Metixene M 131 1 2-methyl-L- serine 1. PBr5 2. NoOH + (from ethoxy- bromobenzene L-2-amino-2- sodium) methyl-3-bromo- propionic acid Reference(s): a Stein, G.A. eta].: J. Am. Chem. Soc. (JACSAT) 77,700 (1955). US 2 868 818 (Merck & Co.; 13.1.1959; appl. 15.12.1953). b Potts, K.T.: J. Chem. Soc. (JCSOA9) 1955, 1632. c DOS 1 543 763 (Merck & Co.; appl. 25.5.1966; USA-prior. 3.6.1965). GB 1 105 103 (Merck & Co.; appl. 1.6.1966; USA-prior. 3.6.1965). alternative syntheses: enantioselective synthesis.from L-tyrosine via the reaction product from N,O-bis(carbobenzoxy)-L-tyrosine with benzaldehyde and its methylation: US 4 508 921 (Merck & Co.; 2.4.1985; appl. 28.6.1984). DL-rnetirosine by reaction ?f ~,~-dimeth~l-4-h~drox~ben~~larnine with ethyl 2-nitropropionate: Saari, W.S.: J. Org. Chern. (JOCEAH) 32,4074 (1967). combination with carbidopa: US 4 389 415 (Merck & Co.; 21.6.1983; USA-prior. 24.1.1978,5.10.1979,20.7.1981). EP 3 353 (Merck & Co.; appl. 24.1.1979; USA-prior. 24.1.1978). Formulation(s): cps. 250 mg Trade Name(s): GB: Dernser (Merck Sharp & USA: Dernser (Merck Sharp & Dohrne); wfm Dohrne) Metixene (Methixene) ATC: N04AA03 Use: antiparkinsonian, antispasmodic RN: 4969-02-2 MF: C2,H2,NS MW: 309.48 EINECS: 225-610-6 LD,,,: 18rng/kg(M,i.v.);430rnglkg(M,p.o.) CN: l-methyl-3-(9H-thioxanthen-9-ylrnethyl)piperidine hydrochloride RN: 1553-34-0 MF: C2,H2,NS . HCI MW: 345.94 EINECS: 216-300-1 LD,,: 18 rngkg (M, i.v.); 346 rnglkg (M, p.0.); 24 rnglkg (R, i.v.); 1460 rnglkg (R, p.0.) hydrochloride monohydrate RN: 7081-40-5 MF: C2,H2,NS . HCl . H20 MW: 363.95 13 12 M Metoclopramide CI thioxonthene 3-chloromethyl- 1 -methylpiperidine y3 N 333 Metixene Reference(s): US 2 905 590 (The Wander Comp.; 22.9.1959; prior. 7.5.1958). Formulation(s): tabl. 2.5 mg, 5 mg, 15 mg (as hydrochloride) Trade Name(s): D: Tremarit (Novartis Pharma) Tremonil (Sandoz; as F: Spasmenzyme (Salvoxyl- hydrochloride hydrate); Wander)-comb.; wfm wfm GB: Tremonil (Wander); wfm I: Tremaril (Sandoz) J: Atosil (Teisan) Cholinfall (Tokyo Tanabe) Dalpan (Grelan) Methyloxan (Nippon Shoji- Kodama) Thioperkin (Hokuriku) USA: Trest (Dorsey); wfm Metoclopramide ATC: A03FAOl Use: anti-emetic, gastric therapeutic RN: 364-62-5 MF: CJ4Hz2CIN302 MW: 299.80 EINECS: 206-662-9 CN: 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide monohy drochIoride RN: 7232-21-5 MF: C,4H22C1N,0, . HCI MW: 336.26 EINECS: 230-634-5 monohydrochloride monohydrate RN: 54143-57-6 MF: CJ4H2,ClN3O2. HC1. H,O MW: 354.28 0 0. + , OH d 6". N t' z t'J t' z HN CH, K 0 4-amino- methyl (1) salicylic 4-omino- ocid solicylote , + H,c/O, /P CH~ CI~. CH,COOH s d OP 'O CH3 HN CH, K HN CH, 0 K 0 dirnethyl methyl 4- methyl 4-acei- sulfote ocetornido- omido-5-chloro- 2-methoxy- Z-methoxy- benzoate benzoate (U) Metoclopramide M 13 13 'CH, I. olurninurn Cl' y I isopropyiote N.N-diethyi- ethylenediornine I Metocloprornide I Reference(s): DE 1 233 877 (Soc. &Etudes Scientifiques et Industrielles de 1'Ile-de-France; appl. 14.7.1962; F-prior. 