BG108328A - 4-(фенил-пиперидин-4-илиден-метил)-бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства - Google Patents

4-(фенил-пиперидин-4-илиден-метил)-бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства Download PDF

Info

Publication number: BG108328A
Authority: BG; Bulgaria
Prior art keywords: phenyl; compound; methyl; ylidene; benzamide
Prior art date: 2001-05-18

Application number

BG108328A

Other languages

Bulgarian (bg)

English (en)

Inventor

William Brown

Christopher Walpole

Zhongyong Wei

Original Assignee

Astrazeneca Ab

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.)

2001-05-18

Filing date

2003-11-07

Publication date

2004-12-30

2003-11-07 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2004-12-30 Publication of BG108328A publication Critical patent/BG108328A/bg

Links

230000036407 pain Effects 0.000 title claims abstract description 9
208000018522 Gastrointestinal disease Diseases 0.000 title claims abstract description 8
208000019901 Anxiety disease Diseases 0.000 title abstract 2
208000027520 Somatoform disease Diseases 0.000 title abstract 2
230000036506 anxiety Effects 0.000 title abstract 2
208000027753 pain disease Diseases 0.000 title abstract 2
TZKLMPPHEAGFJR-UHFFFAOYSA-N 4-[phenyl(piperidin-4-ylidene)methyl]benzamide Chemical class C1=CC(C(=O)N)=CC=C1C(C=1C=CC=CC=1)=C1CCNCC1 TZKLMPPHEAGFJR-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 68
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 16
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 11
150000003839 salts Chemical class 0.000 claims abstract description 9
125000001424 substituent group Chemical group 0.000 claims abstract description 8
125000002541 furyl group Chemical group 0.000 claims abstract description 6
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 6
125000001544 thienyl group Chemical group 0.000 claims abstract description 6
125000001246 bromo group Chemical group Br* 0.000 claims abstract description 5
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 5
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 5
125000002883 imidazolyl group Chemical group 0.000 claims abstract description 3
125000000335 thiazolyl group Chemical group 0.000 claims abstract description 3
125000001425 triazolyl group Chemical group 0.000 claims abstract description 3
-1 CF 3 Chemical group 0.000 claims description 23
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 12
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
208000002193 Pain Diseases 0.000 claims description 9
239000004480 active ingredient Substances 0.000 claims description 7
238000000034 method Methods 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
125000002346 iodo group Chemical group I* 0.000 claims description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
WFWQWTPAPNEOFE-UHFFFAOYSA-N (3-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(O)=C1 WFWQWTPAPNEOFE-UHFFFAOYSA-N 0.000 claims description 2
CAVGWSGRVUUPLY-UHFFFAOYSA-N 4-[(1-benzylpiperidin-4-ylidene)-(3-hydroxyphenyl)methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(O)C=CC=1)=C1CCN(CC=2C=CC=CC=2)CC1 CAVGWSGRVUUPLY-UHFFFAOYSA-N 0.000 claims description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
229910052763 palladium Inorganic materials 0.000 claims description 2
229940095064 tartrate Drugs 0.000 claims description 2
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims 1
JGRISOTXIVNHEM-UHFFFAOYSA-N 4-[(3-hydroxyphenyl)-[1-(1h-imidazol-2-ylmethyl)piperidin-4-ylidene]methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(O)C=CC=1)=C1CCN(CC=2NC=CN=2)CC1 JGRISOTXIVNHEM-UHFFFAOYSA-N 0.000 claims 1
KKKDXIZHAKECPH-UHFFFAOYSA-N 4-[(3-hydroxyphenyl)-[1-(1h-pyrrol-2-ylmethyl)piperidin-4-ylidene]methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(O)C=CC=1)=C1CCN(CC=2NC=CC=2)CC1 KKKDXIZHAKECPH-UHFFFAOYSA-N 0.000 claims 1
ZGHXWEPUBQIIBU-UHFFFAOYSA-N 4-[(3-hydroxyphenyl)-[1-(thiophen-2-ylmethyl)piperidin-4-ylidene]methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(O)C=CC=1)=C1CCN(CC=2SC=CC=2)CC1 ZGHXWEPUBQIIBU-UHFFFAOYSA-N 0.000 claims 1
FZFUOIOHBFULAX-UHFFFAOYSA-N 4-[(3-hydroxyphenyl)-[1-(thiophen-3-ylmethyl)piperidin-4-ylidene]methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(O)C=CC=1)=C1CCN(CC2=CSC=C2)CC1 FZFUOIOHBFULAX-UHFFFAOYSA-N 0.000 claims 1
RWISWBNYFAHLPO-UHFFFAOYSA-N 4-[(3-hydroxyphenyl)-[1-[(4-methoxyphenyl)methyl]piperidin-4-ylidene]methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(OC)=CC=C1CN(CC1)CCC1=C(C=1C=C(O)C=CC=1)C1=CC=C(C(=O)N(C(C)C)C(C)C)C=C1 RWISWBNYFAHLPO-UHFFFAOYSA-N 0.000 claims 1
IOPTYCUDVSURJE-UHFFFAOYSA-N 4-[[1-(furan-2-ylmethyl)piperidin-4-ylidene]-(3-hydroxyphenyl)methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(O)C=CC=1)=C1CCN(CC=2OC=CC=2)CC1 IOPTYCUDVSURJE-UHFFFAOYSA-N 0.000 claims 1
PIPMONPNGJEOIM-UHFFFAOYSA-N 4-[[1-[(4-bromophenyl)methyl]piperidin-4-ylidene]-(3-hydroxyphenyl)methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(O)C=CC=1)=C1CCN(CC=2C=CC(Br)=CC=2)CC1 PIPMONPNGJEOIM-UHFFFAOYSA-N 0.000 claims 1
208000020401 Depressive disease Diseases 0.000 claims 1
208000014540 Functional gastrointestinal disease Diseases 0.000 claims 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
