,
`
`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 & Co., INC.
`Whitehouse Station, NJ, USA
`
`2006
`
`Eton Ex.1119
`1of4
`
`Eton Ex. 1119
`1 of 4
`
`

`

`Library of Congress Catalog Card Number 89-60001
`ISBN Number 0-911910-00—X
`ISBN Number 978-0-91 1910-00-1
`
`Copyright © 2006 by MERCK & CO., INC., Whitehouse Station, NJ, USA
`All rights reserved. No part of this book or electronic product maybe reproduced or used in any form or by any means.
`electronic or mechanical, including photocopying, or by any information storage and retrieval system, Without penmssmn
`in writing from the Publisher. Inquiries should be addressed to The Merck Index Editorial Offices, PO. Box 2000, Merck
`& Co., Inc, Rahway, NJ 07065.
`'
`
`Printed in the USA
`
`Eton Ex.1119
`20f4
`
`Eton Ex. 1119
`2 of 4
`
`

`

`Cystine
`
`2782
`
`[99194044] Stefin l3; CPI-B; NCPI; neutral cys-
`'scmhibitor. Broadly distributed in human cells and
`0513"".
`he woman. 1 cytOSOHC inhibitor to protect against leakage of
`Issues;
`ener-l mes_ Mutations in the cystatin B gene have been
`35050 :31Svalgprogfes“ve,my°ClO.nus epilepsy. 150111 from human
`associate 1 Jan/men, A. Rmne. Btochmz. Biophys. Acid 708, 210
`s
`; 1V. human liver: G. D. J. Green et al., Biochem. J. 218,
`“982 ; from eview of role in Unven’ichtoLundborg disease: A.-E.
`939098 )-E 130 J. 22, 3473-3478 (2003). Mature human form is
`n-glycosylated peptide‘containing 98 amino acid
`wt 11.2 kDa. lsoelectric po1nt: 5.6~6.3.
`.
`[91448-99-6] Post-y—globulin; 7_CSF; y—trace.
`_
`residueS'
`'
`a . uitOUSly in vertebrates; major extracellular cysteine pep-
`Found.Ubl"i,itor in mammals. Isoln from human CSF: J. Clausen,
`.
`Exp- Biol- Med. 107, 170 (1961); from urine of patients
`al dysfunction: E. A. Butler, F. V. Flynn,J. Clin. Pathol. 14,
`'
`mthren61)
`Identification as a cystatin: A. J. Barrett et 12].. Bio-
`172(I%,0 'hys‘ Res. Commun. 120, 631 (1984). Review of bio-
`chem;
`' 5nd clinical role: M. Mussap, M. Plebani, Crit. Rev. Clin.
`chemtslf)’41 467-550 (2004); of efficacy as biomarker for glomer-
`Lab. 561- “0:1 rate: G. Filler et al., Clin. Biochem. 38, 1-8 (2005).
`ula'r'fihlrzvaluation to predict risk of cardiovascular events in elderly
`“‘1‘”; M, G. Shlipak et al., N. Engl. J. Med. 352, 2049 (2005).
`113:“; human form is a. single chain, non-glycosylated peptide
`mining 120 amino acld res1dues; mol wt 13.3 kDa. Isoelectric
`c221"? 9'3_ Electrophoretic mobility: y, (agarose gel electropho—
`Eesis at pH 8.6). E135“ 9.1 (280 nm). Conc in plasma of healthy
`adults: 0.8 to 1.2 mgfl.
`.
`.
`.
`'
`THERAP CAT: Cystatin C as dlagnostic 31d (renal function).
`
`[60-23-1] 2-Aminoethanethiol; mer-
`2779. Cysteamine.
`captamine; B-mercaptoethylamme; 2-am1noethyl mercaptan; thio-
`ethanolamine; decarboxycystetne; MEA; mercamtne; L—1573; Be—
`caplan: Lambratene (formerly). C2H7NS; mol wt 77.15. C
`31.14%. H 9.15%, N 18.16%, S 41.56%. HSCHZCHZNHZ. A
`sulfhydryl compound with a variety of biological effects. Prepn:
`Gabriel, Leupold, Ber. 31, 2837 (1898); Knorr, Rossler, ibid. 36,
`1281 (1903); Mills, Jr., Bogart, J. Am. Chem. Soc. 62, 1173 (1940);
`Weaker, ibid. 57, 2328 (1935); D. A. Shirley, Preparation of 0r-
`ganic Intermediates (Wiley, New York, 1951) p 189. Use in treat-
`ment of paracetamol (acetaminophen) poisoning: L. F. Prescott et
`al.,LattCet 2, 109 (1976); A. L. Harris, Br. Med. J. 284, 825 (1982).
`Effects in nephropathic cystinosis: M. Yudkoff et 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 shown to be a duodenal ulcerogen in rats: H.
