Meprobamate M 1251 I-; / H H OyOH or microbiologicolly with Bacillus & H3 sphoeriws vor. fusiformis ATCC 7055 selenium dioxide, tert-omyl alcohol H H 0 ' Reference(s): US 3 164 618 (Schering Corp., 5.1.1965; prior. 23.7.1957, 8.5.1958). Taub, D. et al.: J. Am. Chem. Soc. (JACSAT) 82,4012 (1960); 80,4435 (1958). Oliveto, E.P. et al.: J. Am. Chem. Soc. (JACSAT) 80,4428 (1958). starting material for a: Slates, H.L.; Wandler, N.L.: J. Org. Chem. (JOCEAH) 22,498 (1957). US 2 671 794 (Glidden; 1954; prior. 1950, 1949). alternative syntheses: from hecogenin: Nathansohn, G.B. et al.: Experientia (EXPEAM) 17,448 (1961). from sitosterin: US 4 041 055 (Upjohn; 9.8.1977; prior. 17.11.1975). Trade Namefs): F: Betalone (Lepetit); wfm Policort (Lepetit)-comb.; USA: Betapar (Parke Davis); wfm I: Corti-Bi (Sidus); wfm wfm Betapred (Schering); wfm Meprobamate ATC: NOSBCOI Use: tranquilizer RN: 57-53-4 MF: C,H,RN20, MW: 218.25 EINECS: 200-337-5 LD,,,: 230 mg/kg (M, i.v.); 750 mglkg (M, p.0.); 350 mg/kg (R, i.v.); 794 mglkg (R, p.0.) CN: 2-methyl-2-propyl-l,3-propanediol dicarbamate 1. COCI, H3C 2. NH3 H3cqcH3 + HCHO -+ CHO 1. phosgene CH3 2-methyl- form- 2-methyl-2- Meprobamate valeraldehyde oldehyde propyl-1,3- propanediol 1252 M Meproscillarin Reference(3): US 2 724 720 (Carter Products; 1955; prior. 1953). Ludwig, B.J.; Piech, E.C.: J. Am. Chem. Soc. (JACSAT) 73,5779 (1951). Formulation(s): f. c. tabl. 200 mg, 400 mg Trade Name(s): D: Meprobamat Saar generics and numerous Harmonin (Yoshitomi) (Philopharm) combination preparations Mepron (Choseido) Visano (Kade) GB: Equagesic (Wy eth)-comb. Mepron (Kanto) F: Equanil (Sanofi Winthrop) I: Meprob (Tariff. Nazionale) Xalogen (Ono) Meprobamate Richard Quanil (Wyeth) USA: Equagesic (Wyeth-Ayerst) (Richard) J: Atraxin (Daiichi) Equanil (Wyeth-Ayerst) Novalm (LDM SantC) Erina (Sumitomo) Miltown (Wallace) Meproscillarin ATC: CO~AB (Rambufaside; Meproscillaridin) Use: cardiac glycoside RN: 33396-37-1 MF: C,,H,O, MW: 544.69 EINECS: 251-493-6 LD,,: 2800pglkg(M,i.v.); 12.5mg/kg(M,p.o.); 5800 pglkg (R, i.v.); 79 mglkg (R, po.) CN: (3~)-3-[(6-deoxy-4-0-methyl-a-~-mannopyrmosyl)oxy]-l4-hydroxybufa-4,2O,22-trienolide O-CH, ethyl 2',3'-proscillaridin- orthoformate (I) proscillaridin triethyl (9. v.) orthofarmate 1. DMF. NaH 2. HCI, CH,OH 1 + H,C-I methyl iodide I Meproscillarin Reference(s): DOS 2 301 382 (Knoll; appl. 12.1.1973). DOS 2 427 976 (Knoll; appl. 10.6.1974). Kubinyi, H.: Arzneim Forsch. (ARZNAD) 28 (I), 491 (1978). alternative syntheses: DE 1 910 207 (Knoll; appl. 28.2.1969). Kubinyi, H.: Arch. Pharm. Ber. Dtsch. Pharm. Ges. (APBDAJ) 304,53 1 (1971). combination with verapamil: DOS 2 746 881 (BASF; appl. 19.10.1977). Formulation(s): tabl. 0.25 mg Trade Name(s): D: Clift (Knoll); wfm Meprylcaine RN: 495-70-5 MF: C,,H2,N02 MW: 235.33 CN: 2-methyl-2-(propy1amino)- 1 -propano1 benzoate (ester) ATC: NOlB Use: local anesthetic benzoyl N-(1.1 -dimethyl- chloride 2-hydroxyethy1)- propylomine I Meprylcaine Reference(s): US 2 421 129 (Oradent Chem.; 1947; prior. 