r Torasemide T 2081 Reference(s): Kingsbury, W.D. et al.: J. Med. Chcm. (JMCMAR) 34 (I), 98 (1991). EP 321 122 (SmithKline Beecham; appl. 30.1 1.1988; USA-prior. 1.12.1987). WO 9 205 785 (SmithKline Beecham; appl. 23.9.199 1; USA-prior. 28.9.1990). Formulation(s): vial 4 mg (as hydrochloride) Trade Namers): D: Hycamtin (SmithKline GB: Hycamtin (SmithKline USA: Hycamtin (SmithKline Bcecham) Beecham) Beecham) F: Hycamtin (SmithKline 1: Hycamtin (SmithKline Beecham) Beecham) Torasemide (AC 4464; BM 0201 5) Use: antihypertensive, loop diuretic RN: 56211-40-6 MF: C,,HmN40,S MW: 348.43 CN: N-[[(1-Methylethyl)amino~carbony1]-4-[(3-methylphcnyl)amino]-3-pyridinesulfonamide sodium salt RN: 72810-59-4 MF: C,,H,N40,S . xNa MW: unspecified 4-hydroxy- pyridine m-taluidine (111) 3-sulfanomido- 4-(3-rnethylani1ino)- pyridine (N) 111, Cu, Q5OC Torasemide H H isopropyl Torasemide isocyanate (V) I 2082 T Toremifene Reference (s): a,b Delarge, J.: Arzneim Forsch. (ARZNAD) 38 (I), la (1988). DE 2 516 025 (A. Christiaens; appl. 12.4.1975; GB-prior. I7.4.l974). stable crystalline modification: DE 3 623 620 (Boehringer Mannheim; appl. 17.8.1985; D-prior. 17.8.1985). injections containing torasemide: DE 3 623 620 (Boehringer Mannheim; D-prior. 12.7.1986). rupidly disintegrating pellets: WO 09 810 754 (Boehringer Mannheim: appl. 9.9.1997; D-prior. 12.9.1996). polynorphism and control of the serum solubility of orally administered torasemide: US 5 914 336 (Boehringer Mannheim; 22.6.1999; USA-prior. 2.6.1998). tablets containing torasemide: WO 9 300 097 (Boehringer Mannheim; appl. 25.6.1992; J-prior. 25.6.1991). use for treatment of brain edema: DE 4 113 820 (Boehringer Mannheim; D-prior. 27.4.1991). Formulation(s): amp. 10.631 mg/2 ml, 21.262 mg/4 ml, 212.62 mgl20 ml (as sodium salt); tab1 2.5 mg, 5mg, 10 mg Trade Narne(s): D: Torem (Berlin-Chemie) Unat (Roche; 1999) Toremifene (FC- I 157a) ATC: L02BA02 Use: antiestrogen, antineoplastic RN: 89778-26-7 MF: C2,H2,CIN0 MW: 405.97 LD,,,: 1700 inglkg (R, p.0.) CN: (Z)-2-[4-(4-chloro-1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethanamine citrate (1:l) RN: 89778-27-8 MF: C2,H2,CIN0. C,H807 MW: 598.09 LD,,,: 3 glkg (R, p.0.) 4-hydroxybenzo- 2-(dimethylamino)- 4-[Z-(dimethylamino)ethoxy]- phenone ethyl chloride benzophenone (I) 1. LiAIHI + hcH0 2. recrystollization from acetone cinnomaldehyde Tosufloxacin T 2083 1. AC20 2. NoOH 3. recrystollizotion from toluene u b H,c'~+o FH3 J+J')Q I Toremifene I Reference(s): EP 95 875 (Farmos; appl. 20.5.1983; SF-prior. 27.5.1982). US 4 696 949 (Farmos; 29.9.1987; appl. 29.1.1986; SF-prior. 