239000003054 catalyst Substances 0.000 claims 1
150000001860 citric acid derivatives Chemical class 0.000 claims 1
229910000041 hydrogen chloride Inorganic materials 0.000 claims 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims 1
229910021653 sulphate ion Inorganic materials 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 abstract description 3
125000004122 cyclic group Chemical group 0.000 abstract description 2
238000006467 substitution reaction Methods 0.000 abstract description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 abstract 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 42
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
239000000243 solution Substances 0.000 description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
239000000203 mixture Substances 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
239000000543 intermediate Substances 0.000 description 11
230000002829 reductive effect Effects 0.000 description 11
239000007787 solid Substances 0.000 description 10
238000012360 testing method Methods 0.000 description 10
241000700159 Rattus Species 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000003814 drug Substances 0.000 description 8
210000002683 foot Anatomy 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
239000002287 radioligand Substances 0.000 description 8
239000007983 Tris buffer Substances 0.000 description 7
230000027455 binding Effects 0.000 description 7
239000012528 membrane Substances 0.000 description 7
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
241000699666 Mus <mouse, genus> Species 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
210000004556 brain Anatomy 0.000 description 6
239000000835 fiber Substances 0.000 description 6
238000003818 flash chromatography Methods 0.000 description 6
239000003446 ligand Substances 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
102000005962 receptors Human genes 0.000 description 6
230000004044 response Effects 0.000 description 6
238000003756 stirring Methods 0.000 description 6
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000000730 antalgic agent Substances 0.000 description 5
239000002775 capsule Substances 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000000843 powder Substances 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
241000699670 Mus sp. Species 0.000 description 4
101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
239000000556 agonist Substances 0.000 description 4
229940035676 analgesics Drugs 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
238000003556 assay Methods 0.000 description 4
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
239000012267 brine Substances 0.000 description 4
INLLPKCGLOXCIV-UHFFFAOYSA-N bromoethene Chemical compound BrC=C INLLPKCGLOXCIV-UHFFFAOYSA-N 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
108700023159 delta Opioid Receptors Proteins 0.000 description 4
102000048124 delta Opioid Receptors Human genes 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
239000012071 phase Substances 0.000 description 4
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
230000009870 specific binding Effects 0.000 description 4
239000000126 substance Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
UBOJYURSFIUEFZ-UHFFFAOYSA-N 2,3-di(propan-2-yl)benzamide Chemical compound CC(C)C1=CC=CC(C(N)=O)=C1C(C)C UBOJYURSFIUEFZ-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
208000004454 Hyperalgesia Diseases 0.000 description 3
241001465754 Metazoa Species 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
206010053552 allodynia Diseases 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
239000013058 crude material Substances 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
230000007794 irritation Effects 0.000 description 3
239000007788 liquid Substances 0.000 description 3
229940005483 opioid analgesics Drugs 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
230000009885 systemic effect Effects 0.000 description 3
KQWVAUSXZDRQPZ-UMTXDNHDSA-N 4-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enyl-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide Chemical group C1=CC(C(=O)N(CC)CC)=CC=C1[C@H](C=1C=C(OC)C=CC=1)N1[C@@H](C)CN(CC=C)[C@H](C)C1 KQWVAUSXZDRQPZ-UMTXDNHDSA-N 0.000 description 2
206010002091 Anaesthesia Diseases 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
108010052285 Membrane Proteins Proteins 0.000 description 2
102000018697 Membrane Proteins Human genes 0.000 description 2
108090000137 Opioid Receptors Proteins 0.000 description 2
102000003840 Opioid Receptors Human genes 0.000 description 2
239000004743 Polypropylene Substances 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
230000001270 agonistic effect Effects 0.000 description 2
230000037005 anaesthesia Effects 0.000 description 2
230000036592 analgesia Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000012148 binding buffer Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
244000309464 bull Species 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
229940110456 cocoa butter Drugs 0.000 description 2
235000019868 cocoa butter Nutrition 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
