SK1602001A3 - 2-substituted-1-piperidyl benzimidazole compounds, process and intermediates for producing thereof, pharmaceutical compositions and use - Google Patents

2-substituted-1-piperidyl benzimidazole compounds, process and intermediates for producing thereof, pharmaceutical compositions and use Download PDF

Info

Publication number: SK1602001A3
Authority: SK; Slovakia
Prior art keywords: alkyl; carbon atoms; group; aromatic; independently selected
Prior art date: 1998-08-06

Application number

SK160-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Fumitaka Ito

Hirohide Noguchi

Hiroshi Kondo

Original Assignee

Pfizer

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.)

1998-08-06

Filing date

1999-07-05

Publication date

2002-09-10

1999-07-05 Application filed by Pfizer filed Critical Pfizer

2002-09-10 Publication of SK1602001A3 publication Critical patent/SK1602001A3/sk

Links

-1 2-substituted-1-piperidyl benzimidazole compounds Chemical class 0.000 title claims description 341
238000000034 method Methods 0.000 title claims description 98
230000008569 process Effects 0.000 title claims description 12
239000008194 pharmaceutical composition Substances 0.000 title claims description 7
239000000543 intermediate Substances 0.000 title description 16
150000001875 compounds Chemical class 0.000 claims abstract description 270
125000003118 aryl group Chemical group 0.000 claims abstract description 147
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 52
239000001257 hydrogen Substances 0.000 claims abstract description 48
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 47
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 37
150000003839 salts Chemical class 0.000 claims abstract description 27
125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 26
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 22
150000002431 hydrogen Chemical group 0.000 claims abstract description 22
229910052760 oxygen Inorganic materials 0.000 claims abstract description 18
125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 15
229910052717 sulfur Inorganic materials 0.000 claims abstract description 14
125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims abstract description 9
229940035676 analgesics Drugs 0.000 claims abstract description 9
239000000730 antalgic agent Substances 0.000 claims abstract description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 191
125000000217 alkyl group Chemical group 0.000 claims description 169
229910052736 halogen Inorganic materials 0.000 claims description 94
150000002367 halogens Chemical group 0.000 claims description 92
150000001412 amines Chemical class 0.000 claims description 86
229910052799 carbon Inorganic materials 0.000 claims description 61
125000001424 substituent group Chemical group 0.000 claims description 60
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
229910052757 nitrogen Inorganic materials 0.000 claims description 50
238000006243 chemical reaction Methods 0.000 claims description 45
125000003386 piperidinyl group Chemical group 0.000 claims description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
150000001721 carbon Chemical group 0.000 claims description 40
125000004433 nitrogen atom Chemical group N* 0.000 claims description 40
125000003342 alkenyl group Chemical group 0.000 claims description 32
229910005965 SO 2 Inorganic materials 0.000 claims description 30
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 30
239000011541 reaction mixture Substances 0.000 claims description 30
238000010992 reflux Methods 0.000 claims description 26
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
239000003054 catalyst Substances 0.000 claims description 24
125000001624 naphthyl group Chemical group 0.000 claims description 24
241000124008 Mammalia Species 0.000 claims description 23
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 22
125000005842 heteroatom Chemical group 0.000 claims description 22
239000012442 inert solvent Substances 0.000 claims description 21
125000006413 ring segment Chemical group 0.000 claims description 20
241000282414 Homo sapiens Species 0.000 claims description 18
125000004093 cyano group Chemical group *C#N 0.000 claims description 18
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 17
125000004043 oxo group Chemical group O=* 0.000 claims description 17
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
125000004429 atom Chemical group 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
239000001301 oxygen Substances 0.000 claims description 16
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 15
229920006395 saturated elastomer Polymers 0.000 claims description 15
125000004385 trihaloalkyl group Chemical group 0.000 claims description 14
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 13
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
125000004193 piperazinyl group Chemical group 0.000 claims description 13
239000011593 sulfur Substances 0.000 claims description 13
125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 12
239000003795 chemical substances by application Substances 0.000 claims description 12
238000005859 coupling reaction Methods 0.000 claims description 12
208000035475 disorder Diseases 0.000 claims description 12
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 11
125000002541 furyl group Chemical group 0.000 claims description 11
125000001188 haloalkyl group Chemical group 0.000 claims description 11
108010020615 nociceptin receptor Proteins 0.000 claims description 11
230000009467 reduction Effects 0.000 claims description 11
125000001544 thienyl group Chemical group 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 10
230000000202 analgesic effect Effects 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 9
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 9
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 8
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 8
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
125000003277 amino group Chemical group 0.000 claims description 8
229910002091 carbon monoxide Inorganic materials 0.000 claims description 8
230000008878 coupling Effects 0.000 claims description 8
239000007822 coupling agent Substances 0.000 claims description 8
238000010168 coupling process Methods 0.000 claims description 8
125000003838 furazanyl group Chemical group 0.000 claims description 8
125000005936 piperidyl group Chemical group 0.000 claims description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
125000003831 tetrazolyl group Chemical group 0.000 claims description 8
125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 claims description 8
125000000335 thiazolyl group Chemical group 0.000 claims description 8
125000004306 triazinyl group Chemical group 0.000 claims description 8
