Yves Gareau's research while affiliated with Merck & Co. and other places

... Various serotonergic receptors, 5-HT 1A , 5-HT 2A , and 5-HT 2C , as expressed in Xenopus laevis oocytes, have been reported to show oleamide-sensitive receptor signals (Thomas et al., 1997), although this was not reproducible in our hands in mammalian expression systems (W. B. Im, C.L. Chio, G. L. Alberts, unpublished observations (Carriere et al., 2000), probably indicating complex conformational perturbations via multiple interaction sites. Overall, these earlier studies have indicated the presence of allosteric modulatory sites at G protein-coupled receptors, but modulatory actions through these sites were limited to local impacts on certain ligandbinding sites, species-dependent modulations, or nonspecific functional perturbations. ...

... Moreover, a pi-sigma interaction at Phe778 and Tyr857, a pi-alkyl interaction at Leu777 and Cys605, and an alkyl interaction at Phe858 are also predicted to form. (5), when docked to 5-LOX (Figure 6a), yielded a binding affinity of -8.5 kcal/mol which is lower compared to Setileuton, a novel selective 5-LOX inhibitor, with a docking score of -9.6 kcal/mol [37]. During inflammation, particularly in asthma, the 5-LOX pathway gives rise to proinflammatory leukotrienes (LTs) which are targets of LT antagonists to reduce inflammation [38]. ...

... This receptor has a key role in osteoclast function (Whyte et al., 2009), cancer cell proliferation (Hu et al., 2011;Pineiro et al., 2011), and hyperalgesia associated with inflammation (Staton et al., 2008). Rinaldi-Carmona, et al., 1994;Showalter et al., 1996) Gifford et al., (1999Rinaldi-Carmona, et al., 1994Hillard et al., (1999) Hanuš et al., (2001) Järbe et al., (1998Khanolkar et al., 1996) Phytocannabinoids Cannabidiol (CBD) HU-210 O-1602 D9THC (Bloom et al., 1997;Freedland et al., 2002;Goldman et al., 1975;Howlett et al., 2004;Margulies and Hammer, 1991;Pontieri et al., 1999;Stein et al., 1998) CB2-selective ligands: JWH-015 JWH-051 L-768242 JWH-139 AM 630 JWH-133 L-759633 L-759656 HU-308 SR144528 Showalter et al., (1996) Huffman et al., (1996) Gallant et al., (1996) Huffman et al., (1996) Huffman et al., (1996Ross et al., 1999) Rinaldi-Carmona, et al., 1994Rinaldi-Carmona, et al., 1994Ross et al., 1999;Showalter et al., 1996) (Matsuda et al., 1990;Pertwee, 2005) Ligands without any CB1/ CB2 selectivity: Hillard et al., (1999;Järbe et al., 1998;Mechoulam and Fride, 1995;Showalter et al., 1996) Ben-Shabat et al., (1998Fride, 1995) Felder andRhee et al., 1998) Hillard et al., (1999Rinaldi-Carmona, et al., 1994;Ross et al., 1999;Showalter et al., 1996) Bayewitch et al., (1996Rhee et al., 1998;Showalter et al., 1996) Busch-Petersen et al., ( ) Hillard et al., (1999Shire et al., 1996;Showalter et al., 1996) McHugh (2012McHugh et al., 2012) GPR55 has been detected in regions of the CNS including the caudate nucleus, putamen, striatum, hippocampus, thalamus, pons, cerebellum, frontal cortex, hypothalamus, and large dorsal root ganglion cells (Ryberg et al., 2007;Sawzdargo et al., 1999). Stimulation of this receptor by several CBs (Δ9-THC, the AEA analog methanandamide, and JWH015) (Lauckner et al., 2008;Ross, 2009) leads to increases in intracellular Ca 2+ , induces the rapid phosphorylation of extracellular signal-regulated kinase (ERK), and activates small GTPase proteins (RhoA, Rac and cdc42) (Ross, 2009). ...

... [6][7][8][9][10][11] Among the two isomers, cis-diazene is the most active reducing agent for CQC and CRC bonds, a process which occurs by concerted transfer of two H atoms and is a highly preferred hydrogenation method. [12][13][14][15] Detailed energetics, structures, and isomerization pathways of diazene have been investigated in numerous quantum chemistry studies. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Spectroscopic investigations of the ground state properties of diazene have been reported. ...

... The reaction was successful even when a free phenolic function was present in the employed acid and the desired β-anomer of the 1-O-acyl-β-D-glucuronide products could be isolated in up to 50% yield. Similarly, regioselective esterification of unprotected allyl glucuronide 11 was Scheme 4: Conversion of allyl glucuronate into various 1-O-esterified allyl glucuronates using anomeric Mitsunobu esterification [36,37]. ...

... The indole ring is a privileged scaffold in medicinal chemistry, 20 and several types of compounds having the indole moiety have been demonstrated to display CB2 activity. [21][22][23][24][25][26][27][28] We found that several of these CB2 ligands contain an N-ethyl morpholine ring structure (Fig. 1). WIN-55212-2 was first reported by Sterling-Winthrop as a nonselective cannabinoid receptor agonist with antiinflammatory activity (K i IJCB1) = 1.9 nM, K i IJCB2) = 0.3 nM), and is regularly used in pharmacological and behavioral research. ...

... Interestingly, caspase-9 did not alter after damage, although Bcl2 and Bax alters [71]. Thus, Bcl2 and Bax may activate caspase-3, but only in pH-dependent autocatalytic processing [72]. In other hand, Sakata et al., indicate that the zebrafish caspase-8 shares significant structural and functional characteristics with its mammalian counterparts. ...

... Gallant et al. [98] have described two indole-derived compounds (see structures below), with binding potency for the human peripheral cannabinoid receptor (CB 2 ) in the nanomolar region, They are highly selective. A new series of rigid 1-aryl-1,4-dihydroindeno[1, 2-c]pyrazole-3-carbox- amides was recently designed [99]. Seven of the new compounds displayed very high in vitro CB 2 -binding affinities. ...

... Since both drugs are optically active [15,16] all tablet formulae were film coated. Tablets were coated in Manesty 150 coating pan (Liverpool, UK). ...

... Our SMILES transformation dictionary is shown in Electronic Supplementary Material. For example, the SMILES and encoding of molecule Montelukast [33] is shown in Fig. 1. ...