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
`
`Pharmacosmos, Exh. 1044, p. 1
`
`

`
`Library of Congress Catalog Card Number 89-6000 l
`ISBN Number 0-911910-00-X
`ISBN Number 978-0-911910-00-l
`
`Copyright © 2006 by MERCK & CO., INC., Whitehouse Station, NJ, USA
`
`All rights reserved. No part of this book or electronic product may be reproduced or used in any form or by any means,
`electronic or mechanical, including photocopying, or by any information storage and retrieval 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
`
`Pharmacosmos, Exh. 1044, p. 2
`
`

`
`Dextranase
`
`2949
`
`2945. Dexetimide. [21888-98-2] (3S)-3-Phenyl-l '-(phenyl(cid:173)
`inethyl)-(3,4' -bipiperidine ]-2,6-dione; (S)-( + )-2-( l -benzyl-4-piperi(cid:173)
`clyl)-2-phenylglutarimide; ( + )-3-( l-benzyl:4-piperidyl)-3-phenyl(cid:173)
`piPeridine-2,6-dione; ( + )- l -benzyl-4-(2 ,6-d1oxo~3-phenyl-3-p1pen­
`.,1)piperidine; dextrobenzet1m1de; dexbenzetumde. C23 H26N2 02;
`JDOI wt 362.46. C 76.2 1%, H 7 .23%, N 7.73%, C! 8.83%'. The
`41exuoenantiomer responsible for the pharmacological act1v1ty. of
`nicemic benzetimide, q.v. Resolution of isomers and comparative
`fiiamtacology : Janssen et.al., Arzneim.-Forsch. 2.1, 1365 (1971) .
`Abs config studies: van W11ngaarden et al., Life Sci. 9, part I, 1289
`(1970); Spek et al., Nature 232, 575 ( 1971 ). Clinical tria ls: De
`$medt et al., J . Clin. Pharmacol. 10, 207 ( 1970).
`
`0
`
`H
`N
`
`Crystals, mp 181-183°. [a) ~ +125° (chloroform).
`Hyd rochloride. [21888-96-0) R- 16470; Trembl ex. C23 H26 ·
`20 2.HCI; mol wt 398.93. Crystals, mp 270-275°. [a] ~ +125°
`thanol). LD50 i.v. in rats: 45 mg/kg (Janssen).
`TI-IERAP CAT: Antiparkinsonian.
`
`2946. Dexmedetomidine. [ 11 3775-47-6) 4-[(IS)- 1-(2,3-Di(cid:173)
`thylphenyl)ethyl]-1 H-imidazole; d-medetomidine; MPV- 1440.
`13 H 16 N2; mol wt 200.28 . C 77.96%, H 8.05%, N 13 .99%. "r
`nergic agonist; (+)-isomer ofmedetomidine, q.v. Prepn: A. J.
`jalainen et al., GB 2206880; eidem , US 4910214 (1989, 1990
`th to Farmos). Physical properti es: R . Raj ala et al., Eur. J .
`'harm. Sci. 1, 219 (1994). Clinical pharmacokinetics : P . Talke
`al, Anesth. Analg. 85, 1136 (1997). Clinical evaluation as anes(cid:173)
`tic adjunct: J . Jalonen et al., Anesthesiology 86, 331 (1997).
`eview of pharmacology and clinical experience for sedation of
`tients in inten sive care: N. Bhana et al., Drugs 59, 263-270
`).
`
`CH3 CH3
`
`u lN H
`H3C~N)
`
`Hyd rochloride. [145108-58-3) Precedex . C 13 H 16 CN2.HCI;
`ol wt 248.75. White or almost white crysta lline powder, mp
`156.5-157.5°. d 1.17 g/cm 3
`. [a] +52.4° (c =I in water). pH of
`% soln in water: 4.3.
`THERAP CAT: Sedative; analgesic.
