CA2078578C - Medical use for tachykinin antagonists - Google Patents

Medical use for tachykinin antagonists Download PDF

Info

Publication number: CA2078578C
Authority: CA; Canada
Prior art keywords: alkyl; phenyl; carbon atoms; optionally; substituted
Prior art date: 1991-09-20
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

CA002078578A

Other languages

English (en)

French (fr)

Other versions

CA2078578A1 (en

Inventor

Russell M. Hagan

Keith T. Bunce

Alan Naylor

Mark Ladlow

Andrew B. Mcelroy

Andrew R. Whittington

Barry A. Coomber

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Glaxo Group Ltd

Original Assignee

Glaxo Group Ltd

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.)

1991-09-20

Filing date

1992-09-18

Publication date

2002-02-05

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27265859&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2078578(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1991-09-20 Priority claimed from GB919120172A external-priority patent/GB9120172D0/en

1992-02-11 Priority claimed from GB929202839A external-priority patent/GB9202839D0/en

1992-02-27 Priority claimed from GB929204151A external-priority patent/GB9204151D0/en

1992-09-18 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1993-03-21 Publication of CA2078578A1 publication Critical patent/CA2078578A1/en

2002-02-05 Application granted granted Critical

2002-02-05 Publication of CA2078578C publication Critical patent/CA2078578C/en

2012-09-18 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

102000003141 Tachykinin Human genes 0.000 title claims abstract description 34
108060008037 tachykinin Proteins 0.000 title claims abstract description 34
239000005557 antagonist Substances 0.000 title abstract description 40
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 51
239000001257 hydrogen Substances 0.000 claims abstract description 50
-1 2-pyridinyl Chemical group 0.000 claims abstract description 49
206010047700 Vomiting Diseases 0.000 claims abstract description 40
150000003839 salts Chemical class 0.000 claims abstract description 40
238000011282 treatment Methods 0.000 claims abstract description 33
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 32
125000005843 halogen group Chemical group 0.000 claims abstract description 30
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
239000012453 solvate Substances 0.000 claims abstract description 13
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 11
238000002360 preparation method Methods 0.000 claims abstract description 11
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 10
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract 2
150000001875 compounds Chemical class 0.000 claims description 98
125000000217 alkyl group Chemical group 0.000 claims description 77
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
125000004432 carbon atom Chemical group C* 0.000 claims description 62
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 55
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
125000001424 substituent group Chemical group 0.000 claims description 35
125000003545 alkoxy group Chemical group 0.000 claims description 34
125000001544 thienyl group Chemical group 0.000 claims description 34
125000004076 pyridyl group Chemical group 0.000 claims description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
125000003118 aryl group Chemical group 0.000 claims description 20
229910052760 oxygen Inorganic materials 0.000 claims description 20
125000002541 furyl group Chemical group 0.000 claims description 19
229910052717 sulfur Inorganic materials 0.000 claims description 19
125000000753 cycloalkyl group Chemical group 0.000 claims description 18
125000001624 naphthyl group Chemical group 0.000 claims description 18
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
239000001301 oxygen Substances 0.000 claims description 16
239000011593 sulfur Substances 0.000 claims description 16
125000001072 heteroaryl group Chemical group 0.000 claims description 15
229910052799 carbon Inorganic materials 0.000 claims description 14
239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 14
150000003254 radicals Chemical group 0.000 claims description 13
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
229910052757 nitrogen Inorganic materials 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 11
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 11
229960004316 cisplatin Drugs 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 11
125000001153 fluoro group Chemical group F* 0.000 claims description 11
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 10
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 10
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
229910052794 bromium Inorganic materials 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 9
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 9
229910052731 fluorine Inorganic materials 0.000 claims description 9
239000011737 fluorine Substances 0.000 claims description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
125000005493 quinolyl group Chemical group 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 8
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 8
125000001786 isothiazolyl group Chemical group 0.000 claims description 8
125000000842 isoxazolyl group Chemical group 0.000 claims description 8
125000002971 oxazolyl group Chemical group 0.000 claims description 8
125000003831 tetrazolyl group Chemical group 0.000 claims description 8
125000001425 triazolyl group Chemical group 0.000 claims description 8
125000001041 indolyl group Chemical group 0.000 claims description 7
125000000335 thiazolyl group Chemical group 0.000 claims description 7
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 6
239000004305 biphenyl Substances 0.000 claims description 6
235000010290 biphenyl Nutrition 0.000 claims description 6
125000004799 bromophenyl group Chemical group 0.000 claims description 6
125000000068 chlorophenyl group Chemical group 0.000 claims description 6
125000001207 fluorophenyl group Chemical group 0.000 claims description 6
206010025482 malaise Diseases 0.000 claims 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 claims description 6
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 6
