Trade Narne(s): D: Athmakhell (Steigerwald); wfrn Bilicordan (Repha); wfm Broncaid (RhGne-Poulenc Pharma); wfm Cardiopax (Wider); wfm Coronar-Homocent (Fides); wfrn Coropar (Redel); wfm Farctil (Gewo); wfm F: Hyperidyst 11 (Vogel & Weber); wfm I: losimitan (Wider); wfm Keldrin (Thiemann); wfrn Puraeton E (Dolorgiet); wfm Solamin (Ardeypharm); wfm Khellin K 1131 Khelline Promethazine Berthier (Labaz); wfrn Kellina (UCB); wfrn Nefrolitin (Geymonat)- comb.; wfrn Vasokellina papaverina (Ange1ini)-comb.; wfm 1132 L Labetalol Labetalol ATC: CO7AGOl Use: antihypertensive (a- and P-receptor blocker) RN: 36894-69-6 MF: C,,H2,N203 MW: 328.41 EINECS: 253-258-3 LD,,,: 97.5 mgkg (M, i.v.); 660 mglkg (M, p.0.); >SO mglkg (R, i.v.); >2 gkg (R, p.0.) CN: 2-hydroxy-5-[l-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]benzaide hydrochloride RN: 32780-64-6 MF: C,yH24N20, . HCl MW: 364.87 EINECS: 251-21 1-1 LD,,,: 47 mglkg (M, i.v.); 1.45 glkg (M, p.0.); 53 mgkg (R, i.v.); 2.1 14 gkg (R, p.0.); >1.5 glkg (dog, p.0.) N-benzyl-1- 5-brornoacetyl- methyl-3-phenyl- solicylamide (I) propylarnine I Labetalol I Hz, Pd-Pt-C - benzylocetone dibenzyl- ornine Reference(s): US 4 012 444 (Allen & Hanburys;.15.3.1977; prior. 29.6.1970). US 4 066 755 (Allen & Hanburys; 3.1.1978; GB-prior. 30.1 1.1973). DOS 2 032 642 (Allen & Hanburys; appl. 1.7.1970; GB-prior. 8.7.1969). DAS 1 643 224 (Allen & Hanburys; appl. 22.9.1967; GB-prior. 23.9.1966,21.4.1967). US 3 705 233 (Allen & Hanburys; 5.12.1972; GB-prior. 23.9.1966). Formulation(s): amp. 5 mglml, 50 mg, 100 mg; tabl. 50 mg, 100 mg, 200 mg, 300 mg, 400 mg (as hydrochloride) Trade Name(s): D: Trandate (Glaxo; 1978); Diurolab (Lebenls)-comb. J: Trandate (Shim Nihon wfm Ipolab (Leben's) Ji tsugy o-Graxo) F: Trandate (Novartis; 1980) Lolum (Lifepharma) USA: Normodyne (Schering- GB: Trandate (Evans; 1977) Pressalolo (Locatelli) Plough; 1984) 1: Abetol (CT) Trandate (Glaxo Wellcome) Trandate (Glaxo Wellcome; Alfabetal (Mitim) Trandiur (Glaxo 1984) Amipres (Salus Research) Wellcome)-comb. Biotens (Kemyos)-comb. Lacidipine ATC: CO~DE; CO~CAO~ (Lacipil; GR-43659X; GX-1048; SN-305) Use: once-daily calcium antagonist, antihypertensive RN: 103890-78-4 MF: C,,H,,NO, MW: 455.55 LD,,: 3150 mgkg (M, p.0.); 880 mglkg (R, p.0.) CN: (6-4-[2-[3-(1,l -dimethylethoxy)-3-oxo- I-propenyl]phenyl]- 1,4-dihydro-2,6-dimethyl-3,s- pyridinedicarboxylic acid diethyl ester pH0 phthal- aldehyde I + (9 CHO 1. CH2CI,. O°C 2. chromatography CHO + triphenylphosphoranylidene- acetic acid 1 ,l -dimethylethyl ester (E)-3-(2-formylphenyl)- 2-propenoic acid 1.1 -dimethylethyl ester (1) HC 0 toluene, 3 Y BO°C ethyl 3-arnino- crotonate (11) 2-formyl- ethyl aceto- Lacidipine cinnamic acid acetate 1134 L Lactulose N.N-dimethyllormomide di-tert-butyl ocetal 1. C2H50H 2. HCI CH3 + 11 b 9 Locidipine 0 CH, H3C 1. C2H50H 2. HCI 8 H3$~~3 + 11 + / H3cw0% - Reference(s): a DE 3 529 997 (Glaxo; appl. 22.8.1985; I-prior. 