`
`2947. Dexpanthenol. [81-13-0) 2 ,4-Dihydroxy-N-(3-hy-
`4roxypropyl)-3,3-dimethylbutanamide; D( +)-a, y-dihydroxy-N-(3-
`hydroxypropyl)-/3./3-dimethylbutyramide; pantothe nylol; N-pan(cid:173)
`toyl-3-propanolamine; pantothenol; pantothenyl alcohol ; Alcopan-
`2SO; Intrapan; Pantenyl ; Pa nthoderm ; Motilyn; Bepanthen; Co(cid:173)
`lyme; Ilopan; Urupan . C9H 19 N04 ; mol wt 205.25. C 52.67%,
`119.33%, N 6.82%, O 31.18%. Prepd by the addition of propanol(cid:173)
`llmine to optically active a,y-dihydroxy-/3,/3-dimethylbutyrolactone:
`Schnider, Jubilee Vol. Emil Barell 1946, 85; CH 227706 (1943); GB
`582156 (1946); US 2413077 ( 1946 to Hoffmann-La Roche). Only
`1he D(+)-form has vitamin activity.
`
`CH20H
`I
`CH2
`I
`CH2
`I
`NH
`I
`c=o
`I
`CH-OH
`I
`H3C-C-CH3
`I
`CH20H
`
`Vi scous, somewhat ~opic liq. Slightly bitter taste. d~g
`1.2. bp0_02 118-1 20°. Easily dee on distn. [aJ b0 +29.5° (c = 5).
`n~ 1.497. Freely sol in water, alcohol, meth anol. Slightly sol in
`ether. Natural pH about 9.5. Reasonably stable to usual steriliza(cid:173)
`tion time and temp in aq solns adjusted to pH 3.0-4.0, but long
`heating causes racemization. Hydrolyzed by alkali and strong acid.
`Usually more stable than salts of pantothenic acid if pH can be
`adjusted between 3 and 5. For add '! stability data see Rubin, J. Am.
`Pharm . Assoc. Sci. Ed. 37, 502 ( 1948). Aq solns can be stabilized
`with pantolactone: US 2898373 (1959).
`di-Form. Panthenol.
`THERAPCAT: Cholinergic; di-form as vitamin.
`THERAP CAT (VET) : Nutritional factor. Dietary source of panto(cid:173)
`thenic acid.
`
`2948. Dextran. (9004-54-0] Gentran; Hemodex; lntradex;
`Promit. A term applied to polysaccharides produced by bacteria
`growing on a sucrose substrate, contg a backbone of D-glucose units
`linked predominantly a-D(l -+ 6). Several organisms produce dex(cid:173)
`trans but only Leuconostoc mesenteroides and L. dextranicum (Lac(cid:173)
`tobacteriaceae) have been used commercially. Chemical and phys(cid:173)
`ical properties of the dextrans vary with the methods of production.
`Native dextrans usually have high mol wt; lower mol wt clinical
`dextrans usually prepared by depolymerization of native dextrans or
`by synthesis. All dextrans are composed exclusively of a-D-gluco(cid:173)
`pyranosyl units , differing only in degree of branching and chain
`length . Prepn: Tarr, Hibbert, Can. J . Res. 5, 414 (1931); Novak,
`Stoycos, US 2841578 (1958 to Commonwealth Eng. of Ohio).
`Enzymic sy nthesis: Su gg, Heh re , J . lmmunol. 43, 119 ( 1942);
`Behrens, Ringpfeil, US 3044940 ( 1962 to Serum Werk Bemburg).
`The crude dextran may be isolated from the culture by precipitation
`with methanol. Continuous dialysis process: Shurter, US 2717853
`( 1955 to C.S.C.). Elimination of pyrogens: Levi, Lozinski, US
`2762727 (1956 to Fross!). Method of producing clinical dextran:
`Novak, Witt, US 2972567 (1961 ). Structure studies: Fowler et al.,
`Can. J . Res. Bl5, 486 (1937); Fairhead et al., ibid. B16, 151 ( 1938);
`Peat et al., J. Chem. Soc. 1939, 581 ; Goldstein, Whelan, ibid. 1962,
`170, 176. 13C-NMR structure study: F. R. Seymour et al., Carbo(cid:173)
`hydr. Res. 51, 179 (1976). Reviews: Evans, Hibbert, Adv. Carbo(cid:173)
`hydr. Chem. 2, 204 (1946); Neely, ibid. 15, 341 (1960); Ricketts,
`Prog. Org. Chem . 5, 73 ( 1961 ); Murphy, Whistler, in Industrial
`Gums, R. L. Whistler, Ed. (Academic Press, New York, 2nd ed.,
`1973) pp 513-542.
