ZA200308103B - Spiropyrazole compounds. - Google Patents

Spiropyrazole compounds. Download PDF

Info

Publication number: ZA200308103B
Authority: ZA; South Africa
Prior art keywords: alkyl; group; compound; phenyl; cycloalkyl
Prior art date: 2001-04-18

Application number

ZA200308103A

Other languages

English (en)

Inventor

R Richard Goehring

Kyle Donald Lee Gary

Parviz Gharagozloo

Sam Victory

Original Assignee

Euro Celtique Sa

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.)

2001-04-18

Filing date

2003-10-17

Publication date

2004-10-18

2003-10-17 Application filed by Euro Celtique Sa filed Critical Euro Celtique Sa

2004-10-18 Publication of ZA200308103B publication Critical patent/ZA200308103B/en

Links

150000001875 compounds Chemical class 0.000 title claims description 101
125000000217 alkyl group Chemical group 0.000 claims description 106
-1 aminocarbonyl- Chemical group 0.000 claims description 100
125000000753 cycloalkyl group Chemical group 0.000 claims description 48
229910052739 hydrogen Inorganic materials 0.000 claims description 39
229910052736 halogen Inorganic materials 0.000 claims description 34
125000001424 substituent group Chemical group 0.000 claims description 34
MKJDUHZPLQYUCB-UHFFFAOYSA-N decan-4-one Chemical compound CCCCCCC(=O)CCC MKJDUHZPLQYUCB-UHFFFAOYSA-N 0.000 claims description 33
125000003545 alkoxy group Chemical group 0.000 claims description 31
229910052799 carbon Inorganic materials 0.000 claims description 30
125000003118 aryl group Chemical group 0.000 claims description 28
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 28
239000001257 hydrogen Substances 0.000 claims description 27
238000000034 method Methods 0.000 claims description 27
150000002367 halogens Chemical class 0.000 claims description 26
108020003175 receptors Proteins 0.000 claims description 25
102000005962 receptors Human genes 0.000 claims description 25
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
125000001072 heteroaryl group Chemical group 0.000 claims description 21
150000002431 hydrogen Chemical group 0.000 claims description 20
208000002193 Pain Diseases 0.000 claims description 17
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 16
125000004093 cyano group Chemical group *C#N 0.000 claims description 16
239000003814 drug Substances 0.000 claims description 16
125000005843 halogen group Chemical group 0.000 claims description 16
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 16
125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
230000004044 response Effects 0.000 claims description 15
108010020615 nociceptin receptor Proteins 0.000 claims description 13
230000000144 pharmacologic effect Effects 0.000 claims description 13
125000002619 bicyclic group Chemical group 0.000 claims description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
108090000137 Opioid Receptors Proteins 0.000 claims description 11
102000003840 Opioid Receptors Human genes 0.000 claims description 10
125000003282 alkyl amino group Chemical group 0.000 claims description 10
125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000003342 alkenyl group Chemical group 0.000 claims description 9
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 9
125000002950 monocyclic group Chemical group 0.000 claims description 9
230000036407 pain Effects 0.000 claims description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
125000004043 oxo group Chemical group O=* 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
125000006310 cycloalkyl amino group Chemical group 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
239000000546 pharmaceutical excipient Substances 0.000 claims description 6
239000012453 solvate Substances 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
125000001624 naphthyl group Chemical group 0.000 claims description 5
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 3
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 3
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
125000004442 acylamino group Chemical group 0.000 claims description 2
125000004945 acylaminoalkyl group Chemical group 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
150000001408 amides Chemical class 0.000 claims description 2
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 9
230000000202 analgesic effect Effects 0.000 claims 6
239000008194 pharmaceutical composition Substances 0.000 claims 6
239000000203 mixture Substances 0.000 description 14
239000000556 agonist Substances 0.000 description 7
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239000006186 oral dosage form Substances 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 6
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 6
208000000094 Chronic Pain Diseases 0.000 description 5
238000009472 formulation Methods 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000003826 tablet Substances 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 4
238000013270 controlled release Methods 0.000 description 4
XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
125000005842 heteroatom Chemical group 0.000 description 4
OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
125000004430 oxygen atom Chemical group O* 0.000 description 4
239000000047 product Substances 0.000 description 4
125000004434 sulfur atom Chemical group 0.000 description 4
239000000725 suspension Substances 0.000 description 4
238000013268 sustained release Methods 0.000 description 4
239000012730 sustained-release form Substances 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
208000005298 acute pain Diseases 0.000 description 3
239000001961 anticonvulsive agent Substances 0.000 description 3
230000001684 chronic effect Effects 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
239000006274 endogenous ligand Substances 0.000 description 3
239000003446 ligand Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
229960005181 morphine Drugs 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
239000000243 solution Substances 0.000 description 3
239000011593 sulfur Substances 0.000 description 3
239000000375 suspending agent Substances 0.000 description 3
TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 description 2
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
KTDZCOWXCWUPEO-UHFFFAOYSA-N NS-398 Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1CCCCC1 KTDZCOWXCWUPEO-UHFFFAOYSA-N 0.000 description 2
DEXMFYZAHXMZNM-UHFFFAOYSA-N Narceine Chemical compound OC(=O)C1=C(OC)C(OC)=CC=C1C(=O)CC1=C(CCN(C)C)C=C(OCO2)C2=C1OC DEXMFYZAHXMZNM-UHFFFAOYSA-N 0.000 description 2
229940127450 Opioid Agonists Drugs 0.000 description 2
BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 2
UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 2
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
