MX2007012162A - Tratamiento de la enfermedad de de parkinson, la apnea obstructiva del sueno, la demencia con cuerpos de lewy, la demencia vascular con ligandos de receptor de h3 de histamina de alquilaminas que no contienen imidazol. - Google Patents
Tratamiento de la enfermedad de de parkinson, la apnea obstructiva del sueno, la demencia con cuerpos de lewy, la demencia vascular con ligandos de receptor de h3 de histamina de alquilaminas que no contienen imidazol.Info
- Publication number
- MX2007012162A MX2007012162A MX2007012162A MX2007012162A MX2007012162A MX 2007012162 A MX2007012162 A MX 2007012162A MX 2007012162 A MX2007012162 A MX 2007012162A MX 2007012162 A MX2007012162 A MX 2007012162A MX 2007012162 A MX2007012162 A MX 2007012162A
- Authority
- MX
- Mexico
- Prior art keywords
- group
- propyl
- alkyl
- piperidine
- use according
- Prior art date
Links
- -1 imidazole alkylamines Chemical class 0.000 title claims abstract description 372
- 208000018737 Parkinson disease Diseases 0.000 title claims abstract description 44
- 238000011282 treatment Methods 0.000 title claims abstract description 33
- 208000001797 obstructive sleep apnea Diseases 0.000 title claims abstract description 26
- 206010067889 Dementia with Lewy bodies Diseases 0.000 title claims abstract description 22
- 201000002832 Lewy body dementia Diseases 0.000 title claims abstract description 22
- 201000004810 Vascular dementia Diseases 0.000 title claims abstract description 20
- 102000004384 Histamine H3 receptors Human genes 0.000 title claims description 18
- 108090000981 Histamine H3 receptors Proteins 0.000 title claims description 18
- 239000003446 ligand Substances 0.000 title claims description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title abstract description 39
- 201000003631 narcolepsy Diseases 0.000 claims abstract description 15
- 239000005557 antagonist Substances 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 254
- 150000001875 compounds Chemical class 0.000 claims description 212
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 144
- 125000003118 aryl group Chemical group 0.000 claims description 110
- 125000004432 carbon atom Chemical group C* 0.000 claims description 109
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 101
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 86
- 125000001424 substituent group Chemical group 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 47
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 37
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 34
- 125000005843 halogen group Chemical group 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 229910052717 sulfur Inorganic materials 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 27
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 229920006395 saturated elastomer Polymers 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 20
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 20
- 125000000468 ketone group Chemical group 0.000 claims description 20
- 125000001624 naphthyl group Chemical group 0.000 claims description 20
- 230000007958 sleep Effects 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 18
- 125000002837 carbocyclic group Chemical group 0.000 claims description 17
- 125000004434 sulfur atom Chemical group 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 150000002576 ketones Chemical class 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 14
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 13
- 206010041349 Somnolence Diseases 0.000 claims description 13
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims description 13
- 150000001336 alkenes Chemical class 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 13
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 claims description 13
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 claims description 12
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000002619 bicyclic group Chemical group 0.000 claims description 12
- UKLJMHXGZUJRTL-UHFFFAOYSA-L calcium;n-cyclohexylsulfamate Chemical group [Ca+2].[O-]S(=O)(=O)NC1CCCCC1.[O-]S(=O)(=O)NC1CCCCC1 UKLJMHXGZUJRTL-UHFFFAOYSA-L 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 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 12
- 230000000694 effects Effects 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 11
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 11
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 claims description 10
- 229940035678 anti-parkinson drug Drugs 0.000 claims description 10
- 125000003435 aroyl group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 9
- 239000000556 agonist Substances 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 150000004677 hydrates Chemical class 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 230000003287 optical effect Effects 0.000 claims description 9
- 150000002923 oximes Chemical group 0.000 claims description 9
- 125000005936 piperidyl group Chemical group 0.000 claims description 9
- NNACHAUCXXVJSP-UHFFFAOYSA-N pitolisant Chemical compound C1=CC(Cl)=CC=C1CCCOCCCN1CCCCC1 NNACHAUCXXVJSP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 208000024891 symptom Diseases 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 150000002829 nitrogen Chemical class 0.000 claims description 8
- 208000019116 sleep disease Diseases 0.000 claims description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 7
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 7
- 150000001345 alkine derivatives Chemical class 0.000 claims description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 7
