Pharmaceutical Substances Syntheses, Patents, Applications - Part 208 potx

Toliprolol T 2071 2-bromo- oniline, copper Tolfenomic ocid benzoic acid Reference(s): US 3 313 848 (Parke Davis; 11.4.1967; prior. 18.6.1964). Formulation(s): cps. 100 mg, 200 mg; s. r. tabl. 300 mg Trade Name(s): J: Clotam (Tobishi Shingaku). Toliprolol ATC: C07AA Use: antiarrhythmic, antihypertensive, antianginal RN: 2933-94-0 MF: C13H21N02 MW: 223.32 EINECS: 220-905-6 LD,,: 28.2 mgkg (M, i.v.) CN: l-[(l-methylethyl)amino]-3-(3-methylphenoxy)-2-propanol hydrochIoride RN: 306-11-6 MF: C13H,,N02. HCl MW: 259.78 EINECS: 206-177-2 LD,,: 40 mgkg (M, i.v.) phenol hydrin 0xy)propylene oxide L l & + ~1% NOOH , &- H2N ,Y3 CH, CH3 0 CH3 isopropyl- omine 3-methyl- epichloro- 3-(3-methylphen- Reference(s): DOS 1 493 454 (Boehringer Ing.; appl. 26.8.1963). NL-appl. 6 409 883 (Boehringer Ing.; appl. 26.8.1963). y3 &TpH3 CH3 Toliprolol Formulation(s): tabl. 10 mg, 50 mg Trade Name(s): D: Doberol (Boehringer Ing.); wfm Tolmetin ATC: MOI ABO3; M02AA21 Use: anti-inflammatory RN: 26171-23-3 MF: C,sH15N03 MW: 257.29 EINECS: 247-497-2 LD,,,: 680 mglkg (M, i.v.); 914 mglkg (M, p.0.); 293 mglkg (R, p.0.) CN: 1-methyl-5-(4-methylbenzoy1)-1 H-pyrrole-2-acetic acid 2072 T Tolmetin sodium salt RN: 3571 1-34-3 MF: C,,H,,NNaO, MW: 279.27 EINECS: 252-687-3 LD,,,: >622 mgtkg (M, i.v.); 899 mgkg (M, p.0.); >724 mglkg (R, i.v.); 9 14 mg/kg (R, p.0.); >800 mg/kg (dog, p.0.) sodium saIt dihydrate RN: 64490-92-2 MF: C,,H14NNa0, .2H,O MW: 315.30 1-methyl- form- dirnethyl- Z-dirnethylarnino- (1) pyrrole oldehyde arnine methyl-1 -methyl- pyrrole chloride (1 -methyl-2- pyrroly1)- aceionitrile Reference(s): US 3 752 826 (McNeil; 14.8.1973; prior. 26.7.1967, 1.7.1968). DAS 1 770 984 (McNeil; appl. 25.7.1968; USA-prior. 26.7.1967, I .7.1968). Carson, J.R. et al.: J. Med. Chem. (JMCMAR) 14,646 (1971). GB 1 428 272 (McNeil; appl. 12.7.1973; USA-prior. 3.8.1972). DOS 2 102 746 (McNeil; appl. 21.1.197 1; USA-prior. 26.1.1970). DOS 2 339 140 (McNeil; appl. 2.8.1973; USA-prior. 3.8.1972). Friedel-Crafts-synthesis wifhout use of AlCl,: DAS 2 51 1 256 (Ethyl Corp.; appl. 14.3.1975; USA-prior. 18.3.1974). GB 1 503 205 (Ethyl Corp.; appl. 19.5.1975; USA-prior. 17.6.1974). GB 1 503 221 (Ethyl Corp.; appl. 6.3.1975; USA-prior. 18.3.1974). GB 1 503 222 (Ethyl Corp.; appl. 6.3.1975; USA-prior. 18.3.1974). allernarive syntheses: US 4 l 1 1 954 (McNeil; 5.9.1978; prior. 20.4.1977). US 4 119 639 (McNeil; 10.10.1978; appl. 27.6.1977). US 4 125 537 (McNeil; 14.1 1.1978; appl. 7.2.1977). DOS 2 552 975 (Sagami; appl. 7.12.1978; J-prior. 8.12.1977). ES 456 334 (Lab. Estedi S. L.; appl. 26.2.1977). combination with acetaminophen or acetylsalicylic acid: US 4 132 788 (McNeil; 2.1.1979; prior. 