Enalaprilat E 74 1 ethyl 2-oxo-4-phenylbutyrate: Weinstock, L.M. et al.: Synth. Cornmun. (SYNCAV) 11, 943 (1981). a Wyvratt, M.J. et al.: J. Org. Chern. (JOCEAH) 49, 2816 (1984). US 4 374 829 (Merck & Co.; 22.2.1983; prior. 11.12.1978). EP 12 401 (Merck & Co.; appl. 10.12.1979; USA-prior. 11.12.1978). US 4 472 380 (Merck & Co.; 18.9. 1984; prior. 1 1.12.1979). Huffmann, H.A. et al.: Tetrahedron Lett. (TELEAY) 40, 33 1 (1999). b US 4 442 030 (Merck & Co.; 10.4.1984; prior. 7.6.1982). c Blacklock, T.J. et al.: J. Org. Chern. (JOCEAH) 53, 836 (1988). processes which employ reaction of activated derivatives of N-[l(S)-ethoxycarbonyl-3-phenylpropyll-L-alanine with L-proline: US 4 716 235 (Kanegafuchi; 29.12.1987; J-prior. 27.8.1985). DOS 3 542 735 (Uriach; appl. 3.12.1985; E-prior. 2.7.1985). US 4 652 668 (Biorneasure; 24.3.1987; appl. 3.7.1985). condensation of L-alanyl-L-proline with 3-phenylpropionaldehyde and cyanides via the corresponding aminonitrile: EP79 521 (Merck & Co.; appl. 3.1 1.1982; USA-prior. 9.11.1981,9.8.1982). Formulation(s): tabl. 2.5 rng, 5 rng, 10 rng, 20 rng (as hydrogen rnaleate) Trade Name(s): D: Pres (Boehringer Ing.; 1984) Xanef (Merck Sharp & Dohrne; 1984) F: Co-Renitec (Merck Sharp & Dohrne-Chibret)-comb. Renitec (Merck Sharp & Dohrne-Chibret; 1985) GB: Innovace (Merck Sharp & Dohrne; 1986) Innozide (Merck Sharp & Dohrne)-comb. I: Converten (Neopharrned; 198.5) Enapren (Merck Sharp & Dohrne; 1985) Naprilene (Sigrna-Tau; 1985) J: Renivace (Banyu; 1986) USA: Lexxel (Astra Merck) Vaseretic (Merck; 1987)- comb. with hydrochlorothiazide Vasotec (Merck; 1986) Enalaprila t (Enalaprilic acid) ATC: C09AA02; C09BA02 Use: angiotensin-converting enzyme inhibitor (for i.v. application as antihypertensive and in congestive heart failure, active metabolite of enalapril (q. v.)) RN: 76420-72-9 MF: C,,H,N20s MW: 348.40 EINECS: 278-459-3 CN: (S)-1-[N-(1-carboxy-3-phenylpropyl)-~-alanyl]-~-proline dihydrate RN: 84680-54-6 MF: C,,H2,N,OS . 2H20 MW: 384.43 enalapril Enalaprilat (4. 4 742 E Endralazine Refererlce(s): Pakhett, A.A. et al.: Nature (London) (NATUAS) 288, 280 (1980). Wyoratt, M.J. et al.: J. Org. Chem. (JOCEAH) 49, 2816 (1984). US 4 374 829 (Merck & Co.; 22.2.1983; USA-prior. 11.12.1978). cf'. literature citcd under enalapril Formulatior~(s): amp. 1 .Z5 mgl1.25 ml Trade Nume(s): D: Pres i.v. (Bochringer Ing.) Xanef i.v. (MSD) USA: Vasotec i.v. (Merck) Endralazine ATC: C02DB03 Use: antihypertensive RN: 39715-02-1 MF: C,,H,,;NSO MW: 269.31 CN: 6-benzoyl-5,6,7,8-tetrahydropyrido[4,3-c]pyndazin-3(2-one 3-hydrazone monomesylate RN: 65322-72-7 MF: C,,H,,N,O. CH,O,S MW: 365.41 LD,,,: 246 rng/kg (M, i.p.) + I ethyl brorno- .O 0 ocetote ethyl 4-0x0-1- pyrrolidine piperidinecorboxylote H2N-NH2 . H20 . 