22.8.1984; 5.7.1985). US 4 801 599 (Glaxo; 31.1.1989; appl. 20.8.1985; I-prior. 22.8.1984,5.7.1985). US 5 01 1 848 (Glaxo; 30.4.1990; appl. 23.1.1989; prior. 20.8.1985; I-prior. 22.8.1984, 5.7.1985). b EP 370 974 (Glaxo; appl. 21.11.1989; I-prior. 21.1 1.1989). c EP 534 520 (Merck + Co.; appl. 5.9.1992; USA-prior. 13.9.1991,28.7.1992). lacidipine for treating arteriosclerosis: EP 499 920 (Glaxo; appl. 8.2.1992; I-prior. 13.2.1991). long-acting formulation for dihydropyridines: EP 301 133 (Syntex; appl. 21.12.1987; USA-prior. 26.7.1987). prolonged-release oral pharmaceuticals: EP 557 244 (Siegfried Pharma; appl. 3.2.1993; CH-prior. 17.2.1993). process for preparation of solid dispersions: WO 9 508 987 (KRKA Tovarna; appl. 26.9.1994; SI-prior. 28.9.1993). Formulation(s): tabl. 2 mg, 4 mg Trade Name(s): D: Motens (Boehringer Ing.) I: Apanil (Fidia) Viapres (Zambon; 199 1) F: Caldine (Boehringer Ing.) Lacipil (Glaxo Wellcome) GB: Motens (Boehringer Ing.) Lacirex (Guidotti; 199 1) Lactulose (Laktulose) ATC: A06ADI 1 Use: laxative RN: 46 18- 18-2 MF: C,2H22011 MW: 342.30 EINECS: 225-027-7 CN: 4-0-P-D-galactopyranosyl-D-fructose CHO alkaline isornerizotion _____d lactose Lactulose Lactylphenetidin L 1 135 Reference(s): Montgomery, E.M.; Hudson, C.S.: J. Am. Chem. Soc. (JACSAT) 52,2101 (1930). use of alkali aluminate: US 3 546 206 (Kraftco; 8.12.1970; prior. 20.9.1967). US 3 850 905 (Kraftco; 26.1 1.1974; prior. 30.12.1972). use of borax and NaOH: JP 7 700 091 (Morinaga Milk Ind.; appl. 13.4.1971). use of MgO, MgCO,: ES 397 810 (Jalup Jaures; appl. 26.11.1971). use of alkali tetraborate: US 3 505 309 (Research Corp.; 7.4.1970; prior. 25.9.1967). use qf alkali metal hydroxide or ammonia: DOS 2 038 230 (Hayashibora; appl. 3 1.7.1970; J-prior. 3 1.7.1969, 2.8.1969). lactulose syrup: DOS 2 224 680 (Morinaga Milk Ind.; appl. 19.5.1972; J-prior. 22.5.1971), lactulose powder: DAS 1 189 839 (N.V. Tervalon; appl. 20.4.1961; N-prior. 22.4.1960). DOS 2 153 106 (Morinaga Milk Ind.; appl. 25.10.1971; J-prior. 31.5.1971). BE 843 777 (Morinaga Milk Ind.; appl. 5.7.1976; J-prior. 4.7.1975, 8.7.1975). DOS 2 038 230 (Hayashibara; appl. 31.7.1970; J-prior. 31.7.1969,2.8.1969). crystalline lactulose: US 5 003 061 (SIRAC; 26.3.1991; I-prior. 1.12.1987). AT 327 224 (Laevosan; appl. 12.10.1973; valid from 15.4.1975). Osten, B.J.: Recl. Trav. Chim. Pays-Bas (RTCPA3) 86,673 (1967). CS 161 498 (M. Tadra et al.; appl. 24.5.1973). Formulationis): gran. 3 g, 5 g, 6 g, 10 g; syrup 3.33 g, 50 %, 66.7 % Trade Namefs): D: Bifiteral (Solvay Arzneimi ttel) Eugalac (Topfer) Lactofalk (Falk) Lactuflor (MIP Pharma) Lacvilac S (Fresenius- Praxis) generic F: Duphalac (Solvay Pharma) Lactylphenetidin (Lactophenin) Fitaxal (Phygihe) Melaxose (Boehringer 1ng.)