239000000841 delta opiate receptor agonist Substances 0.000 description 2
201000010099 disease Diseases 0.000 description 2
238000006073 displacement reaction Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
239000012530 fluid Substances 0.000 description 2
BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
239000012139 lysis buffer Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000000463 material Substances 0.000 description 2
238000002844 melting Methods 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
230000037361 pathway Effects 0.000 description 2
239000008188 pellet Substances 0.000 description 2
229920001155 polypropylene Polymers 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
238000006268 reductive amination reaction Methods 0.000 description 2
230000011514 reflex Effects 0.000 description 2
230000000717 retained effect Effects 0.000 description 2
239000011734 sodium Substances 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000002904 solvent Substances 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
238000003786 synthesis reaction Methods 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
CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 2
235000012431 wafers Nutrition 0.000 description 2
239000011534 wash buffer Substances 0.000 description 2
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
JNTMAZFVYNDPLB-PEDHHIEDSA-N (2S,3S)-2-[[[(2S)-1-[(2S,3S)-2-amino-3-methyl-1-oxopentyl]-2-pyrrolidinyl]-oxomethyl]amino]-3-methylpentanoic acid Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JNTMAZFVYNDPLB-PEDHHIEDSA-N 0.000 description 1
NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-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
ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
ZXAPQWICZVMRRE-UHFFFAOYSA-N 4-[bromo-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-ylidene]methyl]benzoic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1=C(Br)C1=CC=C(C(O)=O)C=C1 ZXAPQWICZVMRRE-UHFFFAOYSA-N 0.000 description 1
125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 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
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000000044 Amnesia Diseases 0.000 description 1
208000031091 Amnestic disease Diseases 0.000 description 1
108010039627 Aprotinin Proteins 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 1
VGGGPCQERPFHOB-UHFFFAOYSA-N Bestatin Natural products CC(C)CC(C(O)=O)NC(=O)C(O)C(N)CC1=CC=CC=C1 VGGGPCQERPFHOB-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
206010058019 Cancer Pain Diseases 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
208000000094 Chronic Pain Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
208000027932 Collagen disease Diseases 0.000 description 1
206010010774 Constipation Diseases 0.000 description 1
206010011224 Cough Diseases 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
108091006027 G proteins Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
241000282412 Homo Species 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
206010021118 Hypotonia Diseases 0.000 description 1
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 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
208000019430 Motor disease Diseases 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
229930193140 Neomycin Natural products 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
229920005372 Plexiglas® Polymers 0.000 description 1
RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
229920002873 Polyethylenimine Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
206010037423 Pulmonary oedema Diseases 0.000 description 1
206010041250 Social phobia Diseases 0.000 description 1
208000020339 Spinal injury Diseases 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
208000006011 Stroke Diseases 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
239000012317 TBTU Substances 0.000 description 1
229920002253 Tannate Polymers 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
208000030886 Traumatic Brain injury Diseases 0.000 description 1
206010046543 Urinary incontinence Diseases 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
230000003187 abdominal effect Effects 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
208000005298 acute pain Diseases 0.000 description 1
230000007815 allergy Effects 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
230000006986 amnesia Effects 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
229940035674 anesthetics Drugs 0.000 description 1
238000010171 animal model Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
239000002249 anxiolytic agent Substances 0.000 description 1
230000000949 anxiolytic effect Effects 0.000 description 1
229940005530 anxiolytics Drugs 0.000 description 1
229960004405 aprotinin Drugs 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
230000001174 ascending effect Effects 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000000872 buffer Substances 0.000 description 1
VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
239000001639 calcium acetate Substances 0.000 description 1
229960005147 calcium acetate Drugs 0.000 description 1
