Tiludronate disodium T 2041 tetroisopropyl methylenedi- phosphonote 1. 12N oq. HCI 2. oq. NoOH 1- tetroisopropyl (4-chloro phenylthio)methylenedi- phosphonote (1) ONa HO-P-ONa II 0 Tiludronote disodium Ohnishi, H.; Nakamura, T.; Tsurukami, H.; Murakami, H.; Abe, M.; Barbier, A,: Bone Miner. (BOMIET) 25 (Suppl. I), Abstr. 11 (1994). synthesis: EP 100 718 (Sanofi; appl. 25.7.1983; F-prior. 29.7.1982). monohydrate of the disodium salt: EP 582 515 (Elf Sanofi; appl. 3.8.1993; F-prior. 5.8.1992). pharmaceutical preparations: WO 9 617 616 (Sanofi; appl. 5.12.1995; F-prior. 6.12.1994). WO 9 641 618 (Sanofi Winthrop; appl. 4.6.1996; USA-prior. 8.6.1995). pharmaceutical compositions: W09 530 421 (Ciba-Geigy AG; appl. 16.1 1.1995; GB-prior. 4.5.1994). JP05 105 632 (Meiji Seika Kaisha; appl. 27.4.1993; J-prior. 6.6.1991). EP 336 851 (Sanofi; appl. 11.10.1989; F-prior. 7.4.1988). combinations: with estrogenes for treatment of osteoporosis: WO 9 214 474 (Norwich Easton Pharmaceuticals; appl. 3.9.1992; USA-prior. 26.2.1991). WO 9 414 455 (Merck & Co.; appl. 7.7.1994; USA-prior. 23.1 2.1992). with parathyroid hormone for treatment of osteoporosis: WO 9 607 418 (Procter and Gamble Company; appl. 14.3.1996; USA-prior. 9.9.1994). WO 9 607 417 (Procter and Gamble Company; appl. 14.3.1996; USA-prior. 9.9.1994). with growth hormone secretagogues for treatment of osteoporosis: W09 511 029 (Merck & Co.; appl. 27.4.1995; USA-prior. 19.10.1993). Formulation(s): tabl. 200 mg, 240 mg (as sodium salt hemihydrate) Trade Name(s): D: Skelid (Sanofi Winthrop) F: Skelid (Sanofi Winthrop) USA: Skelid (Sanofi) 2042 T Timepidium bromide Timepidium bromide ATC: A03 Use: antispasmodic, anticholinergic RN: 35035-05-3 MF: C,,H2,BrNOS2 MW: 400.41 LD,,,: 12 mglkg (M, i.v.); 713 mgkg (M, p.0.); 7 mglkg (R, i.v.); 1213 mglkg (R, p.0.) CN: 3-(di-2-thienylmethylene)-5-methoxy-1,1-dimethylpiperidinium bromide 1. CH30H. HCI CuSO,, Cu 3. H Raney-Ni 2.,~ C HOfiCOOH 2. dimethyl 3 \o&o 0 'CH, sulfate 5-bromo- nicotinic acid methyl N-methyl-5- methoxynipecotate (1) 1. HCI MgBr THF '0 - 2-thienyl- Timepidium bromide magnesium bromide Reference(s): US 3 764 607 (Tanabe Seiyaku; 9.10.1973; appl. 3.6.1971; J-prior. 11.6.1970). FR 2 100 750 (Tanabe Seiyaku; appl. 28.4.1972; J-prior. 11.6.1970). DOS 2 128 808 (Tanabe Seiy-aku; appl. 9.6.1971; J-prior. 