27.5.1982,9.5.1983). Formulation(s): tabl. 20 mg, 60 mg (as citratc) Trade Name(s): D: Fareston (ASTA Medica I: Fareston (Schering-Plough) USA: Fareston (Schering-Plough) AWD) J: Fareston (Nippon Kayaku; GB: Fareston (Orion) as citrate) Tosufloxacin Use: quinolone antibacterial, gyrase inhibitor RN: 108138-46-1 MF: C,,H1,F3N4O3 MW: 404.35 CN: (f)-7-(3-amino- 1 -pyrrolidinyl)- 1 -(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3- carboxylic acid monotosylate RN: 115964-29-9 MF: C,,H,,F,N,O, . C71180,S MW: 576.55 LD,,: 196 mg/kg (M, i.v.); >6 glkg (M, p.0.); 270 mg/kg (R, i.v.); >6 glkg (R, p 0.); >3 gkg (dog, p.0.) . 1. CF3COOH, HCI C, N, CJ 0 CI N, CI 2. SOCl n-C,HgLi F w0,,CH3 A FwCI - monoethyl rnolonote. 0 u n-butyllithiurn ethyl 2,6-dichloro- 5-fluoronicotinate 2.6-dichloro-5-fluoro nicolinoyl chloride 2084 T ' Tralonide ethyl 2.6-dichloro-5-fluoro- triethyl orthoformote 2.4-difluoro- (w nicotinoylacetote (I) aniline 2. KOH 1. 3-ominopyrrolidine ethyl 7-chloro-1-(2.4-di- Tasufloxocin 1luorophenyl)-6-fluoro-l,4- dihydro-4-0x0-1,8- nophthyridine-3-carboxylate Reference(s): DE 3 514 076 (Toyama; appl. 31.10.1985; J-prior. 26.4.1984). US 4 704 459 (Toyama; 3.11.1987; appl. 17.1.1986; J-prior. 23.1.1985, 18.2.1985,7.3.1985, 3.4.1985, 8.5.1985, 14.6.1985). Chu, D.T.W. et al.: J. Med. Chem. (JMCMAR) 29,2363 (1986). Narita, H. et al.: Yakugaku Zasshi (YKKZAJ) 106, 802 (1986). synthesis qf ethyl 2,6-dichloro-5-fluoronicotinate: JP 82/72 981 (H. Matsumoto et al.; appl. 7.5.1982). alternative syntllesis: EP 302 372 (Abbott; appl. 8.2.1989; USA-prior. 4.8.1987). BE 904 086 (Toyama; appl. 14.6.1985; J-prior. 23.1.1985). Formulation(s): tabl. 75 mg, 150 mg (as tosylate) - Trade Name(s): J: Osex (Toyama; 1990) Tosuxacin (Dainabot; 1990) Tralonide ATC: H02AB; R03BA Use: glucocorticoid RN: 21 365-49- 1 MF: C24H2,CI,F20, MW: 489.39 CN: (6a, 1 1 P, 16a)-9,11 -dichloro-6,21-difluoro- 16,17-[(1 -methylethylidene)bis(oxy)Jpregna-1,4-diene-3,20- dione Tramadol T 2085 1. K,CO,. CH,OH 2. CH,SOZCI, pyridine 3. LiBr. CH3COCH3 b 1. potassium corbonate 2. methonesulfonyl chloride 3. lithium bromide 21 -acetoxy-3,20-dioxo-6a- fluoro-l6a,l7-isopropylidene- dioxy-1,4,9(1 1)-pregnotriene (from fludroxycortide, q. v.) 2. ClZ, CHC13. pyridine I 1. potassium fluoride, 2. chlorine F Tralonide DOS 2 225 324 (Syntex; appl. 25.5.1972; USA-prior. 26.5.1971). starting material: US 3 282 929 (American Cyanamid; 1.1 1.1966; prior. 6.7.1964). alternative synthesis: US 3 409 613 (Syntex; 5.1 1.1968; prior. 28.7.1966). ZA 680 282 (Syntex; appl. 15.1.1968). medical use: US 3 934 013 (Syntex; 20.1.1976; prior. 21.2.1975). Trade Name(s): USA: Talidan (Lilly); wfm ATC: N02AX02 Use: analgesic RN: 27203-92-5 MF: C16H2,N02 MW: 263.38 EINECS: 248-319-6 LD,,: 228 mglkg (R, p.0.) CN: cis-(lt)-2-[(dimethylamino)methyl]-l-(3-methoxyphenyl)cyclohexanol hydrochloride RN: 36282-47-0 MF: C,,H2,N02 . HCl MW: 299.84 EINECS: 252-950-2 2086 T Tramazoline H3C\ H3C\ Mg. THF - Z-dimethylamino- B r MgBr rnethylcyclohexanane J-bromo- anisole Tramadol u Reference(s): GB 997 399 (Griinenthal; appl. 1.4.1964; D-prior. 