25.7.1961). FR 1 313 758 (Soc. &Etudes Scientifiques et Industrielles de 1'Ile-de-France; appl. 25.7.1961). US 3 177 252 (Soc. dlEtudes Scientifiques et Industrielles de 1'Ile-de-France; 6.4.1965; F-prior. 25.7.1961). US 3 219 528 (Soc. d'Etudes Scientifiques et Industrielles de 1'Ile-de-France; 23.11.1965; F-prior. 25.7.1961, 5.8.1961,4.11.1961). US 3 357 978 (Soc. &Etudes Scientifiques et Industrielles de l'lle-de-France; 12.12.1967; F-prior. 5.3.1963). alternative syntheses: DOS 1 932 512 (Huhtamaki; appl. 26.6.1969; SF-prior. 28.6.1968). DAS 1 960 130 (Yamanouchi; appl. 29.11.1969; J-prior. 2.12.1968,9.12.1968,4.4.1969). DAS 1 966 453 (Yamanouchi; appl. 29.11.1969; J-prior. 9.12.1968). DAS 2 102 848 (Delmar; appl. 21.1.197 1 ; USA-prior. 21.1.1970). DAS 2 119 724 (Teikoku Hormone Mfg.; appl. 22.4.1971; ~-~rioi. 24.4.1970). DAS 2 162 917 (Soc. &Etudes Scientifiques et Industrielles de 1 'Ile-de-France; appl. 17.12.1971 ; J-prior. 21.12.1970). DAS 2 166 117 (Teikoku Hormone Mfg.; appl. 22.4.197 1 ; J-prior. 24.4.1970). DAS 2 166 1 18 (Teikoku Hormone Mfg.; appl. 22.4.1971 ; J-prior. 24.4.1970). DAS 2 342 934 (Delmar; appl. 24.8.1973; GB-prior. 25.8.1972, 13.12.1972, 16.4.1973). DAS 2 365 988 (Heumann & Co.; appl. 12.7.1973). starting material: DAS 2 335 439 (Heumann & Co.; appl. 12.7.1973). Formulation(s): amp. 10 mg/2 ml, 50 mg1lO ml; cps. 10 mg, 30 mg; drops 4 mg, 5 mg; liquid 4 mg; s. r. cps. 30 mg; sol. 1 mglml, 15 mg115 ml, 5 mg/5 ml; suppos. 10 mg, 20 mg; tabl. 10 mg (as hydrochloride hydrate) Trade Name(s): D: Cerucal (ASTA Medica AW D) Gastronerton (Dolorgiet) Gastrosil (Heumann) Gastro-Timelets (Temmler) Paspertase (Solvay Arzneimitte1)-comb. Paspertin (Solvay Arzneimittel; 1965) generics F: Anausin Metoclopramide (ASTA Medica) CCphalgan (UPSA)-comb. Metoclopramide GNR (GNR-pharma) Primptran (Thera France; 1964) GB: Gastrobid Continus (Napp) Maxolon (Monmouth; 1967) Paramax (Lorex)-comb. I: Citroplus (Irbi) Clopan (Firma) Cronauzan (ASTA Medica) Ede (Teofarma)-comb. Eugastran (Piam)-comb. Geffer (Boehringer Mannh.) Plasil (Lepetit; 1967) Plasil enzimatico (Lepetit)- comb. Randum (Roussel) Viscal (Zoja) J: Donopon-GP (Sana) Peraprin (Taiyo Yakuko Takay ama) Primperan (Fujisawa; 1970) Putoprin (Mohan) Terperan (Teikoku Zoki) USA: Reglan (Robins; 1979) 1314 M Metolazone Metolazone ATC: C03BA08 Use: diuretic, antihypertensive RN: 17560-51-9 MF: C16H,6ClN103S MW: 365.84 EINECS: 241-539-3 LDso: >5 @kg (M, p.0.); >5 @kg (R, p.o.1 CN: 7-chloro-l,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamide 5-chloro-2- ethyl chloro- methyloniline forrnote 5-chloro-N-ethoxy- carbonyl-2-methyl- aniline (I) I. CISO~H H 2. NH3 I 1. chloro- acid 4-sulfomoyl-5-chloro- N-ethoxycorbonyl-2- rnethyloniline 6-sulfarnoyl-7- chloro-isotoic anhydride 2-amino-5-sulf- acetaldehyde ornoyl-4-chloro- dimethyl N-(0-tolyl)- ocetal benzarnide (111) Metolozone DAS 1 620 740 (Pennwalt; appl. 24.12.1966; USA-prior. 