190966-91-7Relevant academic research and scientific papers
UREA DERIVATIVES AS CB1 ALLOSTERIC MODULATORS
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Page/Page column 61; 62, (2021/01/23)
Heteroaryl and aliphatic analogs of diarylurea-based cannabinoid 1 receptor (CB1 R) allosteric modulators of formula (I) are described. Exemplary analogs can provide improved potencies and pharmacokinetic properties. Methods of using the analogs to treat
Synthesis and Pharmacological Evaluation of 1-Phenyl-3-Thiophenylurea Derivatives as Cannabinoid Type-1 Receptor Allosteric Modulators
Nguyen, Thuy,Gamage, Thomas F.,Decker, Ann M.,Barrus, Daniel,Langston, Tiffany L.,Li, Jun-Xu,Thomas, Brian F.,Zhang, Yanan
, p. 9806 - 9823 (2019/11/11)
We previously reported diarylurea derivatives as cannabinoid type-1 receptor (CB1) allosteric modulators, which were effective in attenuating cocaine-seeking behavior. Herein, we extended the structure-activity relationships of PSNCBAM-1 (2) at the central phenyl ring directly connected to the urea moiety. Replacement with a thiophene ring led to 11 with improved or comparable potencies in calcium mobilization, [35S]GTPγS binding, and cAMP assays, whereas substitution with nonaromatic rings led to significant attenuation of the modulatory activity. These compounds had no inverse agonism in [35S]GTPγS binding, a characteristic that is often thought to contribute to adverse psychiatric effects. While 11 had good metabolic stability in rat liver microsomes, it showed modest solubility and blood-brain barrier permeability. Compound 11 showed an insignificant attenuation of cocaine seeking behavior in rats, most likely due to its limited CNS penetration, suggesting that pharmacokinetics and distribution play a role in translating the in vitro efficacy to in vivo behavior.
A useful one-pot procedure for obtaining 2-aryl-5-nitrothiophenes from bromonitromethane and 3-aryl-3-chloro-propenals
Rodríguez-Domínguez, Juan C.,Thomae, David,Seck, Pierre,Kirsch, Gilbert
, p. 286 - 288 (2008/12/20)
A one-pot procedure was developed to prepare new 2-aryl-5-nitrothiophenes efficiently from bromonitromethane and 3-chloro-3-aryl-propenals. Nitrothiophenes were synthesized in good yields with a simple and easy workup procedure. Georg Thieme Verlag Stuttg
2,5-disubstituted thiophenes: inhibitors of 5-lipoxygenase and inducible cyclooxygenase (COX-2) enzymes, composition and use
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, (2008/06/13)
2,5-Disubstituted thiophene derivatives, and more particularly, to 2-aryloxy-5-alkansulfonamido-thiophenes of the general formula: STR1 Wherein, R2 is CF3, C1 -C10 alkyl, or phenyl; X is O, S, or CH2
N-(5-Substituted) thiophene-2-alkylsulfonamides as potent inhibitors of 5-lipoxygenase
Beers, Scott A.,Malloy, Elizabeth A.,Wu, Wei,Wachter, Michael,Ansell, Justin,Singer, Monica,Steber, Michele,Barbone, Arminda,Kirchner, Thomas,Ritchie, David,Argentieri, Dennis
, p. 779 - 786 (2007/10/03)
Compound 4k N-[5-(4-fluoro)phenoxythien-2-yl]methanesulfonamide is representative of a new class of potent inhibitors of 5-lipoxygenase (5-LO). These versatile compounds exhibit dose-dependent inhibition of 5-LO with IC50s ranging from 20-100 nM in the rat basophilic leukemia (RBL-1) cell homogenate assay and submicromolar IC50s in both the RBL-1 and human peripheral blood leukocyte (PBL) whole cell assays. Compound 4k also showed significant anti-inflammatory activity in the adjuvant arthritic rat at an oral dose of 3 mg/kg.