- 150000001721 carbon Chemical group 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 239000011593 sulfur Substances 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 150000003857 carboxamides Chemical class 0.000 claims description 6
- 125000005518 carboxamido group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 6
- POPHMOPNVVKGRW-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7-octahydronaphthalene Chemical compound C1CCC2CCCCC2=C1 POPHMOPNVVKGRW-UHFFFAOYSA-N 0.000 claims description 5
- 206010012289 Dementia Diseases 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000939 antiparkinson agent Substances 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 230000029058 respiratory gaseous exchange Effects 0.000 claims description 5
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 5
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 5
- 150000003457 sulfones Chemical class 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- JEVKRDOAGIIPGY-UHFFFAOYSA-N 1-[3-(4-nitrophenoxy)propyl]piperidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCCCN1CCCCC1 JEVKRDOAGIIPGY-UHFFFAOYSA-N 0.000 claims description 4
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 4
- 125000005978 1-naphthyloxy group Chemical group 0.000 claims description 4
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 4
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 4
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 claims description 4
- XECQIHAUZSJKSI-UHFFFAOYSA-N CN(CCCCCOC1=CC=CC=C1)CC.O(C1=CC=CC=C1)CCCCCN1CCCC1.O(C1=CC=CC=C1)CCCCCN1CCCCC1 Chemical compound CN(CCCCCOC1=CC=CC=C1)CC.O(C1=CC=CC=C1)CCCCCN1CCCC1.O(C1=CC=CC=C1)CCCCCN1CCCCC1 XECQIHAUZSJKSI-UHFFFAOYSA-N 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 4
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 4
- 101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002355 alkine group Chemical group 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 229960004502 levodopa Drugs 0.000 claims description 4
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 4
- QOWOXBFFQOXPHM-UHFFFAOYSA-O oxo-[[1-[[4-(oxoazaniumylmethylidene)pyridin-1-yl]methyl]pyridin-4-ylidene]methyl]azanium;chloride Chemical compound [Cl-].C1=CC(=C[NH+]=O)C=CN1CN1C=CC(=C[NH+]=O)C=C1 QOWOXBFFQOXPHM-UHFFFAOYSA-O 0.000 claims description 4
- HAGDSAQHKMXLNR-UHFFFAOYSA-N 1-[3-(4-propylphenoxy)propyl]piperidine Chemical compound C1=CC(CCC)=CC=C1OCCCN1CCCCC1 HAGDSAQHKMXLNR-UHFFFAOYSA-N 0.000 claims description 3
- WIFMRWGDUJOZFS-UHFFFAOYSA-N 1-[4-[3-(2-methylpiperidin-1-yl)propoxy]phenyl]propan-1-one Chemical compound C1=CC(C(=O)CC)=CC=C1OCCCN1C(C)CCCC1 WIFMRWGDUJOZFS-UHFFFAOYSA-N 0.000 claims description 3
- QGQNOAVSCDLCOU-UHFFFAOYSA-N 10-piperidin-1-yldecan-1-amine Chemical compound NCCCCCCCCCCN1CCCCC1 QGQNOAVSCDLCOU-UHFFFAOYSA-N 0.000 claims description 3
- GCINBWWQZPLPMO-UHFFFAOYSA-N 2-(cyclohexylmethyl)-1-(3-piperidin-1-ylpropyl)guanidine;1-[3-(diethylamino)propyl]-3-phenylurea Chemical compound CCN(CC)CCCNC(=O)NC1=CC=CC=C1.C1CCCCC1CN=C(N)NCCCN1CCCCC1 GCINBWWQZPLPMO-UHFFFAOYSA-N 0.000 claims description 3
- FWWOWPGPERBCNJ-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)-4-oxobutanoic acid Chemical compound OCCOC(=O)CC(O)C(O)=O FWWOWPGPERBCNJ-UHFFFAOYSA-N 0.000 claims description 3
- LHXFUNSDSFWUSK-UHFFFAOYSA-N 3-methyl-1-(5-phenoxypentyl)piperidine;4-methyl-1-(5-phenoxypentyl)piperidine Chemical compound C1CC(C)CCN1CCCCCOC1=CC=CC=C1.C1C(C)CCCN1CCCCCOC1=CC=CC=C1 LHXFUNSDSFWUSK-UHFFFAOYSA-N 0.000 claims description 3
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 3
- WNDNWKMOVBJCTE-UHFFFAOYSA-N C(#N)C1=CC=C(OCCCN2C(CCCC2C)C)C=C1.[N+](=O)([O-])C1=CC=C(OCCCN2CCC(CC2)C)C=C1.[N+](=O)([O-])C1=CC=C(OCCCN2C(CCCC2)C)C=C1 Chemical compound C(#N)C1=CC=C(OCCCN2C(CCCC2C)C)C=C1.[N+](=O)([O-])C1=CC=C(OCCCN2CCC(CC2)C)C=C1.[N+](=O)([O-])C1=CC=C(OCCCN2C(CCCC2)C)C=C1 WNDNWKMOVBJCTE-UHFFFAOYSA-N 0.000 claims description 3
- KCHIGZSQXJTXKL-RLGPXSRBSA-N C1(CC1)C(=O)C1=CC=C(OCCCN2C[C@H](C[C@@H](C2)C)C)C=C1.C(#N)C1=CC=C(OCCCN2C[C@H](C[C@@H](C2)C)C)C=C1 Chemical compound C1(CC1)C(=O)C1=CC=C(OCCCN2C[C@H](C[C@@H](C2)C)C)C=C1.C(#N)C1=CC=C(OCCCN2C[C@H](C[C@@H](C2)C)C)C=C1 KCHIGZSQXJTXKL-RLGPXSRBSA-N 0.000 claims description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 3
- BKRGVLQUQGGVSM-KBXCAEBGSA-N Revanil Chemical compound C1=CC(C=2[C@H](N(C)C[C@H](C=2)NC(=O)N(CC)CC)C2)=C3C2=CNC3=C1 BKRGVLQUQGGVSM-KBXCAEBGSA-N 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 239000012965 benzophenone Substances 0.000 claims description 3
- 150000008366 benzophenones Chemical class 0.000 claims description 3
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 claims description 3
- 229960002802 bromocriptine Drugs 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 229960003587 lisuride Drugs 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 claims description 3
- 230000003389 potentiating effect Effects 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 150000003335 secondary amines Chemical group 0.000 claims description 3
- PCFIPYFVXDCWBW-UHFFFAOYSA-N tricyclo[3.3.1.03,7]nonane Chemical compound C1C(C2)C3CC2CC1C3 PCFIPYFVXDCWBW-UHFFFAOYSA-N 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 2
- IWMKMYSEPKBDGO-UHFFFAOYSA-N 1-(5-naphthalen-2-yloxypentyl)pyrrolidine Chemical compound C=1C=C2C=CC=CC2=CC=1OCCCCCN1CCCC1 IWMKMYSEPKBDGO-UHFFFAOYSA-N 0.000 claims description 2
- SGNQZZYSCBDYED-UHFFFAOYSA-N 1-[4-[3-(2-methylpiperidin-1-yl)propoxy]phenyl]propan-1-one;1-[4-[3-(4-methylpiperidin-1-yl)propoxy]phenyl]propan-1-one Chemical compound C1=CC(C(=O)CC)=CC=C1OCCCN1CCC(C)CC1.C1=CC(C(=O)CC)=CC=C1OCCCN1C(C)CCCC1 SGNQZZYSCBDYED-UHFFFAOYSA-N 0.000 claims description 2
