Pharmaceutical Substances Syntheses, Patents, Applications - Part 216 ppt

Urokinase U 21 51 Ln3 piperarine carbonate I 1.3-dimethyl-6-(3- chloropropylamino)- uracil Urapidil Reference(s): DE 1 942 405 (Byk Gulden; appl. 20.8.1969). US 3 957 786 (Byk Gulden; 18.5.1976; D-prior. 20.8.1969). US 4 067 982 (Byk Gulden; 10.1.1978; prior. 20.8.1970, 8.4.1976). addition compound with furoscmide: GB 1 512 771 (Byk Gulden; appl. 7.2.1977; L-prior. 9.2,1976). Formulation(s): amp. 27.35 mg, 54.7 mg (as hydrochloride); amp. 25 mg, 50 mg; cps. 30 mg, 60 mg (as fumarate): s. r. cps. 30 mg, 60 mg, 90 mg Trade Name(s): D: Alpha-Depressan (OPW) Eupressyl gC1 (Byk) 1: Ebrantil-301-60 (By k Ebrantil (Byk Gulden) Mediatensyl gC1 (DCbat Gulden; as fumarate) F: Eupressyl (Byk; as cardio) Ebrantil-50 (Byk Gulden) hydrochloride) J: Ebrantil (Kaken) Urokinase ATC: BOlAD04 Use: plasminogen activator, fibrinolytic RN: 9039-53-6 MF: unspecified MW: unspecified EINECS: 232-917-9 LD,,: >3000000 iulkg (M, i.v.); >2.727 mglkg (M, p.0.); >3000000 iulkg (R, i.v.); >2.727 mglkg (R, p.0.); >909 pglkg (dog, i.v.) CN: urokinase (enzymektivating) a From human urine. b From culture of renal cells. Enrichment and purification occurs via combined adsorption and elution processes, e. g. on BaSO,, silica gels, DEAE-cellulosis, ion-exchange resins (e. g. Amberlite-IRC-50). Referencefs): a Sobal et al.: Am. J. Physiol. (AJPHAP) 171. 768 (1952). US 2 961 382 (Ortho; 1960; appl. 1957). US 2 983 647 (Leavens; 1961 ; GB-prior. 1955). US 2 989 440 (Ortho; 1961: appl. 1959). US 3 08 1 236 (Warner-Lambert; 12.3.1963; appl. 26.4.1961). DAS 2 616 761 (Hitachi Chemical; appl. 15.4.1976; J-prior. 18.4.1975). DAS 2 629 886 (Asahi; appl. 2.7.1976; J-prior. 4.7.1975). DAS 2 632 212 (Hitachi Chemical; appl. 16.7.1976; J-prior. 16.7.1975). b DAS 2 551 017 (Abbott; appl. 13.1 1.1975; USA-prior. 31.3.1975). 2 152 U Ursodeoxycholic acid purification: White et al.: Biochemistry (BICHAW) 5, 2160 (1966). US 3 256 158 (Abbott; 14.6.1966; appl. 22.3.1963). US 3 542 646 (Green Cross; 24.1 1.1970; J-prior. 22.1 1.1966). DOS 2 143 815 (Mochida; appl. 1.9.1971; J-prior. 5.9.1970). DOS 2 143 816 (Mochida; appl. I .9.1971; J-prior. 4.9.1970). DOS 2 246 969 (Choay; appl. 25.9.1972; F-prior. 24.9.1971, 30.6.1972). US 3 723 251 (Mochida; 27.3.1972; J-prior. 4.9.1970). DAS 2 502 095 (Green Cross; appl. 20.1.1975; J-prior. 22.1.1974, 28.1.1974). GB 1 498 01 8 (Abbott; appl. 3.10.1975; USA-prior. 20.1 1 .l974). DOS 2 809 330 (Sumitomo; appl. 3.3.1978; J-prior. 10.3.1977). DOS 2 823 353 (Sumitomo; appl. 29.5.1978; J-prior. 3.6.1977). US 4 160 697 (Tanabe Seiyaku; 10.7.1979; J-prior. 9.4.1977, 28.4.1977, 30.9.1977). US 4 169 764 (Ajinomoto; 2.10.1979; J-prior. 13.8.1975). s~ubilization in aqueous solution: US 3 950 223 (Ajinomoto; 13.4.1976; J-prior. 