`
`BME EDITION
`
`THE
`
`MERCK INDEX
`
`AN ENCYCLOPEDIA OF
`
`CHEMICALS, DRUGS, AND BIOLOGICALS
`
`ATHIRTEENTH EDITION
`
`Editorial Staff_j
`
`Maryadele J. O’Nei1, Senior Editor
`
`Ann Smith, Senior Associate Editor
`
`Patricia E. Heckelman, Associate Editor
`
`John
`
`Obenchain Jr., ‘Editorial Assistant
`
`Jo Ann R. Gallipeau, Technical Assistant .
`
`Mary Ann D’Arecca, Administrative Associate
`
`Susan Budavari, Editor Emeritus
`
`Published by
`Merck Research Laboratories
`
`Division of
`
`MERCK & CO., INC.
`Whitegouse Station, NJ
`
`2001
`
`|PR2015-01099
`|PR2015-01097
`|PR2015-01100
`|PR2015-01105
`
`Lupin EX1096
`Page 1
`
`
`
`
`
`
`
`C’ MERCVK &‘éo.,"1NC".
`Whitehouse Station, NJ
`
`6 USA
`
`13!: Edition— 1889
`2nd Edition— 1896
`3rd Edition—1907
`4:11 Bdition— 1930
`51:1 Edition— 1940
`6th Edition— 1952
`7th Edition— 1960
`.8th Edition--1968.
`9111 Edition— 1976
`10:11 Edition——— 1983
`11:11 Edition—— 1989
`12th Edition— 1996
`
`'
`
`Libraryof Congress Catalog
`Card”Nurnber 89-60001
`ISBN Number 0911910-13-1
`
`Copyright © 2001 by MERCK & C0,, INC.
`All rights reserved. Copyright under the Universal Copyright Convention
`and the International Copyright Convention.
`Copyright reserved under the Pan-American Copyright Convention.
`Printed in the USA
`
`Page 2
`
`
`
`;fM £¢ Vi §E%/&W97,J2w& %wMemM@wxvmmMmmwaw%3W14»;/;<»a«/8wgs1m2;¢;.ss::y;7wz8>z'¢18>wz;ezgnyzmzze¢<eav;m¢mw48:we2szsm:e,ar;12w,2¢zwmwgnmzenizzrmwxyegmwmzfi/ae;gwm:<%wa2%z~«2ém§~/ezrém/<1/2=rzz4mmmzeezw/rzwgeawmwmzvreirfirfimmizfimyfieswymflvmiw8:%%%$&?A%%§22@%&s¢%w&&?s&£ %§m%a§@W/"‘I
`
`
`
`
`
`Page 2
`
`
`
`
`
`:r, alcohol, ether. LD50 i.p. in femaie
`
`rystals from ethanol-water,.mpv
`
`1 ingestion of C. ruscifolia has been-
`sence of tutln. Symptoms inclu '
`lrlum, convulsions.
`
`;-14-5] Tricyc1o[4.4.0;03'3]dec
`2 88.16%, H 11.84%. Synth
`vc. 84, 3412 (1962); Gautier, De
`45, 297 (1967); Whitlock, Sieflte
`.9 (1968). Absolute configur
`Letters 1968, 5467.
`‘
`~
`
`acid
`Butylcarbamic
`268-36-4]
`hyl]=2—methylpentyl ester; carba.
`-2—methylpentyl ester of butylca:-
`yl-2-propyl-1,3-propanediol dicar-
`lmethylene butylcarbamate carba-
`ltran. C,3H26N,O,,; mol wt 274.36.
`%, O 23.33%. Prepd from 2—meth-
`carbamate + butyl
`isocyanate;
`9 (1960 to Carter Prod.). Compre-
`sberg et al., Anal. Profiles Drug
`r..:»\
`
`I
`J?\
`\O I 3/\/\CH3
`3
`
`roethane + hexane (1I2),,mp' 49-
`
`9,11,~12,13,13a,14’-
`[6879-02-3]
`hoxydibenzo[fih]pyrrolo[l ,2-b-].
`thoxyphenanthro[9,10:6’,7’]indol-
`393.47.. C 73.26%, H 6.92%, N
`lrolndollzidine alkaloid; isomeric
`of I-isomer from Tylaphora cre-
`;/aceae: E. Gellert et al., J. chem.‘
`1 et al., J. Pharm. Sci.‘ 59, 1501
`1: E. Gellert, R. Rudzats, J. Med.
`mer isolated from Ficus septiczz,
`dl—form and structure: E. Gellert
`. Gellert, Austr. J. Chem. 23, 2503
`is: G. R. Donaldson et al., Biochem.
