Salts and Derivatives of Active Pharmaceutical Ingredients (API)

<p>Applications Ivermectin B1a is a major component of Ivermectin (I940800), a semi-synthetic derivative of Abamectin; consists of a mixture of not less than 80% component B1a and not more than 20% component B1b. Antihelmintic (Onchocerca). An invitro inhibitor of SARS-CoV-2/ Covid-19.<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 Chabala, J.C., et al.: J. Med. Chem., 23, 1134 (1980); Campbell, W.C., et al.: Science, 221, 823 (1983); Bennett, J.L., et al.: Parasitol. Today, 4, 226 (1988); Plaisier, A.P., et al.: J. Infect. Dis., 172, 204 (1995);; Caly, L., et al.: Antivir. Res., 178<br></p>

<p>Applications N-Despropyl-macitentan, is an active metabolite which is part of a family of endothelin receptor antagonist that allows for treatment of pulmonary arterial hypertension (PAH)<br>References Atsmon, J., et al.: Clin. Pharmacokinet., 525, 685 (2013); Sidharta, P.N., et al.: Clin. Drug Invest. (2014)<br></p>

<p>Applications The trans metabolite of Latanoprost (L177280), Prostaglandin analog.<br>References Botchkareva, N., et al.: FASEB J., 115, 645 (2001),<br></p>

<p>Applications 4-Chlorobenzal Chloride is an impurity that is formed in the synthesis of Benoxaprofen (B165300); a non-steroidal anti-inflammatory ophthalmic agent.<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 Cockerill, A.F., et al.: J. Chromatogr., 129, 339 (1976); Mathur, K., et al.: Bioorg. Med. Chem., 11, 1915 (2003); Zhao, M., et al.: Bioorg. Med. Chem., 15, 2815 (2007); Roy, K., et al.: Eur. J. Med. Chem., 44, 2913 (2009)<br></p>

<p>Applications 1,2-Bismethylphenidate is an impurity of methylphenidate (M325880), an CNS stimulant.<br>References Greenblatt, E.N., et al.: J. Pharmacol. Exp. Ther., 131, 115 (1961), Padmanabhan, G.R., Anal. Profiles Drug Subs., 10, 473 (1981), Srinivas, N.R., et al.: Pharm. Res., 10, 14 (1993),<br></p>

<p>Applications 1-Chloroethyl Cyclohexyl Carbonate is a genotoxic impurity used in the synthesis of Candesartan Cilexetil. an angiotensin II receptor antagonist.<br>References Kakasaheb, N. et al.: Int. J. Pharm. Sci., 6, 370 (2014); Mao, Y. et al.: Heterocycles, 81, 1503 (2010);<br></p>

<p>Impurity Aceclofenac EP Impurity B<br>Applications Diclofenac Methyl Ester is the methyl ester analogue of Diclofenac (D436450), a known nonsteroidal anti-inflammatory compound and cyclooxygenase (COX) inhibitor. Aceclofenac EP Impurity B<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 Dannhardt, G., et al.: Eur. J. Med. Chem., 36, 109 (2001), Sorbera, L., et al.: Drug Future, 26, 133 (2001), Sorbera, L., et al.: Drug Future, 26, 133 (2001),<br></p>

<p>Applications Diclofenac Amide-13C6 is a labelled analogue of Diclofenac Amide (D436440), which is a potential prodrug of Diclofenac and possible impurity during its commercial synthesis. Diclofenac Amide-13C6 is also an intermediate in synthesizing Diclofenac-13C6 Sodium Salt (D436453), which is a labelled analogue of Diclofenac Sodium Salt (D436450).<br>References Gaudiano, M.C., et al.: J. Pharm. Biomed. Anal., 32, 151 (2003); De Castro, W.V., et al.: Drug Develop. Ind. Pharm., 32, 1103 (2006); Kenny, J. R., et al.: J. Med. Chem., 47, 2816 (2004), Sasaki, A., et al.: J. Pharmacol. Sci., 108, 266 (2008); Dalvie, D., et al.: Chem. Res. Toxicol., 22, 357 (2009)<br></p>

<p>Applications 3-Morpholino-1-(4-(2-oxopiperidin-1-yl)phenyl)-5,6-dihydropyridin-2(1H)-one (cas# 545445-44-1) is a useful research chemical.<br></p>

<p>Applications Dechloro-Rivaroxaban is an impurity of Rivaroxaban (R538000), which is a novel antithrombotic agent. A highly potent and selective, direct FXa inhibitor.<br>References Ansell, J., et al.: Drugs, 64, 1 (2004), Eriksson, B., et al.: J. Thromb. Haemost., 3, 103 (2005), Kubitza, D., et al.: Clin. Pharmacol. Ther., 78, 412 (2005),<br></p>