`Selye, S. Szabo, Nature 244, 458 (1973); S. Szabo, Am. J. Pathol.
`93, 273 (1978); P. Kirkegaard et (1]., 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. Sagar ct al., J.
`Neurosci. 2, 225 (1982). In pituitary tissue, cysteamine is a potent
`depletor of prolactin concentrations in vivo and in vitro: W. J.
`Millard et al., Science 217, 452 (1982). Toxicity studies: E. Bec—
`cari et (11., Arzneim.-Forsch. 5, 421 (1955); D. L. Klayman et al., J.
`5335Chem. 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. LD50 in mice (mg/kg)! 625 orally; 250
`l'p‘ (Klayman); (Srivastava, Field).
`70117§drochtoride C2H7NS.HC1. Crystals from ale, mp 70.2—
`1495. So] in water, alcohol. LD50 (cg/kg): 23.19 i.p. in rats;
`-
`t.v. tn rabbits (Beccari).
`ac
`35E: Experimentally as a radioprotective agent and to produce
`e and chronic duodenal ulcers in rats.
`THERAP CAT: Antidote to acetaminophen.
`11.531120.
`.Cys‘telcflcid. [13100-82-8] 3-Su1foalanine; a—amino—
`4.17% 913321011? aetd. C3H7NOSS; mol wt 169.16. C 21.30%, H
`50311;“ ”.3809 47.29%, 5 18.96%. H00CCH(NH,)CH,-
`gamma: Li: fen isolated from human hair oxidized With perman-
`mally in “1:121:12. Physioi. Chem. 173, 309 (1928). Occurs nor-
`CXpoSedt
`1‘ out” part of the sheep’s fleece, where the wool 15
`0 13111 and weather: Mania, Synge, Adv. Protein Chem. 2,
`
`3 (1945). Prepd from cystine or cysteine by oxidation with bromine
`in water: Frtedmann, Beitr. Chem. Plzysiol. Pathol. 3, 25. 38;
`Gunner. Hoffman, J. Biol. Chem. 72, 435 (1927).
`L-Form, Octahedra or needles from dil alc (also forms a mono-
`hydrate, prismatic needles). When anhydr, (lee 260°.
`[01%’ +8.66°
`(1.85 g in 25 m1). pKal (25°): 1.89; pKa2 11.7:pr about 12.7.
`Soluble tn water. Insol in alcohol.
`DL-Form. Crystals, dec 245°.
`
`[52-90-41 L-Cysteine; Cys; C; B-mercapto—
`2781. Cysteine.
`alanine; (R)-2—amino-3-mercaptopropanoic acid; 2-amino-3-mer-
`captopropionic acid; a-amino-B-thiolpropionic acid; half-cystine;
`thioserine. C3H7NOZS; mol wt 121.16. C 29.74%, H 5.82%, N
`11.56%, 0 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 Cys are linked via a disulfide
`bridge, a common structural 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. 18794928, passim.
`Simple synthesis of racemic cysteine: V. J. Martens et (11., Angew.
`Chem. Int. Ed. 20, 668 (1981). Determn in proteins: J. G. Hoo-
`gerheide, C. M. Campbell, Anal. Biochem. 201, 146 (1992); D.
`Atherton er al., ibid. 212, 98 (1993). Review of biosynthesis: N.
`M. Kredich et (11., Ciba Found. Symp. (Netherlands) 72, 87-99
`(1980). Review of transport in mammalian cells: 5. Bannai, Bia-
`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.
`Ralph at al., J. Electroanal. Chem. 375, 1-15 (1994); of electrosyn-
`thesis: cidem, ibid. 17—27. Review of role in chemo- and radio-
`protectant strategies: J. C. Roberts, Amino Acids 8, 113-124 (1995).
`0
`
`HS
`
`OH
`
`NHg
`
`[01]?)5 +6.5° (5N HCl); [01]?)5 +13.0° (glacial acetic acid).
`Crystals.
`pKl 1.71; pK2 8.33; ng 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
`neutral or slightly alkaline aq solns it is oxidized to cystine by air.
`More stable in acidic solns.
`Hydrochloride.
`[52-89—11 C3H7N02S.HC1. Crystals. dee
`175—178°.
`[ed/i")S +5.0° (5N HCI); [01]?)5 +10.0° (glacial acetic
`acid). Sol in water, alcohol, acetone; the aq soln is acid. Keep
`tightly closed. Decomposes and oxidizes slowly; hygroscopic.
`USE: As dough conditioner.
`THERAP CAT (VET): Has been used as a detoxicant.
`
`[56-89—3] L-Cystine; [R—(R*.R*)]-3,3’-di-
`2782. Cystine.
