15532-75-9

A general and convenient synthesis of N-aryl piperazines from bis(2-chloroethyl)amine hydrochloride and a broad range of anilines in diethylene glycol monomethyl ether is described.

The phenylpiperazine ring which could not be obtained by reacting aniline derivatives with bis(2-bromoethyl)-N-(ethoxycarbonyl)amine (1a) in a wide spectrum of solvents and temperatures was synthesized rapidly on solid support in high yield. By this approach the potent serotonin agonist TFMPP (2) was synthesized in 40 min. in 80% yield. The time scale of this reaction and the simplicity of the work-up match the requirements for short lived neurological radiopharmaceutical production.

RATIONALE: Although amphetamine-type substances (ATS) have been investigated extensively in recent years, scarce data is available on screening tests for piperazine analogues. The need for a universal technique capable of detecting an extensive range of drug compounds becomes increasingly important with the continued emergence of novel drug analogues. METHODS: Desorption electrospray ionisation mass spectrometry (DESI-MS) is a technique that allows examination of compounds in drug materials directly from ambient surfaces. In this study, DESI-MS was utilised in the analysis of ATS including amphetamine (AP), methylamphetamine (MA), 3,4-methylenedioxymethylamphetamine (MDMA), N,N-dimethylamphetamine (DMA), 4-methoxyamphetamine (PMA) and 4-methoxymethylamphetamine (PMMA), and piperazine analogues including 1-benzylpiperazine (BZP), 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP). Semi-porous polytetrafluoroethylene (PTFE or Teflon) sheets welled with a 3 mm hole punch were used to contain the 2 μL liquid sample (spot size 7 mm 2). RESULTS: The limits of detection (LODs) of these compounds using DESI-MS were determined to be in the range 0.02-2.80 μg/mm2. The intra-day and inter-day precision of the technique were 25% and 33%, respectively. DESI-MS was successful in determining the compound of interest and reaction by-products and impurities in the samples tested (such as 1,4-dibenzylpiperazine in BZP samples) with the exception of those present in trace amounts. The effects of common adulterants on the detectability of MA were evaluated. The addition of magnesium stearate to MA significantly enhanced the signal response. CONCLUSIONS: This work has demonstrated the applicability of DESI-MS in the screening and profiling of MDMA, PMMA, BZP, TFMPP, mCPP, MeOPP as well as other complex mixtures. Copyright

Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL).

The present invention provides a heteroaromatic acetamide derivative, a preparation and applications thereof, wherein the derivative comprises a pharmaceutically acceptable salt and/or a solvate thereof. According to the present invention, the experiment results prove that the heteroaromatic acetamide derivative can specifically bind to transient receptor potential ankyrin 1 (TRPA1) and inhibit orreduce the activity of TRPA1, and can be used for treating diseases mediated by TRPA1; and the inhibitor of the present invention further comprises a pharmaceutical composition of the compound, and amethods for preparing the compounds. The derivative has a general formula defined in the specification.

(Chemical Equation Presented) A new silane-promoted nickel-catalyzed amination of aryl chlorides with 0.5 mol % of Ni(acac)2, 1 mol % of 3,5,6,8-tetrabromo-1,10-phenanthroline, and polymethylhydrosiloxane was developed. A broad range of aryl and heteroaryl chlorides can be coupled with secondary amines and anilines to give the desired (het)arylamines in good to excellent yields. The reaction is sensitive to the nature and amount of the silane promoter.

A series of N-arylpiperazines were prepared in a parallel fashion using palladium-catalyzed cross-coupling, or nucleophilic aromatic displacement chemistries, and polymer-assisted sequestration and purification techniques as key steps.

Compounds, compositions, and methods for treating fungal infection by modulating the activity of the fungal kinesin Kip 1 are disclosed.

The present invention relates to novel tetracyclic benzimidazole derivative compounds of the following formula: wherein R1to R10have the meanings described in here. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing tetracyclic benzimidazole derivative compounds.

The present invention relates to polymers characterized by novel silicon linkers based on the carbamyl piperazine moiety, methods of preparing these polymers and their use in the solid phase synthesis of compounds or libraries of compounds embracing a phenyl ring in their structure.

The present invention relates to a fused heterocyclic compound of the formula (I) wherein each symbol is as defined in the specification, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive, and a medicament containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof. The compound of the present invention is a useful antipsychotic agent effective not only for positive symptoms centering on hallucination and delusion characteristic of the acute stage of schizophrenia, but also negative symptoms of apathy, abulia and autism. The inventive compound is expected to make a highly safe antipsychotic agent associated with less side effects, such as extrapyramidal symptoms and endocrine disturbance, which are observed when a conventional antipsychotic agent having a D2receptor blocking action is administered. Therefore, the inventive compound can be used as a therapeutic agent for the diseases such as schizophrenia.

