87789-49-9

Upstream product

• 87789-52-4 ethyl 4-(5-fluoro-2-pyrimidinyl)-1-piperazinecarboxylate 
• 87789-50-2 ethyl 4-<5-fluoro-4-(methylthio)-2-pyrimidinyl>-1-piperazinecarboxylate 
• 110-85-0 piperazine 
• 947533-45-1 2-bromo-5-fluoro-pyrimidine 
• 912556-74-2 tert-butyl 4-(5-fluoropyrimidin-2-yl)piperazine-1-carboxylate 
• 62802-42-0 2-chloro-5-fluoropyrimidine 

Downstream Products

• 133982-66-8 1-(4-fluorophenyl)-4-[5-(fluoro-2-pyrimidinyl)-1-piperazinyl]butanone 
• 88-96-0 phthalamide 
• 99931-58-5 BMY 14786 
• 99931-63-2 α,α-bis(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol 
• 144317-71-5 1-(4-Fluoro-phenyl)-3-[4-(5-fluoro-pyrimidin-2-yl)-piperazin-1-yl]-propan-1-one 

Relevant academic research and scientific papers

The optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119

A series of xanthine compounds derived from the previous hit 20i with modification on the terminal side chain was discovered through ring formation strategy. Systematic optimization of the compounds with rigid heterocycles in the hydrophobic side chain led to the new lead compound HBK001 (21h) with the improved DPP-IV inhibition and moderate GPR119 agonism activity in vitro. As a continuing work to further study the PK and PD profiles, 21h and its hydrochloride (22) were synthesized on grams scale and evaluated on the ADME/T and oral glucose tolerance test (OGTT) in ICR mice. Compound 22 showed the improved bioavailability and blood glucose-lowering effect in vivo compared to its free base 21h probably attributed to its improved solubility and permeability. The preliminary toxicity studies on compound 22 exhibited that the result of mini-Ames was negative and the preliminary acute toxicity LD50 in mice was above 1.5 g/kg, while it showed moderate inhibition on hERG channel with IC50 4.9 μM maybe due to its high lipophilicity. These findings will be useful for the future drug design for more potent and safer dual ligand targeting DPP-IV and GPR119 for the treatment of diabetes.

Cyclic Ureas

Amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

PHENYL mTORC INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

ANTIFUNGAL AGENTS

The invention provides a pyrrole compound, which compound is (a)2-(1,5-dimethyl-3- phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2- oxoacetamideor a deuterated derivative thereof, or(b)2-(1,5-dimethyl-3-phenyl-1H-pyrrol- 2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)-3-hydroxyphenyl)-2-oxoacetamide or a deuterated derivative thereof, or (c) a prodrug of compound (a) or a prodrug of compound (b), or a pharmaceutically acceptable salt or agriculturally acceptable salt of (a), (b) or (c). Also provided are combinations and compositions comprising the compound and known antifungal agents. The invention also relates to the therapeutic use of a compound of the invention in prevention or treatment of fungal diseases. It also relates to the use of:2-(1,5-dimethyl-3-phenyl-1H- pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2-oxoacetamide or an agriculturally acceptable salt thereof, or 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-(4-(4- (5-fluoropyrimidin-2-yl)piperazin-1-yl)-3-hydroxyphenyl)-2-oxoacetamide or an agriculturally acceptable salt thereof, as an agricultural fungicide.

SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF

Provided herein are novel heteroaryl compounds, pharmaceutically acceptable salts and pharmaceutical formulations thereof for selectively inhibiting serotonin reuptake and/or acting as 5-HT1A receptor agonists. Also provided herein are pharmaceutical compositions comprising the heteroaryl compounds and methods of using the pharmaceutical compositions in treating central nervous system (CNS) dysfunction in a mammal, especially a human being.

Synthesis and Biological Characterization of α-(4-Fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol and Analogues as Potential Atypical Antipsychotic Agents

A series of 1-(pyrimidin-2-yl)piperazine derivatives were prepared and evaluated in receptor binding assays and in in vivo behavioral paradigms as potential atypical antipsychotic agents.Compound 16 (BMS 181100 (formerly BMY 14802)) emerged as the lead compound from within the series on the basis of its good activity and duration of action in the inhibition of both conditioned avoidance responding and apomorphine-induced stereotopy in the rat.Compound 16 not only failed to induce catalepsy in the rat but was quite effective in reversing the cataleptic effect of neurolepti c agents, thus indicating a low propensity for causing extrapyramidal side effects.In comparison to reference antipsychotic agents, 16 appeared to be less sedating and was relatively weaker in causing muscle incoordination.The compound was essentially inactive in binding to dopamine D2 receptors and its chronic administration to rats did not result in dopamine receptor supersensitivity.It exhibited modest to weak affinity for 5-HT1A and α1 receptors but was found to be a fairly potent ligand for ? binding sites (IC50 vs (+)--3-PPP = 112 nM).Although the resolved enantiomers of racemic 16 did not show dramatic differences from racemate or from each other in most tests, the R(+) enantiomer was up to 11-fold more potent than its antipode in binding to ? sites.Several studies have indicated that 16 may be a limbic-selective agent which may modulate dopaminergic activity by an indirect mechanism.The compound has been selected for clinical evaluation in the treatment of psychosis.

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

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.

2-pyrimidinyl-1-piperazine derivatives, processes for their preparation and medicaments containing them

The invention relates to substituted 2-pyrimidinyl-1-piperazine derivatives defined herein by formula (I), processes for their manufacture, compositions containing said substituted 2-pyrimidinyl-1-piperazine derivatives as active materials and the use of

Succinimide derivatives, and their production and use

A succinimide derivative of the formula: STR1 wherein R is a pyridyl or pyrimidinyl group substituted with at least one member selected from the group consisting of halogen, lower alkyl, lower alkoxy, cyano, benzyloxy, hydroxyl and amino, and n is an integer of 1 or 2, or a pharmaceutically acceptable acid addition salt thereof. The succinimide derivatives are useful as an anti-anxiety drugs.