Heterocyclic oxime derivatives, process for their preparation and use thereof in the treatment of type II diabetes
Benzoxazole, benzothiazole or indole oxime derivatives (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine) are new. Benzoxazole, benzothiazole or indole oxime derivatives of formula (I) (including analogs with the benzo ring replaced by pyridine, pyra...
Saved in:
Main Authors | , , , , , , , , , |
---|---|
Format | Patent |
Language | English Polish |
Published |
30.04.2007
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Benzoxazole, benzothiazole or indole oxime derivatives (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine) are new. Benzoxazole, benzothiazole or indole oxime derivatives of formula (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine), and their enantiomers, diastereomers and salts are new. [Image] X : O, S, CH 2 or CHR' 2>; R 1>, R 2>H, alkyl, aryl, aralkyl, aryloxy, aralkoxy, alkoxy, OH, NH 2 or mono- or dialkylamino; or R 1> + R 2>=O, =S or =NH; R' 2>group forming an additional bond with R 2>; A : 1-6C alkylene (optionally having one CH 2 replaced by O, S, NRa', phenylene or naphthylene); Ra' : H or alkyl; R 3>, R 4>H, halo, R, OR or NRR'; or R 3> + R 4>group forming an ortho-fused 5- or 6-membered ring (optionally containing an O, S or N heteroatom); R, R', R 5>, R 6>H, alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, cycloalkyl, cycloalkylalkyl or polyhaloalkyl; D : benzene ring (in which case X is other than CHR' 2>); or a pyridine, pyrazine, pyrimidine or pyridazine ring; B : alkyl or alkenyl, both substituted by -CHR 7>R 8> or by R 9>; or -CHR 7>R 8> or R 9>; R 7>-C(Z)OR, -C(Z)NRR', -N(R)C(Z)R' or -N(R)C(Z)OR'; Z : O or S; R 8>aryl, aralkyl, heteroaryl, heteroaralkyl, CN, tetrazole, OR, NRR', -N(R)C(Z)R' or -N(R)C(Z)OR'; R 9>CN, tetrazole, -N(R)C(Z)R', -N(R)C(Z)OR' or -O(CH 2) n-CR 1> 0>R 1> 1>-COOR; n : 0-6; R 1> 0>, R 1> 1>H or alkyl, but not both H; aryl moieties : phenyl, naphthyl or biphenyl (all optionally partially hydrogenated and optionally substituted by 1-3 alkyl, polyhaloalkyl, alkoxy, OH, COOH, CHO, NRaRb, ester, amido, NO 2, CN or halo groups); heteroaryl moieties : 5-10 membered mono- or bicyclic aryl (where one ring is optionally partially hydrogenated in the case of bicyclic systems) containing 1-3 O, S and/or N heteroatom(s) and optionally substituted as for aryl; Rb, Rc : H, alkyl, aryl or heteroaryl; the oxime group -C(R 6>)=NOR 5> has E- or Z-configuration; alkyl moieties have 1-6C, alkenyl or alkynyl moieties 2-6C and cycloalkyl moieties 3-8C. Independent claims are included for: (1) preparation method of (I); and (2) new ketone intermediates of formula (V). [Image] ACTIVITY : Antidiabetic; Antilipemic; Cardiant; Nephrotropic; Ophthalmological; Antipsoriatic; Gynecological; Nootropic; Osteopathic; Antiinflammatory; Antiarteriosclerotic; Anorectic; Cytostatic. In tests in ob/ob mice, oral administration of 10 mg/kg of methyl 3-(4-(2-(6-((methoxyimino)-(phenyl)-methyl)-2-oxo-1,3-benzothiazol-3(2H)-yl)-ethoxy)-phenyl)-2-(2,2,2-trifluoroethoxy)-propanoate (Ia) twice per day for 4 days reduced blood sugar levels by 51% and reduced the weight gain by 80% in comparison with controls, whereas analogous administration of rosiglitazone reduced blood sugar levels by 61% but increased the weight gain by 33% in comparison with controls. MECHANISM OF ACTION : Aldose Reductase Inhibitor; Angiogenesis Inhibitor. |
---|---|
