63558-68-9Relevant academic research and scientific papers
Synthesis and structure-activity relationship analysis of 5-HT7 receptor antagonists: Piperazin-1-yl substituted unfused heterobiaryls
Strekowski, Lucjan,Saczewski, Jaros?aw,Raux, Elizabeth A.,Fernando, Nilmi T.,Klenc, Jeff,Paranjpe, Shirish,Raszkiewicz, Aldona,Blake, Ava L.,Ehalt, Adam J.,Barnes, Samuel,Baranowski, Timothy C.,Sullivan, Shannon M.,Sata?a, Grzegorz,Bojarski, Andrzej J.
, (2016/05/24)
A series of piperazin-1-yl substituted unfused heterobiaryls was synthesized as ligands of the 5-HT7 receptors. The goal of this project was to elucidate the structural features that affect the 5-HT7 binding affinity of this class of compounds represented by the model ligand 4-(3-furyl)-2-(4-methylpiperazin-1-yl)pyrimidine (2). The SAR studies included systematical structural changes of the pyrimidine core moiety in 2 to quinazoline, pyridine and benzene, changes of the 3-furyl group to other heteroaryl substituents, the presence of various analogs of the 4-methylpiperazin-1-yl group, as well as additional substitutions at positions 5 and 6 of the pyrimidine. Substitution of position 6 of the pyrimidine in the model ligand with an alkyl group results in a substantial increase of the binding affinity (note a change in position numbers due to the nomenclature rules). It was also demonstrated that 4-(3-furyl) moiety is crucial for the 5-HT7 binding affinity of the substituted pyrimidines, although, the pyrimidine core can be replaced with a pyridine ring without a dramatic loss of the binding affinity. The selected ethylpyrimidine (12) and butylpyrimidine (13) analogs of high 5-HT7 binding affinity showed antagonistic properties in cAMP functional test and varied selectivity profile-compound 12 can be regarded as a dual 5-HT7 /5-HT2A R ligand, and 13 as a multi-receptor (5-HT7 , 5-HT2A , 5-HT6 and D2 ) agent.
INHIBITORS OF HISTONE DEACETYLASE
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Page/Page column 58, (2010/02/14)
The invention relates to a series of compounds useful for inhibiting histone deacetylase (HDAC) enzymatic activity. The invention also provides a method for inhibiting histone descetylase in a cell using said compounds as well as a method for treating cell proliferative diseases and conditions using said HDAC inhibitors. Further, the invention provides pharmaceutical compositions comprising the HDAC inhibiting compounds and a pharmaceutically acceptable carrier.
PYRIMIDIN-2-ONE COMPOUNDS AND THEIR USE AS DOPAMINE D3 RECEPTOR LIGANDS
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Page 97, (2010/02/08)
The invention relates to pyrimidin-2-one compounds of general formula (I), in addition to the derivatives and tautomers of (I) and the physiologically acceptable salts of said compounds. In said formula: A represents linear or branched C3-C6 alkene, which can have a double bond or triple bond and/or a group Z, which is not adjacent to the nitrogen atom of the pyrimidinone ring and is selected from O, S, C(O), NR3, C(O)NR3, NR3C(O), OC(O) and C(O)O; B represents a group of formula (II), in which X stands for CH2 or N and Y stands for CH2 or CH2CH2, or X-Y can also jointly represent C=CH, C=CH-CH2 or CH-CH=CH; R1 and R 2 are defined as cited in the description and the claims; and Ar represents an optionally substituted aromatic group. The invention also relates to a pharmaceutical agent, containing at least one compound (I) and the tautomers, derivatives and/or acid addition salts of said compound, optionally together with physiologically acceptable carriers and/or auxiliary agents. The invention also relates to the use of compounds of formula (I), and their tautomers, derivatives and pharmacologically acceptable acid addition salts for producing a pharmaceutical agent for treating diseases, which respond to the influence of dopamine D3 receptor ligands.
Synthesis of 2-Chloro-4,6-di(heteroaryl)pyrimidines
Strekowski, Lucjan,Harden, Donald B.,Grubb, William B.,Patterson, Steven E.,Czarny, Agnieszka,et al.
, p. 1393 - 1400 (2007/10/02)
A practical method for the preparation of 2-chloro-4,6-di(heteroaryl)pyrimidines and their 5-methyl homologues from readily available 2-chloropyrimidine and 2-chloro-5-methylpyrimidine, respectively, is described.The method is based on the addition reactions of heteroaryllithium reagents with chloropyrimidines followed by dehydrogenation of the resultant substituted dihydropyrimidines.The use of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone as the dehydrogenation agent gives the best results.Side reactions in the addition step are discussed.