2.4.1963), Formulation(s): amp. 50 mglml, 100 mg/2 ml; cps. 50 mg; drops 100 mglml; eff. tabl. 50 mg; s. r. tabl. 100 mg, 150 mg, 200 mg; suppos. 100 mg; tabl. 50 mg (as hydrochloride) Trade Name(s): D: Amadol (TAD) TRADOL-PUREN (Isis Puren) Trama (Kade) Trama AbZ (AbZ-Pharma) Trama beta (betapharm) Tramadol (ASTA Medica AWD; Dolorgiet; ratiopharm; Stada; ct- Arzneimittel) Tramadura (durachemie) Tramagetic (Azupharma) Tramagit (Krewel Meuselbach) Tramal (Griinenthal) Trama-Sanorania (Sanorania) Tramdolar (Hexal) Tramedphano (medphano) Tramundin (Mundipharma) Tramazoline F: Topalgic (Hoechst HoudC) GB: Tramake (Galen) Zamadol SR (ASTA Medica) Zyndol SR (Searle) I: Contramol (Formenti) Fortradol (Bayer) J: Crispin (Kowa) USA: Ultram (Ortho-McNeil) ATC: ROlAA09 Use: vasoconstrictor, rhinological therapeutic RN: 1082-57-1 MF: CI3HL7N3 MW: 215.30 EINECS: 214-105-6 CN: 4,5-dihydro-N-(5,6,7,8-tetrahydro- 1-naphthaleny1)-1 H-imidazol-2-amine monohy drochloride RN: 37 15-90-0 MF: C13H,,N3 . HC1 MW: 251.76 EINECS: 223-064-3 LD,,,: 11.6 mglkg (M, i.v.); 130 mglkg (M, p.0.); 190 mglkg (R, p.0.) HzNKNH iodide s 5-amino- ammonium letralin rhodonide NH2 H2NyNH 1- + (1) ethylene- Tramozoline Trandolapril T 2087 Reference(s): DE 1 173 904 (Thomae; appl. 5.8.196 1). DE 1 191 381 (Thomae; appl. 24.6.1963; addition to DE 1 173 904). DE 1 195 323 (Thomae; appl. 24.6.1963; addition to DE 1 173 904). Formulation(s): eye drops 0.6 mglml; nasal sprayldrops 1.2 mglml Trade Name(s): D: Biciron Augentropfen Rhinospray (Boehringer I: Rinogutt Spray (Fher) (Alcon) k.1 J: Towk (Tanabe) Ellatun Nasentropfen GB: Dexa-Rhinspray ( Alcon) (Boehringer 1ng.)-comb. Trandolapril (RU-44570) ATC: C09AA10 Use: antihypertensive (ACE inhibitor) RN: 87679-37-6 MF: CxH,,N,O, MW: 430.55 - LD,,: >2 g/kg (R, i. v.); >5 g/kg (R, p. 0.); 3 g/kg (M, i. v.); 3.99 g/kg (M, p. 0.); 2 glkg (dog, p. 0.1 CN: [2S-[1[R*(R*)],2a,3aa,7a~]]-1-[2-[[1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-l-oxopropyl]octahydro- 1H-indole-2-carboxylic acid hydrochloride RN: 87725-72-2 MF: C2,H,,N20S . HC1 MW: 467.01 1. onod. oxidation, CH,OH 1 H2. Pt02. CH3COOH 2' H3c-'F 5'- cN , CH~CI~ CH3 + 1 2. trimethylsilyl cyonide H octohydroindole octohydroindole-2- actohydroindole- carbonitrile (I) 2-corboxylic ocid HOBt, DCC, DMF. N-ethylmorpholine -b 111 ( q N-[1 (S)-ethaxycorbonyl- 3-phenylpropyll- L-olonine (cf. spiropril and irnidapril syntheses) 2088 T Tranexamic acid D: Gopten (Knoll) Tarka (Knoll)-comb. with verapamil