Optimization and Scale-Up of a Lipase-Catalyzed Enzymatic Resolution of an Indole Ester Intermediate for a Prostaglandin D2(DP) Receptor Antagonist Targeting Allergic Rhinitis

2006 ◽  
Vol 10 (3) ◽  
pp. 592-598 ◽  
Author(s):  
Matthew D. Truppo ◽  
Michel Journet ◽  
Ali Shafiee ◽  
Jeffrey C. Moore
Keyword(s):  
Allergic Rhinitis ◽  
Receptor Antagonist ◽  
Scale Up ◽  
Prostaglandin D2 ◽  
Enzymatic Resolution

scholarly journals The Mineralocorticoid Receptor Antagonist Eplerenone Suppress Interstitial Fibrosis in Subcutaneous Adipose Tissue in Type 2 Diabetes Patients

2020 ◽  
Author(s):  
Ada Admin ◽  
Marie Louise Johansen ◽  
Jaime Ibarrola ◽  
Amaya Fernández-Celis ◽  
Morten Schou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Receptor Antagonist ◽  
Subcutaneous Adipose Tissue ◽  
Mineralocorticoid Receptor ◽  
Prostaglandin D2 ◽  
Type I ◽  
Mineralocorticoid Receptor Antagonist ◽  
Subcutaneous Adipose

Activation of the mineralocorticoid receptor (MR) may promote dysfunctional adipose tissue in patients with type 2 diabetes, where increased pericellular fibrosis has emerged as a major contributor. The knowledge of the association between the MR, fibrosis and the effects of an MR antagonist (MRA) in human adipocytes remains very limited. The present sub-study including 30 participants was prespecified as part of the Mineralocorticoid Receptor Antagonist in type 2 Diabetes (MIRAD) trial, randomizing patients to either high dose eplerenone or placebo for 26 weeks. In adipose tissue biopsies, changes in fibrosis were evaluated by immunohistological examinations and by the expression of mRNA and protein markers of fibrosis. Treatment with an MRA reduced pericellular fibrosis, synthesis of the major subunits of collagen type I and VI, and the profibrotic factor α-smooth muscle actin, as compared to placebo in subcutaneous adipose tissue. Furthermore, we found decreased expression of the MR and downstream molecules neutrophil gelatinase–associated lipocalin, galectin-3, and lipocalin-like prostaglandin D2 synthase with an MRA. In conclusions, we present original data demonstrating reduced fibrosis in adipose tissue with inhibition of the MR, which could be a potential therapeutic approach to prevent the extracellular matrix remodeling of adipose tissue in type 2 diabetes.

Scale-up of the enantioselective reaction for the enzymatic resolution of (R,S)-ibuprofen

1995 ◽  
Vol 17 (10) ◽  
pp. 1095-1098 ◽  
Author(s):  
M. Trani ◽  
A. Ducret ◽  
P. Pepin ◽  
R. Lortie
Keyword(s):  
Scale Up ◽  
Enzymatic Resolution ◽  
Enantioselective Reaction

Effect of thromboxane A2-receptor antagonist on bradykinin-induced bronchoconstriction in asthma

1996 ◽  
Vol 80 (6) ◽  
pp. 1973-1977 ◽  
Author(s):  
K. Rajakulasingam ◽  
S. L. Johnston ◽  
J. Ducey ◽  
W. Ritter ◽  
P. H. Howarth ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Geometric Mean ◽  
Thromboxane A2 ◽  
Forced Expiratory Volume ◽  
Significant Inhibition ◽  
Prostaglandin D2 ◽  
Double Blind ◽  
Bronchial Responsiveness ◽  
Significant Difference ◽  
Txa2 Receptor

The role of the thromboxane A2 (TxA2) receptor in bradykinin-induced bronchial responses was investigated in this study by using a selective and potent TxA2-receptor antagonist BAY u 3405. Eleven asthmatic subjects were randomized to receive 50 mg of BAY u 3405 or matched placebo in a crossover and double-blind fashion. Ninety minutes after dosing, serum was taken for drug assay, and subjects underwent provocation with bradykinin or prostaglandin D2 (PGD2) to determine bronchial responsiveness [provocative concentration of agonist required to produce a 20% fall in forced expiratory volume in 1 s from the postdiluent baseline (PC20)]. Pretreatment with BAY u 3405 caused a twofold doubling-dilution reduction in bronchial reactivity to PGD2; the geometric mean PC20 values were 0.132 (0.015-0.871) and 0.034 (0.008-0.095) mg/ml, respectively, for active and placebo days (P = 0.001). There was, however, no significant difference in PC20 values for bradykinin between active and placebo treatment days. We have demonstrated that BAY u 3405 caused a significant inhibition of bronchconstriction induced by inhaled PGD2 but had no influence on bronchial responsiveness to inhaled bradykinin. This study suggests therefore that TxA2 receptors do not play a role in bradykinin-induced bronchoconstriction in asthma.

Effect of ONO-4053, a DP1 (prostaglandin D2 receptor) Antagonist, on Antigen-Induced Nasal Congestion

2015 ◽  
Vol 135 (2) ◽  
pp. AB219
Author(s):  
Shinsuke Yamaguchi ◽  
Yutaka Okada ◽  
Yoko Matsunaga ◽  
Fumio Nambu
Keyword(s):  
Receptor Antagonist ◽  
Nasal Congestion ◽  
D2 Receptor ◽  
Prostaglandin D2
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