Peptides et Protéines

Applications Cyclosporin is an immunosuppressant that has revolutionized organ transplantation through its use in the prevention of graft rejection.A group of nonpolar cyclic oligopeptides with immunosupppressant activity.
References van Wartburg, A., et al.: Prog. Med. Chem., 25, 1 (1988), Jorgensen, K.A., et al.: Scand. J. Imunol., 57, 93 (2003), Vollenbroeker, et al.: Transplant. Proc., 37, 1741 (2005),

Applications C7H13NO3S (cas# 1115-47-5) is a useful research chemical.

Applications N-Acetyl-L-methionine (CAS# 65-82-7) has been useful in the study of metabolic phenotypes of standard and cold-​stored platelets.
References D’Alessandro, A., et al.: Transfusion (Malden, MA, US), 60, S96 (2020)

Applications Used for the synthesis of Bortezomib from L-phenylalanine via dipeptidyl boronic acid ester intermediates.
References Zhu, Y., et al.: J. Med. Chem., 52, 4192 (2009),

Impurity Lisinopril EP Impurity D
Stability Hygroscopic
Applications Lisinopril (S,S,R)-Diketopiperazine (Lisinopril EP Impurity D) is an impurity of Lisinopril (L468985), an orally active angiotensin-converting enzyme (ACE) inhibitor (1).
References 1. Goa, K. et al.: Drugs. 1996 Oct;52(4):564-88.

Applications An immunosuppressant that has revolutionized organ transplantation through its use in the prevention of graft rejection.A group of nonpolar cyclic oligopeptides with immunosupppressant activity.
References van Wartburg, A., et al.: Prog. Med. Chem., 25, 1 (1988), Jorgensen, K.A., et al.: Scand. J. Imunol., 57, 93 (2003), Vollenbroeker, et al.: Transplant. Proc., 37, 1741 (2005),

Applications Labelled N-2-(Hydroxyethyl)-L-valine (H942300). Cotinine and N-(2-hydroxyethyl)valine are markers of passive exposure to tobacco smoke in children.
References Dempsey, D., et al.: Clin. Pharmacol. Ther., 67, 458 (2000), Smith, C., et al.: Food Chem. Toxicol., 41, 807 (20030,

Impurity Levothyroxine N-Formyl Impurity; N-Formyl-T4 (USP)
Applications N-Formyl Thyroxine (Levothyroxine N-Formyl Impurity; N-Formyl-T4 (USP)) is a thyroxine derivative which showed less thyroid activity than Thyroxine Sodium (T425601).
References Basil, B., et al.: Br. J. Pharmacol. Chemother., 5, 315 (1950),

Applications Labelled Bortezomib, which the first proteasome inhibitor to be approved by the US FDA for multiple myeloma, a blood cancer. A reversible inhibitor of the 26S proteasome-a barrel-shaped multiprotein particle found in the nucleus and cytosol of all eukaryotic cells.d6-3%d7-10%d8-86%
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package
References Nawrocki, S.T., et al: Cancer Research, 65, 11510 (2005)

Applications A group of nonpolar cyclic oligopeptides with immunosupppressant activity.
References van Wartburg, A., et al.: Prog. Med. Chem., 25, 1 (1988), Jorgensen, K.A., et al.: Scand. J. Imunol., 57, 93 (2003), Vollenbroeker, et al.: Transplant. Proc., 37, 1741 (2005),

Applications Used in the treatment of cataracts and in the treatment of UV-induced immunosuppression. May act with with lipoic acid (L468725) to reverse age-related metabolic decline and also the indicies of oxidative stress.
References Babizhayev, M., et al.: J. Pharmacol. Toxicol., 1, 201 (2006), Min, J., et al.: J. Neurosci. Res., 86, 2984 (2008), Babizhayev, M., et al.: J. Drug Target., 17, 36 (2009); Hagen et. al, PNAS 99: 1870 (2002); Liu et. al, PNAS 99, 2356 (2002)

Stability Moisture Sensitive
Applications (2S,4S)-Sacubitril is an impurity of Sacubitril (S080895) which is an antihypertensive drug used in combination with valsartan.
References McMurray, J., et al.: N. Eng. J. Med., 371 (2014);

Applications L-Carnitine-L-tartrate (cas# 36687-82-8) is a useful research chemical.