hydrochloride Udramil (Hoechst Marion Roussel; Pohl-Boskamp)- comb. with verapamil hydrochloride (Dl) Tranexamic acid (Acide tranexamique) Trandolapril Udrik (Hoechst Marion Zeddan (Mediolanum) Roussel; Pohl-Boskamp) J: Preran (Hoechst) F: Gopten (Ebewe, A; Knoll) USA: Mavik (Knoll Pharmac.) Odrik (Roussel) Tarka (Knoll Pharmac.) GB: Gopten (Ebewe, A; Knoll) Odrik (Roussel) I: Gopten (Ebewe, A; Knoll) Reference(s): DE 3 15 1 690 (Hoechst AG; appl. 29.12.198 1 ; D-prior. 29.12.198 1) Formulation(s); cps. 0.5 mg, 1 mg, 2 mg; tabl. 2 mg, 4 mg Trade Narne(s): ATC: B02AA02 Use: antifibrinolytic, hemostatic RN: 1197-18-8 MF: C,H,,NO, MW: 157.21 EINECS: 214-818-2 LDSI,: 1350 mgkg (M, i.v.); >10 glkg (M, p.0.); 1200 mglkg (R, i.v.); 11 10 mgkg (dog, i.v.); >5 gkg (dog, p.0.) CN: trans-4-(aminomethyl)cyclohexanecarboxylic acid CH3 COOH COOH HZ. Raney-Co H2/Pt or H2/Ru + 1 C N C N 4-cyano- benzoic acid 4-aminomethyl- benzoic acid cis-trans isamerizatian by heating of the alkali metal salts to 210-240 OC and CooH subsequent separation via salts of sulfonic ocid 4-ominomethyl- Tranexomic acid cyclohexane- corboxylic ocid cis/trans mixture (I) Tranilast T 2089 - - - - - Reference(~): syntheses: Einhorn, A,; Ladisch, C.: Justus Liebigs Ann. Chem. (JLACBF) 310, 194 (1900). Levine, M.; Sedlecky, R.: J. Org. Chem. (JOCEAH) 24, 115 (1959). DAS 1 443 755 (Daiichi Seiyaku; appl. 23.12.1964; J-prior. 24.12.1 963). DAS I 793 841 (Daiichi Seiyaku; appl. 23.12.1964; I-prior. 24.12.1963). GB 1202 189 (Kureha; appl. 13.6.1969; J-prior. 14.6.1968, 12.9.1968, 28.12.1968, 17.2.1969). US 3499 925 (Daiichi ~eiyaku; 10.3.1970: ~-~rior. 23.3.1964, 6.7.1964). DOS 1 568 379 (Daiichi Seiyaku; appl. 13.4.1966; J-prior. 13.4.1965). DOS 2 227 504 (Kowa; appl. 6.6.1972). DAS 2 344 043 (Teijin; appl. 31.8.1973; J-prior. 7.9.1972,30.3.1973). GB 1 409 938 (Asahi; appl. 29.1 1.1973; J-prior. 29.1 1.1972). DAS 2 359 251 (Asahi; appl. 28.1 1.1973; J-prior. 29.1 1.1972). GB 1 410 108 (Asahi; appl. 2.10.1973; J-prior. 2.10.1972). DAS 2623 130 (Kureha; appl. 22.5.1976; J-prior. 27.5.1975). Formulation(s): amp. 250 mg15 ml, 500 mg15 ml; cps. 250 mg, 500 mg; f. c. tabl. Trade Namefs): D: Anvitoff (Knoll) Cyklokapron (Pharmacia & Upjohn) Ugurol (Bayer) F: Exacyl (Sanofi Winthrop) Spotof (CCD) GB: Cyklokapron (Pharmacia & Upjohn) I: Amcacid (Bonomelli); wfm J: Amcacid (Bonomelli- Hommel); wfm Emorhalt (Sigurti); wfm Trancx (Malesci); wfm Transil (Malesci)-comb.; wfm USA: Ugurol (Bayer); wfm 500 mg; tabl. 250 mg Carxamin (Sankyo Zoki) Hexatron (Nihon Shinyaku) Rikavarin (Toyo) Spiramin (Mitsui) Tranexamic Acid (Mohan) Transamin (Daiichi) Cyklokapron (Pharmacia & Upjohn); wfm Tranilast ATC: R06 Use: antiallergic RN: 53902-12-8 MF: C,8H17NOI MW. 327.34 LDlo. 680 mglkg (M, p.o.1; 1 I00 mglkg (R, p.0.); 660 mdkg (dog, p.0.) CN: 2-[[3-(3,4-dimethoxypheny1)-1 -oxo-2-propenyl]amino]benzoic acid anthmnilic 3.4-dimethoxy- I Tronilast acid cinnamoyl chloride Reference(s): DOS 2 402 398 (Kissei; appl. 18.1.1974; J-prior. 