Reagentes Sintéticos

<p>Applications (Chloromethyl)cyclopropane is a used as a reagent to synthesize 6-alkylamino-9-alkylpurines, compounds that have potential to be antipsychotic agents. (Chloromethyl)cyclopropane is also used as a reagent to prepare acylmorphinans, a class of compounds that have analgesic effects in rats.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Kelley, J., et al.: J. Med. Chem., 40, 3207 (1997); Mohacsi, E., et al.: J. Med. Chem., 28, 1177 (1985)<br></p>

<p>Applications Cyclopropylacetylene is used in a variety of chemical reactions in organic syntheses. Used in the synthesis of BACE1 inhibitors used in the treatment of Alzheimer’s disease. It is also used in cycloaddition reactions and the synthesis of fluoromethylsydnones.<br>References Xu, Y. et al.: Bioorg. Med. Chem. Lett., 23, 3075 (2013); Foster, R. et al.: J. Org. Chem., 78, 4049 (2013);<br></p>

<p>Applications A useful synthetic intermediate for carbohydrate synthesis.<br></p>

<p>Applications Aclidinium Bromide is a novel long-acting antimuscarinic bronchodilator in phase II clinical trials for the treatment of chronic obstructive pulmonary disease (1,2).<br>References (1) Gupta, V. and Singh, D.: Expert Rev Respir Med. 6, 581 (2012) (2) De La Motte, S., et al.: Int. J. Clin. Pharmacol. Therap., 50,403 (2012)<br></p>

<p>Applications 1,2-Diaminopropane-N,N,N',N'-tetraacetic Acid is an aminopolycarboxylic acids found at ultra-trace levels in water; Also, it is used in the construction of Eu3+ ion-selective membrane electrode as suitable ionophore.<br>References Nette, D., et al.: Anal. Chim. Acta, 884, 124-132 (2015); Abedi, M. R., et al.: E-J. Chem., 8, S467-S473 (2011)<br></p>

<p>Applications 6-Methoxy-4-pyrimidinamine is used in the synthesis of carbamothiolacrylamides as selective EP2 antagonists in the treatment of neurodegenerative peripheral diseases. Also used in the preparation of PARP-1 inhibitors.<br>References Ganesh, T. et al.: ACS Med. Chem. Lett., 4, 616 (2013); Rhee, H. et al.: Bioorg, Med. Chem., 17, 7537 (2009);<br></p>

<p>Applications 2-Chloro-4-fluorobenzoic Acid s a useful synthetic intermediate. It can be used to prepare aryl aminopyrazole benzamides as oral non-steroidal selective glucocorticoid receptor agonists. It can also be used to synthesize (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives as arginine vasopressin V2 receptor agonists.<br>References Barnett, H., et al.: Bioorg. Med. Chem. Lett., 19, 158 (2009); Tsukamoto, I., et al.: Bioog. Med. Chem., 16, 9524 (2008)<br></p>

<p>Applications 1-Iodo-3-nitrobenzene is a reactant used int he synthesis of Vismodegib (V674700), an, antineoplastic drug that targets the Hedgehog (Hh) pathway. Inhibition of the Hh signaling may be effective in the treatment and prevention of many types of human cancers.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Cao, M., et. al.: Chem. Papers, 68, 1408 (2014); Gupta, S. et al.: Ther. Advances in Med. Oncology 2,237(2010)<br></p>

<p>Applications Dihydrokainic acid is an EAAT2(GLT1)-selective non-transportable inhibitor of L-glutamate and L-aspartate uptake.<br>References Grunewald, M., et al.: J. Biol. Chem., 275, 9684 (2000); Shimamoto, K., et al.: Mol. Pharmacol., 53, 195 (1998);<br></p>

<p>Applications Bevirimat is a HIV-1 maturation inhibitor, targetting the Gag CA-SP1 cleavage site. HIV Inhibitor.<br>References Coric, P. et al.: Eur. J. Med. Chem., 62, 453 (2013); Waki, K. et al.: PLoS Path., 8, e1002997 (2012);<br></p>