4.5.1976). Formulation(s): cps. 200 mg, 400 mg; tabl. 200 mg, 600 mg (as sodium salt) Tolnaftate T 2073 Trade Name(s): D: Tolectin (Cilag-Chemie; Reutol (Errekappa Tolmex (Biopharma); wfm 1977); wfm Euroter.); wfm J: Tolectin (Dainippon) GB: Tolectin (Ortho; 1979); Tolectin (Cilag); wfm USA: Tolectin (Ortho-McNeil; wfm Tolectin (Cilag-Chemie); 1976) I: Index (Edmond); wfm wfm Tolnaftate ATC: DOIAE18 Use: antimycotic, fungicide RN: 2398-96-1 MF: C,,H,,NOS MW: 307.42 EINECS: 219-266-6 LD,,,: 4800 mgkg (M, i.v.); 10 gkg (M, p.0.); >6 gkg (R, p.o.1; >14 gkg (dog, p.o.) CN: methyl (3-methylpheny1)carbamothioic acid.0-2-naphthalenyl ester toluidine 2-naphthol thiophosgene I Tolnaftate Reference(s): US 3 334 126 (Nippon Soda; 1.8.1967; J-prior. 21.6.1961,25.8.1961,9.4.1962, 13.4.1962). GB 967 897 (Nippon Soda; appl. 31.5.1962; J-prior. 21.6.1961, 25.8.1961,9.4.1962, 13.4.1962). Formulation(s): cream 10 mglg; powder 5 mglg; sol. 10 mglml Trade Name(s): D: Sorgoa (Scheurich) F: Sporiline (Schering- J: Alarzin "Strong" Tmatox (~renner-~feka) Plough) (Yamanouchi) Tolnaftat (Pharma GB: Tinaderm-M (Schering- Hi-Alarzin (Yamanomhi)- Wernigerode) Plough) comb. Tonoftal (Essex Pharma) I: Tinaderm (Schering- Separin T (Sumitomo) Plough) USA: Tinactin (Schering); wfm Tolonidine ATC: CO2ACO4 Use: antihypertensive RN: 4201-22-3 MF: C,,H,,C1N3 MW: 209.68 CN: N-(2-chloro-4-methylphenyl)-4,5-dihydro-1H-imidazol-2-amine nitrate RN: 4201-23-4 MF: C,,H,,ClN,. xHNO, MW: unspecified EINECS: 224-105-8 I-CH3. CH,OH HZN&,, + NH: SCN- . -I methyl iodide 2-chloro-4- ammonium N-(2-chloro-4-methyl- methylaniline thiocyanate pheny1)thiourea 2074 T Toloxatone Reference(s): GB 1 034 938 (Boehringer Ing.; valid from 28.9.1964; D-prior. 4.10.1963). (also further methods) Formularion(s): vial 0.5 mglml (as nitrate) Trade Nume(s): F: Euctan (Delalande); wfm Toloxatone ATC: N06AG03 Use: antidepressant, monoaminoxidase inhibitor RN: 29218-27-7 MF: C,,H,,NO, MW: 207.23 EINECS: 249-522-2 LD,,: 1300 mglkg (M, p.0.); 1225 mglkg (R, p.0.) CN: 5-(hydroxymethyl)-3-(3-methylphenyl)-2-oxazolidinone m-toluidine glycide NaOCH, I + 1 - H,C/'O 0-CH, diethyl corbonote 3-(m-toluidino)- 1.2-proponediol (I) Toloxotone I DOS 2 01 1 333 (Delalande; appl. 10.3.1970; GB-prior. 18.3.1969). DOS 2 012 120 (Delalande; appl. 13.13.1970; GB-prior. 