AbstractList | Benzoxazole, benzothiazole or indole oxime derivatives (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine) are new. Benzoxazole, benzothiazole or indole oxime derivatives of formula (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine), and their enantiomers, diastereomers and salts are new. [Image] X : O, S, CH 2 or CHR' 2>; R 1>, R 2>H, alkyl, aryl, aralkyl, aryloxy, aralkoxy, alkoxy, OH, NH 2 or mono- or dialkylamino; or R 1> + R 2>=O, =S or =NH; R' 2>group forming an additional bond with R 2>; A : 1-6C alkylene (optionally having one CH 2 replaced by O, S, NRa', phenylene or naphthylene); Ra' : H or alkyl; R 3>, R 4>H, halo, R, OR or NRR'; or R 3> + R 4>group forming an ortho-fused 5- or 6-membered ring (optionally containing an O, S or N heteroatom); R, R', R 5>, R 6>H, alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, cycloalkyl, cycloalkylalkyl or polyhaloalkyl; D : benzene ring (in which case X is other than CHR' 2>); or a pyridine, pyrazine, pyrimidine or pyridazine ring; B : alkyl or alkenyl, both substituted by -CHR 7>R 8> or by R 9>; or -CHR 7>R 8> or R 9>; R 7>-C(Z)OR, -C(Z)NRR', -N(R)C(Z)R' or -N(R)C(Z)OR'; Z : O or S; R 8>aryl, aralkyl, heteroaryl, heteroaralkyl, CN, tetrazole, OR, NRR', -N(R)C(Z)R' or -N(R)C(Z)OR'; R 9>CN, tetrazole, -N(R)C(Z)R', -N(R)C(Z)OR' or -O(CH 2) n-CR 1> 0>R 1> 1>-COOR; n : 0-6; R 1> 0>, R 1> 1>H or alkyl, but not both H; aryl moieties : phenyl, naphthyl or biphenyl (all optionally partially hydrogenated and optionally substituted by 1-3 alkyl, polyhaloalkyl, alkoxy, OH, COOH, CHO, NRaRb, ester, amido, NO 2, CN or halo groups); heteroaryl moieties : 5-10 membered mono- or bicyclic aryl (where one ring is optionally partially hydrogenated in the case of bicyclic systems) containing 1-3 O, S and/or N heteroatom(s) and optionally substituted as for aryl; Rb, Rc : H, alkyl, aryl or heteroaryl; the oxime group -C(R 6>)=NOR 5> has E- or Z-configuration; alkyl moieties have 1-6C, alkenyl or alkynyl moieties 2-6C and cycloalkyl moieties 3-8C. Independent claims are included for: (1) preparation method of (I); and (2) new ketone intermediates of formula (V). [Image] ACTIVITY : Antidiabetic; Antilipemic; Cardiant; Nephrotropic; Ophthalmological; Antipsoriatic; Gynecological; Nootropic; Osteopathic; Antiinflammatory; Antiarteriosclerotic; Anorectic; Cytostatic. In tests in ob/ob mice, oral administration of 10 mg/kg of methyl 3-(4-(2-(6-((methoxyimino)-(phenyl)-methyl)-2-oxo-1,3-benzothiazol-3(2H)-yl)-ethoxy)-phenyl)-2-(2,2,2-trifluoroethoxy)-propanoate (Ia) twice per day for 4 days reduced blood sugar levels by 51% and reduced the weight gain by 80% in comparison with controls, whereas analogous administration of rosiglitazone reduced blood sugar levels by 61% but increased the weight gain by 33% in comparison with controls. MECHANISM OF ACTION : Aldose Reductase Inhibitor; Angiogenesis Inhibitor. |
Author | CARATO, PASCAL RENARD, PIERRE DACQUET, CATHERINE BOUTIN, JEAN ALBERT LECLERC, VÉRONIQUE INTROVIGNE, CARINE CAIGNARD, DANIEL HENRI PAILLOUX, SYLVIE LEBEGUE, NICOLAS BERTHELOT, PASCAL |
Author_xml | – fullname: INTROVIGNE, CARINE – fullname: BERTHELOT, PASCAL – fullname: RENARD, PIERRE – fullname: DACQUET, CATHERINE – fullname: CAIGNARD, DANIEL HENRI – fullname: CARATO, PASCAL – fullname: PAILLOUX, SYLVIE – fullname: LEBEGUE, NICOLAS – fullname: BOUTIN, JEAN ALBERT – fullname: LECLERC, VÉRONIQUE |
BookMark | eNqNjb0KwjAUhTPo4N87XHeFaungLEoLDg7dS0xPMdAm4eZa9O1NwQdwOofvO3CWaua8w0JxCQF78zG9NeTfdgC1YDtqsSPijkKSiJE6zyRPWE4EQXPy3pF2Lb0iJsPwHVk3VRKGlgFOKDH5BFBVUWv1I53FtZp3uo_Y_HKlttdLfS73CL5BDNrAQZr77VBkx-KU1XWe_7P5AnkkRik |
ContentType | Patent |
DBID | EVB |
DatabaseName | esp@cenet |
DatabaseTitleList | |
