Synonyms:CCK-33;Cholecystokinin;Cholecystokinin 33;Pancreozymin;Uropancreozymin
RIPK2 *data from reagent suppliers
The research focuses on the design and synthesis of a novel, non-peptide cholecystokinin (CCK) receptor agonist, PD 170292, which exhibits a pharmacological profile similar to the CCK analogue JMV180. The study aimed to develop a compound with high affinity and potency for the CCK receptor, potentially useful in treating obesity. The design strategy involved appending a key feature from the peptide CCK receptor selective agonist A-71623 onto a peptoid motif that selectively binds the CCK2 receptor. The synthesis of PD 170292 began with the phenethylamide derivative and involved several steps, including the use of 2-methylphenyl isocyanate, EtO2CCI, TEA, THF, "CH2N2", PhCO2Ag, TEA, TMSCH2CH2OH, HCO2H, and 2-Adoc(R)xMeTrp.O.HBTU, DIPEA, acid, DMF, and TBAF in THF. The compound was analyzed for its binding affinity and functional activity at CCK receptors, showing high nanomolar affinity for the rat pancreatic CCK receptor and behaving as a full agonist at high-affinity sites and an antagonist at low-affinity sites. Experiments included assessing its ability to stimulate amylase release from isolated rat pancreatic acini, its effect on [Ca2+] mobilization in Jurkat cells, and its antagonistic activity against CCK-8S-induced [Ca2+] accumulation. The compound demonstrated high efficacy and potency at the CCK receptor, along with a high affinity CCK2 receptor antagonist profile.
The research focuses on the development of 1,4-benzodiazepine derivatives as Cholecystokinin (CCK-A) receptor agonists for the treatment of obesity. The purpose of the study was to synthesize and screen a series of 1,4-benzodiazepines, specifically N-1-substituted with an N-isopropyl-N-phenylacetamide moiety, for their ability to activate CCK-A receptors, which regulate satiety and could potentially be used as a pharmacotherapeutic intervention for obesity. The researchers demonstrated in vitro agonist activity on isolated guinea pig gallbladder and in vivo induction of satiety in a rat feeding assay following intraperitoneal administration. The study concluded that a novel series of potent and efficacious 1,4-benzodiazepine and 1,4-benzodiazepine-4-N-oxide CCK-A agonists were successfully developed, which showed promising results in both in vitro and in vivo assays. Key chemicals used in the process included 3-amino-1,4-benzodiazepine core, N-isopropyl-N-phenylacetamide (agonist trigger), bromoacetamides, and various substituents at the C-3 position such as phenyl ureas, anilino acetamides, and indolylmethyl groups.
The research aims to develop and evaluate a new series of 4-substituted pipecolic acid derivatives as potential antagonists for the CCK-B receptor. Cholecystokinin (CCK) is a peptide hormone involved in various physiological processes, mediated by two receptors, CCK-A and CCK-B. The study focuses on the CCK-B receptor, which has suggested the existence of two subtypes through experiments using CCK-B ligands. The researchers designed and synthesized a series of dipeptoids with a piperidine ring replacing pyrrolidine, aiming to modify the relative orientation of the aromatic moiety towards the carboxylate while maintaining the essential requirements for CCK-B binding. Key chemicals used in the study include 4-substituted pipecolic acids, 2-Adoc-DL-t-methyltryptophan, and various reagents for synthesis and protection steps, such as Boc2O, NaOH, DEAD, PPh3, and Z-CI. The synthesized dipeptoids were evaluated for their ability to inhibit [3H]pCCK-8 binding to the CCK-B receptor in CHO cells. The results showed a general loss of affinity compared to proline-containing dipeptoids, with the most potent compound (9e) having a Ki value of 175.2 nM for CCK-B receptors. The study concludes that while the piperidine ring does not force the essential features for CCK-B recognition into an optimal fit, the final compounds are better ligands than other similar molecules derived from CCK4. The research also suggests a W-shaped bioactive conformation of peptoid CCK-B antagonists, providing valuable insights for further investigations in this field.
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