Pharmaceutical Substances Syntheses, Patents, Applications - Part 130 docx

Methoxyflurane M 1291 Methoxyflurane ATC: NOIAB03 Use: inhalation anesthetic RN: 76-38-0 MF: C,H4C12F20 MW: 164.97 EINECS: 200-956-0 LD,,: 150 mglkg (M, i.v.); 3600 mgkg (R, p.0.) CN: 2.2-dichloro-1, l -difluoro-1-methoxyethane F KOH CI F H3C-OH . KOH CI,C~ + M h F CI F 1.1-difluoro- 1 ,l -dichloro- 2,Z.Z-trichloro- 2,2-difluoro- ethane ethylene I Methoxyflurane Reference(s): GB 928 786 (Dow; appl. 9.2.1960; USA-prior. 3.4.1959, 20.7.1959). Formulation(s): sol. 125 mg1125 ml Trade Narne(s): D: Penthrane (Abbott); wfm I: Pentrane (Abbott); wfm USA: Penthrane (Abbott); wf'm GB: Penthrane (Abbott); wfm J: Penthrane (Abbott) Methscopolamine bromide (Hyoscine methobromide) ATC: A03 Use: parasympatholytic, antispasmodic RN: 155-41-9 MF: C,,H,,BrNO, MW: 398.30 EINECS: 205-8445 LD,,: 26.806 mgkg (M, i.v.); 619 mg/kg (M, p.0.); 42.5 mglkg (R, i.v.); 3400 mg/kg (R, p.0.) CN: [7(S)-(la,2~,4~,5a,7P)1-7-(3-hydroxy-l-oxo-2-phenylpropoxy)-9,9-dimethyl-3-oxa-9- azoniatricyclo[3.3.1 .02.4]nonane bromide nitrate RN: 6 106-46-3 MF: C,,H,,N20, MW: 380.40 EINECS: 228-065-2 methylsulfate RN: 18067-13-5 MF: C1,H2,N04 , CH3S04 MW: 429.49 EINECS: 241-975-4 H methyl scopolamine bromide Methscopolamine bromide (4. v.1 1292 M Methyclothiazide H rnethscopolarnine nitrate Reference(s): DE 145 996 (E. Merck AG; appl. 1902). US 2 753 288 (Upjohn; 1956; prior. 1952). Formulation(s): cps. 2.5 mg; syrup 1.25 mg/5 ml; tabl. 1.25 mg Trade Name(s): D: Holopon (Byk Gulden); Oragallin S (Hormon- GB: Pamine (Upjohn); wfm wfm Chemie)-comb.; wfm Skopyl (Farillon); wfm Ichtho-Spasmin (1chthyol)- Skopyl (Pharrnacia; as - J: Ace (Ono) comb.; wfm nitrate); wfm Meporamin (Tai yo) Methyscopolamin Spasmo-Bilicura (Mueller USA: Pamine (Upjohn); wfm (Upjohn); wfm Coppingen)-comb.; wfm Methyclothiazide ATC: C03AA08 Use: diuretic RN: 135-07-9 MF: C9H,,C12N304S2 MW: 360.24 EINECS: 205-172-2 LD,,,: 400 mgkg (M, i.v.); 210 glkg (M, p.0.); >4 glkg (R, p.0.) CN: 6-chloro-3-(chloromethyl)-3,4-dihydro-2-methyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,l-dioxide 5-chloro-2.4-di- urea 7-sulfomoyl-6-chloro-3- sulfarnoylaniline oxo-3.4-d1hydro-2H- 1.2.4- benzothiodiazine 1 ,l -dioxide chloro- CI CI ocet- CI H aldehyde Methyclothiazide Reference (s): Close, W.J. et al.: J. Am. Chem. Soc. (JACSAT) 82, 1132 (1960). Formulation(s): tabl. 2.5 mg, 5 mg Trade Name(s): F: Isobar (Jacques Logeais)- Enduronyl (Abbott)-comb.; J: D.A.11-Tablets (Dura) comb. wfm Dallergy (Laser) GB: Enduron (Abbott); wfm I: Enduronil (Abbott)-comb. Dura-Vent (Dura) Methyldopa M 1293 Enduron (Dainippon) Omnihist (We) Enduron (Abbott) Extendryl (Fleming) USA: Aquatensen (Wallace) Mescolor (Horizon) Diutensen-R (Wallace) Methyldopa ATC: C02ABOl Use: antihypertensive RN: 555-30-6 MF: C,,H,,NO, MW: 21 1.22 EINECS: 209-089-2 CN: 3-hydroxy-a-methyl-L-tyrosine H3c-0mCH3 + KCN + (NH4)2C03 + H3C-0 / NKNH H3C-0 H3c-0* 0 (3,4-dimethoxy- potassium ammonium 4-methyl-4-(3.4-di- pheny1)ocetone (I) cyanide corbonote rnethoxybenzy1)hydantoin (U) 1. N-acetylotion 2. rocemote resolution with (-)- 1 -phenylethylomine BO(O*), H~c-o~~;~~~ 3. Her fl- H3C-0 / 1 Methyldopo selective crystallization of the hydrogen sulfites 111 - HO 1. rocemote resolution with (-)-10-comphonulfonic (4-hydroxy-3-meth- oxypheny1)acetone (IV) DL-a-amino-a- vonillylpropionitrile L-a-omino-a- vonillylpropionitrile (V) L-a-omino-a- vonillylpropionomide 1294 M Methyldopa @ Starting products: hornoveratronitrile isoeugenol US 2 868 818 (Mcrck & Co.; 13.1.1959; prior. 15.12.1953). GB 936 074 (Merck & Co.; appl. 18.10.1960; USA-prior. 8.4.1960,24.8.1960). DE 1 171 931 (Merck & Co.; prior. 6.10.1960). Tristram. E.W. et al.: J. Org. Chem. (JOCEAH) 29,2053 (1964). Stein, G.A. et al.: J. Am. Chem. Soc. (JACSAT) 77,700 (1955). Chem. Eng. from 8.1 1.1965; p. 247. US 3 158 648 (Merck & Co.; 24.1 1.1964; prior. 11.7.1961,9.4.1962). Reinhold, D.F. et al.: J. Org. Chem. (JOCEAH) 33, 1209 (1968). FR 1 492 765 (Merck & Co.; appl. 10.10.1963; USA-prior. 11.10.1962, 19.9.1963). similar method via L-a-acetylamina-a-vanillylpropionitrile: GB 1 142 595 (Merck & Co.; appl. 23.5.1967, 12.2.1969). alternative syntheses: US 3 366 679 (Merck & Co.; 30.1.1968; prior. 11.10.1962, 19.9.1963). DOS 2 302 937 (Tanabe; appl. 22.1.1973; J-prior. 22.1.1972). US 3 517 057 (Merck & Co.; 23.6.1970; appl. 21.9.1967). DE 1 235 946 (Boehringer Mannh.; appl. 8.8.1964). DE 1 235 947 (Bayer; appl. 16.1.1963). DE 1 258 416 (Knoll; appl. 9.10.1964). DE 1 269 622 (Knoll; appl. 22.12.1966). - DOS 2 406 898 (BASF; appl. 14.2.1974). AT 250 936 (Egyesiilt; appl. 3.11.1964; HU-prior. 18.11.1963). FR 1 502 972 (Merck & Co.; appl. 21.10.1966; USA-prior. 22.10.1965). FR 1 531 877 (Sankyo; appl. 18.7.1967; J-prior. 11.8.1966, 21.2.1967). GB 1 321 802 (D.D.S.A.; appl. 5.2.1971). Da Steinetal, G.A.: J. Am. ~hek Soc. (JACSAT) 77, 700 (1955). Db GB 2 059 955 (Merck & Co.; appl. 9.9.1980; USA-prior. 13.9.1979, 28.9.1979). medical use: US 3 344 023 (Merck & Co.; 12.4.1983; prior. 8.4.1960,24.8.1960, 1.2.1963; reexamination requcst 21.12.1981). Formulation(s): drg. 250 mg, 500 mg; f. c. tabl. 125 mg, 250 mg, 500 mg; tabl. 250 mg, 500 mg Trade Name(s): D: Caprinol (Bayer Vital)- Sembrina (Boehringer Hydromet (Merck Sharp & comb. Mannh.) Dohme)-comb.; wfm Dopegyt (Thiemann) F: Aldomet (Merck Sharp & Medomet (DDSA); wfm Presinol (Bayer Vital; Dohme-Chibret; 1964) I: Aldomet (Merck Sharp & 1963) GB: Aldomet (Merck Sharp & Dohme) Sali-Presinol (Baycr)- Dohme; 1962); wfm Medopren (Malesci) comb. Dopamet (Berk); wfm Medozide (Malexi)-comb. Methyldopate M 1295 Saludopin (SIT)-comb. Medopa (Kaigai-Nippon Sankaira (Hotta) J: Aldomet (Merck-Banyu) Kay aku) USA: Aldoclor (Merck Sharp & Becanat (Kissei) Meprin (Kyorin) Dohme) Eldopane (Takata- Metholes (Taisho) Aldomet (Merck Sharp & Shionogi) Methoplain (Kowa Dohme; 1963) Ledopan (Mochida) Yakuhin) Aldoril (Merck Sharp 6t Polinal (Yamanouchi) Dohme) and generics Methyldopate ATC: C02ABO1 [Jse: antihypertensive RN: 2544-09-4 MF: C,,H,,NO, MW: 239.27 EINECS: 219-821 -2 CN: 3-hydroxy-a-methyl-L-tyrosine ethyl ester hydrochIoride RN: 2508-79-4 MF: C12H,,N04. HC1 MW: 275.73 EINECS: 219-720-3 rnethyldopa (9. v.) I Methyldopate Reference(s): US 2 868 818 (Merck & Co.; 13.1.1959; prior. 15.12.1953). medical use (for injection): US 3 230 143 (Merck & Co.; 18.1.1966; appl. 22.6.1961, 28.12.1962, 14.5.1965). FR-M 2 153 (Merck & Co.; appl. 20.9.1962; USA-prior. 22.6.1961). Formulatiot~(s): amp. 250 mglml, 500 mglml; f. c. tabl. 125 mg, 250 mg, 500 mg Trade Natne(s): D: Presinol pro inj. (Bayer Methyldopa (Merck Sharp USA: Vital) & Dohme-Chibret) F: Aldomet (Merck Sharp & GB: Aldomet Inj. (Merck Sharp Dohme-Chibret) & Dohme) Aldomet Ester HC 1 Inj. (Merck Sharp & Dohme) Methylergometrine (Methy lergonovine) ATC: G02ABO1 Use: uterotonic, oxytocic RN: 1 13-42-8 MF: C2,H2,N,02 MW: 339.44 EINECS: 204-027-0 LD,,,: 85 mgkg (M, i.v.); 187 mglkg (M, p.0.); 23 mgkg (R, i.v.); 93 mgkg (R, p.0.) CN: [8~(S)]-9,10-didehydro-N-[l-(hydroxymethyl)propyl]-6-methylergoline-8-carboxamide maleate (1:l) RN: 57432-61-8 MF: C2,H2,N302 . C4H404 MW: 455.51 EINECS: 260-734-4 LD,,,: 85 mgkg (M, i.v.); 187 mgkg (M, p.0.); 23 mgkg (R, i.v.); 93 mglkg (R, p.0.) tartrate (2:l) RN: 6209-37-6 MF: CZ0Hz5N3O2. 1/2C4HhOh MW: 828.96 1296 M Methylestrenolone HO N3 CH3 CH3 D-lysergozide (+)-2-omino- 1 -buton01 (I) KOH (isomerizotion) Methylergometrine Reference(s): US 2 265 207 (Sandoz; 1941; CH-prior. 1939). Fonnulation(s): amp. 0.2 mglml; drg. 0.125 mg; drops 0.25 mglml; sol. 0.24 mg1100 ml; tabl. 0.125 mg (as maleate) Trade Name(s): D: Methergin (Novartis I: Methergin (Novartis) Ryegonovin (Morishita) Pharma) J: Levospan (Isei) USA: Ergotrate Maleate (Lilly); Syntometrin (Novartis Metenarin (Teikoku Zoki) wfm Pharma)-comb. Methergin (Sandoz- Methergine (Sandoz); wfm F: Methergin (Novartis) Sankyo) Met hylestrenolone (Normethandrone; Normethandrolone) ATC: G03DC31 Use: progestogen RN: 514-61-4 MF: C,,H2,02 MW: 288.43 EINECS: 208-183-0 CN: (l7P)- 17-hydroxy-l7-methylestr-4-en-3-one CrO,. CH,COOH chromium(L4) 0 oxide orthoformote nandrolone (9. v.) Methylmethionine sulfonium chloride M 1297 I Methylestrenolone I 1. H3C-MgBr - 1. methylmagnes~um bromide w lithium. 