`Dextran 40. LMD; LMWD; L VD; Gentran 40; Rheomacrodex.
`Produced by action of L. mesenteroides on sucrose; average mo! wt:
`40,000.
`Dextran 70. Gentran 70; Hyskon; Macrodex. Average mol wt:
`70,000.
`USE: In soft center confections, as a partial substitute for barley
`malt. Mixed ethers and esters of dextran can be used in lacquers.
`THERAPCAT: Plasma volume expander; Dextran 40 also as blood
`How adjuvant.
`THERAP CAT (VET): Plasma extender.
`
`2949. Dextranase. (9025-70-1) a- 1,6-Glucan 6-glucanohy(cid:173)
`drolase; EC 3.2.1.11. Enzyme which hydrolyzes the a-I -+ 6 glu(cid:173)
`cos idic linkages of the bacterial polysaccharide dextran. Endodex(cid:173)
`tranases (dextranases which preferentially split glucosidic linkages
`remote from end groups) are secreted by various molds and a few
`bacteria. Exodextranases occur predominantly in mammalian tis(cid:173)
`sues. Prepn: from Penicillium lilacinum, P.funiculosum , and Ver(cid:173)
`ticillium coccorum , Nordstrom, Hultin, Sven. Kem. Tidskr. 60, 283
`( 1948), C.A. 43, 3050i (1949); from Aspergillus, Carlson, Carlson,
`Science 115, 43 (1952) , eidem, VS 2709150 (1955 to Enzymatic
`Chemicals), eidem, US 2716084, and Novak, Stoycos, US 2841578
`(1955 and 1958 both to Commonwea lth Eng. of Ohio); from P .
`lilacinum , P.funiculosum, P. verruculosum, and Spicaria violacea,
`Tsuchiya et al., VS 2742399 and Corman, Tsuchiya, US 2776925
`( 1956 and 1957 both to U.S . Secy. Agr.); from P. lilacinum,Charles,
`Farrell, Can. J. Microbial. 3, 239 ( 1957); from Lactobaci/lus bifidus,
`Bailey, Clarke, Biochem. J . 72, 49 (1959). Tested as dental caries(cid:173)
`control agent in hamsters: Fitzgerald et al., J. Am. Dent. Assoc. 76,
`301 (I 968). Review: E. H . Fischer, E. A. Stein, "Cleavage of 0-
`and S-Glycosidic Bonds (Survey)" in The Enzymes vol. 4, P. D.
`
`Consult the Name Index before using this section.
`
`Page 501
`
`Pharmacosmos, Exh. 1044, p. 3
`
`

`
`2950
`
`Dextranomer
`
`Boyer er al., Eds. (Academic Press, New York, 2nd ed., 1960) pp
`304-307.
`USE: In prepn of dextran for clinical use; in dentifrices.
`
`2950. Dextranomer. [56087-11-7] Dextran 2,3-dihydroxy(cid:173)
`propyl 2-hydroxy- I ,3-propanediyl ethers; Debrisan; Debrisorb.
`Three-dimensional hydrophilic network of a dextran polymer,
`Jinked by cross-chains of epichlorohydrin, q.v.; it absorbs moisture
`and small molecules from suppurating wounds. Chronic tissue
`response to implantation : J . Falk, G. Tollerz, Clin. Ther. 1(3) ,
`185 (I 977). Potential a)lergic contact sensitization in gu inea pigs:
`G. Jonsson, ibid. 1(4), 260 (1978). Efficacy in treatment of ulcers
`and wounds: J. Soul, Br. J. Clin . Pract . 32, 172 (1978); P. N.
`Sawyer et al. , Surgery 85, 201 (1979); S. Di Mascio, Am. J. Nurs.
