JPH08504792A - カルシウムチャンネルアンタゴニストとしてのピペリジン誘導体 - Google Patents

カルシウムチャンネルアンタゴニストとしてのピペリジン誘導体

Info

Publication number: JPH08504792A
Authority: JP; Japan
Prior art keywords: formula; compound; tert; hydroxy; piperidine
Prior art date: 1992-12-22
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Pending

Application number

JP6514808A

Other languages

English (en)

Japanese (ja)

Inventor

キング，ロナルド・ジョーゼフ

ブラウン，トマス・ヘンリー

クーパー，デイビッド・グウィン

Original Assignee

スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-12-22

Filing date

1993-12-16

Publication date

1996-05-21

1992-12-22 Priority claimed from GB929226718A external-priority patent/GB9226718D0/en

1993-10-22 Priority claimed from GB939321808A external-priority patent/GB9321808D0/en

1993-12-16 Application filed by スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー filed Critical スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー

1996-05-21 Publication of JPH08504792A publication Critical patent/JPH08504792A/ja

Status Pending legal-status Critical Current

Links

229940127291 Calcium channel antagonist Drugs 0.000 title abstract description 3
150000003053 piperidines Chemical class 0.000 title description 2
150000003839 salts Chemical class 0.000 claims abstract description 26
229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
125000000217 alkyl group Chemical group 0.000 claims abstract description 11
150000002367 halogens Chemical class 0.000 claims abstract description 11
229910052736 halogen Inorganic materials 0.000 claims abstract description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
229910052717 sulfur Inorganic materials 0.000 claims abstract description 10
239000001257 hydrogen Substances 0.000 claims abstract description 9
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
150000002431 hydrogen Chemical class 0.000 claims abstract description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
238000001727 in vivo Methods 0.000 claims abstract description 4
210000004958 brain cell Anatomy 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 103
238000000034 method Methods 0.000 claims description 25
238000006243 chemical reaction Methods 0.000 claims description 24
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 18
239000003814 drug Substances 0.000 claims description 10
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
239000011575 calcium Substances 0.000 claims description 8
210000004027 cell Anatomy 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 7
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 6
229910052791 calcium Inorganic materials 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 5
150000003254 radicals Chemical class 0.000 claims description 5
238000009825 accumulation Methods 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
210000005171 mammalian brain Anatomy 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
SYOXRZPZAYPIKC-UHFFFAOYSA-N 1-(3,5-ditert-butyl-4-hydroxyphenyl)-7-piperidin-1-ylheptan-1-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)CCCCCCN2CCCCC2)=C1 SYOXRZPZAYPIKC-UHFFFAOYSA-N 0.000 claims description 2
ZQZLRJHVVSSOII-UHFFFAOYSA-N 1-(3,5-ditert-butyl-4-hydroxyphenyl)-8-piperidin-1-yloctan-1-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)CCCCCCCN2CCCCC2)=C1 ZQZLRJHVVSSOII-UHFFFAOYSA-N 0.000 claims description 2
KJGHWPZKEFMLEC-UHFFFAOYSA-N 2,6-ditert-butyl-4-(6-piperidin-1-ylhexyl)phenol Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CCCCCCN2CCCCC2)=C1 KJGHWPZKEFMLEC-UHFFFAOYSA-N 0.000 claims description 2
CZHSMAPQYSWIRY-UHFFFAOYSA-N 2,6-ditert-butyl-4-(8-piperidin-1-yloctyl)phenol Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CCCCCCCCN2CCCCC2)=C1 CZHSMAPQYSWIRY-UHFFFAOYSA-N 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
241000124008 Mammalia Species 0.000 claims 1
230000000269 nucleophilic effect Effects 0.000 claims 1
230000001201 calcium accumulation Effects 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
239000000203 mixture Substances 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
-1 Heterocyclic amides Chemical class 0.000 description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 16
239000002904 solvent Substances 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
239000000460 chlorine Substances 0.000 description 14
238000002360 preparation method Methods 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
230000008569 process Effects 0.000 description 9
239000000047 product Substances 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 6
239000012267 brine Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
239000007787 solid Substances 0.000 description 6
229940079593 drug Drugs 0.000 description 5
239000003480 eluent Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
239000000126 substance Substances 0.000 description 5
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 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000012300 argon atmosphere Substances 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
239000002585 base Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000000725 suspension Substances 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
108091006146 Channels Proteins 0.000 description 3
206010012335 Dependence Diseases 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
208000028867 ischemia Diseases 0.000 description 3
239000007788 liquid Substances 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
RDQSIADLBQFVMY-UHFFFAOYSA-N 2,6-Di-tert-butylbenzoquinone Chemical compound CC(C)(C)C1=CC(=O)C=C(C(C)(C)C)C1=O RDQSIADLBQFVMY-UHFFFAOYSA-N 0.000 description 2
TZFKFDQPHRPMKH-UHFFFAOYSA-N 4,4-dibromoheptane Chemical compound CCCC(Br)(Br)CCC TZFKFDQPHRPMKH-UHFFFAOYSA-N 0.000 description 2
ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 2
ITVRBQPTSLQOKK-UHFFFAOYSA-N 7-bromoheptanoyl chloride Chemical compound ClC(=O)CCCCCCBr ITVRBQPTSLQOKK-UHFFFAOYSA-N 0.000 description 2
206010065040 AIDS dementia complex Diseases 0.000 description 2