- HOAGMZZKOJIDLM-UHFFFAOYSA-N 1-[4-[3-(3,6-dihydro-2h-pyridin-1-yl)propoxy]phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1OCCCN1CC=CCC1 HOAGMZZKOJIDLM-UHFFFAOYSA-N 0.000 claims description 2
- YRCDOXWMMRDRRD-UHFFFAOYSA-N 1-[4-[3-(3-methylpiperidin-1-yl)propoxy]phenyl]propan-1-ol Chemical compound C1=CC(C(O)CC)=CC=C1OCCCN1CC(C)CCC1 YRCDOXWMMRDRRD-UHFFFAOYSA-N 0.000 claims description 2
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- HNVIQLPOGUDBSU-UHFFFAOYSA-N 2,6-dimethylmorpholine Chemical compound CC1CNCC(C)O1 HNVIQLPOGUDBSU-UHFFFAOYSA-N 0.000 claims description 2
- 125000005979 2-naphthyloxy group Chemical group 0.000 claims description 2
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- IQWYZGFQBIUUMV-UHFFFAOYSA-N 4-[3-(azepan-1-yl)propoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCCCN1CCCCCC1 IQWYZGFQBIUUMV-UHFFFAOYSA-N 0.000 claims description 2
- KDBMUMWCZLNVHO-JKSUJKDBSA-N 4-[3-[(2s,5r)-5-ethyl-2-methylpiperidin-1-yl]propoxy]benzonitrile Chemical compound C1[C@H](CC)CC[C@H](C)N1CCCOC1=CC=C(C#N)C=C1 KDBMUMWCZLNVHO-JKSUJKDBSA-N 0.000 claims description 2
- NKJJAPIGFNBSKB-UHFFFAOYSA-N 4-chlorobicyclo[2.2.1]heptan-3-one Chemical compound C1CC2CC(=O)C1(Cl)C2 NKJJAPIGFNBSKB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- KEBSSDPOWGILNB-UHFFFAOYSA-N 6-bromo-2,5-dioxatricyclo[6.2.1.01,6]undecane Chemical compound O1CCOC2(Br)C1(C1)CCC1C2 KEBSSDPOWGILNB-UHFFFAOYSA-N 0.000 claims description 2
- QVKZJOHJEDBCBX-UHFFFAOYSA-N 6-chloro-2,5-dioxatricyclo[6.2.1.01,6]undecane Chemical compound O1CCOC2(Cl)C1(C1)CCC1C2 QVKZJOHJEDBCBX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 229930194542 Keto Natural products 0.000 claims description 2
- 241000219171 Malpighiales Species 0.000 claims description 2
- 208000006199 Parasomnias Diseases 0.000 claims description 2
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 2
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 2
- 230000002411 adverse Effects 0.000 claims description 2
- 125000002009 alkene group Chemical group 0.000 claims description 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- VFSFCYAQBIPUSL-UHFFFAOYSA-N cyclopropylbenzene Chemical compound C1CC1C1=CC=CC=C1 VFSFCYAQBIPUSL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 230000004927 fusion Effects 0.000 claims description 2
- BNRNAKTVFSZAFA-UHFFFAOYSA-N hydrindane Chemical compound C1CCCC2CCCC21 BNRNAKTVFSZAFA-UHFFFAOYSA-N 0.000 claims description 2
- 125000005020 hydroxyalkenyl group Chemical group 0.000 claims description 2
- 206010022437 insomnia Diseases 0.000 claims description 2
- 210000004558 lewy body Anatomy 0.000 claims description 2
- 238000012423 maintenance Methods 0.000 claims description 2
- JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 claims description 2
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 claims description 2
- 125000003367 polycyclic group Chemical group 0.000 claims description 2
- 125000006684 polyhaloalkyl group Polymers 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 150000002430 hydrocarbons Chemical group 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- KFFMRYQMDWYABB-UHFFFAOYSA-N 7-chloro-n-[2-[4-(3-piperidin-1-ylpropoxy)phenyl]ethyl]quinolin-4-amine Chemical compound C=1C=NC2=CC(Cl)=CC=C2C=1NCCC(C=C1)=CC=C1OCCCN1CCCCC1 KFFMRYQMDWYABB-UHFFFAOYSA-N 0.000 claims 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
- IFFCPLAPGNFPQT-UHFFFAOYSA-N 1-(5-phenylsulfanylpentyl)pyrrolidine Chemical compound C1CCCN1CCCCCSC1=CC=CC=C1 IFFCPLAPGNFPQT-UHFFFAOYSA-N 0.000 claims 1
- QSHSUPUUQNVVTB-UHFFFAOYSA-N 1-[4-(5-pyrrolidin-1-ylpentoxy)phenyl]ethanol Chemical compound C1=CC(C(O)C)=CC=C1OCCCCCN1CCCC1 QSHSUPUUQNVVTB-UHFFFAOYSA-N 0.000 claims 1
- BFYGTUXTIUICRI-UHFFFAOYSA-N 1-[5-(3-chlorophenoxy)pentyl]pyrrolidine Chemical compound ClC1=CC=CC(OCCCCCN2CCCC2)=C1 BFYGTUXTIUICRI-UHFFFAOYSA-N 0.000 claims 1
- WRFHNWLEAOFJIR-UHFFFAOYSA-N 1-[5-(4-chlorophenoxy)pentyl]pyrrolidine Chemical compound C1=CC(Cl)=CC=C1OCCCCCN1CCCC1 WRFHNWLEAOFJIR-UHFFFAOYSA-N 0.000 claims 1
- YKRXFKFSDWGILY-UHFFFAOYSA-N 1-[5-(4-methoxyphenoxy)pentyl]pyrrolidine Chemical compound C1=CC(OC)=CC=C1OCCCCCN1CCCC1 YKRXFKFSDWGILY-UHFFFAOYSA-N 0.000 claims 1
- BZZGABFEBXYWST-UHFFFAOYSA-N 1-[5-(4-methylphenoxy)pentyl]pyrrolidine Chemical compound C1=CC(C)=CC=C1OCCCCCN1CCCC1 BZZGABFEBXYWST-UHFFFAOYSA-N 0.000 claims 1
- ITOJPDNONZGUKB-UHFFFAOYSA-N 1-[5-(4-nitrophenoxy)pentyl]pyrrolidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCCCCCN1CCCC1 ITOJPDNONZGUKB-UHFFFAOYSA-N 0.000 claims 1
- SHDCMHVGBWJCOB-UHFFFAOYSA-N 1-[5-(4-phenylphenoxy)pentyl]pyrrolidine Chemical compound C1CCCN1CCCCCOC(C=C1)=CC=C1C1=CC=CC=C1 SHDCMHVGBWJCOB-UHFFFAOYSA-N 0.000 claims 1
- LGIQGHPFIIOKPD-UHFFFAOYSA-N 2-methyl-N-(3-piperidin-1-ylpropyl)quinolin-4-amine N-(2-piperidin-1-ylethyl)-1,3-benzothiazol-2-amine N-(6-piperidin-1-ylhexyl)-1,3-benzothiazol-2-amine N-(6-piperidin-1-ylhexyl)quinolin-4-amine Chemical compound CC1=NC2=CC=CC=C2C(=C1)NCCCN1CCCCC1.N1(CCCCC1)CCCCCCNC1=CC=NC2=CC=CC=C12.N1(CCCCC1)CCCCCCNC=1SC2=C(N1)C=CC=C2.N2(CCCCC2)CCNC=2SC1=C(N2)C=CC=C1 LGIQGHPFIIOKPD-UHFFFAOYSA-N 0.000 claims 1
- XDRLZRGXUHHCPA-UHFFFAOYSA-N 2-nitro-5-(6-piperidin-1-ylhexyl)pyridine Chemical group C1=NC([N+](=O)[O-])=CC=C1CCCCCCN1CCCCC1 XDRLZRGXUHHCPA-UHFFFAOYSA-N 0.000 claims 1
- STSUBJWQKKSZQX-UHFFFAOYSA-N 3-[(4-chlorophenyl)methyl]-5-(2-piperidin-1-ylethyl)-1,2,4-oxadiazole Chemical compound C1=CC(Cl)=CC=C1CC1=NOC(CCN2CCCCC2)=N1 STSUBJWQKKSZQX-UHFFFAOYSA-N 0.000 claims 1
