Lercanidipine hydrochloride L 1 15 1 1 - I Lentinon US 3 883 505 (Ajinomoto; 13.5.1975; J-prior. 17.7.1972). DE 2 336 378 (Ajinomoto; appl. 17.7.1973; J-prior. 17.7.1972). Chibara, J. et al.: Cancer Res. (CNREA8) 30, 2776 (1970). Chihara, G. et al.: Nature (London) (NATUAS) 222,637 (1968). structural study: Sasaki, T. et al.: Carbohydr. Res. (CRBRAT) 47,99 (1976). water soluble pharmaceutical formulation: US 4 207 312 (Ajinomoto, Morishita; 10.6.1980; J-prior. 5.2.1975). combination with CSF: EP 326 149 (Green Cross, Morinaga; appl. 27.1.1989; J-prior. 29.1.1988). Formulation(s): vial 1 g Trade Nanze(s): J: Lentinan (Ajinomoto- Morishita; Yamanouchi; 1986) Lercanidipine hydrochloride ATC: C08CA13 Use: treatment of hypertension, vasoselective calcium antagonist RN: 132866-1 1-6 MF: C&,N306 - HCI MW: 648.20 CN: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-[(3,3- diphenylpropyl)melhylamino]- I, I-dimethylethyl methyl ester hydrochloride base RN: 100427-26-7 MF: C3,H4,N306 MW: 61 1.74 acetophenone form- methylbenzyl- aldehyde omine 3-(benzylmethyl- amino)- l-phenyl- propan- 1 -one (I) 1 152 L Lercanidipine hydrochloride Hz, Pd-C, MgBr TH F C2H@H, H Hi$ I+$ - ___, \ \ phenyl- 3-(benzylmethylomino)- 3,S-diphenyl-N- magnesium 1 ,I -diphenyl- methylpropylornine (11) bromide 1 -propon01 , 8S'C CH2 I11 diketene (N) CHO CHJOH 3-nitro- benzalde- hyde (V) 2. HCI. H20 VI. 1. methyl 3-amino- crotonate (VII) H . HCI Lercanidipine hydrochloride 1 tert-butyl ocetoacetote tert-butyl 2-(3-nitro- benzylidene)acetoacetate Letosteine L 1 153 1. SOC12, CH2C12, DMF H H 0 H3C N CH3 H,C N CH, 2.flL n3cUo9n, H+ 3. HCI. H20 Lerconidipine H3c~0~H~$~13 - H3c-0@00H & \ \ NO2 NO2 5-tert-butyl 3-methyl 2.6-dimethyl-5- 2.6-dimethyl-4-(3-nitro- methoxycarbonyl- phenyl)-1.4-dihydro- 4-(3-nitropheny1)- pyridine-3,5-dicorboxylate (WI) 1,4-dihydropyridine- 3-corboxylic acid Reference (s): Leonardi, A. et al.: Eur. J. Med. Chem. (EJMCAS) 33, 399 (1998). a EP 153 016 (Recordati Chem. and Pharm.; appl. 21.1.1985; GB-prior. 14.2.1984). b WO 9 635 668 (Recordati Chern. and Pharm.; appl. 9.5.1996; I-prior. 12.5.1995). preparulion of 3-(benzy1methylarnino)- 1,l-diphenyl- 1-propanol: Morrison; Rinderknecht: J. Chern. Soc. (JOCEAH) 1950, 1510 preparation of 3,3-diphenyl-N-methylpropylamine: DE 925 468 (Farbwerke Hoechst; appl. 13.8.1941) Formulation(s): tabl. 10 mg (as hydrochloride) Trade Name(s): GB: Zanidip (Napp) I: Zanedip (Recordati; 1999) Letosteine ATC: R05CB09 Use: mucoly tic agent RN: 53943-88-7 MF: C,oH,7N04S2 MW: 279.38 EINECS: 258-879-3 CN: 2-[2-[(2-ethoxy-2-oxoethyl)thio]ethyl]-4-thiazolidinecarboxyic acid ocrolein ethyl mercapto- ocetote ethyl (3-oxopropyl- thio)ocetate (I) L-cysteine 1 Letosteine 1 Reference(s): DOS 2 410 307 (Ferlux-Chimie; appl. 22.3.1974; F-prior. 