208000024827 Alzheimer disease Diseases 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
238000005727 Friedel-Crafts reaction Methods 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
206010019196 Head injury Diseases 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
206010021143 Hypoxia Diseases 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
208000019695 Migraine disease Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Chemical compound [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
230000005779 cell damage Effects 0.000 description 2
208000037887 cell injury Diseases 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
239000003086 colorant Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
201000010099 disease Diseases 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
206010015037 epilepsy Diseases 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000003925 fat Substances 0.000 description 2
239000012458 free base Substances 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
230000008570 general process Effects 0.000 description 2
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 description 2
230000007954 hypoxia Effects 0.000 description 2
238000001802 infusion Methods 0.000 description 2
238000002955 isolation Methods 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
206010027599 migraine Diseases 0.000 description 2
230000004770 neurodegeneration Effects 0.000 description 2
208000015122 neurodegenerative disease Diseases 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000012071 phase Substances 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
238000011160 research Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
239000003826 tablet Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
230000000472 traumatic effect Effects 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
ZJKSMQZOMSSYDV-UHFFFAOYSA-N 1-(3,5-ditert-butyl-4-hydroxyphenyl)-6-piperidin-1-ylhexan-1-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)CCCCCN2CCCCC2)=C1 ZJKSMQZOMSSYDV-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
CVVGYBYFWPGOJP-UHFFFAOYSA-N 2,6-ditert-butylbenzene-1,4-dithiol Chemical compound CC(C)(C)C1=CC(S)=CC(C(C)(C)C)=C1S CVVGYBYFWPGOJP-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 1
HBPVGJGBRWIVSX-UHFFFAOYSA-N 6-bromohexanoyl chloride Chemical compound ClC(=O)CCCCCBr HBPVGJGBRWIVSX-UHFFFAOYSA-N 0.000 description 1
JHGJURXAOMDIBR-UHFFFAOYSA-N 8-bromooctanoyl chloride Chemical compound ClC(=O)CCCCCCCBr JHGJURXAOMDIBR-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
ODNGCJLOVMIAEH-UHFFFAOYSA-N Cl.CC(C)(C)c1cc(cc(c1O)C(C)(C)C)C(=O)CCCCCCN1CCCCC1 Chemical compound Cl.CC(C)(C)c1cc(cc(c1O)C(C)(C)C)C(=O)CCCCCCN1CCCCC1 ODNGCJLOVMIAEH-UHFFFAOYSA-N 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
208000006558 Dental Calculus Diseases 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
208000026139 Memory disease Diseases 0.000 description 1
238000006751 Mitsunobu reaction Methods 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
241000212342 Sium Species 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229910052776 Thorium Inorganic materials 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
239000003708 ampul Substances 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
239000000043 antiallergic agent Substances 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
XDFCIPNJCBUZJN-UHFFFAOYSA-N barium(2+) Chemical compound [Ba+2] XDFCIPNJCBUZJN-UHFFFAOYSA-N 0.000 description 1
229940054066 benzamide antipsychotics Drugs 0.000 description 1
150000003936 benzamides Chemical class 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
230000009460 calcium influx Effects 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000002800 charge carrier Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
238000004296 chiral HPLC Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
229940097362 cyclodextrins Drugs 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
206010013663 drug dependence Diseases 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000009472 formulation Methods 0.000 description 1
239000003205 fragrance Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
239000002035 hexane extract Substances 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
229940011051 isopropyl acetate Drugs 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
239000000395 magnesium oxide Substances 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
206010027175 memory impairment Diseases 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
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 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 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
235000014593 oils and fats Nutrition 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
150000003891 oxalate salts Chemical class 0.000 description 1
239000008188 pellet Substances 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
210000003594 spinal ganglia Anatomy 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
208000011117 substance-related disease Diseases 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229910052714 tellurium Inorganic materials 0.000 description 1
PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 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
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
238000012546 transfer Methods 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- 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
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/104—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/108—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Diabetes (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Obesity (AREA)
Biomedical Technology (AREA)
Hematology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Vascular Medicine (AREA)
Endocrinology (AREA)
Rheumatology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Urology & Nephrology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)