<p>Applications N-Carbethoxyphthalimide is used in the synthetic preparation of a novel dual binders as potent, selective, and orally bioavailable tankyrase inhibitors.<br>References Hua, Z., et al.: J. Med. Chem., 56, 10003 (2013);<br></p>

<p>Applications MNI-caged-L-glutamate, is a new caged neuroactive amino acid, that use 4-methoxy-7-nitroindolinyl- (MNI) group to make caged ligands specific for glutamate receptor sub-types. MNI-caged-L-glutamate, rapidly release glutamate when photolysed.<br>References Palma-Cerda, F., et al.: Neuropharmacology, 63, 624 (2012); Canepari, M. J. Neuroscience Methods, 112, 29 (2001);<br></p>

<p>Applications 4-(2,3-Dimethoxyphenyl)butanoic acid is a butyrate analogue with effects on apoptosis, proliferation and histone deacetylase (HDAC) activity in HT-29 colorectal cancer cells.<br>References Scheppach, W., et al.: Eur. J. Cancer, 31A, 1077 (1995), Wu, J., et al.: J. Lipid Res., 46, 1944 (2005), Kiefer, J., et al.: Br. J. Nutr., 96, 803 (2006),<br></p>

<p>Stability Moisture Sensitive<br>Applications 2-Acetamido-5-nitrophenylboronic acid, pinacol ester<br></p>

<p>Applications N-(2,4-Dinitro-5-fluorophenyl)-L-valinamide is used in the synthesis of chiral variants of Marfey’s reagent. It is also used in the preparation of phaeofungin from Phaeosphaeria.<br>References Bhushan, R. et al.: Acta. Chrom., 20, 329 (2008); Singh, S. et al.: J. Nat. Prod., 76, 334 (2013);<br></p>

<p>Stability Hygroscopic<br>Applications 5-Amino-6-nitroquinoline is a reagent used in the synthesis of benzodiazepine sulfonamide-based bombesin receptor 3 agonists. It is also used in the synthesis of quinoxalinediones.<br>References Liu, P. et al.: ACS. Med. Chem. Lett., 2, 933 (2011); Bigge, C. et al.: J. Med. Chem., 38, 5720 (1995);<br></p>

<p>Applications AMG 337 is a potent and selective inhibitor of mesencymal epethelial transition factor (MET factor) which has been implicated in several cancers.<br>References Boezio, A. et al.: J. Med. Chem., 59, 2326 (2016);<br></p>

<p>Applications (S)-(-)-1-(2-Naphthyl)ethanol is a useful biochemical for proteomics research.<br></p>

<p>Applications Diphenyl Phosphite is a reactant used in the synthesis of α-hydroxyphosphonates and α-hydroxyphosphinates for their antioxidant and antimicrobial activity.<br>References Sampath, C. et al.: Phosphor. Sulfur Silicon. Rel. Elem., 191, 95 (2016);<br></p>

<p>Applications TETRAMETHYLAMMONIUM BOROHYDRIDE (cas# 16883-45-7) is a useful research chemical.<br></p>

<p>Applications 1-(2-Chloroethyl)pyrrolidine is a haloalkyl substituted pyrrolidine used in the preparation of various pharmaceutical compound such as the estrogen receptor antagonist Nafoxidine (N212800) and its analogues.<br>References Neyyarapally, A.T. et al.: Ind. J. Chem., 11, 325 (1973); Jones, C.D. et al.: J. Med. Chem., 27, 1057 (1984); Nakata, K. et al.: Molecules, 15, 6773 (2010);<br></p>

<p>Applications N-Acetyl-DL-Valine is an amino acid.<br>References Hirschmann R., et al.: Science, 265, 234 (1994); Gu Z. T., et al.: J. Magn. Reson., 140, 340 (1999); Bodalo, A., et al.: Enzyme Microb. Technol., 24, 381 (1999)<br></p>

