455-91-4Relevant articles and documents
Design, synthesis, and biological evaluation of novel dual PPARα/δ agonists for the treatment of T2DM
Deng, Liming,Hu, Lijun,Li, Zheng,Ren, Qiang,Wang, Xuekun,Xie, Rongrong,Zhou, Zongtao
, (2020/06/01)
Dual PPARα/δ agonists have been considered as potential therapeutics for the treatment of type 2 diabetes mellitus. After comprehensive structure–activity relationship study based on GFT505, a novel dual PPARα/δ agonist compound 6 was identified with highly activities on PPARα/δ and higher selectivity against PPARγ than that of GFT505. The modeling study revealed that compound 6 binds well to the binding pockets of PPARα and PPARδ, which formed multiple hydrogen bonds with key residues related to the activation of PPARα and PPARδ. Moreover, oral glucose tolerance test exhibited that compound 6 exerts dose-dependent anti-diabetic effects in ob/ob mice and reveals similar potency to that of GFT505, the most advanced candidate in this field. These findings suggested that compound 6 is a promising candidate for further researches, and the extended chemical space might help us to explore better PPARα/δ agonist.
Fries rearrangement: Scalable synthesis of key fluoro building blocks 3-fluoro-4-methoxybenzoyl chloride and 1,2-diethoxy-3-fluorobenzene
Yerande, Swapnil G.,Shendage, Deepak M.,Wakchaure, Prasad B.,Phadtare, Ganesh R.,Bhoite, Madhavrao Y.,Gangopadhyay, Ashok Kumar,Nagarajan, Kuppuswamy,Rupp, Richard Helmut
, p. 2426 - 2429 (2014/05/06)
Lewis acid catalyzed Fries rearrangement of 2-fluorophenyl acetate (3) was performed on kg scale. The ortho 5 and para 4 isomers obtained were separated in an industrially feasible way. Compound 4 was then converted into fluorinated building block 3-fluoro-4-methoxybenzoyl chloride (1) while compound 5 was converted into 1,2-diethoxy-3-fluorobenzene (2) in high yields.
PHARMACEUTICAL COMPOUNDS
-
, (2010/11/25)
The invention provides a compound of the formula (I) or a salt, solvate, tautomer or N-oxide thereof; wherein A is a saturated hydrocarbon linker group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; L1 is a bond or a linker selected from C1-C4 alkenylene, C1-C4 alkynylene, -CONR’, -NR’CO, -S, -C(O)-, -C(NR11)-, -C(S)-, -N(R11)2, C(=CHR11), -SO- and -SO2-; or L1 together with t R16 forms and 8-12 membered fused bicyclic heteroaryl ring system; L3 is a bond or a linker selected from CONH and HNCO; provided that L1 and L3 cannot both be linkers simultaneously; and provided also that L1 and L3 cannot both be a bond simultaneously; R16 is an optionally substituted 5- to 12-membered monocyclic or bicyclic carbocyclic or heterocyclic ring; L2 is absent or is a linker selected from C]-C4 alkylene, Ci-C4 alkenylene, Ci-C4 alkynylene, -CONR’-, -NR’CO-, -O-, -S-, -C(O)-, C(=CHR11), C(S)-, -N(R11)2, C3-4 cycloalkanediyl, -SO- and -SO2-; R17 is absent or is C1-6 alkyl or an optionally substituted 5 to 12 membered carbocyclic or heterocyclic ring; provided that when R17 is absent, then L2 is also absent; and R2, R3, R4, R5, R11 and R’ are as defined in the claims.