THE
`MERCK INDEX
`
`AN ENCYCLOPEDIA OF
`CHEMICALS, DRUGS, AND BIOLOGICALS
`
`FOURTEENTH EDITION
`
`Maryadele J. O’Neil, Editor
`Patricia E. Heckelman, Senior Associate Editor
`Cherie B. Koch, Associate Editor
`Kristin J. Roman, Assistant Editor
`
`Catherine M. Kenny, Editorial Assistant
`Maryann R. D’Arecca, Administrative Associate
`
`Published by
`Merck Research Laboratories
`Division of
`
`MERCK & CoO., INC.
`Whitehouse Station, NJ, USA
`
`2006
`
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`Library of Congress Catalog Card Number 89-60001
`ISBN Number 0-911910-00-X
`ISBN Number 978-0-911910-00-1
`
`Copyright © 2006 by MERCK & CO., INC., Whitehouse Station, NJ, USA
`All rights reserved. No part of this book orelectronic product maybe reproduced or used in any form or by any means,
`electronic or mechanical, including photocopying, or by any information storage andretrieval system, without permission
`in writing from the Publisher. Inquiries should be addressed to The Merck Index Editorial Offices, P.O. Box 2000, Merck
`& Co., Inc., Rahway, NJ 07065.
`
`Printed in the USA
`
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`Eton Ex. 1119
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`2782
`
`3 (1945). Prepd from cystine or cysteine by oxidation with bromine
`in water: Friedmann, Beitr. Chem. Physiol. Pathol. 3, 25, 38;
`Gortner, Hoffman, J. Biol. Chem. 72, 435 (1927).
`L-Form. Octahedra or needles from dil alc (also forms a mono-
`hydrate, prismatic needles). When anhydr, dec 260°. [al]? +8.66°
`(1.85 g in 25 ml). pKa, (25°): 1.89; pKa, 8.7; pKb about 12.7.
`Soluble in water. Insol in alcohol.
`DL-Form. Crystals, dec 245°.
`2781. Cysteine.
`[52-90-4] L-Cysteine; Cys; C; B-mercapto-
`alanine; (R)-2-amino-3-mercaptopropanoic acid; 2-amino-3-mer-
`captopropionic acid; a-amino-B-thiolpropionic acid; half-cystine;
`thioserine. C,;H,NO,S; mol wt 121.16. C 29.74%, H 5.82%, N
`11.56%, O 26.41%, S 26.47%. A non-essential amino acid in
`human development. Readily oxides to form a dimeric amino
`acid, cystine, q.v., in which the two Cysare linked via a disulfide
`bridge, a commonstructural feature in proteins. Early chemistry
`and biochemistry: Amino Acids and Proteins, D. M. Greenberg, Ed.
`(Charles C. Thomas, Springfield, IL, 1951) 950 pp., passim; J. P.
`Greenstein, M. Winitz, Chemistry of the Amino Acids vol 1-3 (John
`Wiley and Sons, Inc., New York, 1961) pp. 1879-1928, passim.
`Simple synthesis of racemic cysteine: V. J. Martens et al., Angew.
`Chem. Int. Ed. 20, 668 (1981). Determn in proteins: J. G. Hoo-
`gerheide, C. M. Campbell, Anal. Biochem. 201, 146 (1992); D.
`Atherton et al., ibid. 212, 98 (1993), Review of biosynthesis: N.
`M. Kredich et al., Ciba Found. Symp. (Netherlands) 72, 87-99
`(1980). Review of transport in mammalian cells: S. Bannai, Bio-
`chim. Biophys. Acta 779, 289-306 (1984). Review of effects on
`acrylonitrile toxicity: D. E. Nerland et al., Drug Metab. Rev. 20,
`233-246 (1989). Review of thermodynamics and kinetics: T. R.
`Ralphet al., J. Electroanal. Chem. 375, 1-15 (1994); ofelectrosyn-
`thesis: eidem, ibid. 17-27. Review of role in chemo- and radio-
`protectantstrategies: J. C. Roberts, Amino Acids 8, 113-124 (1995).
`0
`
`Cystine
`99194-04-4] Stefin B; CPI-B; NCPI; neutral cys-
`:
`cystatin at inhibitor. Broadly distributed in humancells and
`pale cytosolic inhibitor to protect against leakage of
`wine P
`fssue : it mes. Mutations tn the cystatin B gene have been
`iysosorlsith progressive myoclonusepilepsy. Isoln from human
`jate
`e300
`:
`jarvinen, A. Rinne, Biochim. Biophys.Acta 708, 210
`plee™ humanliver: G. D.J. Green et al., Biochem. J. 218,
`1982) iReview of role in Unverricht-Lundborg disease: A.-E.