3.1.1966). DOS 2 13 1 622 (Pennwalt; appl. 25.6.1971; USA-prior. 29.6.1970). US 3 360 518 (Wallace & Tiernan; 26.12.1967; prior. 3.1.1966). US 3 557 11 1 (Wallace & Tiernan; 19.1.1971; prior. 29.3.1968). US 3 761 480 (Pennwalt; 25.9.1973; prlor. 10.7.1968, 7.1 1.1969, 15.3.1972). DOS 2 035 657 (Sumitomo; appl. 17.7.1970; J-prior. 22.7.1969, 25.2.1970, 27.3.1970). Formulationfs): tabl. 2.5 mg, 5 mg, 10 mg Trade Namels): D: Zaroxolyn (Hcumann) I: Zaroxolyn (SmithKline J: Normelan (Sandoz- GB: Metenix (Hoechst) ppppppp Beecham) - - - - - Sanky o) - - - Metopimazine M 13 15 USA: Mykrox (Medeva) Zaroxoly n (Medeva) Metopimazine ATC: A04AD05 Use: anti-emetic RN: 14008-44-7 MF: C2,H,N303S2 MW: 445.61 EINECS: 237-8 18-4 CN: 1-[3-[2-(methylsulfonyl)-10H-phenothiazin-l0-yl]propyl~-4-piperidinecarboxamide 2-methylsulfonyl- phenothiozine chloropropone 10-(3-~hloropropyl)- 2-methylsulfonyl- phenothiozine (I) piperidine-4- corboxomide Metopimazine DE 1 092 476 (RhGne-Poulenc; appl. 14.4.1959; F-prior. 24.4.1958). Formulation(s): amp. 10 mgll ml; cps. 15 mg; drg. 2.5 mg; sol. 4 mg/ml, 5 mgI5 ml; suppos. 5 mg; tabl. 2.5 mg Trade Name(& F: Vogalhe (Schwarz) Metoprolol ATC: C07AB02 Use: beta blocking agent RN: 5 1384-5 1- 1 MF: C,,H2,N03 MW: 267.37 EINECS: 253-483-7 LD,,,: 62 mgkg (M, i.v.); 1050 mgkg (M, p.0.); 71.9 mglkg (R, i.v.); 3470 mg/kg (R, p.0.); 60 mgkg (dog, i.v.) CN: 1-[4-(2-methoxyethyl)phenoxy]-3-[(l-methylethyl)amino]-2-propanol tartrate (2:l) RN: 56392-17-7 MF: C,,H2,NOv 1/2C4H,0, MW: 684.82 EINECS: 260-148-9 13 16 M Metrizamide 4-(2-melhoxy- epichloro ethy1)phenol hydrin 0 1,2-epoxy-3-[4-(2- rnethoxyethy1)phen- oxylpropone (I) Reference(s): DAS 2 106 209 (AB Hassle; appl. 10.2.1971; S-prior. 18.2.1970). US 3 873 600 (AB Hassle; 25.3.1975; S-prior. 18.2.1970). US 3 998 790 (AB Hassle; 21.12.1976; appl. 15.1.1974; prior. 19.3.1973). isopropyl- (S)-enantiomer: US 5 034 535 (Astra; 23.7.1991 : S-prior. 22.4.1988). US 5 362 757 (Sepracor; 8.1 1.1994; appl. 16.1 1.1992; prior. 18.3.1991). Metoprolol Formulation(s): amp. 5 mgI5 ml; s. r. f. c. tabl. 200 mg; s. r. tabl. 200 mg; tabl. 50 mg, 100 mg (as tartrate) ornine I Trade Natne(s): D: Azumetop (Azupharma) Beloc (Astra; 1976) Lopresor (Novartis Pharma; 1976) Prelis (Novartis Pharma; 1982) Sigaprolol (Kytta- Siegfried) Treloc (Astra)-comb. generics F: Logimax (Astra)-comb. Logroton (Novartis Pharma SA)-comb. Lopressor (Novartis Pharma SA; 1980) Seloken (Astra; 1980) GB: Betaloc (Astra: 1975) Co-betaloc (Astra; as tartrate)-comb. Lopresor (Novartis; 1975) I: Igroton Lopresor (Novartis)-comb. Lopresor (Novartis; 1978) Seloken (Astra; 1978) Selozide (Astra)-comb. J: Lopresor (Ciba-Geigy) Seloken (Fujisawa; 1983) USA: Lopressor (Novartis; 1978) Metrizamide ATC: VOBABOl Use: X-ray contrast medium RN: 55 134- 1 1-7 MF: C,,H2,13N30, MW: 789.10 CN: 2-[[3-(acetylamino)-5-(acelylmethylamino)-2,4,6-triiodobenzoyl]amino]-2-deoxy-~-glucopyranose rnetrizoic acid (4. v.) rnetrizoyl chloride (I) Metrizoic acid M 13 17 I Metrizamide US 3 701 77 1 (Nyegaard; 31.10.1972: GB-prior. 