1944). local anesthetic effective injection solution: US 2 767 207 (Mizzy Inc.; 1956; prior. 1953). Formulation(s): cream, gel, sol. Trade Name(s): J: Epirocain (Eisai); wfm USA: Oracaine (Mizzy); wfm Meptazinol ATC: N02AX Use: narcotic, analgesic RN: 54340-58-8 MF: C,,H,,NO MW: 233.36 EINECS: 259-109-9 CN: 3-(3-ethylhexahydro-l-methyl-lH-azepin-3-yl)phenol hydrochloride RN: 59263-76-2 MF: C,,H,,NO , HC1 MW: 269.82 EINECS: 261-683-0 LDso: 282 mglkg (M, p.0.); 1260 mgkg (R, p.0.) 1254 M Mepyramine 2-(3-methoxyphenyl)- ethyl 4-iodo- butyronitrile butyrote Hz, Roney-Ni LiAIH4 1 lithium aluminum form- aldehyde Meptazinol I DOS 1 941 534 (Wyeth; appl. 14.8.1969; GR-prior. 16.8.1968,4.9.1968, 28.1.1969). GB 1 285 025 (Wyeth; Complete Specification 12.8.1969; prior. 16.8.1968,4.9.1968, 28.1.1969). alternative syntheses: Bradley, G. et al.: Eur. J. Med. Chem. (EJMCAS) 15,375 (1980). svnrhesis ofenantiomers: DOS 2 105 463 (Wyeth; appl. 5.2.1971; GB-prior. 6.2.1970). combination with ibuprofen: EP 99 186 (Wyeth; appl. 18.6.1983; GB-prior. 8.7.1982). Formularion(s): amp. 100 mglml; tabl. 200 mg (as hydrochloride) Trade Name(s): D: Meptid (Wyeth; as GB: - Meptid (Monmouth) hydrochloride) Mep yramine (Pyrilamine) ATC: D04AA02; RO6ACOl Use: antihistaminic RN: 91-84-9 MF: C,,H2,N,0 MW: 285.39 EINECS: 202-102-2 LD,,,: 23 mglkg (M, i.v.); 220 mglkg (M, p.0.); 950 mglkg (R, p.0.) CN: N-[(4-methoxyphenyl)methyl]-N,N-dimethyl-N-2-pyridinyl-1,2-ethanediamine monohydrochloride RN: 6036-95-9 MF: CI7H2,N3O. HCl MW: 321.85 EINECS: 227-920-7 LD,,,: 25 mglkg (M, i.v.); 325 mglkg (M, p.0.) maleate (1:l) RN: 59-33-6 MF: C,,H2,N,0. C4H404 MW: 401.46 EINECS: 200-422-7 LD,,: 23 mglkg (M, i.v.1; 220 mglkg (M, p.0.); 5 13 mglkg (R, p.0.) Mequitazine M 1255 ONH2 + HCOOH OHC formic 2-amino- 4-methoxy- acid 2-(4-methoxy- pyridine benzoldehyde benzylomino)pyridine (I) 1. sodium amide 2. 2-(dimethylomino)- ethyl chlaride / Mepyramine I Fortnulation(s): amp. 15 mg, 25 mg; cream 2 %; tabl. 25 mg, 100 mg Trade Name(s): D: Praecinal (Pfleger)-comb.; F: wfrn Snup (Kar1spharma)- comb.; wfm GB : Triaminic (Wander)-comb.; wfm USA: Vistosan A (Pharm- Allergen)-comb.; wfrn Nortussine (Norgine Poly-Histine-D (Sanofi; as Pharma)-comb. maleate)-comb.; wfm Triaminic (Novartis)-comb. Rynatan (Wallace; as Anthisan (May & Baker); tannate)-comb.; wfm wfm Triaminic (Novartis Atrohist (Medeva; as Consumer)-comb.; wfm tannate)-comb.; wfm Triotann (Duramed; as tannate)-comb.; wfrn Mequitazine ATC: RO~ADO~ Use: antihistaminic, sedative RN: 29216-28-2 MF: C20H22N2S MW: 322.48 EINECS: 249-521-7 LD,,: 210 mglkg (M, p.0.); 245 mg/kg (R, p.0.) CN: 10-(l-azabicyclo[2.2.2]oct-3-ylmethyl)-I0H-phenothiazine NOH hydride phenothiazine 3-chloromethyl- Mequitazine quinuclidine Reference(s): DOS 2 009 555 (Sogeras; appl. 28.2.1970; GB-prior. 3.3.1969). US 3 987 042 (Auclaire; M. et al.; 19.10.1976; prior. 