851180-84-2Relevant academic research and scientific papers
Neladenoson Bialanate Hydrochloride: A Prodrug of a Partial Adenosine A1 Receptor Agonist for the Chronic Treatment of Heart Diseases
Meibom, Daniel,Albrecht-Küpper, Barbara,Diedrichs, Nicole,Hübsch, Walter,Kast, Raimund,Kr?mer, Thomas,Krenz, Ursula,Lerchen, Hans-Georg,Mittendorf, Joachim,Nell, Peter G.,Süssmeier, Frank,Vakalopoulos, Alexandros,Zimmermann, Katja
, p. 728 - 737 (2017/05/26)
Adenosine is known to be released under a variety of physiological and pathophysiological conditions to facilitate the protection and regeneration of injured ischemic tissues. The activation of myocardial adenosine A1 receptors (A1Rs) has been shown to inhibit myocardial pathologies associated with ischemia and reperfusion injury, suggesting several options for new cardiovascular therapies. When full A1R agonists are used, the desired protective and regenerative cardiovascular effects are usually overshadowed by unintended pharmacological effects such as induction of bradycardia, atrioventricular (AV) blocks, and sedation. These unwanted effects can be overcome by using partial A1R agonists. Starting from previously reported capadenoson we evaluated options to tailor A1R agonists to a specific partiality range, thereby optimizing the therapeutic window. This led to the identification of the potent and selective agonist neladenoson, which shows the desired partial response on the A1R, resulting in cardioprotection without sedative effects or cardiac AV blocks. To circumvent solubility and formulation issues for neladenoson, a prodrug approach was pursued. The dipeptide ester neladenoson bialanate hydrochloride showed significantly improved solubility and exposure after oral administration. Neladenoson bialanate hydrochloride is currently being evaluated in clinical trials for the treatment of heart failure.
PYRAZOLYL PYRIMIDINAMINE COMPOUND AND APPLICATION THEREOF
-
, (2016/12/01)
Disclosed are pyrazolyl pyrimidinamine compounds with structures as shown in Formula I: The definitions of each of the substituents can be seen in the description. The compounds of present invention have a broad spectrum of bactericidal, insecticidal and acaricidal activity, and have good control effect on downy mildew of cucumber, powdery mildew of wheat, corn rust, anthracnosis of cucumber and the like, and especially have better control effect on downy mildew of cucumber, powdery mildew of wheat and anthracnosis of cucumber. The compounds of present invention also show good insecticidal activity, part of the compounds, at very low doses, have excellent control effect on diseases caused by Plutella xylostella, armyworm, Myzus persicae, Tetranychus cinnabarinus etc.
Synthesis and pharmacological evaluation of new N-phenylpiperazine derivatives designed as homologues of the antipsychotic lead compound LASSBio-579
Pompeu, Thais E. T.,Alves, Fernando R. S.,Figueiredo, Carolina D. M.,Antonio, Camila B.,Herzfeldt, Vivian,Moura, Bruna C.,Rates, Stela M. K.,Barreiro, Eliezer J.,Fraga, Carlos A. M.,No?l, Fran?ois
, p. 122 - 134 (2013/10/01)
In an attempt to increase the affinity of our antipsychotic lead compound LASSBio-579 (1-((1-(4- chlorophenyl)-1H-pyrazol-4-yl)methyl)-4-phenylpiperazine; (2)) for the 5-HT2A receptor, we synthesized five new N-phenylpiperazine derivatives using a linear synthetic route and the homologation strategy. The binding profile of these compounds was evaluated for a series of dopaminergic, serotonergic and alpha-adrenergic receptors relevant for schizophrenia, using classical competition assays. Increasing the length of the spacer between the functional groups of (2) proved to be appropriated since the affinity of these compounds increased 3-10-fold for the 5-HT2A receptor, with no relevant change in the affinity for the D2-like and 5- HT1A receptors. A GTP-shift assay also indicated that the most promising derivative (1-(4-(1-(4-chlorophenyl)-1H- pyrazol-4-yl) butyl)-4-phenylpiperazine) (LASSBio-1635) (6) has the expected efficacy at the 5-HT2A receptors, acting as an antagonist. Intraperitoneal administration of (6) prevented apomorphine-induced climbing behavior and ketamine-induced hyperlocomotion in mice, in a dose dependent manner. Together, these results show that (6) could be considered as a new antipsychotic lead compound.