18.3.1969). Fauvan, C.; Douzon, C.: Chim. Ther. (CHTPBA) 3, 324 (1973). Formulation(s): cps. 200 mg Trade Name(s): F: Humoryl (Synthtlabo; I: Umoril (Synthelabo) 1985) Tolperisone T 2075 Tolperisone ATC: M03BX04 Use: vasodilator, antispasmodic, skeletal muscle relaxant RN: 728-88-1 MF: C,6H,3N0 MW: 245.37 EINECS: 222-876-5 CN: 2-methyl-l-(4-methylphenyl)-3-(l-piperidinyl)-l-propanone hydrochloride RN: 3644-61-9 MF: C,,W2,NO . HCI MW: 281.83 LD,,,: 34 mglkg (M, i.v.); 358 mglkg (M, p.0.); 1450 mgkg (R, p.0.); 45 mgkg (dog, i.v.) 4'-rnethylpropio- poraform- piperidine phenone aldehyde hydrochloride Tolperisone Reference(s): JP 203 90165 (Eisai; appl. 4.1 1.1961). Ruddy, A.W.; Buckley, J.S.: J. Am. Chem. Soc. (JACSAT) 72,7 18 (1950). injection solution: DOS 2 362 337 (Gedeon Richter; appl. 14.12.1 973; H-prior. 15.1 .l973). Formulation(s): amp. 100 mg; drg. 50 mg, 150 mg; tabl. 50 mg, 100 mg, 500 mg (as hydrochloride) Trade Narnefs): D: Mydocalm (Strathmann) Kineore (Showa) Nichiperizone (Nissin) F: Mydocalm (Richter); wfm Lasmon (Tanabe) Roystajin (Zensei) J: Abbsa (Sanko) Magnine (Toyo) Sinorum (Towa) Atmosgen (Maruko) Menopatol (Nippon Besnoline (~otobuki: Chemiphar) Kanebo) Muscalm (Nippon Kayaku) Tolpropamine ATC: D04AA12 Use: antihistaminic, antiallergic RN: 5632-44-0 MF: Cl,Hz3N MW: 253.39 EINECS: 227-071-2 CN: N,N,4-trimethyl-y-phenylbenzenepropanamine hydrochloride RN: 3339-11-5 MF: Cl,Hz3N .HCI MW: 289.85 EINECS: 222-082-9 + (CH~O), + Hy'CH3 __* I CH3 bromide CH3 aceto- poraform- dirnethyl- 3-dimethylomino- phenone oldehyde ornine propiophenone 2076 T Tolrestat Reference(s): DE 925 468 (Hoechst; appl. 1941). Fortnulation(s): gel 1 % Trade Name(sJ: D: Brondilat (Albert-Rousse1)- Pragman-Gelee (Albert- comb.; wfm Roussel); wfm Brondiletten (Albert- I: Pragman Gelee (Albert- Rousse1)-comb.; wfm Farma); wfm Tolpropomine Pragman Gelee (Albert- Roussel); wfm J: Pragman Jelly (Tokyo Tanabe) Tolrestat (Tolrestatin) ATC: AlOXAOl Use: aWose reductase inhibitor (prophylaxis of diabetic neuropathy, retinopathy, cataract) RN: 82964-04-3 MF: C,,H,,F,NO,S MW: 357.35 CN: N-[[6-methoxy-5-(trifluoromethyl)-l-naphthalenyl]thioxomethyl]-N-methylglycine H3C-~ H3C.0 hydrogen iodide 1 iodide, copper CF3 methyl 6-methoxy 1 -nophtholene- carboxylate methyl 6-methoxy- 6-methoxy-5-(trifluoro- 5-iado- 1 -naphthalene- rnethyl)naphtholene-I - corboxylote corboxylic acid (1) 1. S0Cl2 1 2. NoOH 2. methyl N-methyl- '0 1. phosphorus glycinote CF3 pentosulfide H3C-0 CF3 methyl N-[[5-(tri1luoromethyl)- Tolrestot 6-methoxy-I -nophthyl]corbonyl]- N-methylglycinote 7 Tolterodine T 2077 Reference (s): EP 59 596 (Ayerst; appl. 24.2.1982; CND-prior. 15.10.1981). US 4 391 825 (Ayerst; appl. 5.7.1983; prior. 13.11.1981; CND-prior. 15.10.1981). US 4 568 693 (Ayerst; 4.2.1986; appl. 9.9.1983; prior. 13.1 1.1981; CND-prior. 2.3.1981). US 4 600 724 (Ayerst; 15.7.1986; appl. 17.7.1985; prior. 13.1 1.1981,9.9.1983; CND-prior. 2.3.1981). US 4 705 882 (Ayerst; 10.1 1.1987; appl. 28.3.1986; prior. 13.1 1.1981,9.9.1983, 17.7.1985; CND-prior. 