Mefruside M 1231 OHC N H,. P~O 111 + u+ % -, F, pyridine-2- a-2-pyridyl-2.8- carboxoldehyde bis(trifluorornethyl)- 4-quinolinernethanol hydrochloride chloral hydrate isatin (VI) 1. LiOH NaOH CF3 1" V 0 2. 2-pyridylmagnesium bromide 1 .l .l -trifluoro- acetone Reference(s): a Ohnmacht, C.J. et al.: J. Med. Chem. (JMCMAR) 14,926 (1971). b DOS 2 806 909 (Roche; appl. 17.2.1978; USA-prior. 17.2.1977). c DOS 2 940 443 (BASF; appl. 5.10.1979). alternative synthesis: EP 103 259 (Roche; appl. 6.9.1983; CH-prior. 10.9.1982). preparation of pure mefloquine hydrochloride: US 4 507 482 (Roche; 26.3.1985; CH-prior. 14.4.1982). EP 92 185 (Roche; appl. 14.4.1983; CH-prior. 14.4.1982). h)~t!,drochloride modijcation E: EP 137 375 (Roche; appl. 20.9.1984; CH-prior. 7.10.1983). Formulation(s): tabl. 250 mg (as hydrochloride) Trade Name(s): D: Lariam (Roche) GB: Lariam (Roche) F: Lariam (Roche; as I: Lariam (Roche) hydrochloride) USA: Lariam (Roche) Mefruside ATC: C03BA05 Use: diuretic RN: 7195-27-9 MF: Cl,Hl,CIN,OSS, MW: 382.89 EINECS: 230-562-4 LD,,,: 500 mglkg (M, i.v.); >10 glkg (M, p.0.); 500 mglkg (R, i.v.); >10 g/kg (R, p.0.); >5 glkg (dog, p.0.) CN: 4-chloro-N'-methyl-N1-[(tetrahydro-2-methyl-2-furanyl)methyl]-1,3-benzenedisulfonamide 1232 M Megestrol acetate H2, Roney-Ni N C H2N CH3 CH3 dimethyl sulfate tetrahydro- furon hydrafuron I NH2 3-sulfomoyl-4- chlorobenzene- sulfonyl chloride NH2 Mefruside CH3 2-methyl-2- (methylamino- methyl)tetro- hydrofuron (I) GB 1 03 1 9 16 (Bayer; appl. 30.1 1.1964; D-prior. 30. I 1.1963). Formulation(s): tabl. 25 mg Trade Namefs): . . D: Baycaron (Bayer Vital) Bendigon (Bayer Vital)- comb. Caprinol (Bayer)-comb.; wfrn Duranifin Sali (durachemie)-comb. Sali-Adalat (Bayer Vital)- comb. Sali-Prent (Bayer Vital)- I: Baycaron (Bayer); wfrn comb. Mefrusal (Bayropharm); Sali-Presinol (Bayer)- wfm comb. Rexitene Plus (LPB)- Thomaeamin (Thomae)- comb.; wfm comb.; wfm J: Baycaron (Yoshitomi) F: Tensid (Bayer Pharma)- comb.; wfrn GB: Baycaron (Bayer) Megestrol acetate ATC: G03D Use: progestogen (palliative treatment of breast and endometrial carcinoma) RN: 595-33-5 MF: Cz4H3z04 MW: 384.52 EINECS: 209-864-5 LD,,: 56 mglkg (M, i.v.) CN: 17-(acetyloxy)-6-methylpregna-4,6-diene-3,20-dione CH3 medroxyprogesterone (9. v.! CH3 megestrol (I) Meglutol M 1233 I Megestrol acetate US 2 891 079 (Searle; 16.6.1959; prior. 23.1.1959). Ringold, H.J. et al.: J. Am. Chem. Soc. (JACSAT) 81, 3712 (1959). Formulation(s): oral susp. 40 mglml; tabl. 20 mg, 40 mg, 160 mg Trade Name(s): D: Megestat (Bristol-Myers GB: Megace (Bristol-Myers Megestil (Boehringer Squibb) Squibb) Mannh.) Niagestin (Novo); wfm I: Megace (Bristol-Myers USA: Megace (Bristol-Myers F: Megace (Bristol-Myers Squibb) Squibb) Squibb) generics Meglutol . ATC: CIOAXOS Use: antihyperlipidemic RN: 503-49-1 MF: C6H,,0, MW: 162.14 EINECS: 207-971-1 LD,,: 7330 mgkg (M, p.0.) CN: 3-hydroxy-3-methylpentanedioic acid ethyl acetate ollylrnognesiurn bromide Reference(s): Rabinowitz, J.L. et al.: Biochem. Prep. (BIPRAP) 6,25 (1958). 