NO327221B1 - Piperidinderivater, fremgangsmate for deres fremstilling, farmasoytisk preparat, anvendelser og mellomprodukter - Google Patents
Piperidinderivater, fremgangsmate for deres fremstilling, farmasoytisk preparat, anvendelser og mellomprodukter Download PDFInfo
- Publication number
- NO327221B1 NO327221B1 NO20042157A NO20042157A NO327221B1 NO 327221 B1 NO327221 B1 NO 327221B1 NO 20042157 A NO20042157 A NO 20042157A NO 20042157 A NO20042157 A NO 20042157A NO 327221 B1 NO327221 B1 NO 327221B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- phenyl
- optionally substituted
- halo
- formula
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 25
- 238000000034 method Methods 0.000 title description 29
- 239000000543 intermediate Substances 0.000 title description 3
- 150000003053 piperidines Chemical class 0.000 title description 2
- 230000008569 process Effects 0.000 title description 2
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 125
- 125000000217 alkyl group Chemical group 0.000 claims description 120
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 87
- 239000002904 solvent Substances 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- -1 C 1 -C 4 alkoxy Chemical group 0.000 claims description 36
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 239000012453 solvate Substances 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 11
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 6
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 3
- 239000007822 coupling agent Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 235000009518 sodium iodide Nutrition 0.000 claims description 3
- 239000013067 intermediate product Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 124
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 85
- 239000000203 mixture Substances 0.000 description 74
- 125000005843 halogen group Chemical group 0.000 description 68
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- 239000000243 solution Substances 0.000 description 51
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
- 235000019439 ethyl acetate Nutrition 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 26
- 238000001819 mass spectrum Methods 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 16
- 239000011737 fluorine Substances 0.000 description 16
- 229910052731 fluorine Inorganic materials 0.000 description 16
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- 229910052801 chlorine Inorganic materials 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 206010039083 rhinitis Diseases 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 125000001153 fluoro group Chemical group F* 0.000 description 9
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 125000003709 fluoroalkyl group Chemical group 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 102000019034 Chemokines Human genes 0.000 description 6
- 108010012236 Chemokines Proteins 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 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
- 239000003480 eluent Substances 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 6
- 102000005962 receptors Human genes 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
- 241001465754 Metazoa Species 0.000 description 5
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- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 4
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- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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SE0103818A SE0103818D0 (sv) | 2001-11-15 | 2001-11-15 | Chemical compounds |
PCT/SE2002/002055 WO2003042205A1 (en) | 2001-11-15 | 2002-11-12 | Piperidine derivatives and their use as modulators of chemokine receptor activity (especially ccr5) |
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CN (1) | CN100398535C (de) |
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BR (1) | BR0214140A (de) |
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RU (1) | RU2345990C2 (de) |
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UA (1) | UA77969C2 (de) |
WO (1) | WO2003042205A1 (de) |
ZA (1) | ZA200403688B (de) |
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SE9902987D0 (sv) * | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