`79, 684 (1979) . Review: R. C . Heel et al., Drugs 18, 89-102
`(1979).
`
`Insol in all solvents; stable in water, salt solns and in alkaline and
`weakly acidic soln.
`TH.ERAPCAT: Vulnerary.
`
`2951. Dextran Sulfate Sodium, [9011-18-1] Dextran sul(cid:173)
`furic acid ester sodium salt; Asuro; Colyonal; Dexulate; Dextrarine;
`MDS. Heparin-like polysaccharide containing approx. 17% S with
`up to three sulfate groups per glucose molecule. Mol wt ranges
`from 4 ,000-500,000 Da; variations in mol wt are associated with
`differences in biological activity. Prepn, properties and anticoagu(cid:173)
`lant activity: A. Gronwall et al. , Upsala Laekarefoeren. Foerh. 50,
`397 (1945); C. R. Ricketts, Biochem. J. 51, 129 (1952). Evaluation
`, of toxicity as a function of mol wt: K. W . Walton, Br. J. Pharmacol.
`9, l ( 1954); of carcinogenicity: I. Hirono et al., Cancer Lett. 18, 29
`( 1983). Use in serum HDL cholesterol determn: P. R. Finley et al.,
`Clin . Chem. 24, 931 (1978); G. R. Warnick et al., ibid. 28, 1379
`(1982). Antiscrapie effect: B. Ehlers, H. Diringer, J. Gen. Virol .
`65, 1325 (1984); R.H. Kimberlin, C. A. Walker,Antimicrob.Agents
`Chemother. 30, 409 (1986). Anti-HIV-1 activity in vitro: H. Mit(cid:173)
`suya et al., Science 240, 646 (I 988); M. Baba et al., Proc. Natl.
`Acad. Sci. USA 85, 6132 (1988).
`White powder from alcohol +ether. Freely sol in water. Activity
`about 17 international heparin units/mg. Aq solns must be buffered
`(e.g., with sodium bicarbonate) to prevent dee during autoclaving.
`USE: Clinical reagent (HDL cholesterol determn).
`THERAPCAT: Anticoagulant.
`
`2952. Dextri-Maltose®. [8006-91-5] Maltose and dextrins
`obtained by enzymic action of barley malt on corn Hour.
`Light, amorphous powder. Readily sol in water or milk. One
`leveled tablespoonful (8 grams) supplies 27 calories.
`USE: As carbohydrate modifier for use with milk and milk
`products in infants ' formu las.
`
`2953. Dextrin. [9004-53-9] Pyrodextrin; torrefaction dex(cid:173)
`trin. (C6 HIOO,),..xH2 0. Produced by the dry heating of unmodi(cid:173)
`fied starches. The term also includes products resulting from en(cid:173)
`zyme or acid-catalyzed hydrolysis of wet starch. Review: R . W .
`Satterthwaite, D. J. Iwinski, in Industrial Gums, R. L. Whistler, Ed.
`(Academic Press, New York, 2nd ed. , 1973) pp 577-599.
`British gum. Starch gum. Produced at high temp in the absence
`of acid. Dark brown color, odorous. High viscosity; very sol in
`
`cold water. Does not reduce Fehling ' s soln; gives reddish-brown
`color with iodine.
`Canary dextrin. Yellow dextrin. Hydrolyzed at high temp for
`long period of time in the presence of small amts of acid. Light
`brown to yellow color, slight odor. Low viscosity; very sol in cold
`water.
`White dextrin. Hydrolyzed at low temp for short period of time
`in the presence of large amts of acid. White color, odorless.
`Slightly sol in cold water giving a red color with iodine. Very sol
`in hot water giving a blue color with iodine.
`USE: Excipient for dry extracts and pills; for preparing emulsions
`and dry bandages; for thickening dye pastes and mordants used in
`printing fabrics in fast colors; sizing paper and fabrics; printing
`tapestries; preparing felt; manuf printer's inks , glues and mucilage;
`polishing cereals; in matches, fireworks , and explosives.