17.8.1973). Formulation(s): syrup 1.25 mg/ml, 2.5 mglml; tabl. 5 mg 1256 M Merbromin Trade Narne(s): D: Metaplexan (RhBne- GB: Primalan (RhBne-Poulenc J: Nipdazin (Nippon Shoji; Poulenc Rorer; 1977) Rorer; 1976) 1983) F: Butix (Pierre Fabre) I: Primalan (RhBne-Poulenc Primalan (Inava; 1976) Rorer; 1985) Merbromin ATC: DO^ (Mercurochrome) Use: antiseptic RN: 55728-51-3 MF: C20H,oBr2Hg0, MW: 706.69 EINECS: 259-779-2 CN: (2',7'-dibromo-3',6'-dihydroxy-3-oxospiro[isobenzofuran-1(3H),9'-[9H]xanthen]-4'-yl)hydroxymercury disodium salt RN: 129-16-8 MF: C20H,Br2HgNa,0, MW: 750.66 EINECS: 204-933-6 LDS,,: 50 mgkg (M, i.v.) Hg\OH Merbromin HgO. CH,COONo Br mercury(l1) oxide Reference(s): US 1 535 003 (E. C. White; 1925; prior. 1921). Forrnulation(s): sol. 2 % Trade Narne(s): D: Mercurochrom-Losung F: Pharmadose (Gilbert) (Krewel Meuselbach) I: Mercurocromo (SIT) Br Mercaptopurine RN: 50-44-2 MF: C,H,N,S MW: 152.18 LDso: 80 mgkg (M, i.v.); 260 mgkg (M, p.0.); 250 mglkg (R, i.v.) CN: 1,7-dihydro-6H-purine-6-thione sulfide hypoxanthine / ~ercaptopurine ATC: LOlBB02 Use: antineoplastic EINECS: 200-037-4 Reference(s): GB 7 13 286 (Wellcome Found.; appl. 195 1). Meropenem M 1257 alternative syntheses: US 2 721 866 (Burroughs Wellcome; 1955; appl. 1954). US 2 724 71 1 (Burroughs Wellcome; 1955; appl. 1954). US 2 933 498 (Burroughs Wellcome; 1960; appl. 1954). Formulation(s): tabl. 50 mg Trade Name(s): D: NERCAP (medac) GB: Puri-Nethol (Glaxo Mern (Tanabe) Puri-Nethol (Glaxo Wellcome) 6-MP (Dojin) Wellcome) I: Ismipur (Nuovo ISM) Thioinosie (Morishita) F: PurinCthol (Glaxo Purinethol (Wellcome) USA: Purinethol (Glaxo Wellcome) J: Classen (Nippon Shoji) Wellcome) Leukerin (Takeda) Meropenem (SM-7338 ; ICI- 194660) ATC: JOlDH02 Use: carbapenem, antibiotic RN: 96036-03-2 MF: CI7Hz5N3O5S MW: 383.47 - LD,: 2650 mgkg (M, i.v.); >5 glkg (M, p.0.); 2850 mgkg (R, i.v.); >5 g/kg (R, p.0.) CN: [4R-[3(3S*,5S*),4a,5~,6~(R*)]]-3-[[5-[(dimethylamino)cwbonyl]-3-pymolidinyl]thio]-6-(l- hydroxyethyl)-4-methyl-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-c~boxylic acid trihydrate RN: 119478-56-7 MF: C,,HZ5N3O5S . 3H20 MW: 437.51 4(R)-ocetoxy-3(R)- benzyl 2-brorno- [I (R)-(tert-butyldi- propionote rnethylsilyloxy)ethyl]- ozetidin-2-one 1. seporotion by chromotogrophy YH3 CH~ 2. CI-?~+CH~ . CH:~~ N(c2H5)3. DMF 3. Hz, Pd-C,CH30H + H3C\ -b 111 so CH3 H3C CH3CH3 1258 M Meropenem 2. &>(oAc)+, toluene. A L-praline p-rnethoxy- benyl ester (VI) In NoOH v11 Mesalazine M 1259 I Meropenem I 1. CH3CN. A 2. HZ, Pd-C,THF + - Reference(s): EP 126 587 (Sumitomo Chemical Co. Ltd; appl. 28.1 1.1984; J-prior. 9.5.1983, 15.6.1983, 12.7.1983, 3.9.1983, 11.11.1983, 10.2.1984). COOH H3C~s.&/cH3 HO CH3 NH ' CH3 synthesis of 4(R)-acetoxy-3(R)-[l (R)-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one: Reider, P.J. et al.: Tetrahedron Lett. (TELEAY) 2293 (1982). Kobayashi, Y. eta].: Tetrahedron (TETRAB) 48,55 (1992). EP 256 377 (Sumitomo Pharmaceuticals Co., Ltd; appl. 24.2.1988; J-prior. 