Qifang Li's research while affiliated with Pfizer and other places

... In favourable cases, this can lead to greatly enhanced potency, selectivity, solubility, and metabolic stability 23,24 . For instance, Pfizer have exploited a spirocyclic THN as the core of their MC4R antagonist PF-07258669 5, which is currently in phase I clinical trials for the treatment of appetite loss (Fig. 1c) 25 . The spirocycle in 5 was rationally designed to enforce a cis-relationship between the N-H bond and the adjacent N(sp 2 ) lone pair, which is the optimal geometry for target binding but opposite to the (trans) conformer favoured in solution for the non-constrained analogue. ...

... IONIS-DGAT2Rx is an antisense oligonucleotide inhibitor of DGAT2 expression which prevents LFC in a phase 2 trial [81]. Another DGAT2 inhibitor named ervogastat (PF-06865571) presented similar efficacy on liver steatosis, without serious gastrointestinal adverse events [82]. It's noting worth that co-administration of ACC inhibitor PF-05221304 and DGAT2 inhibitor PF-06865571 has a stacked efficacy and successfully overcomes the obstacle of ACC [83], although ACC inhibitors alone have obvious adverse effects of elevating serum TG and activating SREBP1c. ...

... Therefore, many previous studies have considered it as an important candidate gene for meat quality and carcass traits in meat-type animals (14,19). Meanwhile, it is also regarded as a candidate gene for milk fat percentage in milktype animals mainly focused on ruminants (25)(26)(27). Many studies have reported that the expression of DGAT2 is significantly associated with meat quality traits and carcass traits, especially on IMF content in pigs, steers, yaks, and chickens (1,2,15,16). ...

... PF-06409577 (27) was synthesized as a direct AMPK activator depicted in Scheme 16 [36]. PF-06409577 exhibited definitive efficacy in the therapy of DN [37]. ...

... nM) has hydrogen bonding interactions with Lys29 and Asn111 ( Figure 3A), and the carboxyl group at position 3 of 12 i (EC 50 = 11.0 nM) has similar hydrogen bonding interactions with the above amino acid residues, but the methoxy group at position 2 has additional hydrogen bonding interactions with Lys29 ( Figure 3B), which may be the reason for its stronger activity than that of 10 c. A study reported in 2018 identified Asn111 as a key residue in binding site, [20] and a research in 2016 also identified Lys29 as a critical residue, [21] supporting the modelling in this study. In summary, Lys29 and Asn111 may be the key binding sites in the AMPK pocket and that compound binding to them can significantly increase activity. ...

... Imidazo [4,5-b]pyridines are an important family of heterocyclic compounds, and their derivatives possess various pharmacological properties [6][7][8][9][10][11]. Examples of pharmacologically active compounds containing an imidazo [4,5b]pyridine skeleton are shown in Figure 1. ...

... [52] Their synthesis can be achieved starting from compound 13 using the previously reported C(sp 3 )À C(sp 2 ) coupling procedure. [53] Finally, catalytic reduction of the double bond in hydrochloride 3 b HCl under relatively mild conditions readily gave diastereomerically pure cis-3-borylated 4-methylpyrrolidine 14 in 80 % yield (Scheme 6). [24] It should be noted that monocyclic cis-isomeric 3,4-disubstituted borylated pyrrolidines are scarcely accessible by direct [3 + 2] cycloaddition of cis-1,2-disubstituted alkenyl boronates [24] (due to low availability of the starting dipolarophiles) or other methods. ...

... Quinoline is a key heterocyclic moiety found in many natural products [1][2][3][4], agrochemicals and pharmaceuticals having potent biological activities, such as antimalarial, antibacterial and anticancer activities [5][6][7][8][9][10][11]. Due to their wide range of applications, selective functionalization of quinolines at various positions has gained significant interest in the last few years [12,13]. In particular, the C2-functionalization of quinolines has been well studied, and various methodologies were established for C-C [14][15][16][17][18][19][20][21][22][23], C-O [24,25] and C-S [26,27] bond formation. Recently C2-selective C-N bond formation has also attracted considerable attention due to the importance of the 2-aminoquinoline motif in medicinal chemistry and pharmaceuticals [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. ...

... One such inhibitor, PF-06649298, was found to completely block citric acid uptake and protect mice from diet-induced glucose intolerance 57 . A more potent inhibitor, PF-06761281, demonstrated dose-dependent reduction in citrate uptake by the liver and kidney, resulting in decreased blood glucose levels in rats 58 . These findings suggest that a chemical inhibitor of SLC13A5 may hold potential as a drug candidate for the treatment of T2DM. ...

... The dose of the DGAT2 inhibitor chosen was based on the dose and pharmacokinetics parameters published previously. 14,32 The phenotypic parameters of the mice treated with iDgat2 are summarized in Table 1. Administration of iDgat2 did not change food intake, body weights, liver weights, blood glucose, or insulin levels. ...