Applications Bivalirudin Trifluoroacetic Acid Salt is an anticoagulant drug that is a direct thrombin inhibitor. It is used for treatment of acute coronary syndromes, and is a safer alternative to heparin due to lower rates of bleeding as an adverse effect of anticoagulant in patients.
References Stone, G., et al.: N. Engl. J. Med, 355, 2203 (2006); Stone, G., et al.: N Engl J Med, 358, 2218 (2008);

Applications A labelled nitrosoamino acid with oncogenic activity.
References Nagasawa, H.T., et al.: J. Med. Chem., 16, 583 (1973)

Applications A Cyclosporin A (C988900) analog, an immunosuppressant.
References Emmer, G., et al.: J. Med. Chem., 37, 1918 (1994), High, K., et al.: J. Biol. Chem., 269, 9105 (1994),

Impurity Lisinopril EP Impurity B/ Anastrozole EP Impurity F
Applications 4-Methylbenzenesulfonic Acid Monohydrate (Lisinopril EP Impurity B) is used in the synthesis of resveratrol. Also used in the synthesis of oxane derivatives as antimalarial agents.
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package
References Davis, M. et al.: Org. Prep. Proc. Int., 45, 304 (2013); Wang, X. et al.: J. Med. Chem., 56, 2547 (2013);

Applications (2R,4R)-Sacubitril is an impurity of Sacubitril (S080895) which is an antihypertensive drug used in combination with valsartan.
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package
References McMurray, J., et al.: N. Eng. J. Med., 371 (2014);

Applications Labelled analogue of L-Vailne. L-Valine is an essential amino acid and one of 20 proteinogenic amino acids. L-Valine cannot be manufactured by the body and must be acquired through diet or supplementation. L-valine is found in grains, dairy products, mushrooms, meats, peanuts and soy proteins. L-Valine has been used in studies to attenuate arrhythmias and induce hypotensive effects.
References Choi, C.W. et al.: Anim. Feed Sci. Technol., 102, 15 (2002); Kolarski, D. et al.: Krmiva, 30, 155 (1988); Oba, M. et al.: J. Dairy Sci., 93, 2044 (2010); Mitrega, K. et al.: Pharmacol. Res., 64, 218 (2011);

Applications Remifentanil derivative.
References James, M.K., et al.: J. Pharmacol. Exp. Ther., 259, 712 (1991), Hoffman, W.E., et al.: Anesthesiology, 79, 107 (1993), Selinger, K., et al.: J. Pharm. Biomed. Anal., 12, 243 (1994), Richardson, T.D., et al.: Expert Opin. Drug Saf., 4, 643 (2005),

Stability Light Sensitive
Applications Protoporphyrin-9 is the precursor to heme sites and chlorophyll.

Applications 5-9-Leuprolide is a metabolite of Leuprolide (L330590), a gonadotropin-releasing hormone (GnRH) analogue acting as an agonist at pituitary GnRH receptors.
References Handelsman, David J., et al.: J. of Steroid Biochem. and Mol. Bio., 141, 113-120 (2014);Okada, Hiroaki, et al.: Pharma. Res., 8(6), 787-91 (1991)

Applications A nitrosoamino acid with oncogenic activity. The LD50 of a single ip dose given to Swiss-Webster mice is 203 +/- 22 mg / kg.
References Nagasawa, H.T., et al.: J. Med. Chem., 16 (5), 583-585 (1973)

Impurity Bortezomib USP Related Compound A
Applications (1R,2R)-Bortezomib is a diastereomer of Bortezomib (B675700), the first proteasome inhibitor to be approved by the US FDA for multiple myeloma, a blood cancer. A reversible inhibitor of the 26S proteasome-a barrel-shaped multiprotein particle found in the nucleus and cytosol of all eukaryotic cells. Targets the ubiquitin-proteasome pathway
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package
References Nawrocki, S.T., et al: Cancer Research, 65, 11510 (2005); Drahl C.: Chem. and Eng. News, 87, 41 (2009)