11.6.1970). Kawazu, M. et al.: J. Med. Chem. (JMCMAR) 15,914 (1972). Formulation(s): cps. 30 mg; vial 7.5 mg Trade Name(s): I: Mepidium (Recordati; J: Sesden (Tanabe Seiyaku; 1987); wfm 1976) Timiperone ATC: NOSAK Use: neuroleptic, antipsychotic RN: 57648-21-2 MF: C22H,4FN,0S MW: 397.52 EINECS: 260-880-9 LD,,,: 500 mglkg (M, p.0.); >I 2.1 mglkg (R, i.v.); 232 mglkg (R, p.0.); 20 mgkg (dog, i.v.1; 85 mglkg (dog, p.0.) CN: 4-[4-(2,3-dihydro-2-thioxo- 1 H-benzimidazol-1 -yl)- 1 -piperidinyl]- 1 -(4-fluoropheny1)- 1-butanone Timolol T 2043 4-chloro-4'-iluoro- ethylene butyrophenone glycol (cf. haloperidol synthesis) H H Hz. Roney-Ni Cs2 __* carbon disufide H 4-(2-nitro- anilina)- piperidine (n) 1 Timiperone 1. Hz, Roney-Ni 2. CS2. KOH KI, H,WOH 1 + 11 , 3 Ht ' \ potassium iodide, - 1 -buton01 F NO2 Referencefs): DOS 2 526 393 (Daiichi Seiyaku; appl. 13.6.1 975). US 3 963 727 (Daiichi Seiyaku; 15.6.1976; J prior. 6.6.1975). Sato, M. et al.: J. Med. Chem. (JMCMAR) 21, 11 16 (1978). alternative syntheses: Sato, M.; Arimoto, M.: Chem. Pharm. Bull. (CPBTAL) 30,719 (1982). Trade Narnefs): J: Tolopelon (Daiichi Seiyaku; 1984) Timolol ATC: C07AA06; C07BA06; C07DA06; SOlEDOl Use: beta blocking agent, antiglaucoma agent, antianginal, antiarrhythmic RN: 26839-75-8 MF: C,,H,,N,O,S MW: 316.43 EINECS: 248-032-6 CN: @)-]-[(I ,I-dimethylethyl)amino]-3-[[4-(4-morpholiny1)- 1,2,5-thiadiazol-3-yl]oxy]-2-propanol 2044 T Timolol maleate RN: 26921-17-5 MF: C,3H,N40,S . C4H404 MW: 432.50 ,s. N,s. N&N + "2 - &N -, NoOH Q CI CI c' Q H0 Q 3.4-dichlaro- rnorpholine 3-chloro-4- 3-hydroxy-4- 1.2.5-thiodiozole morpholino- morpholino- 1.2.5- 1,2,5-thiadiazole (I) thiadiazole (11) epichlorohydrin rocemote resolution with (+)-tortark acid N_______, I Timolol OHC<OH + IIl H*, Pd-C OH CH3 D-glycer- S-(-)-1 -tert-butyl- aldehyde amino-2.3-propanediol (V) isopropylidene- D-glyceroldehyde Reference(s): US 3 619 370 (C. E. Frosst & Co.; 9.11.1971; appl. 21.4.1969). DOS 1 925 956 (C. E. Frosst & Co.; appl. 21.5.1969; USA-prior. 21.4.1969). DOS 1 925 954 (C. E. Frosst & Co.; appl. 21.5.1969; USA-prior. 21.4.1969). US 3 655 663 (C. E. Frosst & Co.; 11.4.1972; appl. 21.4.1969; prior. 22.5.1968). DAS 1 925 956 (C. E. Frosst & Co.; appl. 21.5.1969; USA-prior. 22.5.1968, 21.4.1969). DOS 1 925 955 (C. E. Frosst & Co.; appl. 21.5.1969; USA-prior. 21.4.1969). US 3 657 237 (C. E. Frosst & Co.; 18.4. 1972; appl. 21.4.1969). US 3 718 647 (C. E. Frosst & Co.; 27.2.1973; USA-prior. 21.4.1969, 16.8.1971). US 3 729 469 (C. E. Frosst & Co.; 24.4.1973; prior. 22.5.1968, 21.4.1969,9.9.1971). US 3 812 182 (C. E. Frosst & Co.; 21.5.1914; piorL21.4.19~9,16.8.1971. 1&6.LP73L - - - - - - - - - - Timonacic T 2045 alternative synthesis: US 4 145 550 (Merck Sharp & Dohme; 20.3.1979; prior. 7.8.1975, 8.2.1977, 21.9.1977). 0-acyl-derivatives: US 3 891 639 (Merck Sharp & Dohme; 24.6.1975; appl. 19.4.1973). US 4011 217 (Merck Sharp & Dohme; 8.3.1977; appl. 26.2.1975; prior. 19.4.1973). combinations with diuretics: US 4 178 374 (Merck & Co.; 11.12.1979; prior. 16.8.1974,3.3.1975, 21.10.1976, 10.4.1978). GB 1 495 034 (Merck & Co.; appl. 11.8.1975; USA-prior. 