27.6.1969,9.2.1970). DOS 2 03 1 724 (Nyegaard; appl. 26.6.1970; GB-prior. 27.6.1969,9.2.I97O). Formularion(s): amp. 3.75 g, 6.75 g (12.5 %, 13.5 %, 18.75 %) Trade Name(s): D: Amipaque (Schering; F: Amipaque (Sterling USA: Amipaque (Wjnthrop- 1977); wfm Winthrop; 1980); wfm Breon; 1975); wfm Arnipaque (Schering); wfrn J: Amipaque (Schering; 1981) Metrizoic acid ATC: V08AA02 Use: X-ray contrast medium RN: 1949-45-7 MF: Cl2HI1I3N2O4 MW: 627.94 EINECS: 217-761-1 LD,,: 10 g/kg (M, i.v.); >46.8 mg/kg (M, p.0.); 14.3 glkg (R, i.v.); 38.1 mglkg (R, p.0.) CN: 3-(acetylamino)-5-(acetylmethylamino)-2,4,6-triiodobenzoic acid monosodium salt RN: 7225-61-8 MF: C1,Hlo13N2Na04 MW: 649.92 EINECS: 230-624-0 arnidotrizoic acid dirnethyl (4. v.1 sulfate Metrizoic acid Reference(s): GB 973 881 (Nyegaard; appl. 5.12.1960; N-prior. 8.12.1959). GB 987 796 (Nyegaard; appl. 26.2.1962; N-prior. 28.2.1961). US 3 178 473 (Nyegaard; 13.4.1965; appl. 2.3.1962). Formulafion(s): amp. 100 mg, 150 mg, 260 mg, 350 mg, 370 mg, 440 mg (as Ca-, Mg-, Na- and meglumine salt) 13 18 M Metronidazole Trade Name(s): D: Ronpacon (Cilag-Chemie); F: Isopaque (Winthrop); wfm USA: Isopaque (Winthrop); wfrn wfm 1: Isopaque (Torii); wfm Metronidazole ATC: AOlAB17;D06BXO1;GO1AFO1; JOIXDOI; POlABOl Use: chemotherapeutic (trichomonas) RN: LD,,,: CN: 443-48-1 MF: C6HyN303 MW: 171.16 EINECS: 207-136-1 3800 mgkg (M, p.0.); 3 glkg (R, p.o.1 2-methyl-5-nitro- 1 H-imidazole-1-ethanol 2-methyl- 2-methyl-5- irnidozole nitroirnidozole (I) I Metronidazole ethylene oxide Formularion(s): cps. 250 mg, 375 mg; f. c. tabl. 250 mg, 400 mg; suppos. 100 mg (vaginal); tabl. 250 mg, 400 mg; vaginal tabl. 100 mg; vial 5 g11000 ml Trade Name(s): D: Arilin (Wolff) GB: Canesten-Clont- Kombipack. (Bayer) Clont (Bayer Vital) Flagyl (Rhbne-Poulenc Rorer) Fossyol (Merckle) generics F: Flagyl (Specia) I: Rodogyl (Specia)-comb. Rozagel (Biorga) Tergynan (Bouchara)- comb. Anabact (ASTA Medica AWD) Elyzol (Dumex) Flagyl (Rhbne-Poulenc Rorer) Metrogel (Novartis) Rozex (S tafford-Miller) Zidoval(3M) Deflamon (SPA) Flagyl (Farmitalia) Metronid (Formulario Naz.) Metronidazolo Same (Savoma) Vagilen (Farmigea) .I: Asuzol (Fuji) Flagyl (Shionogi) Nida (Toyo Pharmar) Takimetol (Nakataki) Trichocide (Green Cross) Wagitran (Nakataki) USA: Flagyl (SCS) Flagyl (SCS; as hydrochloride) Flagyl (Searle) Helidac (Procter & Gamble) Metyrapone ATC: V04CDO1 Use: adrenocorticostatic RN: 54-36-4 MF: CI4HI4N,O MW: 226.28 EINECS: 200-206-2 CN: 2-methyl-l,2-di-3-pyridinyl-1-propanone Mexazolam M 1319 cathodic reduction 3-ocetyl- pyridine [Hg-cathode. -2.4 V, fiN> 1~ unul rN\ conc. H so4 -A - HU Reference(s): Chart, J.J. et a].: Experientia (EXPEAM) 14, 151 (1958). Allen, M.J.: J. Org. Chern. (JOCEAH) 15,435 (1950). - (pinacol-synthesis) Bencze, W.L.; Allen, M.J.: J. Am. Chern. Soc. (JACSAT) 81,4015 (1959). 