Applications (S)-Lisinopril (L468985) impurity. Lisinopril Impurity G (Dimer Impurity)

Impurity Levothyroxine beta-Hydroxy Impurity / Levothyroxine beta-Hydroxy T4 Impurity
Applications It has been prepared for testing as possible antithyroid. It showed some thyromimetic activity.
References Wawzone, S., et al.: J. Med. Chem., 6, 442 (1963),

Impurity Lisinopril EP Impurity F
Applications Lisinopril Cyclohexyl Analogue (Lisinopril EP Impurity F) is a Lisinopril (L468985) impurity.
References Paraskevas, G., et al.: J. Pharm. Biomed. Anal., 29, 865 (2002),

Applications R,S,S-Isomer of Lisinopril (L468985).
References Goa, K.L., et al.: Drugs, 52, 564 (1996), Chaturvedi, N., et al.: Lancet, 351, 28 (1998)

Applications (R)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid, is an amino acid building block used in peptide synthesis. With a growing peptide drug market the fast, reliable synthesis of peptides is of great importance.

Impurity Teriparatide Impurity
Applications A fragment of human parathyroid hormone (hPTH) peptide sequence containing the 30 N-terminal residues of hPTH.
References Niall, et al.: Proc. Natl. Acad. Sci., 71, 384 (1974);

Applications Sacubitril is an antihypertensive drug used in combination with valsartan. The combination drug, valsartan/sacubitril, known during trials as LCZ696 and marketed under the brand name, Entresto, is a treatment for heart failure.
References McMurray, J., et al.: N. Eng. J. Med., 371 (2014)

Applications Oxytocin Acetate is the principal uterus-contracting and lactation-stimulating hormone of the posterior pituitary gland.
References Pierce, et al.: J. Biol. Chem., 199, 929 (1952), Tuppy, et al.: Biochem. Biophys. Acta, 11, 449 (1953), Cash, et al.: J. Med. Pharm. Chem., 5, 413 (1962), Nachtmann, F., et al.: Anal. Profiles Drug Subs., 10, 563 (1981),

Applications N-Glycylproline was found to exhibit anti-ischemic effects on the metabolism of neuroactive amino acids and indices of energy turnover in the neocortex of rats after experimental brain ischemia.
References Bashun, Z.N., et al.: Neurochem. J., 7, 39 (2013);

Applications Labelled L-Methionine, an essential aminoacid for human development. Hepatoprotectant; antidote (acetominophen poisoning); urinary acidifier.
References Benevenga, N.J., et al.: J. Agric. Food Chem., 22, 2 (1974), Fleisher, L.D., et al.: Clin. Endocrinol. Metab., 3, 37 (1974), Meinnel, T., et al.: Biochimie, 75, 1061 (1993),

Applications Glecaprevir is an antiviral drug used in the treatment of patients with hepatitis C virus (HCV) genotype 1-6, of special interest for the treatment of patients with chronic kidney disease also suffering from HCV.
References Kwo, P., et. al.: J. Hepatol, 67, 263 (2017)Gane, E., et. al.: N. Engl. J. Med, 377, 1448 (2017)

Applications L-Thioproline is used to create a monolayer on gold electrodes for the determination Copper(II). L-Thioproline has shown to be an effect inhibitor of proline absorption in Saccharomyces chevalieri.
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package
References Cui, X., et. al.: Sci. China Chem., 53, 257 (2010); Magana-Schwenchke, N., Schwencke, J.: BBA-Biomembranes, 173, 313 (1969)

Applications Carfilzomib is a second-generation proteasome inhibitor that is used as a treatment in relapsed and refractory multiple myeloma.
References Fostier, K., et al.: Oncotargets. Therap., 5, 237 (2012); Geurink, P.P., et al.: J. Med. Chem., 56, 1262 (2013); McCormack, P.L., et al.: Drugs., 72, 2023 (2012);

Applications NN703 (Tabimorelin) is an orally active growth hormone (GH) secretagogue intended for use as an alternative to daily injections of GH. In vitro studies in human liver microsomes have indicated that NN703 is a mechanism-based inhibitor of CYP3A4.
References Fabre, G., et al.: Biochem. Pharmacol., 37, 4389 (1988), Thummel, K., et al.: Clin. Pharmacol. Ther., 59, 491 (1996), Yu, D., et al.: J. Clin. Pharmacol., 39, 1203 (1999),