2.3.1981). US 4 946 987 (Ayerst; 7.8.1990; appl. 20.6.1988; prior. 13.11.1981,9.9.1983, 17.7.1985,28.3.1986; CND-prior. 2.3.1981). Sestanj, K. et al.: J. Med. Chem. (JMCMAR) 27,255 (1984). synthesis of methyl 6-methoxy-1-naphthalenecarboxylate: Price, C.C. et al.: J. Am. Chem. Soc. (JACSAT) 69,2261 (1947). synthesis of 6-methoxy-5-(trifluoromethyl)naphthalene-l-carboxylic acid: EP 245 679 (Ethyl Corp.; appl. 24.4.1987; USA-prior. 12.5.1986). US 4 629 808 (Ethyl Corp.; 16.12.1986; appl. 20.6.1985). US 4 590 010 (Ethyl Corp.; 20.5.1986; appl. 18.4.1985). US 4 562 286 (Occidental Chem. Corp.; 31.12.1985; appl. 1.1 1.1984). US 4 560 794 (Occidental Chem. Corp.; 24.12.1985; appl. 1.1 1,1984). US 4 408 077 (Ayerst; 4.10.1983; appl. 13.1 1.1981). EP 59 596 (Ayerst; appl. 24.2.1982; CND-prior. l5.lO.l981,2.3.I98l). Sestanj, K. et al.: J. Med. Chem. (JMCMAR) 27, 255 (1984). pharmaceutical composition for treatment of diabetic complications: JP 61 078 725 (American Home; appl. 17.9.1985; USA-prior. 20.9.1984). medical use to improve hearing in diabetics: US 4 783 486 (American Home; 8.1 1.1988; appl. 6.1 1.1987). medical use to improve wound healing: US 4 751 243 (American Home; 14.6.1988; appl. 18.6.1986). medical use for treatment of periodontal disease: US 4731 380 (American Home; 153.1988; appl. 26.8.1986). medical use for stimulation of immune response: EP 256 629 (American Home; appl. 9.6.1987; USA-prior. 12.6.1 986). medical use as antihypertensive in diabetics: EP 245 951 (American Home; appl. 9.4.1987; USA-prior. 17.4.1986). Formulation(s): cps. 200 mg; tabl. 200 mg Trade Name(s): 1: Alredase (Wyeth; 1990); J: Tolrestat (Wyeth-Ayerst); wfm wfm Lorestat (Recordati; 1990); USA: Alredase (Wyeth-Ayerst); wfm wfm To1 terodine (Kabi 2234; PNU-200583) ATC: G04BD07 Use: agent for urinary incontinence, muscarinic receptor antagonist RN: 124937-51-5 MF: C,H,,NO MW: 325.50 CN: (R)-2-[3-[Bis(l-methylethyl)amino]-l-phenylpropyl]-4-methylphenol tartrate RN: 124937-52-6 MF: C2,H3,N0 . C4H606 MW: 475.58 2078 T Tolycaine K2CO3, CH30H. 6 + 9 H~SO,.IXW, acetone. H~C-I + I methyl iodide CH3 COOH p-crcsol cinnornic acid 1. LiAIH4, ~~c~0-c~~ o/T~~ CH3 CH3 methyl 3-(2-rnethoxy- (11) 5-methylphenyl)-3- phsnylpropionote (I) 1. CH3CN, A y3 2. BBr3. CH,C12 + HN CH3 - A 1. acetonitrile H,C CH3 2. boron tribromide CH.3 diisopropylornine L-(+)-tartaric acid _____+ Tolterodine - Reference(sJ: EP 325 571 (Kabi Vitrum; appl. 20.1 .l989; S-prior. 22.1.1988). pharmaceurical compositions containing anti-incontinence agents: WO 9 81 1 888 (American Home Products Corp.; appl. 17.9.1997; USA-prior. 