-comb. Transulose (Schwarz)- comb. GB: Duphalac (Solvay) Lactugal (Galen) 1: Diacolon (Piam) Duphalac (UCM) Epalfen (Zambon) Lactoger (Ripari-Gero) Lacvolac (Boehringer Mannh.) Lassifar (Lafare) Normase (Molteni) Osmolac (Savio IBN) USA: Duphalac (Solvay) lxxose (ECR) ATC: N02B Use: analgesic, antipyretic, antirheumatic RN: 539-08-2 MF: CI,H,,NO, MW: 209.25 EINECS: 208-708-3 CN: N-(4-ethoxypheny1)-2-hydroxypropanamide DL-lactic acid p-phenetidine Lactylphenetidin 1136 L Lamivudine Reference(s): DRP 70 250 (Chem. Fabr. formerly Goldenberg Geromont; 1892). Formulation(s): tabl. 200 mg Trade Name(s): D: Octadon (Thiemann)- Quadronal (ASTA)-comb.; comb.; wfm wfm Lamivudine (3 TC; BCH-790; GR- 109714X; (-)sddc) ATC: J05AF05 Use: antiviral, reverse transcriptase inhibitor RN: 134678-17-4 MF: CmH,lN303S MW: 229.26 CN: (2R-cis)-4-amino-l-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone (2s-cis)-form RN: 134680-32-3 MF: CmH,lN303S MW: 229.26 racemate RN: 136891-12-8 MF: CmH,,N303S MW: 229.26 benzoyloxy- rnercoptoocet- acetaldehyde (I) aldehyde di- methyl ocetol NH2 NH2 1. hexornethyldisilozone 2. trirnethylsilyl triflote or SnCI, cl0 + 6, b H cytosine (111) (m arnberlite, cytidine dearninose CH,OH (enontinspecific hydrolysis) IV- b BCH 189 (roc.) (V) I Lornivvdine Lamivudine L 1137 trimethyl phosphate 1. 5'-nucleotidose from Crotolus otrox 2. bocteriol olkoline phosphotose 1. Lewis acid H3Cbo (+)-mereapto- lactic acid (W) I-Si(CH3)3 M + 111 . trimethylsilyl iodide (X) @ OHC-COOH + glyoxylic acid 1. separation 2. deprotection -, Fl 1. Lewis acid 1. resolution 2 VIIl CH, 2. H3C-OH , SOCI2 VII * XI reduction ___, 1138 L Lamivudine thioglycolic 2-(tert-butyldiphenyl- acid silyloxyrnethyl)-5-0x0- oxy- 1,J-oxothiolane (XII) 1. cieCI , SnCI4 2. N+[(cH~)~-cH~]~ F-, THF + 111 v trans-5-hydroxy-1.3- trirnethyl oxathiolane-2- orthoformats carboxylic ocid 2.6-lutidine, 1. H3cn1 . DMF Reference(s): a,bEP 382 526 (IAF Biochem. Int.; appl. 16.8.1990; USA-prior. 8.2.1989). WO 9 117 159 (IAF Biochem. Int.; appl. 14.1 1.1991; GB-prior. 2.5.1990). Bcach, I.W. et al.: J. Org. Chem. (JOCEAH) 57 (8), 2217 (1992). (synthesis via L-gulosc see also WO 9 210 496). c Humber, D C. et al.: Tetrahedron Lett. (TELEAY) 33 (32), 4625 (1992). d Drugs Future (DRFUD4) 18 (41,319-323 (1993). e WO 9 l l l 186 (Emory Univ.; appl. 31 .I. 1991; USA-prior. 1.2.1990). US 5 210 085 (Emory Univ.; 22.2.1991; USA-prior. 1.2.1990). f WO 9 429 301 (Biochem. Pharma. Inc.; appl. 7.6.1994; GB-prior. 7.6.1993). process that avoids Lewis acids: WO 9 529 174 (Glaxo; appl. 21.4.1995; GB-prior. 23.4.1994). Lamotrigine L 1139 crystalline new form: EP 517 145 (Glaxo; appl. 2.6.1992; GB-prior. 3.6.1991). use for treating and preventing hepatitis B infection: EP 494 119 (P. Bellean; IAF Biochem. Int.; Biochem. Pharma. Inc.; appl. 3.1.1992; GB-prior. 3.1.1991). composition for HIV infections: EP 513 917 (Glaxo; appl. 11.5.1992; GB-prior. 16.5.1991). WO 9 504 525 (Andrulis Pharm.; appl. 3.8.1994; USA-prior. 4.8.1993). combination with zidovudine and loviride: WO 9 601 110 (Janssen Pharm.; appl. 23.6.1995; EP-prior. 