UA74023C2 - Cyanopyrrolidine derivatives - Google Patents
Cyanopyrrolidine derivatives Download PDFInfo
- Publication number
- UA74023C2 UA74023C2 UA2003065269A UA2003065269A UA74023C2 UA 74023 C2 UA74023 C2 UA 74023C2 UA 2003065269 A UA2003065269 A UA 2003065269A UA 2003065269 A UA2003065269 A UA 2003065269A UA 74023 C2 UA74023 C2 UA 74023C2
- Authority
- UA
- Ukraine
- Prior art keywords
- group
- carbon atoms
- optionally substituted
- hydrogen atom
- chain
- Prior art date
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- QJRYYOWARFCJQZ-UHFFFAOYSA-N pyrrolidine-1-carbonitrile Chemical class N#CN1CCCC1 QJRYYOWARFCJQZ-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 172
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 65
- 125000005843 halogen group Chemical group 0.000 claims abstract description 61
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 60
- -1 hydroxyimino Chemical group 0.000 claims abstract description 58
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 5
- 229910052717 sulfur Chemical group 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 73
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 125000003277 amino group Chemical group 0.000 claims description 40
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 33
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 25
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 21
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
- 230000005764 inhibitory process Effects 0.000 claims description 16
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 102000003779 Dipeptidyl-peptidases and tripeptidyl-peptidases Human genes 0.000 claims description 12
- 108090000194 Dipeptidyl-peptidases and tripeptidyl-peptidases Proteins 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 11
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 125000001041 indolyl group Chemical group 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 10
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 10
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 8
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000001118 alkylidene group Chemical group 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 208000026278 immune system disease Diseases 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000000676 alkoxyimino group Chemical group 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 claims description 2
- 102000035195 Peptidases Human genes 0.000 claims 1
- 108091005804 Peptidases Proteins 0.000 claims 1
- 241001393742 Simian endogenous retrovirus Species 0.000 claims 1
- 239000002515 guano Substances 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- 235000019833 protease Nutrition 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 abstract 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
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- 239000011593 sulfur Chemical group 0.000 abstract 1
- 238000000034 method Methods 0.000 description 201
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- 238000006243 chemical reaction Methods 0.000 description 96
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 78
- 239000000243 solution Substances 0.000 description 70
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
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- 239000007864 aqueous solution Substances 0.000 description 48
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- 238000003756 stirring Methods 0.000 description 43
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- 239000000203 mixture Substances 0.000 description 34
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 31
- 229920006395 saturated elastomer Polymers 0.000 description 29
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 238000004440 column chromatography Methods 0.000 description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 239000011780 sodium chloride Substances 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
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- 239000012074 organic phase Substances 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 13
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 10
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
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- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 10
- LNWWQYYLZVZXKS-UHFFFAOYSA-N 1-pyrrolidin-1-ylethanone Chemical compound CC(=O)N1CCCC1 LNWWQYYLZVZXKS-UHFFFAOYSA-N 0.000 description 9
- 102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 9
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- 239000002253 acid Substances 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 9
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
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- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 150000007529 inorganic bases Chemical class 0.000 description 7
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 6
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- FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
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- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
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- 230000037396 body weight Effects 0.000 description 5
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
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- 238000002474 experimental method Methods 0.000 description 4
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- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 3
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000344036 | 2000-11-10 | ||
PCT/JP2001/009818 WO2002038541A1 (fr) | 2000-11-10 | 2001-11-09 | Derives de cyanopyrrolidine |
Publications (1)
Publication Number | Publication Date |
---|---|
UA74023C2 true UA74023C2 (en) | 2005-10-17 |
Family
ID=34074163
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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UA2003065269A UA74023C2 (en) | 2000-11-10 | 2001-09-11 | Cyanopyrrolidine derivatives |
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CN (2) | CN100371323C (zh) |
UA (1) | UA74023C2 (zh) |
ZA (1) | ZA200302591B (zh) |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW492957B (en) * | 1996-11-07 | 2002-07-01 | Novartis Ag | N-substituted 2-cyanopyrrolidnes |
CO5150173A1 (es) * | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
-
2001
- 2001-09-11 UA UA2003065269A patent/UA74023C2/uk unknown
- 2001-11-09 CN CNB2005100832013A patent/CN100371323C/zh not_active Expired - Fee Related
- 2001-11-09 CN CN200510125155.9A patent/CN1772733A/zh active Pending
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2003
- 2003-04-02 ZA ZA200302591A patent/ZA200302591B/en unknown
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Publication number | Publication date |
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CN1772733A (zh) | 2006-05-17 |
ZA200302591B (en) | 2004-07-02 |
CN100371323C (zh) | 2008-02-27 |
CN1715269A (zh) | 2006-01-04 |
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