JP6514808A 1992-12-22 1993-12-16 カルシウムチャンネルアンタゴニストとしてのピペリジン誘導体 Pending JPH08504792A (ja)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
GB929226718A GB9226718D0 (en)	1992-12-22	1992-12-22	Compounds
GB9226718.6		1992-12-22
GB9321808.9		1993-10-22
GB939321808A GB9321808D0 (en)	1993-10-22	1993-10-22	Compounds
PCT/EP1993/003629 WO1994014786A1 (en)	1992-12-22	1993-12-16	Piperidine derivatives as calcium channel antagonists

Publications (1)

Publication Number	Publication Date
JPH08504792A true JPH08504792A (ja)	1996-05-21

Family

ID=26302202

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP6514808A Pending JPH08504792A (ja)	1992-12-22	1993-12-16	カルシウムチャンネルアンタゴニストとしてのピペリジン誘導体

Country Status (8)

Country	Link
EP (1)	EP0675883A1 (de)
JP (1)	JPH08504792A (de)
KR (1)	KR950704284A (de)
CN (1)	CN1092415A (de)
AU (1)	AU5833494A (de)
CA (1)	CA2152394A1 (de)
MX (1)	MX9400070A (de)
WO (1)	WO1994014786A1 (de)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH1039525A (ja) *	1996-07-26	1998-02-13	Konica Corp	電子写真感光体

