133982-60-2

Upstream product

• 371-42-6 4-Fluorothiophenol 
• 627-18-9 1-bromo-3-propanol 
• 627-30-5 1-chloro-3-hydroxypropane 

Downstream Products

• 150666-84-5 3-p-fluorobenzenesulfonylpropan-1-ol 
• 1020734-48-8 3-[(fluorophenyl)sulfonyl]propan-1-ol 
• 104605-77-8 (3-bromopropyl)(4-fluorophenyl)sulfane 
• 1359850-03-5 1-(4-chlorophenyl)-4-(3-((4-fluorophenyl)thio)propyl)-1,4-diazepane 
• 1359849-93-6 1-(4-chlorophenyl)-4-(3-((4-fluorophenyl)thio)propyl)piperazine 
• 1359849-95-8 1-(3-((4-fluorophenyl)thio)propyl)-4-(4-(trifluoromethyl)phenyl)piperazine 
• 1359850-01-3 2-(4-(3-((4-fluorophenyl)thio)propyl)piperazin-1-yl)pyrimidine 
• 1347812-49-0 1-(3-((4-fluorophenyl)thio)propyl)-4-(pyridin-2-yl)piperazine 
• 1359849-84-5 4-(4-chlorophenyl)-1-(3-((4-fluorophenyl)thio)propyl)piperidine 
• 34933-71-6 4-(4-chlorophenyl)-1-(3-((4-fluorophenyl)thio)propyl)piperidin-4-ol 
• 1610700-31-6 3-((4-fluorophenyl)thio)propyl 4-methylbenzenesulfonate 
• 1357348-83-4 3-((4-fluorophenyl)-thio)propyl methanesulfonate 
• 202666-41-9 thioacetic acid S-[3-(4-phenylsulfanyl-benzenesulfonyl)-propyl] ester 
• 202666-40-8 3-(4-phenylsulfanyl-benzenesulfonyl)-propan-1-ol 

Relevant academic research and scientific papers

Structure-Kinetic Profiling of Haloperidol Analogues at the Human Dopamine D2 Receptor

Haloperidol is a typical antipsychotic drug (APD) associated with an increased risk of extrapyramidal side effects (EPSs) and hyperprolactinemia relative to atypical APDs such as clozapine. Both drugs are dopamine D2 receptor (D2R) antagonists, with contrasting kinetic profiles. Haloperidol displays fast association/slow dissociation at the D2R, whereas clozapine exhibits relatively slow association/fast dissociation. Recently, we have provided evidence that slow dissociation from the D2R predicts hyperprolactinemia, whereas fast association predicts EPS. Unfortunately, clozapine can cause severe side effects independent of its D2R action. Our results suggest an optimal kinetic profile for D2R antagonist APDs that avoids EPS. To begin exploring this hypothesis, we conducted a structure-kinetic relationship study of haloperidol and revealed that subtle structural modifications dramatically change binding kinetic rate constants, affording compounds with a clozapine-like kinetic profile. Thus, optimization of these kinetic parameters may allow development of novel APDs based on the haloperidol scaffold with improved side-effect profiles.

Identification of a new selective dopamine D4 receptor ligand

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.

Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents

Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contributes to changes in binding to the receptors of interest. This strategy has resulted in the identification of several new agents, compounds 16, 18, 19, 23, 24 and 25, with binding profiles which satisfy our stated criteria for agents to act as potential atypical antipsychotics. This research demonstrates that haloperidol can serve as a useful lead in the identification and design of new agents that target multiple receptors associated with antipsychotic pharmacology.

Structure-activity relationship studies of SYA 013, a homopiperazine analog of haloperidol

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.

THIOL SULFONE METALLOPROTEASE INHIBITORS

This invention is directed to proteinase (protease) inhibitors, and more particularly to thiol sulfone inhibitors for matrix metalloproteinase 13(MMP-13), compositions of proteinase inhibitors, intermediates for the syntheses of proteinase inhibitors, processes for the preparation of proteinase inhibitors and processes for treating pathological conditions associated with pathological matrix metalloproteinase activity related to MMP-13.

Novel cyclic amide derivatives

Novel compounds represented by the following formula (I) that act as a ligand to sigma receptor/binding cite and a medicament comprising the same as an active ingredient: wherein X represents an alkyl group, an aryl group, a heterocyclic group or the like; Q represents a group represented by —CH2—, —CO—, —O—, —CH(OR7)— or the like wherein R7 represents a hydrogen atom, an alkyl group or the like; n represents an integer of from 0 to 5; R1 and R2 each represent a hydrogen atom, an alkyl group or the like; B represents either of the following groups: wherein R3, R4, R5, and R6 each represent a hydrogen atom, a halogen atom, an alkoxyl group or the like; m represents 1 or 2; and the ring of: represents an aromatic heterocyclic ring.

THIOL SULFONE METALLOPROTEASE INHIBITORS

This invention is directed to proteinase (protease) inhibitors, and more particularly to thiol sulfone inhibitors for matrix metalloproteinase 13(MMP-13), compositions of proteinase inhibitors, intermediates for the syntheses of proteinase inhibitors, processes for the preparation of proteinase inhibitors and processes for treating pathological conditions associated with pathological matrix metalloproteinase activity related to MMP-13.

Discovery of a novel series of selective MMP inhibitors: Identification of the γ-sulfone-thiols

We have discovered a new series of potent MMP inhibitors that are selective for MMP-13 over MMP-1 incorporating a γ-sulfone thiol.

Agents for treatment of brain ischemia

A series of 5-halopyrimidin-2-ylpiperazinylalkyl derivatives having useful anti-ischemic properties for treatment and prevention of dirorders resulting from brain and/or spinal cord anoxia.