30.7.1986, 26.6.1987) (trihydrate). preparation of p-lactams: JP 01 075 488 (Sumitomo Pharmaceuticals Co., Ltd; appl. 22.3.1989; J-prior. 17.9.1982). JP 60 233 076 (Sumitomo Chemical Co., Ltd; appl. 19.11.1985; CA-prior. 3.5.1984). stable ophthalmic oily suspensions containing P-lactams: JP 06 340 529 (Sumitomo Pharma; Santen Pharma Co. Ltd; J-prior. 1.6.1993, 13.12.1994). stable topical film preparations: JP 06 001 718 (Sumitomo Pharma; appl. 11.1.1994; J-prior. 17.6.1992). in combination with penicillin, cephalosporin, penem and carbapenem antibiotics: EP 640 607 (Hoffmann-La Roche; appl. 1.3.1995; CH-prior. 24.8.1993; 31.5.1994). synergistic antimicrobial pharmaceutical compositions containing carbapenem and cephalosporins or penicillins: EP 384 410 (Banya Pharmaceuticals Co., Ltd; appl. 29.8.1990; J-prior. 21.2.1989, 14.4.1989). synergistic effects with human monoclonal antibody: EP 441 395 (Sumitomo Pharmaceuticals Co., Ltd; appl. 14.8.1991 ; J-prior. 8.2.1990). manufacture of sterilized dried sodium carbonate for pharmaceutical compounds: JP 04 198 137 (Sumitomo Pharmaceuticals Co., Ltd; appl. 17.7.1992; J-prior. 28.1.1990). Formulation(s): amp. 500 mg, 1 g; vial 250 mg, 500 mg, 1000 mg meropenem trihydrate equivalent Trade Name(s): D: Meronem (Griinenthal; GB: Meronem (Zeneca) J: Meropen (Sumitomo) Zeneca) I: Merrem (Zeneca); wfm USA: Merrem (Zeneca) Mesalazine (5-ASA; Fisalamine; Mesalamine) ATC: A07EC02 Use: treatment of gastrointestinal disorders (ulcerative colitis, Crohn's disease) RN: 89-57-6 MF: C;H;N03 MW: 153.14 EINECS: 201-919-1 LD,,,: 68 1 mglkg (M, i.p.); 5 gkg (M, p.0.); 132 mglkg (R, i.p.); 2800 mg/kg (R, p.0.) CN: 5-amino-2-hydroxybenzoic acid 1260 M Mesalazine 3-nitrobenzoic acid salicylic 5-nitrosalicylic acid (I) acid Mesalazine u NaN02, aq. HCI aN;cl- - sodium salicylate v aniline 5-phenylazosalicylic acid sodium salt (11) NaSH or H2/Raney-Ni I1 , 5-(4-sulfophenylazo)- salicylic acid Active metabolite of sulfasalazine. Reference(s): a US 2 198 249 (Du Pont; 1940; appl. 1938). b Weil, H. et al.: Ber. Dtsch. Chem. Ges. (BDCGAS) 55, 2664 (1922). c DOS 3 638 364 (Bayer; appl. 11.1 1.1986). DD 255 941 (VEB Chem. Pharm. Oranienburg; appl. 24.12.1986). d EP 253 788 (Nobelkemi; appl. 17.6.1987; S-prior. 7.7.1986). review: The Merck Index, 1 lth Ed., 5806 (Rahway 1989). . [4R-[3(3S*,5S*),4a,5~,6~(R*)] ]-3 -[ [ 5-[ (dimethylamino)cwbonyl ]-3 -pymolidinyl]thio ]-6 -( l- hydroxyethyl )-4 -methyl-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-c~boxylic acid trihydrate RN: 11947 8-5 6-7 . 5434 0-5 8-8 MF: C,,H,,NO MW: 233.36 EINECS: 25 9-1 0 9-9 CN: 3-( 3-ethylhexahydro-l-methyl-lH-azepin-3-yl)phenol hydrochloride RN: 5926 3-7 6-2 MF: C,,H,,NO , HC1 MW: 269.82 EINECS: 26 1-6 8 3-0 LDso:. 25 1-4 9 3-6 LD,,: 2800pglkg(M,i.v.); 12.5mg/kg(M,p.o.); 5800 pglkg (R, i.v.); 79 mglkg (R, po.) CN: (3~ )-3 -[ (6-deoxy- 4-0 -methyl-a-~-mannopyrmosyl)oxy]-l4-hydroxybufa-4,2O,22-trienolide O-CH,