- KQCGHXAUBIANET-UHFFFAOYSA-N 3-chloro-n-methyl-n-(4-piperidin-1-ylbutyl)benzenesulfonamide Chemical group C=1C=CC(Cl)=CC=1S(=O)(=O)N(C)CCCCN1CCCCC1 KQCGHXAUBIANET-UHFFFAOYSA-N 0.000 claims 1
- CTUPSSVYEBTCNI-UHFFFAOYSA-N 3-methyl-1-[3-(4-nitrophenoxy)propyl]piperidine Chemical compound C1C(C)CCCN1CCCOC1=CC=C([N+]([O-])=O)C=C1 CTUPSSVYEBTCNI-UHFFFAOYSA-N 0.000 claims 1
- DKPZVUAFSFRTQZ-UHFFFAOYSA-N 4-[3-(3-methylpiperidin-1-yl)propoxy]benzonitrile Chemical compound C1C(C)CCCN1CCCOC1=CC=C(C#N)C=C1 DKPZVUAFSFRTQZ-UHFFFAOYSA-N 0.000 claims 1
- BNFFRTKRGJYLNN-UHFFFAOYSA-N 6,6-dimethylbicyclo[3.1.1]hept-4-ene Chemical compound C1C2=CCCC1C2(C)C BNFFRTKRGJYLNN-UHFFFAOYSA-N 0.000 claims 1
- PBHJONMFXWRJDI-UHFFFAOYSA-N 7-chloro-N-(10-piperidin-1-yldecyl)quinolin-4-amine 7-chloro-N-(12-piperidin-1-yldodecyl)quinolin-4-amine 7-chloro-N-[4-(3-piperidin-1-ylpropoxy)phenyl]quinolin-4-amine Chemical compound ClC1=CC=C2C(=CC=NC2=C1)NC1=CC=C(C=C1)OCCCN1CCCCC1.ClC1=CC=C2C(=CC=NC2=C1)NCCCCCCCCCCCCN1CCCCC1.ClC1=CC=C2C(=CC=NC2=C1)NCCCCCCCCCCN1CCCCC1 PBHJONMFXWRJDI-UHFFFAOYSA-N 0.000 claims 1
- KQQJOBYYDOVVTN-UHFFFAOYSA-N 7-chloro-n-[4-(3-piperidin-1-ylpropoxy)phenyl]quinolin-4-amine Chemical compound C=1C=NC2=CC(Cl)=CC=C2C=1NC(C=C1)=CC=C1OCCCN1CCCCC1 KQQJOBYYDOVVTN-UHFFFAOYSA-N 0.000 claims 1
- RIHBXSRKISJUEL-UHFFFAOYSA-N BrC1=CC=C(OCCCN2CCCCC2)C=C1.C(CC)(=O)C1=CC=C(OCCCN2CCC(CC2)C)C=C1.C(C)OC(CC)C1=CC=C(OCCCN2C(CCCC2)C)C=C1 Chemical compound BrC1=CC=C(OCCCN2CCCCC2)C=C1.C(CC)(=O)C1=CC=C(OCCCN2CCC(CC2)C)C=C1.C(C)OC(CC)C1=CC=C(OCCCN2C(CCCC2)C)C=C1 RIHBXSRKISJUEL-UHFFFAOYSA-N 0.000 claims 1
- ZTKJIQTWYJVMLX-ACDBXBHQSA-N C(#N)C1=CC=C(OCCCN2CCC(CC2)C)C=C1.C(C)(=O)C1=CC=C(OC[C@@H](CN2CCCCC2)C)C=C1.C1(CC1)C(=O)C1=CC=C(OCCCN2CCCCC2)C=C1 Chemical compound C(#N)C1=CC=C(OCCCN2CCC(CC2)C)C=C1.C(C)(=O)C1=CC=C(OC[C@@H](CN2CCCCC2)C)C=C1.C1(CC1)C(=O)C1=CC=C(OCCCN2CCCCC2)C=C1 ZTKJIQTWYJVMLX-ACDBXBHQSA-N 0.000 claims 1
- AFSIBFQZBOJFHY-UHFFFAOYSA-N CC1(C(CCC1(C(=O)O)O)(C)C(=O)OC(=O)C2(CCC(C2(C)C)(C(=O)O)O)C)C Chemical group CC1(C(CCC1(C(=O)O)O)(C)C(=O)OC(=O)C2(CCC(C2(C)C)(C(=O)O)O)C)C AFSIBFQZBOJFHY-UHFFFAOYSA-N 0.000 claims 1
- NQWKTKOGTQLBSF-UHFFFAOYSA-N CCN(CC)CCCOC1=CC=C(C#N)C=C1.C1=CC(C(=O)CC)=CC=C1OCCCN1CCCCC1 Chemical compound CCN(CC)CCCOC1=CC=C(C#N)C=C1.C1=CC(C(=O)CC)=CC=C1OCCCN1CCCCC1 NQWKTKOGTQLBSF-UHFFFAOYSA-N 0.000 claims 1
- OUGKHGLPXPGXJM-UHFFFAOYSA-N ClC1=CC=C2C(=CC=NC2=C1)NCCCCCCCCCCCCN1CCCCC1.ClC1=CC=C2C(=CC=NC2=C1)NCCCCCCCCCCN1CCCCC1.ClC1=CC=C2C(=CC=NC2=C1)NCCCCCCCCN1CCCCC1.ClC1=CC=C2C(=CC=NC2=C1)NCCCCN1CCCCC1 Chemical compound ClC1=CC=C2C(=CC=NC2=C1)NCCCCCCCCCCCCN1CCCCC1.ClC1=CC=C2C(=CC=NC2=C1)NCCCCCCCCCCN1CCCCC1.ClC1=CC=C2C(=CC=NC2=C1)NCCCCCCCCN1CCCCC1.ClC1=CC=C2C(=CC=NC2=C1)NCCCCN1CCCCC1 OUGKHGLPXPGXJM-UHFFFAOYSA-N 0.000 claims 1
- MJNPESXRDDPLIM-UHFFFAOYSA-N ClC1=CC=C2C(=CC=NC2=C1)NCCCN1CCCCC1.CC1=NC2=CC=CC=C2C(=C1)NCCCCCCN1CCCCC1.CC1=NC2=CC=CC=C2C(=C1)NCCCN1CCCCC1.N1(CCCCC1)CCCCCCNC1=CC=NC2=CC=CC=C12 Chemical compound ClC1=CC=C2C(=CC=NC2=C1)NCCCN1CCCCC1.CC1=NC2=CC=CC=C2C(=C1)NCCCCCCN1CCCCC1.CC1=NC2=CC=CC=C2C(=C1)NCCCN1CCCCC1.N1(CCCCC1)CCCCCCNC1=CC=NC2=CC=CC=C12 MJNPESXRDDPLIM-UHFFFAOYSA-N 0.000 claims 1
- 125000006267 biphenyl group Chemical group 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- YAUKNAMQCYYNID-IYBDPMFKSA-N cyclopropyl-[4-[3-[(3s,5r)-3,5-dimethylpiperidin-1-yl]propoxy]phenyl]methanone Chemical compound C1[C@@H](C)C[C@@H](C)CN1CCCOC1=CC=C(C(=O)C2CC2)C=C1 YAUKNAMQCYYNID-IYBDPMFKSA-N 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- 238000013467 fragmentation Methods 0.000 claims 1
- 238000006062 fragmentation reaction Methods 0.000 claims 1
- CYYQXNIJWSBZLW-UHFFFAOYSA-N n-cyclohexyl-4-piperidin-1-ylpiperidine-1-carbothioamide Chemical compound C1CC(N2CCCCC2)CCN1C(=S)NC1CCCCC1 CYYQXNIJWSBZLW-UHFFFAOYSA-N 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical class [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 abstract description 14
- 238000000034 method Methods 0.000 abstract description 8
- 229960001340 histamine Drugs 0.000 abstract description 7
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 17
- 239000003395 histamine H3 receptor antagonist Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 125000000524 functional group Chemical group 0.000 description 7
- 150000001602 bicycloalkyls Chemical group 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 239000003453 histamine agonist Substances 0.000 description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- 206010062519 Poor quality sleep Diseases 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 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 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- 208000004547 Hallucinations Diseases 0.000 description 3
- 208000027089 Parkinsonian disease Diseases 0.000 description 3
- 206010034010 Parkinsonism Diseases 0.000 description 3
- 125000004414 alkyl thio group Chemical group 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 210000005064 dopaminergic neuron Anatomy 0.000 description 3
- 229910052740 iodine Chemical group 0.000 description 3
- 239000011630 iodine Chemical group 0.000 description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- MLWBBIHNWWLNFG-UHFFFAOYSA-N 1-[3-(4-bromophenoxy)propyl]piperidine Chemical compound C1=CC(Br)=CC=C1OCCCN1CCCCC1 MLWBBIHNWWLNFG-UHFFFAOYSA-N 0.000 description 2
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- ZJECUTJEYMYITR-FMOMHUKBSA-N C(#N)C1=CC=C(OCCCN2CC(CCC2)C)C=C1.C(#N)C1=CC=C(OCCCN2CCC(CC2)C)C=C1.C(C)(=O)C1=CC=C(OC[C@@H](CN2CCCCC2)C)C=C1 Chemical compound C(#N)C1=CC=C(OCCCN2CC(CCC2)C)C=C1.C(#N)C1=CC=C(OCCCN2CCC(CC2)C)C=C1.C(C)(=O)C1=CC=C(OC[C@@H](CN2CCCCC2)C)C=C1 ZJECUTJEYMYITR-FMOMHUKBSA-N 0.000 description 2