11 hydrozine 0 0 hydrate ethyl l-ethoxycorbonyl- 4-0x0-3-piperidylocetote 1. HCI HC 0 N 3v'f . OH 2. phasphary 0 0 chloride ethyl 2.3,4.40.5.6,7,8- 3-chlora-5,6,7,8- octohydro-3-0x0-6- tetrohydropyrido- pyrido[4.3-clpyridozine- [4,3-clpyridozine (111) corboxylote (11) I/ H2N-NH2 . H20 benzoyl hydrozine ' 1 &NmNyNH2 1 chloride 0 hydrate 6-benzoyl-3-chloro- 5,6,7,8-tetrahydro- Enflurane E 743 Referencefs): DOS 2 221 808 (Sandoz; appl. 4.5.1972; CH-prior. 11.5.1971, 26.5.1971, 28.5.1971, l5.10.197l). CH 565 797 (Sandoz; appl. 16.3.1972). Schenker, E.; Salzmann, R.: Arzne1m Forsch. (ARZNAD) 29, 1835 (1979). Formda?rion(s): cps. 5 mg, 10 mg (as mcsylatc) a Tmde Name(s): : D: Miretilan (Sandoz); wfm : Enflurane ATC: NOIAB04 Use: inhalation anesthetic RN: 13838-16-9 MF: C,H,ClF,O MW: 184.49 EINECS: 237-553-4 ' LD,: 5 mVkg (M, p.0.); 5450 pllkg (R, p.0.) CN: 2-chloro-l-(difluoromethoxy)-l, l -2-trifluoroethane 2-chloro-1,1,2-tri- 2-chloro-1.1,2-tri- fluomethyl methyl ether fluoroethyl dichloromethyl ether Reference( s): DE 1 643 591 (Ar Reduction Comp.; prior. 2.10.1967). US 3 469 01 1 (Air Reduction Comp.; 23.9.1969; appl. 3.10.1966). US 3 527 813 (Air Reduction Comp.; 8.9.1970; prior. 3.10.1966,4.9.1968). Terrell, R.C. et al.: J. Med. Chem. (JMCMAR) 14, 517 (1971). Fomulation(s): liquid for inhalation 125 ml, 250 ml Tmde Name(s): D: Enfluran-Pharmacia Ethrane (Abbott; 1976) USA: Ethrane (Ohmeda) Inhalationsfliissigkeit GB: Ethrane (Abbott); wfm (Pharmacia & Upjohn) J: Ethrane (Dainippon; 198 1) Enoxacin ATC: JOlMA04 Use: antibiotic (gyrase inhibitor), antibacterial RN: 7401 1-58-8 MF: C,,H,,FN403 MW: 320.32 LD,,: >SO00 mglkg (M, p.0.); >5000 mgfkg (R, p.0.) CN: l-ethyl-6-fluoro-l,4-dihydro-4-oxo-7-(l-piperazinyl)- l,8-naphthyridine-3-carboxylic acid 744 E Enoximone CI N CI 3. Hz. Pd-C + ~~c-0 N? + ~~c-0 b I O2N CNH 2.6-dichlom- 1 -ethoxycarbonyl- 3-nitro- piperazine pyridine 2 HBF,. (C2H5)20 3 A 2 letrofluorobor~c acid. dlethyl ether (1) 6-arn~na-3-fluara-2- 0 0 0 0 diethyl ethoxy- (m) rnethylenernalonale 1. KZC03 HN? pH, 2. NaOH rrr + fCH3 CN N, N 1 F WcooH o ethyl 1 Enoxocin I iodide L I Reference(s): EP 9 425 (Roger Bellon, Dainippon; appl. 24.8.1979; J-prior. 25.8.1978,20. 12.1978, 29.1 2.1978). US 4 352 803 (Dainippon; 5.10.1982; J-prior. 25.8.1978). US 4 359 578 (Dainippon; 5.10.1982; J-prior. 25.8.1978). Formulation(s): f. c. tab]. 200 mg, 300 mg, 400 mg Trade Name(s): D: Enoxor (Pierre Fabre GB: Comprecin (Parke Davis); J: Flumark (Dainippon; 1986) Pharma) wfm USA: Penetrex (RhBne-Poulenc F: Enoxor (Sinbio) I: Bactidan (Recordati) Rorer) Enoximone (RMI- 17043) ATC: COlCE03 Use: cardiotonic, phosphodiesterase inhibitor RN: 77671-31-9 MF: C,,H,,N,O,S MW: 248.31 CN: 1,3-dihydro-4-methyl-5-[4-(methylthio)benzoyl]-2H-imidazol-2-one P Entacapone E 745 hydroxyacetone urea 1.3-dihydro- 4-methyl-2H- irnidazol-2-one (I) 4-(rnethylthi0)- benzoyl chloride I Enoxirnone I Reference(s): DOS 3 021 792 (Richardson-Merrell; appl. 11.6.1980; USA-prior. 