125000001425 triazolyl group Chemical group 0.000 claims description 8
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 7
208000002193 Pain Diseases 0.000 claims description 7
239000012298 atmosphere Substances 0.000 claims description 7
150000001602 bicycloalkyls Chemical group 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 7
238000005984 hydrogenation reaction Methods 0.000 claims description 7
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 7
125000002098 pyridazinyl group Chemical group 0.000 claims description 7
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 claims description 6
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 6
239000003638 chemical reducing agent Substances 0.000 claims description 6
125000002883 imidazolyl group Chemical group 0.000 claims description 6
208000027866 inflammatory disease Diseases 0.000 claims description 6
125000001786 isothiazolyl group Chemical group 0.000 claims description 6
125000000842 isoxazolyl group Chemical group 0.000 claims description 6
125000002971 oxazolyl group Chemical group 0.000 claims description 6
125000003373 pyrazinyl group Chemical group 0.000 claims description 6
125000003226 pyrazolyl group Chemical group 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
125000000168 pyrrolyl group Chemical group 0.000 claims description 6
HWKDYXZIGNJAEI-UHFFFAOYSA-N 1-[1-(1-phenylcyclononyl)piperidin-4-yl]benzimidazol-2-amine Chemical compound NC1=NC2=CC=CC=C2N1C(CC1)CCN1C1(C=2C=CC=CC=2)CCCCCCCC1 HWKDYXZIGNJAEI-UHFFFAOYSA-N 0.000 claims description 5
IZQZQZPJZMYDBK-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)-1-[1-(1-phenylcycloheptyl)piperidin-4-yl]benzimidazole Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2N1C1CCN(C2(CCCCCC2)C=2C=CC=CC=2)CC1 IZQZQZPJZMYDBK-UHFFFAOYSA-N 0.000 claims description 5
HLMKNZZADDTPSW-UHFFFAOYSA-N 3-[1-[1-(1-phenylcycloheptyl)piperidin-4-yl]benzimidazol-2-yl]sulfonylpropan-1-amine Chemical compound NCCCS(=O)(=O)C1=NC2=CC=CC=C2N1C(CC1)CCN1C1(C=2C=CC=CC=2)CCCCCC1 HLMKNZZADDTPSW-UHFFFAOYSA-N 0.000 claims description 5
230000003444 anaesthetic effect Effects 0.000 claims description 5
BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 claims description 5
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 5
229910052751 metal Inorganic materials 0.000 claims description 5
239000002184 metal Substances 0.000 claims description 5
230000003533 narcotic effect Effects 0.000 claims description 5
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 5
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
VRQBSPPLPSYLDI-UHFFFAOYSA-N 1-[1-(1-phenylcycloheptyl)piperidin-4-yl]benzimidazole Chemical compound C1CC(N2C3=CC=CC=C3N=C2)CCN1C1(C=2C=CC=CC=2)CCCCCC1 VRQBSPPLPSYLDI-UHFFFAOYSA-N 0.000 claims description 4
BCDYNHNOGFFARB-UHFFFAOYSA-N 1-[1-(1-phenylcyclooctyl)piperidin-4-yl]benzimidazol-2-amine Chemical compound NC1=NC2=CC=CC=C2N1C(CC1)CCN1C1(C=2C=CC=CC=2)CCCCCCC1 BCDYNHNOGFFARB-UHFFFAOYSA-N 0.000 claims description 4
208000024827 Alzheimer disease Diseases 0.000 claims description 4
208000019901 Anxiety disease Diseases 0.000 claims description 4
208000027796 Blood pressure disease Diseases 0.000 claims description 4
206010008748 Chorea Diseases 0.000 claims description 4
206010010904 Convulsion Diseases 0.000 claims description 4
206010012289 Dementia Diseases 0.000 claims description 4
208000030814 Eating disease Diseases 0.000 claims description 4
208000019454 Feeding and Eating disease Diseases 0.000 claims description 4
208000004454 Hyperalgesia Diseases 0.000 claims description 4
208000035154 Hyperesthesia Diseases 0.000 claims description 4
208000018737 Parkinson disease Diseases 0.000 claims description 4
208000013200 Stress disease Diseases 0.000 claims description 4
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
230000036506 anxiety Effects 0.000 claims description 4
230000004872 arterial blood pressure Effects 0.000 claims description 4
208000012601 choreatic disease Diseases 0.000 claims description 4
230000036461 convulsion Effects 0.000 claims description 4
235000014632 disordered eating Nutrition 0.000 claims description 4
206010015037 epilepsy Diseases 0.000 claims description 4
230000002757 inflammatory effect Effects 0.000 claims description 4
229910052742 iron Inorganic materials 0.000 claims description 4
CKPXHAZHEPHPAI-UHFFFAOYSA-N n-methyl-1-[1-(1-methylcyclooctyl)piperidin-4-yl]benzimidazol-2-amine Chemical compound CNC1=NC2=CC=CC=C2N1C(CC1)CCN1C1(C)CCCCCCC1 CKPXHAZHEPHPAI-UHFFFAOYSA-N 0.000 claims description 4
229910052763 palladium Inorganic materials 0.000 claims description 4
229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
108090000765 processed proteins & peptides Proteins 0.000 claims description 4
201000000980 schizophrenia Diseases 0.000 claims description 4
239000011701 zinc Substances 0.000 claims description 4
229910052725 zinc Inorganic materials 0.000 claims description 4
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 claims description 3
UXODGZKIRWQGQB-UHFFFAOYSA-N 1-[1-(1-methylcyclooctyl)piperidin-4-yl]-2-(4-methylpiperazin-1-yl)benzimidazole Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2N1C1CCN(C2(C)CCCCCCC2)CC1 UXODGZKIRWQGQB-UHFFFAOYSA-N 0.000 claims description 3
PHHTZPIIQLOHGD-UHFFFAOYSA-N 1-[1-(1-phenylcycloheptyl)piperidin-4-yl]-2-piperidin-4-ylbenzimidazole Chemical compound C1CNCCC1C1=NC2=CC=CC=C2N1C1CCN(C2(CCCCCC2)C=2C=CC=CC=2)CC1 PHHTZPIIQLOHGD-UHFFFAOYSA-N 0.000 claims description 3
AYXVSHDJSMLFAB-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)-1-[1-(1-phenylcyclooctyl)piperidin-4-yl]benzimidazole Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2N1C1CCN(C2(CCCCCCC2)C=2C=CC=CC=2)CC1 AYXVSHDJSMLFAB-UHFFFAOYSA-N 0.000 claims description 3
IRQQGEILIDANLP-UHFFFAOYSA-N 2-[1-[1-(1-phenylcycloheptyl)piperidin-4-yl]benzimidazol-2-yl]oxyethanamine Chemical compound NCCOC1=NC2=CC=CC=C2N1C(CC1)CCN1C1(C=2C=CC=CC=2)CCCCCC1 IRQQGEILIDANLP-UHFFFAOYSA-N 0.000 claims description 3
GNGGSSTUWQJFRZ-UHFFFAOYSA-N 3-amino-1-[1-[1-(1-phenylcycloheptyl)piperidin-4-yl]benzimidazol-2-yl]propan-1-one Chemical compound NCCC(=O)C1=NC2=CC=CC=C2N1C(CC1)CCN1C1(C=2C=CC=CC=2)CCCCCC1 GNGGSSTUWQJFRZ-UHFFFAOYSA-N 0.000 claims description 3
VHBWJOUMJTZEOL-UHFFFAOYSA-N 4-[1-[1-(1-methylcyclooctyl)piperidin-4-yl]benzimidazol-2-yl]piperazine-1-carboximidamide Chemical compound C1CC(N2C3=CC=CC=C3N=C2N2CCN(CC2)C(N)=N)CCN1C1(C)CCCCCCC1 VHBWJOUMJTZEOL-UHFFFAOYSA-N 0.000 claims description 3
PNAJYGIMBRJVNO-UHFFFAOYSA-N 4-[1-[1-(1-phenylcycloheptyl)piperidin-4-yl]benzimidazol-2-yl]piperidine-1-carboximidamide Chemical compound C1CN(C(=N)N)CCC1C1=NC2=CC=CC=C2N1C1CCN(C2(CCCCCC2)C=2C=CC=CC=2)CC1 PNAJYGIMBRJVNO-UHFFFAOYSA-N 0.000 claims description 3
206010002091 Anaesthesia Diseases 0.000 claims description 3
KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 3
206010071368 Psychological trauma Diseases 0.000 claims description 3
239000007868 Raney catalyst Substances 0.000 claims description 3
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 3
229910000564 Raney nickel Inorganic materials 0.000 claims description 3
FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 claims description 3
229910021626 Tin(II) chloride Inorganic materials 0.000 claims description 3
150000008065 acid anhydrides Chemical class 0.000 claims description 3
230000037005 anaesthesia Effects 0.000 claims description 3
230000003925 brain function Effects 0.000 claims description 3
239000006274 endogenous ligand Substances 0.000 claims description 3
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 3
230000001965 increasing effect Effects 0.000 claims description 3
VHRXDWNQAQJXOG-UHFFFAOYSA-N n-[1-[1-(1-phenylcycloheptyl)piperidin-4-yl]benzimidazol-2-yl]acetamide Chemical compound CC(=O)NC1=NC2=CC=CC=C2N1C(CC1)CCN1C1(C=2C=CC=CC=2)CCCCCC1 VHRXDWNQAQJXOG-UHFFFAOYSA-N 0.000 claims description 3
KNCDKEASIWXFDM-UHFFFAOYSA-N n-methyl-1-[1-(1-methylcyclononyl)piperidin-4-yl]benzimidazol-2-amine Chemical compound CNC1=NC2=CC=CC=C2N1C(CC1)CCN1C1(C)CCCCCCCC1 KNCDKEASIWXFDM-UHFFFAOYSA-N 0.000 claims description 3
FHGVYXYINTZCLI-UHFFFAOYSA-N n-methyl-1-[1-(1-phenylcycloheptyl)piperidin-4-yl]benzimidazol-2-amine Chemical compound CNC1=NC2=CC=CC=C2N1C(CC1)CCN1C1(C=2C=CC=CC=2)CCCCCC1 FHGVYXYINTZCLI-UHFFFAOYSA-N 0.000 claims description 3
239000004084 narcotic analgesic agent Substances 0.000 claims description 3
230000000324 neuroprotective effect Effects 0.000 claims description 3
230000036407 pain Effects 0.000 claims description 3
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
229910052697 platinum Inorganic materials 0.000 claims description 3
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
229910001415 sodium ion Inorganic materials 0.000 claims description 3
239000001119 stannous chloride Substances 0.000 claims description 3
235000011150 stannous chloride Nutrition 0.000 claims description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 claims description 2
230000003213 activating effect Effects 0.000 claims description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
125000000304 alkynyl group Chemical group 0.000 claims description 2
125000004069 aziridinyl group Chemical group 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
150000001735 carboxylic acids Chemical class 0.000 claims description 2
230000002708 enhancing effect Effects 0.000 claims description 2
230000029142 excretion Effects 0.000 claims description 2
150000003948 formamides Chemical class 0.000 claims description 2
125000004438 haloalkoxy group Chemical group 0.000 claims description 2
230000006872 improvement Effects 0.000 claims description 2
230000001404 mediated effect Effects 0.000 claims description 2
230000004112 neuroprotection Effects 0.000 claims description 2
238000005897 peptide coupling reaction Methods 0.000 claims description 2
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230000028327 secretion Effects 0.000 claims description 2
125000003884 phenylalkyl group Chemical group 0.000 claims 3
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 claims 1
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 claims 1
125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims 1
208000014674 injury Diseases 0.000 claims 1
230000003236 psychic effect Effects 0.000 claims 1
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 1
230000008733 trauma Effects 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 9
125000006701 (C1-C7) alkyl group Chemical group 0.000 abstract description 4
101500026205 Rattus norvegicus Nociceptin Proteins 0.000 abstract description 3
125000001475 halogen functional group Chemical group 0.000 abstract 1
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical group [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 396
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 213
239000000243 solution Substances 0.000 description 155
238000005481 NMR spectroscopy Methods 0.000 description 126
239000007787 solid Substances 0.000 description 121
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 97
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 88
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 86
229910000041 hydrogen chloride Inorganic materials 0.000 description 86
239000000203 mixture Substances 0.000 description 79
238000004458 analytical method Methods 0.000 description 75
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
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125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
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YQLZOAVZWJBZSY-UHFFFAOYSA-N decane-1,10-diamine Chemical compound NCCCCCCCCCCN YQLZOAVZWJBZSY-UHFFFAOYSA-N 0.000 description 1
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150000002009 diols Chemical class 0.000 description 1
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DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
LKKAWMNEPUOSKW-UHFFFAOYSA-N ethyl 4-isothiocyanatopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(N=C=S)CC1 LKKAWMNEPUOSKW-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
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BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
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UGVPKMAWLOMPRS-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].CC[CH2-] UGVPKMAWLOMPRS-UHFFFAOYSA-M 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
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RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
239000006187 pill Substances 0.000 description 1
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WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical class [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
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125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
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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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—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
- A61P25/28—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
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
- 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
- C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
- C07D211/36—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 no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
- 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
- C07D401/14—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 three or more hetero rings