- YUXWTPRFKRWXRT-UHFFFAOYSA-N C1(CCCC1)C(=O)C1=CC=C(OCCCN2CCCCC2)C=C1.C1(CCC1)C(=O)C1=CC=C(OCCCN2CCCCC2)C=C1.C(CC)(=O)C1=CC=C(OCCCN2CC(CCC2)C)C=C1 Chemical compound C1(CCCC1)C(=O)C1=CC=C(OCCCN2CCCCC2)C=C1.C1(CCC1)C(=O)C1=CC=C(OCCCN2CCCCC2)C=C1.C(CC)(=O)C1=CC=C(OCCCN2CC(CCC2)C)C=C1 YUXWTPRFKRWXRT-UHFFFAOYSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 229940115480 Histamine H3 receptor antagonist Drugs 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 108090000189 Neuropeptides Proteins 0.000 description 2
- 101710138657 Neurotoxin Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 2
- 208000010340 Sleep Deprivation Diseases 0.000 description 2
- 206010040981 Sleep attacks Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 125000002877 alkyl aryl group Chemical group 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 208000008784 apnea Diseases 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
- 229960004170 clozapine Drugs 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 229960003530 donepezil Drugs 0.000 description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229960003980 galantamine Drugs 0.000 description 2
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000003382 histamine H3 receptor agonist Substances 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 231100000863 loss of memory Toxicity 0.000 description 2
- 231100000897 loss of orientation Toxicity 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 239000002581 neurotoxin Substances 0.000 description 2
- 231100000618 neurotoxin Toxicity 0.000 description 2
- 125000000962 organic group Chemical group 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 2
- 229950010883 phencyclidine Drugs 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 125000005592 polycycloalkyl group Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229960004136 rivastigmine Drugs 0.000 description 2
- 201000002859 sleep apnea Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
- ZTYVJNYCCVFJGR-UHFFFAOYSA-N 1-[3-(3,3-dimethylbutoxy)propyl]piperidine Chemical compound CC(C)(C)CCOCCCN1CCCCC1 ZTYVJNYCCVFJGR-UHFFFAOYSA-N 0.000 description 1
- TXASRZUEBKMBEF-UHFFFAOYSA-N 1-[3-(3-piperidin-1-ylpropoxy)propyl]piperidine Chemical compound C1CCCCN1CCCOCCCN1CCCCC1 TXASRZUEBKMBEF-UHFFFAOYSA-N 0.000 description 1
- NARGXXYOOWIJLL-UHFFFAOYSA-N 1-[3-(4-ethylphenoxy)propyl]piperidine Chemical compound C1=CC(CC)=CC=C1OCCCN1CCCCC1 NARGXXYOOWIJLL-UHFFFAOYSA-N 0.000 description 1
- LTAJHAFDPKOAJV-UHFFFAOYSA-N 1-[4-(3-piperidin-1-ylpropoxy)phenyl]propan-1-one Chemical compound C1=CC(C(=O)CC)=CC=C1OCCCN1CCCCC1 LTAJHAFDPKOAJV-UHFFFAOYSA-N 0.000 description 1
- PORNTIHIVVJHQE-UHFFFAOYSA-N 1-[4-[3-(diethylamino)propoxy]phenyl]ethanone Chemical compound CCN(CC)CCCOC1=CC=C(C(C)=O)C=C1 PORNTIHIVVJHQE-UHFFFAOYSA-N 0.000 description 1
- ORPONTZKLQPKSS-UHFFFAOYSA-N 1-[5-(4-methoxyphenoxy)pentyl]pyrrolidine;1-[5-(4-methylphenoxy)pentyl]pyrrolidine Chemical compound C1=CC(C)=CC=C1OCCCCCN1CCCC1.C1=CC(OC)=CC=C1OCCCCCN1CCCC1 ORPONTZKLQPKSS-UHFFFAOYSA-N 0.000 description 1
- ARXUNWQEEIWRFV-UHFFFAOYSA-N 1-[6-phenyl-1-(6-phenyl-3-piperidin-1-ylhexoxy)hexan-3-yl]piperidine Chemical compound C=1C=CC=CC=1CCCC(N1CCCCC1)CCOCCC(N1CCCCC1)CCCC1=CC=CC=C1 ARXUNWQEEIWRFV-UHFFFAOYSA-N 0.000 description 1
- WFJFGMLKAISFOZ-UHFFFAOYSA-N 1-amino-3-iminourea Chemical compound NN=C(O)N=N WFJFGMLKAISFOZ-UHFFFAOYSA-N 0.000 description 1
- 125000006021 1-methyl-2-propenyl group Chemical group 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- VZGBGKHEMQIUPH-UHFFFAOYSA-N 2-(3-piperidin-1-ylpropoxy)-1,3-benzothiazole Chemical compound N=1C2=CC=CC=C2SC=1OCCCN1CCCCC1 VZGBGKHEMQIUPH-UHFFFAOYSA-N 0.000 description 1
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- PSLFPYLRAFNSFK-UHFFFAOYSA-N 2-fluoro-4-(3-piperidin-1-ylpropoxy)benzonitrile;3-methyl-1-[3-(4-nitrophenoxy)propyl]piperidine Chemical compound C1=C(C#N)C(F)=CC(OCCCN2CCCCC2)=C1.C1C(C)CCCN1CCCOC1=CC=C([N+]([O-])=O)C=C1 PSLFPYLRAFNSFK-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- OIBSLXVQMNELOL-UHFFFAOYSA-N 3-cyclopentyl-n-(3-pyrrolidin-1-ylpropyl)propanamide Chemical compound C1CCCN1CCCNC(=O)CCC1CCCC1 OIBSLXVQMNELOL-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- PFHGPNGSWIHVIR-XAEMHTEYSA-N 4-[3-[(3r,5s)-3,5-dimethylpiperidin-1-yl]propoxy]benzonitrile;1-[4-[3-(2-methylpiperidin-1-yl)propoxy]phenyl]propan-1-one;1-[4-[3-(4-methylpiperidin-1-yl)propoxy]phenyl]propan-1-one Chemical compound C1[C@@H](C)C[C@@H](C)CN1CCCOC1=CC=C(C#N)C=C1.C1=CC(C(=O)CC)=CC=C1OCCCN1CCC(C)CC1.C1=CC(C(=O)CC)=CC=C1OCCCN1C(C)CCCC1 PFHGPNGSWIHVIR-XAEMHTEYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- HCBKPHUOZCGJGQ-UHFFFAOYSA-N 7-chloro-n-[2-[4-(3-piperidin-1-ylpropoxy)phenyl]ethyl]quinolin-4-amine;7-chloro-n-[4-(3-piperidin-1-ylpropoxy)phenyl]quinolin-4-amine Chemical compound C=1C=NC2=CC(Cl)=CC=C2C=1NC(C=C1)=CC=C1OCCCN1CCCCC1.C=1C=NC2=CC(Cl)=CC=C2C=1NCCC(C=C1)=CC=C1OCCCN1CCCCC1 HCBKPHUOZCGJGQ-UHFFFAOYSA-N 0.000 description 1
- IRBAWVGZNJIROV-SFHVURJKSA-N 9-(2-cyclopropylethynyl)-2-[[(2s)-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=C2C3=CC=C(C#CC4CC4)C=C3CCN2C(=O)N=C1OC[C@@H]1COCCO1 IRBAWVGZNJIROV-SFHVURJKSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010001541 Akinesia Diseases 0.000 description 1
- 206010006100 Bradykinesia Diseases 0.000 description 1
