CRF mediates numerous stress-related endocrine, autonomic, metabolic, and behavioral responses. We present the synthesis and chemical and biological properties of astressin B analogues {cyclo(30-33)[D-Phe(12),Nle(21,38),C(α)MeLeu(27,40),Glu(30),Lys(33)]-acetyl-h/r-CRF(9-41)}. Out of 37 novel peptides, 17 (2, 4, 6-8, 10, 11, 16, 17, 27, 29, 30, 32-36) and 16 (3, 5, 9, 12-15, 18, 19, 22-26, 28, 31) had k(i) to CRF receptors in the high picomolar and low nanomole ranges, respectively. Peptides 1, 2, and 11 inhibited h/rCRF and urocortin 1-induced cAMP release from AtT20 and A7r5 cells. When Astressin C 2 was administered to adrenalectomized rats at 1.0 mg subcutaneously, it inhibited ACTH release for >7 d. Additional rat data based on the inhibitory effect of (2) on h/rCRF-induced stimulation of colonic secretory motor activity and urocortin 2-induced delayed gastric emptying also indicate a safe and long-lasting antagonistic effect. The overall properties of selected analogues may fulfill the criteria expected from clinical candidates.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959268 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.5b00926 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Manganese-Promoted Cyclization Reaction of Enynones with Tetrasulfides: Synthesis of Multisubstituted Furanmethyl Disulfides.
J Org Chem
September 2024
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, PR China.
A tandem cyclization reaction of enynones with tetrasulfides has been developed under manganese-promoted conditions, leading to the high-yield formation of various furanmethyl disulfides. This reaction is characterized by readily available starting materials, mild reaction conditions, and a broad substrate scope, making it attractive and practical. It provides a new strategy for the synthesis of disulfide-containing functionalized furans.
View Article and Find Full Text PDFHalogenated Phenylpyridines Possessing Chemo-Selectivity for Diverse Molecular Architectures.
ACS Omega
July 2024
Department of Chemistry and Chemistry Research Center, Laboratories for Advanced Materials, United States Air Force Academy, Colorado Springs, Colorado 80840, United States.
Pentafluoropyridine was used as a molecular building block for the installation of aryl bromides, affording a series of multisubstituted halogenated arenes. This operationally simplistic methodology offers precise regioselectivity, ease of scalability, and high purity. F Nuclear magnetic resonance (NMR) served as a key diagnostic tool for structural characterization, given the sensitivity with various aryl bromine substitutions on the fluorinated pyridine ring.
View Article and Find Full Text PDFPhoto-cycloaddition reactions of vinyldiazo compounds.
Nat Commun
May 2024
Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas, USA.
Heterocyclic rings are important structural scaffolds encountered in both natural and synthetic compounds, and their biological activity often depends on these motifs. They are predominantly accessible via cycloaddition reactions, realized by either thermal, photochemical, or catalytic means. Various starting materials are utilized for this purpose, and, among them, diazo compounds are often encountered, especially vinyldiazo compounds that give access to donor-acceptor cyclopropenes which engage in [2+n] cycloaddition reactions.
View Article and Find Full Text PDFA Phosphine-Free Air-Stable Mn(II)-Catalyst for Sustainable Synthesis of Quinazolin-4(3)-ones, Quinolines, and Quinoxalines in Water.
J Org Chem
April 2024
Department of Chemistry, Indian Institute of Engineering Science and Technology, Botanic Garden, Howrah, Shibpur 711103, India.
The synthesis, characterization, and catalytic application of a new phosphine-free, well-defined, water-soluble, and air-stable Mn(II)-catalyst [Mn(L)(HO)Cl](Cl) ([]Cl) featuring a 1,10-phenanthroline based tridentate pincer ligand, 2-(1-pyrazol-1-yl)-1,10-phenanthroline (), in dehydrogenative functionalization of alcohols to various -heterocycles such as quinazolin-4(3)-ones, quinolines, and quinoxalines are reported here. A wide array of multisubstituted quinazolin-4(3)-ones were prepared in water under air following two pathways via the dehydrogenative coupling of alcohols with 2-aminobenzamides and 2-aminobenzonitriles, respectively. 2-Aminobenzyl alcohol and ketones bearing active methylene group were used as coupling partners for synthesizing quinoline derivatives, and various quinoxaline derivatives were prepared by coupling vicinal diols and 1,2-diamines.
View Article and Find Full Text PDFIdentification of new multi-substituted 1H-pyrazolo[3,4-c]pyridin-7(6H)-ones as soluble guanylyl cyclase (sGC) stimulators with vasoprotective and anti-inflammatory activities.
Bioorg Chem
March 2024
Laboratory of Medicinal Chemistry, Department of Pharmacy, University of Patras, Patras, GR-26500, Greece. Electronic address:
Herein, we describe the rational design, synthesis and in vitro functional characterization of new heme-dependent, direct soluble guanylyl cyclase (sGC) agonists. These new compounds bear a 1H-pyrazolo[3,4-c]pyridin-7(6H)-one skeleton, modified to enable efficient sGC binding and stimulation. To gain insights into structure-activity relationships, the N6-alkylation of the skeleton was explored, while a pyrimidine ring, substituted with various C5'-polar groups, was installed at position C3.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!