`939 (1984 EMBO J. 22, 3473-3478 (2003). Mature humanform is
`sjo! cy a non-glycosylated peptide containing 98 aminoacid
`a singlena wt 11.2 kDa. Isoelectric point: 5.6-6.3.
`:
`C.
`[91448-99-6] Post-y-globulin; y-CSF; -+-trace.
`iquitously in vertebrates; major extracellular cysteine pep-
`ree in mammals. Isoln from human CSF: J. Clausen,
`Found |
`i
`tidase inhi
`c, Exp. Biol. Med. 107, 170 (1961); from urineofpatients
`proc. ae sfunction: E. A. Butler, F. V. Flynn, J. Clin. Pathol. 14,
`withee Identification as a cystatin: A. J. Barrett et al., Bio-
`12 ae hys. Res. Commun. 120, 631 (1984). Review ofbio-
`chem.
`PI nd clinical role: M. Mussap, M.Plebani, Crit. Rev. Clin.
`chemistry 467-550 (2004); of efficacy as biomarker for glomer-
`Lab. iol rate: G. Filler et al., Clin. Biochem. 38, 1-8 (2005).
`ularfi ‘reunion to predict risk of cardiovascular events in elderly
`ClinicML.G.Shlipak et al., N. Engl. J. Med. 352, 2049 (2005).
`is Sarat form is a single chain, non-glycosylated peptide
`a 120 amino acid residues; mol] wt 13.3 kDa. Isoelectric
`eee 9.3, Electrophoretic mobility: y; (agarose gel electropho-
`Ee at pH 8.6). E!%, 9.1 (280 nm). Concin plasmaof healthy
`adults: 0.8 to 1.2 mg/l.
`. 3
`.
`THERAP CAT: Cystatin C as diagnostic aid (renal function).
`2779, Cysteamine.
`[60-23-1] 2-Aminoethanethiol; mer-
`captamine; f-mercaptoethylamine; 2-aminoethyl mercaptan; thio-
`ethanolamine; decarboxycysteine; MEA; mercamine; L-1573; Be-
`captan; Lambratene (formerly). C,H7NS; mol wt 77.15. C
`31.14%, H 9.15%, N 18.16%, S 41.56%. HSCH,CH,NH). A
`sulfhydryl compound with a variety of biological effects. Prepn:
`Gabriel, Leupold, Ber. 31, 2837 (1898); Knorr, Réssler, ibid. 36,
`1281 (1903); Mills, Jr., Bogart, J. Am. Chem. Soc. 62, 1173 (1940);
`Wenker, ibid. 57, 2328 (1935); D. A. Shirley, Preparation of Or-
`ganic Intermediates (Wiley, New York, 1951) p 189. Usein treat-
`ment of paracetamol (acetaminophen) poisoning: L. F. Prescott et
`al., Lancet 2, 109 (1976); A. L. Harris, Br. Med. J. 284, 825 (1982).
`Effects in nephropathic cystinosis: M. Yudkoffet al., N. Engl. J.
`Med. 304, 141 (1981). Radioprotective effects: R. P. Bird, Radiat.
`Res. 72, 290 (1980); C. J. Koch, R. L. Howell, ibid. 87, 265 (1981).
`Cysteamine has been shownto be a duodenalulcerogenin rats: H.
`Selye, S. Szabo, Nature 244, 458 (1973); S. Szabo, Am. J. Pathol.
`93, 273 (1978); P. Kirkegaard etal., Scand. J. Gastroenterol. 15,621
`(1980). Review: S. Szabo, Lab. Invest. 51, 121 (1984). It has also
`been found to deplete somatostatin concentration: S. Szabo, S.
`Reichlein, Endocrinology 109, 2255 (1981); S. M. Sagaret al., J.
`Neurosci. 2, 225 (1982). In pituitary tissue, cysteamineis a potent
`depletor of prolactin concentrations in vivo and in vitro: W.J.
`Millardet al., Science 217, 452 (1982). Toxicity studies: E. Bec-
`cari et al., Arzneim.-Forsch, 5, 421 (1955); D. L. Klaymanetal., J.
