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Beginning in March 2020, New York City began the fight against coronavirus disease 2019. Health care workers were faced with a disease that led to significant morbidity and mortality with no proven therapies. As hospitals became inundated with patients and underwent rapid expansion of capacity, resources such as drugs, protective and medical equipment, and hospital staff became limited. Pharmacists played a critical role in the management of clinical care and drug delivery during the pandemic. As members of the department of pharmacy within NewYork‐Presbyterian Hospital, we describe our experiences and processes to overcome challenges faced during the pandemic. Strict inventory management through the use of daily usage reports, frequent communication, and minimization of waste was critical for the management of drug shortages. The creation of guidelines, protocols, and restrictions were not only used to mitigate drug shortages, but also helped educate health care providers and guided medication use. Managing technology through setting up new automatic dispensing cabinets to address hospital expansions and modifying the electronic order entry system to include new protocols and drug shortage information were also vital. Additional key pharmacist functions included provision of investigational drug service support and training of pharmacists, prescribers, nurses, and respiratory therapists to educate and standardize medication use. Through implementation of operational and clinical processes, pharmacists managed critical drug inventory and guided patient treatment. As the pandemic continues, pharmacists will remain vital members of the multidisciplinary team dedicated to the fight against the virus. This article is protected by copyright. All rights reserved.

The effect of hypoxia on 3T3-L1 cell differentiation was examined in confluent cultures incubated with differentiation medium (DM) followed by incubation in growth medium (GM). Control cultures remained in GM throughout the incubation period. Eight days after the incubation, cells were assessed either for changes in morphology by staining with Oil Red O/hematoxylin or harvested to measure protein kinase C activity. Morphological examination of stained cells showed almost complete differentiation of normoxic cells to adipocytes when exposed to DM. By contrast hypoxia caused a dramatic inhibition of differentiation under similar media conditions with only 34 ± 4% of cells accumulating fat deposits. Cultures sustained in GM under normoxic or hypoxic conditions were devoid of any fat deposits, reflecting an undifferentiated phenotype. Normoxic cells exposed to DM exhibited a significantly lower membrane to cytosolic ratio of protein kinase C in comparison with cells maintained in GM, which is consistent with differentiated and undifferentiated phenotypes, respectively. In comparison with normoxic cells incubated in DM, cells exposed to hypoxia under similar media conditions exhibited a significantly higher membrane to cytosolic ratio of protein kinase C, indicating sustained activation of the enzyme. In addition, cells in differentiation medium exposed to hypoxia in the presence of the protein kinase C inhibitors staurosporine or H7 exhibited a significant increase in the number of fat accumulating cells when compared with hypoxic controls. These studies indicate that chronic hypoxia impairs the differentiation of 3T3-L1 cells to adipocytes in association with the sustained activation of protein kinase C, which appears to play a role in mediating this process. © 1994 Wiley-Liss, Inc.

Treatment of heterocyclic o-aminonitriles and o-aminoesters 1a-5a with dibromotriphenylphosphorane gives iminophosphoranes 1b-5b which undergo a facile aza-Wittig reaction at room temperature with phenyl isocyanate to provide the carbodiimides 1c-5c. Treatment of the latter intermediates with ammonia leads to intramolecular ring closure of the initially formed guanidines to provide the fused 4-aminopyrimidines and 4(3H)-pyrimidinones 1d-Sd.

Two series of cyclic ureas modified at the P1/P1′ residue were prepared and evaluated for HIV protease inhibition and whole cell antiviral activity. Compounds 8b, 10 (3- and 4-pyridylmethyl analogs) and 6b (4-methoxy analog) showed significant improvement in antiviral activity relative to lead compounds DMP323 and DMP 450.

A series of 4,4-disubstituted quinolinones was prepared and evaluated as HIV-1 reverse transcriptase inhibitors. The C-3 substituted compound 9h displayed improved antiviral activity against clinically significant single (K103N) and double (K103N/L100I) mutant viruses.

Treatment of heterocyclic o-aminonitriles and o-aminoesters 1a-5a with dibromotriphenylphosphorane gives iminophosphoranes 1b-5b which undergo a facile aza-Wittig reaction at room temperature with phenyl isocyanate to provide the carbodiimides 1c-5c. Treatment of the latter intermediates with ammonia leads to intramolecular ring closure of the initially formed guanidines to provide the fused 4-aminopyrimidines and 4(3H)-pyrimidinones 1d-Sd.

A series of indole-O-glucosides and C-glucosides was synthesized and evaluated in SGLT1 and SGLT2 cell-based functional assays. Compounds 2a and 2o were identified as potent SGLT2 inhibitors and screened in ZDF rats.

A series of benzo-fused heteroaryl-O-glucosides was synthesized and evaluated in SGLT1 and 2 cell-based functional assays. Indole-O-glucoside 10a and benzimidazole-O-glucoside 18 exhibited potent in vitro SGLT2 inhibitory activity.

A series of substituted spirobenzazepines was prepared and evaluated as V1a and V2 dual vasopressin receptor antagonists. Compounds 7p and 7q have been shown to be not only potent inhibitors of vasopressin receptors, but also have exhibited an excellent overall pharmaceutical suitability profile.

The practical and highly diastereoselective syntheses of CF3-substituted dihydroquinazolinones via 1,4-additions of nucleophiles to chiral auxiliary substituted 2(3H)-quinazolinones is described. This methodology is applied to the syntheses of the NNRTIs (nonnucleoside reverse transcriptase inhibitors) DPC 961 (1) and DPC 083 (2), which are useful for the treatment of HIV (human immunodeficiency virus). The synthesis of DPC 961 (1) requires three steps, proceeds in >55% overall yield from the keto-aniline 9, and gives synthetic access to DPC 083 (2). In addition, the scope of the new diastereoselective 1,4-addition chemistry is investigated. The first preparation of DPC 961 (1) described in this paper is a derivatization fractional crystallization protocol.

A series of 3,3-disubstituted quinoxalinones was prepared and evaluated as HIV-1 reverse transcriptase inhibitors. The N-allyl (6b and 6f), N-cyclopropylmethyl (6a, 6g, 6h, and 6k) and N-carboalkoxy (6m-6y) substituted compounds displayed activity comparable or better than Efavirenz and GW420867X.

Etude de la cycloaddition des deux composes du titre avec le t-butyldimethylsiloxymethyl-2 cyclohexadiene-1,3