<p>Applications (1R,2R,3S,5R)-(-)-2,3-Pinanediol is a bicyclic monoterpene diols that has been shown to induce differentiation of S91 melanoma and PC12 pheochromocytoma cells and thus provide possible therapeutic and sunless tanning use. (1R,2R,3S,5R)-(-)-2,3-Pinanediol is a microbial oxidation product of (-)-β-pinene, a flavor and fragrance monoterpene.<br>References Farooq, A. et al.: Zeitsch. Naturforsch. C J. Biosci., 57, 686 (2002); Brown, D.A. et al.: Pigment Cell Res., 12, 36 (1999);<br></p>

<p>Applications 2-Fluoropyridine acts as a reagent in the synthesis of aminopyrimidines with antimicrobial and antifungal properties.<br>References Hedidi, M., et al.: Eur. J. Org. Chem., 39, 5903 (2017)<br></p>

<p>Applications 2-(2-Aminophenyl)-1H-benzimidazole is a chemical reagent used in the synthesis of small molecule inhibitors targeting ubiquitin-like domains for treatments of diseases caused by the cellular accumulation of damaged proteins. Also used in the synthesis of pharmaceutical agents targeting leishmania related parasites.<br>References Keurulainen, L. et al.: Bioorg. Med. Chem. Lett., 25, 1933 (2015); He, Y. et al.: Bioorg. Med. Chem., 23, 2798 (2015);<br></p>

<p>Stability Very Hygroscopic<br>Applications Labelled Plerixafor, it is a hematopoietic stem cell (HSC) mobilizer that inhibits the CXCR4 chemokine receptor and blocks binding of its ligand, stromal cell-derived factor-1-α (SDF-1-α). This agent was approved on Dec. 15, 2008, as treatment in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize HSCs to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM).<br>References Xie, T., et al.: Science, 290, 328 (2000), Leone, D., et al.: J. Pharmacol. Exp. Ther., 305, 1150 (2003), Chigaev, A., et al.: J. Immunol. 178, 6828 (2007), Kiel, M., et al.: Cell Stem Cell, 1, 204 (2007),<br></p>

<p>Applications Diethyl Bromomalonate is a chemical constituent of the asymmetric cyclopropanation of chalcones. Also used in the preparation of nanaplatforms for NIR imaging-guided photodynamic therapy of cancer cells.<br>References Herchl, R. et al.: Tetra. Lett., 54, 2472 (2013); Liu, X. et al.: Chem. Comm., 49, 3224 (2013);<br></p>

<p>Stability Moisture Sensitive<br>Applications Heptanoyl Chloride is used in the synthesis of novel class of 2-Aminopyrimidines as CDK1 and CDK2 inhibitors.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Samanta, R., et al.: Org. Lett., 14, 5518 (2012); Sabbah, M., et al.: Bioorg. Med. Chem., 20, 4727 (2012);<br></p>

<p>Applications 4-Pyridineacetic Acid Hydrochloride is used in the preparation of a highly tumor-selective organometallic ruthenium(II)-Arene complex.<br>References Clavel, C.M., et. al.: J. Med. Chem., 57, 3546 (2014)<br></p>

<p>Applications 4-Methoxybenzenemethanamine is used in the synthesis of COX2 inhibitors based on a pyrimidine scaffold. Also used in the preparation of SIRT1 inhibitors. Used in anti-cancer treatments.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Tietz, O. et al.: Org. Biomol. Chem., Eur. J. Med. Chem., 69, 125 (2013);<br></p>

<p>Applications 4-Nitro-benzeneethanol is a useful synthetic intermediate. It can be used to synthesize N-phenylethylindole carboxamides as SAR study of allosteric modulators of CB1 receptor. It can also be used to prepare 2-aza-2'-deoxyinosine-containing oligodeoxyribonucleotide duplexes.<br>References Piscitelli, F., et al.: J. Med. Chem., 55, 5627 (2012); Acedo, M., et al.: J. Org. Chem., 60, 6262 (1995)<br></p>

