36505-84-7Relevant articles and documents
Buspirone Analogues. 1. Structure-Activity Relationships in a Series of N-Aryl- and Heteroarylpiperazine Derivatives
Yevich, J. P.,Temple, D. L.,New, J. S.,Taylor, Duncan P.,Riblet, L. A.
, p. 194 - 203 (1983)
A series of analogues of buspirone was synthesized in which modifications were made in the aryl moiety, alkylene chain length, and cyclic imide portion of the molecule.These compounds were tested in vitro for their binding affinities to rat brain membrane sites labeled by either the dopamine antagonist spiperone or the α1-adrenergic antagonist WB-4101.Compounds were also tested in vivo for tranquilizing properties and induction of catalepsy.Potency at the spiperone binding site was affected by alkylene chain length and imide portion composition.Nonortho substituents on the aryl moiety had little effect on spiperone binding affinity.Structure-activity relationships of ortho substituents demonstrated only modest correlations between the receptor binding data and physical parameters of the substituents.The complex nature of the drug-receptor interactions may be understood in terms of the fit of buspirone to a hypothetical model of the dopamine receptor.
Nucleophilic aromatic substitution reactions under aqueous, mild conditions using polymeric additive HPMC
Ansari, Tharique N.,Borlinghaus, Niginia,Braje, Leon H.,Braje, Wilfried M.,Handa, Sachin,Ogulu, Deborah,Wittmann, Valentin
supporting information, p. 3955 - 3962 (2021/06/17)
The use of the inexpensive, benign, and sustainable polymer, hydroxypropyl methylcellulose (HPMC), in water enables nucleophilic aromatic subsitution (SNAr) reactions between various nucleophiles and electrophiles. The mild reaction conditions facilitate a broad functional group tolerance that can be utilized for subsequent derivatization for the synthesis of pharmaceutically relevant building blocks. The use of only equimolar amounts of all reagents and water as reaction solvent reveals the greenness and sustainability of the methodology presented herein.
Large-steric-hindrance N-heterocyclic carbene palladium complex, preparation method and application thereof, and synthesis method of sonidegib based on large-steric-hindrance N-heterocyclic carbene palladium complex
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Paragraph 0195; 0202-0204, (2021/01/24)
The invention belongs to the technical field of organic synthesis and chemical catalysis, and discloses a large-steric-hindrance N-heterocyclic carbene palladium complex, a preparation method thereof,an application of the complex in efficient catalysis of a C-N coupling reaction under a room-temperature air condition, and a synthesis method of sonidegib based on the complex. According to the large-steric-hindrance N-heterocyclic carbene palladium complex, diphenyl imidazole serves as a main ligand framework, functionalized allyl serves as an auxiliary ligand, the functionalized allyl is introduced beside a metal center of a catalyst to serve as an auxiliary ligand, the catalytic activity and stability are remarkably improved, the large-steric-hindrance N-heterocyclic carbene palladium complex can be applied to efficient catalysis of a CN coupling reaction, particularly, the CN coupling reaction can be efficiently catalyzed under the room temperature condition, and the yield can reachup to 99%. The invention also provides a method for synthesizing sonidegib by taking aryl/aliphatic amine and aryl chloride as reactants and a three-step method at room temperature under the catalysisof a palladium catalytic system, the synthetic method has few steps, and the total yield can reach 74.5%.
Fast continuous alcohol amination employing a hydrogen borrowing protocol
Labes, Ricardo,Mateos, Carlos,Battilocchio, Claudio,Chen, Yiding,Dingwall, Paul,Cumming, Graham R.,Rincón, Juan A.,Nieves-Remacha, Maria José,Ley, Steven V.
supporting information, p. 59 - 63 (2019/01/11)
A continuous flow method for the direct conversion of alcohols to amines via a hydrogen borrowing approach is reported. The method utilises a low loading (0.5%) of a commercial catalyst system ([Ru(p-cymene)Cl2]2 and DPEPhos), reagent grade solvent and is selective for primary alcohols. Successful methylation of amines using methanol and the direct dimethylamination of alcohols using commercial dimethylamine solution are reported. The synthesis of two pharmaceutical agents Piribedil (5) and Buspirone (25) were accomplished in good yields employing these new methods.
