Disease relevance of CCRIS 4334

• Here, we show that KN-62, 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine, a specific cell-permeable inhibitor of CamK-II substantially protected neurons from (1) acute NMDA toxicity and (2) hypoxia/hypoglycemia-induced neuronal injury in fetal rat cortical cultures [1].
• Among them, phenylpiperazine compounds with two-carbon length alkyl chains, 2a and 2b, appeared by high analgesic with little toxicity having neither an antiinflammatory effect nor opioid receptor affinity [2].
• Cataracts in dogs following subchronic administration of the phenylpiperazine antihypertensive agent PD 78787 [3].
• All the phenylpiperazine derivatives stimulated the flexor reflex in the spinal rat and evoked hyperthermia in rats at a high ambient temperature (28 degrees C) and in rabbits [4].

High impact information on CCRIS 4334

• 1-[N, O-bis-(5-isoquinolinesulphonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine (KN-62), an inhibitor of calcium-dependent camodulin protein kinase II, inhibits both insulin- and hypoxia-stimulated glucose transport in skeletal muscle [5].
• The highest affinity (IC50 = 0.50 nM) and selectivity for the 5-HT(1A) receptor were showed by 1-phenylpiperazine 2a with a three-membered alkyl chain bearing a 5-methoxytetralin-1-yl ring in the omega position [6].
• Nefazodone is a phenylpiperazine antidepressant with 5-HT2 antagonism and 5-HT reuptake inhibition [7].
• Structure-activity relationships for alpha 1-adrenoceptor affinity are presented and indicate that compounds with substitution at the ortho position on the benzene ring of the phenylpiperazine side chain moiety are more potent than those without substitution and/or substitutions at the 3- and 4-positions [8].
• Autophosphorylation was inhibited by the CaMKII(281-302) peptide, which corresponds to the CaMKII autoinhibitory domain, and by 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine (KN-62), a specific CaM kinase antagonist [9].

Biological context of CCRIS 4334

• The parent compound, unsubstituted phenylpiperazine (PP), had the lowest affinity for the [3H]ketanserin binding site [10].
• The platelet aggregation experiments demonstrated that marked alteration of the electronic and hydrophobic properties of phenylpiperazine by ring substitution did not impart 5-HT2 agonist activity [10].
• Flesinoxan, a new phenylpiperazine derivative has been shown to lower blood pressure in different species after both oral and i.v. administration [11].
• This work investigated the pharmacokinetics of a new N-phenylpiperazine derivative (LASSBio-581), active on dopaminergic system [12].
• Pharmacokinetics and tissue distribution of a new heterocyclic N-phenylpiperazine derivative (LASSBio-581) in rats [12].

Anatomical context of CCRIS 4334

• Effects of KN-62 (1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine), a specific Ca++/calmodulin (CaM)-dependent protein kinase inhibitor, were examined on the rate of spontaneous beating and the intracellular Ca++ transient of cultured myocytes from fetal mouse ventricle [13].

Associations of CCRIS 4334 with other chemical compounds

• In this study, we examined the influence of the actions of the halogenated phenylpiperazine LY 165,163 at dopamine D1, D2 and D3 receptors on its 5-HT1A agonist properties in vivo [14].
• Eltoprazine, a phenylpiperazine derivative, selectively reduces offensive aggression in animal models [15].
• WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride) is an achiral phenylpiperazine derivative that binds with high affinity and selectivity to the 5-HT1A receptor [16].
• The in vivo regional distribution and pharmacological profile of a novel iodinated phenylpiperazine derivative, [123I]p-MPPI (4-(2'-methoxy-)phenyl-1-[2'-(N-2"pyridinyl)-p-iodobenzamido-]ethy l- piperazine), in the rat brain were evaluated for use as a potential in vivo imaging agent for 5-HT1A receptors [17].
• The metabolites in the rat and the dog were 4-hydroxyphenylpiperazine glucuronide (M1), 1,4-dihydroxyphenyl glucuronide (M2), 1,4-dihydroxyphenyl sulfate (M3) and phenylpiperazine (M4) [18].

Gene context of CCRIS 4334

• Novel phenylpiperazine derivatives as dual cytokine regulators with TNF-alpha suppressing and IL-10 augmenting activity [19].
• Phenylpiperazine derivatives were synthesized as dual cytokine regulators with TNF-alpha suppressing and IL-10 augmenting activity [19].
• Novel potent neuropeptide Y Y5 receptor antagonists: Synthesis and structure-activity relationships of phenylpiperazine derivatives [20].
• The in vivo imaging of a novel iodinated phenylpiperazine derivative for 5-HT1A receptors, [123I]p-MPPI (4-(2'-methoxy-)phenyl-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido-] ethyl-piperazine), using single photon emission computed tomography (SPECT), was evaluated in nonhuman primates [21].
• Design and synthesis of an orally active GPIIb/IIIa antagonist based on a phenylpiperazine scaffold [22].

Analytical, diagnostic and therapeutic context of CCRIS 4334

• The phenylpiperazine 25 was further found to block SRS-A-related symptomatology after intravenous administration in two animal models [23].
• Validated HPLC method for determination of LASSBio-581, a new heterocyclic N-phenylpiperazine derivative, in rat plasma [24].

References