abandoned
2006
- 2006-02-02 IL IL173515A patent/IL173515A0/en unknown
2011
- 2011-10-14 JP JP2011226490A patent/JP2012072145A/ja active Pending

Also Published As

Publication number	Publication date
TW200524909A (en)	2005-08-01
JP2012072145A (ja)	2012-04-12
IL173515A0 (en)	2006-07-05

Publication	Publication Date	Title
US6933311B2 (en)	2005-08-23	Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
US8247413B2 (en)	2012-08-21	Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
CA2476936A1 (fr)	2003-08-28	Composes azabicycliques fusionnes qui inhibent le recepteur (vr1) sous-type 1 du recepteur vanilloide
US20050113576A1 (en)	2005-05-26	Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
US20030158188A1 (en)	2003-08-21	Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
RU2059622C1 (ru)	1996-05-10	Производные пиразола или их фармацевтически приемлемые кислотно-аддитивные соли
AU2010257277B2 (en)	2011-08-18	Fused compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
CA2479150A1 (fr)	2003-10-02	Derives heteroaromatiques d'uree en tant que modulateurs du recepteur vr-1 pour traiter la douleur
AU2006253842A1 (en)	2006-12-07	Novel cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation
US7595332B2 (en)	2009-09-29	Amides that inhibit vanilloid receptor subtype 1 (VR1)
WO2003076408A2 (fr)	2003-09-18	Derives d'indazole qui sont des activateurs de guanylate cyclase soluble
MX2010010262A (es)	2010-12-06	Metodos para la elaboracion de agentes para el sistema nervioso central que son antagonistas del trpv1.
CA2743534A1 (fr)	2005-02-24	Composes azabicycliques fusionnes inhibant le recepteur vanilloide de sous-type 1 (vr1)

Legal Events

Date	Code	Title	Description
2011-06-13	EEER	Examination request
2013-10-01	FZDE	Dead	Effective date: 20130806