125000000168 pyrrolyl group Chemical group 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 5
239000002462 tachykinin receptor antagonist Substances 0.000 claims description 5
DTQNEFOKTXXQKV-HKUYNNGSSA-N (2s,3s)-n-[(2-methoxyphenyl)methyl]-2-phenylpiperidin-3-amine Chemical group COC1=CC=CC=C1CN[C@@H]1[C@H](C=2C=CC=CC=2)NCCC1 DTQNEFOKTXXQKV-HKUYNNGSSA-N 0.000 claims description 4
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical group ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 4
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 4
208000019695 Migraine disease Diseases 0.000 claims description 4
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 4
RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
239000002246 antineoplastic agent Substances 0.000 claims description 4
125000002837 carbocyclic group Chemical group 0.000 claims description 4
150000001721 carbon Chemical group 0.000 claims description 4
229960004397 cyclophosphamide Drugs 0.000 claims description 4
230000001404 mediated effect Effects 0.000 claims description 4
206010027599 migraine Diseases 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
239000002464 receptor antagonist Substances 0.000 claims description 4
229940044551 receptor antagonist Drugs 0.000 claims description 4
230000002829 reductive effect Effects 0.000 claims description 4
239000003053 toxin Substances 0.000 claims description 4
231100000765 toxin Toxicity 0.000 claims description 4
108700012359 toxins Proteins 0.000 claims description 4
206010061974 Gastrointestinal obstruction Diseases 0.000 claims description 3
208000027601 Inner ear disease Diseases 0.000 claims description 3
241000534944 Thia Species 0.000 claims description 3
230000003247 decreasing effect Effects 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
230000005176 gastrointestinal motility Effects 0.000 claims description 3
229960005181 morphine Drugs 0.000 claims description 3
239000000014 opioid analgesic Substances 0.000 claims description 3
229940005483 opioid analgesics Drugs 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
231100000614 poison Toxicity 0.000 claims description 3
239000002574 poison Substances 0.000 claims description 3
230000002980 postoperative effect Effects 0.000 claims description 3
230000035935 pregnancy Effects 0.000 claims description 3
230000005855 radiation Effects 0.000 claims description 3
238000001959 radiotherapy Methods 0.000 claims description 3
229920006395 saturated elastomer Polymers 0.000 claims description 3
208000027491 vestibular disease Diseases 0.000 claims description 3
208000009935 visceral pain Diseases 0.000 claims description 3
FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 2
108010006654 Bleomycin Proteins 0.000 claims description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
244000284152 Carapichea ipecacuanha Species 0.000 claims description 2
DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 2
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 2
108010092160 Dactinomycin Proteins 0.000 claims description 2
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 2
206010028980 Neoplasm Diseases 0.000 claims description 2
101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 2
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 2
RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000005037 alkyl phenyl group Chemical group 0.000 claims description 2
125000005336 allyloxy group Chemical group 0.000 claims description 2
229960001561 bleomycin Drugs 0.000 claims description 2
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 2
201000011510 cancer Diseases 0.000 claims description 2
125000005518 carboxamido group Chemical group 0.000 claims description 2
125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
229960005243 carmustine Drugs 0.000 claims description 2
JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 2
ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims description 2
229960000684 cytarabine Drugs 0.000 claims description 2
229960003901 dacarbazine Drugs 0.000 claims description 2
229960000640 dactinomycin Drugs 0.000 claims description 2
229960004679 doxorubicin Drugs 0.000 claims description 2
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 2
229960005420 etoposide Drugs 0.000 claims description 2
229960002949 fluorouracil Drugs 0.000 claims description 2
125000004970 halomethyl group Chemical group 0.000 claims description 2
229960005208 ipecacuanha Drugs 0.000 claims description 2
229960002247 lomustine Drugs 0.000 claims description 2
229960000485 methotrexate Drugs 0.000 claims description 2
229960004857 mitomycin Drugs 0.000 claims description 2
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 2
125000005646 oximino group Chemical group 0.000 claims description 2
125000004043 oxo group Chemical group O=* 0.000 claims description 2
CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 2
229960000624 procarbazine Drugs 0.000 claims description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
150000003413 spiro compounds Chemical class 0.000 claims description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
229960003048 vinblastine Drugs 0.000 claims description 2
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 2
229960004528 vincristine Drugs 0.000 claims description 2
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 4
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
125000006528 (C2-C6) alkyl group Chemical group 0.000 claims 1
VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims 1
239000002742 neurokinin 1 receptor antagonist Substances 0.000 claims 1
238000000034 method Methods 0.000 abstract description 20
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XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
239000000203 mixture Substances 0.000 description 27
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
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239000000243 solution Substances 0.000 description 14
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CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Epidemiology (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Psychiatry (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Otolaryngology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Peptides Or Proteins (AREA)
Plural Heterocyclic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