<p>Applications (5-Amino-2-butyl-3-benzofuranyl)[4-[3-(dibutylamino)propoxy]phenyl]methanone is an intermediate used in the synthesis of dronedarone hydrochloride (I), a class III antiarrhythmia drug for the prevention of cardiac arrhythmias such as atrial fibrillation.<br>References Mali, A. C., et al.: Org. Proc. Res. Dev., 17, 863 (2013)<br></p>

<p>Applications Disalicylimide is an impurity of Deferasirox (D228650), an orally active tridentate iron chelator.<br>References Hershko, C., et al.: Blood, 97, 1115 (2001), Galanello, R., et al.: J. Clin. Pharmacol., 43, 565 (2003), Nick, H., et al.: Curr. Med. Chem., 10, 1065 (2003),<br></p>

<p>Applications 3”-O-Demethyl Ivermectin is an impurity of Ivermectin (I940800), an antiparasitic drug that is active against a wide variety of nematode and arthropod parasites and is used to treat scabies and lice in humans. An invitro inhibitor of SARS-CoV-2/ Covid-19.<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 Campbell, W., et al.: Science, 221, 823 (1983); Glaziou, P., et al.: Trop. Med. Parasitol., 45, 253 (1994); Meinking, T., et al.: New Engl. J. Med., 333, 26 (1995); Caly, L., et al.: Antivir. Res., 178<br></p>

<p>Applications Bimatoprost 13,14-Epoxide is the impurity of Bimatoprost (B386800), which is an antiglaucoma agent. Bimatoprost is an synthetic prostamide; structurally related to prostaglandin F2α.<br>References Brandt, J.D., et al.: Ophthalmology, 108, 1023 (2001), Woodward, D.F., et al.: J. Pharmacol. Exp. Ther., 305, 772 (2003), Quinones, R., et al.: J. Ocul. Pharmacol. Ther., 20, 115 (2004)<br></p>

<p>Applications Impurity of Allopurinol (A547300), an xanthine oxidase inhibitor used in treatment of hyperuricemia and chronic gout. Antiurolithic.<br>References Benezra, S.A., et al.: Anal. Profiles Drug Subs., 7, 1, (1978), Dalbeth, N., et al.: Rheumatology, 44, 1090 (2005), Dinarello, C., et al.: J. Exp. Med., 201, 1355 (2005),<br></p>

<p>Applications S(+)-N-(2-(2-Thienyl)ethyl)-2-chlorophenyl Glycine Methyl Ester Hydrochloride is an impurity from Clopidogrel (C587250) which acts as an anti-platelet agent.<br>References Zhu, Y. et al.: ACS. Med. Chem. Lett., 4, 349 (2013); Feuerstein, G., et al.: Exp. Opin. Invest. Drugs, 4, 425 (1995)<br></p>

<p>Applications 1-​(4-​Aminophenyl)​-​5,​6-​dihydro-​3-​(4-​morpholinyl)​-​2(1H)​-​pyridinone is an intermediate in the synthesis of Apixaban (A726700), A potent, direct, selective, and orally active inhibitor of coagulation factor Xa. It is a potential new oral coagulant that may be useful prevention of venous thromboembolism in total hip, knee replacement orthopedic surgery and stroke in treatment of patient with venous thromboembolic disorder or with atrial fibrillation.<br>References Nevuluri, N. et al.: Monat. fuer Chem., 148, 1477 (2017);<br></p>

<p>Impurity Leflunomide EP Impurity H<br>Stability Hygroscopic<br>Applications 2-Cyano-N-[4-(trifluoromethyl)phenyl]acetamide (Leflunomide EP Impurity H) is used to prepare aminothiophene carboxylates and carboxamides as adenosine A1 receptor allosteric enhancers. It is also used to synthesize (1,2,3-triazol-4-yl)benzenamines as inhibitors against VEGF receptors 1 and 2.<br>References Nikolakopoulos, G., et al.: Bioorg. Med. Chem., 14, 2358 (2006); Kiselyov, A., et al.: Bioorg. Med. Chem. Lett., 19, 1344 (2009)<br></p>

<p>Applications Ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate is an impurity of Febuxostat (F229000), which is a xanthine oxidase/xanthine dehydrogenase inhibitor, used for treatment of hyperuricemia and chronic gout.<br>References Okamoto, K., et al.: J. Biol. Chem., 278, 1848 (2003); Mayer, M.D., et al.: Am. J. Therap., 12, 22 (2005); Tomlinson, B., et al.: Curr. Opin. Invest. Drugs, 6, 1168 (2005);<br></p>

<p>Impurity Tiotropium bromide EP impurity C<br>Applications (1R,3S,5S)-3-(2-Hydroxy-2,2-di(thiophen-2-yl)acetoxy)-8,8-dimethyl-8-azabicyclo[3.2.1]oct-6-en-8-ium Bromide is an impurity in the synthesis of Tiotropium Bromide (T444850), a muscarinic receptor antagonist. Bronchodilator.<br>References Haddad, E.-B., et al.: Mol. Pharmacol., 45, 899 (1994); Donohue, J. F., et al.: Chest, 122, 47 (2002); Profita, M., et al.: Allergy, 60, 1361 (2005); Dusser, D., et al.: Eur. Respir. J., 27, 547 (2006);<br></p>