`[04 (1968); E. Battaner, D. Vas-
`254, 316 (1971). Mode of action
`lrollman, Mol. Pharmacol. 8, 538
`.Antibiotics (N.Y.) 6, 47 (1983).
`
`OCH3
`
`I
`
`I
`
`'
`
`OCH3
`
`OCH3
`
`OCH3
`
`Tymazoline
`
`9902
`
`.411-Form. Needles from chloroform + methanol, mp 219-
`21/°.
`.
`1
`/2f[-Form. Crystals from methanol, dec 218—220°. uv max:
`263, 342, 360 nm (log .9 4.81, 3.25, 3.09). [ct]? -45” (c = 0.74
`in chloroform). pKa (50% aq ethanol): 6.7.
`d.-Form. ~Crystals from methanol, mp~~220—222°.
`+20.5°. .
`'
`r
`<
`—
`,,
`.
`
`[ct]]2)2
`.
`
`(13aS)-9,11,l2,13,1'3a,—
`[482-20-2]
`' .9899. Tylophorine.
`14—Hexahyd,ro_-2,3,6,7—tetramethoxydibenzo[fih]pyrrolo[l,-
`2_b]isoqu_inoline; 2,3,6,7-tetramethoxyphenanthro[9,10:6’,7’]-
`indolizidine. C2,,H27NO;; mol wt_ 393.47. C 73.26%, H 6.92%,
`N 3.56%, 016.26%. Major alkaloid from Tylaphora asthma-
`tica Wight et Arn., Asclepiadaceae. Also found in other Ascle-
`piadaceae, Moraeeae, Urticaceae Vand Lauraceae. Naturally
`occurring form originally isolated and reported to be levorota—
`tory; later corrected to dextrorotatory. Isolnz A. N. Ratnagir—
`iswaran, K. Venkatachalam, Indian J. Med. Res. 22, 433 (1935);
`R. N. Chopra et al., Arch. Pharm. 275,236 (1937); T. R. Gov-
`indachaii et al., J. Chem. Soc. 1954, 2801. Structure: eidem,
`Tetrahedron 9, 53 (1960). Absolute configuration: eidem, J.
`Chem. Soc. Perkin Trans. I 1974, 1161. Synthesis of the :11-
`form: eidem, Chem. & Ind. (London) 1960, 664; N. A. Khatri
`et'al., J. Am. Chem. Soc. 1103,6387 (1981). Synthesis and ver-
`ification of dextrorotation of naturally occuning form: T. F.
`Buckley 3rd, H. Rapoport, J. Org. Chem. 48, 4222 (1983); J. E.
`Nordlander, F. G. Njoroge, ibid. 52, 1627 (1987). Stereoselec-
`tivc synthesis of l-form: M. Ihara et al., Tetrahedron Letters
`29,4135 (1988). Biosynthesis: Mulchandani et al., Phytochem-
`istry 8, 1931 (1969); ibid 10, 1047 (1971); D. S. Bhakuni, V.
`K. Mangla, Tetrahedron 37, 401 (1981). Pharmacology: C. Go-
`palakrishnan et al., Indian]. Med. Res. 69, 513 (1979); 71, 940
`(1980).
`
`
`
`OCH3
`
`Crystals, dec 282—284°. [tug +15° (c = 0.7 in chloroform);
`[a]%,1 +73° (c = 0.7 in chloroform). uv max in ethanol: 257,
`286, 339, 356 nm (log a 4.7, 4.42, 3.28, 3.19). Unstable in
`solutions, decompositionwith yellowing sets in promptly ac-
`companied by decreasing rotatory strength. ,
`1
`-
`~
`l-Form. Colorless crystals, dec 286—287°.
`[ac]%7 —11.6° (c
`= 1.07 in chloroform); uv max 255, 290, 340, 352 nm (log 5
`4.74, 4.49, 3.30, 2.93). Sol in chlorofoirn; slightly sol in abs
`alc, ether, cold benzene. Practically insolin water.
`dl-Form. Crystals from chloroform + ethanol, mp 292°. .
`
`. Tylosin; [l401—69—0] Tylan. C451-177N017; mol wt
`9900..
