Tizanidine T 2061 Tizanidine ATC: M03BX02 Use: skeletal muscle relaxant RN: 51322-75-9 MF: C,H,CIN,S MW. 253.72 LD,,: 235 mgkg (M, p.0.); 600 mgkg (R, p.0.) CN: 5-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,l,3-benzothiadiazol-4-amine hydrochloride RN: 64461-82-1 ME C9H8CIN5S . HCl MW: 290.18 1. HNO,. H,SO, 2. Fe, CH3COOH C12CS *I CI 2 CI CI thiophosgene 4-chloro- 1,2- 5-chloro-2.1.3- N Hz diominobenzene benzothiadiazole KOH CI leod(ll) NCS MyN*~~2 acetate s 5-chloro-4- ethylene- isothiocyanoto- diornine 2,l ,J-bcnzo- thiodiazole Refermce(s): DE 2 322 880 (Sandoz; appl. 22.1 1.1973; prior. 7.5.1973). US 3 843 668 (Sandoz; 22.10.1974; appl. 8.5.1973; CH-prior. 9.5.1972). CH 579 565 (Sandoz; appl. 15.3.1973). synthesis of 4-amino-5-chloro-2,1,3-benzothiadiazole: Pesin, V.G.;. Khaletskil, A.M.: Zh. Obshch. Khim. (ZOKHA4) 27,2599 (1957). C.A. (CHABA8) 52,7292. Smith, W.T.; Chen, W Y.: J. Org. Chem. (JOCEAH) 27,676 (1962). Formulation(s): tabl. 2 mg, 4 mg, 6 mg (as hydrochloride) Trade Name(s): D: Sirdalud (Sanofi Winthrop; GB: Zanaflex (Athena) USA: Zanaflex (Athena) 1985) J: Teonelin (Sandoz) Tobramycin ATC: JOIGBOI; SOIAA12 Use: antibiotic RN: 32986-56-4 MF: C,,H,,NSO, MW: 467.52 EINECS: 251-322-5 LD,,,: 72.5 mgkg (M, i.v.); >I 1500 mgkg (M, p.0.); 104 mgkg (R, i.v.); >7500 mglkg (R, p.0.) CN: 0-3-amino-3-deoxy-a-~-glucopyranosyl-(1+6)-0-[2,6-diamino-2,3,6-trideoxy-cr-o-rib0-hexopyranosy~- (1 +4)]-2-deoxy-D-streptamine 2062 T Tobramycin sulfate RN: 49842-07-1 MF: CL,H,N,09. xH,SO, MW: unspecified EINECS: 256-499-2 LD,,,: 77 mgkg (M, i.v.); >I0500 mglkg (M, p.0.); 126 mglkg (R, i.v.) from fermentation solutions of Streptomyces tenebrarius (ATCC 17920) or (ATCC 17921) bekanomycin ('1. v.) ATP. E. coli R11 (IFO-13560) + adenosine triphosphate - - 2. Raney-Ni. H20 1. trimethylchlorosilow. triphenylphasphine. N.0-bis(trimethylsilyl)ocetamide Tobrarnycin u Reference(s): a US 3 69 1 279 (Lilly; 12.9.1972; prior. 15.4.1970, 12.2.1969, 17.9.1965). DE 1 792 819 (Lilly). b DOS 2 514 985 (Takeda; appl. 5.4.1975; J-prior. 10.4.1974, 25.6.1974). Okutani, T. et al.: J. Am. Chen~. Soc. (JACSAT) 99, 1278 (1977). alternative syntheses: DOS 2 361 159 (Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai; appl. 7.1 2.1973; J-prior. K12.1972). UOS 2 533 985 (Meiji Seika Kaisha; appl. 30.7.1975; J-prior. I .8.1974). Tagaki, Y. et al.: J. Antibiot. (JANTAJ) 26,403 (1973). total synthesis; Tanabe, M. et al.: Tetrahedron Lett. (TELEAY) 1977, 3607. Formulation(s): amp. 40 mg, 80 mg (as sulfate); eyc drops 3 mglml; ointment 3 mglg; vial 20 mg, 40 mg, 80 mg (as sulfatc) Tocainide T 2063 Trade Name(s): D: Burlamycin (medphano) Tobrex (Alcon) J: Tobracin (Shionogi Gernebcin (Lilly; 1975) GB: Nebcin (King) Seiyaku) TOBRA-cell (cell pharm) I: Nebicina (Lilly) USA: Nebcin (Lilly; 1975) Tobramain (Alcon; 1982) Tobrex (Firma) TobraDex (Alcon) F: Nebcine (Lilly) Tobrex (Alcon) - Tocainide ATC: COlBB03 Use: antiarrhythmic RN: 41708-72-9 MF: Cl,H16N,0 MW: 192.26 EINECS: 255-505-0 LD,,: 94 mglkg (M, i.v.) CN: 2-amino-N-(2,6-dimethylpheny1)propanamide 2.6-dimethyl- Z-brorno- aniline propionyl bromide Reference(s): US 4 218 477 (Astra; 19.8.1980; prior. 