2-Imidazoline

443871329 Imidazoline numbering.png 120px Skeletal formula of imidazoline Imidazoline 3D ball.png 150 Ball-and-stick model of the imidazoline molecule 4,5-Dihydro-1H-imidazole 2-Imidazoline4,5-Dihydro-1,3-diazole correct CAS 504-75-6 103920 correct EBI 53094 correct chemspider 61464 207-999-4 2431371 correct FDA D36R5YLK6R 68156 1/C3H6N2/c1-2-5-3-4-1/h3H,1-2H2,(H,4,5) MTNDZQHUAFNZQY-UHFFFAOYAB correct chemspider 1S/C3H6N2/c1-2-5-3-4-1/h3H,1-2H2,(H,4,5) correct chemspider MTNDZQHUAFNZQY-UHFFFAOYSA-N N\1=C\NCC/1 3 6 2 2-Imidazoline (Preferred IUPAC name: 4,5-dihydro-1H-imidazole) is one of three isomers of the nitrogen-containing heterocycle imidazoline, with the formula C3H6N2. The 2-imidazolines are the most common imidazolines commercially, as the ring exists in some natural products and some pharmaceuticals. They also have been examined in the context of organic synthesis, coordination chemistry, and homogeneous catalysis. Synthesis thumb|left|400px|Synthesis of imidazolines from nitrile and from ester precursors. A variety of routes exist for the synthesis of imidazolines, Crouch RD Synthetic routes toward 2-substituted 2-imidazolines Tetrahedron March 2009 65 12 2387–2397 10.1016/j.tet.2008.12.022 with the most common methods involving the condensation of 1,2-diamines (e.g. ethylenediamine) with nitriles or esters. The nitrile based route is essentially a cyclic Pinner reaction; it requires high temperatures and acid catalysis and is effective for both alkyl and aryl nitriles. left As natural products Imidazoline has been found in various natural products. Natural molecules topsentin D and spongotine B were discovered in several marine sponges. These metabolites have received considerable attention because of their potent properties such as antitumor, antiviral, and anti-inflammatory activities. Guinchard X, Vallée Y, Denis JN Total synthesis of marine sponge bis(indole) alkaloids of the topsentin class The Journal of Organic Chemistry 72 10 3972–3975 May 2007 17444688 10.1021/jo070286r Biological role Many imidazolines are biologically active. Macinnes N, Duty S Locomotor effects of imidazoline I2-site-specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway British Journal of Pharmacology 143 8 952–959 December 2004 15545290 1575965 10.1038/sj.bjp.0706019 Most bio-active derivatives bear a substituent (aryl or alkyl group) on the carbon between the nitrogen centers. Some generic names include oxymetazoline, xylometazoline, tetrahydrozoline, and naphazoline. Applications Pharmaceutical 2-imidazolines have been investigated as antihyperglycemic, anti-inflammatory, antihypertensive, antihypercholesterolemic, and antidepressant reagents. Liu H, Du DM March 2009 Recent Advances in the Synthesis of 2-Imidazolines and Their Applications in Homogeneous Catalysis Advanced Synthesis & Catalysis 351 4 489–519 10.1002/adsc.200800797 Dardonville C, Rozas I Imidazoline binding sites and their ligands: an overview of the different chemical structures Medicinal Research Reviews 24 5 639–661 September 2004 15224384 10.1002/med.20007 31258438 The imidazoline-containing drug clonidine is used alone or in combination with other medications to treat high blood pressure. It is also used in the treatment of dysmenorrhea, hypertensive crisis, Tourette's syndrome and attention deficit hyperactivity disorder (ADHD). Clonidine October 2008 Pubmed Health https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000623/ https://web.archive.org/web/20100628173619/https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000623/ 28 June 2010 As p53 activators Cis-imidazolines act as small-molecule antagonists of MDM2. These compounds bind MDM2/X in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice. The most active compounds are nutlin-3a Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA 6 In vivo activation of the p53 pathway by small-molecule antagonists of MDM2 Science 303 5659 844–848 February 2004 14704432 10.1126/science.1092472 2004Sci...303..844V 16132757 and rg-7112, Vu B, Wovkulich P, Pizzolato G, Lovey A, Ding Q, Jiang N, Liu JJ, Zhao C, Glenn K, Wen Y, Tovar C, Packman K, Vassilev L, Graves B 6 Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development ACS Medicinal Chemistry Letters 4 5 466–469 May 2013 24900694 4027145 10.1021/ml4000657 but some other analogs also activate p53. Bazanov DR, Pervushin NV, Savin EV, Tsymliakov MD, Maksutova AI, Sosonyuk SE, Kopeina GS, Lozinskaya NA 6 December 2021 Sulfonamide derivatives of cis-imidazolines as potent p53-MDM2/MDMX protein-protein interaction inhibitors https://link.springer.com/10.1007/s00044-021-02802-w Medicinal Chemistry Research en 30 12 2216–2227 10.1007/s00044-021-02802-w 241788123 1054-2523 subscription Bazanov DR, Pervushin NV, Savitskaya VY, Anikina LV, Proskurnina MV, Lozinskaya NA, Kopeina GS 2,4,5-Tris(alkoxyaryl)imidazoline derivatives as potent scaffold for novel p53-MDM2 interaction inhibitors: Design, synthesis, and biological evaluation Bioorganic & Medicinal Chemistry Letters 29 16 2364–2368 August 2019 31196710 10.1016/j.bmcl.2019.06.007 189815065 Bazanov DR, Pervushin NV, Savin EV, Tsymliakov MD, Maksutova AI, Savitskaya VY, Sosonyuk SE, Gracheva YA, Seliverstov MY, Lozinskaya NA, Kopeina GS 6 Synthetic Design and Biological Evaluation of New p53-MDM2 Interaction Inhibitors Based on Imidazoline Core Pharmaceuticals 15 4 444 April 2022 35455441 9027661 10.3390/ph15040444 free Surfactants Surfactants based around 2-imidazoline, such as sodium lauroamphoacetate, are used in personal care products where mildness and non-irritancy are particularly important (e.g. baby products, "no more tears" shampoos etc.). Tyagi R, Tyagi VK, Pandey SK Imidazoline and its derivatives: an overview Journal of Oleo Science 56 5 211–222 2007 17898484 10.5650/jos.56.211 free As precursors of imidazoles Imidazoles can be prepared from dehydrogenation of imidazolines. Ishihara M, Togo H 2006 An Efficient Preparation of 2-Imidazolines and Imidazoles from Aldehydes with Molecular Iodine and (Diacetoxyiodo)benzene Synlett 2 227–230 10.1055/s-2005-923604 Homogeneous catalysis As a structural analogue of 2-oxazolines, 2-imidazolines have been developed as ligands in coordination chemistry. The substitutions on the nitrogen atom in the imidazoline ring provide opportunities for fine-tuning the electronic and steric properties. Some of the complexes function as catalysts for Suzuki–Miyaura couplings, Mizoroki–Heck reactions, Diels–Alder reactions, asymmetric allylic substitution, [3,3] sigmatropic rearrangement, Henry reactions. File:Dehydrogenation of imidazoline.png See also Imidazoline receptor Imidazolidine References