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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Psychiatry (AREA)
Anesthesiology (AREA)
Cardiology (AREA)
Obesity (AREA)
Heart & Thoracic Surgery (AREA)
Toxicology (AREA)
Hospice & Palliative Care (AREA)
Diabetes (AREA)
Hematology (AREA)
Addiction (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Psychology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

SK160-2001A 1998-08-06 1999-07-05 2-substituted-1-piperidyl benzimidazole compounds, process and intermediates for producing thereof, pharmaceutical compositions and use SK1602001A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IBPCT/IB98/01206		1998-08-06
PCT/IB1999/001239 WO2000008013A2 (fr)	1998-08-06	1999-07-05	Composés de 1-pipéridyl benzimidazole substitué en 2, agonistes du récepteur orl1

Publications (1)

Publication Number	Publication Date
SK1602001A3 true SK1602001A3 (en)	2002-09-10

Family

ID=11004738

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK160-2001A SK1602001A3 (en)	1998-08-06	1999-07-05	2-substituted-1-piperidyl benzimidazole compounds, process and intermediates for producing thereof, pharmaceutical compositions and use

Country Status (44)

Country	Link
US (1)	US6172067B1 (fr)
EP (1)	EP1102762B1 (fr)
JP (1)	JP3367945B2 (fr)
CN (1)	CN1317968A (fr)
AP (1)	AP2001002063A0 (fr)
AR (1)	AR018686A1 (fr)
AT (1)	ATE227716T1 (fr)
AU (1)	AU749166B2 (fr)
BG (1)	BG105301A (fr)
BR (1)	BR9912778A (fr)
CA (1)	CA2339621C (fr)
CZ (1)	CZ2001397A3 (fr)
DE (1)	DE69903953T2 (fr)
DK (1)	DK1102762T3 (fr)
EA (1)	EA200100104A1 (fr)
EE (1)	EE200100075A (fr)
ES (1)	ES2185357T3 (fr)
GE (1)	GEP20033000B (fr)
GT (1)	GT199900125A (fr)
HK (1)	HK1040188A1 (fr)
HN (1)	HN1999000105A (fr)
HR (1)	HRP20010089B1 (fr)
HU (1)	HUP0103567A3 (fr)
ID (1)	ID27212A (fr)
IL (1)	IL141029A0 (fr)
IS (1)	IS5812A (fr)
MA (1)	MA26659A1 (fr)
NO (1)	NO20010603L (fr)
NZ (1)	NZ509299A (fr)
OA (1)	OA11590A (fr)
PA (1)	PA8477701A1 (fr)
PE (1)	PE20000868A1 (fr)
PL (1)	PL346211A1 (fr)
PT (1)	PT1102762E (fr)
SI (1)	SI1102762T1 (fr)
SK (1)	SK1602001A3 (fr)
SV (1)	SV1999000099A (fr)
TN (1)	TNSN99142A1 (fr)
TR (1)	TR200100403T2 (fr)
TW (1)	TW513424B (fr)
UY (1)	UY25659A1 (fr)
WO (1)	WO2000008013A2 (fr)
YU (1)	YU8201A (fr)
ZA (1)	ZA200100900B (fr)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6340681B1 (en) *	1999-07-16	2002-01-22	Pfizer Inc	2-benzimidazolylamine compounds as ORL-1-receptor agonists
SE9902987D0 (sv)	1999-08-24	1999-08-24	Astra Pharma Prod	Novel compounds
SE9903544D0 (sv)	1999-10-01	1999-10-01	Astra Pharma Prod	Novel compounds
ATE306488T1 (de) *	2000-01-05	2005-10-15	Pfizer	Benzimidazol-verbindungen zur verwendung als orl1-rezeptor-antagonisten
GB2359081A (en)	2000-02-11	2001-08-15	Astrazeneca Uk Ltd	Pharmaceutically active thiazolopyrimidines
GB2359078A (en)	2000-02-11	2001-08-15	Astrazeneca Uk Ltd	Pharmaceutically active pyrimidine derivatives
GB2359551A (en)	2000-02-23	2001-08-29	Astrazeneca Uk Ltd	Pharmaceutically active pyrimidine derivatives
GB0005642D0 (en)	2000-03-10	2000-05-03	Astrazeneca Uk Ltd	Chemical compounds
SE0003828D0 (sv)	2000-10-20	2000-10-20	Astrazeneca Ab	Novel compounds
AU2002224038B2 (en) *	2000-11-15	2006-03-09	Banyu Pharmaceutical Co., Ltd.	Benzimidazole derivatives
GB0104050D0 (en)	2001-02-19	2001-04-04	Astrazeneca Ab	Chemical compounds
GB0107228D0 (en)	2001-03-22	2001-05-16	Astrazeneca Ab	Chemical compounds
SE0101322D0 (sv)	2001-04-12	2001-04-12	Astrazeneca Ab	Novel compounds
EP2172468A1 (fr)	2001-04-18	2010-04-07	Euro-Celtique S.A.	Composés de benzimidazolone
PT1385515E (pt)	2001-04-18	2008-09-15	Euro Celtique Sa	Compostos de espiropirazole
BR0209128A (pt) *	2001-04-18	2005-11-01	Euro Celtique Sa	Compostos, composições farmacêuticas, métodos para o tratamento de dores, métodos para a modulação de uma resposta farmacológica e usos de compostos