28.7.1971). US 4 237 068 (Astra; 2.12.1980; prior. 8.1.1973). DE2 235 745 (Astra; appl. 21.7.1972; USA-prior. 28.7.1971). enantiomers: DOS 2 400 540 (Astra; appl. 7.1.1974; USA-prior. 8.1.1973). GB 1 461 602 (Astra; appl. 7.1.1974; USA-prior. 8.1.1973). Forrnulation(s): f. c. tabl. 400 mg, 600 mg (as hydrochloride) Tocoinide Trade Name(s): D: Xylotocan (Astra; 1982) GB: Tonocard (Astra; 1981); USA: Tonocard (Astra Merck; wfm 1984) a-Tocopherol (Vitamin E) ATC: AIlHA03 Use: antisterility vitamin RN: 10191-41-0 MF: C,,HS,O, MW: 430.72 EINECS: 233-466-0 CN: 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-ol D-compound RN: 59-02-9 MF: C,,H,,O, MW: 430.72 EINECS: 200-412-2 a-Tocopherol acetate (Vitamin E acetate) RN: 7695-91-2 MF: C3,H,,03 MW: 472.75 EINECS: 231-710-0 CN: 3,4-dihydro-2,5,7,8-tetramcthyl-2-(4,8,12-trimethyltridecyl)-2H-l-benzopyran-6-ol acetate D-6-acetate RN: 58-95-7 MF: C,,H5,O, MW: 472.75 ElNECS: 200-405-4 @ total synthesis H3c$0H + mid condensation ogento, HO CH3 2.3.5-trlrnethyl- hydroquinone isophytol partial synthesis (lrorn p-, 7-, and 6 -tocopherols, occurring in vegetable oils together with a-tocopherol), e.g. from 7-tocopherol HCI H~Cm:y3 + HP=O + H3 CH3 CH, CH, CH3 HO Reference(s): a DRP 7 13 749 (Roche; appl. 1939; CH-prior. 1938). DRP 73 1 972 (Roche; appl. 1938; CH-prior. 1938). DE 960 720 (Roche; appl. 1955; USA-prior. 1954). DAS 1 909 1 64 (Roche; appl. 24.2.1969; USA-prior. 27.2.1968, 19.1 1.1968). DAS 2 208 795 (Diamond Shamrock; appl. 24.2.1972; USA-prior. 25.2.1971). DOS 2 743 920 (Nisshin Flour Milling; appl. 29.9.1977; J-prior. 29.9.1976). US 4 055 575 (SCM Corp.; 25.10.1977; prior. 20.3.1975). US 4 115 466 (SCM Corp.; 19.9.1978; prior. 20.3.1975, 16.10.1975,6.10.1977). b US 2 519 863 (Eastman Kodak; 1950; appl. 1949). DE 909 095 (Eastman Kodak; appl. 1950; USA-prior. 1946). DE 91 1 732 (Eastman Kodak; appl. 1950; USA-prior. 1945). DE 1 056 143 (Eastman Kodak; appl. 1956; USA-prior. 1955). US 2 592 53 1 (Eastman Kodak; 1952; appl. 1949). US 2 592 628 (Eastman Kodak; 1952; appl. 1949). US 2 592 630 (Eastman Kodak; 1952; appl. 1949). US 4 122 094 (Lever Brothers; 24.10.1978; prior. 