239000000730 antalgic agent Substances 0.000 description 2
229940125681 anticonvulsant agent Drugs 0.000 description 2
239000000935 antidepressant agent Substances 0.000 description 2
229940005513 antidepressants Drugs 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
229910052792 caesium Inorganic materials 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
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239000003086 colorant Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 2
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125000001183 hydrocarbyl group Chemical group 0.000 description 2
LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 2
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CXJONBHNIJFARE-UHFFFAOYSA-N n-[6-(2,4-difluorophenoxy)-1-oxo-2,3-dihydroinden-5-yl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=2CCC(=O)C=2C=C1OC1=CC=C(F)C=C1F CXJONBHNIJFARE-UHFFFAOYSA-N 0.000 description 2
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VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
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UVITTYOJFDLOGI-UHFFFAOYSA-N (1,2,5-trimethyl-4-phenylpiperidin-4-yl) propanoate Chemical compound C=1C=CC=CC=1C1(OC(=O)CC)CC(C)N(C)CC1C UVITTYOJFDLOGI-UHFFFAOYSA-N 0.000 description 1
LGFMXOTUSSVQJV-NEYUFSEYSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;(4r,4ar,7s,7ar,12bs)-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol;1-[(3,4-dimethoxyphenyl)methyl]-6 Chemical compound Cl.Cl.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 LGFMXOTUSSVQJV-NEYUFSEYSA-N 0.000 description 1
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125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
125000006017 1-propenyl group Chemical group 0.000 description 1
OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 1
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125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
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IYNWSQDZXMGGGI-NUEKZKHPSA-N 3-hydroxymorphinan Chemical compound C1CCC[C@H]2[C@H]3CC4=CC=C(O)C=C4[C@]21CCN3 IYNWSQDZXMGGGI-NUEKZKHPSA-N 0.000 description 1
125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
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VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
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KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
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VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
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229960004270 nabumetone Drugs 0.000 description 1
229960000805 nalbuphine Drugs 0.000 description 1
NETZHAKZCGBWSS-CEDHKZHLSA-N nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 description 1
229960000938 nalorphine Drugs 0.000 description 1
239000004090 neuroprotective agent Substances 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
HNDXBGYRMHRUFN-CIVUWBIHSA-N nicomorphine Chemical compound O([C@H]1C=C[C@H]2[C@H]3CC=4C5=C(C(=CC=4)OC(=O)C=4C=NC=CC=4)O[C@@H]1[C@]52CCN3C)C(=O)C1=CC=CN=C1 HNDXBGYRMHRUFN-CIVUWBIHSA-N 0.000 description 1
229960004300 nicomorphine Drugs 0.000 description 1
HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 description 1
229960000965 nimesulide Drugs 0.000 description 1
229940121367 non-opioid analgesics Drugs 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 description 1
229950011519 norlevorphanol Drugs 0.000 description 1
WCJFBSYALHQBSK-UHFFFAOYSA-N normethadone Chemical compound C=1C=CC=CC=1C(CCN(C)C)(C(=O)CC)C1=CC=CC=C1 WCJFBSYALHQBSK-UHFFFAOYSA-N 0.000 description 1
229960004013 normethadone Drugs 0.000 description 1
229950006134 normorphine Drugs 0.000 description 1
WCDSHELZWCOTMI-UHFFFAOYSA-N norpipanone Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)CC)CCN1CCCCC1 WCDSHELZWCOTMI-UHFFFAOYSA-N 0.000 description 1
229950007418 norpipanone Drugs 0.000 description 1
125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
229940127240 opiate Drugs 0.000 description 1
239000003399 opiate peptide Substances 0.000 description 1
239000000014 opioid analgesic Substances 0.000 description 1
229940005483 opioid analgesics Drugs 0.000 description 1
229960001027 opium Drugs 0.000 description 1
239000007935 oral tablet Substances 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
229960003294 papaveretum Drugs 0.000 description 1
VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
229960005301 pentazocine Drugs 0.000 description 1
229960000482 pethidine Drugs 0.000 description 1
LOXCOAXRHYDLOW-UHFFFAOYSA-N phenadoxone Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)CC)CC(C)N1CCOCC1 LOXCOAXRHYDLOW-UHFFFAOYSA-N 0.000 description 1
229950004540 phenadoxone Drugs 0.000 description 1
ZQHYKVKNPWDQSL-KNXBSLHKSA-N phenazocine Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@@H]2[C@@H]1C)CN2CCC1=CC=CC=C1 ZQHYKVKNPWDQSL-KNXBSLHKSA-N 0.000 description 1
229960000897 phenazocine Drugs 0.000 description 1
CFBQYWXPZVQQTN-QPTUXGOLSA-N phenomorphan Chemical compound C([C@]12CCCC[C@H]1[C@H]1CC3=CC=C(C=C32)O)CN1CCC1=CC=CC=C1 CFBQYWXPZVQQTN-QPTUXGOLSA-N 0.000 description 1
229950011496 phenomorphan Drugs 0.000 description 1
IPOPQVVNCFQFRK-UHFFFAOYSA-N phenoperidine Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC(O)C1=CC=CC=C1 IPOPQVVNCFQFRK-UHFFFAOYSA-N 0.000 description 1
229960004315 phenoperidine Drugs 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
PXXKIYPSXYFATG-UHFFFAOYSA-N piminodine Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCCNC1=CC=CC=C1 PXXKIYPSXYFATG-UHFFFAOYSA-N 0.000 description 1
229950006445 piminodine Drugs 0.000 description 1
IHEHEFLXQFOQJO-UHFFFAOYSA-N piritramide Chemical compound C1CC(C(=O)N)(N2CCCCC2)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 IHEHEFLXQFOQJO-UHFFFAOYSA-N 0.000 description 1
229960001286 piritramide Drugs 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
ZXWAUWBYASJEOE-UHFFFAOYSA-N proheptazine Chemical compound C=1C=CC=CC=1C1(OC(=O)CC)CCCN(C)CC1C ZXWAUWBYASJEOE-UHFFFAOYSA-N 0.000 description 1
229950010387 proheptazine Drugs 0.000 description 1
XJKQCILVUHXVIQ-UHFFFAOYSA-N properidine Chemical compound C=1C=CC=CC=1C1(C(=O)OC(C)C)CCN(C)CC1 XJKQCILVUHXVIQ-UHFFFAOYSA-N 0.000 description 1
229950004345 properidine Drugs 0.000 description 1
ZBAFFZBKCMWUHM-UHFFFAOYSA-N propiram Chemical compound C=1C=CC=NC=1N(C(=O)CC)C(C)CN1CCCCC1 ZBAFFZBKCMWUHM-UHFFFAOYSA-N 0.000 description 1
229950003779 propiram Drugs 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical compound C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 description 1
229960004739 sufentanil Drugs 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229960001402 tilidine Drugs 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Dental Preparations (AREA)
Solid-Sorbent Or Filter-Aiding Compositions (AREA)