16.8.1974, 3.3.1975). medical use for treatment of glaucoma: GB 1 524 405 (Merck & Co.; appl. 23.9.1976; USA-prior. 26.9.1975). Fonulation(s): eye drops 1 mg/ml, 2.5 mg/ml, 5 mglml, 1 mg/ml (as maleate); tabl. 5 mg, 10 mg, 20 mg (as maleate); tabl. 25 mg in comb. with hydrochlorothiazide Trade Name(s): D: Arutimol (Chauvin ankerpharm) Chibro-Timoptol (Chibret; 1979) dispatim (CIBA Vision) duratimol (durachemie) Moducrin (Merck Sharp & Dohme; 1978)-comb. Timo-COMOD (Ursapharm) Timo ED0 (Mann) Timohexal (Hexal) Timolol-ratiopharm (ratiopharm) Timomann (Mann) Tim-Ophthal (Winzer) Timosine (Chibret) Timo-Stulln (Pharma Stulln) F: Digaol (Leurquin) Gaoptol (Eurphta) Moducren (Merck Sharp & I: Dohme-Chibret)-comb. Nyolol (CIBA Vision Ophthalmics) Ophtim (ThCa) Timabak (ThCa) Timacor (Merck Sharp &. Dohme-Chibret) Timoptol (Merck Sharp & Dohme-Chibret) numerous combination preparations J: GB: Betim (Leo; as maleate) USA: Blocadren (Merck Sharp & Dohme; 1974) Glaucol (Baker Norton) Moducren (Morson)-comb. Prestim (Leo)-comb. Timoptol (Merck Sharp & Dohme) Blocadren (Merck Sharp & Dohme) Cusimolol (Alcon) Droptimol (Farmigea) Equiton (Bruschettini)- comb. Oftimolo (Farm~la) Timicon (Merck Sharp & Dohme)-comb. Timoptol (Merck Sharp & Dohme) Timoptol (Merck-Banyu) Blocadren (Merck Sharp & Dohme; 1983) Timolide (Merck Sharp & Dohme; 1981) Timoptic (Merck Sharp & Dohme; 1978) generics Timonacic (Thiazolidincarbonsaure) ATC: A05 Use: liver therapeutic, choleretic RN: 444-27-9 MF: C4H7N02S MW: 133.17 EINECS: 207-146-6 LD,,: 400 mglkg (M, p.0.); 875 mg/kg (R, p.0.) CN: 4-thiazolidinecarboxylic acid arginine salt RN: 57631-15-9 MF: C4H7N02S . C6HI4N4O, MW: 307.38 L-cysteine forrnoldehyde ( Tirnonocic I 2046 T Tinazoline hydrochloride Reference(s): FR-M 3 184 (Sogespar; appl. 4.2.1963). Formulation(s): drinking amp. 100 mg (as arginine salt); tabl. 400 mg Trade Name(s): F: Hkpalidine (Riker- Tiadilon (Dexo; as arginine Tiazolidin (Solvay Pharma) Mediarik) salt) Thiohiline (Riker); wfm I: Sulfile (Poli) Tinazoline hydrochloride ATC: ROlA Use: vasoconstrictor, nasal decongestant RN: 55107-60-3 MF: C,,HIIN,S~ HCI MW: 253.76 CN: 3-[(4,5-dihydro-IH-imidazol-2-yl)thio]-1 H-indole rnonohydrochloride tinaznline RN: 62882-99-9 MF: CIIHllN3S MW: 217.30 ethylene diomine ethylene- thiourea tinomline hydriodide (I) ion exchange (Amberlite IRA 400) I I Tinazoline hydrochloride I DOS 2 427 207 (Ciba-Geigy; appl. 6.5.1974; CH-prior. 14.6.1973). Nagarajan, N. et al.: Indian J. Chem. (IJOCAP) 20B, 672 (1981). synthesis of ethylenethiourea: DOS 2 703 31 2 (Bayer, appl. 27.1.1977). Trade Nume(s): IN: Varsyl (Ciba-Geigy; 1988) Tinidazole ATC: JOIXD02; POlAB02 Use: chemotherapeutic (trichomonas), antiprotozoal, antiamebia RN: 19387-91-8 MF: CRH,,N,04S MW: 247.28 EINECS: 243-014-4 LD,,,: >250 mglkg (M. i.v.); 3200 mglkg (M, p.0.); >250 mglkg (R, i.v.); 2710 mglkg (R, p.0.) CN: 1 -[2-(ethylsulfo1~yl)ethyI]-2-methyl-5-nitro-lH-imidazole Tinoridine T 2047 p-toluenesulfonyl 2-(ethylsulfonyl) chloride ethanol 2-methyl-5- nitroirnidozole 2-(ethylsulfonyl)ethyl p-toluenesulfonote (I) Tinidozole Reference(s): US 3 376 31 1 (Pfizer; 2.4.1968; appl. 5.8.1966; prior: 26.10.1964). DAS 1 745 780 (Pfizer; appl. 8.2.1967; USA-prior. 5.8.1966). Miller, M.W. et al.: J. Med. Chem. (JMCMAR) 13, 849 (1970). Formulation(s): f. c. tabl. 1 g Trade Name(s): D: Simplotan (Pfizer; 1971) I: Fasigin N (Pfizer) USA: Fasigyn (Pfizer); wfm F: Fasigyne 500 (Pfizer) Trimonase (Tosi-Novara) Simplotan (Pfizer); wfm GB: Fasigyn (Pfizer; 1982) J: Fasigyn (Pfizer Taito) Tinoridine ATC: M01; NO2 Use: analgesic, anti-inflammatory RN: 24237-54-5 MF: C,7H2,N202S MW: 316.43 EINECS: 246-102-0 LD,,: 5.4 gkg (M, p.0.); >10.2 glkg (R, p.0.) CN: 2-amino-4,5,6,7-tetrahydro-6-(phenylmethyl)th1eno[2,3-]pyridine-3-carboxylic acid ethyl ester monohy drochloride RN: 25913-34-2 MF: C,7H2,N202S . HC1 MW: 352.89 EINECS: 247-342-9 LD,,,: 1601 mgkg (M, p.0.); 1200 mgkg (R, p.0.) A S. OdH, C2H50H + Nc'-'fowCH3 - 0 sulfur, rnorpholine 1 -benzyl-4- ethyl cyono piperidone ocetote Tinoridine DE 1 812 404 (Yoshitomi; appl. 3.12.1968; J-prior. 4.12.1967). US 3 563 997 (Yoshitomi; 16.2. 1971; J-prior. 4.12.1967). Formulation(s): cps. 50 mg, 100 mg (as hydrochloride) 2048 T Tiocarlide Trade Name(s): J: Nonflamin (Yoshitomi) Tiocarlide (Thiocarlide) ATC: J04AD02 Use: tuberculostatic, leprostatic RN: 91 0-86- 1 MF: C23H32N202S MW: 400.59 EINECS: 213-006-5 CN: N,hr-bis[4-(3-methylbutoxy)phenyl]thiourea isopentyl 4-nilrophenol 4-isopentyloxy- 1 - bromide sodium salt nitrobenzene 4-isopentyloxy- I Tiocarlide aniline (I) Re&rence(s): US 2 703 815 (Ciba; 1955; appl. 1951). Trade Name(s): GB: Isoxyl (Continental I: Isoxyl (Lusofarmaco); wfm Pharma); wfm Tioclomarol ATC: BOLAAI I Use: anticoagulant RN: 22619-35-8 MF: C22H,6C1204S MW: 447.34 EINECS: 245-132-1 CN: 3-[3-(4-chlorophenyl)-I-(5-chloro-2-thienyl)-3-hydroxypropyl]-4-hydroxy-2H-l-ben~opyran-2-one CHO ~)5 CI H20, C2H50H dioxane, piperidine +I 4-hydroxy- CI coumarin 4'-chloro- 2-chlaro-5- acetophenone thiophene- carboxoldehyde 1" Tioconazole T 2049 AI[O-CH(CH3)2]3, isoproponol b oluminum isopropylote Tioclomorol Reference(s): ZA 6 707 267 (Lipha; appl. 7.8.1968; F-prior. 