Database_xml | – sequence: 1 dbid: EVB name: esp@cenet url: http://worldwide.espacenet.com/singleLineSearch?locale=en_EP sourceTypes: Open Access Repository |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine Chemistry Sciences |
DocumentTitleAlternate | Pochodne oksymów heterocyklicznych, ich sposób wytwarzania i ich zastosowanie w leczeniu cukrzycy typu II |
ExternalDocumentID | PL1502590TT3 |
GroupedDBID | EVB |
ID | FETCH-epo_espacenet_PL1502590TT33 |
IEDL.DBID | EVB |
IngestDate | Fri Jul 19 13:07:50 EDT 2024 |
IsOpenAccess | true |
IsPeerReviewed | false |
IsScholarly | false |
Language | English Polish |
LinkModel | DirectLink |
MergedId | FETCHMERGED-epo_espacenet_PL1502590TT33 |
Notes | Application Number: PL20040291901T |
OpenAccessLink | https://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20070430&DB=EPODOC&CC=PL&NR=1502590T3 |
ParticipantIDs | epo_espacenet_PL1502590TT3 |
PublicationCentury | 2000 |
PublicationDate | 20070430 |
PublicationDateYYYYMMDD | 2007-04-30 |
PublicationDate_xml | – month: 04 year: 2007 text: 20070430 day: 30 |
PublicationDecade | 2000 |
PublicationYear | 2007 |
RelatedCompanies | Les Laboratoires Servier |
RelatedCompanies_xml | – name: Les Laboratoires Servier |
Score | 2.6772683 |
Snippet | Benzoxazole, benzothiazole or indole oxime derivatives (I) (including analogs with the benzo ring replaced by pyridine, pyrazine, pyrimidine or pyridazine) are... |
SourceID | epo |
SourceType | Open Access Repository |
SubjectTerms | CHEMISTRY HETEROCYCLIC COMPOUNDS HUMAN NECESSITIES HYGIENE MEDICAL OR VETERINARY SCIENCE METALLURGY ORGANIC CHEMISTRY PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS |
Title | Heterocyclic oxime derivatives, process for their preparation and use thereof in the treatment of type II diabetes |
URI | https://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20070430&DB=EPODOC&locale=&CC=PL&NR=1502590T3 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1bS8MwFD7MKeqbTkXnhQjSJ4ur6dbtYQhrNzbZpUiVvY01FyhoW9bOy7_3JFunL_oWTiDk9uUkX06-ANwo_RMqHceU7J6bdlijZrNJuWmFnFucCWbp74BG40b_2X6c1qcliIq3MFon9EOLIyKiGOI91-t1-kNieTq2MrsLIzQlD72g7RnF6dhRElaG12l3_Yk3cQ3XbftDY_yEwEbn3qoFdAu21S5ayex3XzrqUUr626P0DmDHx8Li_BBK6WsF9tzi47UK7I7W992YXEMvO4JFXwWuJOyLYQ1J8hm9CcJx-rxr5e7slqSrkH-Cu1Ci6X-0iJWydxKTeczJMhMqZyESSaJYJckmzpygTdGxZDAgBR97DNe9buD2Taz8bNNRM39YNDOg9ATKcRKLUyCIMlqfh7JhMWozKdFHN2XYsoXNcDyEOIPq3-VU_8s8h_0V16luVy6gnC-W4hKddB5e6e79BgnHmhk |
link.rule.ids | 230,309,786,891,25594,76906 |
linkProvider | European Patent Office |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1bT8IwFD5BNOKbokbxVhOzJxcZHQweiAkbZOiAxUzDG2FdlyzRbWHDy7_3tDD0Rd-a06Tp7etpv55-BbgR-ic0NAw1ZI1A1f06VdttGqiaHwRawDjT5HdAo3HLftYfps1pCaLiLYzUCf2Q4oiIKIZ4z-V6nf6QWJaMrczu_AhNyf3A61pKcTo2hISVYvW6fXdiTUzFNLuuo4yfENjo3Dt1j27BtiHEecXO6aUnHqWkvz3KYB92XCwszg-glL5WoWIWH69VYXe0vu_G5Bp62SEsbBG4krAvhjUkyWf0xkmA0-ddKndntyRdhfwT3IUSSf-jha-UvZOYzOOALDMuchY8CUkUiyTZxJkTtAk6lgyHpOBjj-B60PdMW8XKzzYdNXOdopkepcdQjpOYnwBBlNHm3A9bGqM6C0P00e3Q7-hcZzgenJ9C7e9yav9lXkHF9kbOzBmOH89gb8V7ipuWcyjniyW_QIed-5eyq78BaI6dBg |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Apatent&rft.title=Heterocyclic+oxime+derivatives%2C+process+for+their+preparation+and+use+thereof+in+the+treatment+of+type+II+diabetes&rft.inventor=INTROVIGNE%2C+CARINE&rft.inventor=BERTHELOT%2C+PASCAL&rft.inventor=RENARD%2C+PIERRE&rft.inventor=DACQUET%2C+CATHERINE&rft.inventor=CAIGNARD%2C+DANIEL+HENRI&rft.inventor=CARATO%2C+PASCAL&rft.inventor=PAILLOUX%2C+SYLVIE&rft.inventor=LEBEGUE%2C+NICOLAS&rft.inventor=BOUTIN%2C+JEAN+ALBERT&rft.inventor=LECLERC%2C+V%C3%89RONIQUE&rft.date=2007-04-30&rft.externalDBID=T3&rft.externalDocID=PL1502590TT3 |