<p>Applications 1,4-Diazabicyclo[2.2.2]octane is an aliphatic amine that is used as a catalyst in organic synthesis.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Baghernejad, B.: Eur. J. Chem., 1, No pp. given (2010); Guzonas, D., et al.: Langmuir, 6, 11002 (1990)<br></p>

<p>Applications Tetraethyl Orthocarbonate is used in the synthesis of chemokine receptor-5 inhibitors against HIV-1. Also used in the synthesis of benzobisoxazoles used in the preparation of organic semiconductors.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Kazmierski, W. et al.: J. Med. Chem., 54, 3756 (2011); Mike, J. et al.: Org. Lett., 10, 4915 (2008);<br></p>

<p>Applications (1,3-Dioxolan-2-ylmethyl)triphenylphosphonium Bromide is used as a reactant in the synthesis of ketolides methyloxoerythromycins with antibacterial activity as highly potent against macrolide-resistant and susceptible respiratory pathogens.<br>References Agouridas, C., et al.: J. Med. Chem., 41, 4080 (1998);<br></p>

<p>Applications Magnesium Bromide Hexahydrate is an inorganic salt used in the synthesis of superconductors and nanowires. Also present in polymer nanocomposites to improve conductivity.<br>References Alam, M. et al.: Polym. Int., 63, 1465 (2014); McDonald, T. et al.: J. Am. Chem. Soc., 135, 7056 (2012);<br></p>

<p>Applications An intermediate of synergistic pesticide Boscalid. Also, used in the preparation of thieno[2.3-b]pyrrole derivatives as cannabinoid receptor agonists useful in mono- and combination therapy of diseases.<br>References Granger, D., et al.: Arthritis Rheum., 37, 1053 (1994), Robinson, R., et al.: J. Med. Chem., 39, 10 (1996),<br></p>

<p>Applications 3,5-Di-t-butyl-2-hydroxybenzaldehyde is a salicylaldehyde derivative with antibacterial activity used in the preparation nickel complexes. 3,5-Di-t-butyl-2-hydroxybenzaldehyde is structurally related to 3,5-di-t-butylcatechol (DTCAT) but is not as potent an activator of rat skeletal muscle ryanodine receptor Ca2+ channel (RyRC).<br>References Tuerkkan, B. et al.: Trans. Met. Chem., 36, 679 (2011); Fusi, F. et al.: Biochem. Biopharmacol., 69, 485 (2005);<br></p>

<p>Applications An Aurora kinase inhibitor, used to treat patients with chromic myeloid leukemia. It is a COVID19-related research product.<br>References Fancelli, D., et al.: J. Med. Chem., 49, 7247 (2006), Carpinelli, P., et al.: Mol. Canc. Ther., 6, 3158 (2007), Coumar, M., et al.: J. Med. Chem., 52, 1050 (2009),<br></p>

<p>Applications N,N,N-Tributyl-1-butanaminium Salt with (E)-3-Hydroxy-2-propenal is a useful reagent for preparation of crystalline (±)​-​fecapentaene.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Pfaendler, H., et al.: J. Am. Chem. Soc., 108, 1338 (1986);<br></p>

<p>Applications 1,3-Dichloro-5-isocyanatobenzene is a reagent used in the synthesis of carbamate and aryl ether substituted pyrazinones as corticotropin releasing factor-1 receptor antagonists as well as the synthesis of novel triazolor pyridine derivatives.<br>References Ahuja, V. et al.: Bioorg. Med. Chem. Lett., Zhang, L. et al.: Turk. J. Chem., 39, 876 (2015);<br></p>

<p>Applications Chiral ligand for metal mediated asymmetric catalysis.<br>References Inui, Y., et al.: Chem. Pharm. Bull., 57, 1158 (2009), Lam, K., et al.: Eur. J. Med. Chem., 45, 5527 (2010),<br></p>

<p>Applications A reactant used in the preparation of Duloxetine (D721000) metabolites.<br>References Kuo, F. et al.: Bioorg. Med. Chem. Lett., 14, 5233 (2004)<br></p>