CA002078578A 1991-09-20 1992-09-18 Medical use for tachykinin antagonists Expired - Lifetime CA2078578C (en)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
GBGB9120172.3		1991-09-20
GB919120172A GB9120172D0 (en)	1991-09-20	1991-09-20	Chemical compounds
GBGB9202839.8		1992-02-11
GB929202839A GB9202839D0 (en)	1992-02-11	1992-02-11	Chemical compounds
GBGB9204151.5		1992-02-27
GB929204151A GB9204151D0 (en)	1992-02-27	1992-02-27	Medicaments

Publications (2)

Publication Number	Publication Date
CA2078578A1 CA2078578A1 (en)	1993-03-21
CA2078578C true CA2078578C (en)	2002-02-05

Family

ID=27265859

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002078578A Expired - Lifetime CA2078578C (en)	1991-09-20	1992-09-18	Medical use for tachykinin antagonists

Country Status (14)

Country	Link
US (7)	US5360820A (2)
EP (4)	EP1082959A1 (2)
JP (1)	JP3020757B2 (2)
KR (1)	KR100233323B1 (2)
AT (1)	ATE195867T1 (2)
AU (1)	AU657996B2 (2)
CA (1)	CA2078578C (2)
DE (1)	DE69231395T3 (2)
DK (1)	DK0533280T4 (2)
ES (1)	ES2149767T5 (2)
GR (1)	GR3034682T3 (2)
IL (1)	IL103214A (2)
PT (1)	PT533280E (2)
TW (1)	TW311139B (2)