19.9.1996) Formulation(sJ: f. c. tabl. 1 mg, 2 mg (as maleate) Trade Name(s): D: Detrusitol (Pharmacia & GB: Detrusitol (Pharmacia & USA: Detrol (Pharmacia & Upjohn; 1998) Upjohn) Upjohn) F: Detrusitol (Pharmacia & I: Detmsitii (Pharmacia & Upjohn) Upjohn) Tolycaine ATC: NOlRB Usc: local anesthetic RN: 3686-58-6 MF: C,,H2,N203 MW: 278.35 EINECS: 222-97G-9 CN: 2-[[(diethylamino)acetyl]aminol-3-methylnoc acid methyl ester monohydrochloride RN: 7210-92-6 MF: C,sH22N203 . HC1 MW: 3 14.8 1 EINECS: 230-590-7 LDSo: 60 mgkg (M, i.v.); 44 mgkg (R, i.v.) methyl 3-methyl- chloroocetyl onthronilate chloride Reference(s): DE 1 018 070 (Bayer; appl. 26.9.1955). Formulation(s): vial 0.0814 ml (as hydrochloride) Trade Narne(s1. . . D: Baycain (Bayer); wfm F: Campovit (Bayer-Pharma)- J: Baycain (Bayer) Tardocillin (Bayer)-comb. comb.; wfm Topiramate (KW-6485; McN-4853; RWJ- 17021-000) ATC: N03AXll Use: anticonvulsant RN: 97240-79-4 MF: C12H2,N0,S MW: 339.37 LD,,: >I500 mgkg (R, i.p.) CN: 2,3:4,5-bis-0-(1-methylethylidene)-~-~-fructopyranose sulfamate 8-D-tructo- ocetone pyranose 2,3:4.5-bis-0-(1 -methyl- ethylidene)-8-D-fructo- pyranose (I) CIS02NH2. NOH I. sulfamoyl chloride Topiromate 2080 T Topotecan 1. S02C12, pyridine 2. NoN5, ocetonitrile 3. Cu, CH,OH I Referencefs): a Maryanoff, B.E. et al.: J. Med. Chem. (JMCMAR) 30,880-887 (1987). EP 138 441 (McNeillab Inc.; appl. 25.9.1984; USA-prior. 26.9.1983, 11.2.1985). b EP 533 483 (McNeillab Inc.; appl. 18.9.1992; USA-prior. 19.9.1991,5.8.1992). Forrnularion(s): tabl. 50 mg, I00 mg, 200 mg Trade Narne(s): GB: Topamax (Janssen-Cilag) USA: Topamax (Ortho-McNeil) Topotecan (NSC-609669; SK&F-S 104864-A) ATC: LOlXX17 Use: antineoplastic, topoisomerase I- inhibitor RN: 123948-87-8 MF: C2,H2,N30, MW: 421.45 CN: (S)-lO-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-l H-pyrano[3',4':6,7]indolizino[1,2-blquinoline- 3,14(4H,12H)-dione monohy drochloride RN: 119413-54-6 MF: C2,H2,N,0,. HCI MW: 457.91 acetate RN: 123948-88-9 MF: CZ3Hz3N7O5. C2H402 MW: 481.51 dihydrochloride RN: 123949-07-5 MF: C,,H2,N,OS. 2HCI MW: 494.38 3. CH COOH, H 0 - 0 2. lead tetraacetote comptothecin 10-hydroxycomptothecin (1) Topotecan hydrochloride 1. CH,COOH FH3 2. HCI + H2C=0 + m, CH3 . mgkg (R, i.p.) CN: 2,3:4,5-bis- 0-( 1-methylethylidene )-~ -~ -fructopyranose sulfamate 8-D-tructo- ocetone pyranose 2,3:4.5-bis- 0-( 1 -methyl- ethylidene )-8 -D-fructo- pyranose (I) CIS02NH2 RN: 420 1-2 2-3 MF: C,,H,,C1N3 MW: 209.68 CN: N-(2-chloro-4-methylphenyl )-4 ,5-dihydro-1H-imidazol-2-amine nitrate RN: 420 1-2 3-4 MF: C,,H,,ClN,. xHNO, MW: unspecified EINECS: 22 4-1 0 5-8 I-CH3 skeletal muscle relaxant RN: 72 8-8 8-1 MF: C,6H,3N0 MW: 245.37 EINECS: 22 2-8 7 6-5 CN: 2-methyl-l-(4-methylphenyl )-3 -( l-piperidinyl)-l-propanone hydrochloride RN: 364 4-6 1-9 MF: C,,W2,NO . HCI MW: