76315-01-0Relevant articles and documents
Scale-Up Synthesis of IID572: A New β-Lactamase Inhibitor
Casarez, Anthony,Furegati, Markus,Koch, Guido,Nocito, Sandro,Reck, Folkert,Schuetz, Heiner,Simmons, Robert
, p. 1244 - 1253 (2020)
The new potentially best-in-class β-lactamase inhibitor IID572 was discovered by a late-stage functionalization approach. An alternative synthesis was developed to satisfy the short-term material need for toxicological studies in animals. The new synthetic strategy was built on two key features, an intramolecular azomethine ylide [3 + 2] cycloaddition that allowed the efficient formation of molecular complexity from readily available starting materials and an enzymatic resolution that resulted in high optical purity of a key intermediate.
NOVEL SELECTIVE KAPPA OPIOID RECEPTOR ANTAGONISTS AND METHODS RELATED THERETO FOR TREATMENT OF ADDICTION AND NEUROPATHIC PAIN
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Paragraph 00076, (2020/05/28)
Disclosed is a composition and method for a therapeutic treatment that is able to combat certain conditions such as addiction, alcohol dependence, opioid abuse treatment, neurological disorders, neuropathic pain, and combinations thereof. The compounds act by acting as selective antagonist to the kappa (K) opioid receptor, which, when present leads to the inhibition of conditions, providing increased performance over known treatments. The disclosed compounds also shows the ability to cross the blood-brain-barrier in a highly efficient manner. The disclosed compounds are shown to be effective in the nanomolar range.
Design, Synthesis, and Pharmacokinetic Evaluation of Phosphate and Amino Acid Ester Prodrugs for Improving the Oral Bioavailability of the HIV-1 Protease Inhibitor Atazanavir
Subbaiah, Murugaiah A.M.,Mandlekar, Sandhya,Desikan, Sridhar,Ramar, Thangeswaran,Subramani, Lakshumanan,Annadurai, Mathiazhagan,Desai, Salil D.,Sinha, Sarmistha,Jenkins, Susan M.,Krystal, Mark R.,Subramanian, Murali,Sridhar, Srikanth,Padmanabhan, Shweta,Bhutani, Priyadeep,Arla, Rambabu,Singh, Shashyendra,Sinha, Jaydeep,Thakur, Megha,Kadow, John F.,Meanwell, Nicholas A.
supporting information, p. 3553 - 3574 (2019/04/17)
Phosphate and amino acid prodrugs of the HIV-1 protease inhibitor (PI) atazanavir (1) were prepared and evaluated to address solubility and absorption limitations. While the phosphate prodrug failed to release 1 in rats, the introduction of a methylene spacer facilitated prodrug activation, but parent exposure was lower than that following direct administration of 1. Val amino acid and Val-Val dipeptides imparted low plasma exposure of the parent, although the exposure of the prodrugs was high, reflecting good absorption. Screening of additional amino acids resulted in the identification of an l-Phe ester that offered an improved exposure of 1 and reduced levels of the circulating prodrug. Further molecular editing focusing on the linker design culminated in the discovery of the self-immolative l-Phe-Sar dipeptide derivative 74 that gave four-fold improved AUC and eight-fold higher Ctrough values of 1 compared with oral administration of the drug itself, demonstrating a successful prodrug approach to the oral delivery of 1.
