Tandospirone T 1971 1: Omn~c (Yamanouchi) USA: Flomax (Boehringer 1. Harnal (Yamanouchi) Ingelheim; 1997) f Tandospirone (SM-3997 (as citrate)) ATC: NOSBX Use: anxiolytic, antidepressant RN: 87760-53-0 MF: C,,H2,N502 MW: 383.50 CN: (3aa,4P,7P,7aa)-hexahydro-2-[4-[4-(2-pyrimidinyl lpiperazinyl]butyl]-4,7-methano-1 H- soi in dole- 1,3(2H)-dione citrate RN: 112457-95-1 MF: C2,H2,N5O2. C,H,O, MW: 575.62 1-(pyrirnidin-2-yl)- piperazine H n 1. 190°C H n 2. HZ, cat. __* norborn-5-ene- ZexoJexa-dicarboxylic ocid anhydride pyridine, A 1 + II + norbarnane- 2exo.3exo-dicarboxylic acid anhydride (11) gN_,~3J:9 H Tandospirone Reference(s): EP 82 402 (Sumitomo Chem.; appl. 29.6.1983; J-prior. 22.12.1981,3.6.1982). JP60 087 262 (Sumitomo Chem.; appl. 16.5.1985; USA-prior. 19.1.1983). JP 63 010 760 (Sumitomo Chem.; appl. 18.1.1988; J-prior. 1.7.1986). use oftandospirone: a) treuling depression: US 5 01 1 841 (Pfizer; appl. 30.4.1991; USA-prior. 14.1 1.1989). b) as psychotropic agents: US 5 521 313 (Bristol-Myers Squibb; appl. 28.5.1996; USA-prior. 5.5.1994). c) as 5-HT,A-receptor agonist: WO 9 605 817 (Medinova SF; appl. 29.2.1996; GB-prior. 23.8.1994) I 1972 T Tazanolast dosage forms: US 5 330 762 (Alza Corp.; appl. 19.7.1994; USA-prior. 27.1.1993). US 5 246 71 1 (Alza Corp.; appl. 21.9.1993; USA-prior. 27.2.1992, 10.9.1992). US 5 246 710 (Alza Corp.; appl. 22.9.1993; USA-prior. 27.2.1992, 10.9.1992). US 5 185 158 (Alza Corp.; appl. 9.2.1993; USA-prior. 27.2.1992). synergistic compositions with 8-hydroxy-2-(dipropy1amino)tetraline and idazoxan: US 5 124 346 (Pfizer; appl. 23.6.1992; USA-prior. 23.4.1991). synthesis of I: Kikuo, I. et al.: Chem. Pharm. Bull. (CPBTAL) 39, 2288 (1991). Wu et al.: J. Med. Chem. (JMCMAR) 15,477 (1972). Forrnulation(s): tabl. 5 mg, 10 mg Trade Narne(s): J: Sediel (Sumitorno) Tazanolast ATC: R03DX Use: antiallergic, antiasthmatic RN: 82989-25-1 MF: C,,H,,N,O, MW: 289.30 LD,,,: 1121 mgikg (M, i.v.); >4 glkg (M, p.0.); 11 19 mgikg (R, i.v.); >4 glkg (R, p.0.); >4 glkg (dog, p.0.) CN: oxo[[3-(lH-tetrazol-5-yl)phenyl]amino]acetic acid butyl ester NoN3, AcOH Sn, HCI QcN sodium ozide N-N 3-nitro- benzonitrile 5-(3-nitropheny1)- 3-(5-tetrazoly1)- tetrozole oniline (I) pyridine I + CI$O~CH3 + 0 oxolic ocid monochloride butyl ester I Tomnolast Reference(s): JP 82 01 1 975 (Wakamoto; appl. 21.1.1982; J-prior. 25.6.1980). JP 57 01 1 975 (Wakamoto; appl. 21.1.1982; J-prior. 21.1.1982; prior. 25.6.1980). synthesis of 3-(5-tetrazoly1)aniline I: McManus, J.M.; Herbst, R.M.: J. Org. Chem. (JOCEAH) 24, 1044 (1959). medical use as inhibitor of SRS-A-release: DOS 3 530 780 (Wakamoto; appl. 28.8.1985; J-prior. 24.12.1984, 29.3.1985). US 4 778 816 (Wakamoto; 18.10.1988; appl. 17.9.1985; J-prior. 24.12.1984, 29.3.1985). Tazarotene T 1973 Trade Namefs): J: Tazalest (Wakamoto; Tazanol (Torii; 1990). 1990). Tazarotene (AGN- 190 168) ATC: D05B Use: antipsoriatic, acnc therapeutic, rctinoid RN: 118292-40-3 MF: Cz1H2,NO2S MW: 351.47 CN: 6-[(3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl)ethynyl]-3-pyridinecarboxylic acid ethyl ester NoOH, acetone benzene <CH3 CH3 J-methyl- thiophenol 3-methyl- 2-butenyl 2-butenyl bromide phenyl sufide 4,4-dimethyl- acetyl 3,4-dihydro- chloride thiopyran (I) Cl I1 + lithium diisopropylamide diethyl chlorophosphate 6-ethynyl-4,4-dimethyl- 3.4-dihydro-2H-1 -benzo- thiopyran (111) ethyl 6-chloro- Tazorotene nicotinate Referencefs): EP 284 261 (Allergan Inc.; USA-prior. 13.3.1987). EP 284 288 (Allergan Inc.; USA-prior. 20.3.1987). US 5 089 509 (Allergan Inc.; USA-prior. 20.3.1989). Formulution(s): gel 0.5 mglg, 1 mg/g 1974 T Teclothiazide Trade Name(s): D: Zorac (Pharm-Allergan) GB: Zorac (Allergan) USA: Tazorac (Allergan) Teclothiazide (Tetrachlormethiazide; Trichlormethylhydrochlorothiazide) ATC: C03AX Use: diuretic RN: 4267-05-4 MF: CRH7Cl4N3O4S2 MW: 415.11 EINECS: 224-253-3 CN: 6-chloro-3,4-dihydro-3-(trichloromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide I ,I -dioxide 5-chloro-2,4-di- chloral sulfornoyloniline (cf. chlorothiozide synthesis) Teclothiozide I Reference(s): Novello, F.C. et al.: J. Org. Chem. (JOCEAH) 25, 970 (1960). Close, W.J. et al.: J. Am. Chem. Soc. (JACSAT) 82, 1 132 (1960). Farmulatiort(s): tabl. 18 mg Trade Namr(s): F: Chymodrex (Pharmuka)- comb.; wfm Tegafur (Ftorafur) ATC: LOIBC03 Use: antineoplastic RN: 17902-23-7 MF: C,H9FN203 MW: 200.17 EINECS: 241-846-2 LD,,,: 800 mdkg (M, i.v.); 775 mglkg (M, p.0.); 685 mg/kg (R, i.v.); 930 mglkg (R, p.0.);. 34 mglkg (dog, p.0.) CN: 5-fluoro-I -(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidined1one monosodium salt RN: 28721-46-2 MF: C,H,FN,NaO, MW: 222.15 pyndine, CaCI2. 105- 1 10 OC I + CO Tegafur 2.3-dihydro- furan El Reference(s): a US 3 635 946 (S. A. Giller el al.; 18.1.1972; appl. 21.12.1967,22.7.1969). US 3 912734 (S. A. Giller et al.; 14.10.1975; appl. 1.6.1973; SU-prior. 20.11.1972). GB 1 168 391 (Inst. Organitschesk. sinteza, Riga; appl. 8.1.1968). DAS 1 695 297 (Inst. Organitschesk. sinteza, Riga; appl. 10.1.1968). US 4 039 546 (S. A. Giller et al.; 2.8.1977; appl. 28.4.1975). GB 1 503 614 (Univ. of Utah; appl. 14.4.1975; USA-prior. 6.5.1974). US 4 107 162 (Asahi; 15.8.1978; J-prior. 10.1 1.1975). with dimethyldichlorosilane: DOS 2 834 698 (Toshin Chemical; appl. 8.8.1978; J-prior. 19.9.1977, 14.12.1977). b DOS 2653 398 (Takeda; appl. 24.1 1.1976; J-prior. 28.1 1.1975; 19.1.1976; 13.7.1976). DOS 2 657 709 (Takeda; appl. 20.12.1976; J-prior. 25.12.1975). DOS 2 709 838 (Nikken Chemical; appl. 7.3.1977; J-prior. 26.61976, 28.8.1976). US 4 121 037 (Nikken Chemical; 17.10.1978; J-prior. 26.6.1976, 28.8.1976). DOS 2 709 839 (Nikken Chemical; appl. 7.3.1977; J-prior. 23.6.1976). GB 1 522 860 (Mitsui Toatsu; appl. 7.12.1976; J-prior. 24.12.1975,9.l. 1976, 22.1.1976, 20.5.1976). DOS 2 744 956 (ABIC; appl. 6.10.1977: IL-prior. 12.10.1976). US 4 159 378 (Toshin Chemical; 26.6.1979; J-prior. 19.9.1977, 14.12.1977). alternative synlhesis (also suitable for optical antipodes): WS 2723 450 (Roche; appl. 24.5.1977; A-prior. 28.5.1976). further syntheses: Yasumoto, M. et al.: J. Med. Chem. (JMCMAR) 21, 738 (1978). DOS 2 648 239 (Rikagaku Kenkyusho; appl. 25.10.1976; J-prior. 24.lO.l975,4.12.lV75,5.l.lV76, 15.3.1976, 11.5.1976). Formulation(s): tabl. 2.5 mg, 5 mg, 10 mg Trade Name(s): 1: Citofur (Lusofarrnaco) I: Coparogin (Nippon Chemiphar) Daiyalose (Daito) Exonal (Toyama) Fental (Kanebo) FH (Mitsui) Filacul (Torii) Flopholin (Tsuruhara) Franroze (Hishiyama) FTR (Tenyosha) Fulaid (Takeda) Fulfeel (Kyorin) Furofluor (Green Cross) Furofutran (Taiyo) Futol-P (Teisan) Futraful (Taiho) Geen (Taturni) Helpa (Teikoku) Helpa Taito (Pfizer) Icalus (Isei) Lamar (Tokyo Tanabe) Natira U (Mohan) Neberk (Fuji) Nitobanil (Kyowa) Pharmic (Toyo Pharmar) Rescrel (Nikken) 1976 T Tegafur-Uracil Rial (Toa Eiyo) Richina (Takata) Sinoflurol (Kaken) Tefsiel C (Towa) Sunfural (Toyo Jozo) Youfural (Showa) Tegafur-Uracil ATC: LOIBC03 Use: antineoplastic RN: 74578-38-4 MF: C,H,FN20, . C,H4N,02 MW: 3 12.26 LD,,: 1275 mgkg (M, p.0.); 1580 mgkg (R, p.0.); 150 mglkg (dog, p.0.) CN: 5-fluoro- I -(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione mixt. with 2,4(1 H,3H)-pyrimidinedione Tegofur Urocil (4. v.) ~~56 046 8 13 (Taiho; appl. 27.9.1979). Yamamoto, J. et al.: Arzneim Forsch. (ARZNAD) 31, 1276 (1981). Formulation[s): cps. 100 mg; drg. 100 mg in comb. with 224 mg uracil Trade Name(s): J: UFT (Miguel-Otsuka) Teicoplanin (Teichomycin) ATC: JOI XA02 Use: antibacterial, antibiotic RN: 61036-62-2 MF: C41.43HSI.53C1N4017~ MW: unspecified LD,,,: 715 mglkg (M, i.v.); 160 mglkg (R, i.v.); >900 mg/kg (dog, i.m.); 750 mgkg (dog, i.v.) CN: teicoplanin Teichomycin A, RN: 61 036-63-3 MF: unspecified MW: unspecified Teichomycin A2 RN: 61036-64-4 MF: unspecified MW: unspecified LD,,,: 275 mglkg (M, i.v.); >1 g/kg (M, p.0.) compound R formula Teicoplonin A 2-1 Teicoplonin A 2-2 Teicoplonin A 2-3 Teicoplanin A 2-4 Teicoplonin A 2-5 Reference(s): DE 2 608 216 (Lepetit; appl. 28.2.1976; GB-prior. 5.3.1975). US 4 239 751 (Lepetit; 16.12.1980; GB-prior. 5.3.1975). Parenti, F. et al.: J. Antibiot. (JANTAJ) 31, 276 (1978). Bardone, M.R. et al.: J. Antibiot. (JANTAJ) 31, 170 (1978). Coronelli, C. et al.: 1. Antibiot. (JANTAJ) 37, 621 (1984). Borghi, A. et al.: 1. Antibiot. (JANTAJ) 37, 615 (1984). 1978 T Telmesteine isolation of teichomycin A, factors: US 4 542 018 (Lepetit; 17.9.1985; appl. 7.6.1983; GB-prior. 8.6.1982). Formulation(s): vial 100 mg, 200 mg, 400 mg (lyo.) Trade Name(s): D: Targocid (Hoechst; 1989) GB: Targocid (Hoechst; 1990) I: Targosid (Hoechst Marion F: Targocid (Marion Merrell) Roussel) Telmesteine RN: 122946-43-4 MF: C,H,,NO,S MW: 205.23 LDs,,: 415 mglkg (R, i.p.); >4000 mg/kg (R, p.0.) CN: (R)-3,4-thiazolidinedicarboxylic acid 3-ethyl ester (R)-4-thiazolidine- ethyl carboxylic acid chloroformate Reference(s): US 4 874 776 (Yason; 17.10.1989; appl. 11.7.1988) lysine salt: EP 348 541 (Yason; appl. 29.6.1988). Formulation(s): sachets 300 mg; syrup 3 % ATC: ROSCB Use: mucolytic agent Telmesteine I Trade Name(s): I: Muconorm (Prospa Italia) Reolase (Pulitzer) Telmisar tan (BIBR 277; BIBR 277SE) ATC: C09CA07 Use: antihypertensive, angiotensin 11 receptor blocker RN: 144701 -48-4 MF: C3,H,,N4O2 MW: 514.63 CN: 4'-[(I ,4'-Dimethyl-2'-propy1[2,6'-bi-1H-benzimidazol]-l'-yl)methyl][l,l'-biphenyl]-2-carboxylic acid methyl 4-amino-3- butyryl methylbenzaote chloride Telmisartan T 1979 methyl 4-butyrornido- 3-methyl-5-nitrobenzoate methyl 2-propyl-4- rnethylbenzimidazole 6-corboxylote (11) H 1. 'NH* NoOH, CH30H/H20 2. PPA. 150°C I1 1. N-methyl-a- phenylenediomine 2. polyphosphoric ocid 4-methyl-6-(1 -methyl- tert-butyl 4'-(bromo benzimidazol-2-yl)-2- rnethy1)biphenyl-2- propylbenzirnidazale (In) corboxylate acetic ocid HOOC Telmisartan ~ies, U. et al.: J. Med. Chem. (JMCMAR) 36,4040-4051 (1993) EP502 314 (Thomae; 9.9.1992; appl. 31.1.1992; D-prior. 6.2.1991) DE4 408 497 (Thomae; 21.9.1995; appl. 14.3.1994; D-prior. 14.3.1 994) use for the treatment ofa condition associated with hylmia or unpaired metabolic function: WO 9 920 260 (Eurogene Ltd.; appl. 19.10.1998; GB-prior. 17.10.1997) use to treat symptomatic heart failure: WO 9 830 216 (Merck + Co.; appl. 7.1.1998; USA-prior. 10.1 .l997) method to treat cardiojibrosis with a combination ofan ATII-antagonist and spironolactone: W09 640 256 (G. D. Searle; appl. 5.6.1996; USA-prior. 7.6.1995) Fomulation(s): tabl. 40 mg, 80 mg Trade Name(s): D: Micarhs (Boehringer Ingelheim; 1998) 1980 T Temafloxacin Temafloxacin ATC: JOIMAOS (TA- 167) Use: quinolone antibacterial, gyrase inhibitor RN: 108319-06-8 MF: C2,H,,F3N303 MW: 417.39 CN: 1-(2,4-difluoropheny1)-6-fluoro- 1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid monohydrochloride RN: 105784-61-0 MF: C2,H,,F3N303. HCl MW: 453.85 2,4-dichloro-5- diethyl carbonate fluoroacetophenone 1. Ac20 2.H2N& - 2. 1. NaH NaOH rCH3 1 + F A I1 ~~c-0 oncH3 2. 2,4-difluoro- aniline clmo F v cb 0 0 triethyl orthoformate COOH ethyl 2-(2.4-dichloro-5-fluoro- benzoy1)-3-(2.4-difluoro- aniline)-2-propenoate CH3 1. @ 2. NoOH ___* 0 7-chloro-1-(2.4-difluoro- N1-ethoxycorbonyl- phenyl)-6-fluoro-1.4- 2-methylpiperazine dihydro-4-0x0-3-quinoline- corboxylic acid (11) Reference(s): EP 13 1 839 (Abbott; appl. 3.7.1984; USA-prior. 18.7.1983). Temafloxocin US 4 730 000 (Abbott; 8.3.1988; prior. 18.7.1983; 9.4.1984, 6.12.1984,7.10.1985,4.8.1987). EP 350 950 (Abbott; appl. 14.7.1989; USA-prior. 15.7.1988). medicul use for treatment of AIDS related infections: EP 437 128 (RhBne-Poulenc; appl. lO.12.1990; F-prior. 1 1.12.1989). i.v. formulation with improved tolerability: WO 9 109 525 (Abbott; appl. 20.12.1990; USA-prior. 29.12.1989). Formulation(s): tabl. 300 mg, 400 mg, 600 mg (as hydrochloride) Trude Nume(s): GB: Teflox (Abbott; ICI; 1991); USA: Omniflox (Abbott-Zeneca); wfm wfm . ethyl 2-( 2.4-dichloro-5-fluoro- benzoy1 )-3 -( 2.4-difluoro- aniline )-2 -propenoate CH3 1. @ 2. NoOH ___* 0 7-chloro- 1-( 2.4-difluoro- N1-ethoxycorbonyl- phenyl )-6 -fluoro-1. 4- 2-methylpiperazine. 10831 9-0 6-8 MF: C2,H,,F3N303 MW: 417.39 CN: 1-( 2,4-difluoropheny1 )-6 -fluoro- 1,4-dihydro- 7-( 3-methyl-1-piperazinyl )-4 -oxo-3-quinolinecarboxylic acid monohydrochloride RN: 10578 4-6 1-0 MF:. RN: 426 7-0 5-4 MF: CRH7Cl4N3O4S2 MW: 415.11 EINECS: 22 4-2 5 3-3 CN: 6-chloro-3,4-dihydro- 3-( trichloromethyl )-2 H-1,2,4-benzothiadiazine-7-sulfonamide I ,I -dioxide 5-chloro-2,4-di- chloral