Nicholas A. Meanwell's research while affiliated with Baruch S. Blumberg Institute and other places

... 18 F-BMS-986192, which was evaluated in non-small cell lung cancer and melanoma, demonstrated a correlation with pathologic evaluation and responses using this method but was challenging to synthesize and was isolated in only modest radiochemical yields (13,14). 18 F-BMS-986229 is a macrocyclic peptide with high affinity for PD-L1, tight binding with a slow off-rate from the receptor, rapid clearance from non-PD-L1-expressing tissues, and the ability to be isolated in higher yields while also being less challenging to synthesize than 18 F-BMS-986192 (15,16). Preclinical evaluations of 18 F-BMS-986229 demonstrated specific binding to PD-L1-expressing tissues in vitro and in vivo (15,16). ...

... 18 F-BMS-986192, which was evaluated in non-small cell lung cancer and melanoma, demonstrated a correlation with pathologic evaluation and responses using this method but was challenging to synthesize and was isolated in only modest radiochemical yields (13,14). 18 F-BMS-986229 is a macrocyclic peptide with high affinity for PD-L1, tight binding with a slow off-rate from the receptor, rapid clearance from non-PD-L1-expressing tissues, and the ability to be isolated in higher yields while also being less challenging to synthesize than 18 F-BMS-986192 (15,16). Preclinical evaluations of 18 F-BMS-986229 demonstrated specific binding to PD-L1-expressing tissues in vitro and in vivo (15,16). ...

... Finally, multiparametric characterization with flow cytometry can be used to support a rationale for therapeutic combinations. Wichroski et al. recently reported the discovery of potent small molecules targeting DGKα/ζ, integrating flow cytometry assays to reveal enhancement of TCR signaling under conditions where antigen presentation was rate-limiting [53]. Downregulation of MHC-I and reduced neoantigen presentation is a hallmark of PD-1 or PD-L1 immune checkpoint resistance [54], providing a rationale to combine DGKα/ζ with immune checkpoint blockade in the clinic. ...

... Table 4. A comparison of anti-HIV-1 activity values of bevirimat (3) and the compounds 17-19 [47,48]. The investigation of the structure-activity relationships of a series of HIV-1 maturation inhibitors based on the compound 17s ( Figure 3) continued by the subsequent incorporation of novel C-17 amine substituents to reduce the overall basicity of the target compounds [47]. ...

... Ritanserin was originally discovered as a 5-HT2A receptor antagonist (31). Despite some similarity to ritanserin, the naphthyridinone series from Bristol-Myers Squibb was identified through various parallel phenotypic T cell screens (32). For one hit, a quinolone (compound 1/BMS-684, Table 2B), the respective targets were identified as DGKa and DGKz. ...

... We only used anagrelide and 2H5F in the current study. Anagrelide is a blood thinner used to treat thrombocythemia by reducing the platelet count to prevent megakaryocyte maturation in the bone marrow without interfering with other progenitor cells [24]. Also, 2-hydroxy-5-fluoropyrimidine (2H5F) is converted to 5-fluorouracil by hepatic aldehyde oxidase [25,26]; 5-fluorouracil inhibits metabolic processes in cells and is incorporated into RNA in tumor cells more often than normal cells. ...

... From the perspective of drug development, the most synthetically useful LSF methods enable the selective C-H installation of small groups that have the capacity to positively influence key biological characteristics of a drug molecule without considerably altering its structural feature 13 . Notably, a variety of emerging small alkyl groups and aliphatic ring systems have been increasingly exploited in medicinal chemistry for their advantageous physicochemical properties and applications as bioisosteres [14][15][16] . ...

... Popular pyrimidines (33) and pyridazines (34) are also tolerated under the standard reaction conditions. 14a, 27 We next turned our attention toward common azoles. Pyrazole (35) and isothiazole (36) were tolerated under the reaction conditions. ...

... GSK878 is a newly described HIV-1 inhibitor that binds to a mature capsid (CA) hexamer in a pocket identified initially as a binding site for the CA inhibitor PF-74 . GSK878 is involved in early (pre-integration) and late (postintegration) HIV-1 replication and is associated with altered stability in the HIV-1 CA core (Gillis et al., 2023). ...

... Decarboxylative cross coupling has seen increasing use for rapidly appending alkyl fragments to arenes of all types (Figure 1B). [12][13][14][15] Whereas the scope of such couplings is broad when primary and secondary acids and their redox-active esters (RAEs) are employed, extending that reactivity to tertiary acids has been a vexing problem. [16][17][18][19] For instance, the simple coupling of RAE/acid 1ab with pyrimidine 2 fails under the most modern of conditions (chemical, photochemical, electrochemical), delivering at most 9% yield. ...