22.3.1973). US 4 032 534 (Ferlux-Chimie; 28.6.1977; F-prior. 22.3.1973). Formulation(s): cps. 50 mg; gran. 25 mgldose, 50 mg Trade Name(s): F: Viscotiol (Evans Medical) I: Letofort (Salus Research) 1 154 L Letrozole Viscotiol (Schiapparelli J: Viscotiol (ISF) Searle) Letrozole (CGS-20267) RN: 112809-51-5 MF: CI7H,,N, MW. 285.31 CN: 4,4'-(1H-1,2,4-triazol-l-ylmethylene)bis[benzonitrile] CH,CI, H room temperature - 4-(bromomethy1)- 1H-1.2.4- benzonitrile triozole ATC: L02BG04 Use: antineoplastic, aromatase inhibitor benzonitrile (1) Reference (s): EP 236 940 (Ciba-Geigy; appl. 5.3.1987; USA-prior. 7.3.1986). 4-fluoro- alternativ preparation of l with K2C03/KI in acetone: US 4 978 672 (Ciba-Geigy; appl. 6.9.1988; USA-prior. 7.3.1986,7.3.1988). Letrozole cornhination with 5-c*-reductase inhibitors: WO 9 218 132 (Merck & Co.; appl. 6.4.1992; USA-prior. 17.4.1991). benzonitrile use to treat androgen deficiencies: DE 445 368 (Schering AG; appl. 22.9.1994; D-prior. 22.9.1994). Formulation(s): tabl. 2.5 mg Pade Name(s): D: Femara (Novartis Pharma) GB: Femara (Novartis) F: Femara (Novartis) USA: Femara (Novartis) Leucinocaine ATC: NOlB Use: local anesthetic RN: 92-23-9 MF: C,7H2,N202 MW: 292.42 CN: 2-(diethylamino)-4-methyl-l-pentanol4-arninobenzoate (ester) monomesylate RN: 135-44-4 MF: C,,H,,N,O, . CH,O,S MW: 388.53 EINECS: 20.5- 19 1-6 Levallorphan L 1155 0 CI CH CH3 CH CH3 'i' cH3 No, C,H,OH 'b? cH3 4 NO2 I H~c'-"+CH~ ' HO&~~, I-nitrobenzoy~' 0 chloride N.N-diethylleucine ethyl ester yy3 N CH, NH2 Leucinocaine DRP 464 484 (Chem. Fabr:Flora; appl. 1923; CH-prior. 1922). Formulation(s): amp. 200 mg14 ml Trade Narnefs): D: Panthesin-Balsam Panthesin-Hydergin (Sandoz); wfm (Sandoz)-comb.; wfm Levallorphan Use: morphine antagonist, narcotic antagonist RN: 152-02-3 MF: C,,HZ5NO MW: 283.42 EINECS: 205-799-1 LD,,,: 949 mglkg (R, p.0.) CN: 17-(2-propeny1)morphinan-3-01 hydrogen tartrate RN: 71-82-9 MF: C,,HZ5NO . C4H606 MW: 433.50 pyridine hydrochloride ~NH (+_)-I -(4-rnethoxybenzy1)- 1,2,3.4,5,6,7,8-octohydro- isoquinoline (cf. levorphanol synthesis) (+)-1-(4-hydroxybenzy1)- 1,2.3.4.5,6,7,8-octohydro- isoquinoline (I) 1156 L Levamisole (+)-tortoric ocid BrACH2 . K2C03 I + b I1 'Y'l oily) bromide -OH (-)- 1 -(4-hydmxybenzyl)- 1,2,3.4.5.6.7.8-octohydro- isoquinoline H3P04 DLOH \\ CH2 (-)-2-ollyl-144- Levollorphon hydroxybenzy1)- 1.2.3.4.5,6.7,8- octohydroisoquinoline (11) Hellerbach, J.; Griissner, A.; Schnider, 0.: Helv. Chim. Acta (HCACAV) 39, 429 (1956). Ehrhart, Ruschig I, 13 1- 132. Formulation(s): amp. 1 mglml Trude Name(s): D: Lorfan (Roche); wfm J: Lorfan (Takeda); wfm GB: Lorfan (Roche); wfm USA: Lorfan (Roche); wfm Levamisole ATC: P02CE01 Use: anthelmintic, immunostimulant (tetramisole is used only in veterinary range as anthelmintic) RN: 14769-73-4 MF: CllHI2N2S MW: 204.30 EINECS: 238-836-5 LD,,: 22 mgkg (M, i.v.); 210 mgkg (M, pa.); 24 mglkg (R, i.v.); 480 mg/kg (R, p.0.) CN: (S)-2,3,5,6-tetrahydro-6-phenylimidazo~2,I-b]thiazole monohydrochloride RN: 16595-80-5 MF: CIIH12N2S . HCI MW: 240.76 EINECS: 240-654-6 Tetramisole RN: 5036-02-2 MF: C,,H,,N,S MW: 204.30 EINECS: 225-729-3 CN: (+_)-2,3,5,6-tetrahydro-6-phcnylimidazo[2,l-b]thiazole monohy drochloride RN: 5086-74-8 MF: C,, HI,N,S . HC1 MW: 240.76 EINECS: 225-799-5 LDsO: 22 mgkg (M, i.v.); 210 mglkg (M, p.0.); 24 mgkg (R, i.v.); 480 mdkg (R, p.0.) phenacyl 2-imino- bromide thiozolidine (I) 0 CH, 9' 0 Nys (-JY ,NJ~=. sodium boronate (11) Tetromisole (111) racemote resolution with I I 0-1 0-comphorsulfonic ocid 111 styrene oxide (N) 1. SOCI, 2. (H3C-C0)20 1- 1. SOCI, H2N NH2 2 (H,C-CO)20 or K2C0, N + VI + VII -b v thiourea (VIII) u ethonolomine WNH 0 HCI H20. HCI ___* + v 1158 L Levamisole 2-amino-1 - 2-brornaethyl phenylethanol isothiocyanate Reference(s): a,bUS 3 274 209 (Janssen; 20.9.1966; prior. 11.5.1964, 3.8.1964,2.10.1964,7.4.1965). Raeymaekers, A.H.M. et al.: J. Med. Chem. (JMCMAR) 9, 545 (1966). c Spicer, L.D. et al.: J. Org. Chem. (JOCEAH) 33, 1350 (1968). DAS 1 795 651 (ICI; appl. 13.7.1966; AUS-prior. 31.8.1965, 8.9.1965). GB 1 076 109 (American Cyanamid; appl. 11 .I 1.1965; USA-prior. 5.10.1965). US 3 679 725 (American Cyanamid; 25.7.1972; prior. 5.10.1965, 22.9.1967, 11.6.1970). GB 1 131 798 (ICI; appl. 4.7.1966; AUS-prior. 31.8.1965,8.9.1965). DAS 1 795 651 (ICI; appl. 13.7.1966; AUS-prior. 31.8.1965, 8.9.1965). GB 1 131 799 (ICI; appl. 4.7.1966; AUS-prior. 19.7.1965, 26.7.1965, 31.8.1965, 8.9.1965). GB 1 131 800 (ICI; appl. 4.7.1966; AUS-prior. 19.7.1965, 26.7.1965, 31.8.1965, 8.9.1965). US 3 478 047 (ICI; 11.1 1.1969; GB-prior. 10.12.1965). d DOS 2 233 481 (ICI; appl. 7.7.1972; GB-prior. 