`iesChem. 12, 510 (1969); P. K. Srivastava, L. Field,ibid. 18, 798
`).
`Crystals by sublimation in vacuo. Disagreeable odor. mp 97-
`98.5°. Oxidizes to cystamine on standing in air. Freely sol in
`water, alkaline reaction. LDsp in mice (mg/kg): 625 orally; 250
`‘Pp. (Klayman);(Srivastava, Field).
`1ppttochloride. C,H,NS.HCI. Crystals from alc, mp 70.2-
`ie Sol im water, alcohol. LDso (cg/kg): 23.19 i.p. in rats;
`al in rabbits (Beccari).
`ER Experimentally as a radioprotective agent and to produce
`ute and chronic duodenal ulcers in rats.
`THERAP CAT: Antidote to acetaminophen.
`Pla Cysteic Acid. [13100-82-8] 3-Sulfoalanine; a-amino-
`4: ahs acid. C;H,NO,S; mol wt 169.16. C 21.30%, H
`S0H. Hy
`%, O 47.29%, S 18.96%. HOOCCH(NH,)CH)-
`Banate: i been isolated from human hair oxidized with perman-
`Mally in oe Z. Physiol. Chem. 173, 309 (1928). Occurs nor-
`Xposed 5 a Outer part of the sheep’s fleece, where the woolis
`light and weather: Martin, Synge, Adv. Protein Chem.2,
`
`HS
`
`‘OH
`
`NH2
`
`Crystals. [a]? +6.5° (SN HCI); [a]? +13.0° (glacial acetic acid).
`pK, 1.71; pK, 8.33; pK; 10.78. Absorption spectrum: Abderhal-
`den, Rossner, Z. Physiol. Chem. 178, 160 (1928). Freely sol in
`water, alcohol, acetic acid, ammonia water. Insol in ether, acetone,
`ethyl acetate, benzene, carbon disulfide, carbon tetrachloride. In
`neutralorslightly alkaline aq solnsit is oxidized to cystine by air.
`Morestable in acidic solns.
`Hydrochloride.
`[52-89-1] C;H,;NO,S.HCI. Crystals, dec
`175-178°.
`[e]?> +5.0° (SN HCl); [a]? +10.0° (glacial acetic
`acid). Sol in water, alcohol, acetone; the aq soln is acid. Keep
`tightly closed. Decomposesand oxidizes slowly; hygroscopic.
`USE: As dough conditioner.
`THERAP CAT (VET): Has been used as a detoxicant.
`
`2782. Cystine.
`[56-89-3] L-Cystine; [R-(R*,R*)]-3,3’-di-
`thiobis[2-aminopropanoic acid]; dicysteine; 8,8’-dithiodialanine;
`a-diamino-f-dithiolactic acid; 8,B'-diamino-8,8'-dicarboxydiethyl
`disulfide; bis(8-amino-8-carboxyethyl) disulfide; Gelucystine. C,-
`H,2N,045,4; mol wt 240.30. C 29.99%, H 5.03%, N 11.66%, O
`26.63%, S 26.69%. Non-essential amino acid for human develop-
`ment. Formedby the dimerization of two cysteines, q.v. through the
`sulfur. These disulfide bridges occur both within and between
`polypeptides; often found in extracellular proteins. First amino
`acid described in 1810 by Wollaston. Isoln from horn hydrolysate:
`K. A. H. Moérner, Z. Physiol. Chem. 28, 595 (1899). Early chem-
`istry and biochemistry: Amino Acids and Proteins, D. M. Green-
`berg, Ed. (Charles C. Thomas, Springfield, IL, 1951) 950 pp. pas-
`sim; J. P. Greenstein, M. Winitz, Chemistry of the Amino Acids vols
`1-3 (John Wiley and Sons, Inc., New York, 1961) pp. 1879-1928,
`passim. Distribution in protein: R. C. Fahey etal., J. Mol. Evol.
`10, 155 (1977). Review of lysosomaltransport including patho-
`physiology: W. Gahl in Pathophysiol. Lysosomal Transp., I. G.
`Thoene, Ed. (CRC Press, Boca Raton, FL, 1992) pp 45-71. Review
`of thermodynamicsand kinetics: T. R. Ralph er al., J. Electroanal.
`Chem. 375, 1-15 (1994); of electrosynthesis: eidem, ibid. 17-27.
`
`Consult the Name Index before using this section.