ES2322158T3 (es) *	2001-04-18	2009-06-17	Euro-Celtique S.A.	Derivados 1-(4-piperidinil)-1,3-dihidro-2h-indol-2-ona y compuestos afines como analogos de la nociceptina y ligandos del orl-1 para el tratamiento del dolor.
US6828440B2 (en)	2001-04-18	2004-12-07	Euro-Celtique, S.A.	Spiroindene and spiroindane compounds
US20030040479A1 (en) *	2001-07-02	2003-02-27	Omeros Corporation	Rotational intrathecal analgesia method and device
EP1406629A1 (fr) *	2001-07-02	2004-04-14	Omeros Corporation	Procede visant a induire une analgesie, qui comprend l'administration alternee d'un agoniste de recepteur d'opioides et d'un agoniste de recepteur 1 du type recepteur d'opioides, et pompe a perfusion implantable
SE0102716D0 (sv) *	2001-08-14	2001-08-14	Astrazeneca Ab	Novel compounds
SE0103818D0 (sv) *	2001-11-15	2001-11-15	Astrazeneca Ab	Chemical compounds
WO2003049736A1 (fr) *	2001-12-11	2003-06-19	Sepracor, Inc.	Piperidines 4-substitues, et methodes d'utilisation
WO2003082333A1 (fr)	2002-03-29	2003-10-09	Mitsubishi Pharma Corporation	Remede contre les troubles du sommeil
GB0221828D0 (en)	2002-09-20	2002-10-30	Astrazeneca Ab	Novel compound
GB0221829D0 (en) *	2002-09-20	2002-10-30	Astrazeneca Ab	Novel compound
DE10252665A1 (de) *	2002-11-11	2004-06-03	Grünenthal GmbH	4-Aminomethyl-1-aryl-cyclohexylamin-Derivate
DE10252666A1 (de) *	2002-11-11	2004-08-05	Grünenthal GmbH	N-Piperidyl-cyclohexan-Derivate
SE0301369D0 (sv)	2003-05-09	2003-05-09	Astrazeneca Ab	Chemical compounds
GB0315203D0 (en) *	2003-06-28	2003-08-06	Celltech R&D Ltd	Chemical compounds
US8067603B2 (en)	2003-09-25	2011-11-29	Solvay Pharmaceuticals B.V.	Benzimidazolone and quinazolinone derivatives as agonists on human ORL1 receptors
GB0328243D0 (en)	2003-12-05	2004-01-07	Astrazeneca Ab	Methods
WO2005060947A2 (fr) *	2003-12-19	2005-07-07	Sri International	Ligands agonistes et antagonistes du recepteur de la nociceptine
WO2006038738A1 (fr) *	2004-10-08	2006-04-13	Takeda Pharmaceutical Company Limited	Agent de régulation du fonctionnement d'un récepteur
ATE488235T1 (de)	2005-01-11	2010-12-15	Neurosearch As	Neue 2-amino-benzimidazolderivate und ihre verwendung als modulatoren calciumaktivierter kaliumkanäle mit geringer leitfähigkeit
CA2654666A1 (fr) *	2006-07-03	2008-01-10	Neurosearch A/S	Compositions pharmaceutiques
NZ578078A (en)	2007-01-16	2011-11-25	Purdue Pharma Lp	Heterocyclic-substituted piperidine as orl-1 ligands
MX379353B (es)	2007-08-31	2025-03-10	Purdue Pharmal P	Compuesto de piperidina tipo quinoxalina sustituida y uso de los mismos.
US8119661B2 (en) *	2007-09-11	2012-02-21	Astrazeneca Ab	Piperidine derivatives and their use as muscarinic receptor modulators
MY153948A (en)	2008-07-21	2015-04-15	Purdue Pharma Lp	Substituted-quinoxaline-type bridged-piperidine compounds and the uses thereof
KR20130108543A (ko)	2010-08-05	2013-10-04	암젠 인코포레이션	역형성 림프종 키나제를 억제하는 벤즈이미다졸 및 아자벤즈이미다졸 화합물
WO2013103598A2 (fr)	2012-01-06	2013-07-11	Novus International Inc.	Agents tensio-actifs à base de sulfoxyde
EP2812372B1 (fr)	2012-02-09	2018-09-26	Novus International Inc.	Hétéroatomes contenant des dimères cycliques
JO3300B1 (ar)	2012-06-06	2018-09-16	Novartis Ag	مركبات وتركيبات لتعديل نشاط egfr
US9452143B2 (en)	2012-07-12	2016-09-27	Novus International, Inc.	Matrix and layer compositions for protection of bioactives
US9085561B2 (en) *	2012-07-30	2015-07-21	Purdue Pharma L.P.	Cyclic urea- or lactam-substituted quinoxaline-type piperidines as ORL-1 modulators
WO2014102594A2 (fr) *	2012-12-27	2014-07-03	Purdue Pharma L.P.	Composés de pipéridine de type benzimidazole substitué et leurs utilisations
EP2976077A4 (fr)	2013-03-22	2016-11-30	Scripps Research Inst	Benzimidazoles substitués en tant que modulateurs d'un récepteur de nociceptine
SG11201607706SA (en) *	2014-03-20	2016-10-28	Capella Therapeutics Inc	Benzimidazole derivatives as erbb tyrosine kinase inhibitors for the treatment of cancer
CN112707851A (zh)	2015-11-12	2021-04-27	诺华丝国际股份有限公司	作为溶剂的含硫化合物
US10584306B2 (en)	2017-08-11	2020-03-10	Board Of Regents Of The University Of Oklahoma	Surfactant microemulsions