03. "202 I - ozone. hydrogen peroxide medical use: US 3 629 449 (Aligarh Muslim University; 21.12.1971; prior. 22.4.1968). Meglutol Formulation(s): cps. 500 mg; tabl. 1 g Trade Name(s): I: Mevalon (Guidotti) 1234 M Melengestrol acetate Melengestrol acetate ATC: G03D Use: progestogen, antineoplastic RN: 2919-66-6 MF: C25H3204 MW: 396.53 EINECS: 220-859-7 CN: 17-(acetyloxy)-6-methyl-l6-methylenepregna-4.6-diene-3.20-dione melengestrol RN: 5633-18-1 MF: C23H3003 MW: 354.49 EINECS: 227-073-3 H202, NaOH C"3 . hydragen peroxide CH3 CH3 38-acetoxy-6.16-dimethyl- (1) 20-0x0-5,16-pregnadiene 2. O O , H~C~SO~H H3cJ-o~cH3 3. CH,OH, HCI I b HO O~O . NOC(CH3313 I1 b 1 -4-benzo- aluminum tri- quinane tert-butylate Melengestrol acetate GB 886 619 (British Drug Houses; valid from 14.6.1960; prior. 28.12.1959). starting material: GI3 850 423 (British Drug Houses; valid from 26.6.1959; prior. 9.7.1958). GB 870 286 (British Drug Houses; valid from 19.10.1959; prior. 4.1 1.1958). Kirk, D.N. et al.: J. Chem. Soc. (JCSOA9) 1961, 2821. alternative synthesis: US 3 117 966 (British Drug Houses; 14.1.1964; prior. 27.9.1961). Trade Narne(s): USA: MGA (Upjohn); wfm Melitracen M 1235 Meli tracen ATC: N06AA14 Use: antidepressant RN: 51 18-29-6 MF: C2,HZ5N MW: 291.44 EINECS: 225-858-5 LD,,,: 52 mglkg (M, i.v.); 3 15 mglkg (M, p.0.); 170 mg/kg (R, p.0.) CN: 3-(10,l O-dimethyl-9(10H)-anthracenylidene)-N,N-dimethyl- I -propanamine hydrochloride RN: 10563-70-9 MF: C2,H2,N . HCI MW: 327.90 EINECS: 234- 150-5 LD,,,: 52mgkg(M,i.v.); 315mgkg(M,p.o.); 170 mglkg (R, p.0.) FH3 CW-N, & + H3C-[ CH3 I 3-dimethylominopropyl- - magnesium chloride onthrone methyl 10,lO-dimethyl- iodide anthrone HCI Reference(s): US 3 177 209 (Kefalas; 6.4.1965; GB-prior. 16.9.1960. 17.2.1961) US 3 190 893 (Kefalas; 22.6.1965; GB-prior. 17.2.1961). DE 1 177 633 (Kefalas; appl. 14.2.1962; GB-prior. 17.2.1961). DE 1 294 375 (Kefalas; appl. 7.9.1961; GB-prior. 16.9.1960). Holm, T.: Acta Chem. Scand. (ACHSE7) 17, 2437 (1963). Formulation(s): amp. 2U mg/2 ml; drg. 10 mg, 25 mg Trade Namers): D: Trausabun (Ryk Gulden); I: Deanxit (Lusofarmaco)- wfm comb. Trausabun (Promonta); Melixeran (Lusofarmaco) w fm J: Thyme01 (Takeda) Meloxicam (UH-AC 62XX) ATC: MOlAC06 Use: anti-inflammatory, cyclooxygenase-2 inhibitor RN: 71 125-38-7 MF: C,,H,,N30,S, MW: 351.41 CN: 4-hydroxy-2-methyl-N-(5-n~ethy1-2-thiazolyl)-2H- 1,2-benzothiazine-3-carboxamide 1 ,I -dioxide 1236 M Melperone 1. CIYO\~~, 0 2. NoOCH3, toluene, butonol 3. H,C-I b 0 soccharin (q. v.) methyl 4-hydroxy-2-methyl- 2H-1.2-benzothiozine- 3-corboxylate 1 .l -dioxide (I) 2-omino-5- methylthiozole I Meloxicam CH3 Reference(s): DE 2 756 113 (Thomae GmbH; 21.6.1979; D-prior. 