Pharmaceutical Substances Syntheses, Patents, Applications - Part 131 potx

Methylprednisolone M 1301 hydrocortisone (q v.) ethylene glycol 1. H,C-MgBr 2. 2n H2S0, bromide enzymotic dehydrogenation [Septomyxo offinis (ATCC 6737)] 111 b 6a-methyl- hydrocortisone (111) Methylprednisolone L Ui 2 897 218 (Upjohn; 28.7.1959; appl. 23.1 1.1956; prior. 23.4.1956). Speero, G.G. et al.: J. Am. Chem. Soc. (JACSAT) 78,6213 (1956); 79, 1515 (1957). alternative syntheses: US 3 053 832 (Schering Corp.; 11.9.1962; prior. 29.4.1957). Fried, J.H. et al.: J. Am. Chem. Soc. (JACSAT) 81,1235 (1959). US 4 041 055 (Upjohn; 9.8.1977; appl. 17.1 1.1975). Formulation(s): amp. 20 mg, 30 mg, 40 mg, 60 mg, 80 mg; cream 0.1 %; ointment 0.1 %; tabl. 6 mg, 24 mg, 60 mg Trade Narne(s): D: Advantan (Schering) Depo-Medrate (Pharmacia & Upjohn) Medrate (Pharmacia & Upjohn) Metypred (Orion Pharma) Urbason (Hoechst) F: DCpo-Medrol (Pharmacia & Upjohn) Mtdrol (Pharmacia & Upjohn) Soh-MMrol (Pharmacia & Upjohn) GB: Medrone (Pharmacia & Upjohn) I: Advantan (Schering) Asmacortone (Nuovo Cons. Sanit. Naz.) Avancort (Farmades) Depo Medrol (Upjohn) Emmetip (Zanoni) Esametone (Lisapharma) Firmacort (Firma) Medrol (Upjohn) Urbason Retard (Hoechst) Dura-Meth (Foy); wfm Medrol Loz. Antiance J: Medrol (Upjohn) Medrol (Upjohn); wfm (Upjohn)-comb. USA: A-methapred (Abbott); Neo-Medrol (Upjohn)- Metilpre (Formulario Naz.) wfm comb.; wfm Neomedrol Veriderm Depo-Medrol (Upjohn; as Soh-Medrol (Upjohn; as (Upjohn)-comb. acetate); wfm 21 -hemisuccinate); wfm Solu-medrol (Upjohn) Depo-Predate (Legere); generic Urbason (Hoechst) wfm Methyltestosterone ATC: G03BA02; G03EKO1 Use: androgen RN: 58-18-4 MF: C2,H3,O2 MW: 302.46 EINECS: 200-366-3 LD,,,: 1860mglkg (M, p.0.); 2500 mgkg (R, p.0.) CN: (1 7P)-I 7-hydroxy-17-methylandrost-4-en-3-one ondrostenolone methyl- magnesium iodide CrO, oxide 0 Reference(s): US 2 143 453 (Ciba; 1939; CH-prior. 1935). US 2 374 369 (Ciba; 1945; CH-prior. 1939). US 2 374 370 (Ciba; 1945; CH-prior. 1939). Ruzicka, L.: Helv. Chim. Acta (HCACAV) 18, 1487 (1935). starting material: The Merck Index, 2846 (Rahway 1976). alternative syrztheses: US 2 384 335 (Alien Property Custodian; 1945; NL-prior. 1936). US 2 386 331 (Ciba; 1945; CH-prior. 1938). US 2 435 013 (Ciba; 1948; CH-prior. 1941). Bharucha, K.R.: Expcrientia (EXPEAM) 14, 5 (1958). Formulution(s): cps. 5 mg, 10 mg, 25 mg Trade Nume(s): D: Femoviron Dragees Gerobion (Merck)-comb.; Hormocomut B (AGM)- (Albert-Rousse1)-comb.; wfm comb.; wfm wfm Gevrabon (Cedra)-comb.; Hormo-Gerobion (Merck)- wfnt - - - - - - - comb_; wLm - - - Methylthioninium chloride M 1303 Hormovitastan (ASTA)- comb.; wfrn Klimax Taeschner (Taeschner); wfrn Lipogeron 300 (Nattermann)-comb.; wfrn Medigeron (Medice)- comb.; wfrn Pasuma (Cascan)-comb.; wfrn Primodian (Schering)- comb.; wfm Primogeron (Schering)- comb.; wfrn Reginol (Merz)-comb.; wfrn Testifortan (Promonta)- comb.; wfrn Tropodil (Tropon)-comb.; wfm GB : Viracton plus (Promonta)- comb.; wfrn F: ClimatCrine (Lucien)- 1 : comb.; wfm J: Glosso-StCrandryl (Roussel); wfrn TriphosadCnine Methyltestostkrone ComposC (D6bat)-comb.; USA: wfm Veinotrope MCthyltestostCron (Lobica); wfrn Mepilin (Duncan, Flockhart)-comb.; wfrn Perandren (Ciba); wfrn Testovis (SIT) Enarmon Tab. (Teikoku Zoki) Primodian (Nihon Schering)-comb. Sanstron (Sankyo) Android (ICN) Estratest (Solvay) Testred (ICN) Virilon (Star) Methylthioninium chloride (Methylenblau; Methylene blue) ATC: V03AB 17; V04CG05 Use: diagnostic (for gastric function test), antidote (cyanide poisonings) RN: 61-73-4 MF: C,,H,,ClN,S MW: 319.86 EINECS: 200-515-2 LD,,: 77 mgkg (M, i.v.); 3500 mg/kg (M, p.0.); 1250 mgkg (R, i.v.); 1180 mglkg (R, p.0.) CN: 3,7-bis(dimethy1amino)phenothiazin-5-ium chloride trihydrate RN: 7220-79-3 MF: C,,H,p,CIN,S . 3H20 MW: 373.91 4-ornino-N,N-di- rnethyloniline +aNH cl- + QNm3 HCI, 85 OC E3c-bi - iH 1 , + CH3 Reference(s): Ullmanns Encykl. Tech. Chem., 4. Aufl., Vol. 8, 237. H C \ry a;&CH3 I CH3 CI- CH3 (1) N.N-dimethyl- Formulation(s): amp. 10 mg/ml, 50 mg/ml, 100 mg/ml; tabl. 65 mg Methylthioniniurn chloride Trade Name(s): D: Methylenblau Vitis Collyre Bleu Laitel (Neopharma) (Leurquin)-comb. F: Antiseptique- Calmante(Chauvin)-comb. aniline I Mictasol Bleu (Martin- Johnson & Johnson-MSD)- comb. 1304 M Methylthiouracil Pastilles MonlCon Blu Meti (Formulario Naz.) Urolene Blue (Star (Tou1ade)-comb. USA: Urised (Po1yMedica)- Pharmaceut.) Stilla (Phygi6ne)-comb. comb. I: Blu Di Meti (Scfm) Methylthiouracil ATC: H03BAO1 Use: thyroid therapeutic RN: 56-04-2 MF: C,H,N,OS MW: 142.18 EINECS: 200-252-3 LD,,: 1500 mglkg (R, p.0.) CN: 2,3-dihydro-6-methyl-2-thioxo-4(lH)-pyrimidinone ethyl thiourea ocetoocetote 1 Methylthiourocil Reference (s): List, R.: Justus Liebigs Ann. Chem. (JLACBF) 236, 1 (1886). Anderson, G.W. et al.: J. Am. Chem. Soc. (JACSAT) 67,2197 (1945). Formulation(s): tabl. 0.025 g, 0.1 g Trade Name(s): D: Pitufren comp. F: Frenantol Comp. (Laroche USA: Muracin (Organon); wfm (Brunnengraber)-comb.; Navarron); wfm wfm J: Methiocil (Chugai) Methyprylon ATC: N05CE02 Use: hypnotic RN: 125-64-4 MF: CI,H,,NO2 MW: 183.25 EINECS: 204-745-4 LD,,,: 275 mglkg (M, i.v.); 890 mglkg (M, p.0.); 380 mglkg (R, i.v.); 860 mglkg (R, p.0.); 300 mglkg (dog, p.0.) CN: 3,3-diethyl-5-methyl-2,4-piperidinedione ethyl 2.2-di- methyl ethylaceto- formote (I) ocetote ethyl 2,2-di- ethyl-4-(hydroxy- methylene)- ocetoocetote Methysergide M 1305 ethyl 5-omina- 3,3-diethyl- 3,3-diethyl- 1,2.3.4-tetm- hydropyridine- 2.4-dione piperidine- 2.4-dione (In) 0 Methypryton Reference(s): US 2 680 116 (Hoffmann-La Roche; 1954; CH-prior. 1951). DRP 634 284 (Hoffmann-La Roche; 1935). US 2 151 047 (Hoffmann-La Roche; prior. 1938). Formulation(s): tabl. 200 mg Trade Narne(s): D: Noludar (Roche); wfm J: Noctan (Yamanouchi) GB: Noludar (Roche) USA: Noludar (Roche); wfm - Methysergide ATC: N02CA04 Use: serotonin antagonist, antimigraine agent RN: 36 1-37-5 MF: C2,H27N,02 MW: 353.47 EINECS: 206-644-0 LD,,,: 185 mglkg (M, i.v.); 440 mgkg (M, p.0.) CN: [8~(S)]-9,10-didehydro-N-[l-(hydroxymethyl)propyl]-l,6-dimethylergoline-8-carboxamide hydrogen maleate (1:l) - RN: 129-49-7 MF: C2,H2,N3O2 . C4H404 MW: 469.54 EINECS: 204-950-9 1. KNH2, liq. NH, H3c'3s-ll"&NH - N = I H CH3 CH3 methylergornetrine Methyserqide (4. v.1 Reference(s): US 3 113 133 (Sandoz; 3.12.1963; CH-prior. 18.5.1956). US 3 218 324 (Sandoz; 16.1 1.1965; ~H-~rior. 18.5.1956,20.3.1957, 16.4.1957,7.3.1958, 11.3.1960). DE 1 076 137 (Sandoz: appl. 7.5.1957; CH-prior. 18.5.1956,20.3.1957). Formulation(s): s. r. tabl. 3 mg; tabl. 1 mg, 2 mg (as hydrogen maleate) 1306 M Metiazinic acid Trude Name($): D: Deseril-retard (Novartis GB: Deseril (Novartis) Sansert (Sandoz; as Pharma) I: Deserril (Sandoz) maleate); wfm F: Dtsernil Sandoz (Novartis) USA: Sansert (Sandoz); wfm Metiazinic acid (Acide metiazinique) ATC: M01; NO2 Use: anti-inflammatory RN: 13993-65-2 MF: C,,H,,NO,S MW 271.34 EINECS: 237-795-0 LD,,,: 350 mglkg (M, i.v.); 800 mglkg (M, p.0.); 495 mglkg (R, p.0.); 2 glkg (dog, p.0.) CN: 10-methyl-1OH-phenothiazine-2-acetic acid 2-acetyl-10-methyl- phenothiazine n f"0 N> KOH_ rnorpholine I Metiorinic acid FH3 Reference(s): GR 1 048 680 (Rhhe-Poulenc; appl. 27.10.1965; F-prior. 29.10.1 964, 30.10.1964, 28.12.1964,24.9.1965). ester derivatives: US 3 424 748 (Rhhe-Poulenc; 28.1.1969; F-prior. 22.10.1965,25.8.1966). Forrnulation(s): cps. 125 mg, 250 mg Trade Narntfs): F: Soridermal (Specia); wfm I: Soripal (Carlo Erba); wfrn J: Roimai (Nippon Rhodia) Soripal (Specia); wfm - Soripal (Farmilalia); wfm Soripal (Torii) Meticillin (Methicillin) ATC: JOlCF03 Use: antibiotic RN: 61-32-5 MF: C,,H,,N,O,S MW: 380.42 EINECS: 200-505-8 LD,,,: 3720 mglkg (M, i.v.) CN: [2S-(2n,5a,6~)]-6-[(2,6-dimethoxybenzoyl)amino]-3,3-dimethy-7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2-carboxylic acid sodium salt monohydrate RN: 7246- 14-2 MF: C17H,,N2Na06S . H20 MW: 420.42 S0CI2 * chloride 2.6-dirnethoxy- benzoic acid ~ - - - N(C2H5)3 , 6-orninopeni- cillanic acid Meticillin I Meticrane M 1307 Reference(s): US 2 951 839 (Beecham; 6.9.1960; GB-prior. 15.7.1959). Fonnulation(s): amp. 0.5 g, 1 glml. 4 g, 6 g (as sodium salt) Trade Name(s): D: Cinopenil (Hoechst); wfm Phistaph (Bristol); wfm Celbenin (Beecham- F: Chibro-Flabelline (Merck GB: Celbenin (Beecham; 1960) Massengill); wfm Sharp & Dohme-Chibret)- I: Staficyn (Firma) Staphcillin (Bristol); wfm comb.; wfm J: Methocillin (Meiji) Flabelline (Delagrangc); Staphcillin (Banyu) wfm USA: Azapen (Pfizer); wfm Meticrane ATC: C03BA09 Use: diuretic RN: 1084-65-7 MF: C,,H,,N04S2 MW: 275.35 EINECS: 214- 112-4 LD,,: 325 mg/kg (M, i.v.); >20 glkg (M, p.0.); 445 mglkg (R, i.v.); >I6 glkg (R, p.0.) CN: 3,4-dihydro-6-methyl-2H-1-benzothiopyran-7-sulfonamidc 1,l-dioxide (C,H9),Nt OH- HOOC H3C 0 4-methyl- ocrylic 6-methyl-thio- thiophenol acid chromon-4-one (1) 6-methyl- thiochroman 6-methyl- thiochromon I, 1 -dioxide (11) CIS03H I1 + chlorosul- fonic acid Meticrone L Reference(s): FR 1 365 504 (S.1.F.A; appl. 24.5.1963). Formulation(s): tabl. 150 mg Trade Namefs): F: Fontilix (Diamant); wfrn J: Aresten (Nippon Shinyaku) 1308 M Metildigoxin Metildigoxin (Medigoxin; P-Methyldigoxin) ATC: COlAA08 Use: cardiac glycoside RN: 30685-43-9 MF: C,,H,O,, MW: 794.98 EINECS: 250-292-0 CN: (3~,5~,12~)-3-[(0-2,6-dideoxy-4-O-methyl-~-~-ribo-hexopyranosyl-(1~4)-0-2,6-dideoxy-~-~-ribo- hexopyranosyl-(I +4)-2,6-dideoxy-P-D-ribo-hexopyranosyl)oxy]- 12,14-dihydroxycard-20(22)-enolid~ H~C/O\ //' Ba(OH),, AI2O3. DMF + s -b OQ \O CH3 digoxin dimethyl sulfate I Metildigoxin DE 1 643 665 (Boehringer Mannh.; appl. 20.9.1967). DOS 1 961 034 (Boehringer Mannh.; appl. 5.12.1969). US 3 538 078 (Boehringer Mannh.; 3.1 1.1970; D-prior. 7.5.1968). methylation with methyl mesylate: DOS 2 734 401 (LEK; appl. 29.7.1977; YU-prior. 20.8.1976). US 4 145 528 (LEK; 20.3.1979; YU-prior. 20.8.1976). Formulation(s): amp. 0.2 mg; tabl. 0.1 mg, 0.15 mg Metipranolol M 1309 Trade Nante(s): D: Lanitop (Boehringer I: Cardiolan (Tosi-Novara) Miopat (Polifarma) Mannh.; 1971) Lanitop (Boehringer J: Lanirapid (Yamanouchi; F: Lanitop (Roussel); wfm Mannh.; 1973) 1979) Metipranolol ATC: SOIED04 Use: beta blocking agent RN: 22664-55-7 MF: C17H27N04 MW: 309.41 EINECS: 245-151-5 CN: 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxyJ-2,3,6-trimethylphenol 1-acetate 4-acetoxy-2.3.5- epichloro- trimethylphenol (I) hydrin Metipranolal Rejerence(s): DOS 1 668 964 (Spofa; appl. 1968; P-prior. 1967). CS 1 150 020 (L. Blaha; appl. 26.11.1970). synthesis oj4-acetoxy-2,3,5-trimethylphenol: DOS 2 314 600 (Teijin; appl. 23.3.1973; J-prior. 25.3.1972). Forrnulation(s): drg. 20 mg; eye drops 1 mglml, 3 mglml, 6 mglml (0.1 %, 0.3 %, 0.6 %); tabl. 20 mg Trade Name(s): D: Retamann (Mann) Torrat (Boehringer Mannh.) F: BCtanol (Europhta) Normoglaucon (Mann)- Tri-Torrat (Boehringer I: Tbroptin (CIBA Vision)- comb. Mannh.) comb. Metirosine (Metyrosine; a-Methyltyrosine) ATC: C02KBO1 Use: antihypertensive (at phcochromocytoma) RN: 672-87-7 MF: C,,H,,N03 MW: 195.22 EINECS: 21 1-599-5 CN: a-methyl-L-tyrosine phenyl- (1) acetone a-methyl-DL-phenyl- alanine hydrochloride (11) 1. NaOH 11 , 2. dichloro- acetyl - chloride N-dichloroacetyl- O2N a-methyl-DL- phenylolanine 1. H,SO,, NaNO, racemate resolution a-methyl-Dl- tyrasine (N) 80. - HO Metirosine (4-methaxypheny1)- acetone racernate resolution - IV - . P-Methyldigoxin) ATC: COlAA08 Use: cardiac glycoside RN: 3068 5-4 3-9 MF: C,,H,O,, MW: 794.98 EINECS: 25 0-2 9 2-0 CN: (3~,5~,12~ )-3 -[ ( 0-2 ,6-dideoxy-4-O-methyl- ~-~ -ribo-hexopyranosyl-(1~4 )-0 -2 ,6-dideoxy- ~-~ -ribo-. (3~,5~,12~ )-3 -[ ( 0-2 ,6-dideoxy-4-O-methyl- ~-~ -ribo-hexopyranosyl-(1~4 )-0 -2 ,6-dideoxy- ~-~ -ribo- hexopyranosyl-(I +4 )-2 ,6-dideoxy-P-D-ribo-hexopyranosyl)oxy ]- 12,14-dihydroxycard-20(22)-enolid~ H~C/O //' Ba(OH),, AI2O3. DMF + s -b OQ O. Gerobion (Merck)-comb.; Hormocomut B (AGM )- (Albert-Rousse1)-comb.; wfm comb.; wfm wfm Gevrabon (Cedra)-comb.; Hormo-Gerobion (Merck )- wfnt - - - - - - - comb_; wLm - - - Methylthioninium