9.7.1971, 6.4.1972). DOS 2 264 911 (ICI; appl. 7.7.1972; GB-prior. 9.7.1971, 6.4.1972). US 3 855 234 (ICI; 17.12.1974; GB-prior. 9.7.1971,6.4.1972). US 4 070 363 (ICI; 24.1.1978; GB-prior. 13.4.1974). US 4 107 170 (American Cyanamid; 15.8.1978; prior. 18.6.1973, 24.1.1974, 29.10.1975, 14.2.1977). e DAS 2 034 081 (Chinoin; appl. 9.7.1970; H-prior. 1.10.1969). other methods: US 3 726 894 (American Cyanamid; 10.4.1973; prior. 24.6.1971). DOS 2 326 308 (ICI; appl. 23.5.1973; GB-prior. 23.5.1973). US 3 845 070 (ICI; 29.10.1974; GB-prior. 27.7.1971). FR 2 224 472 (P. R. Dick, M. Rombi; appl. 5.4.1973). US 4 090 025 (American Cyanamid; 16.5.1978; prior. 26.4.1973, 8.11 .l976). FR-appl. 2 359 844 (Propharma; appl. 28.7.1976). FR-appl. 2 364 21 8 (Propharma; appl. 14.9.1976). racemate resolution of tetramisole: US 3 463 786 (American Cyanamid; 26.8.1969; prior. 1.6.1966, 19.12.1967). with D- 10-camphersulfonic acid: DAS 1 645 99 1 (American Cyanamid; appl. 18.8.1967; USA-prior. 18.8.1966). US 3 565 907 (American Cyanamid; 23.2.1971; prior. 18.8.1966,23.4.1969). Bullock, M.W. et al.: J. Med. Chem. (JMCMAR) 11, 169 (1968). with N-(p-to1uenesulfonyl)-L-glutamic acid: US 3 579 530 (ICI; 18.5.1971; AUS-prior. 24.8.1967, 11.1.1968, 18.1 .l968). DAS 1 795 217 (ICI; appl. 23.8.1968; AUS-prior. 24.8.1967, 11.1.1968, 18.1.1968). with N-(p-toluenesu1fonyl)-1-pyroglutamic acid and 2,3-0,O-diaroyl-(+)-tartaric acids: DAS 1 907 609 (ICl; appl. 14.2.1969; GB-prior. 14.2.1968). with di-(p-toluoy1)-(+)-tartaric acid: DAS 2 020 142 (RhBne-Poulenc; appl. 24.4.1970; F-prior. 24.4.1969). Levobunolol L 1159 regioselective levamisole synthesis by use of optical active rlzodium-DIOP-complexes (asymmetric hydrogenation of 3-acyl-l-(2-metho~ethyl)-4-phenyl-4-imidazolin-2-ones): DOS 2 7 18 058 (American Cyanamid; appl. 22.4.1977; USA-prior. 26.4.1976, 8.1 1.1976). DOS 2 718 059 (American Cyanamid; appl. 22.4.1977; USA-prior. 26.4.1976, 8.11.1976). US 4 087 61 1 (American Cyanamid; 2.5.1978; prior. 26.4.1976, 8.11.1976). US 4 166 824 (American Cyanamid; 4.9.1979; prior. 14.6.1977, 14.4.1978). racemization with bases: US 3 673 206 (American Cyanamid; 27.6.1972; prior. l4.7.1966,2.4.1969). via 1-vinyl-4-phenyl-2-imidazolidinthione: US 3 726 894 (American Cyanamid; 10.4.1973; appl. 24.6.1971). levamisole resp. tetramisole embonate: DAS 1 817 509 (ICI; appl. 30.12.1968; GB-prior. 8.1.1968). use for treatment of scabies: DOS 2 828 200 (Johnson & Johnson; appl. 27.6.1978; USA-prior. 