`
`Page 467
`
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`awOMwaooe
`
`Sas
`
`aTRAATSSSee
`
`oe
`a2
`
`Page 468
`
`Consult the Name Index before usine thic «.
`
`Eton Ex. 1119
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`
`s5-Dioxide
`
`.
`ethanol, mp 212-213°. La}p! +1530 ¢
`2: 281.0, 212.5 nm (€
`13171, 10239," i
`water).
`£9259).
`a
`12: 272.5 nm (
`Antineoplastic.
`THERAP CAT:
`,..
`‘
`115-93-5] Phosphorothioic
`acid 9,
`Cythioate.
`[11>-
`2785.v1yphentyl] 0,0-dimethy esterPhosphorothigs U4
`(aminosv hyl ester O-ester with p-hydroxy enzenesulfon, aig
`0,0-dimet y Q-p-sulfamoylphenylphosphorothioate, CLppl
`0.0-dimethy
`CgH12NOsPS3: mol wt 297,29
`69).
`ENT-25640; ProveO-3691%, P 10.42%, S 21.57%. pes,
`H 4.07%, N 4-7
`cond and R.I. Hewitt, G. Berkethan™6
`eee
`Berkelhammer isPietah Cyanamid). Pharmacodynann
`3179560 ee 1. Goulding, J. Econ. Entomol. 63, 1640 a
`G. Smith,
`‘ctoparasiticide: C. P. Doval, I. Gupta, Indig, Ve 0),
`Efficacy ome: P. M. Bowen,N.J. Caldwell, Vet. Med. Smay
`°°!
`allAnin EF
`SSeT (1982). Toxicity data: E. E. Kenaga, W, 5
`in.
`’
`Allis
`Bull. Entomol. Soc. Am. 15, 85 (1969).
`me
`
`reneTeenyLneeeern
`
`HCO
`HcO.\_-9
`o=u
`
`Q 0
`4
`SNH,
`
`Crystals, mp 70-71°. n® 1.5346. LDspoorally in Tats: 169
`mg/kg (Kenaga, Allison).
`nat
`USE: Insecticide.
`THERAP CAT (VET): Ectoparasiticide.
`2786. Cytidine.
`[65-46-3] 4-Amino-1-8-D-ribofuranosy).,
`(1H)-pyrimidinone; cytosine riboside; 1-B-D-ribofuranosyleytosing
`CoH,3N30s; mol wt 243.22. C 44.44%, H 5.39%, N 17.28%,9
`32.89%. Constituent of nucleic acids, Isoln from yeast nucleic
`acid: Levene, Jacobs, Ber. 43, 3154 (1910); Levene, La Forge,iti
`45, 608 (1912). Sepn from other nucleosides by ion-exchange
`chromatography: Cohn in Chargaff-Davidson, The Nucleic Acids
`vol. I (New York, 1955) p 211. Synthesis: Howard etal., J. Chen,
`Soc. 1947, 1052. Crystal structure: Furberg et al., Acta Crystal.
`logr. 18, 313 (1965). Review: Basic Principles in Nucleic Acid
`Chemistry vol. 1, P. O. P. Ts’o, Ed. (Academic Press, New Yor,
`1974) passim.
`
`NH2
`
`N~
`
`a 0
`
`HO
`
`OH
`
`HO
`
`Long needles from 90% ethanol, dec 220-230°. [a]? +31"
`0.7in water). Freely sol in water,less sol in alcohol. pK (amino.
`cationic) 4.22; pK (sugar,anionic) 12.5. uv max (pH 8.2): 271m
`(© 9100); (pH 2.2).
`8.2)
`2718
`193 (1963)
`): 280 nm (© 13400), Voetet al., Biopolym
`(C,
`Sulfate.
`224-225° (dec H13N30;)2.H,S0,. Long prismatic necdles
`with effervescence). [a]Bo +34°; [cr]345 +43
`Sanedettidylic Acid,
`[85-94-9] Cytidine-2’-monott®
`phate: i tdylic acid a; 2'-cytidinephosphoric acid; cytidine-? a C
`33.45% aaa acid; 2'-CMP. CyH)4N3OgP; mol wl oO
`inhibite, ene N 13.00%, O 39.60%, P 9.58%. Ribonwé i
`Chem. Sc a from yeastribonucleic acid: Cohn, Carte 5, $07
`yh,
`2s 2606 (1950); Loring et al., J. Biol. Chem. 1M
`:
`ey nee
`Rammler aoehorylation of N®,03',0° -tribenzoy!6YLag
`structure ne, 7 ae Chem. Soc. 84, 3112 gine scien
`179, 495 (1973) ta ofthe trihydrate: Kartha ef a
`:
`Keviews: See Cytidine.
