IL172457A

IL172457A - Fused compounds containing an ureido group that inhibit vanilloid receptor subtype 1 (vr1) receptor for treating disorders caused by vanilloid receptor activity and process for their preparation

Fused compounds containing an ureido group that inhibit vanilloid receptor subtype 1 (vr1) receptor for treating disorders caused by vanilloid receptor activity and process for their preparation

Info

Publication number: IL172457A
Authority: IL; Israel
Prior art keywords: compound; formula; inden; dihydro; indazol
Prior art date: 2003-06-12

Application number

IL172457A

Other languages

English (en)

Other versions

IL172457A0 (en

Original Assignee

Abbott Lab

Priority date

2003-06-12

Filing date

2005-12-08

Publication date

2011-12-29

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=33555102&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IL172457(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2003-06-12 Priority claimed from US10/459,925 external-priority patent/US7015233B2/en

2004-06-09 Priority claimed from US10/864,068 external-priority patent/US7375126B2/en

2005-12-08 Application filed by Abbott Lab filed Critical Abbott Lab

2006-04-10 Publication of IL172457A0 publication Critical patent/IL172457A0/en

2011-12-29 Publication of IL172457A publication Critical patent/IL172457A/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 660
238000000034 method Methods 0.000 title claims abstract description 149
230000008569 process Effects 0.000 title claims abstract description 52
108010025083 TRPV1 receptor Proteins 0.000 title claims abstract description 32
102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 title claims description 21
230000000694 effects Effects 0.000 title description 7
102000005962 receptors Human genes 0.000 title description 7
108020003175 receptors Proteins 0.000 title description 7
108010062740 TRPV Cation Channels Proteins 0.000 title description 5
102000011040 TRPV Cation Channels Human genes 0.000 title description 5
238000002360 preparation method Methods 0.000 title description 5
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 title 1
150000003839 salts Chemical class 0.000 claims abstract description 62
241000124008 Mammalia Species 0.000 claims abstract description 27
230000036407 pain Effects 0.000 claims abstract description 18
230000002401 inhibitory effect Effects 0.000 claims abstract description 17
208000004454 Hyperalgesia Diseases 0.000 claims abstract description 9
206010046543 Urinary incontinence Diseases 0.000 claims abstract description 7
230000002757 inflammatory effect Effects 0.000 claims abstract description 6
208000035154 Hyperesthesia Diseases 0.000 claims abstract description 5
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 363
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 224
-1 carboxyalkyi Chemical group 0.000 claims description 155
125000000217 alkyl group Chemical group 0.000 claims description 110
239000000203 mixture Substances 0.000 claims description 110
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 102
229910052739 hydrogen Inorganic materials 0.000 claims description 100
239000001257 hydrogen Substances 0.000 claims description 100
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 94
229910001868 water Inorganic materials 0.000 claims description 93
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 90
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 87
239000002904 solvent Substances 0.000 claims description 74
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 66
239000004202 carbamide Substances 0.000 claims description 59
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 57
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 54
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 48
239000002253 acid Substances 0.000 claims description 37
229910052736 halogen Inorganic materials 0.000 claims description 36
150000002367 halogens Chemical class 0.000 claims description 35
125000003545 alkoxy group Chemical group 0.000 claims description 33
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 33
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 33
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 31