0 as intermediate mentioned in: US 2 923 710 (Ciba; 2.2.1960, prior. 14.7.1958). US 2 966 493 (Ciba; 27.12.1960; appl. 10.3.1958). Forntulation(s): cps. 250 mg Trade Name(s): D: Metopiron (Ciba); wfrn GB: Metopirone (Novartis) J: Metopiron (Ciba-Geigy- F: Metopirone (Novartis I: Metopiron (Ciba); wfm Takeda) Pharma SA) USA: Metopirone (Ciba); wfm Mexazolam ATC: NO5 Use: tranquilizer, anxiolytic RN: 31868-18-5 MF: C,8H,6C12N202 MW: 363.24 LD,,: 4571 rngkg (M, p.0.); 4500 rngkg (R, p.0.) CN: 10-chloro-l l b-(0-chloropheny1)-2,3,7,ll b-tetrahydro-3-rnethyloxazolo[3,2-6][1,4]benzodiazepin-6(5H)- one CI $1 / + iBr - CI $1 NH2 NH OL~r 2-amino-2'5 bromoacetyl (I) dichlorabenzo- chloride phenone 2-amino-1 - proponol I Mexozalam Heference(s): Migadera, T. et al.: J. Med. Chem. (JMCMAR) 14,520 (1971). JP 4 941 439 (Sankyo; appl. 21.12.1970). 1320 M Mexenone Formulation(s): 0.5 mg, 1 mg Trade Name(s): J: Melex (Sankyo) Mexenone ATC: D02B Use: ultraviolet screen RN: 1641-17-4 MF: C,SH1403 MW: 242.27 EINECS: 21 6-691-9 CN: (2-hydroxy-4-methoxyphenyl)(4-methylphenyl)methanone /C"3 dc + bo/CH3 AICI,. DMF H3C 4-rnethylbenzoyl 1,3-dirneth- chloride oxybenzene Reference(s): US 2 773 903 (American Cyanamid; 1956; prior. 1955). Formulation(s): cream 4 % Trade Name(s): GB: Uvistat (WB Pharmaceuticals); wfm Mexenone Mexiletine ATC: COlBB02 Use: anticonvulsant, antiarrhythmic RN: 3 1828-71-4 MF: C, ,Hl,NO MW: 179.26 EINECS: 250-825-7 LD,,,: 23 mglkg (M, i.v.); 320 mglkg (M, p.0.); 41 mglkg (R, i.v.) CN: 1-(2,6-dimethy1phenoxy)-2-propanamine hydrochloride RN: 5370-01-4 MF: C,,H,,NO . HCl MW: 215.72 EINECS: 226-362-1 LD,,: 21 mglkg(M,i.v.); 272mglkg(M,p.o.); 27 mglkg (R, i.v.); 330 mglkg (R, p.0.); 19 mglkg (dog, i.v.); 356 mglkg (dog, p.0.) sodium 2.6-di- chloroocetone 1 -(2.6-dimethyl- methylphenolate phenoxy)-2-propanone (I) H2N-OH Hz. Roney-Ni I hydroxyl- amine Mexiletine . 5-chloro- 2- ethyl chloro- methyloniline forrnote 5-chloro-N-ethoxy- carbonyl-2-methyl- aniline (I) I. CISO~H H 2. NH3 I 1. chloro- acid 4-sulfomoyl-5-chloro- N-ethoxycorbonyl- 2-. EINECS: 23 7-8 1 8-4 CN: 1-[ 3-[ 2-( methylsulfonyl )-1 0H-phenothiazin-l0-yl]propyl ~-4 -piperidinecarboxamide 2-methylsulfonyl- phenothiozine chloropropone 1 0-( 3-~ hloropropyl )- 2-methylsulfonyl- phenothiozine. RN: 1756 0-5 1-9 MF: C16H,6ClN103S MW: 365.84 EINECS: 24 1-5 3 9-3 LDso: >5 @kg (M, p.0.); >5 @kg (R, p.o.1 CN: 7-chloro-l,2,3,4-tetrahydro-2-methyl- 3-( 2-methylphenyl )-4 -oxo-6-quinazolinesulfonamide