The design and preparation of metabolically protected new arylpiperazine 5-HT1A ligands
Tandon, Manish,O'Donnell, Mary-Margaret,Porte, Alex,Vensel, David,Yang, Donglai,Palma, Rocio,Beresford, Alan,Ashwell, Mark A.
, p. 1709 - 1712 (2007/10/03)
New arylpiperazines related to buspirone, gepirone and NAN-190 were designed and screened in silico for their 5-HT1A affinity and potential sites of metabolism by human cytochrome P450 (CYP3A4). Modifications to these structures were assessed in silico for their influence on both 5HT 1A affinity and metabolism. Selected new molecules were synthesized and purified in a parallel chemistry approach to determine structure activity relationships (SARs). The resulting molecules were assessed in vitro for their 5HT1A affinity and half-life in a heterologously expressed human CYP3A4 assay. Molecular features responsible for 5-HT1A affinity and CYP3A4 stability are described.
Process for the preparation of high purity buspiron and the hydrochloride thereof
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, (2008/06/13)
Process for the preparation of 8 -[4 -[4-(pyrimidine-2-yl)-piperazine-1-yl]-butyl]-8-aza-spiro[4.5]decane-7,9-dione (buspiron) of the Formula I STR1 and the hydrochlorides thereof having high purity by continuously adding a solution of 8-[4-[4-(pyrimidine-2-yl)-piperazine-1-yl]-but-2 -inyl]-8-aza-spiro[4.5]decane-7,9-dione of the formula II STR2 formed with an inert organic solvent having a concentration of at least 40% by weight to a suspension of a hydrogenation catalyst in an inert organic solvent and optionally converting the 8-[4-[4-(pyrimidine-2-yl)-piperazine-1-yl]-butyl]-8-aza-spiro[4.5]decane-7,9-dione thus obtained into the hydrochloride thereof.
PD(O)-CATALYSED SYHTHESIS OF BUSPIRONE AND GEPIRONE
Kuo, David L.
, p. 1463 - 1470 (2007/10/02)
A novel synthetic approach to buspirone and its analogue (gepirone) is described, in which 3 subunits, namely 2-(1-piperazinyl)pyrimidine, a bifunctional allylderivative, and an imide were efficiently assembled via a Pd(O)-catalysed amination-imidation sequence followed by a hydrogenation.
Synthesis and anxiolytic activity of N-substituted cyclic imides (1R*,2S*3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3-b icyclo[2.2.1]heptanedicarboxime (Tandospirone) and related compounds
Ishizumi,Kojima,Antoku
, p. 2288 - 2300 (2007/10/02)
A series of cyclic imides bearing a ω-(4-aryl and 4-heteroaryl-1-piperazinyl)alkyl moieties was synthesized and tested in vivo for anxiolytic activity. The in vitro binding affinities of these compounds were also examined for 5-HT(1A) receptor sites. Structure-activity relationships within these series are discussed. One of these compounds, (1R*,2S*,3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3- bicyclo[2.2.1]heptanedicarboximide (1: tandospirone), was found to be equipotent with buspirone in its anxiolytic activity and more anxio-selective than buspirone and diazepam. Tandospirone (1) is currently undergoing clinical evaluation as a selective anxiolytic agent.
Pharmaceutically useful polymorphic modification of buspirone
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, (2008/06/13)
Buspirone hydrochloride can exist in two polymorphic forms and the newly discoverd lower melting form, which is thermodynamically favored at pharmaceutically relevant temperatures, offers advantage in manufacture of buspirone pharmaceutical compositions .
Process for buspirone hydrochloride polymorphic crystalline form conversion
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, (2008/06/13)
A process for conversion of one polymorphic crystalline form of buspirone into its other polymorphic crystalline form.