`thiobis[2-aminopropanoic acid]; dicysteine; B,B’-dithiodialanine;
`a-diamino-B-dithiolactic acid; [3,3’-diamino-B,B'~dicarboxydiethyl
`disulfide; bis(B-amino-[B-carboxyethyl) disulfide; Gelucystine. C6-
`H12N204SZ; mol wt 240.30. C 29.99%, H 5.03%, N 11.66%, 0
`26.63%, S 26.69%. Non-essential amino acid for human develop-
`ment. Formed by 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. Morner, 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 et al.. J. Mol. Evol.
`10, 155 (1977). Review of lysosomal transport including patho-
`physiology: W. Gahl in Pathophysiol. Lysasomal Transp., J. G.
`Thoene, Ed. (CRC Press, Boca Raton, FL, 1992) pp 45-71. Revtew
`of thermodynamics and kinetics: T. R. Ralph et al., J. Electroanal.
`Chem. 375, 1-15 (1994); of electrosynthesis: eidem, ibid. 17-27.
`
`Consult the Name Index before using this section.
`
`Page 467
`
`Eton Ex.1119
`3of4
`
`Eton Ex. 1119
`3 of 4
`
`

`

`2783
`
`NH;
`
`0
`
`L,cystine S,
`
`HOWS\s/YLOH
`
`NH;
`
`O
`
`20
`o
`. a]
`Hexagonal tablets from water. dec 260-261 (51331113: [811761)33353
`—223.4° (1.th HCl). pK, 1; pK2 2.1: ng 8.02. P 745- 0 523; at
`Soly in water (g/l) at 25°: 0.112; at 50°: 0.239;:t
`e 118.501)’
`100°: 1.142. Quite sol in no solns below pH 2 or at
`.0V IP Absorp-
`curves: Sano. Biochem. Z. 168, 14 (1926).
`lnsol In a CChim. Fr.
`lion spectrum: Marchlewski, Nowolonowna, Bull. SOC-
`l
`[4139 163. 166(1926).
`0
`D-Fhrm.
`[349-46-2] Crystals.
`[011,230 +223 (LON BC” 5° y
`in water at 25°: 0.057 g/l.
`.
`m
`7
`Dl.-Form.
`[923-32-0] Crystals. Soly ln water at 25 . 0-05
`g/l-
`.
`.
`mesa-Form. [6020-39-9] Crystals. Solyln water. 0.056 15/!-
`2783. L-Cystine S,S-Dioxide.
`[30452-69-8] 2-Ammgife
`carboxyethyl 2-amino-2-carboxyethanethiosulfonate: 14-91;; 30
`thiosulfonale; sacysyl-cysteinc. CGHUNzOhSz: mol W12.
`1
`'
`C 26.47%. H 4.44%, N 10.29%. 0 35.25%. S 23.5%. Odeatloln
`product of cystine. Prepn: G. Toennies. T. F. Lavmc, J. Bu? -
`Chem. 113, 571 (1936); R. Emilozzi, L. Pichat. Bull. Soc. Chlm.
`Fr. 1959, 1887. Orignally thought to be a mixture oftwo lsomers.
`cystine S.S-dioxide and cystine S,S’-dioxide: G. E. Utzlnger, Ex-
`perientia 17, 374 (1961). Elucidaton of structures: G. Axelson 81‘
`al., Spectrochim. Acm 23A, 2015 (1967); L. D. Setlawan €10!ququ
`Interface Anal. 7, 188 (1985). Use in determn ofsulfite: T. Ubuka
`at al., Anal. Biochem. 126, 273 (I982): idem er al., ibid. 140, 449
`(1984).
`
`NH2 0 0
`\V/
`
`H0
`
`0
`
`5W \S/YILOH
`
`NH2
`
`Solid, relatively unstable in aqueous solns; disproportionates to
`cystine and cysteine sulfinic acid.
`USE: In detection of sulfites and thiosulfate.
`
`[147-94—4] 4-Amino-l-B-D—arabinofura-
`2784. Cytarabine.
`nosyl-2(1H)-pyrimidinone; l—B—D—arabinofuranosylcytosine; Ara-C;
`B-cytosine arabinoside; aracytidine; CHX-3311; U-19920; Alexan;
`Aracytine; Cytosar; Depocyte; Udicil. C9H13N3 05; mol wt 243.22.
`C 44.44%, H 5.39%, N 17.28%, 0 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). NMR soln structure of Ara-C
`within a DNA dodecamer: B. I. Schweitzer et al., Biochemistry 33,
`11460 (1994). Crystal structure of complex with human topoiso-
`merase I: I. E. Chrencik et al., J. Biol. Chem. 278, 12461 (2003).
`Clinical pharmacology and toxicology: R. C. Donehower et al.,
`Cancer Treat. Rep. 70, 1059 (1986). Symposium on clinical phar-
`macology, pharmacokinetics and efficacy in leukemia: Scand. J.