9.6.1976, 13.5.1977). DOS 2 606 830 (BASF; appl. 20.2.1976). Todralazine T 2065 Formulation(s): amp. 100 mg12 ml, 100 mglml; cps. 100 iu, 200 iu, 300 iu, 400 iu, 500 iu; drg. 100 mg (as tartrate) Trade Name(s): D: Biopto-E (Jenapharrn) Equiday (Solvay Arzneimi ttel) Evit-Geritan (Chefaro) Malton-E (Sertiirner) Optovitl-forte/fortissimum (Hermes) Pexan (Worwag) Puncto E (ASTA Medica AWD) Tocorell (Sanorell) Vitamin E-Dragees (Wiedemann) Vit. E Stada (Stada) numerous combination preparations F: Alvity (Solvay Pharma)- comb. Capsules Pharmaton (Boehringer 1ng.)-comb. Carencyl (Riom)-comb. Cirkan suppositoires (Sinbio)-comb. Difrarel E (Leurquin)- comb. Hydrosol polyvitamink B.O.N. (Doms-Adrian)- comb. Hydrosol polyvitaminC Roche (Roche)-comb. Lofenalac Mead Johnson (Bristol-Myers Squibb)- comb. NutrigCne (GNR-pharma)- comb. Survitme (Roche Nicholas)-comb. Toco 500 (Pharma 2000) Tocogestan (ThCramex)- comb. - Tocomine (Eurorga) UvCsttrol (Crinex)-comb. Vkliten (Wyeth-Leder1e)- comb. Vivamyne (Whitehall) comb. numerous combination preparations GB: Ketovite (Paines & Byme)- comb. 1: E-Vitum (Lipha) Ephynal (Roche) Evion (Bracco) Evion Forte (Bracco) Evitina (CT) Midium (Teofarma)-comb. Rovigon (Roche)-comb. Salonpas (Farmila)-comb. Tocalfa (ASTA Medica)- comb. J: Ephelon (Kowa) Ephynal (Roche) Eseblon (Seiko-Fuso) Esuverol (Sanko) Euvel (Nippon Chemiphar) Inazin (Tanabe) Ivet (Kuroishi-Nippon Shiny aku) Juvelux (Eisai) Juvevitan (Toyo Jozo) Kenton (Sawai) Magiron E (Choseido) Nichivita E (Nichiiko) Sunfull S (Maruishi) Takaron (Shiki) Tocophal (Chugai) Tocorol (Daigo Eiyo) Tokobera (Nakano) Tokos-E (Nippon Shoji) Welvin-E (Ono) Yurica (Kobayashi Kako) USA: Ccfol (Abbott)-comb. Materna (Leder1e)-comb. Megadosc (Arm-comb. combination preparations and generics Todralazine (Ecarazine) ATC: C02 Use: antihypertensive RN: 14679-73-3 MF: C,IH,2N,0, MW: 232.24 LD,,: 60 mgkg (M, i.v.); 110 mglkg (R, i.v.); 31 8 mgkg (R, p.0.) CN: 2-(1-phthalazinyl)hydrazinecarhoxylic acid ethyl ester monohydrochloride RN: 3778-76-5 MF: CIIH,2N402. HCI MW: 268.70 LD5,,: 300 mg/kg (M, i.v.); 516 mg/kg (M, p.0.); 240 rnglkg (R, i.v.); 598 mglkg (R, p.0.) CI 0-CH, + K NaHCOJ 0 hydrolozine ethyl chloro- Todralozine (9. v.) formate 2066 T Tofenacin Reference(s): RE 647 722 (Polfa; appl. 11.5.1964; P-prior. 1 1.5.1963,9.12.1963). Formulation(s): powder 10 % (as hydrochloride); tabl. 10 mg, 30 mg Trade Name(s): J: Aperdor (Tokyo Tanabe) Dypirecohl (Daito Koeki) Hydrapron (Isei) Apiracohl (Kyowa) Ecara (Toyo Pharmar) Marukunan (Zensei) Atapren (Sumitomo) Ecarocohl (Nihon Mohazorin (Mohan) Bihyst (Ohta) Iyakuhin) Seirof (Maruko) Deprezid (Ono) Ekahain (Towa) Tofenacin ATC: N04; N06A Use: antiparkinsonian, antidepressant RN: 15301-93-6 MF: C,,H,,NO MW: 255.36 EINECS: 239-338-0 CN: N-methyl-2-[(2-methyIphenyl)phenylmethoxy]ethanamine hydrochloride RN: 10488-36-5 MF: C,,H,,NO. HC1 MW: 291.82 EINECS: 234-01 1-9 LD,,,: 32 mglkg (M, i.v.); 182 mglkg (M, p.0.); 15 mgkg (R, i.v.); 400 mglkg (R, p.0.); 90 mgkg (dog, p.0.) 