ES2285485T3 - Derivados de piperidina como moduladores del receptor ccr5. - Google Patents
Derivados de piperidina como moduladores del receptor ccr5. Download PDFInfo
- Publication number
- ES2285485T3 ES2285485T3 ES04749185T ES04749185T ES2285485T3 ES 2285485 T3 ES2285485 T3 ES 2285485T3 ES 04749185 T ES04749185 T ES 04749185T ES 04749185 T ES04749185 T ES 04749185T ES 2285485 T3 ES2285485 T3 ES 2285485T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- phenyl
- optionally substituted
- baselineskip
- heteroaryl
- Prior art date
- 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
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 title claims description 11
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 title claims description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 153
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 98
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 70
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 42
- 239000001257 hydrogen Substances 0.000 claims abstract description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 32
- 125000003118 aryl 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 28
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 24
- 239000012453 solvate Substances 0.000 claims abstract description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 19
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 15
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 14
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000005553 heteroaryloxy group Chemical group 0.000 claims abstract description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 239000001301 oxygen Substances 0.000 claims abstract description 8
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims abstract description 7
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 6
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 6
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 323
- -1 R 13 Chemical compound 0.000 claims description 111
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 98
- 125000005843 halogen group Chemical group 0.000 claims description 72
- 125000003545 alkoxy group Chemical group 0.000 claims description 53
- 239000002904 solvent Substances 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 33
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 32
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 26
- 239000000460 chlorine Substances 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 230000008878 coupling Effects 0.000 claims description 6
- 238000010168 coupling process Methods 0.000 claims description 6
- 238000005859 coupling reaction Methods 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 101100294110 Caenorhabditis elegans nhr-43 gene Proteins 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
- 101100294112 Caenorhabditis elegans nhr-47 gene Proteins 0.000 claims description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 3
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 2
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 7
- 125000001475 halogen functional group Chemical group 0.000 abstract 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 51
- 239000000203 mixture Substances 0.000 description 50
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 36
- 238000002360 preparation method Methods 0.000 description 36
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 34
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 125000001153 fluoro group Chemical group F* 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 22
- 206010039083 rhinitis Diseases 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 18
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 208000006673 asthma Diseases 0.000 description 11
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 11
- 125000004076 pyridyl group Chemical group 0.000 description 11
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- 125000003709 fluoroalkyl group Chemical group 0.000 description 8
- 229910052736 halogen Inorganic materials 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
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- 208000030507 AIDS Diseases 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
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- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 6
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
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- 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
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- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
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| SE0302155 | 2003-07-31 | ||
| SE0302155A SE0302155D0 (sv) | 2003-07-31 | 2003-07-31 | Chemical compounds |
| SE0401420 | 2004-06-03 | ||
| SE0401420A SE0401420D0 (sv) | 2004-06-03 | 2004-06-03 | Chemical compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2285485T3 true ES2285485T3 (es) | 2007-11-16 |
Family
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| Application Number | Title | Priority Date | Filing Date |
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| ES04749185T Expired - Lifetime ES2285485T3 (es) | 2003-07-31 | 2004-07-26 | Derivados de piperidina como moduladores del receptor ccr5. |
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| EP (1) | EP1654229B1 (enExample) |
| JP (1) | JP2007500694A (enExample) |
| AR (1) | AR045183A1 (enExample) |
| AT (1) | ATE361911T1 (enExample) |
| DE (1) | DE602004006424T2 (enExample) |
| ES (1) | ES2285485T3 (enExample) |
| TW (1) | TW200510307A (enExample) |
| UY (1) | UY28447A1 (enExample) |
| WO (1) | WO2005009959A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| SE529058C2 (sv) | 2005-07-08 | 2007-04-17 | Plasma Surgical Invest Ltd | Plasmaalstrande anordning, plasmakirurgisk anordning, användning av en plasmakirurgisk anordning och förfarande för att bilda ett plasma |
| SE529053C2 (sv) | 2005-07-08 | 2007-04-17 | Plasma Surgical Invest Ltd | Plasmaalstrande anordning, plasmakirurgisk anordning och användning av en plasmakirurgisk anordning |
| SE529056C2 (sv) | 2005-07-08 | 2007-04-17 | Plasma Surgical Invest Ltd | Plasmaalstrande anordning, plasmakirurgisk anordning och användning av en plasmakirurgisk anordning |
| JP2010503714A (ja) | 2006-09-18 | 2010-02-04 | エフ.ホフマン−ラ ロシュ アーゲー | オクタヒドロピロロ[3,4−c]ピロール誘導体、抗ウイルス剤としてのそれらの使用 |
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| PE20001420A1 (es) * | 1998-12-23 | 2000-12-18 | Pfizer | Moduladores de ccr5 |
| US6432981B1 (en) * | 1999-06-11 | 2002-08-13 | Merck & Co., Inc. | Cyclopentyl modulators of chemokine receptor activity |
| SE0103818D0 (sv) * | 2001-11-15 | 2001-11-15 | Astrazeneca Ab | Chemical compounds |
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| GB0127547D0 (en) * | 2001-11-16 | 2002-01-09 | Astrazeneca Ab | Chemical compounds |
| AR042628A1 (es) * | 2002-12-20 | 2005-06-29 | Astrazeneca Ab | Derivados de piperidina como moduladores del receptor ccr5 |
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2004
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Also Published As
| Publication number | Publication date |
|---|---|
| AR045183A1 (es) | 2005-10-19 |
| UY28447A1 (es) | 2005-02-28 |
| US20070112022A1 (en) | 2007-05-17 |
| ATE361911T1 (de) | 2007-06-15 |
| JP2007500694A (ja) | 2007-01-18 |
| TW200510307A (en) | 2005-03-16 |
| WO2005009959A1 (en) | 2005-02-03 |
| DE602004006424D1 (de) | 2007-06-21 |
| EP1654229B1 (en) | 2007-05-09 |
| DE602004006424T2 (de) | 2008-05-15 |
| EP1654229A1 (en) | 2006-05-10 |
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