`Haematol. 36, Suppl. 44, 1-74 (1986). Review of development of 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
`
`H0
`
`Page 468
`
`lalé“ +153. (9 ‘
`, mp 212—2l3°.
`281.0, 212.5 nm (s 1317]_ 102303-1153”
`.
`”“0
`
`(s 925?).
`
`[115—93—5] Phosphorothioic Bold
`e.
`1] 0,0-dimethyl ester: phosphormhiOIOM
`ester with P'lhfidro’r‘lybenzenesmfengnitcid
`lpheny p osp Orolhiome. C
`lde,
`1 0_p-sulfam0y
`.
`I
`[”26
`.
`43?]Proban. CsHIZNO5PSZ’ mol Wt 297'29- C 32 691‘
`'
`32%.
`.4
`O 26.91%, P 10.42%. S 21.57%, prep": Q
`ENT-256
`005004 and R. I. PleWitt, G. Berkelham
`Berkelhammefl Ulsggs to Am. Cyanamld). PhaMacOdynanzlfel-Jls
`1c:
`61
`3179560 (19 L. Goulding’ J, Econ. Entomol. 63, 1640 Is H,
`5
`G. Smlth. R.
`Wide; c. P. Doval, 1. Cum, “$0,533,111,
`Efficacy 35 ”mp“
`N I. Caldwell, Vet. Med s
`. _M,Bowen,
`-
`. ma”
`55, 390 (1978522). Toxicity data: E. E. Kenaga, W, E.
`A
`Him:
`'
`. 77, 79 (1
`Alumni
`$111,111. Entomol. Soc. Am. 15, 85 (1969).
`
`H co
`1130150 /0
`(11:11
`
`\\//
`
`Crystals, mp 70-71°.
`mg/kg (Kenaga. Allison).
`.. -
`USE: Insecticide.
`THERAP CAT (VET): Ectoparasmclde.
`
`"2135 1-5346' LD50 orally in rats; 160
`
`[65-46-3] 4-Amino—1-_,8-D-ribofuranosy1.2.
`2786. Cytidine.
`(1H)-pyrimidinone; cytosine ribostde; l~3-D‘rlbofuranosylcytosine,
`C9H13N305; mol wt 243.22. C 44.44%, H 5.39%, N 17.28%,0
`32.89%. Constituent of nucleic aClds. Isoln from yeast nucleic
`acid: Levene, Jacobs, Ber. 43, 3154 (1910); Levene, La Forge, ibid.
`45, 608 (1912). Sepn from other nucleosides by ion-exchange
`chromatography: Cohn in Chargaff—Davidson, The Nucleic Acid,
`vol. I (New York, 1955) p 211. Synthesis: Howard et al.,J. Chem,
`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 York,
`1974) passim.
`
`NH2
`
`HO
`
`OH
`
`Long needles from 90% ethanol, dec 220-230o_ [0511235 +319 (c:
`0.7_ in .water). Freely so] in water, less sol in alcohol. pK (amino.
`catlonlc) 4.22; pK (sugar, anionic) 12.5. uv max (pH 8.2): 271m
`(B 9100); (pH 2.2): 280 nm (8 13400), Voet et al., Biopab’m’” ’
`.
`.
`m
`Sulfate.
`(C
`224.225c (dec 9H13N305)2-H2304. Long prlsmatlc needl€5>
`with effervescence). [a] $9 +34°; [“1336 +430'
`phi-(37}. Zi-Cytidylic Acid.
`[85-94-9] Cytidine-2'-m°"?p:::
`’ cl] ldy11° acld a; 2’—Cytidinephosphoric acid; CytidmC-z pO C
`33 457 -cytosyllc acid; 2’-CMP. c,1—1,.,N.OSP;r1101W‘3Z3‘2 'ase
`0
`. N 13.00%, 0 39.60%, P 9.58%. Rim“Cle
`_
`-_
`
`P
`
`Rammlgrfkghosphorylation of N".03’.05 '-triben20)’lcyélrvslal
`0111113,], Am Ch
`S
`1962).
`.‘
`Stru
`-
`em. 0c. 84 3112(
`”a!
`179C219: alnd conformation 0f the trihydrate: Kartha ct alas”
`’
`( 973). Reviews: See Cytidine.
`‘
`
`.
`
`V
`
`.
`
`I
`
`Av(Sa:we“--a:.Q
`
`‘11
`
`
`
`nnnxaaO'a’fi'i‘i.‘
`
`9‘9
`
`'1':-
`0)
`
`1:2-.aL":-«..71r.
`
`Consult the Name Index before using thin --
`
`Eton Ex.1119>
`4of4
`
`Eton Ex. 1119
`4 of 4
`
`