Applications Perfluorophenol is used in the synthesis of PGA-films as biodegradable polymers. It also participates in the synthesis of tripod macrocyclic Gd(III) chelates for cancer molecular MRI.
References Lee, K. et al.: Langmuir., 20, 2531 (2004); Zhou, Z. et al.: Biomater., 34, 7683 (2013);

Impurity Bortezomib USP Impurity I
Applications (R)-Hydroxy Des(boric acid) Bortezomib is an impurity in the synthesis of Bortezomib (B675700), the first proteasome inhibitor to be approved by the US FDA for multiple myeloma, a blood cancer. A reversible inhibitor of the 26S proteasome-a barrel-shaped multiprotein particle found in the nucleus and cytosol of all eukaryotic cells. Targets the ubiquitin-proteasome pathway.
References Nawrocki, S.T., et al: Cancer Research, 65, 11510 (2005); Drahl C. et al.: Chem. and Eng. News, 87, 41 (2009)

Stability Hygroscopic and Moisture Sensitive
Applications Bortezomib is the first proteasome inhibitor to be approved by the US FDA for multiple myeloma, a blood cancer. A reversible inhibitor of the 26S proteasome-a barrel-shaped multiprotein particle found in the nucleus and cytosol of all eukaryotic cells. Targets the ubiquitin-proteasome pathway.
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package
References Nawrocki, S.T., et al: Cancer Research, 65, 11510 (2005); Drahl C.: Chem. and Eng. News, 87, 41 (2009);

Applications Labelled Voclosporin (V678500). A new agent for the treatment of noninfectious uveitis. Uveitis is an inflammatory, putative Th1-mediated autoimmune disease that affects various parts of the eye and is a leading cause of visual loss. Voclosporin, a rationally designed novel calcineurin inhibitor, exhibits a favorable safety profile, a strong correlation between pharmacokinetic and pharmacodynamic response, and a wide therapeutic window. Immunosuppressant.
References Aspeslet, L., et al.: Transplant Proc., 33, 1048 (2001), Cho, M., et al.: Arthritis Rheum., 46, 1202 (2002), Staatz, C., et al.: Clin. Pharmacokinet., 43, 623 (2004),

Applications Teduglutide-d8 TFA salt x hydrate (Leu-methyl-d3+Phe-d5) is an isotopically labelled form of Teduglutide (T013795), which is glucagon-like peptide-2 (GLP-2) analogue that is used for the treatment of short bowel syndrome.
References Jeppesen, P., et al.: Gut, 54, 1224 (2005)
Chemical Name: Jeppesen, P., et al.: Gut, 54, 1224 (2005)

Stability Temperature Sensitive, Hygroscopic
Applications An intermediate in the synthesis of the acyclic amino carboxylic acid L-Methionine sulfoximine.
References Lee, B., et al.: J. Biol. Chem., 283, 28361 (2008), Nordqvist, A., et al.: Bioorg. Med. Chem., 16, 5501 (2008), Balog, E., et al.: Biochem., 48, 3005 (2009),

Applications 3,3’,5-Triiodo-L-thyronine 4’-O-Sulfate is the sulfoconjugated metabolite of 3,3’,5-Triiodo-L-thyronine (T795380).
References Rooda, S.J. et al.: J. Clin. Endocrinol. Metab., 69, 552 (1989); Everts, M. E. et al.: Metab. Clin. Exp., 43, 1282 (1994); Pinna, G. et al.: Endocrinology, 143, 1789 (2002);

Impurity Bortezomib USP Impurity G
Stability Hygroscopic
Applications (1S,2S)-Bortezomib is an isomer of Bortezomib (B675700), proteasome inhibitor. (1S,2S)-Bortezomib has been seen to inhibit serine proteases shown to lower cellular Aβ concentrations, associated with Alzheimer’s or hypertension.
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package
References Hardy, J. et al.: Science, 297, 353 (2002); Paris, D. et al.: Mol. Med. 17, 149 (2011);