<p>Stability Moisture Sensitive<br>Applications Zinc Di[bis(trifluoromethylsulfonyl)imide] is a reactant used in the assembly of pyrene-based Schiff base MII4L6 architectures.<br>References Ronson, T. et al.: J. Am. Chem. Soc., 137, 14502 (2015); Riddell, I. et al.: Chem. Sci., 6, 3533 (2015);<br></p>

<p>Applications 6-Bromopurine is a brominated derivative of purine used in various organic syntheses. Used in the synthesis of several benzo-fused scaffolds with purine or pyrimidine moietes which display antitumor and anticancer properties.<br>References Morales, F. et al.: Eur, J. Med. Chem., 76, 118 (2014); Cushing, T. et al.: J. Med. Chem., 58, 480 (2015); Jansen, R., et al.: Clin. Biochem., 38, 362 (2005),<br></p>

<p>Applications 2-Phenyl-1,2-benzoselenazol-3-one acts as an antiinfammatory compounds,, in addition to that it acts as a modulator of KVβ subunits.<br>References Wendel, A. et al.: Biochem. Pharmacol., 33, 3241 (1984);<br></p>

<p>Applications 2-(Tributylstannyl)oxazole is a useful reactant in preparation of potent, selective and efficacious reversible α-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Boger, D., et al.: J. Med. Chem., 48, 1849 (2005);<br></p>

<p>Applications An intermediate for polycyclic indazole derivatives that are ERK inhibitors.<br>References Orjales, A., et al.: J. Med. Chem., 46, 5512 (2003), Mariappan, P., et al.: J. Eur. Urology., 51, 67 (2007), Hughes, J., et al.: Bioorg. Med. Chem. Lett., 18, 4872 (2008), Kielbasa, W., et al.: Drug Metab. Dispos., 37, 137 (2009),<br></p>

<p>Applications GI 254023X is an ADAM10 metaloproteinase inhibitor.<br>References Hoettecke, N., et. al.: Neurodegeneration Diseases, 7, 232 (2010)<br></p>

<p>Applications 2,4-Dichloro-5-trifluoromethylpyrimidine is a reactant in the preparation of pyrimidine derivatives as inhibitors of gene ALK protein Kinase phosphorylating kinase and as cell proliferation inhibitors.<br>References Yang, E.H., et. al.: Bull. Korean Chem. Soc., 34, 3129 (2013)<br></p>

<p>Applications Methyl 11-bromoundecanoate is a brominated fatty acid building block, used in the synthesis of Emmyguyacins A and B, which are proposed inhibitors of the influenza virus.<br>References Jana, S.; et al.: Org. Lett., 20, 6938 (2018).<br></p>

<p>Applications Antineoplastic adjunct (chemosensitizer).<br>References Boesch, D., et al.: exp. Cell Res., 196, 26 (1991), Lush, R.M., et al.: J. Clin. Pharmacol., 37, 123 (1997), Scott, M.G., et al.: Clin. Chem., 43, 505 (1997), Advani, R., et al.: Blood, 93, 787 (1999),<br></p>

<p>Applications An indole derivative used in synthesis of matrix metalloprotease inhibitors.<br>References Somei, M., et al.: Nat. Prod. Rep., 22, 73 (2005),<br></p>

<p>Applications BAY 57-1293 Methanesulfonate Salt is used in biological studies as an antiviral agents for treating and preventing shingles and a method of treating zoster(herpes) associated pain as it is a potent helicase primase inhibitor.<br>References Kleyman, G., et al.: Nat. Med., 8, 392 (2002); Wozniak, M.A., et al.: Antiviral Res., 99, 401 (2013);<br></p>

<p>Applications 3'-Bromo-4'-methylacetophenone is used as a starting material in the synthesis of mansonone E which is used to make mansonone E dervivatives. These derivatives are potent inhibitors of topoisomerase II (Topo II) and topoisomerase I (Topo I) and are also potent antitumor agents. 3'-Bromo-4'-methylacetophenone is also used as a reagent in the synthesis of BAF312, Siponimod which has been tested in the treatment of patients suffering from relapsing-remitting multiple sclerosis.<br>References Fang, X., et al.: J. Chem. Res., 38, 137 (2014); Huang, Z., et al.: Eur. J. Med. Chem., 68, 58 (2013); Pan, S., et al.: ACS Med. Chem. Lett., 4, 333 (2013)<br></p>