18.6.1979, 7.2.1980). GB 2 055 364 (Richardson-Merrell; appl. 18.6.1980; USA-prior. 18.6.1979,7.2.1980). US 4405 635 (Richardson-Merrell; appl. 13.9.1982; prior. 18.6.1979, 7.2.1980, 13.6.1980, 18.2.1981, 30.4.1982). EP 58 435 (Richardson-Merrell; appl. 18.2.1982; USA-prior. 18.2.198 1). Schnettler, R.A. et al.: J. Med. Chem. (JMCMAR) 25, 1477 (1982). synthesis of 1,3-dihydro-4-methyl-2H-imidazol-2-one: WO 8 602 070 (Pfizer; appl. 26.9.1984). Formulation(s): amp. 100 mgl20 ml Trade Name(s): D: Perfan (Hoechst) GB: Perfan (Hoechst; 1989) I: Perfan (Lepetit) Entacapone ATC: N04BX02 Use: antiparkinsonian RN: 130929-57-6 MF: C14H,,N305 MW: 305.29 CN: (E)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide vanillin 5-nitro vanillin N,N-diethyl- cyonoacetornide Entocapone Referencefs): DE 3 740 383 (Orion Yhtymae Oy; appl. 27.1 1.1987; FI-prior. 28.1 1.1986). 746 E Enviomycin prepararion of 5-nitrovanillin: Menke; Bentley: J. Am. Chem. Soc. (JACSAT) 20,316 (1898) Forrnularion(s): f. c. tabl. 200 mg; tabl. 200 mg Trade Narnefs): D: Comtess (Orion Pharma; F: Comtan (Novartis) I: Comtan (Novartis) 1998) GB: Comtess (Orion) USA: Comtan (Orion) Enviomycin (Tuberactinomycin N) ATC: JO4AB Use: antibiotic RN: 33 103-22-9 MF: C25H43N130,n MW: 685.70 LD,,,: 370 mglkg (M, i.v.); >3 g/kg (M, p.0.); 640 mglkg (R, i.v.); >3 glkg (R, p.0.) CN: (R)-I -(three-4-hydroxy-L-3,6-diaminohexanoic acid)-6-[L-2-(2-amino-1,4,5,6-tetrahydro-4- pyrimidinyl)glycine]viomycin suIfate (2:3) RN: 53760-33-1 MF: C,,H,3N,,0,0~ 3/2H2SO4 MW: 1665.63 'OH Enviornycin From fermentation solutions of Srreptornyces griseoverticillatus Val: tuberacricus FERM P-619. Referencefs): DOS 2 133 181 (Toyo Jozo; appl. 30.6.1971; J-prior. 30.6.1970). US 3 892 732 (Toyo Jozo; 1.7.1975; J-prior. 30.6.1970). Ando, T. et a].: J. Antibiot. (JANTAJ) 24,680 (1971). Formulation(s): vial 1 g (as sulfate) Trade Name(s): J: Tuberactin (Toyo Jozo) TUM (Toyo Jozo) Epanolol (ICI- 141 292) ATC: C07AB10 Use: PI-adrenoceptor antagonist, antihypertensive RN: 86880-51-5 MF: C2,H2,N,04 MW: 369.42 CN: N-[2-[[3-(2-cyanophenoxy)-2-hydroxypropyI]amino]ethyl]-4-hydroxybenzeneacetamide Eperisone E 747 H ,(J yN-"tw2 + H2N*NH2 / 0 methyl 4-benzyloxy- ethylene- N-(2-arninoethy1)-4-benzyloxy- phenylacetate diamine phenylacetarnide (1) 1.2-epoxy-3-(2- cyanophenoxy)- prapone N-[Z-[3-(2-cyanophenoxy)-2-hydroxy. propylarnino]ethyl]-4-benzyloxy- phenylacetarnide (n) 1 Epanolol I Reference(s): DE 2 362 568 (ICI; appl. 20.6.1974; GB-prior. 17.9.1973). DOS 2525 133 (ICI; appl. 5.6.1975; GB-prior. 5.6.1974). US 4 141 987 (ICI; 27.2.1979; GB-prior. 5.6.1974). US4 221 807 (ICI; 9.9.1980; GB-prior. 5.6.1974). US4 260 632 (1CI; 7.4.1981; GB-prior. 5.6.1974). US 4 327 113 (ICI; 27.4.1982; GB-prior. 5.6.1974). US 4 387 099 (ICI; 7.6.1983; GB-prior. 