13.1 1.1967; 13.12.1966) Formulation(s): tabl. 4 mg Trade Name(s): F: Apegmone (Lipha SantC) Tioconazole ATC: DO1 ACO7; GO I AFO8 Use: antimycotic, topical antifungal RN: 65899-73-2 MF: C,,H,3C13N,0S MW: 387.72 EINECS: 265-973-8 LD,,: 1870 mgkg (M, p.0.); 770 mglkg (R, p.0.) CN: 1-[2-[(2-chloro-3-thienyl)methoxy]-2-(2,4-dichlorophenyl)ethyl]-lH-imidazole L) hydride 1 -(2,4-dichloro- 2-chloro-3- phenyl)-2- (chloromethyl) (1H-imidazol-1 -yl)- thiophene ethanol (cf. miconozole synthesis) DE 2 619 381 (Pfizer; appl. 30.4.1976; GB-prior. 30.4.1975). US 4 062 996 (Pfizer; 13.12.1977; appl. 30.4.1976; GB-prior. 30.4.1 975) Formulation(s): cream 10 mglg; lotion 10 mglg; ointment vaginal 6.5 %; powder 1 g1100g; spray 1 g1100g Trade Name(s): D: Mykontral (LAW) Trosyd (Pfizer; 1986) J: Trosy (Taito Pfizer; 1984) Trosyl (Pfizer); wfm GB: Trosyl (Pfizer; 1988) USA: Vagistat (Bristol-Myers F: Gyno-Trosyd (Pfizer; 1986) I: Trosyd (Roerig) (Irbi) Squibb) 2050 T Tioguanine Tioguanine (Thioguanine) ATC: LOlBB03 Use: antineoplastic RN: 154-42-7 MF: C,H,NSS MW: 167.20 EINECS: 205-827-2 LD,,,: 160 mglkg (M, p.0.) CN: 2-amino-l,7-dihydro-6H-purin-6-thione S p2s5 phosphorus pentosulfide guanine 1 Tioguonine 1 Refirence(s): US 2 697 709 (Burroughs Wellcome; 1954; GB-prior. 1951). US 2 884 667 (Burroughs Wellcome; 1959; prior. 1955). US 2 800 473 (Burroughs Wellcome; 1957; appl. 1955). US 3 019 224 (Burroughs Wellcome; 1962; appl. 1955). US 3 132 144 (Burroughs Wellcome; 5.5.1964; appl. 10.7.1959). Elion, G.B.; Hitchings, G.H.: J. Am. Chem. Soc. (JACSAT) 77, 1676 (1955). Formulation(s): tabl. 40 mg Trade Name(s): D: Thioguanh-Wellcome 1: Thioguanine Wellcome USA: Thioguanine Tablo~d (Glaxo Wellcome) (Claxo Wellcome) (Glaxo Wellcome) GB: Lanvis (Glaxo Wellcome) Tiomesterone (Thiomesterone) ATC: A14 Use: anabolic, androgen RN: 2205-73-4 MF: C2,H3,04S2 MW: 450.66 EINECS: 218-614-4 CN: (1 a,7a, 17P)-1,7-bis(acety1thio)- 17-hydroxy- 17-methylandrost-4-en-3-one 17p-hydroxy-17-methyl- thioocetic Tiornesterone 50x0- 1.4,6-androstotriene acid Reference(sJ: US 3 087 942 (Merck AG; 30.4.1963; D-prior. 29.10.1960). Kramer, J.M. et al.: Chem. Ber. (CHREAM) 96,2803 (1963), starting material: GB 854 343 (British Drug Houses; valid from 4.3.1959; prior. 13.3.1958). Formulation(s): 15 mg, 30 mg . anticoagulant RN: 2261 9-3 5-8 MF: C22H,6C1204S MW: 447.34 EINECS: 24 5-1 3 2-1 CN: 3-[ 3-( 4-chlorophenyl)-I-(5-chloro-2-thienyl )-3 -hydroxypropyl ]-4 -hydroxy-2H-l-ben~opyran-2-one CHO ~)5 CI H20,. androgen RN: 220 5-7 3-4 MF: C2,H3,04S2 MW: 450.66 EINECS: 21 8-6 1 4-4 CN: (1 a,7a, 17P )-1 ,7-bis(acety1thio )- 17-hydroxy- 17-methylandrost-4-en-3-one 17p-hydroxy-17-methyl- thioocetic Tiornesterone. (dog, p.0.) CN: 4-[ 4-( 2,3-dihydro-2-thioxo- 1 H-benzimidazol-1 -yl )- 1 -piperidinyl ]- 1 -( 4-fluoropheny1 )- 1-butanone Timolol T 2043 4-chloro-4'-iluoro- ethylene butyrophenone glycol