7.1 2.1972). crystallized urokinase: Lesuk et al.: Science (Washington, D.C.) (SCIEAS) 147, 880 (1965). Formulation(s): vial 5000 iu/ml, 250000 id5 ml, 2500 iu, 50000 iu, 100000 iu, 250000 iu, 500000 iu, 600000 iu. Trade Name(s): D: Actosolv (Hoechst) Alphakinase (Alpha) Corase (medac) Rheotromb (curasan) Urokinase-medac (medac) F: Actosolv urokinase (Hoechst HoudC) Urokinase Choay (Sanofi Persolv (Lepetit) Winthrop) Purochin (Sclavo Pharma) GB: Ukidan (Serono) Ukidan (Serono) I: Actosolv (Hoechst Marion Urochinase (Crinos; Sanofi Roussel) Winthrop) Alfakinasi (Alfa J: Urokinase (Green Cross) Wassermann) USA: Abbokinase (Abbott) Kisolv (Ecupharma) Ursodeoxycholic acid ATC: A05AA02 Use: choleretic RN: 128-13-2 MF: C,H4,04 MW: 392.58 EINECS: 204-879-3 CN: (3a,5P,7P)-3,7-dihydroxycholan-24-oic acid H,C, COOH Cr03, CH3COOH HO.+' 8 H chromium trioxide ' 0 chenodeoxycholic ocid (9. v.) Ursodeoxycholic acid U 2 1 53 1. ozeotropic distillation with toluene 2. CqHgOH, Na I b Ursodeoxycholic acid I Reference(s): FR 1 372 109 (Tanabe; appl. 23.9.1 963; J-prior. 3 1.10.1 962). Formulation(s): cps. 225 mg, 250 mg, 300 mg; f. c. tabl. 250 mg, 400 mg; gran. 5 %; tabl. 150 mg Trade Name(s): D: Cholit-Ursan (Fresenius) Cholofalk (Falk) Peptarom (Fresenius) UDC (Hexal) Urso (Heumann) Ursochol (Inpharzam) Ursofalk (Falk) F: Arsacol (Zambon) Delursan (Hoechst Houdt) Destolit (Marion Merrell) Ursolvan (S ynthklabo) GB: Combidol (CD Pharm.)- comb. Destolit (Hoechst) Ursofalk (Tliames) I: Biliepar (Ibirn) Desocol (Campugnani) Deursil (Sanofi Winthrop) Fraurs (Francia Farm.) Galmax (Max Farma) Lentorsil (Italfarmaco) Litoff (Caber) Litursol (Cdnos) Ursacol (Zambon Italia) Ursilon (IBI) Ursobil (ABC-Torino) Ursoflor (So. se Pharm.) Ursolisin (Magis) generics J: Like (SS Se1yaku)-comb. Urso (Tanabe) Urso 100 (Tanabe) Zeria Ichoyaku (Zeria Shinyaku Kogyo)-comb. USA: Actigall (Novartis) 2154 V Valaciclovir Valaciclovir (BW-256U; 256 U 87) ATC: JO5ABI I Use: antiviral, prodrug of aciclovir RN: 124832-26-4 MF: C,,H2,,N604 MW: 324.34 CN: L-valine 2-((2-amino- 1,6-dihy dro-6-0x0-YH-purin-9-y1)methoxylethy I ester monohydrochloride RN: 124832-27-5 MF: C,,HaN604. HCI MW: 360.80 dicyclohexylcorbodiimide 4-dimethylorninopyridine DMF F I HOOC '3'3 Reference(s): EP 308 065 (Wellcome Found. Ltd; appl. 12.8.1988; GB-prior. 15.8.1987,5.11.1987). 0 H*. Pd-C 0 CH, 2-[(2-amino-1.6-dihydro-6-0x0- combination with lamotrigine: WO 9 505 179 (Wellcome Found. Ltd; appl. 17.8.1994; GB-prior. 18.8.1993). - 0 CH, Volociclovir water-duprrsihle tablets: WO 9 213 527 (Wellcome Found. Ltd; appl. 29.1.1.992; GB-prior. 3O.l.l99l,22.Il.l991, 25.1 1.1991). 9H-purin-9-yl)rnethoxy]ethyl N-[(benzyloxy)corbonyl]-L-vollnate (I) medical use for preventing post lterpelic neuralgia: GB 2 282 759 (SmithKline Beecham; appl. 14.10.1994; GB-prior. 