5.6.1974). Large, M.S.; Smith, L.H.: J. Med. Chem. (JMCMAR) 25, 1286 (1982). synthesis of N-(2-aminoethy1)-4-benzyloxyphenylacetamide: DOS 2 362 568 (ICI; appl. 17.12.1973; GB-prior. 15.1 2.1972, 17.9.1973). Formulation(s): tabl. Trade Name(s): GB: Visacor (ICI); wfm Eperisone RN: 64840-90-0 MF: C,,H,,NO MW: 259.39 LD,,: 1024 mgkg (M, p.0.); 1850 mgkg (R, p.0.) CN: I-(4-ethylpheny1)-2-methyl-3-(1 -piperidinyl)-I -propanone ATC: A03AC Use: skeletal muscle relaxant hydrochloride RN: 56839-43-1 MF: C,,H2,N0. HCI MW: 295.85 LD5,: 43 mgkg (M, i.v.); 324 mglkg (M, p.0.); 51 mgkg (R, i.v.); 1002 mgkg (R, p.0.); >750 mglkg (dog, p.0.) Reference(s): DOS 2 458 638 (Eisai; appl. 11.12.1974; J-prior. 14.12.1973). US 4 181 803 (Eisai; 1.1.1980; J-prior. 14.12.1973). US 39 995 047 (Eisai; 30.1 1.1976; J-prior. 14.12.1973). 4'-ethylpropio- form - piperidine alternative syntheses: JP 7 930 178 (Asahi; appl. 5.8.1977). JP 7 932 480 (Asahi; appl. 19.8.1977). JP 7 936 274 (Asahi; appl. 24.8.1977). Eperisone Formulation(s): tabl. 50 mg (as hydrochloride) phenane aldehyde Trade Name(s): J: Atines (Takeda) Dechozyl (Sawai) Epenard (Tai yo) Epeso (Teikoku) Evonton (Tatsumi) Rinpral (Nichiiko) Miolease (Hotta) Sunbazon (Toyo Jozo) Myonabase (Kotobuki) Myonal (Eisai; 1983) ATC: R01 AA03; R01 AB05; R03CA02; SOlFB02 Use: sympathomimetic RN: 299-42-3 MF: C,,H,,NO MW: 165.24 EINECS: 206-080-5 LD,,: 74 mglkg (M, i.v.); 689 mglkg (M, p.0.); 600 mglkg (R, p.0.) CN: [R-(R*,S*)]-a-[l-(methylamino)ethyl]benzenemethanol hydrochloride RN: 50-98-6 MF: C,,H,,NO. HCI MW: 201.70 EINECS: 200-074-6 LD,,,: 95 mglkg (M, i.v.); 400 mglkg (M, p.0.); 69 mglkg (R, i.v.) sulfate (2:l) RN: 134-72-5 MF: Cl,,H15N0 1/2H2S04 MW: 428.55 EINECS: 205-154-4 LD,,,: 8 12 mglkg (M, p.0.); 102 mglkg (R, i.v.); 404 mglkg (R, p.0.) H 0 enzymatically with sccharomyces cerevisio; $ + HO benzaldehyde sucrose (-)-1 -hydroxy- 1 -phenylacetone ("phenylacetylcorbinol") (I) Epicillin E 749 methyl amine Reference(s): Budesinsky-Protiva, 24-27. US 1 956 950 (E. Bilhuber; 1934; D-prior. 1930). DD 51 651 (D. Groger, H P. Schmauder, H. Frommel; appl. 15.10.1965). DL-ephedrine by hydrogenation of N-methylaminopropiophenone: DRP 469 782 (E. Merck; appl. 1926). Formulation(s): amp. 10 mg, 25 mg, 50 mg (as hydrochloride); drg. 2.5 mg, 10 mg; sol. 100 mgIlO ml; syrup 100 mg1100 ml, lgI1000 ml (as hydrochloride); syrup 26.7 mgllOO ml (as sulfate); tabl. 10 mg, 25 mg, 50 mg Trade Name(s): D: Antifohnon (Siidmedica)- comb. Asthma 6-N (Hobein)- comb. Ephepect (Bolder)-comb. Ephetonin (Merck); wfm Equisil (K1ein)-comb. Felsol (Roland)-comb. Fomagrippin (Michal1ik)- comb. Hevertopect (Hevert)- comb. Medigel (Medice)-comb. Perdiphen (Schwabe1 Spitzner)-comb. Pulmocordio (Hevert)- comb. Rhinoguttae (Leyh)-comb. Stipo Nasenspray (Repha)- comb. F: GB: 1: Vencipan (Artesan)-comb. Wick MediNait (Wick Pharma)-comb. generic