Applications Teduglutide TFA Salt is a polypeptide consisting of 33 amino acids. It is glucagon-like peptide-2 (GLP-2) analogue that is used for the treatment of short bowel syndrome.
References Jeppesen, P., et al.: Gut, 54, 1224 (2005)

Applications Thyroxine Methyl Ester is the methyl ester analog of Thyroxine (T425600) with high cross reactivity with thyroxine-specific monoclonal antibodies of humans and lab animals. It is an inhibitor of malate dehydrogenase.Thyroxine Methyl Ester is suitable for malate dehydrogenase (MDH) related research.
References Mpoko, C.N. et al.: Clin. Chim. Acta, 146, 215 (1985); Maggio, E.T. et al.: Biochim. Biophys. Acta Enzymol., 522, 284 (1978);

Applications Sugammadex Sodium-deuterated, is the labaled analogue of Sugammadex Sodium (S698100), which is the first in a class of drugs called selective relaxant binding agents that offers improved termination of the paralytic effects of neuromuscular blocking agents and may have many potential peri-operative benefits.
References Welliver, M., et al.: Drug Des. Devel. Ther., 2, 49 (2008);

Applications A group of nonpolar cyclic oligopeptides with immunosupppressant activity.
References van Wartburg, A., et al.: Prog. Med. Chem., 25, 1 (1988), Jorgensen, K.A., et al.: Scand. J. Imunol., 57, 93 (2003), Vollenbroeker, et al.: Transplant. Proc., 37, 1741 (2005),

Applications Sacubitril Impurity 2 is an impurity of Sacubitril (S080895) which is an antihypertensive drug used in combination with valsartan.
References McMurray, J., et al.: N. Eng. J. Med., 371 (2014);

Stability Hygroscopic
Applications One of the thyroid hormones involved in the maintenance of metabolic homeostasis. Synthesized and stored as amino acid residues of thyroglobulin, the major protein component of the thyroid follicular colloid. Synthesis and secretion are regulated by the pituitary hormone (TSH). Deiodinated in peripheral tissues to the active metabolite, liothyronine. The D-form has very little activity as a thyroid hormone, but has been used to treat hyperlipidemia.
References Post, A., et al.: Anal. Profiles Drug Subs., 5, 225 (1976), Nelson, J.C., et al.: Clin. Chem., 34, 1737 (1988), Fischer, D.A., et al.: Clin. Chem., 42, 135 (1996), Cavalieri, R.R., et al.: Thyroid, 7, 177 (1997),

Applications Impurity of Bivalirudin, a direct thrombin inhibitor acting as an anticoagulant through inhibition of the enzyme thrombin.
References Bertrand, O. et al.: Am. J. Cardio., 110, 599 (2012); Patti, G. et al.: Am. J. Cardio., 110, 478 (2012);

Applications Romidepsin is a histone deacetylase inhibitor that can alter chromatin structure and gene transcription leading to multiple changes in cellular protein production. This may result in cell cycle arrest and tumor growth inhibition. Romidepsin has shown anti-proliferative activity in vitro against multiple mouse and human tumor cell lines and in vivo in human tumor xenograft models. Romidepsin can be administered with a second agent, such as a cytotoxic agent, a steroidal agent, a proteasome inhibitor, or a kinase inhibitor.
References Ueda, H., et al.: J. Antibiot., 47, 301 (1994), Weidle, U., et al.: Anticancer Res., 20, 1471 (2000), Kitazono, M., et al.: Cancer Res., 61, 6328 (2001), Sandor, V., et al.: Clin. Cancer Res., 8, 718 (2002),

Stability Hygroscopic
Applications A selective HIV protease inhibitor. An analogue of Ritonavir. Antiviral. It is a COVID19-related research product.
References Sham, H.L., et al.: Antimicrob. Ag. Chemother., 42, 3218 (1998), Kumar, G.N., et al.: Drug Metab. Dispos., 27, 86 (1999), Murphy, R.L., et al.: Antiviral Ther., 4, Suppl. 3, 85 (1999)