`
`2783
`
`-Cystine S,
`
`NH2
`
`0
`
`NH2
`
`20
`
`mea
`°
`a al
`Hexagonaltablets from water, dec 260-261 ee eeae
`—223.4° (1.0N HCl). pK, 1; pK2 2.1; pK3 8.02; p mes 0.523: at
`Soly in water (g/l) at 25°: 0.112; at 50°: ine : “HB. Soly
`100°: 1,142. Quite sol in aq solns below pH 2 or abov . ped
`curves: Sano, Biochem. Z. 168, 14 (1926). Insol in a Pon Fr.
`tion spectrum: Marchlewski, Nowotonowna, Bull. Soc.
`[4] 39, 163, 166 (1926).
`.
`1
`p-Form.
`[349-46-2] Crystals. [a]20 +223°
`(1.0N HCD. Soly
`in water at 25°: 0.057g/l.
`‘
`33
`7
`DL-Form.
`[923-32-0] Crystals. Soly in water at 25°: 0.05
`meso-Form. [6020-39-9] Crystals. Soly in water: 0.056 gil.
`2783.
`1-Cystine S,S-Dioxide.
`[30452-69-8] Ppa?
`carboxyethyl 2-amino-2-carboxyethanethiosulfonate; fo 30
`thiosulfonate; sacysyl-cysteine. CgH,.N20,S2; mol wt 2
`suet
`C 26.47%, H 4.44%, N 10.29%, O 35.25%, S 23.55%. er
`productof cystine. Prepn: G. Toennies, T. F. Lavine, J. Bio .
`Chem. 113, 571 (1936); R. Emilozzi, L. Pichat, Bull. Soc. Chim.
`Fr. 1959, 1887. Orignally thought to be a mixture of two isomers,
`cystine S,S-dioxide and cystine S,S'-dioxide: G. E. Utzinger, Ex-
`perientia 17, 374 (1961). Elucidaton of structures: G. Axelson et
`al., Spectrochim. Acta 23A, 2015 (1967); L. D. Setiawanet al., Surf.
`Interface Anal. 7, 188 (1985). Use in determnofsulfite: T. Ubuka
`et al., Anal. Biochem. 126, 273 (1982); idemetal., ibid. 140, 449
`(1984).
`
`HO.
`
`0
`vo
`
`Ss
`
`OH
`
`Solid, relatively unstable in aqueous solns; disproportionates to
`cystine andcysteinesulfinic acid.
`USE: In detection ofsulfites and thiosulfate.
`
`[147-94-4] 4-Amino-1-8-D-arabinofura-
`2784. Cytarabine.
`nosyl-2(1H)-pyrimidinone; 1-8-D-arabinofuranosylcytosine; Ara-C;
`B-cytosine arabinoside; aracytidine; CHX-3311; U-19920; Alexan;
`Aracytine; Cytosar; Depocyte; Udicil. CyH,,;N30,; mol wt 243.22.
`C 44.44%, H 5.39%, N 17.28%, O 32.89%. Nucleoside analog;
`converted by cellular kinases into the active metabolite, AraCTP.
`Prepn: J. H. Hunter, US 3116282 (1963 to Upjohn); T. Y. Shen et
`al., J. Org. Chem. 30, 835 (1965). NMRsoln structure of Ara-C
`within a DNA dodecamer: B. I. Schweitzeret al., Biochemistry 33,
`11460 (1994). Crystal structure of complex with human topoiso-
`merase I: J. E. Chrencik et al., J. Biol. Chem. 278, 12461 (2003).
`Clinical pharmacology and toxicology: R. C. Donehoweret al.,
`Cancer Treat. Rep. 70, 1059 (1986). Symposium onclinical phar-
`macology, pharmacokinetics and efficacy in leukemia: Scand. J,
`Haematol. 36, Suppl. 44, 1-74 (1986). Review of developmentof a
`high dose treatment for acute myeloid leukemia: R. L. Capizzi,
`Invest. New Drugs 14, 249-256 (1996); of cellular metabolism and
`mechanism of action: S. Grant, Adv. Cancer Res. 72, 197-233
`(1998).
`
`NH2
`
`HO
`
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