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AU657552B2 (en) *	1991-05-31	1995-03-16	Pfizer Inc.	Quinuclidine as substance P antagonists
EP1082959A1 (en)	1991-09-20	2001-03-14	Glaxo Group Limited	NK1 Antagonists for the treatment of depression
US5444074A (en) *	1992-04-15	1995-08-22	Merck Sharp & Dohme Limited	Piperidine tachykinin receptor antagonists
US5719147A (en) *	1992-06-29	1998-02-17	Merck & Co., Inc.	Morpholine and thiomorpholine tachykinin receptor antagonists
US6048859A (en)	1992-06-29	2000-04-11	Merck & Co., Inc.	Morpholine and thiomorpholine tachykinin receptor antagonists
US5637699A (en) *	1992-06-29	1997-06-10	Merck & Co., Inc.	Process for preparing morpholine tachykinin receptor antagonists
GB9216911D0 (en) *	1992-08-10	1992-09-23	Merck Sharp & Dohme	Therapeutic agents
US5837711A (en) *	1992-10-28	1998-11-17	Pfizer Inc.	Substituted quinuclidines as substance P antagonists
CA2149242C (en) *	1992-11-12	1998-08-04	Fumitaka Ito	Quinuclidine derivative for treatment of inflammatory and gastrointestinal disorders
FR2700472B1 (fr)	1993-01-19	1995-02-17	Rhone Poulenc Rorer Sa	Association synergisante ayant un effet antagoniste des récepteurs NK1 et NK2.
GB9305593D0 (en) *	1993-03-18	1993-05-05	Smithkline Beecham Plc	Pharmaceuticals
GB9305718D0 (en)	1993-03-19	1993-05-05	Glaxo Group Ltd	Medicaments
US5496833A (en) *	1993-04-13	1996-03-05	Merck Sharp & Dohme Limited	Piperidine tachykinin receptor antagonists
DE69404306T2 (de)	1993-05-28	1997-10-30	Pfizer	Verfahren zur herstellung und optischen auflösung von 2-phenyl-3-aminopiperidine
US5393762A (en) *	1993-06-04	1995-02-28	Pfizer Inc.	Pharmaceutical agents for treatment of emesis
FR2710842B1 (fr) *	1993-10-07	1995-11-24	Rhone Poulenc Rorer Sa	Nouvelle application thérapeutique de dérivés de perhydroisoindole.
EP0653208A3 (en) *	1993-11-17	1995-10-11	Pfizer	Substance P antagonists for the treatment or prevention of sunburn.
US5610165A (en) *	1994-02-17	1997-03-11	Merck & Co., Inc.	N-acylpiperidine tachykinin antagonists
IL112778A0 (en) *	1994-03-04	1995-05-26	Merck & Co Inc	Substituted heterocycles, their preparation and pharmaceutical compositions containing them
US5491140A (en) *	1994-06-30	1996-02-13	Eli Lilly And Company	Naphthyl tachykinin receptor antagonists to treat physiological conditions
MX9700271A (es)	1994-07-12	1997-05-31	Lilly Co Eli	Antagonistas heterociclicos del receptor de taquinicina.
WO1996014845A1 (en) *	1994-11-10	1996-05-23	Pfizer Inc.	Nk-1 receptor antagonists for the treatment of eye disorders
US5576317A (en) *	1994-12-09	1996-11-19	Pfizer Inc.	NK-1 receptor antagonists and 5HT3 receptor antagonists for the treatment of emesis
AU4467396A (en)	1994-12-12	1996-07-10	Omeros Medical Systems, Inc.	Irrigation solution and method for inhibition of pain, inflammation and spasm
EP2301562B1 (en) *	1994-12-12	2013-04-17	Omeros Corporation	Irrigation solution and method for inhibition of pain, inflammation and spasm
GB9426102D0 (en) *	1994-12-23	1995-02-22	Merck Sharp & Dohme	Pharmacuetical compositions
US5565568A (en) *	1995-04-06	1996-10-15	Eli Lilly And Company	2-acylaminopropanamides as tachykinin receptor antagonists
WO1996041633A1 (en) *	1995-06-08	1996-12-27	Eli Lilly And Company	Methods of treating cold and allergic rhinitis
AU5966096A (en) *	1995-06-09	1997-01-09	Eli Lilly And Company	Methods of treating cold and allergic rhinitis
GB9513972D0 (en) *	1995-07-08	1995-09-06	Merck Sharp & Dohme	Pharmaceutical compositions
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- 1992-09-16 EP EP99200338A patent/EP0919245A3/en not_active Withdrawn
- 1992-09-18 KR KR1019920017021A patent/KR100233323B1/ko not_active Expired - Lifetime
- 1992-09-18 JP JP4275091A patent/JP3020757B2/ja not_active Expired - Lifetime
- 1992-09-18 CA CA002078578A patent/CA2078578C/en not_active Expired - Lifetime
- 1992-09-18 IL IL10321492A patent/IL103214A/en not_active IP Right Cessation
- 1992-09-18 US US07/946,635 patent/US5360820A/en not_active Expired - Lifetime
- 1992-09-18 AU AU24583/92A patent/AU657996B2/en not_active Expired
- 1992-09-29 TW TW081107713A patent/TW311139B/zh not_active IP Right Cessation
1994
- 1994-06-30 US US08/269,079 patent/US5538982A/en not_active Expired - Lifetime
1995
- 1995-12-27 US US08/579,294 patent/US5798363A/en not_active Expired - Lifetime
1996
- 1996-09-03 US US08/706,836 patent/US6326383B1/en not_active Expired - Fee Related
1999
- 1999-05-14 US US09/311,570 patent/US6191139B1/en not_active Expired - Lifetime
2000
- 2000-10-26 GR GR20000402369T patent/GR3034682T3/el unknown
2001
- 2001-11-05 US US09/985,679 patent/US7214692B2/en not_active Expired - Fee Related
2004
- 2004-11-18 US US10/990,462 patent/US7342028B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
EP0916346A2 (en)	1999-05-19
IL103214A (en)	1999-03-12
DE69231395D1 (de)	2000-10-05
US6326383B1 (en)	2001-12-04
AU2458392A (en)	1993-03-25
EP0533280A1 (en)	1993-03-24
PT533280E (pt)	2001-01-31
JPH06107563A (ja)	1994-04-19
DE69231395T2 (de)	2001-02-01
US20020052351A1 (en)	2002-05-02
DK0533280T4 (da)	2005-02-28
EP0533280B1 (en)	2000-08-30
KR930017563A (ko)	1993-09-20
EP1082959A1 (en)	2001-03-14
KR100233323B1 (ko)	1999-12-01
GR3034682T3 (en)	2001-01-31
US7214692B2 (en)	2007-05-08
IL103214A0 (en)	1993-02-21
ES2149767T5 (es)	2005-06-16
US5360820A (en)	1994-11-01
US6191139B1 (en)	2001-02-20
TW311139B (2)	1997-07-21
DK0533280T3 (da)	2001-01-02
US7342028B2 (en)	2008-03-11
ES2149767T3 (es)	2000-11-16
AU657996B2 (en)	1995-03-30
ATE195867T1 (de)	2000-09-15
US5538982A (en)	1996-07-23
EP0533280B2 (en)	2004-12-01
US20050085414A1 (en)	2005-04-21
US5798363A (en)	1998-08-25
JP3020757B2 (ja)	2000-03-15
CA2078578A1 (en)	1993-03-21
EP0916346A3 (en)	2000-12-06
DE69231395T3 (de)	2005-07-21
EP0919245A2 (en)	1999-06-02
EP0919245A3 (en)	2000-11-15

Legal Events

Date	Code	Title	Description
1997-07-22	EEER	Examination request
2012-09-18	MKEX	Expiry

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