16.10.1993). Formulution(s): f. c. tabl. 500 mg; tabl. 500 mg, 1 g (as hydrochloride) Trade Nameis): D: Valtrex (Glaxo Wellcome) GB: Valtrex (Glaxo Wellcome; USA: Valtrex (Glaxo Wellcome; F: Ztlitrex (Glaxo Wellcome; as hydrochloride) as hydrochloride) as hydrochloride) Valdetamide (Novonnl; Dicthy lpenlenamide) ATC: N05C Use: hypnotic RN: 512-48-1 MF: C,H,,NO MW: 155.24 EINECS: 208-143-2 LD,,,: 400 mglkg (R, p.0.); 300 mglkg (dog, p.0.) CN: 2,2-diethyl-4-pentenamide Valethamate bromide V 2 155 CN NOOC~H~ ""xO "C~B' + LO o L~H3 ' H3C o kti3 COOH ethyl ethyl ethyl diethyl- bromide cyonoocetote cyonoocetote phenylsodium ally1 chloride 1 Voldetamide Reference(s): DRP 473 329 (I. G. Farben; appl. 1925). DRP 616 876 (I. G. Farben; appl. 1930). DRP 622 875 (1. G. Farben; appl. 193 1). GB 253 950 (I. G. Farben; appl. 1926; D-prior. 1925). reaction of diethylacetonitrile with ally1 chloride in presence of sodium bis(trimethylsi1yl)amide: DOS 2 5 18 122 (Hoechst; appl. 24.4.1975). from diethylacetaldehyde: DOS 2 753 440 (Diamalt; appl. 30.11.1977). Formulation(s): drg. 50 mg; tabl. 300 mg Trade Name(s): D: Arantil (Hoechst)-comb.; Insomnia (ICN); wfm Novo-Dolestan (Much); wfm Nocturetten (Starke)- wfm Betadorm-N (Woe1m)- comb.; wfm comb.; wfm Valethamate bromide ATC: A03 Use: antispasmodic RN: 90-22-2 MF: C19H,,BrN0, MW: 386.37 EINECS: 201-977-8 LD,,: 4200 pglkg (M, i.v.); 330 mglkg (M, p.0.); 4200 pglkg (R, i.v.); 1260 mglkg (R, p.0.) CN: N,N-diethyl-N-methyl-2-[(3-methy1-1-oxo-2-phenylpentyl)oxy]ethanaminium bromide 1. S0CI2 1. N0NH2 1 1. sodium omide 1. thionyl chloride 2. sec-butyl H3C 2. 2-diethylomino- bromide CH3 CH3 ethanol benzyl cyanide 3-methyl-2- 3-methyl-2-phenyl- phenylvolero- voleric acid nitrile 2156 V Valproic acid Volethomote bromide Referencers): DE 969 245 (Kali-Chemie; appl. 1953). DE 971 136 (Kali-Chemie; appl. 1953). Formulation(s): amp. 8 mg; drg. 10 rng; suppos. 20 mg Trade Narne(s); D: Epidosin (Kali-Chemie); wfm I: Epidosin (Sir); wfm J: Barespan Tab. (Hishiyama) Baretaval (Shin Fuso) Beruhgen (Nissin) Cranfupan (Nichiiko) Elist (Sana-Torii) Epidosin (Toyo Jozo) Funapan (Funai) Kaichyl (Samoa) Letamate (Mohan) Pastan (Maruko) Release V (Mochida) Resitan (Grelan) Shikitan (Shiki) Shinmetane (Towa) Study (Toyo Pharmar) Ulban-Q (Toho) Valate (Marishita) Valemate (Taiho) Valemeton (Sanko) Valethalin (Hokuriku) Valethamin (Sawai) Valproic acid ATC: N03AGO1 Use: anticonvulsanl, antiepileptic RN: 99-66-1 MF: C8H,,02 MW: 144.21 EINECS: 202-777-3 LD,,: 1098 mgkg (M, p.0.); 670 mglkg (R, p.0.) CN: 2-propylpentanoic acid sodium salt RN: 1069-66-5 MF: C,H,5Na02 MW: 166.20 EINECS: 213-961-8 LD,,: 750 rnglkg (M, i.v.1; 977 mglkg (M, p.0.); 509 rnglkg (R, i.v.); 670 mgkg (R,'p.o.); 1420 mglkg (dog, p.0.) calcium salt dihydrate RN: 138995-18-3 MF: C,,H3,Ca0, . 2H20 MW: 362.52 P~OPY~ ethyl cyono- bromide acetate ethyl dipropyl- cyanoacetote (I) dipropyl- ocetonitrile NoOH H 0 NoOH I b H3C>cN H3C H3c>c00H H3C Valsartan V 2157 Reference (s): FR-M 2 442 (H. E. J M. Meunier; appl. 17.10.1962). GB 980 279 (H. E. J M. Meunier; appl. 14.10.1963; F-prior. 17.10.1962). US 3 325 361 (Chemetron Corp.; 13.6.1967; F-prior. 