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5677291A (en) *	1993-12-10	1997-10-14	Hoechst Marion Roussel, Inc.	Method of lowering serum cholesterol levels with 2,6-di-alkyl-4-silyl-phenols
US5998401A (en) *	1995-02-28	1999-12-07	Eli Lilly And Company	Naphthyl compounds, intermediates, compositions, and methods
US5795876A (en) *	1996-04-30	1998-08-18	Hoechst Marion Rousssel, Inc.	Method of inhibiting vascular cell adhesion molecule-1 and treating chronic inflammatory diseases with 2, 6-di-alkyl-4-silyl-phenols
US5608095A (en) *	1996-04-30	1997-03-04	Hoechst Marion Roussel, Inc.	Alkyl-4-silyl-phenols and esters thereof as antiatherosclerotic agents
US6114572A (en) *	1996-11-20	2000-09-05	Hoechst Marion Roussel, Inc.	Substituted phenols and thiophenols useful as antioxidant agents
US6121463A (en) *	1997-06-24	2000-09-19	Hoechst Marion Roussel, Inc.	Alkyl-4-silylheterocyclic phenols and thiophenols useful as antioxidant agents
US6133467A (en) *	1997-06-25	2000-10-17	Hoechst Marion Roussel, Inc.	2,6-di-t-butyl-4-[(dimethyl-4-methoxyphenylsilyl)-methyl-oxy]phenol and 2,6-di-t-butyl-4-[(dimethyl-2-methoxy-phenylsilyl)methyloxy]phenol
WO1999043658A1 (en)	1998-02-27	1999-09-02	Warner-Lambert Company	Heterocyclic substituted aniline calcium channel blockers
US6166052A (en)	1998-03-11	2000-12-26	Warner-Lambert Company	Heteroaryl alkyl alpha substituted peptidylamine calcium channel blockers
US6951862B2 (en)	1998-06-30	2005-10-04	Neuromed Technologies, Inc.	Calcium channel blockers comprising two benzhydril moieties
US6943168B2 (en)	1998-06-30	2005-09-13	Neuromed Technologies Inc.	Calcium channel inhibitors comprising benzhydril spaced from piperazine
US7186726B2 (en)	1998-06-30	2007-03-06	Neuromed Pharmaceuticals Ltd.	Preferentially substituted calcium channel blockers
US6387897B1 (en)	1998-06-30	2002-05-14	Neuromed Technologies, Inc.	Preferentially substituted calcium channel blockers
ES2233493T3 (es) *	1999-12-21	2005-06-16	Mitsubishi Pharma Corporation	Agentes terapeuticos y/o profilacticos para trastornos del sistema nervioso.
JP2009500340A (ja) *	2005-06-29	2009-01-08	メルクエンドカムパニーインコーポレーテッド	４−フルオロ−ピペリジンｔ型カルシウムチャネルアンタゴニスト
CA3145096A1 (en)	2018-06-27	2020-01-02	Cornell University	Substituted alkylphenols as hcn1 antagonists

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3233828A1 (de) *	1982-09-11	1984-03-15	Basf Ag, 6700 Ludwigshafen	Aryloxyalkylamine, verfahren zu ihrer herstellung und ihre verwendung zur bekaempfung unerwuenschten pflanzenwuchses
DE3421810A1 (de) *	1984-06-12	1985-12-12	Basf Ag, 6700 Ludwigshafen	Phenylalkylamine - bioregulatoren
DE3706585A1 (de) *	1987-02-25	1988-09-08	Schering Ag	Aryl- und aryloxy-substituierte tert.-alkylenamine, verfahren zu ihrer herstellung und ihre pharmazeutische verwendung
AU676993B2 (en) *	1991-06-27	1997-04-10	Virginia Commonwealth University	Sigma receptor ligands and the use thereof

1993
- 1993-12-16 CA CA002152394A patent/CA2152394A1/en not_active Abandoned
- 1993-12-16 AU AU58334/94A patent/AU5833494A/en not_active Abandoned
- 1993-12-16 EP EP94904162A patent/EP0675883A1/de not_active Withdrawn
- 1993-12-16 KR KR1019950702552A patent/KR950704284A/ko not_active Withdrawn
- 1993-12-16 JP JP6514808A patent/JPH08504792A/ja active Pending
- 1993-12-16 WO PCT/EP1993/003629 patent/WO1994014786A1/en not_active Ceased
- 1993-12-21 CN CN93112958A patent/CN1092415A/zh active Pending
1994
- 1994-01-03 MX MX9400070A patent/MX9400070A/es unknown

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH1039525A (ja) *	1996-07-26	1998-02-13	Konica Corp	電子写真感光体

Also Published As

Publication number	Publication date
AU5833494A (en)	1994-07-19
CA2152394A1 (en)	1994-07-07
EP0675883A1 (de)	1995-10-11
MX9400070A (es)	1994-07-29
WO1994014786A1 (en)	1994-07-07
CN1092415A (zh)	1994-09-21
KR950704284A (ko)	1995-11-17