- NRJOKFCURCCBCM-DFJBSKDZSA-N C(CC)(=O)C1=CC=C(OCCCN2CCC(CC2)C)C=C1.C(#N)C1=CC=C(OCCCN2C[C@H](C[C@H](C2)C)C)C=C1.C(#N)C1=CC=C(OCCCN2[C@H](CC[C@@H](C2)CC)C)C=C1 Chemical compound C(CC)(=O)C1=CC=C(OCCCN2CCC(CC2)C)C=C1.C(#N)C1=CC=C(OCCCN2C[C@H](C[C@H](C2)C)C)C=C1.C(#N)C1=CC=C(OCCCN2[C@H](CC[C@@H](C2)CC)C)C=C1 NRJOKFCURCCBCM-DFJBSKDZSA-N 0.000 description 1
- MOCMPZUFRHYVNI-UHFFFAOYSA-N C(CC)(=O)C1=CC=C(OCCCN2CCC(CC2)C)C=C1.C(CC)(=O)C1=CC=C(OCCCN2C(CCCC2)C)C=C1.OC(CC)C1=CC=C(OCCCN2CCC(CC2)C)C=C1 Chemical compound C(CC)(=O)C1=CC=C(OCCCN2CCC(CC2)C)C=C1.C(CC)(=O)C1=CC=C(OCCCN2C(CCCC2)C)C=C1.OC(CC)C1=CC=C(OCCCN2CCC(CC2)C)C=C1 MOCMPZUFRHYVNI-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 241001573498 Compacta Species 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- BJPGUIJCGUNGDJ-UHFFFAOYSA-N FC1=CC=C(OCCCCCN2CCCC2)C=C1.[N+](=O)([O-])C=1C=C(OCCCCCN2CCCC2)C=CC1 Chemical compound FC1=CC=C(OCCCCCN2CCCC2)C=C1.[N+](=O)([O-])C=1C=C(OCCCCCN2CCCC2)C=CC1 BJPGUIJCGUNGDJ-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 206010021079 Hypopnoea Diseases 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 description 1
- QKDDJDBFONZGBW-UHFFFAOYSA-N N-Cyclohexy-4-(imidazol-4-yl)-1-piperidinecarbothioamide Chemical compound C1CC(C=2NC=NC=2)CCN1C(=S)NC1CCCCC1 QKDDJDBFONZGBW-UHFFFAOYSA-N 0.000 description 1
- 206010061137 Ocular toxicity Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- 241001061127 Thione Species 0.000 description 1
- 206010044245 Toxic optic neuropathy Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000004018 acid anhydride group Chemical group 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000005024 alkenyl aryl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 150000007854 aminals Chemical class 0.000 description 1
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003502 anti-nociceptive effect Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 230000001262 anti-secretory effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical group C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- UUQMNUMQCIQDMZ-UHFFFAOYSA-N betahistine Chemical compound CNCCC1=CC=CC=N1 UUQMNUMQCIQDMZ-UHFFFAOYSA-N 0.000 description 1
- 229960004536 betahistine Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- ZSCYJHGJGRSPAB-UHFFFAOYSA-N carbamic acid Chemical compound NC(O)=O.NC(O)=O ZSCYJHGJGRSPAB-UHFFFAOYSA-N 0.000 description 1
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 231100000876 cognitive deterioration Toxicity 0.000 description 1
- 125000004367 cycloalkylaryl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- OLHQOJYVQUNWPL-UHFFFAOYSA-N dimaprit Chemical compound CN(C)CCCSC(N)=N OLHQOJYVQUNWPL-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 229940005501 dopaminergic agent Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000004341 endo-2-norbornyl group Chemical group [H]C1([H])C([H])([H])[C@@]2([H])C([H])([H])[C@]1([H])C([H])([H])[C@@]2([H])* 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 125000004340 exo-2-norbornyl group Chemical group [H]C1([H])C([H])([H])[C@@]2([H])C([H])([H])[C@]1([H])C([H])([H])[C@]2([H])* 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 229940124806 histamine H3 agonist Drugs 0.000 description 1
- 230000000742 histaminergic effect Effects 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000001690 micro-dialysis Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229960001165 modafinil Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- YNTOKMNHRPSGFU-UHFFFAOYSA-N n-Propyl carbamate Chemical compound CCCOC(N)=O YNTOKMNHRPSGFU-UHFFFAOYSA-N 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000003557 neuropsychological effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 231100000327 ocular toxicity Toxicity 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002385 psychotomimetic effect Effects 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
- 229960001879 ropinirole Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 150000007659 semicarbazones Chemical group 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229930004725 sesquiterpene Natural products 0.000 description 1
- 150000004354 sesquiterpene derivatives Chemical class 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000028838 turning behavior Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000012043 vestibular reflex Effects 0.000 description 1
- 230000021542 voluntary musculoskeletal movement Effects 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000002256 xylenyl group Chemical group C1(C(C=CC=C1)C)(C)* 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Anesthesiology (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05290727A EP1707203A1 (en) | 2005-04-01 | 2005-04-01 | Treatment of parkinson's disease obstructive sleep apnea, dementia with lewy bodies, vascular dementia with non-imidazole alkylamines histamine H3- receptor ligands |
| US66861805P | 2005-04-06 | 2005-04-06 | |
| PCT/IB2006/000739 WO2006103546A2 (en) | 2005-04-01 | 2006-03-30 | Treatment of parkinson's disease, obstructive sleep apnea, dementia with lewy bodies, vascular dementia with non-imidazole alkylamines histamine h3-receptor ligands |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2007012162A true MX2007012162A (es) | 2007-11-22 |
Family
ID=35169680
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2007012162A MX2007012162A (es) | 2005-04-01 | 2006-03-30 | Tratamiento de la enfermedad de de parkinson, la apnea obstructiva del sueno, la demencia con cuerpos de lewy, la demencia vascular con ligandos de receptor de h3 de histamina de alquilaminas que no contienen imidazol. |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US8486947B2 (enExample) |
| EP (2) | EP1707203A1 (enExample) |