17.10.1962). methods: GB 1 522450 (Labaz; appl. 3.6.1977; F-prior. 15.3.1977). GB 1 529 786 (Labaz; appl. 3.6.1977; F-prior. 15.3.1977). US 4 155 929 (Labaz; 22.5.1979; prior. 25.5.1977, 10.5.1978). Formulation(s): amp. 300 mgl3 ml; cps. 150 mg, 300 mg, 500 mg (as free acid); sol. 300 mglml; s. r. drg. 300 mg (as sodium salt); syrup 250 mg15 ml, 300 mgl5 ml; tabl. 250 mg, 333 mg (as calcium salt dihydrate); tabl. 150 mg, 300 mg Trade Name(s): D: Convulex (Byk Gulden) Leptilan (Geigy) GB: Convulex (Pharmacia & Convulex (Promonta) Orfiril (Desitin) Upjohn) Convulsofin (ASTA F: Dtpakine (Sanofi I: Depakin (Sanofi Winthrop) Medica AWD; Boehringer Winthropj J: Depaken (Kyowa Hakko) Mannh.) DCpakine Chrono (Sanofi USA: Depakene (Abbott) Ergenyl (Labaz) Winthrop) Valsartan (CGP-48933) ATC: C09CA03 Use: antihypertensive, angiotensin I1 blocker RN: 137862-53-4 MF: C,,H2,N,O3 MW: 435.53 CN: N-(l-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)[l,1'-biphenyl]-4-yl]methyl]-~-valine 2'-cyonobiphenyl- methyl L-volinote 4-corboxoldehyde hydrochloride valeryl chloride methyl N-voleryl- N-[(2'-cyonobiphenyl- 4-yl)methyl]-L-volinde (It) - - 2158 V Vancomycin tributyltin azide I Valsarton I Reference(s): US 5 399 578 (Ciba-Geigy; 21.3.1995; appl. 29.1 2.1992; CH-prior. 19.2.1990, 5.7.1990). EP 443 983 (Ciba-Geigy; appl. 12.2.1991; CH-prior. 19.2.1990). Biihlmayer, P. et al.: Bioorg. Med. Chem. Lett. (BMCLE8) 1994,4 (I), 29. use for treating diabetic nephropathy: WO 9 524 901 (Ciba-Geigy; appl. 7.3.1995; CH-prior. 17.3.1994). use to treat post-ischaemic renal failure: WO 9 7 13 5 13 (Novartis; appl. 24.9.1996; CH-prior. 6.10.1995). WO 9 702 032 (MSD-Chibret; appl. 26.6.1996; GB-prior. 13.2.1996; USA-prior. 30.6.1995). combination with aldosterone antagonists: WO 9 640 256 (Searle; appl. 5.6.1996; USA-prior. 7.6.1995). WO 9 640 255 (Scarle; appl. 5.6.1996; USA-prior. 7.6.1995). WO 9 640 257 (Searle; appl. 5.6.1996; USA-prior. 7.6.1995). WO 9 640 258 (Searle; appl. 5.6.1996; USA-prior. 7.6.1995). combination with bennzepril: WO 9 631 234 (Ciba-Geigy; appl. 2.4.1996; CH-prior. 7.4.1995). use for treatment of glaucoma and neurodegeneralion: WO 9 521 609 (Ciha-Geigy; appl. 26.1.1995; EP-prior. 8.2.1994). Formulation(s): cps. 80 mg, 160 mg; tabl. 40 mg, 80 mg, 160 mg Trade Name(s): D: Diovan (Novartis) GB: Diovan (Ciba) USA: Diovan (Novartis) F: Tareg (Novartis) I: Tareg (Novartis Farma) Vancom ycin ATC: A07AA09;JOlXAOl Use: antibiotic RN: 1404-90-6 MF: C,,H,,C12N,0, MW: 1449.27 EINECS: 215-772-6 LDSo: 430 mglkg (M, i.v.) CN: [3S-[3R*,6S*(S*),7S*,22S*,23R*,26R*,36S*,38aS*]]-3-(2-amino-2-oxoethyl)-44-[[2-0-(3-a~no-2,3,6- trideoxy-3-C-methyl-or-~-lyxo-hcxopyranosyl)-~-~-glucopyranosyl]oxy]- 10,19-dichloro- 2,3,4,5,6,7,23,24,25,26,36,37,38,38a-~etradecahydro-7,22,28,30,32-pentahydroxy-6-[[4-methyl-2- (methylamino)- l-oxopentyl]arnino]-2,5,24,38,39-pentaoxo-22H-8,11: 18,2 1-dietheno-23,36- (iminomethan0)-13,16:31,35-dimetheno-1 H,16H-[I ,6,9]oxadiazacyclohexadecino[4,5- m][10,2,16]benzoxadiazacyclotetracosine-26-carboxylic acid hydrochloride RN: 1404-93-9 MF: C,,H,,C12N,024 . xHC1 MW: unspecified LD,,,: 489 mglkg (M, i.v.); >5 glkg (M, p.0.); 319 mglkg (R, i.v.); >10 glkg (R, p.0.) Vecuronium bromide V 2 159 I Vancornycin OH Arnphoteric glycopeptid antibiotic from Nocardia orientalis (NRRL 2450, 2451, 2452). Reference(s): US 3 067 099 (Eli Lilly; 4.12.1962; appl. 16.9.1955). purijication via the diphosphate: EP 145 484 (Eli Lilly; appl. 11.12.1984; USA-prior. 12.12.1983). structure: Williamson, M.P.; Williams, D.H.: J. Am. Chem. Soc. (JACSAT) 103,6580 (1981). Formulation(s): cps. 250 mg; vial 500 mg/g, 500 mg/lO ml, 500 mg115 ml, 1 g115 ml, 10 g1lOO ml (as hydrochloride) Trade Narne(s): D: AB-Vancomycin (Astrapin) F: Vancocine (Lilly) I: Vancocina (Lilly) VANCO (Reusch) Vancomycine Dakota J: Vancomycin (Shionogi) Vancomycin CP (Lilly) Pharm (Dakota) USA: Vancocin (Lilly) Vancomycin "Lederle" Vancomycine Lederle generic (Lederle) (Wyeth-Lederle) Vanco-saar (Chephasaar) GB: Vancocin (Eli Lilly) Vecuronium bromide ATC: M03AC03 Use: muscle relaxant RN: 50700-72-6 MF: C3,H5,BrN,04 MW: 637.74 EINECS: 256-723-9 CN: 1-[(2~,3a,5a,16~,17~)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-l-methylpiperidinium bromide 3-chloroper- H benzoic acid 5a-androst-2- isopropenyl en-1 7-one ocetate - 2160 V Venlafaxine sodium ocetyl H chloride Reference(s): US 4 237 126 (Akzo; 2.12.1980; appl. 20.8.1979; GB-prior. 5.9.1978). US 4 297 351 (Akzo; 2.12.1980; appl. 20.8.1979; GB-prior. 5.9.1978). Buckett, W.R. et al.: J. Med. Chem. (JMCMAR) 16, 116 (1973). methyl injection solution: EP 8 824 (Akzo; appl. 15.8.1979; GB-prior. 5.9.1978). Vecuronium bromide . Formulation(s); amp. 4 mglml; vial 10 mg bromide Trade Nanle(s): D: Norcuron (Organon; 1983) I: .Norcuron (Organon F: Norcuron (Organon); wfm Tcknika) GB: Norcuron (Organon J: Masculax (Organon) Teknika); 1983 USA: Norcuron (Organon; 1984) Venlafaxine (Wy-45030) ATC: N06AA22 Use: antideprcssant, norephedrine uptake inhibitor RN; 93413-69-5 MF: CI7H,NO, MW: 277.41 CN: (2)- 1 -[2-(dimethylamino)- 1-(4-methoxyphenyl)ethyl]cyclohexanol monohy drochloride RN: 99300-78-4 MF: C,,H,,NO, HC1 MW: 313.87 . trideoxy-3-C-methyl-or-~-lyxo-hcxopyranosyl )-~ -~ -glucopyranosyl]oxy ]- 10,19-dichloro- 2,3,4,5,6,7,23,24,25,26,36,37,38,38a-~etradecahydro-7,22,28,30,32-pentahydroxy- 6-[ [4-methyl- 2- (methylamino )-. 1-[ (2~,3a,5a,16~,17~ )-3 ,17-bis(acetyloxy )-2 -( 1-piperidinyl)androstan-16-yl]-l-methylpiperidinium bromide 3-chloroper- H benzoic acid 5a-androst- 2- isopropenyl en-1 7-one ocetate - 2160 V Venlafaxine. RN: 140 4-9 0-6 MF: C,,H,,C12N,0, MW: 1449.27 EINECS: 21 5-7 7 2-6 LDSo: 430 mglkg (M, i.v.) CN: [3S-[3R*,6S*(S*),7S*,22S*,23R*,26R*,36S*,38aS*] ]-3 -( 2-amino-2-oxoethyl )-4 4-[ [ 2-0 -( 3-a~no-2,3, 6- trideoxy-3-C-methyl-or-~-lyxo-hcxopyranosyl )-~ -~ -glucopyranosyl]oxy]-