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3318900A (en) *	1964-05-06	1967-05-09	Janssen Pharmaceutica Nv	Derivatives of benzimidazolinyl piperidine
JPS5297978A (en) *	1976-06-02	1977-08-17	Yoshitomi Pharmaceut Ind Ltd	Preparation of alicyclic derivatives
US5821219A (en)	1995-08-11	1998-10-13	Oregon Health Sciences University	Opioid antagonists and methods of their use
ATE233812T1 (de)	1995-08-15	2003-03-15	Euroscreen Sa	Peptide mit pronociceptiveigenschaften
US5866346A (en)	1995-09-27	1999-02-02	Indiana Unversity Foundation	Methods of using dynorphins as ligands for XOR1 receptor
EP0898568B1 (fr) *	1996-04-19	2006-10-04	Neurosearch A/S	1-(4-piperidyl)-benzimidazoles presentant une activite neurotrophique
EP0813065A3 (fr)	1996-06-13	1998-07-22	F. Hoffmann-La Roche Ag	Modulation de la fonction d'un récepteur LC-132(analogue à opioide)
EP0829481A1 (fr) *	1996-09-16	1998-03-18	Pfizer Inc.	Dérivés de l'acide morphinane hydroxamique
US5718912A (en) *	1996-10-28	1998-02-17	Merck & Co., Inc.	Muscarine agonists
ATE276242T1 (de)	1997-05-30	2004-10-15	Banyu Pharma Co Ltd	2-oxoimidazol-derivate
WO1999003880A1 (fr)	1997-07-15	1999-01-28	Novo Nordisk A/S	Analogues de nociceptine
US5929035A (en)	1998-04-14	1999-07-27	Regents Of The University Of Michigan	Methods of treating intestinal disorders
ID29137A (id)	1998-07-27	2001-08-02	Schering Corp	Ligan-ligan afinitas tinggi untuk reseptor nosiseptin orl-1

