Title:
抗炎症性2-オキソチアゾールおよび2-オキソオキサゾール
Document Type and Number:
Japanese Patent JP2013506639
Kind Code:
A
Abstract:
A compound of formula (I)
wherein X is O or S;
R 1 is H, OH, SH, nitro, NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , halo, haloC 1-6 alkyl, CN, C 1-6 -alkyl, OC 1-6 alkyl, C 1-6 alkylCOOH, C 1-6 alkylCOOC 1-6 alkyl, C 2-6 -alkenyl, C 3-10 cycloalkyl, C 6-10 aryl, C 1-6 alkylC 6-10 aryl, heterocyclyl, heteroaryl, CONH 2 , CONHC 1-6 alkyl, CON(C 1-6 alkyl) 2 , OCOC 1-6 alkyl, or is an acidic group, such as a group comprising a carboxyl, phosphate, phosphinate, sulfate, sulfonate, or tetrazolyl group;
R 2 is as defined for R 1 or R 1 and R 2 taken together can form a 6-membered aromatic ring optionally substituted by up to 4 groups R 5 ;
R 3 is H, halo (preferably fluoro), or CHal 3 (preferably CF 3 );
each R 5 is defined as for R 1 ;
V 1 is a covalent bond or a C 1-20 alkyl group, or C 2-20 -mono or multiply unsaturated alkenyl group; said alkyl or alkenyl groups being optionally interupted by one or more heteroatoms selected from O, NH, N(C 1-6 alkyl), S, SO, or SO 2 ;
M 1 is absent or is a C 5-10 cyclic group or a C 5-15 aromatic group; and
R 4 is H, halo, OH, CN, nitro, NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , haloC 1-6 alkyl, a C 1-20 alkyl group, or C 2-20 -mono or multiply unsaturated alkenyl group, said C 1-20 alkyl or C 2-20 alkenyl groups being optionally interupted by one or more heteroatoms selected from O, NH, N(C 1-6 alkyl), S, SO, or SO 2 ;
with the proviso that the group V 1 M 1 R 4 as a whole provides at least 4 backbone atoms from the C(R 3 ) group;
or a salt, ester, solvate, N-oxide, or prodrug thereof;
for use in the treatment of a chronic inflammatory condition.
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Inventors:
Cocotos, George
Johansen, Berito
Magurioti, Victoria
Tsacos, Michael
Johansen, Berito
Magurioti, Victoria
Tsacos, Michael
Application Number:
JP2012531448A
Publication Date:
February 28, 2013
Filing Date:
October 01, 2010
Export Citation:
Assignee:
Avexin AS
International Classes:
C07D277/04; A61K31/426; A61K31/428; A61P1/04; A61P9/00; A61P11/00; A61P13/12; A61P17/00; A61P17/02; A61P17/08; A61P19/02; A61P25/00; A61P29/00; A61P37/08; C07D277/20; C07D277/24; C07D277/32
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| JPH11509835A | 1999-08-31 | |||
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MARSILJE,T.H. ET AL: "Design, synthesis, and biological evaluation of simplified α-Keto heterocycle, trifluoromethyl keto", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 11, no. 20, JPN6016002134, 2003, pages 4487 - 4501, ISSN: 0003366629
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CHIKASHITA,H. ET AL.: "General reactivity of 2-lithiobenzothiazole to various electrophiles and the use as a formyl anion e", BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, vol. 61(10), JPN6014032271, 1988, pages 3637 - 48, ISSN: 0002866973
SCHMIDT,U. ET AL.: "Amino acids and peptides; 58. Synthesis of optically active 2-(1-hydroxyalkyl)-thiazole-4-carboxyli", SYNTHESIS, vol. (12), JPN6014032272, 1986, pages 992 - 8, ISSN: 0002866974
MARTIN,T. ET AL.: "Highly Efficient Borylation Suzuki Coupling Process for 4-Bromo-2-ketothiazoles: Straightforward Acc", ORGANIC LETTERS, vol. 11(16), JPN6014032275, 2009, pages 3693 - 1, ISSN: 0002866975
AHN,K. ET AL.: "Novel Mechanistic Class of Fatty Acid Amide Hydrolase Inhibitors with Remarkable Selectivity", BIOCHEMISTRY, vol. 46(45), JPN6014032268, 2007, pages 13019 - 13030, ISSN: 0002866969
COSTANZO,M.J. ET AL.: "Potent, Small-Molecule Inhibitors of Human Mast Cell Tryptase. Antiasthmatic Action of a Dipeptide-B", JOURNAL OF MEDICINAL CHEMISTRY, vol. 46(18), JPN6014032269, 2003, pages 3865 - 3876, ISSN: 0002866970
MYLLYMAKI,M.J. ET AL.: "Design, Synthesis, and In Vitro Evaluation of Carbamate Derivatives of 2-Benzoxazolyl- and 2-Benzoth", JOURNAL OF MEDICINAL CHEMISTRY, vol. 50(17), JPN6014032280, 2007, pages 4236 - 4242, ISSN: 0002866971
VASUDEVAN,A. ET AL: "Heterocyclic ketones as inhibitors of histone deacetylase", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 13, no. 22, JPN6015021455, 2003, pages 3909 - 3913, XP055664963, ISSN: 0003084721, DOI: 10.1016/j.bmcl.2003.09.007
DATABASE REGISTRY, JPN7016000115, 2 September 2009 (2009-09-02), pages 1179358 - 89, ISSN: 0003241230
DATABASE REGISTRY, JPN7016000116, 23 March 2007 (2007-03-23), ISSN: 0003241231
DATABASE REGISTRY, JPN7016000117, 16 November 1984 (1984-11-16), pages 82605 - 58, ISSN: 0003241232
MCGRATH,M.E. ET AL: "Structure-Guided Design of Peptide-Based Tryptase Inhibitors", BIOCHEMISTRY, vol. 45, no. 19, JPN6016002132, 2006, pages 5964 - 5973, XP008139509, ISSN: 0003366628, DOI: 10.1021/bi060173m
MARSILJE,T.H. ET AL: "Design, synthesis, and biological evaluation of simplified α-Keto heterocycle, trifluoromethyl keto", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 11, no. 20, JPN6016002134, 2003, pages 4487 - 4501, ISSN: 0003366629
DATABASE REGISTRY, JPN7016000118, 23 March 2007 (2007-03-23), ISSN: 0003366630
Attorney, Agent or Firm:
Ikeuchi, Sato & Partners