36374-49-9Relevant academic research and scientific papers
Phosphodiesters as GPR84 Antagonists for the Treatment of Ulcerative Colitis
Chen, Lin-Hai,Fang, You-Chen,Nan, Fa-Jun,Xiao, Yu-Feng,Xie, Xin,Zhang, Qing
, p. 3991 - 4006 (2022/03/14)
GPR84 is a proinflammatory G protein-coupled receptor associated with several inflammatory and fibrotic diseases. GPR84 antagonists have been evaluated in clinical trials to treat ulcerative colitis, idiopathic pulmonary fibrosis, and nonalcoholic steatohepatitis. However, the variety of potent and selective GPR84 antagonists is still limited. Through high-throughput screening, a novel phosphodiester compound hit 1 was identified as a GPR84 antagonist. The subsequent structural optimization led to the identification of compound 33 with improved potency in the calcium mobilization assay and the ability to inhibit the chemotaxis of neutrophils and macrophages upon GPR84 activation. In a DSS-induced mouse model of ulcerative colitis, compound 33 significantly alleviated colitis symptoms and reduced the disease activity index score at oral doses of 25 mg/kg qd, with an efficacy similar to that of positive control 5-aminosalicylic acid (200 mg/kg, qd, po), suggesting that compound 33 is a promising candidate for further drug development.
Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations
Betori, Rick C.,May, Catherine M.,Scheidt, Karl A.
, p. 16490 - 16494 (2019/11/03)
Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.
SPIRO COMPOUNDS USEFUL AS ANTAGONISTS OF THE H1 RECEPTOR
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Page/Page column 31-32, (2009/03/07)
The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, for treating diseases and conditions of the central nervous system (CNS), in particular sleep disorders.
Tricyclic alkylamides as melatonin receptor ligands with antagonist or inverse agonist activity
Lucini, Valeria,Pannacci, Marilou,Scaglione, Francesco,Fraschini, Franco,Rivara, Sivia,Mor, Marco,Bordi, Fabrizio,Plazzi, Pier Vincenzo,Spadoni, Gilberto,Bedini, Annalida,Piersanti, Giovanni,Diamantini, Giuseppe,Tarzia, Giorgio
, p. 4202 - 4212 (2007/10/03)
This work reports the design and synthesis of novel alkylamides, characterized by a dibenzo[a,d] cycloheptene nucleus, as melatonin (MLT) receptor ligands. The tricyclic scaffold was chosen on the basis of previous quantitative structure-activity studies on MT1 and MT2 antagonists, relating selective MT2 antagonism to the presence of an aromatic substituent out of the plane of the MLT indole ring. Some dibenzo seven-membered structures were thus selected because of the noncoplanar arrangement of their benzene rings, and an alkylamide chain was introduced to fit the requirements for MLT receptor binding, namely, dibenzocycloheptenes with an acylaminoalkyl side chain at position 10 and dibenzoazepines with this side chain originating from the nitrogen atom bridging the two phenyl rings. Binding affinity at human cloned MT1 and MT2 receptors was measured by 2[125I] iodomelatonin displacement assay and intrinsic activity by the GTPγS test. The majority of the compounds were characterized by higher affinity at the MT2 than at the MT 1 receptor and by very low intrinsic activity values, thus confirming the importance of the noncoplanar arrangement of the two aromatic rings for selective MT2 antagonism. Dibenzocycloheptenes generally displayed higher MT1 and MT2 affinity than dibenzoazepines. N-(8-Methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-ylmethyl)propionamide (4c) and -butyramide (4d) were the most selective MT2 receptor antagonists of the series, with MT2 receptor affinity comparable to that of melatonin and as such among the highest reported in the literature for MLT receptor antagonists. The acetamide derivative 4b produced a noticeable reduction of GTPγS binding at MT2 receptor, thus being among the few inverse agonists described.
Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain
de Paulis,Betts,Smith,Mobley,Manier,Sulser
, p. 1021 - 1026 (2007/10/02)
Analogues of clozapine, some prepared by a novel, shorter synthesis than those described previously, were evaluated as potential antipsychotic agents using clozapine binding sites in rat forebrain that are nonmuscarinic and nondopaminergic in nature and f
Ueber die Bildung von dibenzoanellierten Siebenring-Alkinen
Lorch, Margret,Meier, Herbert
, p. 2382 - 2391 (2007/10/02)
The multi-step preparations and the thermal and alkaline fragmentations of the 1,2,3-selenadiazoles 13 and 23 are described.The most interesting feature of this investigation is the formation of the highly strained cycloalkynes 4 and 5 which were trapped in situ.
2-(Arylmethyl)arylacetic Acids as Potential Antiinflammatory Agents
Brancaccio, Giovanni,Larizza, Angelo,Lettieri, Guglielmo,Monforte, Pietro
, p. 998 - 1000 (2007/10/02)
The title compounds 2 have been synthesized and tested for antiinflammatory activity.The synthetic method, consisting of the chemical sequence 3-aryl-1H-indenes (4) 2-(aroyl)arylacetic acids (5) 2, appears to be of value because of its simplicity