235000011092 calcium acetate Nutrition 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
239000003086 colorant Substances 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
230000008602 contraction Effects 0.000 description 1
230000002920 convulsive effect Effects 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
238000002059 diagnostic imaging Methods 0.000 description 1
238000012631 diagnostic technique Methods 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
208000010643 digestive system disease Diseases 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
108010054812 diprotin A Proteins 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
206010013663 drug dependence Diseases 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
201000006549 dyspepsia Diseases 0.000 description 1
229940009662 edetate Drugs 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
229950007655 esilate Drugs 0.000 description 1
229950000206 estolate Drugs 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000009472 formulation Methods 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
238000011990 functional testing Methods 0.000 description 1
208000018685 gastrointestinal system disease Diseases 0.000 description 1
238000002695 general anesthesia Methods 0.000 description 1
239000003193 general anesthetic agent Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
210000000548 hind-foot Anatomy 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
230000002519 immonomodulatory effect Effects 0.000 description 1
239000002955 immunomodulating agent Substances 0.000 description 1
229940121354 immunomodulator Drugs 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000010874 in vitro model Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
230000003910 liver physiology Effects 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229940049920 malate Drugs 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
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
230000036640 muscle relaxation Effects 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 1
229960004127 naloxone Drugs 0.000 description 1
DKJCUVXSBOMWAV-PCWWUVHHSA-N naltrindole Chemical compound N1([C@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CC2=C3[CH]C=CC=C3N=C25)O)CC1)O)CC1CC1 DKJCUVXSBOMWAV-PCWWUVHHSA-N 0.000 description 1
229960004927 neomycin Drugs 0.000 description 1
208000004296 neuralgia Diseases 0.000 description 1
239000000842 neuromuscular blocking agent Substances 0.000 description 1
208000021722 neuropathic pain Diseases 0.000 description 1
229960002715 nicotine Drugs 0.000 description 1
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000003921 oil Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
210000001428 peripheral nervous system Anatomy 0.000 description 1
RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
229920001993 poloxamer 188 Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
238000002600 positron emission tomography Methods 0.000 description 1
230000002980 postoperative effect Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000008569 process Effects 0.000 description 1
ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
208000020016 psychiatric disease Diseases 0.000 description 1
208000005333 pulmonary edema Diseases 0.000 description 1
238000010926 purge Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000010802 sludge Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000010902 straw Substances 0.000 description 1
208000011117 substance-related disease Diseases 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
210000002820 sympathetic nervous system Anatomy 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
229920003002 synthetic resin Polymers 0.000 description 1
239000000057 synthetic resin Substances 0.000 description 1
239000007885 tablet disintegrant Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
PKNKIFGUCYQMRH-UHFFFAOYSA-N tert-butyl 4-[(4-methoxycarbonylphenyl)methylidene]piperidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1C=C1CCN(C(=O)OC(C)(C)C)CC1 PKNKIFGUCYQMRH-UHFFFAOYSA-N 0.000 description 1
BWUILNMXUUMHPV-UHFFFAOYSA-N tert-butyl 4-bromo-4-[bromo-(4-methoxycarbonylphenyl)methyl]piperidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1C(Br)C1(Br)CCN(C(=O)OC(C)(C)C)CC1 BWUILNMXUUMHPV-UHFFFAOYSA-N 0.000 description 1
ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
229950009811 ubenimex Drugs 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
208000009935 visceral pain Diseases 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
- 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
- A61P25/22—Anxiolytics
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
- 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
- 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
- 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
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Addiction (AREA)
Psychiatry (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Physical Education & Sports Medicine (AREA)
Pulmonology (AREA)
Vascular Medicine (AREA)
Psychology (AREA)
Orthopedic Medicine & Surgery (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)