2-methyl- 2-methylomino- benzhydrol (I) ethanol Tofenocin u - '0. ' methylamine 2-chloro- ethanol Reference(s): US 3 407 258 (Brocades-Stheeman; 22.10.1968; GB-prior. 30.1 1.1962). Trade Nume(s): CB: Elamol (Brocades); wfm Tofisopam T 2067 Tofisopam ATC: N05BA23 Use: tranquilizer, anxiolytic RN: 22345-47-7 MF: CzzHz6N204 MW: 382.46 EINECS: 244-922-3 LD,,,: 415 mag (M, i.v.); 3800mglkg (M, p.0.); 103 mgikg (R, i.v.); 825 mglkg (R, p.0.) CN: 1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine diisohornoeugenol (from diisoeugenol) 6-(1-ocetylpropy1)- 3,4,3'.4'-tetromethoxy- benzophenone HCI, CHJOH b H2N-NH2 . H20 hydrozine hydrate I Tofisopom Reference(s): DAS 1 670 642 (Egyt; appl. 8.12.1967; H-prior. 9.12.1966). educt: Doering, W. v. E.; Berson, J.A.: J. Am. Chem. Soc. (JACSAT) 72, 1118 (1950). Formulation(s): tabl. 50 mg Trade Narne(s): F: Grandaxine (Ozothine); Seriel (Sinbio); wfm wfm J: Grandaxin (Mochida) Tolazamide ATC: AIOBBOS Use: antidiabetic RN: 1156-19-0 MF: C,,H,,N,O,S MW: 31 1.41 EINECS: 214-588-3 LDsO: 1 glkg (M, p.0.); >5 ag (R, p.0.) CN: N-[[(hexahydro-lH-azepin-l-yl)amino]carbonyl]-4-methylbenzenesulfonamide 2068 T Tolazoline p-toluene- ethyl chloro- sulfonamide forrnate ethyl N-(p-tolyl- sulfonyl)carbomOte (1) 1 -ornino- hexohydroazepine Reference(s): US 3 063 903 (Upjohn; 13.1 1.1962; appl. 29.3.1961; prior. 9.6.1959). GB 887 886 (Upjohn; appl. 29.9.1960). DE 1 196 200 (Hoechst; appl. 27.12.1961). Wright, J.B.; Willette, R.E.: J. Med. Chenl. (JMCMAR) 5, 815 (1962). Formulahm(s): tabl. 250 mg, 500 mg Trade Name(s). D: Norglycin (Upjohn); wfm 1: Diabewas (IBI); wfm J: Tollnase (Upjohn) GB; Tolanase (Pharmacia & Diabewas (Wassermann); USA: Tolazamlde (Mylan) Upjohn) wfm Tolinase (Upjohn); wTm Tolazoline ATC: C04AB02; M02AX02 Use: vasodilator, antiadrenergic RN: 59-98-3 MF: C,nH,2N2 MW: 160.22 EINECS: 200-448-9 LD,,: 40 mgkg (M, i.v.); 350 mgkg (M, p.0.) CN: 4,s-dihydro-2-(phenyImethy1)-IH-imidazole monohydrochloride RN: 59-97-2 MF: CI0H,,N2. HC1 MW: 196.68 EINECS: 200-447-3 LD,,,: 56.7 mgkg (M, i.v.); 400 mg/kg (M, p.0.); 85 mgkg (R, i.v.); 1200 mgkg (R, p.0.) NC~ + H~C-OH 5 H3Cv0q NH , OHCI 'NH ethylene- benzyl cyonide ethyl 2-phenylacet- diomine imidote hydrochloride em Tolozoline Reference(s): US 2 161 938 (Ciba; 1939; D-prior. 1934). DRP 615 227 (A. Sonn; 1934). alternative syntheses: DRP 687 196 (Ciba; appl. 1938; CH-prior. 1937). DE 842 063 (Ciba; CH-prior. 1945). Tolbutamide T 2069 Fomulation(s): amp. 10 mg/ml Trade Name(s): D: Priscol (CIBA Vision) J: Benzolin(Nissin) USA: Priscoline (Ciba); wfm GB: Priscol (Ciba); wfm Imidalin (Yamanouchi) I: Priscofen (Ciba)-comb.; Priscol (Ci ba-Geigy- wfm Takeda) Tolbutamide ATC: AlOBB03; V04CA01 Use: antidiabetic RN: 64-77-7 MF: C12Hl,N203S MW: 270.35 EINECS: 200-594-3 LD,: 770 mg/kg (M, i.v.); 490 mglkg (M, p.0.); 700 mglkg (R, i.v.); 2490 mg/kg (R, p.0.) CN: N-[(butylamino)carbonyl]-4-methylbenzenesulfonamide Reference(s): US 2 968 158 (Hoechst; Upjohn; 17.1.1961; D-prior. 