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 29
125000003118 aryl group Chemical group 0.000 claims description 29
125000001188 haloalkyl group Chemical group 0.000 claims description 26
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 25
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 25
125000004438 haloalkoxy group Chemical group 0.000 claims description 25
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 25
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 25
125000004966 cyanoalkyl group Chemical group 0.000 claims description 23
238000011282 treatment Methods 0.000 claims description 22
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
239000012298 atmosphere Substances 0.000 claims description 20
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 20
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 19
125000000623 heterocyclic group Chemical group 0.000 claims description 18
238000004519 manufacturing process Methods 0.000 claims description 18
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 17
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 17
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 16
238000003756 stirring Methods 0.000 claims description 16
125000004414 alkyl thio group Chemical group 0.000 claims description 15
125000000304 alkynyl group Chemical group 0.000 claims description 15
125000005243 carbonyl alkyl group Chemical group 0.000 claims description 15
125000004093 cyano group Chemical group *C#N 0.000 claims description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
208000035475 disorder Diseases 0.000 claims description 15
125000003342 alkenyl group Chemical group 0.000 claims description 14
125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 14
125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 13
125000003710 aryl alkyl group Chemical group 0.000 claims description 13
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
125000004967 formylalkyl group Chemical group 0.000 claims description 12
125000004995 haloalkylthio group Chemical group 0.000 claims description 12
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 11
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 10
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 claims description 10
YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 claims description 10
INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 claims description 8
238000010438 heat treatment Methods 0.000 claims description 8
235000010288 sodium nitrite Nutrition 0.000 claims description 8
238000000605 extraction Methods 0.000 claims description 6
125000001072 heteroaryl group Chemical group 0.000 claims description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
239000012279 sodium borohydride Substances 0.000 claims description 6
229910000033 sodium borohydride Inorganic materials 0.000 claims description 6
GNRVWTIJRDMIID-UHFFFAOYSA-N 1-(5-tert-butyl-2-fluoro-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound FC1CC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 GNRVWTIJRDMIID-UHFFFAOYSA-N 0.000 claims description 5
125000002757 morpholinyl group Chemical group 0.000 claims description 5
125000004193 piperazinyl group Chemical group 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
125000005961 oxazepanyl group Chemical group 0.000 claims description 4
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 4
HESYILDXDKYKKC-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(6-methoxy-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C12=CC(OC)=CC=C2CCC1NC(=O)NC1=CC=CC2=C1C=NN2 HESYILDXDKYKKC-UHFFFAOYSA-N 0.000 claims description 3
OUIHQJINQZAAFC-UHFFFAOYSA-N 1-(4-bromo-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1CC=2C(Br)=CC=CC=2C1NC(=O)NC1=CC=CC2=C1C=NN2 OUIHQJINQZAAFC-UHFFFAOYSA-N 0.000 claims description 3
VPSCJCQPUGKRNC-UHFFFAOYSA-N 1-(5-tert-butyl-2,3-dihydro-1h-inden-1-yl)-3-isoquinolin-5-ylurea Chemical compound N1=CC=C2C(NC(=O)NC3C4=CC=C(C=C4CC3)C(C)(C)C)=CC=CC2=C1 VPSCJCQPUGKRNC-UHFFFAOYSA-N 0.000 claims description 3
XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical class NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 claims description 3
125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