Piperazine derivatives of the formula I in which R1and R2have the meanings given in claim1are dopamine ligands with a selectivity for the D4 receptor and are suitable for the treatment and prophylaxis of states of anxiety, depression, schizophrenia, obsessions, Parkinson's disease, tardive dyskinesia, nausea and disorders of the gastro-intestinal tract.

This invention relates to a novel solution phase process for the preparation of amide, carbamate, and sulfonamide combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.

A Pd/P(t-Bu), catalyst system has revealed very high activity and selectivity for the amination of N-(hetero)aryl halides with unprotected piperazine. A wide variety of N-(hetero)arylpiperazines could be prepared using this catalyst. Turnover numbers up to 6400mol/mol have been obtained.

1-Arylpiperazines, finding wide applicability in pharmaceuticals were synthesized easily under microwave irradiation from bis(2-chloroethyl)amine hydrochloride and substituted anilines without any solvent. The reaction time was just 1-3 mins. 1-Arylpiperazines were synthesized in 53 to 73% yields. Potent serotonin ligands like Trifluoromethylphenylpiperazine (TFMPP) and 3-Chlorophenylpiperazine (mCPP) were also prepared in just 1 min and 2 mins respectively.

Novel α-mercapto-alkylamines in all possible racemic, enantiomeric and diastereoisomeric forms of the formula STR1 wherein n, R 1, R 2, X, A, R 3A and R 4A are set forth in the claims and their non-toxic, pharmaceutically acceptable acid addition salts having excellent analgesic, psychotropic and enkephalinase inhibiting properties.

Antiviral compounds (I): the symbols being as defined in the specification, are efficacious against infections caused by a variety of DNA viruses, RNA viruses and retroviruses. Other specified compounds also exhibit activity. The compounds have a wider spectrum of activity than known antiviral substances.

Novel 3-aryloxy and 3-arylthioazetidinecarboxamides having utility in a method of treating convulsions and epilepsy and compositions therefor are disclosed having the formula: STR1 wherein Z is oxygen or sulfur; B is oxygen or sulfur; Ar is pyridyl or halo-substituted-pyridyl, phenyl or substituted phenyl; R1 and R2 are selected from hydrogen, loweralkyl, aryl, allyl, substituted allyl, propargyl, cycloalkyl, loweralkylcycloalkyl, cycloalkylloweralkyl, arylloweralkyl, diloweralkylaminoloweralkyl, and R1 and R2 when taken with the adjacent nitrogen atom may form a heterocyclic radical; R3 is hydrogen, loweralkyl, aryl or arylloweralkyl, and the geometrical isomers thereof, excepting that when R3 is hydrogen, Z is oxygen, B is oxygen, and Ar is phenyl or phenyl substituted by trifluoromethyl or aminocarbonyl, then R1 and R2 cannot be a combination of hydrogen and loweralkyl, and the further exception that when R3 is hydrogen, Z is oxygen, B is oxygen, and Ar is phenyl or phenyl substituted by fluoro, loweralkyl, loweralkoxy, trifluoromethyl, acetyl, or aminocarbonyl, then R1 and R2 cannot both be hydrogen.

A succinimide derivative of the formula: STR1 wherein A is straight or branched C2 -C6 alkylene or alkenylene, B is straight or branched C3 -C5 alkylene, D is straight or branched C2 -C3 alkylene, E is straight or branched C2 -C3 alkylene, R1 and R2 are each hydrogen or C1 -C4 alkyl, or they may form a single bond and R3 is a phenyl group optionally substituted with C1 -C4 alkyl, C1 -C4 alkoxy, halogen and/or trifluoromethyl, a 2-pyridyl group optionally substituted with halogen, a 2-pyrimidyl group optionally substituted with halogen, a group of the formula: STR2 (in which R4 is hydrogen or phenyl), a group of the formula: CO--R5 (in which R5 is adamantyl or furyl) or hydroxy (C2 -C4) alkyl, and an acid addition salt thereof, which are useful as anti-anxiety drugs and/or anti-allergic drugs.

Phenoxyalkyl substituted-1,2,4-triazolones having anti-depressant properties typified by 2-3-4-(3-chlorophenyl)-1-piperazinyl!propyl!-5-ethyl-4-(2-phenoxyethyl)-2H-1,2, 4-triazol-3(4H)-one are disclosed.