CN100352817C - 用作5－HT1f激动剂的吡啶酰基哌啶 - Google Patents
用作5－HT1f激动剂的吡啶酰基哌啶 Download PDFInfo
- Publication number
- CN100352817C CN100352817C CNB038073633A CN03807363A CN100352817C CN 100352817 C CN100352817 C CN 100352817C CN B038073633 A CNB038073633 A CN B038073633A CN 03807363 A CN03807363 A CN 03807363A CN 100352817 C CN100352817 C CN 100352817C
- Authority
- CN
- China
- Prior art keywords
- methyl
- pyridin
- substituted
- ylacyl
- piperidin
- 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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- 239000000556 agonist Substances 0.000 title description 9
- YSWVIKAWHDUJFE-UHFFFAOYSA-N piperidin-1-yl(pyridin-2-yl)methanone Chemical class C=1C=CC=NC=1C(=O)N1CCCCC1 YSWVIKAWHDUJFE-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 169
- 239000001257 hydrogen Substances 0.000 claims abstract description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 47
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 36
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 206010015866 Extravasation Diseases 0.000 claims abstract description 28
- 239000002253 acid Substances 0.000 claims abstract description 28
- 230000036251 extravasation Effects 0.000 claims abstract description 28
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 26
- 206010027599 migraine Diseases 0.000 claims abstract description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 26
- 238000011282 treatment Methods 0.000 claims abstract description 22
- 101000941893 Felis catus Leucine-rich repeat and calponin homology domain-containing protein 1 Proteins 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 10
- 230000003213 activating effect Effects 0.000 claims abstract description 8
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
- 230000002265 prevention Effects 0.000 claims abstract description 6
- -1 furylPyridyl Chemical group 0.000 claims description 106
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 65
- 239000002904 solvent Substances 0.000 claims description 45
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 23
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- FEYDZHNIIMENOB-UHFFFAOYSA-N 2,6-dibromopyridine Chemical compound BrC1=CC=CC(Br)=N1 FEYDZHNIIMENOB-UHFFFAOYSA-N 0.000 claims description 13
- 125000006239 protecting group Chemical group 0.000 claims description 13
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- 125000005843 halogen group Chemical group 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000003545 alkoxy group Chemical class 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
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- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
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- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 7
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- 125000001041 indolyl group Chemical group 0.000 claims description 7
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- 238000006467 substitution reaction Methods 0.000 claims description 5
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- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- FILKGCRCWDMBKA-UHFFFAOYSA-N 2,6-dichloropyridine Chemical compound ClC1=CC=CC(Cl)=N1 FILKGCRCWDMBKA-UHFFFAOYSA-N 0.000 claims description 3
- 125000002393 azetidinyl group Chemical group 0.000 claims description 3
- SNIABFMMCKVXSY-UHFFFAOYSA-N benzoylazanium;chloride Chemical compound Cl.NC(=O)C1=CC=CC=C1 SNIABFMMCKVXSY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical class NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 claims description 2
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 3
- 230000004064 dysfunction Effects 0.000 claims 1
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- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
- 101150039275 Htr1f gene Proteins 0.000 abstract 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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| US36908802P | 2002-03-29 | 2002-03-29 | |
| US60/369,088 | 2002-03-29 |
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| CN110437205A (zh) * | 2018-08-24 | 2019-11-12 | 广东东阳光药业有限公司 | 吡啶烯基哌啶衍生物及其用途 |
| US10899770B2 (en) | 2017-02-20 | 2021-01-26 | Hangzhou Solipharma Co., Ltd. | Crystal form of ACP-196 salt and preparation method, pharmaceutical composition, and use thereof |
| CN113045540A (zh) * | 2019-12-27 | 2021-06-29 | 上海天慈国际药业有限公司 | 一种拉司米地坦的制备方法 |
| WO2022079591A1 (en) * | 2020-10-14 | 2022-04-21 | Alembic Pharmaceuticals Limited | Pharmaceutical composition of lasmiditan and process of preparation thereof |
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| CN1340045A (zh) * | 1999-02-10 | 2002-03-13 | 伊莱利利公司 | 5－ht1f激动剂 |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20190233393A1 (en) * | 2016-07-15 | 2019-08-01 | Solipharma Llc | Crystalline form of receptor agonist, and manufacturing method and pharmaceutical composition thereof |
| US10669256B2 (en) * | 2016-07-15 | 2020-06-02 | Hangzhou Solipharma Co., Ltd. | Crystalline forms of lasmiditan, preparation methods, pharmaceutical compositions and uses thereof |
| US10899770B2 (en) | 2017-02-20 | 2021-01-26 | Hangzhou Solipharma Co., Ltd. | Crystal form of ACP-196 salt and preparation method, pharmaceutical composition, and use thereof |
| CN110437205A (zh) * | 2018-08-24 | 2019-11-12 | 广东东阳光药业有限公司 | 吡啶烯基哌啶衍生物及其用途 |
| CN110437205B (zh) * | 2018-08-24 | 2022-07-08 | 广东东阳光药业有限公司 | 吡啶烯基哌啶衍生物及其用途 |
| CN113045540A (zh) * | 2019-12-27 | 2021-06-29 | 上海天慈国际药业有限公司 | 一种拉司米地坦的制备方法 |
| CN113045540B (zh) * | 2019-12-27 | 2024-02-13 | 上海天慈国际药业有限公司 | 一种拉司米地坦的制备方法 |
| WO2022079591A1 (en) * | 2020-10-14 | 2022-04-21 | Alembic Pharmaceuticals Limited | Pharmaceutical composition of lasmiditan and process of preparation thereof |
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