TW201000096A - Four-membered ring-condensed pyrrolidine derivatives, and preparation method and medical use thereof - Google Patents

Four-membered ring-condensed pyrrolidine derivatives, and preparation method and medical use thereof Download PDF

Info

Publication number: TW201000096A
Authority: TW; Taiwan
Prior art keywords: compound; group; acid; pyrrolidine; membered ring
Prior art date: 2007-06-04

Application number

TW097123297A

Other languages

English (en)

Chinese (zh)

Inventor

Peng-Cho Tang

zhi-gang Lin

Jia-Liang Yang

fu-qiang Zhao

Yang Wang

Qian Wang

Original Assignee

Shanghai Hengrui Pharm Co 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.)

2007-06-04

Filing date

2008-06-23

Publication date

2010-01-01

2008-06-23 Application filed by Shanghai Hengrui Pharm Co Ltd filed Critical Shanghai Hengrui Pharm Co Ltd

2010-01-01 Publication of TW201000096A publication Critical patent/TW201000096A/zh

Links

238000002360 preparation method Methods 0.000 title claims abstract description 35
150000003235 pyrrolidines Chemical class 0.000 title claims description 4
239000003814 drug Substances 0.000 claims abstract description 10
239000003112 inhibitor Substances 0.000 claims abstract description 8
101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 claims abstract description 7
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
229940124597 therapeutic agent Drugs 0.000 claims abstract description 4
FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 claims abstract 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 95
150000001875 compounds Chemical class 0.000 claims description 63
-1 butoxy carbonyl 2,3-dihydropyrrole-2-carboxylate Chemical compound 0.000 claims description 49
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 42
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 42
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
238000006243 chemical reaction Methods 0.000 claims description 34
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
239000002904 solvent Substances 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
239000002253 acid Substances 0.000 claims description 20
125000003118 aryl group Chemical group 0.000 claims description 20
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 16
125000000217 alkyl group Chemical group 0.000 claims description 16
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 15
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 15
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
125000001072 heteroaryl group Chemical group 0.000 claims description 12
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DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 8
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 8
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125000003545 alkoxy group Chemical group 0.000 claims description 7
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125000006239 protecting group Chemical group 0.000 claims description 4
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238000005658 halogenation reaction Methods 0.000 claims 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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TW097123297A 2007-06-04 2008-06-23 Four-membered ring-condensed pyrrolidine derivatives, and preparation method and medical use thereof TW201000096A (en)

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CNA2007101089154A CN101318925A (zh)	2007-06-04	2007-06-04	吡咯烷并四元环类衍生物、其制备方法及其在医药上的用途

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CN102260265B (zh)	2010-05-24	2015-09-02	上海阳帆医药科技有限公司	六氢吡咯[3,4-b]吡咯衍生物、其制备方法及其用途
CN108341766B (zh) *	2017-01-24	2020-08-14	南京药石科技股份有限公司	一种3-氮杂双环[3.1.0]己烷盐酸盐的制备方法
CN108164506B (zh) *	2018-02-02	2021-03-16	上海交通大学	一种dpp-4酶抑制剂及其制备和应用

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2007
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CN101318925A (zh)	2008-12-10
WO2008148279A1 (fr)	2008-12-11

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