125000003386 piperidinyl group Chemical group 0.000 claims description 3
ZQOHBQZZPJFTBS-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(4-piperidin-1-yl-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC1CCC2=C1C=CC=C2N1CCCCC1 ZQOHBQZZPJFTBS-UHFFFAOYSA-N 0.000 claims description 2
UOHCGMBECWOBEU-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(4-pyrrolidin-1-yl-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC1CCC2=C1C=CC=C2N1CCCC1 UOHCGMBECWOBEU-UHFFFAOYSA-N 0.000 claims description 2
ZBISBOUCIVCJOF-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(5-methoxy-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C1CC2=CC(OC)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 ZBISBOUCIVCJOF-UHFFFAOYSA-N 0.000 claims description 2
YPTLZNNIGSSJPU-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(5-methyl-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C1CC2=CC(C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 YPTLZNNIGSSJPU-UHFFFAOYSA-N 0.000 claims description 2
SVYGRCSOIPQXGO-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(5-piperidin-1-yl-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=2)CCC1=CC=2N1CCCCC1 SVYGRCSOIPQXGO-UHFFFAOYSA-N 0.000 claims description 2
ICPVUQZAKSTNQF-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(6-methyl-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C12=CC(C)=CC=C2CCC1NC(=O)NC1=CC=CC2=C1C=NN2 ICPVUQZAKSTNQF-UHFFFAOYSA-N 0.000 claims description 2
PCUDEEPQUVIGBR-UHFFFAOYSA-N 1-(4,5-dimethoxy-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1CC2=C(OC)C(OC)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 PCUDEEPQUVIGBR-UHFFFAOYSA-N 0.000 claims description 2
FCINXFUMHCCMJT-UHFFFAOYSA-N 1-(4-chloro-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1CC=2C(Cl)=CC=CC=2C1NC(=O)NC1=CC=CC2=C1C=NN2 FCINXFUMHCCMJT-UHFFFAOYSA-N 0.000 claims description 2
YCAAQLHPLMLUQY-UHFFFAOYSA-N 1-(5,6-dimethoxy-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1=2C=C(OC)C(OC)=CC=2CCC1NC(=O)NC1=CC=CC2=C1C=NN2 YCAAQLHPLMLUQY-UHFFFAOYSA-N 0.000 claims description 2
SBVPKBZNKRFVGA-UHFFFAOYSA-N 1-(5-chloro-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1CC2=CC(Cl)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 SBVPKBZNKRFVGA-UHFFFAOYSA-N 0.000 claims description 2
BGZQKFANVOPJDS-UHFFFAOYSA-N 1-(5-tert-butyl-2,2-difluoro-1,3-dihydroinden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound FC1(F)CC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 BGZQKFANVOPJDS-UHFFFAOYSA-N 0.000 claims description 2
NHEQTPFLJJJJKT-UHFFFAOYSA-N 1-(6-fluoro-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C12=CC(F)=CC=C2CCC1NC(=O)NC1=CC=CC2=C1C=NN2 NHEQTPFLJJJJKT-UHFFFAOYSA-N 0.000 claims description 2
NHZJKQDNRCCOFK-UHFFFAOYSA-N 1-(6-fluoro-5-piperidin-1-yl-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound FC1=CC=2C(NC(=O)NC=3C=4C=NNC=4C=CC=3)CCC=2C=C1N1CCCCC1 NHZJKQDNRCCOFK-UHFFFAOYSA-N 0.000 claims description 2
BZQKTMPYJAGFNO-UHFFFAOYSA-N 1-[4-(azepan-1-yl)-2,3-dihydro-1h-inden-1-yl]-3-(1h-indazol-4-yl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC1CCC2=C1C=CC=C2N1CCCCCC1 BZQKTMPYJAGFNO-UHFFFAOYSA-N 0.000 claims description 2
150000001555 benzenes Chemical class 0.000 claims description 2
229940077388 benzenesulfonate Drugs 0.000 claims description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 2
FMQJAOGMNNKCBV-UHFFFAOYSA-N methyl 4-[[5-(trifluoromethyl)-2,3-dihydro-1h-inden-1-yl]carbamoylamino]indazole-1-carboxylate Chemical compound C1CC2=CC(C(F)(F)F)=CC=C2C1NC(=O)NC1=C2C=NN(C(=O)OC)C2=CC=C1 FMQJAOGMNNKCBV-UHFFFAOYSA-N 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 14
TYOYXJNGINZFET-GOSISDBHSA-N 1-[(1r)-5-tert-butyl-2,3-dihydro-1h-inden-1-yl]-3-(1h-indazol-4-yl)urea Chemical compound N([C@H]1C2=CC=C(C=C2CC1)C(C)(C)C)C(=O)NC1=CC=CC2=C1C=NN2 TYOYXJNGINZFET-GOSISDBHSA-N 0.000 claims 4
125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
UJHPWLQNPUIFJU-UHFFFAOYSA-N 1-(5-tert-butyl-2,3-dihydro-1h-inden-1-yl)-3-(3-methylisoquinolin-5-yl)urea Chemical compound C1CC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=C2C=C(C)N=CC2=CC=C1 UJHPWLQNPUIFJU-UHFFFAOYSA-N 0.000 claims 2