18.1.1973). US 3 940 422 (Kissei; 24.2.1976; appl. 17.1.1974; J-prior. 18.1.1973). US 4 070 484 (Kissei; 24.1.1978; prior. l8.l.1973). Formvlation(s): cps. 100 mg, eye drops 0.5 %; gran. 10 % Trade Name(s): 3: Rizaben (Kissei; 1982) Tranylcypromine ATC: N06AF04 Use: psychoanaleptic, antidepressant RN: 155-09-9 MF: C9Hl,N MW: 133.19 EINECS: 205-841-9 LD,,,: 64 mgkg (M, p.0.) CN: trans-(+)-2-phenylcyclopropanamine sulfate (2:l) RN: 13492-01-8 MF: C,H,,N. l/2H2S04 MW: 364.47 EINECS: 236-807-1 LD,,: 37 mglkg (M, i.v.); 38 mg/kg (M, p.0.) styrene ethyl ethyl 2-phenyl- diazoocetate cyclopropone- carboxylote trans-2-phenyl- cyclopropane- carboxylic acid (I) 1. N0N3 2. HCI 1 - thionyl chloride aide trans-2-phenyl- Tranylcyprornine cyclopropone- corbonyi chloride US 2 997 422 (Smith Kline & French; 22.8.1961; prior. 9.1.1959). DOS 2 649 700 (Nelson Res. & Dev.; appl. 29.10.1976; USA-prior. 3 1.10.1 975). US 4 016 204 (Nelson Res. & Dev.; 5.4.1977; appl. 31.10.1975). Burger, A,; Yost, W.L.: I. Am. Chem. Soc. (JACSAT) 70, 2198 (1948). Formulation(s): drg. 10 mg; tabl. 10 mg (as sulfate) Trade Name(s): D: Jatrosom (Procter & GB: Parnate (SmithKline I: Parmodalin (Sanofi Gamble) Beecham) Winthrop)-comb. F: Tylciprine (ThCraplix); Parstelin (SmithKline USA: Parnate (SmithKline wfm Beecham)-comb. Beecham) Trazodone ATC: N06AX05 Use: antidepressant, anxiolytic RN: 19794-93-5 MF: C19H22ClNS0 MW: 371.87 EINECS: 243-317-1 LD j,,: 9 1 mglkg (M, i.v.); 6 10 mgkg (M, p.0.); 91 mglkg (R, i.v.); 690 mg/kg (R, p.0.) CN: 2-[3-[4-(3-chlorophenyl)-l-piperazinyl]propyl]-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one monohydrochloride RN: 25332-39-2 MF: Cl,H22ClN50~ HCI MW: 408.33 EINECS: 246-855-5 LDs(,: 91 mgkg (M, i.v.); 584 mglkg (M, p.0.); 91 mglkg (R, i.v.); 690 mglkg (R, p.0.); >40 mglkg (dog, i.v.); 500 mglkg (dog, p.0.) . 10813 8-4 6-1 MF: C,,H1,F3N4O3 MW: 404.35 CN: (f )-7 -( 3-amino- 1 -pyrrolidinyl )- 1 -( 2,4-difluorophenyl )-6 -fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine- 3- carboxylic acid monotosylate RN: 11596 4-2 9-9 . 2.6-dichloro-5-fluoro- triethyl orthoformote 2.4-difluoro- (w nicotinoylacetote (I) aniline 2. KOH 1. 3-ominopyrrolidine ethyl 7-chloro- 1-( 2.4-di- Tasufloxocin 1luorophenyl )-6 -fluoro-l, 4-. (dog, p. 0.1 CN: [2S-[1[R*(R*)],2a,3aa,7a~] ]-1 -[ 2-[ [ 1-( Ethoxycarbonyl )-3 -phenylpropyl]amino]-l-oxopropyl]octahydro- 1H-indole-2-carboxylic acid hydrochloride RN: 8772 5-7 2-2 MF: C2,H,,N20S .