and numerous combination preparations Ephedroides "3" (Silbert et Ripert); wfm generic and numerous combination preparations CAM (Shire) numerous combination preparations Codeinol (Saba)-comb. Deltatarinolo (Lepetit)- comb. Paidorinovit (SIT)-comb. Rinopumilene (Montefarmaco) Rinovit (SIT)-comb. combination preparations J: Ephedrine "Nagai" (Dainippon) numerous generic and combination preparations USA: Broncholate (Sanofi; as hydrochloride)-comb. Kie (Laser; as hydrochloride)-comb. Marax (Pfizer; as sulfate) Pretz-D (Parnell; as sulfate)-comb. Quadrinal (Knoll Labs.; as hydrochloride)-comb. Rynatuss (Wallace; as tannate)-comb. numerous combination preparations ATC: JOlCA07 Use: antibiotic RN: 26774-90-3 MF: C,,H,,N,O,S MW: 351.43 EINECS: 248-001-7 LD,: 3870 mgkg (M, i.p.) CN: [2S-[2a,Sa,6P(S*)]]-6-[(amino- 1,4-cyclohexadien- 1 -ylacetyl)amino]-3,3-dimethyl-7-oxo-4-thia- 1 - azabicyclo[3.2.0]heptane-2-carboxylic acid monosodium salt RN: 34735-40-5 MF: C,,H,N,NaO,S MW: 373.41 750 E Epimestrol -CUGn methyl acetoacetate NH, NH, D(-)-a-phenyl- D-2-(1.4-cyclo- glycine hexodieny1)- glycine COOH CI-COOC2H5, N(C2H5), S CH3 ethyl chlora- L 8, formate 6-amino- penicillanic ocid COOH O+ N+~3 'S H CH3 NH,H I Epicillin I Reference(s): US 3 485 819 (Squibb; 23.12.1969; USA-prior. 2.7.1968). DAS 1 967 020 (Squibb; appl. 23.6.1969; USA-prior. 2.7.1968) tnicrobiological acylation by means of Aptmnocladiutn aranearurn (ATCC 20453). , US 4 073 687 (Shionogi; 14.2.1978; J-prior. 12.5.1976). Formulation(s): f. c. drg. 1000 mg; vial 2125.4 mg, 5313.5 mg (as sodium salt) Trade Name(s): D: Spectacillin (Sandoz); wfm F: Dexacilline (Squibb); wfrn I: Dexacillin (Squibb); wfm Epimestrol ATC: G03GB03 Use: estrogen (ovulation stimulant), anterior, pituitary activator RN: 7004-98-0 MF: C,,H,,O, MW: 302.41 EINECS: 230-278-0 CN: (1 6a, 17a)-3-methoxyestra- 1,3,5(IO)-triene- 16,17-did 3.1 6a.17~-trihydroxy- dimethyl sulfate 1,3.5(10)-estrotriene Rrfcrence(s): NL 95 257 (Organon; appl. 1958). starting n~aterial and alternative synthesis: US 2 584 271 (Searle; 1952; prior. 1948). Prelog, V. et al.: Helv. Chim. Acta (HCACAV) 28,250 (1945). Epimestrol alrernative synthesis: Caglioti, L.; Magi, M.: Tetrahedron (TETRAB) 19, 1127 (1963). . CN: 1,3-dihydro-4-methyl- 5-[ 4-( methylthio)benzoyl ]-2 H-imidazol-2-one P Entacapone E 745 hydroxyacetone urea 1.3-dihydro- 4-methyl-2H- irnidazol-2-one (I) 4-( rnethylthi0 )- benzoyl. [2S-[2a,Sa,6P(S*)] ]-6 -[ (amino- 1,4-cyclohexadien- 1 -ylacetyl)amino ]-3 ,3-dimethyl-7-oxo-4-thia- 1 - azabicyclo[3.2.0]heptane-2-carboxylic acid monosodium salt RN: 3473 5-4 0-5 MF: C,,H,N,NaO,S MW: 373.41 750 . yN-"tw2 + H2N*NH2 / 0 methyl 4-benzyloxy- ethylene- N-(2-arninoethy1 )-4 -benzyloxy- phenylacetate diamine phenylacetarnide (1) 1.2-epoxy- 3-( 2- cyanophenoxy )- prapone N-[Z-[ 3-( 2-cyanophenoxy )-2 -hydroxy.