<p>Impurity Propafenone EP Impurity E; Propafenone BP Impurity E; Propafenone USP Impurity E<br>Applications Depropylamino Chloro Propafenone (Propafenone EP Impurity E; Propafenone BP Impurity E; Propafenone USP Impurity E) is an impurity of Propafenone (D288655).<br>References Hollmann, M., et al.: Arzneim.-Forsch., 33, 763 (1983); Bryson, H. M., et al.:Drugs, 45, 85 (1993);<br></p>

<p>Stability Toxic<br>Applications Riluzole 5-Trifluoromethoxy Isomer is an impurity of Riluzole (R510000); a neuroprotective agent. Riluzole modulates glutamatergic transmission. It is a glutamate release inhibitor and an anticonvulsant.<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 Gunakkunru, A., et al.: Asian J. Chem., 19, 2843 (2007); Mizoule, J., et al.: Neuropharmacology, 24, 767 (1985); Wahl, F., et al.: Eur. J. Pharmacol., 230, 209 (1993); Bensimon, G., et al.: N. Engl. J. Med., 330, 585 (1994)<br></p>

<p>Stability Hygroscopic<br>Applications AR-C133913XX is an metabolte of Ticagrelor (T437700) which is the first reversible oral P2Y12 receptor antagonist, provides faster, greater, and more consistent ADP-receptor inhibition than Clopidogrel. Ticagrelor is 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>

<p>Applications 3-Hydroxy-1-methyl-pyridinium Bromide is a degradation product of Pyridostigmine Bromide (P991705), which is a cholinergic and it is used in the treatment of myasthenia gravis, and is a pre-exposure antidote to chemical warfare agents.<br>References Kayihan, G., et al.: Toxicol. Environ. Chem., 92, 1783 (2010), Yu, Q., et al.: Bioorg. Med. Chem., 18, 4687 (2010), Voicu, V., et al.: J. Pharm. Biomed. Anal., 52, 508 (2010)<br></p>

<p>Impurity Tiotropium EP Impurity B<br>Applications Scopine Di(2-thienylglycolate) (Tiotropium EP Impurity B) is a precursor to Tiotropium Bromide.<br>References Buchwald, P., et al.: Pharmazie., 55, S210 (2000),<br></p>

<p>Applications 4-Hydroxythiobenzamide is used in the synthesis of PPARα agonists used in increasing HDLc levels. Also used in the synthesis of potent CDK5 inhibitors in the treatment of Alzheimer’s disease.<br>References Sierra, M. et al.: J. Med. Chem., 50, 685 (2007); Zhong, W. et al.: Bioorg. Med. Chem. Lett., 17, 5384 (2007);<br></p>

<p>Applications Febuxostat n-butyl Isomer is an impurity of Febuxostat (F229000) which is a xanthine oxidase/xanthine dehydrogenase inhibitor.<br>References Osada, Y., et al.: Eur. J. Pharmacol., 241, 183 (1993); Okamoto, K., et al.: J. Biol. Chem., 278, 1848 (2003); Mayer, M.D., et al.: Am. J. Therap., 12, 22 (2005); Tomlinson, B., et al.: Curr. Opin. Invest. Drugs, 6, 1168 (2005)<br></p>

<p>Applications Diclofenac-13C6 is a labelled analogue of Diclofenac Acid (D436465), which is a nonsteroidal anti-inflammatory compound and decycloxygenase (COX) inhibitor. Diclofenac-13C6 is also an intermediate in synthesizing Diclofenac-13C6 Sodium Salt (D436453), which is a labelled analogue of Diclofenac Sodium Salt (D436450).<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 Yagi, K., et. al.: Biol. Pharm. Bull., 37, 1234 (2014); Kenny, J. R., et al.: J. Med. Chem., 47, 2816 (2004); Sasaki, A., et al.: J. Pharmacol. Sci., 108, 266 (2008); Dalvie, D., et al.: Chem. Res. Toxicol., 22, 357 (2009); Kenny, J. R., et al.: J. Med. Chem., 47, 2816 (2004), Sasaki, A., et al.: J. Pharmacol. Sci., 108, 266 (2008); Dalvie, D., et al.: Chem. Res. Toxicol., 22, 357 (2009)<br></p>

<p>Applications 4-Hydrazinobenzoic Acid, is an organic building block used for the synthesis of various chemical and pharmaceutical compounds. It can be used for the synthesis of Deferasirox (D228650), an orally active tridentate iron chelator.<br>References Ying, Ch., et al.: Xiandai Yaowu Yu Linchuang, 27, 446 (2012); Galanello, R., et al.: J. Clin. Pharmacol., 43, 565 (2003), Nick, H., et al.: Curr. Med. Chem., 10, 1065 (2003);<br></p>