ZA200308103A 2001-04-18 2003-10-17 Spiropyrazole compounds. ZA200308103B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US28467501P	2001-04-18	2001-04-18

Publications (1)

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ZA200308103B true ZA200308103B (en)	2004-10-18

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Application Number	Title	Priority Date	Filing Date
ZA200308103A ZA200308103B (en)	2001-04-18	2003-10-17	Spiropyrazole compounds.

Country Status (28)

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US (2)	US6635653B2 (de)
EP (1)	EP1385515B1 (de)
JP (1)	JP4342181B2 (de)
KR (1)	KR100628292B1 (de)
CN (1)	CN1516584A (de)
AT (1)	ATE403429T1 (de)
AU (1)	AU2002311833B2 (de)
BR (1)	BR0209127A (de)
CA (1)	CA2444634C (de)
CY (1)	CY1108454T1 (de)
CZ (1)	CZ20032849A3 (de)
DE (1)	DE60228071D1 (de)
DK (1)	DK1385515T3 (de)
ES (1)	ES2312584T3 (de)
HK (1)	HK1062885A1 (de)
HU (1)	HUP0401333A3 (de)
IL (2)	IL158485A0 (de)
MX (1)	MXPA03009604A (de)
NO (1)	NO20034660L (de)
NZ (1)	NZ528978A (de)
PL (1)	PL367263A1 (de)
PT (1)	PT1385515E (de)
RU (1)	RU2299883C2 (de)
SI (1)	SI1385515T1 (de)
UA (1)	UA74439C2 (de)
WO (1)	WO2002085355A1 (de)
YU (1)	YU82403A (de)
ZA (1)	ZA200308103B (de)

