246146-55-4 Usage
Uses
Used in Pharmaceutical Industry:
BIIE 0246 is used as a research compound for studying the role of neuropeptide Y (NPY) and its receptors in various physiological processes and disorders. Its ability to selectively target the NPY2-R makes it a valuable tool in understanding the underlying mechanisms of NPY signaling and its potential therapeutic applications.
Used in Neuroscience Research:
In the field of neuroscience, BIIE 0246 is used as a selective antagonist to investigate the involvement of NPY2-R in neuronal functions and behaviors. This can help researchers gain insights into the role of NPY2-R in cognitive processes, mood regulation, and other neurological conditions.
Used in Drug Development:
Due to its high lipophilicity and selective binding to NPY2-R, BIIE 0246 can be utilized in the development of novel therapeutic agents targeting NPY2-R. This may lead to the creation of new drugs for the treatment of various disorders, such as obesity, anxiety, depression, and other conditions related to NPY signaling.
Used in Membrane Biology Studies:
BIIE 0246's propensity to accumulate in membranes near the receptors makes it a useful tool in studying membrane biology and the interaction between lipophilic compounds and biological membranes. This can provide valuable information on the behavior of drugs and other molecules in cellular environments.
Biological Activity
Potent, selective and competitive non-peptide antagonist for the neuropeptide Y Y 2 receptor (IC 50 = 15 nM). Displays > 650-fold selectivity over Y 1 , Y 4 and Y 5 receptors. Active in vivo .
references
[1]. doods h, gaida w, wieland ha, et al. biie0246: a selective and high affinity neuropeptide y y(2) receptor antagonist. eur j pharmacol, 1999, 384(2-3): r3-5.[2]. el bahh b, cao jq, beck-sickinger ag, et al. blockade of neuropeptide y(2) receptors and suppression of npy's anti-epileptic actions in the rat hippocampal slice by biie0246. br j pharmacol, 2002, 136(4): 502-509.[3]. dumont y, cadieux a, doods h, et al. biie0246, a potent and highly selective non-peptide neuropeptide y y(2) receptor antagonist. br j pharmacol, 2000, 129(6): 1075-1088.[4]. abbott cr, small cj, kennedy ar, et al. blockade of the neuropeptide y y2 receptor with the specific antagonist biie0246 attenuates the effect of endogenous and exogenous peptide yy(3-36) on food intake. brain res, 2005, 1043(1-2): 139-144.[5]. bacchi f, mathé aa, jiménez p, et al. anxiolytic-like effect of the selective neuropeptide y y2 receptor antagonist biie0246 in the elevated plus-maze. peptides, 2006, 27(12): 3202-3207.
Check Digit Verification of cas no
The CAS Registry Mumber 246146-55-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,4,6,1,4 and 6 respectively; the second part has 2 digits, 5 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 246146-55:
(8*2)+(7*4)+(6*6)+(5*1)+(4*4)+(3*6)+(2*5)+(1*5)=134
134 % 10 = 4
So 246146-55-4 is a valid CAS Registry Number.
InChI:InChI=1/C49H57N11O6/c50-46(51)53-25-13-22-40(45(64)52-26-27-58-47(65)59(34-14-3-1-4-15-34)60(48(58)66)35-16-5-2-6-17-35)54-41(61)32-49(23-11-12-24-49)33-42(62)56-28-30-57(31-29-56)43-36-18-7-8-19-37(36)44(63)55-39-21-10-9-20-38(39)43/h1-10,14-21,40,43H,11-13,22-33H2,(H,52,64)(H,54,61)(H,55,63)(H4,50,51,53)/t40-,43?/m0/s1
246146-55-4Relevant academic research and scientific papers
Application of the guanidine-acylguanidine bioisosteric approach to argininamide-type NPY Y2 receptor antagonists
Pluym, Nikola,Brennauer, Albert,Keller, Max,Ziemek, Ralf,Pop, Nathalie,Bernhardt, Guenther,Buschauer, Armin
, p. 1727 - 1738 (2012/01/14)
Strongly basic groups such as guanidine moieties are crucial structural elements, but they compromise the drug-likeness of numerous biologically active compounds, including ligands of G-protein-coupled receptors (GPCRs). As part of a project focused on the search for guanidine bioisosteres, argininamide-type neuropeptideY (NPY) Y2 receptor (Y2R) antagonists related to BIIE0246 were synthesized. Starting from ornithine derivatives, NG-acylated argininamides were obtained by guanidinylation with tailor-made mono-Boc-protected N-acyl-S-methylisothioureas. The compounds were investigated for Y2R antagonism (calcium assays), Y2R affinity, and NPY receptor subtype selectivity (flow cytometric binding assays). Most of the NG-substituted (S)-argininamides showed Y2R antagonistic activities and binding affinities similar to those of the parent compound, whereas NG-acylated or -carbamoylated analogues with a terminal amine were superior (Y2R: Ki and KB values in the low nanomolar range). This demonstrates that the basicity of the compounds, although 4-5 orders of magnitude lower than that of guanidines, is sufficient to form key interactions with acidic amino acids of the Y2R. The acylguanidines bind with high affinity and selectivity to Y2R over the Y1, Y4, and Y5 receptors. As derivatization of the amino group is tolerated, these compounds can be considered building blocks for the preparation of versatile fluorescent and radiolabeled pharmacological tools for invitro studies of the Y2R. The results support the concept of bioisosteric guanidine-acylguanidine exchange as a broadly applicable approach to retain pharmacological activity despite decreased basicity.