1999
- 1999-06-25 MA MA25646A patent/MA26659A1/fr unknown
- 1999-06-28 TW TW088110899A patent/TW513424B/zh not_active IP Right Cessation
- 1999-07-05 IL IL14102999A patent/IL141029A0/xx unknown
- 1999-07-05 NZ NZ509299A patent/NZ509299A/en not_active Application Discontinuation
- 1999-07-05 CN CN99810857A patent/CN1317968A/zh active Pending
- 1999-07-05 HK HK02101444.8A patent/HK1040188A1/zh unknown
- 1999-07-05 ID IDW20010284D patent/ID27212A/id unknown
- 1999-07-05 AU AU43859/99A patent/AU749166B2/en not_active Ceased
- 1999-07-05 CA CA002339621A patent/CA2339621C/fr not_active Expired - Fee Related
- 1999-07-05 SI SI9930151T patent/SI1102762T1/xx unknown
- 1999-07-05 AP APAP/P/2001/002063A patent/AP2001002063A0/en unknown
- 1999-07-05 GE GEAP19995740A patent/GEP20033000B/en unknown
- 1999-07-05 TR TR2001/00403T patent/TR200100403T2/xx unknown
- 1999-07-05 BR BR9912778-4A patent/BR9912778A/pt not_active Application Discontinuation
- 1999-07-05 DK DK99926688T patent/DK1102762T3/da active
- 1999-07-05 WO PCT/IB1999/001239 patent/WO2000008013A2/fr not_active Ceased
- 1999-07-05 EE EEP200100075A patent/EE200100075A/xx unknown
- 1999-07-05 PL PL99346211A patent/PL346211A1/xx not_active Application Discontinuation
- 1999-07-05 OA OA1200100031A patent/OA11590A/en unknown
- 1999-07-05 YU YU8201A patent/YU8201A/sh unknown
- 1999-07-05 SK SK160-2001A patent/SK1602001A3/sk unknown
- 1999-07-05 HU HU0103567A patent/HUP0103567A3/hu unknown
- 1999-07-05 CZ CZ2001397A patent/CZ2001397A3/cs unknown
- 1999-07-05 HN HN1999000105A patent/HN1999000105A/es unknown
- 1999-07-05 AT AT99926688T patent/ATE227716T1/de not_active IP Right Cessation
- 1999-07-05 EP EP99926688A patent/EP1102762B1/fr not_active Expired - Lifetime
- 1999-07-05 DE DE69903953T patent/DE69903953T2/de not_active Expired - Fee Related
- 1999-07-05 PT PT99926688T patent/PT1102762E/pt unknown
- 1999-07-05 TN TNTNSN99142A patent/TNSN99142A1/fr unknown
- 1999-07-05 ES ES99926688T patent/ES2185357T3/es not_active Expired - Lifetime
- 1999-07-05 HR HR970081A patent/HRP20010089B1/xx not_active IP Right Cessation
- 1999-07-05 EA EA200100104A patent/EA200100104A1/ru unknown
- 1999-07-05 JP JP2000563646A patent/JP3367945B2/ja not_active Expired - Fee Related
- 1999-07-06 AR ARP990103264A patent/AR018686A1/es active IP Right Grant
- 1999-07-15 PE PE1999000717A patent/PE20000868A1/es not_active Application Discontinuation
- 1999-07-16 PA PA19998477701A patent/PA8477701A1/es unknown
- 1999-07-16 SV SV1999000099A patent/SV1999000099A/es not_active Application Discontinuation
- 1999-08-05 US US09/369,208 patent/US6172067B1/en not_active Expired - Fee Related
- 1999-08-06 GT GT199900125A patent/GT199900125A/es unknown
- 1999-08-13 UY UY25659A patent/UY25659A1/es not_active Application Discontinuation
2001
- 2001-01-16 IS IS5812A patent/IS5812A/is unknown
- 2001-02-01 ZA ZA200100900A patent/ZA200100900B/xx unknown
- 2001-02-05 NO NO20010603A patent/NO20010603L/no not_active Application Discontinuation
- 2001-03-01 BG BG105301A patent/BG105301A/xx unknown