IKMATCBNKRNPBM-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(4-methyl-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C1CC=2C(C)=CC=CC=2C1NC(=O)NC1=CC=CC2=C1C=NN2 IKMATCBNKRNPBM-UHFFFAOYSA-N 0.000 claims 1
QDWZACMXOZMDBC-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(7-methyl-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C1=2C(C)=CC=CC=2CCC1NC(=O)NC1=CC=CC2=C1C=NN2 QDWZACMXOZMDBC-UHFFFAOYSA-N 0.000 claims 1
SVYGRCSOIPQXGO-HXUWFJFHSA-N 1-(1h-indazol-4-yl)-3-[(1r)-5-piperidin-1-yl-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C([C@H](C1=CC=2)NC(=O)NC=3C=4C=NNC=4C=CC=3)CC1=CC=2N1CCCCC1 SVYGRCSOIPQXGO-HXUWFJFHSA-N 0.000 claims 1
SVYGRCSOIPQXGO-FQEVSTJZSA-N 1-(1h-indazol-4-yl)-3-[(1s)-5-piperidin-1-yl-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C([C@@H](C1=CC=2)NC(=O)NC=3C=4C=NNC=4C=CC=3)CC1=CC=2N1CCCCC1 SVYGRCSOIPQXGO-FQEVSTJZSA-N 0.000 claims 1
NBBJYIVJMJCFCE-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(2-methylpiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound CC1CCCCN1C1=CC=C(C(CC2)NC(=O)NC=3C=4C=NNC=4C=CC=3)C2=C1 NBBJYIVJMJCFCE-UHFFFAOYSA-N 0.000 claims 1
PNBWVYYXZCLQRU-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(3-methylpiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1C(C)CCCN1C1=CC=C(C(CC2)NC(=O)NC=3C=4C=NNC=4C=CC=3)C2=C1 PNBWVYYXZCLQRU-UHFFFAOYSA-N 0.000 claims 1
GHAQCPBCRKBIGN-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(4-phenylpiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=2)CCC1=CC=2N(CC1)CCC1C1=CC=CC=C1 GHAQCPBCRKBIGN-UHFFFAOYSA-N 0.000 claims 1
RZFOJZILWOUWLX-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(4-piperidin-1-ylpiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=2)CCC1=CC=2N(CC1)CCC1N1CCCCC1 RZFOJZILWOUWLX-UHFFFAOYSA-N 0.000 claims 1
QLDCRXZBQVZDEZ-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(trifluoromethyl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1CC2=CC(C(F)(F)F)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 QLDCRXZBQVZDEZ-UHFFFAOYSA-N 0.000 claims 1
WFTZESZPFIQNRC-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-[4-(trifluoromethyl)piperidin-1-yl]-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1CC(C(F)(F)F)CCN1C1=CC=C(C(CC2)NC(=O)NC=3C=4C=NNC=4C=CC=3)C2=C1 WFTZESZPFIQNRC-UHFFFAOYSA-N 0.000 claims 1
DEHOJLUMBBKMOD-UHFFFAOYSA-N 1-(5-bromo-2,3-dihydro-1h-inden-1-yl)-3-isoquinolin-5-ylurea Chemical compound N1=CC=C2C(NC(=O)NC3C4=CC=C(C=C4CC3)Br)=CC=CC2=C1 DEHOJLUMBBKMOD-UHFFFAOYSA-N 0.000 claims 1
YYVBBZUGFCWXBA-UHFFFAOYSA-N 1-(5-fluoro-2,3-dihydro-1h-inden-1-yl)-1-(1h-indazol-4-yl)urea Chemical compound C1CC2=CC(F)=CC=C2C1N(C(=O)N)C1=CC=CC2=C1C=NN2 YYVBBZUGFCWXBA-UHFFFAOYSA-N 0.000 claims 1
TYOYXJNGINZFET-UHFFFAOYSA-N 1-(5-tert-butyl-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1CC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 TYOYXJNGINZFET-UHFFFAOYSA-N 0.000 claims 1
JMWSQSYRBYDBND-UHFFFAOYSA-N 1-(5-tert-butyl-2,3-dihydro-1h-inden-2-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1C2=CC(C(C)(C)C)=CC=C2CC1NC(=O)NC1=CC=CC2=C1C=NN2 JMWSQSYRBYDBND-UHFFFAOYSA-N 0.000 claims 1
FGZOWQBNDORKQL-GOSISDBHSA-N 1-[(1r)-5-(2-cyanopropan-2-yl)-2,3-dihydro-1h-inden-1-yl]-3-(1h-indazol-4-yl)urea Chemical compound N([C@H]1C2=CC=C(C=C2CC1)C(C)(C#N)C)C(=O)NC1=CC=CC2=C1C=NN2 FGZOWQBNDORKQL-GOSISDBHSA-N 0.000 claims 1
PCUDEEPQUVIGBR-HNNXBMFYSA-N 1-[(1s)-4,5-dimethoxy-2,3-dihydro-1h-inden-1-yl]-3-(1h-indazol-4-yl)urea Chemical compound N([C@@H]1C2=CC=C(C(=C2CC1)OC)OC)C(=O)NC1=CC=CC2=C1C=NN2 PCUDEEPQUVIGBR-HNNXBMFYSA-N 0.000 claims 1
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238000000638 solvent extraction Methods 0.000 description 1
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210000000278 spinal cord Anatomy 0.000 description 1
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238000013222 sprague-dawley male rat Methods 0.000 description 1
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
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238000005809 transesterification reaction Methods 0.000 description 1
238000001890 transfection Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
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125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
238000005406 washing Methods 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