| JP (3) | JP5546761B2 (enExample) |
| KR (1) | KR101308527B1 (enExample) |
| CN (1) | CN101171009B (enExample) |
| AU (1) | AU2006228413C1 (enExample) |
| BR (1) | BRPI0612216B1 (enExample) |
| CA (1) | CA2603656C (enExample) |
| CY (1) | CY1114636T1 (enExample) |
| DK (1) | DK1863487T4 (enExample) |
| EA (1) | EA016007B1 (enExample) |
| ES (1) | ES2426008T5 (enExample) |
| HR (1) | HRP20130748T4 (enExample) |
| MA (1) | MA29353B1 (enExample) |
| ME (1) | ME01713B (enExample) |
| MX (1) | MX2007012162A (enExample) |
| NO (1) | NO343603B1 (enExample) |
| NZ (1) | NZ561940A (enExample) |
| PL (1) | PL1863487T5 (enExample) |
| PT (1) | PT1863487E (enExample) |
| RS (1) | RS52911B2 (enExample) |
| SG (1) | SG147415A1 (enExample) |
| SI (1) | SI1863487T2 (enExample) |
| TN (1) | TNSN07365A1 (enExample) |
| UA (1) | UA94902C2 (enExample) |
| WO (1) | WO2006103546A2 (enExample) |
| ZA (1) | ZA200708086B (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9108948B2 (en) | 2006-06-23 | 2015-08-18 | Abbvie Inc. | Cyclopropyl amine derivatives |
| CN101472887A (zh) | 2006-06-23 | 2009-07-01 | 艾博特公司 | 作为组胺h3受体调节物的环丙胺衍生物 |
| FR2903904A1 (fr) * | 2006-07-21 | 2008-01-25 | Bioprojet Soc Civ Ile | Association de modafinil et d'un antagoniste ou agoniste inverse du recepteur h3 |
| NZ574873A (en) | 2006-07-25 | 2012-03-30 | Cephalon Inc | Pyridazinone derivatives as h3 inhibitors |
| US8153813B2 (en) | 2007-12-20 | 2012-04-10 | Abbott Laboratories | Benzothiazole and benzooxazole derivatives and methods of use |
| CA2712897A1 (en) | 2008-01-30 | 2009-08-06 | Pharmacopeia, Inc. | Substituted spirocyclic piperidine derivatives as histamine-3 (h3) receptor ligands |
| FR2932479A1 (fr) | 2008-06-13 | 2009-12-18 | Servier Lab | Nouveaux derives azabicycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| US9186353B2 (en) | 2009-04-27 | 2015-11-17 | Abbvie Inc. | Treatment of osteoarthritis pain |
| WO2012037258A1 (en) | 2010-09-16 | 2012-03-22 | Abbott Laboratories | Processes for preparing 1,2-substituted cyclopropyl derivatives |
| US9181275B2 (en) | 2011-08-11 | 2015-11-10 | Abbvie Inc. | Mercaptoamidine derivatives and methods of use |
| WO2013151982A1 (en) | 2012-04-03 | 2013-10-10 | Arena Pharmaceuticals, Inc. | Methods and compounds useful in treating pruritus, and methods for identifying such compounds |
| SG11201502210VA (en) * | 2012-10-05 | 2015-04-29 | Vtvx Holdings I Llc | Treatment of mild and moderate alzheimer's disease |
| EP3391886A1 (en) | 2017-04-19 | 2018-10-24 | Novartis AG | The use of a h3r inverse agonist for the treatment of shift work disorder |
| US20200281522A1 (en) | 2019-03-06 | 2020-09-10 | Medtronic Xomed, LLC | System and method for improved obstructive sleep apnea diagnostic for implantable devices |
| EP4248969A1 (en) | 2022-03-23 | 2023-09-27 | Bioprojet | Use of pitolisant for treating severe fatigue |
| WO2024201139A1 (en) | 2023-03-31 | 2024-10-03 | Bioprojet Pharma | Polymorph form of pitolisant hydrochloride |
| TW202535385A (zh) | 2023-10-16 | 2025-09-16 | 法商拜爾普羅傑特醫藥有限公司 | 必托里賽（ｐｉｔｏｌｉｓａｎｔ）之新穎調配物及使用方法 |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5815945A (ja) * | 1981-07-21 | 1983-01-29 | Teikoku Hormone Mfg Co Ltd | 新規なフエノキシアルキルアミン誘導体 |
| FR2579596B1 (fr) | 1985-03-26 | 1987-11-20 | Inst Nat Sante Rech Med | (imidazolyl-4) piperidines, leur preparation et leur application en therapeutique |
| FR2671083B1 (fr) | 1990-12-31 | 1994-12-23 | Inst Nat Sante Rech Med | Nouvelles 4-(4-imidazolyl) piperidines substituees en 1, leur preparation ainsi que leurs applications therapeutiques. |
| ES2108107T3 (es) | 1991-02-27 | 1997-12-16 | Seed Capital Investments | Derivados de imidazol que tienen actividad antagonista en el receptor h3 de histamina. |
| AU671092B2 (en) | 1991-12-18 | 1996-08-15 | Schering Corporation | Imidazolyl or imidazoylalkyl substituted with a four or five membered nitrogen containing heterocyclic ring |
| EP0619818B1 (en) | 1991-12-18 | 1996-07-10 | Schering Corporation | Imidazoylalkyl substituted with a six membered nitrogen containing heterocyclic ring |
| FR2686084B1 (fr) | 1992-01-10 | 1995-12-22 | Bioprojet Soc Civ | Nouveaux derives de l'imidazole, leur preparation et leurs applications therapeutiques. |
| US5486526A (en) * | 1992-04-01 | 1996-01-23 | The University Of Toledo | Histamine H3 -receptor antagonists and therapeutic uses thereof |
| US5380858A (en) | 1992-04-01 | 1995-01-10 | The University Of Toledo | Process for the preparation of intermediates useful for the synthesis of histamine receptor antagonists |
| US5639775A (en) | 1992-04-01 | 1997-06-17 | The University Of Toledo | 4-[4'-piperodinyl or 3'-pirrolidinyl] substituted imidazoles as H3 -receptor antagonists and therapeutic uses thereof |
| WO1994017058A1 (fr) | 1993-01-25 | 1994-08-04 | The Green Cross Corporation | Compose d'imidazole |
| JP3522790B2 (ja) | 1993-06-08 | 2004-04-26 | 花王株式会社 | Ｈ３−レセプター刺激薬 |
| WO1995006037A1 (en) | 1993-08-27 | 1995-03-02 | Vrije Universiteit | New imidazole derivatives having agonistic or antagonistic activity on the histamine h3 receptor |
| GB9319534D0 (en) * | 1993-09-22 | 1993-11-10 | Boots Co Plc | Therapeutic agents |
| AU693142B2 (en) | 1993-11-15 | 1998-06-25 | Schering Corporation | Phenyl-alkyl imidazoles as H3-receptor antagonists |
| GB9411045D0 (en) * | 1994-06-02 | 1994-07-20 | Smithkline Beecham Plc | Compounds and use |
| FR2732017B1 (fr) | 1995-03-21 | 2000-09-22 | Inst Nat Sante Rech Med | Nouveaux derives de l'imidazole antagonistes et/ou agonistes du recepteur h3 de l'histamine, leur preparation et leurs applications therapeutiques |