BG108328A 2001-05-18 2003-11-07 4-(фенил-пиперидин-4-илиден-метил)-бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства BG108328A (bg)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
SE0101767A SE0101767D0 (sv)	2001-05-18	2001-05-18	Novel compounds

Publications (1)

Publication Number	Publication Date
BG108328A true BG108328A (bg)	2004-12-30

Family

ID=20284170

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG108328A BG108328A (bg)	2001-05-18	2003-11-07	4-(фенил-пиперидин-4-илиден-метил)-бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства

Country Status (25)

Country	Link
US (1)	US20040138259A1 (fr)
EP (1)	EP1395574B1 (fr)
JP (1)	JP2005507372A (fr)
KR (1)	KR20030094423A (fr)
CN (1)	CN1547579A (fr)
AR (1)	AR033756A1 (fr)
AT (1)	ATE287400T1 (fr)
BG (1)	BG108328A (fr)
BR (1)	BR0209667A (fr)
CA (1)	CA2446331A1 (fr)
CO (1)	CO5540304A2 (fr)
CZ (1)	CZ20033087A3 (fr)
DE (1)	DE60202679T2 (fr)
EE (1)	EE200300543A (fr)
HU (1)	HUP0401285A2 (fr)
IL (1)	IL158695A0 (fr)
IS (1)	IS7024A (fr)
MX (1)	MXPA03010438A (fr)
NO (1)	NO20035118D0 (fr)
PL (1)	PL366389A1 (fr)
RU (1)	RU2003131968A (fr)
SE (1)	SE0101767D0 (fr)
SK (1)	SK13932003A3 (fr)
WO (1)	WO2002094810A1 (fr)
ZA (1)	ZA200308635B (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CL2004000754A1 (es) *	2003-04-11	2005-02-25	Janssen Pharmaceutica Nv	Uso de compuestos derivados de 4-fenil-4-(1h-imidazol-2-il)piperidina, como agonistas delta-opioides no peptidicos, para preparar un medicamento util en prevenir o tratar trastornos del sistema nervioso central.
KR20060010811A (ko) *	2003-05-16	2006-02-02	아스트라제네카 아베	디아릴메틸리덴 피페리딘 유도체, 그의 제조 및 그의 용도
SE0301443D0 (sv) *	2003-05-16	2003-05-16	Astrazeneca Ab	Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof
WO2005005478A2 (fr) *	2003-07-02	2005-01-20	Bayer Healthcare Ag	Diagnostics et traitements de maladies associees au recepteur opioide delta 1 (oprd1) couple a une proteine g
KR101255074B1 (ko)	2003-10-01	2013-04-16	아돌로 코포레이션	스피로시클릭 헤테로시클릭 유도체 및 이의 사용 방법
US7598261B2 (en)	2005-03-31	2009-10-06	Adolor Corporation	Spirocyclic heterocyclic derivatives and methods of their use
US7576207B2 (en)	2006-04-06	2009-08-18	Adolor Corporation	Spirocyclic heterocyclic derivatives and methods of their use
WO2008033299A2 (fr)	2006-09-12	2008-03-20	Adolor Corporation	Méthodes d'amélioration de la fonction cognitive