Applications Tert-butyl Acetate is a common solvent used in the production of various industrial cleansers, thinners and adhesives and is also known as a VOC.Environmental contaminants; Food contaminants
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package
References Mackay, D., et al.: SAR. QSAR. Enviro. Res., 23, 205 (2012); Yang, Y.S., et al.: Toxicol. Res., 26, 293 (2010);

Applications A major metabolite of Lopinavir (L469480) . It is a COVID19-related research product.
References Molla, A., et al.: J. Virology, 250, 255 (1998), Sham, H., et al.: Antimicrob. Agents Chemother., 42, 3218 (1998), Kumar, G., et al.: Drug Metab. Dispos., 27, 86 (1999),

Impurity Levothyroxine T4-Hydroxyacetic Acid; T4-Hydroacetic Acid (USP)
Stability Hygroscopic
Applications 3,5,3',5'-Tetraiodo Thyromandelic Acid (Levothyroxine T4-Hydroxyacetic Acid; T4-Hydroacetic Acid (USP)) is a thyroid hormone analogue, a Thyroxine (T425600) impurity.
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package
References Horst, C., et al.: Biochem. J., 261, 945 (1989), Kvetny, J., et al.: Horm. Metab. Res., 24, 322 (1992), Yamauchi, K., et al.: J. Biol. Chem., 274, 8460 (1999), Davis, P., et al.: J. Endocrinol. Invest., 25, 377 (2002),

Applications Thyroxine 4-O-β-D-Glucuronide is a major metabolite and glucuronide conjugate of Thyroxine (T425600) formed via the glucuronidation of the phenyl hydroxyl group.
References Tong, Z. et al.: Drug Metab. Dispos., 35, 2203 (2007); West, C.D. et al.: J. Clin. INvest., 42, 1134 (1963);

Applications Immunostimulant used in patients with cell-mediated immunodepression.
References Gu, C., et al.: Pharm. Res., 25, 979 (2008), Fliri, A., et al.: J. Med. Chem., 52, 8038 (2009), Giagulli, C., et al.: Int. Immunopharmacol., 9, 1366 (2009),

Stability Hygroscopic
Applications γ-Cyclodextrin is used as nanomolecular encapsulation for drug delivery and pharmaceuticals. Used in the synthesis of unilamellar vesicles.
References Ikeda, A. et al.: Chem. Comm., 50, 1288 (2014); Gudmundsdottir, B. et al.: J. Ocular Pharm. Ther., 30, 35 (2014);

Applications 3-Mercaptopropionic Acid (cas# 107-96-0) is a compound useful in organic synthesis.
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package

Applications A labelled selective HIV protease inhibitor. An analogue of Ritonavir. Antiviral. It is a COVID19-related research product.
References Sham, H.L., et al.: Antimicrob. Ag. Chemother., 42, 3218 (1998), Kumar, G.N., et al.: Drug Metab. Dispos., 27, 86 (1999), Murphy, R.L., et al.: Antiviral Ther., 4, Suppl. 3, 85 (1999)

Applications Essential aminoacid for human development. Hepatoprotectant; antidote (acetominophen poisoning); urinary acidifier.
References Benevenga, N.J., et al.: J. Agric. Food Chem., 22, 2 (1974), Fleisher, L.D., et al.: Clin. Endocrinol. Metab., 3, 37 (1974), Meinnel, T., et al.: Biochimie, 75, 1061 (1993),

Applications Labelled Oxytocin. The principal uterus-contracting and lactation-stimulating hormone of the posterior pituitary gland.
References Pierce, et al.: J. Biol. Chem., 199, 929 (1952), Tuppy, et al.: Biochem. Biophys. Acta, 11, 449 (1953), Cash, et al.: J. Med. Pharm. Chem., 5, 413 (1962), Nachtmann, F., et al.: Anal. Profiles Drug Subs., 10, 563 (1981),

Applications Carfilzomib (2R,4R)-Diol is a derivative of Carflizomib (C183460), a second-generation proteasome inhibitor that is used as a treatment in relapsed and refractory multiple myeloma.
References Fostier, K., et al.: Oncotargets. Therap., 5, 237 (2012); Geurink, P.P., et al.: J. Med. Chem., 56, 1262 (2013); McCormack, P.L., et al.: Drugs., 72, 2023 (2012);