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2002
- 2002-04-18 AT AT02739163T patent/ATE403429T1/de active
- 2002-04-18 RU RU2003133455/04A patent/RU2299883C2/ru not_active IP Right Cessation
- 2002-04-18 MX MXPA03009604A patent/MXPA03009604A/es active IP Right Grant
- 2002-04-18 CA CA2444634A patent/CA2444634C/en not_active Expired - Fee Related
- 2002-04-18 EP EP02739163A patent/EP1385515B1/de not_active Expired - Lifetime
- 2002-04-18 ES ES02739163T patent/ES2312584T3/es not_active Expired - Lifetime
- 2002-04-18 CN CNA028121767A patent/CN1516584A/zh active Pending
- 2002-04-18 CZ CZ20032849A patent/CZ20032849A3/cs unknown
- 2002-04-18 KR KR1020037013821A patent/KR100628292B1/ko not_active IP Right Cessation
- 2002-04-18 US US10/126,506 patent/US6635653B2/en not_active Expired - Lifetime
- 2002-04-18 YU YU82403A patent/YU82403A/sh unknown
- 2002-04-18 PL PL02367263A patent/PL367263A1/xx not_active Application Discontinuation
- 2002-04-18 JP JP2002582928A patent/JP4342181B2/ja not_active Expired - Fee Related
- 2002-04-18 NZ NZ528978A patent/NZ528978A/en not_active IP Right Cessation
- 2002-04-18 DE DE60228071T patent/DE60228071D1/de not_active Expired - Lifetime
- 2002-04-18 AU AU2002311833A patent/AU2002311833B2/en not_active Ceased
- 2002-04-18 UA UA20031110381A patent/UA74439C2/uk unknown
- 2002-04-18 HU HU0401333A patent/HUP0401333A3/hu unknown
- 2002-04-18 WO PCT/US2002/012376 patent/WO2002085355A1/en not_active Application Discontinuation
- 2002-04-18 SI SI200230748T patent/SI1385515T1/sl unknown
- 2002-04-18 IL IL15848502A patent/IL158485A0/xx unknown
- 2002-04-18 BR BRPI0209127-5A patent/BR0209127A/pt not_active Application Discontinuation
- 2002-04-18 PT PT02739163T patent/PT1385515E/pt unknown
- 2002-04-18 DK DK02739163T patent/DK1385515T3/da active
2003
- 2003-06-19 US US10/601,174 patent/US20040087641A1/en not_active Abandoned
- 2003-10-17 NO NO20034660A patent/NO20034660L/no not_active Application Discontinuation
- 2003-10-17 ZA ZA200308103A patent/ZA200308103B/en unknown
- 2003-10-19 IL IL158485A patent/IL158485A/en not_active IP Right Cessation
2004
- 2004-08-03 HK HK04105726.6A patent/HK1062885A1/xx not_active IP Right Cessation
2008
- 2008-10-27 CY CY20081101206T patent/CY1108454T1/el unknown

Also Published As

Publication number	Publication date
KR100628292B1 (ko)	2006-09-27
CY1108454T1 (el)	2014-04-09
CZ20032849A3 (en)	2004-03-17
ES2312584T3 (es)	2009-03-01
NO20034660L (no)	2003-12-17
IL158485A (en)	2009-09-01
PT1385515E (pt)	2008-09-15
KR20040008159A (ko)	2004-01-28
DK1385515T3 (da)	2008-10-27
DE60228071D1 (de)	2008-09-18
US20030027834A1 (en)	2003-02-06
YU82403A (sh)	2006-08-17
SI1385515T1 (sl)	2008-12-31
PL367263A1 (en)	2005-02-21
EP1385515A4 (de)	2004-06-30
MXPA03009604A (es)	2004-04-02
NZ528978A (en)	2004-06-25
US6635653B2 (en)	2003-10-21
UA74439C2 (uk)	2005-12-15
US20040087641A1 (en)	2004-05-06
CA2444634C (en)	2011-06-07
NO20034660D0 (no)	2003-10-17
WO2002085355A1 (en)	2002-10-31
CA2444634A1 (en)	2002-10-31
HUP0401333A3 (en)	2004-11-29
CN1516584A (zh)	2004-07-28
RU2299883C2 (ru)	2007-05-27
BR0209127A (pt)	2006-03-21
JP4342181B2 (ja)	2009-10-14
IL158485A0 (en)	2004-05-12
ATE403429T1 (de)	2008-08-15
HUP0401333A2 (hu)	2004-10-28
RU2003133455A (ru)	2005-05-10
HK1062885A1 (en)	2004-12-03
AU2002311833B2 (en)	2005-04-28
EP1385515A1 (de)	2004-02-04
JP2004531531A (ja)	2004-10-14
EP1385515B1 (de)	2008-08-06

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