cancel
Showing results for 
Search instead for 
Did you mean: 
tfujimoto
Contributor

Riociguat : BAY 63-2521(Phase-III), sGC Stimulator / Bayer

0 Kudos
tfujimoto
Contributor

MK-0668, VLA-4 Antagonist / Merck

0 Kudos
tfujimoto
Contributor

γ-Secretase Inhibitors with Excellent in Vivo Activity / Merck

0 Kudos
tfujimoto
Contributor

5-Hydroxyindole-2-Carboxylic Acid Amides, H3R Inverse Agonists / Hoffmann-La Rohe

H3R inverse agonists was designed by feasible pharmacophore model. It is interesting that rat microsomal clearance is negatively correlated with pKa, and hERG correlation model is relying solely on two descriptors, the percentage of membrane-bound compound in PAMPA, and log D.

http://pubs.acs.org/doi/pdf/10.1021/jm900409x

0 Kudos
tfujimoto
Contributor

Motilin R Antagonists: From Tetrapeptide to Orally Available Peptidomimetics / Chugai

Drug design focused on downsizing the molecular weight of macrocyclic peptide GM-109. Dipeptide analogues of Phe-Thy(tBu) as essential pharmacophore was synthesized, and then orally available dipeptide antagonists were discovered.

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TF9-4WBC1N6-1-1&_cdi=5221&_user=2645672&_o...


0 Kudos
tfujimoto
Contributor

Physicochemical Determinants of Human Renal Clearance / Pfizer

This report is about an analysis of the interrelation of physicochemical properties and the human renal clearance for a data set of 391 drugs or compounds tested n humans.

http://pubs.acs.org/doi/pdf/10.1021/jm900403j

0 Kudos
tfujimoto
Contributor

CB2 Agonists Using Parallel Synthesis Protocols: a Lipophilic Efficiency (LipE) Analysis / Pfizer

The lipophilic efficiency is defined by pIC50 (potency) - clogP (lipophilicity), so that this descriptor is a good reference index of druglikeness. This paper reported that analysis of the lipophilic efficiency of parallel synthesized compounds provided new insight for the design of potent, metabolically stable CB2 agonists.

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TF9-4WBK788-1-1&_cdi=5221&_user=2645672&_o...

0 Kudos
tfujimoto
Contributor

SEN12333/WAY-317538, Novel α7 nAchR Agonist / Wyeth, Siena

SEN12333/WAY-317538 is a selective alpha7 nicotinic acetylcholine R agonist with excellent in vitro and in vivo profiles, excellent brain penatration and oral bioavailability, and demonstrates in vivo efficacy in multiple behavioral cognition models. The SAR and biological evaluation of this series of compounds is discussed.
http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TF8-4WBK784-4-3&_cdi=5220&_user=2645672&_o...

0 Kudos
tfujimoto
Contributor

MK-0533, A SPARM / Merck

MK-0533 was Merck's clinical candidate (Phase-II, but now discontinued) of SPARM. The indole scaffold was probably originated from their traditional drug of indomethacin as a NSAID. SAR was featured by Fig. 1. The drug design was N-shuffle of indole to prevent deasylation. MK-0533 showed good in vivo efficacy and reduced side-effects at animal models.

More recently, they published a SPARM with weak alpha-PPAR activity.

http://pubs.acs.org/doi/pdf/10.1021/jm900097m

http://pubs.acs.org/doi/pdf/10.1021/jm900367w

0 Kudos
tfujimoto
Contributor

Cyclohexamine Class of NPY Y1R Antagonists / Banyu

Optimization of NPY1R antagonists with reducing hERG and SERT activity was reported. hERG binding was avoided by replacement of one of the phenyl of diphenylmethane structure with pyrrolidine amide. On the other hand, SERT activity was reduced by lowering basicity of amine. The calculated basicity of difluoroethylamine 2m (pKa = 6.02) and trifluoroethylamine 3i (pKa = 4.24) were lower than ethylamine 2m (pKa = 10.25). In fact, SERG activity of 2m and 2n were negligible.


http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TF9-4WJBBS5-1-3&_cdi=5221&_user=2645672&_o...


0 Kudos