65655-72-3Relevant academic research and scientific papers
Development of CNS multi-receptor ligands: Modification of known D2pharmacophores
Etukala, Jagan R.,Zhu, Xue Y.,Eyunni, Suresh V.K.,Onyameh, Edem K.,Ofori, Edward,Bricker, Barbara A.,Kang, Hye J.,Huang, Xi-Ping,Roth, Bryan L.,Ablordeppey, Seth Y.
, p. 3671 - 3679 (2016/07/21)
Several known D2pharmacophores have been explored as templates for identifying ligands with multiple binding affinities at dopamine and serotonin receptors considered as clinically relevant receptors in the treatment of neuropsychiatric disease
Identification of a new selective dopamine D4 receptor ligand
Sampson, Dinithia,Zhu, Xue Y.,Eyunni, Suresh V.K.,Etukala, Jagan R.,Ofori, Edward,Bricker, Barbara,Lamango, Nazarius S.,Setola, Vincent,Roth, Bryan L.,Ablordeppey, Seth Y.
, p. 3105 - 3114 (2014/06/09)
The dopamine D4 receptor has been shown to play key roles in certain CNS pathologies including addiction to cigarette smoking. Thus, selective D4 ligands may be useful in treating some of these conditions. Previous studies in our laboratory have indicated that the piperazine analog of haloperidol exhibits selective and increased affinity to the DAD4 receptor subtype, in comparison to its piperidine analog. This led to further exploration of the piperazine moiety to identify new agents that are selective at the D4 receptor. Compound 27 (K iD4 = 0.84 nM) was the most potent of the compounds tested. However, it only had moderate selectivity for the D4 receptor. Compound 28 (KiD4 = 3.9 nM) while not as potent, was more discriminatory for the D4 receptor subtype. In fact, compound 28 has little or no binding affinity to any of the other four DA receptor subtypes. In addition, of the 23 CNS receptors evaluated, only two, 5HT1AR and 5HT2BR, have binding affinity constants better than 100 nM (Ki 4-selective ligand for probing disease treatments involving the D4 receptor, such as assisting smoking cessation, reversing cognitive deficits in schizophrenia and treating erectile dysfunction. Thus, further optimization, functional characterization and evaluation in animal models may be warranted.
Structure-activity relationship studies of SYA 013, a homopiperazine analog of haloperidol
Peprah, Kwakye,Zhu, Xue Y.,Eyunni, Suresh V.K.,Etukala, Jagan R.,Setola, Vincent,Roth, Bryan L.,Ablordeppey, Seth Y.
experimental part, p. 1671 - 1678 (2012/04/10)
Structure-activity relationship studies on 4-(4-(4-chlorophenyl)-1,4- diazepan-1-yl)-1-(4-fluorophenyl)butan-1-one (SYA 013), a homopiperazine analog of haloperidol has resulted in an understanding of the effect of structural modifications on binding affinity at dopamine and serotonin receptor subtypes. Further exploration, using bioisosteric replacement strategies has led to the identification of several new agents including compounds 7, 8, 11 and 12 which satisfy the initial criteria for further exploration as new antipsychotic agents. In addition, compound 18, a D3 selective tropanol, has been identified as having the potential for further optimization into a useful drug which may combat neuropsychiatric diseases.
Benzothiazoles as probes for the 5HT1A receptor and the serotonin transporter (SERT): A search for new dual-acting agents as potential antidepressants
Zhu, Xue Y.,Etukala, Jagan R.,Eyunni, Suresh V.K.,Setola, Vincent,Roth, Bryan L.,Ablordeppey, Seth Y.
experimental part, p. 124 - 132 (2012/08/08)
The synthesis and evaluation of several benzothiazole-based compounds are described in an attempt to identify novel dual-acting 5HT1A receptor and SERT inhibitors as new antidepressants. Binding affinities at the 5HT 1A receptor and
Functionalized orthoesters as powerful building blocks for the efficient preparation of heteroaromatic bicycles
Bastug, Gulluzar,Eviolitte, Christophe,Markó, István E.
supporting information; experimental part, p. 3502 - 3505 (2012/08/08)
By combining substituted anilines with functionalized orthoesters, an efficient and connective methodology for the preparation of benzoxazole, benzothiazole, and benzimidazole derivatives has been established. The versatility of this approach enables the development of new libraries of heterocycles containing multifunctional sites.
Substituted 1,2,3,4-Tetrahydroaminonaphthols: Antihypertensive Agents, Calcium Channel Blockers, and Adrenergic Receptor Blockers with Catecholamine-Depleting Effects
Atwal, Karnail S.,O'Reilly, Brian C.,Ruby, Eric P.,Turk, Chester F.,Aberg, Gunnar,et al.
, p. 627 - 635 (2007/10/02)
Substituted 1,2,3,4-tetrahydroaminonaphthols were found to be calcium channel blockers with antihypertensive properties.These compounds also possessed adrenergic β-receptor blocking activity.From the structure-activity studies, no clear correlation emerged between the in vitro calcium channel blocking activity and the acute antihypertensive activity in cannulated spontaneously hypertensive rats.Extensive pharmacological testing of selected compounds indicated that aminonaphthols are antihypertensive agents with many pharmacological properties.The relative contribution of various pharmacological actions toward the observed antihypertensive activity is unclear.Since the clinically useful calcium channel blocker verapamil is structurally related to these compounds, one of the aminonaphthols, trans-3--1,2,3,4-tetrahydro-6,7-dimethoxy-2-naphthalenol (12), was compared with verapamil for calcium channel blocking activity, adrenergic blocking activity, and catecholamine-depleting activity.Both compopunds were found to be equipotent in these test systems.