`I
`916.10. C 60.31%, H 8.47%, Nv1.53%, O 29.69%. Macrolide
`antibiotic isolated from a strain of Streptomycetesfradiae found
`in soil from Thailand: Hamill et al., Antibiot. & Chemother. 11,
`328 (1961); eidem, US 3178341/(1965 to Lilly). Prodn in batch
`and chemostat cultures: P. P. Gray, S. Bhuwapathanapun, Bio-
`tech. Bioeng. 22, 1785 (1980). Partial structure: Morin, Gor-
`man, Tetrahedron Letters 1964, 2339. Structure: Morin et al.,
`ibid. 1970, 4737; Achenbach et al., Ber. 108, 2481 (1975). Con-
`figurational study: S. Omura et al., Tetrahedron Letters 1977,
`1045. Abs config: eidem, J. Antibiot. 33, 915 (1980); N. D.
`Jones et al.,
`ibid. 35, 420 (1982). Synthesis-of tylonolide, the
`aglycone: S. Masamune et al., J. Am. Chem. Soc. 98, 7874
`(1976); K. Tatsuta et al., Tetrahedron Letters 22, 3997 (1981).
`Relationship of ribosomal binding and antibacterial properties:
`J. W. Corcoran et al., J. Antibiot. 30, 1012 (1977). Biosynthesis
`
`studies: E. T. Seno et al., Antimicrob. Ag. Chemother. 11, 455
`(1977); S. Omura et al., J. Antibiot. 31, 254 (1978).
`
`
`
`[o.]g5 -—46° (c = 2 in
`Crystals from water, mp 128-132°.
`methanol). uv max: 282 nm (E{Z;,, 245). Soly in water at 25°:
`5_mg/ml. Sol in lower alcohols, esters and ketones, in chlori-
`nated hydrocarbons, benzene, ether. Solns are stable at pH 4-
`9; at pH <4 another active compd, desmycosin is formed.
`Hydl-o'chloride.' C46H77NO,7.HCl. Crystals from ethanol +
`ether, mp 141-145°.
`THERAP CAT (VET): Antibacterial.
`
`[25301-O2-4] 4—(1,1,3,3-Tetramethy1-
`-.9901. Tyloxapol.
`buty1)phenol polymer with formaldehyde and oxirane; oxyethyl-
`ated tertiary octylphenol formaldehyde polymer; p-isooctyl-
`polyoxyethylenephenol formaldehyde polymer; tyloxypal; Al-
`evaire; Superinone; Triton A-20; Triton WR—1339. Nonionic
`detergent with surface—tension—reducing properties. Prepn:
`Bock, Rainey, US 2454541 (1948 to Rohm & Haas); J. W. Com-
`forth et al., Nature 168, 150 (1951). Use to induce exptl hy-
`perlipidemia: A. Kellner et al., J. Exp. Med. 93, 373 (1951); P.
`E. Schurr et al., Lipids 7, 68 (1972). Use as ophthalmic excip—
`ient: D. E. Guttman et al., J. Pharm. Sci. 50, 305 (1961). Phase
`behavior of mixtures with water: K. Westesen, Int. J. Pharm.
`102, 91 (1994); K. Westesen, M. H. J. Koch,
`ibid. 103, 225
`(1994). Tissue distribution and excretion: R; L. DeAngelis et
`al., Xenobiotica 25, 521 (1995).
`
`
`
`R = (CH2CH2O),H
`x = 8 ~ 10
`m < 6
`
`d2° 1.0963. Cloud point: 92—97°. Slowly but freely misc with
`water. Sol in benzene, toluene, chloroform, carbon tetrachlo-
`ride, carbon disulfide, acetic acid. Alkaline pH. Oxidized by
`metals.
`'
`"
`' Combination with colfosceril palmitate and hexadecanol,
`see Exosurf‘®
`,
`V
`USE: Phar/maceutic aid (dispersing agent; excipient). To in-
`duce exptl hyperlipidemia in animal models.
`‘
`Tl-IERAP CAT: Mucolytic.
`, 9902. Tymazoline.
`[24243-97-8,] 4,5—Dihydro-2-[[5-me-
`thyl-2-(1-methylethyl)phenoxy]1nethyl]-1H-imidazole; 2-[(thy—
`myloxy)methyl]-2-imidazoline; 2-(thymyloxymethyl)glyoxali—
`dine; 2-[(p -mentha- 1 ,3 ,5-trien-2-yloxy)methyl]-2—irnidazoline.
`CMHZONZO; mol wt 232.32. C 72.38%, H 8.68%, N 12.06%, 0
`6.89%. Prepd from an alkylvthymyloxyacetimidate and ethyl-
`enediamine: Sonn, US 2149473 (1939 to Ciba); Djerassi,
`
`
`
`
`
`
`
`Consult the Name Index before using this section.
`
`Page 1751
`
`Page 3
`
`
`
`Page 3