| CA2222099A1 (en) | 1995-05-30 | 1996-12-05 | Gliatech, Inc. | 1h-4(5)-substituted imidazole derivatives |
| US5652258A (en) | 1995-05-30 | 1997-07-29 | Gliatech, Inc. | 2-(4-imidazoyl) cyclopropyl derivatives |
| WO1996040126A1 (en) | 1995-06-07 | 1996-12-19 | Gliatech, Inc. | 1h-4(5)-substituted imidazole derivatives |
| PL328369A1 (en) | 1996-02-09 | 1999-01-18 | Black James Foundation | Ligands of histamin h receptor |
| JP3925579B2 (ja) | 1998-02-03 | 2007-06-06 | 日本精工株式会社 | 潤滑剤供給体、並びに前記潤滑剤供給体を備える転がり軸受、リニアガイド装置及びボールねじ装置 |
| EP0982300A3 (en) * | 1998-07-29 | 2000-03-08 | Societe Civile Bioprojet | Non-imidazole alkylamines as histamine H3 - receptor ligands and their therapeutic applications |
| US6136559A (en) * | 1998-10-07 | 2000-10-24 | Ortho Pharmaceutical Corporation | DNA encoding as human histamine receptor of the H3 subtype |
| EP1186594B1 (en) * | 1999-06-11 | 2009-08-05 | Toyama Chemical Co., Ltd. | N-alkoxyalkyl-n,n-dialkylamine derivatives or salts thereof, and remedies for nerve degeneration diseases containing the same |
| GB9924941D0 (en) * | 1999-10-22 | 1999-12-22 | Univ Manchester | Treatment of dyskinesia |
| US6620839B2 (en) * | 2000-07-13 | 2003-09-16 | Abbott Laboratories | 1,3-disubstituted and 1,3,3-trisubstituted pyrrolidines as histamine-3 receptor ligands and their therapeutic applications |
| HK1053110A1 (zh) | 2000-08-08 | 2003-10-10 | Ortho-Mcneil Pharmaceutical, Inc. | 作為h3受體配體的非咪唑芳氧基烷基胺 |
| WO2002013821A1 (en) | 2000-08-17 | 2002-02-21 | Gliatech, Inc. | Novel alicyclic imidazoles as h3 agents |
| JP2004506685A (ja) * | 2000-08-21 | 2004-03-04 | グリアテツク・インコーポレイテツド | 食欲の制御と肥満の治療のためのヒスタミンｈ３受容体逆アゴニストの使用 |
| EP1373218B9 (en) * | 2001-03-29 | 2008-12-03 | Ortho-McNeil-Janssen Pharmaceuticals, Inc. | Imidazolyl derivatives useful as histamine h3 receptor ligands |
| EP1451225A1 (en) * | 2001-11-15 | 2004-09-01 | Ortho-McNeil Pharmaceutical, Inc. | Agonists of recombinant human histamine h3 receptor |
| WO2003050099A1 (en) * | 2001-12-10 | 2003-06-19 | Ortho-Mcneil Pharmaceutical, Inc. | Phenylalkynes |
| JP2006505590A (ja) | 2002-10-23 | 2006-02-16 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ヒスタミンｈ３受容体調節物質としてのフェニルピペリジンおよびフェニルピロリジン |
| FR2856596B1 (fr) * | 2003-06-27 | 2007-04-27 | Bioprojet Soc Civ | Nouvelle association medicamenteuse psychiatrique et utilisation d'une antagoniste ou agoniste inverse du recepteur h3 de l'histamine pour preparer un medicament prevenant des effets indesirables de psychotropes. |
| WO2005007644A1 (ja) * | 2003-06-27 | 2005-01-27 | Banyu Pharmaceutical Co., Ltd | ヘテロアリールオキシ含窒素飽和へテロ環誘導体 |
| SE0302116D0 (sv) * | 2003-07-21 | 2003-07-21 | Astrazeneca Ab | Novel compounds |
| CA2551037A1 (en) | 2003-09-22 | 2005-03-31 | Banyu Pharmaceutical Co., Ltd. | Novel piperidine derivative |
-
2005
- 2005-04-01 EP EP05290727A patent/EP1707203A1/en not_active Withdrawn
-
2006
- 2006-03-29 AU AU2006228413A patent/AU2006228413C1/en active Active
- 2006-03-30 MX MX2007012162A patent/MX2007012162A/es active IP Right Grant
- 2006-03-30 JP JP2008503613A patent/JP5546761B2/ja active Active
- 2006-03-30 CN CN2006800157656A patent/CN101171009B/zh active Active
- 2006-03-30 SI SI200631636T patent/SI1863487T2/sl unknown
- 2006-03-30 SG SG200807447-8A patent/SG147415A1/en unknown
- 2006-03-30 EA EA200702135A patent/EA016007B1/ru not_active IP Right Cessation
- 2006-03-30 PT PT67444661T patent/PT1863487E/pt unknown
- 2006-03-30 BR BRPI0612216-7A patent/BRPI0612216B1/pt active IP Right Grant
- 2006-03-30 RS RS20130359 patent/RS52911B2/sr unknown
- 2006-03-30 ES ES06744466T patent/ES2426008T5/es active Active
- 2006-03-30 PL PL06744466T patent/PL1863487T5/pl unknown
- 2006-03-30 EP EP06744466.1A patent/EP1863487B2/en active Active
- 2006-03-30 WO PCT/IB2006/000739 patent/WO2006103546A2/en not_active Ceased
- 2006-03-30 NZ NZ561940A patent/NZ561940A/en unknown
- 2006-03-30 ME MEP-2013-98A patent/ME01713B/me unknown
- 2006-03-30 HR HRP20130748T patent/HRP20130748T4/hr unknown
- 2006-03-30 KR KR1020077025126A patent/KR101308527B1/ko active Active
- 2006-03-30 UA UAA200710712A patent/UA94902C2/ru unknown
- 2006-03-30 DK DK06744466.1T patent/DK1863487T4/da active
- 2006-03-30 CA CA2603656A patent/CA2603656C/en active Active
- 2006-03-30 US US11/909,778 patent/US8486947B2/en active Active
-
2007
- 2007-09-20 ZA ZA200708086A patent/ZA200708086B/xx unknown
- 2007-09-26 TN TNP2007000365A patent/TNSN07365A1/fr unknown
- 2007-09-27 MA MA30254A patent/MA29353B1/fr unknown
- 2007-10-09 NO NO20075086A patent/NO343603B1/no unknown
-
2013
- 2013-08-14 CY CY20131100705T patent/CY1114636T1/el unknown
-
2014
- 2014-01-06 JP JP2014000383A patent/JP5955872B2/ja active Active
-
2016
- 2016-03-09 JP JP2016045424A patent/JP2016106142A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5955872B2 (ja) | 非イミダゾールアルキルアミンヒスタミンｈ３−受容体リガンドによるパーキンソン病、閉塞性睡眠時無呼吸、レビー小体型認知症、血管性認知症の治療 | |
| US7169928B2 (en) | Non-imidazole alkylamines as histamine H3-receptor ligands and their therapeutic applications | |
| KR100797603B1 (ko) | 섬유근육통을 치료하기 위한 도파민 ｄ2/ｄ3 수용체작용제의 사용 | |
| US8106041B2 (en) | Combination product comprising an antagonist or inverse agonist of histamine receptor H3 and an antipsychotic and antidepressant agent, and use thereof for the preparation of a medicament that prevents the adverse effects of psychotropic drugs | |
| TWI453013B (zh) | N-(2,4-二甲基-6-嗎啉-4-基-吡啶-3-基〉3,3-二甲基-丁醯胺之用途以及包含該化合物之醫藥品 | |
| US20090082353A1 (en) | Treatment of epilepsy with non-imidazole alkylamines histamine h3-receptor ligands |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Grant or registration |