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2898339A (en) *	1957-07-29	1959-08-04	Wm S Merrell Co	N-substituted benzhydrol, benzhydryl, and benzhydrylidene piperidine
US4581171A (en) *	1983-07-27	1986-04-08	Janssen Pharmaceutica, N.V.	[[Bis(aryl)methylene]-1-piperidinyl]alkyl-pyrimidinones useful for treating psychotropic disorders
US4816586A (en) *	1987-07-29	1989-03-28	Regents Of The University Of Minnesota	Delta opioid receptor antagonists
US5140029A (en) *	1989-01-09	1992-08-18	Janssen Pharmaceutica N.V.	2-aminopyrimidinone derivatives
US4939137A (en) *	1989-06-28	1990-07-03	Ortho Pharmaceutical Corporation	Ring-fused thienopyrimidinedione derivatives
US5683998A (en) *	1991-04-23	1997-11-04	Toray Industries, Inc.	Tricyclic triazolo derivatives, processes for producing the same and the uses of the same
US5574159A (en) *	1992-02-03	1996-11-12	Delta Pharmaceuticals, Inc.	Opioid compounds and methods for making therefor
TW548271B (en) *	1996-12-20	2003-08-21	Astra Pharma Inc	Novel piperidine derivatives having an exocyclic double bond with analgesic effects
US6436959B1 (en) *	1998-12-23	2002-08-20	Ortho-Mcneil Pharmaceutical, Inc.	4-[aryl(piperidin-4-yl)]aminobenzamides
SE0001207D0 (sv) *	2000-04-04	2000-04-04	Astrazeneca Canada Inc	Novel compounds

2001
- 2001-05-18 SE SE0101767A patent/SE0101767D0/xx unknown
2002
- 2002-05-16 MX MXPA03010438A patent/MXPA03010438A/es unknown
- 2002-05-16 IL IL15869502A patent/IL158695A0/xx unknown
- 2002-05-16 EE EEP200300543A patent/EE200300543A/xx unknown
- 2002-05-16 US US10/477,854 patent/US20040138259A1/en not_active Abandoned
- 2002-05-16 KR KR10-2003-7014944A patent/KR20030094423A/ko not_active Application Discontinuation
- 2002-05-16 WO PCT/SE2002/000946 patent/WO2002094810A1/fr not_active Application Discontinuation
- 2002-05-16 CN CNA02810191XA patent/CN1547579A/zh active Pending
- 2002-05-16 PL PL02366389A patent/PL366389A1/xx not_active Application Discontinuation
- 2002-05-16 RU RU2003131968/04A patent/RU2003131968A/ru not_active Application Discontinuation
- 2002-05-16 HU HU0401285A patent/HUP0401285A2/hu unknown
- 2002-05-16 DE DE60202679T patent/DE60202679T2/de not_active Expired - Fee Related
- 2002-05-16 CZ CZ20033087A patent/CZ20033087A3/cs unknown
- 2002-05-16 BR BR0209667-6A patent/BR0209667A/pt not_active Application Discontinuation
- 2002-05-16 CA CA002446331A patent/CA2446331A1/fr not_active Abandoned
- 2002-05-16 JP JP2002591483A patent/JP2005507372A/ja active Pending
- 2002-05-16 SK SK1393-2003A patent/SK13932003A3/sk unknown
- 2002-05-16 AT AT02733703T patent/ATE287400T1/de not_active IP Right Cessation
- 2002-05-16 AR ARP020101812A patent/AR033756A1/es not_active Application Discontinuation
- 2002-05-16 EP EP02733703A patent/EP1395574B1/fr not_active Expired - Lifetime
2003
- 2003-11-05 ZA ZA200308635A patent/ZA200308635B/en unknown
- 2003-11-07 BG BG108328A patent/BG108328A/bg unknown
- 2003-11-11 IS IS7024A patent/IS7024A/is unknown
- 2003-11-12 CO CO03100160A patent/CO5540304A2/es not_active Application Discontinuation
- 2003-11-17 NO NO20035118A patent/NO20035118D0/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
IL158695A0 (en)	2004-05-12
EE200300543A (et)	2004-02-16
IS7024A (is)	2003-11-11
BR0209667A (pt)	2004-04-20
DE60202679T2 (de)	2006-03-30
CA2446331A1 (fr)	2002-11-28
AR033756A1 (es)	2004-01-07
JP2005507372A (ja)	2005-03-17
ATE287400T1 (de)	2005-02-15
PL366389A1 (en)	2005-01-24
DE60202679D1 (de)	2005-02-24
CO5540304A2 (es)	2005-07-29
EP1395574B1 (fr)	2005-01-19
KR20030094423A (ko)	2003-12-11
RU2003131968A (ru)	2005-05-10
SE0101767D0 (sv)	2001-05-18
US20040138259A1 (en)	2004-07-15
CN1547579A (zh)	2004-11-17
NO20035118D0 (no)	2003-11-17
CZ20033087A3 (cs)	2004-05-12
SK13932003A3 (sk)	2004-05-04
WO2002094810A1 (fr)	2002-11-28
MXPA03010438A (es)	2004-03-09
EP1395574A1 (fr)	2004-03-10
HUP0401285A2 (hu)	2004-12-28
ZA200308635B (en)	2005-02-07