Also Published As

Publication number	Publication date
EP1102762A2 (fr)	2001-05-30
CN1317968A (zh)	2001-10-17
EA200100104A1 (ru)	2001-08-27
JP3367945B2 (ja)	2003-01-20
HUP0103567A3 (en)	2003-01-28
AU4385999A (en)	2000-02-28
JP2002522431A (ja)	2002-07-23
OA11590A (en)	2004-08-18
HRP20010089A2 (en)	2002-02-28
SV1999000099A (es)	2000-09-05
AU749166B2 (en)	2002-06-20
BR9912778A (pt)	2001-09-25
AR018686A1 (es)	2001-11-28
HRP20010089B1 (en)	2003-04-30
UY25659A1 (es)	2000-02-23
MA26659A1 (fr)	2004-12-20
NO20010603D0 (no)	2001-02-05
TW513424B (en)	2002-12-11
AP2001002063A0 (en)	2001-03-31
US6172067B1 (en)	2001-01-09
DE69903953D1 (de)	2002-12-19
CA2339621A1 (fr)	2000-02-17
PT1102762E (pt)	2003-02-28
PL346211A1 (en)	2002-01-28
EE200100075A (et)	2002-06-17
ATE227716T1 (de)	2002-11-15
NZ509299A (en)	2003-05-30
GT199900125A (es)	2001-01-27
ZA200100900B (en)	2002-08-28
PE20000868A1 (es)	2000-08-31
ID27212A (id)	2001-03-08
WO2000008013A2 (fr)	2000-02-17
NO20010603L (no)	2001-04-05
CA2339621C (fr)	2005-04-05
TNSN99142A1 (fr)	2005-11-10
IL141029A0 (en)	2002-02-10
PA8477701A1 (es)	2000-09-29
WO2000008013A3 (fr)	2000-03-23
DE69903953T2 (de)	2003-03-27
ES2185357T3 (es)	2003-04-16
YU8201A (sh)	2003-07-07
GEP20033000B (en)	2003-06-25
SI1102762T1 (en)	2003-04-30
HN1999000105A (es)	2000-11-11
CZ2001397A3 (cs)	2002-05-15
TR200100403T2 (tr)	2001-07-23
BG105301A (en)	2001-12-29
HUP0103567A2 (hu)	2002-02-28
DK1102762T3 (da)	2002-12-16
EP1102762B1 (fr)	2002-11-13
IS5812A (is)	2001-01-16
HK1040188A1 (zh)	2002-05-31

Publication	Publication Date	Title
SK1602001A3 (en)	2002-09-10	2-substituted-1-piperidyl benzimidazole compounds, process and intermediates for producing thereof, pharmaceutical compositions and use
US6423725B1 (en)	2002-07-23	4-(2-keto-1-benzimidazolinyl)piperidine compounds as ORL1-receptor agonists
JP3276111B2 (ja)	2002-04-22	Ｏｒｌ１−レセプターアゴニストとしての２−ベンズイミダゾリルアミン化合物
US6294555B1 (en)	2001-09-25	1-[(1-Substituted-4-piperidinyl)methyl]-4-piperidine derivative, process for producing the same, medicinal compositions containing the same and intermediates of these compounds
EP1499596B1 (fr)	2008-11-05	Antagonistes muscariniques
WO2000009506A1 (fr)	2000-02-24	Derives de 1h-imidazopyridine
CA2330092C (fr)	2005-03-22	Composes de benzimidazole utilises comme agonistes du recepteur orl1
CN101903342B (zh)	2012-11-21	取代的n-苯基-吡咯烷基甲基吡咯烷酰胺及其作为组胺h3受体调节剂的治疗用途
CA2444595A1 (fr)	2002-10-31	Derives de benzimidazolone
JPWO2002040019A1 (ja)	2004-03-18	ベンズイミダゾール誘導体
IL161699A (en)	2012-12-31	Piperidine derivatives, process for their preparation, pharmaceutical compositions comprising them and uses thereof in the manufacture of medicaments
WO2007111227A1 (fr)	2007-10-04	Compose d'acylaminopiperidine
JP2007055940A (ja)	2007-03-08	ピラゾロピリミジン誘導体
US6465478B1 (en)	2002-10-15	1,3,8-Triuazaspiro(4,5)decanone compounds as ORL1-receptor agonists
US20030109549A1 (en)	2003-06-12	2-Substituted-1-piperidyl benzimidazole compounds as ORL1-receptor agonists
EP2464646B1 (fr)	2014-05-07	Procédé pour la préparation d'inhibiteurs de la cathepsine s
MXPA00007051A (en)	2001-07-03	4-(2-keto-1-benzimidazolinyl)piperidine compounds as orl1-receptor agonists
WO2000031061A1 (fr)	2000-06-02	Derives de 2-oxo-imidazole
JPWO2006080519A1 (ja)	2008-06-19	ジアミン誘導体
MXPA01001331A (en)	2003-02-17	2-substituted-1-piperidyl benzimidazole compounds as orl1-receptor agonists
MXPA01000116A (en)	2002-06-05	Benzimidazole compounds as orl1-receptor agonists
HK1139678A (en)	2010-09-24	4-alkoxypyridazine derivatives as fast dissociating dopamine 2 receptor antagonists