114744-84-2Relevant articles and documents
The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen der p 1: An innovative approach to the treatment of allergic asthma
Newton, Gary K.,Perrior, Trevor R.,Jenkins, Kerry,Major, Meriel R.,Key, Rebekah E.,Stewart, Mark R.,Firth-Clark, Stuart,Lloyd, Steven M.,Zhang, Jihui,Francis-Newton, Nicola J.,Richardson, Jonathan P.,Chen, Jie,Lai, Pei,Garrod, David R.,Robinson, Clive
, p. 9447 - 9462 (2014)
Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma.
One-pot synthesis of Weinreb amides employing 3,3-dichloro-1,2-diphenylcyclopropene (CPI-Cl) as a chlorinating agent
Shekharappa,Roopesh Kumar,Sureshbabu, Vommina V.
supporting information, p. 790 - 798 (2019/03/26)
The synthesis of Nα-protected amino alkyl Weinreb amides starting from the corresponding α-amino acids as well as carboxylic acids has been delineated through the in situ generation of acid chlorides using CPI-Cl as a chlorinating agent. The protocol is simple; the reaction conditions employed were mild, and compatible with all the three commonly used urethane protecting groups namely, Boc, Cbz and Fmoc groups. The resulting Weinreb amides are obtained in good yields as optically pure products.
ALIPHATIC PROLINAMIDE DERIVATIVES
-
Paragraph 0142; 0143; 0144, (2018/04/11)
This invention is directed to novel aliphatic prolinamide derivatives of Formula I, and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of age-related macular degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry-AMD, wet-AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention. The compounds of the invention are inhibitors of HTRAl. Thus, the compounds of the invention are useful in the prevention and treatment of a wide range of diseases mediated (in whole or in part) by HTRAl. The compounds of the invention are also useful for inhibiting HTRAl protease activity in an eye or locus of an arthritis or related condition.