0 ammonia 3-0.1 7a-dimethyl- estrodiol 1. Li. NH3 2. Cm3. CH3COOH contd. os under , r 1. lithium, ammonia 2. chromium(VI) oxide estrone 3-methyl ether a,b Djerassi, C. et al.: J. Am. Chem. Soc. (JACSAT) 76,4092 (1954). c US 2 744 122 (Syntex; 1956; MEX-prior. 1951). US 2 774 777 (S yntex; 1956; prior. 1952). Djerassi, C. et al.: J. Am. Chem. Soc. (JACSAT) 76,4092 (1954). alternative synthesis: US 2 849 461 (P. de Ruggieri; 1958; appl. 1957). Trade Name(s): D: Gynikosid (Boehringer F: Orgasttron (Organon); wfm USA: Methalutin (Parke Davis); Mannh.)-comb.; wfm wfm Methy lmethionine sulfonium chloride ATC: A02 (Methiosulfonii chloridum; MMS; Vitamin U) Use: peptic ulcer therapeutic, antidote RN: 1 1 15-84-0 MF: C,H,,CINO,S MW: 199.70 EINECS: 214-231-1 LD,,: 259 mgkg (M, i.v.); >6 g/kg (M, p.0.); 432 mglkg (R, i.v.); >6 glkg (R, p.0.) CN: (S)-(3-amino-3-carboxypropyl)dimethylsulfonium chloride bromide RN: 33515-1 1-6 MF: C,H,ABrNO,S MW: 244.15 iodide RN: 3493-11-6 MF: C,H,JNO,S MW: 291.15 1298 M Methylpentynol H C NH2 \s-COOH + H3C-CI - / H C + NH2 'I- ' \~'-"%ooH CH3 L-rnethionine methyl Methylrnethionine sulfoniurn chloride chloride I I Referencefs): DE 1 239 697 (Degussa; appl. 20.2.1963). therapy of renal diseases: US 4 122 189 (Kaken; 24.10.1978; J-prior. 3 1.3.1976). GB 1 538 000 (Kaken; appl. 30.3.1977; J-prior. 31.3.1976). DOS 2 714 391 (Kaken; appl. 3 1.3.1977; J-prior. 31.3.1976), hyperlipidernic effect: Seri, K. et al.: Arzneim Forsch. (ARZNAD) 28, 171 1 (1978). Formulation(s): drg. 12.5 mg; sol. 0.4 gI100 g Trade Narne(s): D: Medosalgon (Loges)- I: Quamon (Neopharmed; as New Edion-U (SS Seiyaku) comb.; wfm methylsulfate); wfm Nichigreen U (Nichiiko) Stacho-Zym (Kattwiga)- J: Cabagin (Kowa) Showa U (Showa) comb.; wfm Gaston U (Tokyo Hosei) U-vit. (Hamari) F: Ardesyl (Beytout); wfm Kizankohl (Sanko) .Vitas U (Kaken) Lobarthrose (Opodex); Kizankohl U (Sanko) Yucron (Daigo Eiyo) wfm New U-TIV (Zeria)-comb. combination preparations Methylpentynol ATC: (Meparfynol) Use: RN: 77-75-8 MF: C,H,,O MW: 98.15 EINECS: 201-055-5 LD,,,: 525 mglkg (M, p.0.) CN: 3-methyl- 1 -pentyn-3-01 NO5CM 15 sedative Reference(s): DRP 285 770 (Bayer; 1913). DRP 289 800 (Bayer; 1913). DRP 291 1 85 (Bayer; 1914). No or NoNHZ. liq. NH, HCECH + OwCH3 H3C acetylene butonone Forrnulafion(s): cps. 250 mg OH CH3 HCFC~/ CH3 Methylpentynol Trade Narne(s): D: Allotropal (Heyl); wfm N-Oblivon (LatCma; as Melval (Kattwiga)-comb.; methylpentynol wfm carbamate); wfm F: N-Oblivon (Latema); wfrn GB: Insomnol (Medo); wfrn Oblivon (British Schering); wfrn USA: Dormison (Schering); wfrn Methylphenidate M 1299 Methylphenidate ATC: N06BA04 Use: psychotonic RN: 1 13-61 MF: CI4HlyNO2 MW: 233.31 EINECS: 204-028-6 LD,,: 41 mgkg (M, i.v.); 150 mg/kg (M, p.0.); 48 mgkg (R, i.v.); 367 mg/kg (R, p.0.) CN: a-phenyl-2-piperidineacetic acid methyl ester hydrochloride RN: 298-59-9 MF: C,,HlyN02. HCl MW: 269.77 EINECS: 206-065-3 LD,,: 40 mgkg (M, i.v.); 60 mg/kg(M, p.0.); 50 mgkg (R, i.v.); 350 mg/kg (R, p.0.) benzyl 2-chloro- phenyl- cyanide pyridine (2-pyridyl)- acetonitrile methyl phenyl- (2-pyridiy1)- ocetote (1) HP. Pt 1 + Reference(s): US 2 507 631 (Ciba; 1950; CH-prior. 1944). & 0, CH3 Methylphenidate separation of diastereomers: US 2 957 880 (Ciba; 1960; CH-prior. 1953). Panizzon, L.: Helv. Chim. Acta (HCACAV) 27, 1748 (1948). Formulation(s): amp. 20 mg; tabl. 5 mg, 10 mg, 20 mg (as hydrochloride) Trade Name(s): D: Ritalin (Novartis Pharma) I: Ritalin (Ciba); wfm USA: Ritalin (Novartis) F: Ritaline (Novartis) J: Ritalin (Ciba-Geigy- GB: Ritalin (Novartis) Takeda) Methylphenobarbital (Mephobarbital; Methylphenobarbitone) ATC: N03AAOl Use: anticonvulsant, sedative RN: 115-38-8 MF: C,,H14N,0, MW: 246.27 EINECS: 204-085-7 LD,,: 300 mglkg (M, p.0.) CN: 5-ethyl-1 -methyl-5-phenyl-2,4,6(1 H,3H,5H)-pyrimidinetrione 1300 M Methylprednisolone NoOC,H, diethyl axalate benzyl ethyl phenyl- cyanide acetate CH3 diethyl 3-0x0- diethyl ethyl- phenylmolonote (11) diethyl phenyl- rnolonote rnethylureo DRP 537 366 (I. G. Farben; 1929). DRP 590 175 (I. G. Farben; 1932). Formulation(s): tabl. 30 mg, 60 mg, 200 mg Trade Narne(s): NoOC2H5 b n ethyl bromide Methylphenobarbital D: Prominal (Bayer); wfm Prominalette (Bracco); GB: Prominal (Sanofi Winthrop) wfm 1: Prominal (Bracco); wfm J: Pro-mind (Bayer) USA: Mebaral (Sanofi) Methylprednisolone ATC: D07AAO1; DlOAA02; H02AB04 Use: glucocorticoid RN: 83-43-2 MF: C22H3,0s MW: 374.48 EINECS: 201-476-4 LD,,: >4 glkg (R, p.0.) CN: (6a,11 @-I 1,17,21-trihydroxy-6-methylpregna-1,4-diene-3,20-dione acetate RN: 53-36-1 MF: C24H3206 MW: 416.51 EINECS: 200-171-3 LD,,,: >10 g/kg (R, P.o.) succinate RN: 2921-57-5 MF: CZhH340R MW: 474.55 EINECS: 220-863-9 succinate sodium salt RN: 2375-03-3 MF: C,6H,3Na0, MW: 496.53 EINECS: 219-156-8 LD,,,: 750 mg/kg (M, i.v.); >5 g/kg (M, p.0.); 640 mglkg (R, i.v.); >5 glkg (R, p.0.) . 6-chloro- 3-( chloromethyl )-3 ,4-dihydro-2-methyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,l-dioxide 5-chloro-2.4-di- urea 7-sulfomoyl-6-chloro- 3- sulfarnoylaniline oxo-3.4-d1hydro-2H- 1.2. 4-. with (-) -1 0-comphonulfonic (4-hydroxy-3-meth- oxypheny1)acetone (IV) DL-a-amino-a- vonillylpropionitrile L-a-omino-a- vonillylpropionitrile (V) L-a-omino-a- vonillylpropionomide 1294. [7(S )-( la,2~,4~,5a,7P) 1-7 -( 3-hydroxy-l-oxo-2-phenylpropoxy )-9 ,9-dimethyl-3-oxa- 9- azoniatricyclo[3.3.1 .02.4]nonane bromide nitrate RN: 6 10 6-4 6-3 MF: C,,H,,N20, MW: 380.40 EINECS: 22 8-0 6 5-2 methylsulfate RN: 1806 7-1 3-5 MF: