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Pharmaceutical Substances Syntheses, Patents, Applications - Part 123 pps

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Medazepam M 1221 Pectite (Kissei) Pelmain (Sawai) Radcol (Nippon Universal) Thibrin (Kyowa-Hoei) Sekinin (Tokyo Hosei) Zeotin (Toa Eiyo) Medazepam ATC: N05BA03 Use: tranquilizer, anxiolytic RN: 2898-12-6 MF: Cl6H,JlN2 MW: 270.76 EINECS: 220-783-4 LD,,: 475 mgfkg (M, p.0.); 900 mglkg (R, p.0.) CN: 7-chloro-2,3-dihydro-1-methyl-5-phenyl-1H-1,4-benzodiazepine 2-amino-5- chloro- benzophenone 1. NaH 2. H3C-I LiAIH, lithium olanote I Medazepam glycine ethyl ester I - 1. sodium hydride 2. methyl iodide H~N-~~~ MgBr nitrobenzene, K2C03 Cu(CH3COO), -, c 1 C N ethylenediomine 2,5-dichloro- phenyl- 1 -(2,5-dichloro- benzonitrile magnesium phenyl)-1-phenyl- bromide methylimine 4-chloro- p-toluene- oniline sulfochloride 4-chloro-1 -tosylamino- benzene H,c/O\ /P 0//S'Oy~~3 NaOCH3 , I1 dimethyl sulfote 1222 M Medibazine 4-chloro-1 -(N-methyl- 4-chloro-N- Losylamino)benzene (It) methylaniline N-(4-chloropheny1)- benzoyl N-methylethylene- chloride diamine (111) Reference(s): a,bUS 3 109 843 (Roche; 5.1 1.1963; appl. 21.6.1962; prior. 28.7.1961). US 3 131 178 (Roche; 28.4.1964; prior. 28.7.1961,4.12.1961,21.6.1962). Sternbach, L.H. et al.: J. Org. Chem. (JOCEAH) 28,2456 (1963). c DAS 1 934 385 (Sumitomo; appl. 7.7.1969). d DAS 1 695 188 (Roche; appl. 23.5.1967; USA-prior. 3.6.1966). DAS 1 795 81 1 (Roche; appl. 23.5.1967). alternative syntheses: US 3 141 890 (Roche; 21.7.1964; prior. 28.7.1961,4.12.1961, 21.6.1962). US 3 144 439 (Roche; 11.8.1964; prior. 28.7.l961,4.12.l96I, 21.6.1962). DE 1 445 864 (Roche; appl. 27.7.1962; USA-prior. 28.7.1961). DOS 2 204 484 (Sumitomo; appl. 31.1.1972; J-prior. 9.2.1971, 6.4.1971,28.5.1971). DOS 2 217 301 (Sumitomo; appl. 10.4.1972; J-prior. 12.4.1971). I-demethyl-derivative from 5-chloro-2-(2,3-dioxop~perazino)benzophenone: DAS 1 906 254 (Sumitomo; appl. 7.2.1969; J-prior. 2.4.1968). DAS 1 965 980 (Sumitomo; appl. 7.2.1969; J-prior. 2.4.1968). Formulation(s): cps. 5 rng, I0 mg; tabl. 2.5 mg, 5 mg, 10 rng Trade Name(s): D: Medazepam AWD I: Debrum (Sigma-Tau)- Kobazepam (Nihon Tabletten (ASTA Medica comb. Iy akuhin) AWD) Nobriurn (Roche) Metonas (Kanto) Rudotel Tabletten (OPW) J: Azepamid (Taiyo) Narsis (Sumitomo) F: Nobriurn (Roche); wfm Cerase (Torii) Nobrium (Nippon Roche) GB: Nobrium (Roche); wfm Resmit (Shionogi) Medibazine ATC: C01 Use: coronary vasodilator RN: 53-31-6 MF: C,,H,,N202 MW: 386.50 EINECS: 200-168-7 LD,,,: 4 1 mgkg (M, i.v.) CN: l-(1,3-benzodioxol-5-ylmethyl)-4-(diphenylmethyl)piperazine Medifoxamine M 1223 Reference(s): US 3 119 826 (Science Union; 28.1.1964; F-prior. 12.4.1961). 1-(3.4-methylenedioxy- benzhydryl Trade Narne(s): F: Vialibran (Servier); wfm Medibozine Medifoxamine benzy1)piperozine chloride ATC: N06A Use: antidepressant RN: 32359-34-5 MF: C1,H,,N02 MW: 257.33 EINECS: 251-01 1-4 LD,,: 750 mgikg (M, p.0.) CN: N,N-dimethyl-2,2-diphenoxyethanamine fumarate (1:l) RN: 16604-45-8 MF: C,,H,,N02. C4H4O4 MW: 373.41 EINECS: 240-657-2 C I 0 COOH uoH + >COOH - 0 C I "'8 phenol dichloroocetic diphenoxyocetic ocid acid (I) I + 7 2. dimethylornine diphenoxy-N.N-di- I Medifoxomine ( rnethylocetomide Reference(s): FR 5 498 (Lab. Gerda; appl. 1966). Brunet, M.A. et al.: Bull. Soc. Chim. Fr. (BSCFAS), 2000 (1967). additional synthesis: FR 2 645 147 (Lab. Rolland; appl. 3.4.1989). FR 2 601 004 (Lab. Rolland; appl. 7.7.1986). FR 2 588 553 (Lab. Rolland; appl. 16.10.1985). EP 226 475 (Lab. Rolland; appl. 22.7.1985). synthesis of diphenoxyacetic acid: Alphen, J. van: Recl. Trav. Chim. Pays-Bas (RTCPA3) 46, 144 (1927). Scheibler, H.; Depner, M.: J. Prakt. Chem. (JPCEAO) 7, 60 (1958). DE 561 281 (Chem. Fabrik von Heyden; appl. 1930), also EP 226 475, FR 2 601 004. 1224 M Medrogestone medical use for treatment of cerebral hypoxia and senility: FR 2 589 357 (Lab. Rolland; appl. 5.11.1985). FR 2 583 639 (Lab. Rolland; appl. 24.6.1985). Formularion(s): tabl. 50 mg Trade Name(s): F: ClCdial (Lipha SantC) Medrogestone ATC: G03DB03 Use: progestogen RN: 977-79-7 MF: C,,H,,O, MW: 340.51 EINECS: 213-555-0 LD,,,: 850 mglkg (g.p., p.0.) CN: 6,17-dimethylpregna-4,6-diene-3,20-dione & Me ,,vCH3 \~'3 H,C 1 O/ OH , CHCI3, 0 'C peroxyocetic acid HO ' methyl 3@-hydroxy-17a- rnethyl-ondrost-5-ene-17- corboxylote Cr03. H,C-CO-CH3 chromium(VI) oxide methylmagnesium bromide thionyl chloride CI CI nr chloronil (N)* CH~ Medrogestone Medroxyprogesterone acetate M 1225 - 2. methyl iodide 38-ocetoxy-6-methyl- 20-0x0-5.16-pregnodiene (from dehydropregnenolone. onologously to o) 1. Oppenouer oxidation 2. IV Reference(s): a US 3 133 913 (American Home Products, 19.5.1964; appl. 11.9.1961). Deghenghi, R.; Gaudry, R.: J. Am. Chem. Soc. (JACSAT) 83,4668 (1961). starting material: Plattner, P.A. et al.: Helv. Chim. Acta (HCACAV) 31,603 (1948). b Deghenghi, R. et al.: J. Med. Chem. (JMCMAR) 6,301 (1963). starting material: Bum, D. et al.: J. Chem. Soc. (JCSOA9) 1957,4092. alternative syntheses: US 3 170 936 (American Home Products; 23.2.1965; appl. 7.8.1963). US 3 210 387 (American Home Products; 5.10.1965; appl. 6.5.1963; CDN-prior. 28.1 1.1962). Formulation(s): tabl. 5 mg, 25 mg Trade Name(s): D: Presomen (Solvay Prothil (Solvay I: Colprone (Wyeth) Arzneimitte1)-comb. Arzneimittel) USA: Colprone (Ayerst); wfm F: Colprone (Wyeth-Lederle) Medroxyprogesterone acetate ATC: G02B; G03D Use: antineoplastic, progestogen RN: 71-58-9 MF: C2,H,,O4 MW: 386.53 EINECS: 200-757-9 LD,,,: >16 glkg (M, p.0.); >6.4 g/kg (R, p.0.); >5 glkg (dog, p.0.) CN: (6cr)-17-(acetyloxy)-6-methylpregn-4-ene-3,20-dione 5a.17~-dihydroxy- 3,20-dioxo-6P-methyl- pregnone HCI. CHCIJ - CH3 17-hydroxy-6~- methylprogesterone (I) I226 M Medroxv~rogesterone acetate ocetic anhydride (11) CH3 Medroxyprogesterone ocetote 17-hydroxy- ethylene progesterone glycol ocid bromide Referenceis): a US 3 147 290 (Upjohn; I .9.1964; appl. 17.5.1961; prior. 23.1 1.1956). Ellis, B. et a].: J. Chem. Soc. (JCSOA9) 1957, 4092. starting material: cf literature cited under a b US 3 061 616 (~ocleta Farmaceutici Italia; 30.10.1962; appl. 17.9.1958; GB-prior. 24.4.1958). DE 1 097 986 (Syntex; appl. 29.8.1957; MEX-prior. 8.9.1956). Babcock, J.C. et al.: J. Am. Chem. Soc. (JACSAT) 80,2904 (1958). starting material: Bernstein, S. et al.: J. Am. Chem. Soc. (JACSAT) 76, 5674 (1954). The Merck Index, 4756 (Rahway 1976). alternative syntheses: DE 1 081 456 (British Drug Houses; appl. 21.8.1958; GR-prior. 13.8.1957). DE 1 101 415 (Searle; appl. 24.9.1958; USA-prior. 27.9.1957). US 3 043 832 (Ormonoterapia Richter; 10.7.1962; appl. 28.4.1961; I-prior. 27.2.1961). review: Ehrhardt, Ruschig 111,352, Medrylamine M 1227 Formulation(s): amp. 500 mg, 1 g; susp. 500 mg; susp. 150 mglml, 500 mglml; tabl. 2.5 mg, 5 mg, 10 mg, 100 mg, 200 mg, 250 mg, 400 mg, 500 mg Trade Name(s): D: Clinofem (Pharmacia & Upjohn)-comb. Clinovir (Pharmacia & Upjohn) Depo-Clinovir (Pharmacia & Upjohn) Farlutal (Pharmacia & Upjohn) MPA (Hexa1)-comb. F: Depo-Prodasone (Pharmacia & Upjohn)- comb. Depo-Provera (Pharmacia & Upjohn) Divina (1nnothCra)-comb. Farlutal (Pharmacia & Upjohn) Gestoral (Novartis) Prodasone (Pharmacia & Upjohn) GB: Depo-Provera (Pharmacia & Upjohn) Farlutal (Pharmacia & Upjohn) Provera (Pharmacia & Upjohn) combination preparations I: Depo-Provera (Upjohn) Farlutal (Farmitalia) Lutoral (Midy) Provera (Upjohn) J: Hysron (Kyowa) Provera (Upjohn) USA: Amen (Carnrick) Depo-Provera (Pharmacia & Upjohn) Premphase (Wyeth-Ayerst) Prempro (Wyeth-Ayerst) Provera (Pharmacia & Upjohn) Medry lamine ATC: R06 Use: topical antihistaminic RN: 524-99-2 MF: C1,H2,N02 MW: 285.39 EINECS: 208-368-6 CN: 2-[(4-methoxyphenyl)phenylmethoxy]-N,N-dimethylethanamine hydrochloride RN: 6027-00-5 MF: CI~H2,N02. HC1 MW: 321.85 EINECS: 227-888-4 LD,,,: 148 mglkg (M, i.p.) "c"% + ~0-~~~3 I / CH3 4- methoxy- 2-dimethylamino- Medrylamine benzhydryl 'ethanol chlor~de Reference(s): US 2 668 856 (UCB; 1954; appl. 1948). Formulation(s): ointment 20 mglg (2 %) (as hydrochloride) Trade Name(s): D: Corti-Postafen (UCB)- Postafen Salbe (UCB); comb.; wfm wfm Medrysone ATC: SOlBA08 Use: glucocorticoid RN: 2668-66-8 MF: C,,H,,O, MW: 344.50 EINECS: 220-208-7 LD,,,: 338 mglkg (R, i.p.) CN: (6a, 11 P)- 11 -hydroxy-6-methylpregn-4-ene-3,20-dione 1228 M Mefenamic acid 1. ethylene glycol, p-toluene- 0 sulfonic acid CH, 2. lithium alanate 6a-methyl-l l -oxo- progesterone Medrysane I Reference(s): US 2 864 837 (Upjohn; 1958; prior. 1958). US 2 968 655 (Upjohn; 1961; prior. 1956). starting material: Spero, G.B. et al.: J. Am. Chem. Soc. (JACSAT) 78, 6213 (1956). US 2 968 655 (Upjohn; 1961; prior. 1956). Formulation(s): eye drops 10 mg; eye ointment 10 mg Trade Name(s): D: Ophtocortin (Winzer) generic Spectramedryn (Pharm- I: Medramil (Farmigea)- Allergan) comb. F: Medryson Faure (CIBA USA: HMS Liquifilm (Allergan); Vision) wfm Medrocort (Upjohn); wfm Mefenamic acid ATC: MOlAGOl Use: anti-inflammatory, antirheumatic, analgesic RN: 61-68-7 MF: ClsHl,NO, MW: 241.29 EINECS: 200-513-1 LD,,,: 96 mglkg (M, i.v.); 525 mglkg (M, p.0.); 112 mgkg (R, i.v.); 740 mgkg (R, p.0.) CN: 2-[(2,3-dimethylphenyl)amino]benzoic acid copper(l1) acetate potassium 2,3-dimethyl- Mefenamic acid 2-bromo- aniline benzoate Reference($): US 3 138 636 (Parke Davis; 23.6.1964; appl. 23.6.1960). DE 1 163 846 (Parke Davis; appl. 22.6.1961; USA-prior. 23.6.1960). alternative syntheses: DAS 1 186 073 (Parke Davis; appl. 30.4.1963; CDN-prior. 18.9.1962). DAS 1 186 074 (Parke Davis; appl. 30.4.1963; CDN-prior. 18.9.1962). DAS 1 186 870 (Parke Davis; appl. 30.4.1963; CDN-prior. 18.9.1962). DAS 1 186 871 (Parke Davis; appl. 30.4.1963; CDN-prior. 18.9.1962). Formulation(s): cps. 250 mg; powder 500 mg, 1 g; suppos. 125 mg, 500 mg; susp. 50 mg Mefenorex M 1229 Trade Narne(s): D: Parkemed (Parke Davis) J: Baphameritin M USA: Ponstan (Parke Davis); Ponalar (Parke Davis) (Hishiy ama) wfm F: Ponstyl (Parke Davis) Bonabol (Sawai) Ponstel (Parke Davis) GB: Meflam (Trinity) Pontal (Parke Davis- Ponstan (Elan) Sank y 0) I: Lysalgo (SIT) Spantac (Uji) Mefenorex ATC: A08AA09 Use: appetite depressant RN: 17243-57-1 MF: C,,H,,ClN MW: 21 1.74 EINECS: 241-279-0 CN: N-(3-chloropropy1)-a-methylbenzeneethanamine hydrochloride RN: 5586-87-8 MF: CI2H&lN . HCl MW: 248.20 EINECS: 226-985-9 LD,,: 49 mgkg (M, i.v.); 230 mglkg (M, p.0.); 35 mglkg (R, i.v.); 410 mglkg (R, p.0.) phenylacetone 3-amino- chloride Mefenorex 1 -proponol Referencefs): DE 1 210 873 (Hoffmann-La Roche; appl. 18.3.1959). Formulation(s): drg. 40 mg (as hydrochloride) Trade Narnefs): D: Rondimen (ASTA Medica F: Incital (Pierre Fabre SantC) AWD; as hydrochloride) USA: Anexate (Roche); wfm Mefexamide ATC: N05C Use: psychoanaleptic, CNS stimulant RN: 1227-61-8 MF: C,SH24N,0, MW: 280.37 EINECS: 214-963-1 LD,,: 168 mglkg (M, i.v.); 1500 ~glkg (M, p.0.) CN: N-[2-(diethylamino)ethyl]-2-(4-methoxyphenoxy)acetamide monohydrochloride RN: 3413-64-7 MF: C,,H,N203 . HCl MW: 316.83 EINECS: 222-304-4 hydroquinone chloroocetic 4-methoxy- monomethyl acid phenoxyocetic ether acid 1230 M Mefloquine R+rence(s): Thuillier, G.; Rumpf, P.: Bull. Soc. Chim. Fr. (BSCFAS) 1960, 1786. N,N-diethyl- For~nulation(s): amp. 150 mg; tabl. 150 mg Mefexomide Trade Narne(s): F: MCfCxadyne (Anphar); Timodyne (Anphar); wfm wfm I: Perneuron (Crinos); wfm ethylenediomine Mefloquine ATC: POIBAOS Use: antimalarial RN: 53230-10-7 MF: C,,H,$,N,O MW: 378.32 CN: (R*,S*)-(+)-a-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol monohydrochloride RN: 51773-92-3 MF: C,,H,,F,N,O~HCl MW: 414.78 EINECS: 257-412-0 LD,,,: 880 mglkg (R, p.0.) 2-trifluoro- ethyl Y,Y.Y- 2.8-bis(trifluoro- 2,B-bis(trifluoro- methyl- trifluorooceto- methyl)-4-hydroxy- methyl)-4-bromo- aniline (I) acetate quinoline quinoline (11) n-CIHo-Li butyl- lithium Li COOH (from 2-bromo- 2,&bis(trifIuoro- 2,8-bis(trifluoro- pyridine) methyl)-4-lithio- methyl)-4-quinoline- quinoline (Ill) corboxylic acid (N) . >5 glkg (dog, p.0.) CN: (6cr )-1 7-( acetyloxy )-6 -methylpregn-4-ene-3,20-dione 5a.17~-dihydroxy- 3,20-dioxo-6P-methyl- pregnone HCI. CHCIJ - CH3 17-hydroxy-6 ~- methylprogesterone (I) I226. CN: 7-chloro-2,3-dihydro-1-methyl-5-phenyl-1H-1,4-benzodiazepine 2-amino- 5- chloro- benzophenone 1. NaH 2. H3C-I LiAIH, lithium olanote I Medazepam glycine ethyl ester I - 1 414.78 EINECS: 25 7-4 1 2-0 LD,,,: 880 mglkg (R, p.0.) 2-trifluoro- ethyl Y,Y.Y- 2.8-bis(trifluoro- 2,B-bis(trifluoro- methyl- trifluorooceto- methyl )-4 -hydroxy- methyl )-4 -bromo- aniline (I)

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