Discovery of CS-2100, a potent, orally active and S1P3-sparing S1P1 agonist
摘要:
S1P(3)-sparing S1P(1) agonists have attracted attention as a suppressant of autoimmunity with reduced side effects. Our synthetic efforts and extensive SAR studies led to the discovery of 10b named CS-2100 with the EC50 value of 4.0 nM for human S1P(1) and over 5000-fold selectivity against S1P(3). The in vivo immunosuppressive efficacy was evaluated in rats on host versus graft reaction and the ID50 value was determined at 0.407 mg/kg. The docking studies of CS-2100 with the homology model of S1P(1) and S1P(3) showed that the ethyl group on the thiophene ring of CS-2100 was sterically hindered by Phe263 in S1P(3), not in the case of Leu276 in S1P(1). This observation gives an explanation for the excellent S1P(3)-sparing characteristic of CS-2100. (C) 2011 Elsevier Ltd. All rights reserved.
ACTIVE ESTER COMPOUND AND COMPOSITION AND CURED PRODUCT OBTAINED USING THE SAME
申请人:DIC Corporation
公开号:US20200207700A1
公开(公告)日:2020-07-02
The present invention aims to provide a means by which a cured product to be obtained has a low dielectric loss tangent and higher heat resistance. Specifically, provided are an active ester compound represented by chemical formula (1):
(where in chemical formula (1), Ar
1
is a substituted or unsubstituted first aromatic ring group, and each Ar
2
is independently a substituted or unsubstituted second aromatic ring group, in which at least one of Ar
1
and Ar
2
has an unsaturated bond-containing substituent, and n is an integer of 2 or 3), a curable composition containing the active ester compound, and a cured product thereof.
Process for stereoselective synthesis of 2-hydroxymethyl chromans
申请人:Wyeth
公开号:US20030105342A1
公开(公告)日:2003-06-05
A process for the stereoselective synthesis of 2-hydroxymethyl-chromans of formula (II) is provided
1
where R, R
1
, R
2
and R
3
are as defined herein. The compound of formula (II) is prepared using an optically active benzene compound of formula (I)
2
where R
0
is as defined herein. The 2-hydroxymethyl-chroman compounds of formula (II) are useful as intermediates for preparing a variety of medicinal agents.
Select metal salts of mono and di aromatic sulfonic acids and aliphatic sulfonic acids are effective latent acid catalysts in coating compositions capable of acid catalyzed crosslinking and provide coating compositions with lower cure temperature and quicker cure times than encountered with conventional sulfonic acid catalysts, have excellent storage stability and avoid drawbacks of epoxy and amine blocked sulfonic acid catalysts.
Herein, we have designed and demonstrated a copper-catalyzed intramolecular SEAr reaction−oxidation process to access styryl-/alkenyl-substituted xanthone derivatives. This protocol affords a variety of substituted xanthone derivatives in moderate to high yields. The protocol has been demonstrated by gram-scale syntheses.
在此,我们设计并展示了一种铜催化的分子内 S E Ar 反应-氧化过程,以获得苯乙烯基/烯基取代的氧杂蒽酮衍生物。该协议提供了多种中等至高产率的取代氧杂蒽酮衍生物。该协议已通过克级合成得到证明。