28.6.1977). US 4 150 141 (Johnson & Johnson; 17.4.1979; appl. 28.6.1977). aqueous tetramisole preparation: DAS 2 036 113 (ICI; appl. 21.7.1970; AUS-prior. 21.7.1969). Formulation(s): tabl. 30 mg, 50 mg, 150 mg (as levamisole hydrochloride) Trade Name(s): D: Ergamisol (Janssen-Cilag) I: Ergamisol (Janssen) F: Solaskil (Specia) USA: Ergamisol (Janssen) Levobunolol ATC: SOlED03 Use: beta blocking agent RN: 47141-42-4 MF: C,7H2sN0, MW: 291.39 CN: (S)-5-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-3,4-dihydro-l(2H)-naphth~lenone hydrochloride RN: 27912-14-7 MF: C,,H,,NO, . HCI MW: 327.85 EINECS: 248-725-3 LD,,,: 78 mgkg (M, i.v.); 1220 mglkg (M, p.0.); 25 mgkg (R, i.v.); 700 mglkg (R, p.0.); 100 mglkg (dog, p.0.) CH3 r + H,C+NH, + o H (21 CH3 "3"xl-h-" H3C CH3 tert-butyl- (*)-5-(2-hydroxy-3- omine tert-butylominopropoxy)- 1 -tetralone (11) 1160 L Levocabastine rocemote resolution with I-tartaric acid 11 Levobunolol Reference(s): DE 1 948 144 (Warner-Lambert; appl. 23.9.1969; USA-prior. 23.9.1968). DE 1 967 162 (Warner-Lambert; appl. 23.9.1969; USA-prior. 23.9.1968). US 3 641 152 (Warner-Lambert; 8.2.1972; prior. 23.9.1968). rucemare resolution: DOS 2 046 043 (Warner-Lambert; appl. 17.9.1970; USA-prior. 17.9.1969). Fortnulation(s): eye drops 0.1 %, 0.25 %, 0.5 %J (5 mg/ml) (as hydrochloride) Trade Nnme(s): D: Vistagan Liquifilm (Pharm- F: Bttagan (Allergan) I: Vistagan (Allergan; 1987) Allergan; 1985) GB: Betagan (Allergan) Levocabastine (R-50; 547) ATC: RO1 AC02; S01GX02 Use: antihistaminic (H,-selective) RN: 79516-68-0 MF: C2,H2,FN20, MW: 420.53 CN: [3S-[1(cis),3~,4~J]-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenyl-4-pipendinecarboxylic acid monohydrochloride RN: 79547-78-7 MF: C26H2,FN20, . HCI MW: 456.99 NoOCH3, xylene NaOCH, + . . 1 F H2C- F 4-fluoro- methyl ocrylote phenyl- ocetonitrile I -(4-fluoropheny1)- 1 -cyono-4-0x0- cyclohexone (11) . H3c~0~H~$~13 - H3c-0@00H & NO2 NO2 5-tert-butyl 3-methyl 2.6-dimethyl- 5- 2.6-dimethyl- 4-( 3-nitro- methoxycarbonyl- phenyl )-1 .4-dihydro- 4-( 3-nitropheny1 )- pyridine-3,5-dicorboxylate. CN: 1,4-Dihydro-2,6-dimethyl- 4-( 3-nitrophenyl )-3 ,5-pyridinedicarboxylic acid 2-[ (3, 3- diphenylpropyl)melhylamino ]- I, I-dimethylethyl methyl ester hydrochloride base RN: 10042 7-2 6-7 MF:. 5394 3-8 8-7 MF: C,oH,7N04S2 MW: 279.38 EINECS: 25 8-8 7 9-3 CN: 2-[ 2-[ (2-ethoxy-2-oxoethyl)thio]ethyl ]-4 -thiazolidinecarboxyic acid ocrolein ethyl mercapto- ocetote ethyl (3-oxopropyl- thio)ocetate