CZ301323B6 - Chinuklidinkarbamátové deriváty a lécivé kompozice je obsahující - Google Patents
Chinuklidinkarbamátové deriváty a lécivé kompozice je obsahující Download PDFInfo
- Publication number
- CZ301323B6 CZ301323B6 CZ20031758A CZ20031758A CZ301323B6 CZ 301323 B6 CZ301323 B6 CZ 301323B6 CZ 20031758 A CZ20031758 A CZ 20031758A CZ 20031758 A CZ20031758 A CZ 20031758A CZ 301323 B6 CZ301323 B6 CZ 301323B6
- Authority
- CZ
- Czechia
- Prior art keywords
- azoniabicyclo
- octane
- formula
- group
- azabicyclo
- Prior art date
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- 239000000203 mixture Substances 0.000 title description 21
- DSTLXMSUVMLNBP-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octane;carbamate Chemical class NC(O)=O.C1CC2CCN1CC2 DSTLXMSUVMLNBP-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 235
- -1 carbamate compound Chemical class 0.000 claims abstract description 205
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 33
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 208000018522 Gastrointestinal disease Diseases 0.000 claims abstract description 10
- 208000012931 Urologic disease Diseases 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 9
- 150000001450 anions Chemical class 0.000 claims abstract description 9
- 208000014001 urinary system disease Diseases 0.000 claims abstract description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 208000010643 digestive system disease Diseases 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 7
- 208000018685 gastrointestinal system disease Diseases 0.000 claims abstract description 7
- 230000000241 respiratory effect Effects 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
- 125000006267 biphenyl group Chemical group 0.000 claims abstract description 3
- 208000035475 disorder Diseases 0.000 claims abstract description 3
- KZGBMDVPRFXGCT-UHFFFAOYSA-N [3-(1-azabicyclo[2.2.2]octan-2-yl)phenyl]-benzylcarbamic acid hydrochloride Chemical compound Cl.N12C(CC(CC1)CC2)C=2C=C(C=CC2)N(C(O)=O)CC2=CC=CC=C2 KZGBMDVPRFXGCT-UHFFFAOYSA-N 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 185
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 119
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 22
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000002723 alicyclic group Chemical group 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 claims description 7
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 7
- 150000003431 steroids Chemical class 0.000 claims description 7
- 108010008405 Muscarinic M3 Receptor Proteins 0.000 claims description 6
- 230000003266 anti-allergic effect Effects 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000011541 reaction mixture Substances 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- 102000007202 Muscarinic M3 Receptor Human genes 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 150000004657 carbamic acid derivatives Chemical class 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 229940100198 alkylating agent Drugs 0.000 claims description 4
- 239000002168 alkylating agent Substances 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- BDLKVZCRRROJRY-FQEVSTJZSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 BDLKVZCRRROJRY-FQEVSTJZSA-N 0.000 claims description 3
- LIAJJEHSFRHBLC-KRWDZBQOSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)N(CCCC)C1=CC=CC=C1 LIAJJEHSFRHBLC-KRWDZBQOSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 239000013066 combination product Substances 0.000 claims description 3
- 229940127555 combination product Drugs 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 238000002414 normal-phase solid-phase extraction Methods 0.000 claims description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- YOQUTGNBIRSXNF-KRWDZBQOSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] n-cyclopentyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)N(C1CCCC1)CC1=CC=CS1 YOQUTGNBIRSXNF-KRWDZBQOSA-N 0.000 claims description 2
- KZJQTCGYGSMOSC-NRFANRHFSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)N(C=1C=CC=CC=1)CCC1=CC=CC=C1 KZJQTCGYGSMOSC-NRFANRHFSA-N 0.000 claims description 2
- 239000005557 antagonist Substances 0.000 claims description 2
- CQAMPEQWAJLGTK-UHFFFAOYSA-N benzyl-(4-fluorophenyl)carbamic acid Chemical compound C=1C=C(F)C=CC=1N(C(=O)O)CC1=CC=CC=C1 CQAMPEQWAJLGTK-UHFFFAOYSA-N 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 1
- PAZJAFKVOUZUPG-RARKWRLQSA-M [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)N(CCC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 PAZJAFKVOUZUPG-RARKWRLQSA-M 0.000 claims 1
- QPRWDHVZZSSIHZ-QMAMVGRZSA-M [Br-].C1CC([C@H](C2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CC[N+]12C(C)C1=CC=CC=C1 Chemical compound [Br-].C1CC([C@H](C2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CC[N+]12C(C)C1=CC=CC=C1 QPRWDHVZZSSIHZ-QMAMVGRZSA-M 0.000 claims 1
- WKFZHVFBHYHYAK-UHFFFAOYSA-N benzyl(phenyl)carbamic acid Chemical compound C=1C=CC=CC=1N(C(=O)O)CC1=CC=CC=C1 WKFZHVFBHYHYAK-UHFFFAOYSA-N 0.000 claims 1
- 229940125388 beta agonist Drugs 0.000 claims 1
- DJLYFOLCFWQWQG-UHFFFAOYSA-N octane;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCCCCCCC DJLYFOLCFWQWQG-UHFFFAOYSA-N 0.000 claims 1
- BDDIUTHMWNWMRJ-UHFFFAOYSA-N octane;hydrobromide Chemical compound Br.CCCCCCCC BDDIUTHMWNWMRJ-UHFFFAOYSA-N 0.000 claims 1
- MZEJYTHCXCYSHD-UHFFFAOYSA-N phenyl(thiophen-2-ylmethyl)carbamic acid Chemical compound C=1C=CC=CC=1N(C(=O)O)CC1=CC=CS1 MZEJYTHCXCYSHD-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 23
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 4
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- 238000005481 NMR spectroscopy Methods 0.000 description 96
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Classifications
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
Landscapes
- Health & Medical Sciences (AREA)
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- Cardiology (AREA)
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- Otolaryngology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200003084 | 2000-12-22 |
Publications (2)
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| CZ20031758A3 CZ20031758A3 (en) | 2004-03-17 |
| CZ301323B6 true CZ301323B6 (cs) | 2010-01-13 |
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| CZ20031758A CZ301323B6 (cs) | 2000-12-22 | 2001-12-20 | Chinuklidinkarbamátové deriváty a lécivé kompozice je obsahující |
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Families Citing this family (121)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| MXPA03000141A (es) | 2000-06-27 | 2003-05-27 | S A L V A T Lab Sa | Carbamatos derivados de arilalquilaminas. |
| SK8002003A3 (en) | 2000-12-22 | 2004-05-04 | Almirall Prodesfarma Ag | Quinuclidine carbamate derivatives and their use as M3 antagonists |
| EP1353919B1 (en) | 2000-12-28 | 2006-07-26 | Almirall Prodesfarma AG | Novel quinuclidine derivatives and medicinal compositions containing the same |
| US7067261B2 (en) | 2001-12-14 | 2006-06-27 | Targacept, Inc. | Methods and compositions for treatment of central nervous system disorders |
| KR100944580B1 (ko) * | 2001-12-20 | 2010-02-25 | 치에시 파마슈티시 에스.피.아. | 1-알킬-1-아조니아비시클로[2.2.2]옥탄 카르바메이트유도체 및 이의 무스카린 수용체 길항제로서의 용도 |
| ES2203327B1 (es) * | 2002-06-21 | 2005-06-16 | Almirall Prodesfarma, S.A. | Nuevos carbamatos de quinuclidina y composiciones farmaceuticas que los contienen. |
| ES2204295B1 (es) | 2002-07-02 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de quinuclidina-amida. |
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- 2001-12-20 AT AT01989610T patent/ATE305468T1/de not_active IP Right Cessation
- 2001-12-20 SI SI200130426T patent/SI1345937T1/sl unknown
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| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20101220 |