16.12.1977). ophthalmic solutions: wo 9 301 814 (Lab. Europhta; appl. 17.7.1992; F-prior. 18.7.1991). plaster for high-bioavailability: JP 04 321 624 (Hisamitsu Pharm.; appl. 19.4.1991; J-prior. 19.4.1991). combination with 5-lipoxygenase inhibitors: WO 9 641 626 (Searle & Co.; appl. 11.6.1996; USA-prior. 12.6.1995). combination with leukotriene A hydrolase inhibitor: WO 9 641 625 (Searle & Co.; appl. 11.6.1996; USA-prior. 12.6.1995). combination with leukotriene inhibitors: WO 9 641 645 (Searle & Co.; appl. 11.6.1996; USA-prior. 12.6.1995). medical use: WO 9 703 667 (Merck & Co.; appl. 15.7.1996; USA-prior. 19.7.1995). Formulation(s): cps. 7.5 mg; supp. 7.5 mg, 15 mg; tabl. 7.5 mg Trade Name(s): D: Mobec (Boehringer Ing.) F: Mobic (Boehringer Ing.) GB: Mobic (Boehringer Ing.) Melperone (Methy lperone; Metylperon) RN: 3575-80-2 MF: C,#,,FNO MW: 263.36 CN: 1-(4-fluorophenyl)-4-(4-methyl-l-piperidinyl)-l-butanone ATC: NOSAD03 Use: neuroleptic hydrochloride RN: 1622-79-3 MF: C,,H,,FNO . HCl MW: 299.82 EINECS: 216-599-9 LD,,,: 35 mgkg (M, i.v.); 230 mglkg (M, p.0.); 40 mglkg (R, i.v.); 330 mglkg (R, p.0.) Melphalan M 1237 4-methyl- 4-chloro-4'-fluoro- piperidine butyrophenone I Melperone I Reference (s): US 3 816 433 (Ferrosan; 11.6.1974; prior. 24.7.1964,22.3.1966, 29.4.1968, 5.10.1970). DE 1 268 146 (Ferrosan; appl. 28.7.1964; GB-prior. 29.7.1963). Formulation(s): amp. 50 mg12 rnl; drg. 10 mg, 25 mg, 50 mg, 100 mg; sol. 25 mg/5 ml (as hydrochloride) Trade Name(s): D: Eunerpan (Knoll) Melphalan ATC: LOlAA03 Use: antineoplastic RN: 148-82-3 MF: C13H,,C12N,02 MW: 305.21 EINECS: 205-726-3 LD,,: 20.8 mg/kg (M, i.v.); 4.1 mgkg (R, i.v.); 11.2 mg/kg (R, p.0.) CN: 4-[bis(2-chloroethyl)amino]-L-phenylalanine HCI 02'" O2N 4-nitro-L- phenylolonine 4-nitro-L-phenyl- olonine ethyl ester hydrochloride (I) phtholic onhydride (11) ethylene oxide 1238 M Memantine Reference(s): US 3 032 584 (Nat. Res. Dev. Corp.; 1.5.1962; GB-prior. 17.3.1953). US 3 032 585 (Nat. Res. Dev. Corp.; 1.5.1962; GB-prior. 3.12.1954). synthesis of intermediate [I: EP 233 733 (Kureha; appl. 5.2.1987; J-prior. 19.2.1986). Formulation(s): amp. 50 mg/lO ml; tabl. 2 mg, 5 mg Trade Name(s): D: Alkeran (Glaxo Wellcome) GB: Alkeran (Glaxo Wellcome) I: Alkeran (Glaxo Wellcome) F: Alk6ran (Glaxo Wcllcorne) Alkeran (Calmic) USA: Alkeran (Glaxo Wellcome) Memantine ATC: N06DXOI LJse: antispasmodic, rnyatonolytic, antiparkinsonian, muscle relaxant RN: 19982-08-2 MF: C12H2,N MW: 179.31 CN: 3,s-dimcthyltricyclo[3.3.1. 13.']decan- 1-amine hydrochloride RN: 41 100-52-1 MF: C,,H,,N. HCI MW: 215.77 1.3-dimethyl- 1 -bromo-3.5-di- adamantane methyladamantone 1 -0cetamido-3.5- dimethyl- adomontane (1) NaOH, diethylene glycol,A b H3C Reference(s): US 3 391 142 (Eli Lilly; 2.7.1968; appl. 9.2.1966). Gerzon, K. et al.: J. Med. Chem. (JMCMAR) 6,760 (1963). H3C 1,3-dimethyl-adamantane: Schleyer, P. v. R.; Nicholas, R.D.: Tetrahedron Lett. (TELEAY) 9, 305 (1961). Formulation(s): amp. 10 mg; drops 10 mglg; f. c. tahl. 10 mg (as hydrochloride) Menadiol diacetate M 1239 Trade Name(s): D: Akatinol (Merz) Menadiol diacetate (Acetomenadione; Acetomenaftone) ATC: All Use: antihemorrhagic, vitamin K- derivative (prothrombogenic) RN: 573-20-6 MF: ClSH140, MW: 258.27 EINECS: 209-352-1 CN: 2-methyl-l,4-naphthalenediol diacetate diphosphate dicalcium salt RN: 74347-27-6 MF: C,,H,Ca20,P, MW: 410.28 rnenadione (4. v.) rnenadiol El @? 0 CH, K 0 Menadiol diacetate Reference(s): Horii et al.: Pharm. Bull. (PHBUA9) 5, 82 (1957). Formulation(s): amp. 8.86 mglml (as diphosphate dicalcium salt) Trade Narne(s): D: Pertix-Solo-Hommel GB: Ketovite (Paines & Byme)- J: Kativ (Takeda) (Hommel) comb. Menadiol sodium diphosphate ATC: All Use: antihemorrhagic vitamin RN: 13 1-1 3-5 MF: ClIH,Na4OUP, MW: 41 8.05 EINECS: 205-01 2- 1 LD,,,: 350 mglkg (M, s.c.); 23 1 mglkg (R, i.p.) CN: 2-methyl-l,4-naphthalenediol bis(dihydrogen phosphate) tetrasodium salt hexahydrate RN: 6700-42-1 MF: C,,H,Na,O,P, , 6H20 MW: 530.18 menadiol diphosphate RN: 84-98-0 MF: Cl,H120uP2 MW: 334.16 1240 M Menadione menadiol Menadiol sodium diphasphate Reference(s): Fieser, L.F. et a].: J. Am. Chem. Soc. (JACSAT) 62, 228 (1940). US 2 380 621 (Roche; 1945; CH-prior. 1942). US 2 345 690 (Roche; 1944; appl. 1941). US 2 354 132 (Roche; 1944; appl. 1940). synthesis of intermediate 11: EP 233 733 (Kureha; appl. 5.2.1987; J-prior. 19.2.1986). Formulation(s): amp. 10 mgll ml, tabl. 10 mg Trade Name(s): D: Styptobion (Merck)-comb.; GB: Synkavit (Roche); wfm USA: Synkavite (Roche; as wfm J: Kativ (Takeda) hexahydrate); wfm Menadione (Menaphthone; Menaquinone; Vitamin K3) ATC: B02BA02 Use: antihemorrhagic vitamin (prothrombogenic) RN: 58-27-5 MF: CllH,O, MW: 172.18 EINECS: 200-372-6 LD,,,: 500 mglkg (M, p.0.) CN: 2-methyl-] ,4-naphthalenedione 2-methyl- naphthalene Reference(s): a oxidation with chromic acid and derivatives: 0 Menadione Fieser, L.F. et al.: J. Am. Chem. Soc. (JACSAT) 61, 2559, 3216 (1939). US 2 402 226 (Velsicol; 1946; appl. 1943). b oxidation with hydrogen peroxide: Arnold; Larson: J. Org. Chem. (JOCEAH) 5, 250 (1940). US 2 373 003 (Univ. of Minnesota; 1945; appl. 1941). Adam, W. et al.: Angew. Chem. (ANCEAD) 106,2545 (1994). Formulation(s): tabl. 2 mg . 291 9-6 6-6 MF: C25H3204 MW: 396.53 EINECS: 22 0-8 5 9-7 CN: 1 7-( acetyloxy )-6 -methyl-l6-methylenepregna-4.6-diene-3.20-dione melengestrol RN: 563 3-1 8-1 MF: C23H3003 MW: 354.49 EINECS: 22 7-0 7 3-3 . cyclooxygenase-2 inhibitor RN: 71 12 5-3 8-7 MF: C,,H,,N30,S, MW: 351.41 CN: 4-hydroxy-2-methyl-N-(5-n~ethy 1-2 -thiazolyl )-2 H- 1,2-benzothiazine-3-carboxamide 1 ,I -dioxide 1236 M Melperone 1 38-acetoxy-6.16-dimethyl- (1) 2 0-0 x 0-5 ,16-pregnadiene 2. O O , H~C~SO~H H3cJ-o~cH3 3. CH,OH, HCI I b HO O~O . NOC(CH3313 I1 b 1 -4 -benzo- aluminum tri- quinane tert-butylate