<p>Stability Unstable in solution. Small amounts of precipitate should have no effect on use.<br>Applications 1-Chloro-N,N-2-trimethylpropenylamine acts as a reagent in the synthesis and antitumor activity of (-)-bassianolide in human cancer cells through cell cycle arrest. Enantioselective total synthesis of nannocystins A and A0 as elongation factor 1 inhibitors. Total synthesis of (-)-caprazamycin A with antibacterial activity against Mycobacterium tuberculosis (TB) via diastereoselective aldol reaction.<br>References Mun, B., et al.: Bioorg. Chem., 69, 64 (2016); Huang, J., et al.: Org. Lett., 18, 4702 (2016); Nakamura, H., et al.: Angew. Chem., Int. Ed., 54, 3136 (2015)<br></p>

<p>Applications 1,4,7-triazonane (cas# 4730-54-5) is a useful research chemical.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br></p>

<p>Stability Hygroscopic<br>Applications A selective serotonin reuptake inhibitor (SSRI). Used as an antidepressant.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Wong, D.T., et al.: Life Sci., 15, 471 (1974), Goldstein, D.J., et al.: Br. J. Psychiat., 166, 660 (1995), Ni, Y.G., et al.: Proc. Nat. Acad. Sci. USA, 94, 2036 (1997)<br></p>

<p>Applications α,α,α-Trifluorotoluene, is used as a specialty solvent in organic synthesis and an intermediate in the production of pesticides and pharmaceuticals.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Skelly, P. D., et al.: Handbook for Critical Cleaning, 1, 191 (2011);<br></p>

<p>Applications (S)​-​(+)​-​Pantolactone is a versatile cyclic ester reactant used in the preparation of tunable ligands carbohydrate-derived diarylphosphinites for asymetric catalysis hydrovinylation of styrene derivatives.<br>References Park, H., RajanBabu, T.: J. Am. Chem. Soc., 124, 734 (2002);<br></p>

<p>Applications Piperonylamine is a metabolite of dopamine analogs.<br>References Goodwin, B.L., et al.: Xenobiotica, 24, 129 (1994),<br></p>

<p>Applications 4-(Trifluoromethyl)benzonitrile is used in the synthesis of quinazolines for amidines. Also used in the synthesis of s-transferase p1-1 and cancer cell proliferation.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Lv, Y. et al.: Chem. Comm., 49, 6349 (2013); Yang, X. et al.: J. Med. Chem., 53, 1015 (2010);<br></p>

<p>Applications JNJ 17203212 is a high affinity TRPV1 receptor antagonist.<br></p>

<p>Applications 2-Acetamido-4-fluorophenylboronic acid, pinacol ester<br></p>

<p>Applications ML141 is a potent selective reversible non-competitive inhibitor of Rho family GTPase use in the treatment of bacterial infections.<br>References Hong, L. et al.: J. Biol. Chem., 288, 8531 (2013)<br></p>

<p>Applications 4,4’,(5’)-Di-(tert-butylcyclohexano)-18-crown-6 is a crown ether-based sorbent used in the analysis and separation of minerals.<br>References Yankovskaya, V. et al: J. Radioanal. Nucl. Chem., 314, 119 (2017);<br></p>

<p>Applications ent-Ticagrelor is the enantiomer of Ticagrelor (T437700); the first reversible oral P2Y12 receptor antagonist that provides faster, greater, and more consistent ADP-receptor inhibition than Clopidogrel. Used in the treatment of acute coronary syndromes (ACS).<br>References Matetzky, S., et al.: Circulation, 109, 3171 (2004); Bassand, J., et al.: Eur. Heart J., 28, 1598 (2007); Jakubowski, J., et al.: Cardiovasc. Drug Rev., 25, 357 (2007)<br></p>