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SE0301369D0 (sv) * | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Chemical compounds |
SE0302090D0 (sv) * | 2003-07-16 | 2003-07-16 | Astrazeneca Ab | Chemical compounds |
EP1654229B1 (de) * | 2003-07-31 | 2007-05-09 | AstraZeneca AB | Piperidinderivate als ccr5-rezeptormodulatoren |
US7550485B2 (en) * | 2003-10-14 | 2009-06-23 | Wyeth | Substituted N-heterocycle derivatives and methods of their use |
SE0303396D0 (sv) * | 2003-12-16 | 2003-12-16 | Astrazeneca Ab | Chemical compounds |
ES2431524T3 (es) | 2004-04-13 | 2013-11-26 | Incyte Corporation | Derivados de piperazinilpiperidina como antagonistas de los receptores de quimiocinas |
TW200610761A (en) * | 2004-04-23 | 2006-04-01 | Astrazeneca Ab | Chemical compounds |
CN1329374C (zh) * | 2004-06-09 | 2007-08-01 | 上海靶点药物有限公司 | 作为ccr5拮抗剂的化合物 |
SE0401656D0 (sv) * | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | Chemical compounds |
SE0401657D0 (sv) * | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | Chemical compounds |
SE0403084D0 (sv) | 2004-12-17 | 2004-12-17 | Astrazeneca Ab | Chemical process |
US20080108586A1 (en) * | 2006-09-06 | 2008-05-08 | Incyte Corporation | Combination therapy for human immunodeficiency virus infection |
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TWI703130B (zh) * | 2014-03-07 | 2020-09-01 | 瑞士商赫爾辛保健股份有限公司 | 對位取代的不對稱脲及其醫療用途 |
EA037040B1 (ru) | 2016-03-22 | 2021-01-29 | Хелсинн Хелскеа Са | Асимметричные бензолсульфонилмочевины и их применение в качестве модуляторов рецептора грелина |
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GB0107228D0 (en) * | 2001-03-22 | 2001-05-16 | Astrazeneca Ab | Chemical compounds |
-
2001
- 2001-11-15 SE SE0103818A patent/SE0103818D0/xx unknown
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2002
- 2002-11-01 TW TW091132376A patent/TW200407139A/zh unknown
- 2002-11-12 PL PL02369758A patent/PL369758A1/xx not_active Application Discontinuation
- 2002-11-12 MX MXPA04004503A patent/MXPA04004503A/es active IP Right Grant
- 2002-11-12 HU HU0402261A patent/HUP0402261A3/hu unknown
- 2002-11-12 AR ARP020104333A patent/AR037351A1/es unknown
- 2002-11-12 AU AU2002353691A patent/AU2002353691B2/en not_active Ceased
- 2002-11-12 NZ NZ532411A patent/NZ532411A/en not_active IP Right Cessation
- 2002-11-12 CA CA002464347A patent/CA2464347A1/en not_active Abandoned
- 2002-11-12 EP EP02789054A patent/EP1448548A1/de not_active Withdrawn
- 2002-11-12 US US10/495,196 patent/US7192973B2/en not_active Expired - Fee Related
- 2002-11-12 JP JP2003544041A patent/JP4459622B2/ja not_active Expired - Fee Related
- 2002-11-12 IL IL16169902A patent/IL161699A0/xx unknown
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- 2002-11-12 RU RU2004111601/04A patent/RU2345990C2/ru not_active IP Right Cessation
- 2002-11-12 WO PCT/SE2002/002055 patent/WO2003042205A1/en active Application Filing
- 2002-11-12 KR KR1020047007364A patent/KR20050044470A/ko not_active Application Discontinuation
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Also Published As
Publication number | Publication date |
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NZ532411A (en) | 2005-11-25 |
PL369758A1 (en) | 2005-05-02 |
TW200407139A (en) | 2004-05-16 |
JP2005510522A (ja) | 2005-04-21 |
HUP0402261A3 (en) | 2009-07-28 |
MXPA04004503A (es) | 2004-08-11 |
CN100398535C (zh) | 2008-07-02 |
JP4459622B2 (ja) | 2010-04-28 |
US20040267016A1 (en) | 2004-12-30 |
HUP0402261A2 (hu) | 2005-02-28 |
US20070161646A1 (en) | 2007-07-12 |
ZA200403688B (en) | 2005-08-10 |
NO20042157L (no) | 2004-08-11 |
IL196059A (en) | 2010-04-29 |
AU2002353691B2 (en) | 2008-04-03 |
MY137144A (en) | 2008-12-31 |
US7192973B2 (en) | 2007-03-20 |
WO2003042205A1 (en) | 2003-05-22 |
IL161699A (en) | 2012-12-31 |
SE0103818D0 (sv) | 2001-11-15 |
RU2345990C2 (ru) | 2009-02-10 |
CA2464347A1 (en) | 2003-05-22 |
BR0214140A (pt) | 2004-10-19 |
CN1585763A (zh) | 2005-02-23 |
UA77969C2 (en) | 2007-02-15 |
RU2004111601A (ru) | 2005-10-20 |
IS7256A (is) | 2004-05-10 |
IL161699A0 (en) | 2004-09-27 |
AR037351A1 (es) | 2004-11-03 |
KR20050044470A (ko) | 2005-05-12 |
EP1448548A1 (de) | 2004-08-25 |
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