Publication	Publication Date	Title
BG108333A (bg)	2004-12-30	4(фенил-пиперазинил-метил) бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства
SK14232002A3 (sk)	2003-06-03	Hydroxyfenylpiperidin-4-ylidénmetylbenzamidové deriváty na liečbu bolesti
BG108326A (bg)	2004-12-30	4-(фенил-пиперидин-4-илиден-метил)-бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства
BG108327A (bg)	2004-12-30	4-(фенил-пиперидин-4-илиден-метил)-бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства
SK8832002A3 (en)	2003-03-04	N-diarylmethylpiperazine derivatives, the use thereof and pharmaceutical compositions comprising same
SK14242002A3 (sk)	2003-06-03	Chinolinylpiperidin-4-ylidénmetylbenzamidové deriváty na liečbu bolesti
BG108329A (bg)	2004-12-30	4-(фенил-пиперидин-4-илиден-метил)-бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства
BG108328A (bg)	2004-12-30	4-(фенил-пиперидин-4-илиден-метил)-бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства
BG108330A (bg)	2004-12-30	4-(фенил-(пиперидин-4-ил)-амино)-бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства
BG108331A (bg)	2004-10-29	4-(фенил-(пиперидин-4-ил)-амино)-бензамидни производни и тяхното използване за лечението на болка, потиснатост или стомашно-чревни разстройства
BG108334A (bg)	2004-12-30	4-(фенил-(пиперидин-4-ил)-амино)-бензамидни производни и тяхното използване за лечение на болка, потиснатост или стомашно-чревни разстройства
AU2002305985A1 (en)	2002-12-03	4-(phenyl-piperidin-4-ylidene-methyl)-benzamide derivatives and their use for the treatment of pain, anxiety or gastrointestinal disorders
AU2002305986A1 (en)	2002-12-03	4-(penyl-piperidin-4-ylidene-methyl)-benzamide derivatives and their use for the treatment of pain, anxiety or gastrointestinal disorders
AU2002307616A1 (en)	2002-12-03	4-(phenyl-piperidin-4-ylidene-methyl)-benzamide derivatives and their use for the treatment of pain anxiety or gastrointestinal disorders