`
`2954. Dextroamphetamine. [5 J -64-9] (aS)-a-Methylben(cid:173)
`zeneethanamine; ( + )-a-methylphenethylamine; d-amphetam ine;
`(S)- J-phenyl-2-aminopropane; d-/3-phenylisopropylamine; dexam(cid:173)
`phetamine. C 9 H 13 N ; mol wt 135.21. C 79.95 %, H 9.69%, N
`10.36%. Prepn by resolution of amphetamine: Temmler, GB
`508757 (1939); Nabenhauer, US 2276508 (1942 to SK&F); Magid(cid:173)
`son, Garkusha, J. Gen. Chem. USSR 11, 339 (1941); from D-phenyl(cid:173)
`alanine: D. B. Repke et al., J. Pharm. Sci. 67, 1167 ( 1978).
`Toxicity data: E. J . Warawa et al. , J . Med. Chem. 18, 71 ( 1975).
`GC-MS determn in urine: V. A Tetlow, J. Merrill, Ann. Clin. Bio(cid:173)
`chem. 33, 50 (1996). Review of pharmacology: S. J. Chee, Neuro(cid:173)
`sci. Biobehav. Rev. 16, 481-496 (1992).
`
`~CHs
`~H2
`
`v
`
`Sulfate. [51-63-8] Dexamin; Dexedrine; Dextrostat. White,
`odorless, crystalline powder with bitter taste. mp >300°. [a]g>
`+21.8° (c = 2) . Freely sol in water (about 1:10); slightly sol in
`alcohol (about I :800). Insol in ether. pH 5% aq soln: 5.0 to 6.0.
`LD50 orally in mice: 10 mg/kg (Warawa).
`Tannate. [1407-85-8] Tanphetamin; Synatan. Prepn: Caval(cid:173)
`lito, US 2950309 (1960 to Irwin, Neisler and Co.).
`Note: This is a controlled substance (stimulant): 21 CFR,
`1308.12.
`THERAPCAT: CNS stimulant; anorexic.
`
`2955. Dextromoramide. [357-56-2] J-[(3S)-3-Methyi-4-
`(4-morpholinyl)-l-oxo-2,2-diphenylbuty l]pyrrolid ine; (+)- I -(3-
`methyl-4-morpholino-2,2-diphenylbutyryl)pyrrolidine; 4-[2-meth(cid:173)
`yl-4-oxo-3,3-diphenyl-4-(1-pyrrolidiny l)butyl]morpholine; d-2,2-
`diphenyl-3-methyl-4-morpholinobutyrylpyrrolidine; pyrroJamidol;
`R-875; SKF-5137; d-Moramid(e); Palfium; Palphium; Jetrium; D•(cid:173)
`morlin. C 25 H 32 N 2 0 2 ; mo) wt 392.53. C 76.50 %, H 8.22%, N
`7.14%, 0 8.15%. Synthesis: Janssen, J. Am. Chem. Soc. 78, 3862
`( 1956); GB 822055 (1959 to Janssen).
`
`Crystals, mp 180-184°. [aJb0 +25.5° (c = 5 in benzene). uv maX
`(0.0IN isopropanol-HCI): 254, 260, 264 nm. Practically insol 1~
`water. Soly in O.IN HCl: 1:25 (w/v). Soly (g/100 ml) in ethan~.
`50; in methanol 40; in acetone 50; in ethyl acetate 40; in benzene
`'
`in chloroform 5. Sol in ether.
`Bitartrate. C25 H32 N2 0 2 .C4 H6 0 6• Minute crystals, bitter tas:·
`Dec 189-192°. Soly (w/v) at 25 °: Water 20%, chloroform 30
`'
`methanol 40%, ethanol 100%, acetone 100%.
`1
`Note: This is a controlled substance (opiate): 21 CFR, ! 308. I ·
`THERAPCAT: Analgesic (narcotic).
`2956. Dezocine. [53648-55-8] (SR,\ IS, !3S)-13-Amin°;(~:
`6,7 ,8,9,10,l I , 12-octahydro-5-methyl-5, 11 -methanobenzocY
`
`Page 502
`
`Consult the Name Index before using this section.
`
`Pharmacosmos, Exh. 1044, p. 4