Publication	Publication Date	Title
JPH08504792A (ja)	1996-05-21	カルシウムチャンネルアンタゴニストとしてのピペリジン誘導体
JPH05507720A (ja)	1993-11-04	ロイコトリエンｂ↓４アンタゴニスト
JPH07503463A (ja)	1995-04-13	カルシウムチャンネル拮抗薬としてのアザビシクロ化合物
AU649468B2 (en)	1994-05-26	3-substituted piperidine derivatives
JPH08505375A (ja)	1996-06-11	置換基をもつトリオール類
JPH08504419A (ja)	1996-05-14	カルシウムチャンネル拮抗薬としてのアリールオキシアルキル置換環状アミンの使用および新規フェニルオキシアルキルピペリジン誘導体
US5773463A (en)	1998-06-30	Indane and tetrahydronaphthalene derivatives as calcium channel antagonists
JPH09512542A (ja)	1997-12-16	Ｄ▲下４▼リセプタ拮抗剤としてのベンゾフラン誘導体
EP0360685A1 (de)	1990-03-28	1-[(Diarylmethoxy)alkyl]-pyrrolidine und -piperidine, Verfahren zu ihrer Herstellung und Arzneimittel, die sie enthalten
EP0524846A1 (de)	1993-01-27	2-(Piperidin-1-yl)ethanolderivate, ihre Herstellung und ihre Anwendung in der Therapie
JPH037257A (ja)	1991-01-14	ピリジン誘導体及びそれを有効成分とする向精神剤
EP0718286B1 (de)	1998-07-29	3-Alkoxybenzylpiperidin-Derivate as melatonergisches Mittel
JPH02306962A (ja)	1990-12-20	新規ｎ―置換―１―デオキシノジリマイシン誘導体及びそれを含有する癌細胞転移抑制剤
JP2002516859A (ja)	2002-06-11	メラトニン作動性薬剤であるヘテロ環シスシクロプロパン誘導体
FR2536398A1 (fr)	1984-05-25	Nouveaux composes heterocycliques
JPH09500383A (ja)	1997-01-14	カルシウムチャネル拮抗剤活性を有するキノリジジン
JPH07503462A (ja)	1995-04-13	カルシウムチャンネル拮抗薬としてのアザビシクロ化合物
EP1828125B1 (de)	2008-04-09	Arylpiperazinderivate und deren verwendung als für den dopamin-d3-rezeptor selektive liganden
JPH09504014A (ja)	1997-04-22	カルシウムチャネル拮抗薬としてのアミン誘導体類
JPH09504016A (ja)	1997-04-22	虚血性発作治療用複素環式アミン類
EA017631B1 (ru)	2013-02-28	Кристаллическое основание транс-1-((1r,3s)-3-фенил-6-хлороиндан-1-ил)-3,3-диметилпиперазина
EP0050072B1 (de)	1984-12-27	Cyclopropylmethyl-Piperazine, deren Herstellungsverfahren und deren Verwendung in der Therapeutik
JPH05506440A (ja)	1993-09-22	アルコキシ置換ジヒドロベンゾピラン―２―カルボン酸およびその誘導体
NZ233002A (en)	1992-07-28	3-(aminoalkyl)benzothiopyran derivatives and pharmaceutical compositions
JP2956788B2 (ja)	1999-10-04	スピロイソインドリン化合物、その製造方法、それを含有する神経症を治療するための医薬およびそれを製造するための中間体

JPH08504792A - カルシウムチャンネルアンタゴニストとしてのピペリジン誘導体 - Google Patents

Info

Links

Classifications

Landscapes

Applications Claiming Priority (5)

Publications (1)

Family

ID=26302202

Family Applications (1)

Country Status (8)

Cited By (1)

Families Citing this family (16)

Family Cites Families (4)

Cited By (1)

Also Published As

Similar Documents