8.8.1955). DE974 062 (Hoechst; appl. 9.8.1955). p-toluenesulfonarnide butyl isocyanate alternative method: DAS 2 053 740 (Brunnengraber; appl. 2.11.1970). Ruschig, H. et al.: Arzneim Forsch, (ARZNAD) 8,448 (1958). Tolbutarnide Formulation(s): tabl. 500 mg, 1 g sodium salt Trade Name(s): D: Artosin (Boehringer GB: Rastinon (Hoechst) Mannh.) I: Glucosulfa (Lipha)-comb. Orabet (Berlin-Chemie) J: Abeformin T (Maruko) Rastinon (Hoechst) Diabex-T (Funai) Tolbutamid R.A.N. Dibetos (Kodama) (R.A.N.) F: Dolipol (Hoechst) Nigloid (Universal) Rankmin (Maruishi) Rastinon (Hoechst) Unimide 500 (Sanko) Urerubon (Seiko) Insilange-D (Horita) USA: Tolbutamide Tablets Mellitos D (Ono) (MYW Tolcapone (Ro-40-7592) ATC: N04BXOl Use: antiparkinsonian, COMT inhibitor RN: 134308-13-7 MF: C,,H,,NO, MW: 273.24 CN: (3,4-Dihydroxy-5-nitrophenyl)(4-methylphenyl)methanone 2070 T Tolfenamic acid 1 4-brornotoluene 4-benzyloxy-3-methoxy- 4-benzyloxy-3-rnethoxy- benzoldehyde 4'-methylbenzhydrol (I) 1. HN03. CH3COOH 2. HBr. CH3COOH I 1. pyridiniurn chlorochromote Tolcopone I verotrole p-methyl- benzoyl chloride a EP 237 929 (Hoffmann-La Roche; appl. 11.3.1987; CH-prior. 1 1.3.1986; 9.1.1987). b EP 855 379 (Hoffmann-La Roche; appl. 15.1.1998; EP-prior. 22.1.1997). process for the manufacture of a powdery preparation: WO 9 8 16 204 (Hoffmann-La Roche; appl. 13.10.1997; EP-prior. 14.10.1996; CH-prior. 25.1 1.1996). pharmaceutical composition for treating Parkinsons's diseuse: WO 9 831 355 (Britannia Pharm.; appl. l4.l.lgY8; GB-prior. 16.1.1997). Formulation(s): tabl. 100 mg, 200 mg Trade Name(s): D: Tasmar (Hoffmann-La GB: Tasmar (Roche); wfm USA: Tasmar (Roche; 1998); Roche; 1997); wfm 1: Tasmar (Roche); wfm wfm Tolfenamic acid ATC: MOIAG02 Use: anti-inflammatory, analgesic RN: 13710-1 9-5 MF: C,4H,2C1N02 MW: 261.71 EINECS: 237-264-3 LD,,,: 280 mglkg (M, p.0.); 225 mglkg (R, p.0.) CN: 3-[(3-chloro-2-methyIphenyl)amino]benzoic acid . 0-3 -amino-3-deoxy-a-~-glucopyranosyl-(1+6 )-0 -[ 2,6-diamino-2,3,6-trideoxy-cr-o-rib0-hexopyranosy ~- (1 +4) ]-2 -deoxy-D-streptamine 2062 T Tobramycin sulfate RN: 4984 2-0 7-1 MF: CL,H,N,09. xH,SO, MW: unspecified EINECS: 25 6-4 9 9-2 . EINECS: 23 1-7 1 0-0 CN: 3,4-dihydro-2,5,7,8-tetramcthyl- 2-( 4,8,12-trimethyltridecyl )-2 H-l-benzopyran-6-ol acetate D-6-acetate RN: 5 8-9 5-7 MF: C,,H5,O, MW: 472.75 ElNECS: 20 0-4 0 5-4 @ total. 5132 2-7 5-9 MF: C,H,CIN,S MW. 253.72 LD,,: 235 mgkg (M, p.0.); 600 mgkg (R, p.0.) CN: 5-chloro-N-(4,5-dihydro-1H-imidazol-2-yl )-2 ,l,3-benzothiadiazol-4-amine hydrochloride RN: 6446 1-8 2-1