Novel Tricyclic-α-alkyloxyphenylpropionic Acids: Dual PPARα/γ Agonists with Hypolipidemic and Antidiabetic Activity
摘要:
Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC50 = 0.36 muM) and PPARgamma (EC50 = 0.17 muM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.
Novel Tricyclic-α-alkyloxyphenylpropionic Acids: Dual PPARα/γ Agonists with Hypolipidemic and Antidiabetic Activity
摘要:
Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC50 = 0.36 muM) and PPARgamma (EC50 = 0.17 muM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.
The present invention relates to compounds of the general formula (I)
The compounds are useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR).
The present invention relates to compounds of the general formula (I)
1
The compounds are useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR).
PHOTOACID GENERATOR FOR CHEMICALLY AMPLIFIED PHOTORESISTS
申请人:International Business Machines Corporation
公开号:US20220308448A1
公开(公告)日:2022-09-29
In an approach to improve the field of photoacid generators (PAGs) through a new photoacid generator, in particular to a photoacid generator comprising a new polycyclic aromatic photoacid generator compound anion, and a photoresist composition, comprising said photoacid generator. Embodiments the present invention relate to a method of generating an acid using said photoresist composition and a method of forming a patterned materials feature on a substrate.