Design and Synthesis of Hydroxylamine Derivatives as Indoleamine - 2,3 - Dioxygenase Inhibitors
type: CreativeWork
description: Current research describing therole of indoleamine 2,3-dioxygenase (IDO) and its mechanism of action suggests that the inhibition of IDO with small molecule inhibitors, especially in conjunction with chemotherapy, can provide an effective and novel cancer treatment strategy. This inspired our search for potent and biocompatible IDO inhibitors. A survey of commercially available, stable mimics of the indolenylper oxo intermediate led to our lead compound, O-benzylhydroxylamine, which exhibited sub-micromolar inhibition towards IDO. Structure-activity studies were conducted and focused on the design and synthesis of O benzylhydroxylamine analogues. The addition of a second aryl ring was discovered to be advantageous and resulted in a series of di-aryl analogues Derivatization around the aryl ring(s) with halogen atoms afforded the most potent analogues, displaying nanomolar level cell-based potency, with limited toxicity. The superior ceullar activity of these inhibitors makes them excellent candidates for further biological exploration as therapeutic agents.
abstract: Current research describing therole of indoleamine 2,3-dioxygenase (IDO) and its mechanism of action suggests that the inhibition of IDO with small molecule inhibitors, especially in conjunction with chemotherapy, can provide an effective and novel cancer treatment strategy. This inspired our search for potent and biocompatible IDO inhibitors. A survey of commercially available, stable mimics of the indolenylper oxo intermediate led to our lead compound, O-benzylhydroxylamine, which exhibited sub-micromolar inhibition towards IDO. Structure-activity studies were conducted and focused on the design and synthesis of O benzylhydroxylamine analogues. The addition of a second aryl ring was discovered to be advantageous and resulted in a series of di-aryl analogues Derivatization around the aryl ring(s) with halogen atoms afforded the most potent analogues, displaying nanomolar level cell-based potency, with limited toxicity. The superior ceullar activity of these inhibitors makes them excellent candidates for further biological exploration as therapeutic agents.
author: Winters, Maria
date published: 2014-01-01T08:00:00Z
date modified: 2026-07-24T01:23:46Z
provider: Bryn Mawr University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Bryn Mawr University