1.7.1994). Formulation(s): f. c. tabl. 100 mg; oral sol. 10 mglml; sol. 1 %; tabl. 150 mg Trade Name(s): D: Combivir (Glaxo GB: Combivir (Glaxo Epivir (Glaxo Wellcome) Wellcome)-comb. with Wellcome)-comb. with J: Epivir (Nippon Wellcome) Zidovudine Zidovudine USA: Combivir (Glaxo Epivir (Glaxo Wellcome) Epivir (Glaxo Wellcome) Wellcome)-comb. with Zeffix (Glaxo Wellcome) Zeffix (Glaxo Wellcome) Zidovudine F: Epivir (Glaxo Wellcome) I: Combivir (Glaxo Epivir (Glaxo Wellcome) Wellcome)-comb. with 3TC (Glaxo Wellcome) Zidovudine Lamotrigine (B W-430C) ATC: N03AX09 Use: anticonvulsant, glutamate inhibitor RN: 84057-84-1 MF: C,H,Cl,N5 MW: 256.10 EINECS: 281-901-8 LD,,: 245 mg/kg (M, p.0.); 205 mg/kg (R, p.0.) CN: 6-(2,3-dichloropheny1)-1,2,4-triazine-3,5-diamine 1. SOCI* Q, + CO2 -2% c, 2. CuCN , KI CI CI +OOH TziGz? ct CI CI 0 potossiurn iodide 2,3-dichloro- carbon 2.3-dichloro- 2.3-dichlorobe,nzoyl 1 -iodobenzene dioxide benzoic ocid cyanide (1) 1. HN03 H 2. KOH. CH,OH I + -b orninoguanidine Reference(s): US 4 560 687 (Wellcome; 24.12.1985; appl. 5.3.1984; prior. 15.9.1981, 29.5.1980; GB-prior. 1.6.1979). US 4 602 017 (Wellcome; 22.7.1986; appl. 27.2.1984; prior. 15.9.1981,29.5.1980; GB-prior. 1.6.1979). EP 21 121 (Wellcome; appl. 30.5.1980; GB-prior. 1.6.1979). US 5 912 345 (Glaxo Wellcome; 15.6.1999; appl. 29.12.1995; GB-prior. 30.12.1994). Formulation(s): tabl. 5 mg, 25 mg, 50 mg, 100 mg, 200 mg 1140 L Lanatoside C ~ -~~ - - - - - Trade Name(~): D: Lamictal (Glaxo Wellcornel GB: Lamictal (Glaxo Wellcome; USA: Lamictal (Glaxo Wellcome; Desi tin) 1995) 1998) F: Lamictal (Novartis) I: Lamictal (Wellcome) Lanatoside C (Lanatoside) ATC: COlAA06 Use: cardiac glycoside RN: 17575-22-3 MF: C,,H,,O,,, MW: 985.13 EINECS: 241-546-1 CN: (3~,5~,12~)-3-[(0-~-~-glucopyranos~l-(1+4)-0-3-0-acety1-2,6-dideoxy-~-d-ribo-hexopyranosy1- (1 44)-0-2,6-dideoxy-P-D-ribo-hexopyranosyl-1 +4)-2,6-dideoxy-~-~-ribo-hexopyranosyl)oxy]-l2,14- dih ydroxycard-20(22)-enolide deslanoside RN: 17598-65-1 MF: C,,H,,O,, MW: 943.09 NH4CI. CH3COOC2H5 Digitalis lonota -b 'Lonota-Reintannoid' (1) partition between Pb(OH)Z. H,O. CH,OH CHCI, and CH,0H/H20 1 b digilanid - 11 + I11 + IV (gross glycoside) separation from lanatoside A ond B lanotoside C (I) + ntsie A (I) + anatsi B () i] I Lonotoside C . 1757 5-2 2-3 MF: C,,H,,O,,, MW: 985.13 EINECS: 24 1-5 4 6-1 CN: (3~,5~,12~ )-3 -[ ( 0-~ -~ -glucopyranos~l-(1+4 )-0 - 3-0 -acety 1-2 ,6-dideoxy-~-d-ribo-hexopyranosy 1- (1 44 )-0 -2 ,6-dideoxy-P-D-ribo-hexopyranosyl-1. 229.26 CN: (2R-cis )-4 -amino-l-[ 2-( hydroxymethyl )-1 ,3-oxathiolan-5-yl ]-2 (1H)-pyrimidinone (2s-cis)-form RN: 13468 0-3 2-3 MF: CmH,lN303S MW: 229.26 racemate RN: 13689 1-1 2-8 MF: CmH,,N303S. mglkg (R, p.0.) CN: ( 6-4 -[ 2-[ 3-( 1,l -dimethylethoxy )-3 -oxo- I-propenyl]phenyl ]- 1,4-dihydro-2,6-dimethyl-3,s- pyridinedicarboxylic acid diethyl ester pH0 phthal- aldehyde I + (9 CHO