Venlafaxine V 2161 4-methoxyphenyl- Cyclo- acetonitrile hcxanane (I) HCHO , HCOOH ____+ 0/CH3 Venlataxine I N.N-dirnethyl-4- rnethoxyphenyl- thioacetomide N.N-dimethyl-a- (1 -hydroxycyclohexyl) 4-methoxyphenyl- thioacetamide (111) Hz, Raney-Ni Ul 3 a ' EP 112 669 (American Homc Products; 4.7.1984; USA-prior. 13.12.1982). b GB 2 227 743 (Wyeth & Brother Ltd; 8.8.1990; GB-prior. 1.2.1989). combination with opioid antagonists: WO 9 609 047 (Du Pont Merck Pharm. Co.; 28.3.1996; USA-prior. 19.9.1994). combination with 0-blockers: EP687 472 (Eli Lilly & Co.; 20.2.1995; USA-prior. 19.7.1994). controlled release formulation: WO 9 427 589 (Alza Corp.; 8.12.1994; USA-prior. 27.5.1993). Formulation(s): tabl. 25 mg, 37.5 mg, 50 mg, 75 mg, 100 mg (as hydrochloride) Trade Narne(s): D: 'Trevilor (Wyeth) I: Efexor (Wyeth-Lederle) GB: Efexor (Wyeth) USA: Effexor (Wyeth-Ayerst) 2162 V Verapamil Verapamil (Iproveratril) ATC: C08DAOl Use: coronary vasodilator RN:. 52-53-9 MF: C2,H3,N2O4 MW: 454.61 EINECS: 200-145-1 LD,,: 1520 pg/kg (M, i.v.); 130 mglkg (M, p.0.); 7250 yg/kg (R, i.v.); 163 mg/kg (R, p.0.) CN: a-[3-[[2-(3,4-dimethoxyphenyl)ethyl~ethylamino]propyl]-3,4-dimethoxy-a-(l- methylethyl)benzeneacetonitrile monohydrochloride RN: 152-1 1-4 MF: CuH,,NI04. HCI MW: 491 .O7 EINECS: 205-800-5 LD,,,: 5795 pglkg (M, i.v.); 163 mglkg (M, p.0.); 16 mglkg (R, i.v.); 108 mglkg (R, p.0.); >400 mglkg (dog, p.0.) 3.4-dimethoxy- isopropyl phenylacetonitrile chloride 1 -brorno-3- N-[Z-(3,4-dimethoxy- chloroprapone phenyl)ethyl]methylarnine Reference(s): DE 1 154 810 (Knoll; appl. 28.4.1961). DE 1 158 083 (Knoll; appl. 19.12.1962). US 3 261 859 (Knoll; 19.7.1966; D-prior. 28.4.1961). alternative synthesis: DAS 2 263 527 (Teikoku Hormaone Mfg.; appl. 27.12.1972; J-prior. 25.12.1971). DAS 2 63 1 222 (Knoll; appl. 12.7.1976). US 4 115 432 (Knoll; 19.9.1978; D-prior. 12.7.1976). (-)-verapamil: DAS 2 059 923 (Knoll; appl. 5.12.1970). Formularion(s): amp. 5 mg/2 ml; drg. 40 mg, 80 mg, 120 mg; f. c. tabl. 40 mg, 80 mg, 120 mg; s. r. cps. 120 mg, 180 mg, 240 mg; s. r. tabl. 120 mg, 240 mg; vial 5 mgl2 ml (as hydrochloride) Trade Nan~e(s): D: Azupamil (Azupharma) Cardioprotect (Kytta- Dignover (Sankyo) Siegfried) Durasoptin (durachemie) Vesnarinone V 2163 Elthon (Knoll)-comb. with diazepam Falicard (ASTA Medica AWD) Isoptin (Knoll; as hydrochloride) Isoptin S (Knoll)-comb. Jenapamil (Jenapharm) Tarka (Knoll)-comb. Vera (ct-Arzneimittel) Verabeta (betapharm) Verahexal (Hexal) Veramex (Sanofi Winthrop) Verasal (TAD) Vera-Sanorania (Sanorania) Veroptinstada (Stadapharm) F: Isoptine (Knoll) Isoptine LP (Knoll) Novapamyl LP (Wycth- Lederle) Verapamil Bayer (Bayer Classics) Verapamil MSD LP (Merck Sharp & Dohme-Chibret) GB: Berkatcns (Berk) Cordilox (Baker Norton) Securon (Knoll) Tarka (Knoll)-comb. Univex (RPK) I: lsoptin (Knoll) Quasar (Kavizza) J: Vasolan (Eisai) USA: Calan (Searle) Isoptin (Knoll) 1Brka (Knoll) Verelan (Lederle) generics Vesnarinone (OPC-82 12) ATC: COlCX Use: cardiotonic RN: 81840-15-5 MF: C,H2,N,0, MW. 395.46 LD,,,: >I200 mglkg (M, i.p.); 56.3 mglkg (M, i.v.); >7594 mg/kg (M, p.0.); > 1200 mglkg (M, s.c.); >I200 mglkg (R, i.p.); 79.3 mg/kg (R, i.v.); >7594 mglkg (R, p.0.); 63.3 mglkg (dog, i.v.); 13 g/kg (dog, p.0.) CN: 1-(3,4-dimethoxybenzoyl)-4-[1,2,3,4-tetrahydro-2-oxo-6-quinolinyl]piperazine HzN pethoxyacryloyl p-nitro- aniline p-aminoacet- chloride anilide 1. H,SO, H 2. bis(pbromoethyl)- amine hydrobromide ethoxyacrylanilide (I) 2(1 H)-quinolinone 6-piperorino-3.4-dihydro- 3.4-dimethoxy- 2(1H)-quinolinone (Il) benroyl chloride Vesnorinone I DE 3 142 982 (Otsuka; appl. 29.10.1981 ; J-prior. 31 .lO.l98O). Tominaga, M. et al.: Chem. Pharm. Bull. (CPBTAL) 32,2100 (1984). alternative synthesis: DE 3 153 260 (Otsuka; appl. 29.10.1981; J-prior. 3 1 .lO.l980). 9 2164 V Vetrabutine Trade Name(s): J: Arkin-Z (Otsuka; 1990) USA: Arkin (Otsuka); wfm Vetrabutine (Profenveramine; Revatrine) ATC: A03 Use: uterus relaxant RN: 3735-45-3 MF: C2,H2,N02 MW: 313.44 CN: a-(3,4-dimethoxyphenyl)-N,N-dimethylbenzenebutanamine hydrochloride RN: 5974-09-4 MF: C,,H,,NO,. HCI MW: 349.90 EINECS: 227-771-8 LD,,,: 500 mglkg (R, p.0.) 3.4-dimethoxy- hydrogen dimethyl- benzoldehyde cyonide omine (3.4-dimethoxypheny1)- dimethylamino- ocetonitrile (I) J-phenylpropyl- magnesium bromide I Vetrobutine I Reference(s): DE 963 424 (Thomae; appl. 1954). Formulation(s): amp. 50 mg Pade Name(s): D: Monzal (Thomae); wfm Vidarabine ATC: J05AB03; S01AD06 Use: antiviral RN: 5536-17-4 MF: C,,H,,N50, MW: 267.25 EINECS: 226-893-9 LDso: 442 mg/kg (M, i.v.); 7800 pglkg (M, p.0.); 302 mglkg (R, i.v.); >5 glkg (R, p.0.) CN: 9-P-~-arabinofuranosyl-9H-purine-6-amine Vidarabine V 2165 monohydrate RN: 24356-66-9 MF: C,,H,,N504. H20 MW: 285.26 LD,,: >7950 pglkg (M, p.0.) 5'-dihydrogen phosphate RN: 29984-33-6 MF: C,,H,,N,O,P MW: 347.22 LD,,: 1200 mgkg (R, i.v.) 5'-dihydrogen phosphate disodium salt RN: 71002-10-3 MF: C,oH,,N,Na,07P MW: 391. EINECS: 19 fermentation of Streptornyces ontibioticus NRRL 3238 vidarobine (1) 1. POCI3. NoOH 2. NH, 3. ion exchange on Dowex I-X, I 1. phosphoryl chloride b 0 H Vidorobine phasphote Reference(s): fermentation: GB 1 159 290 (Parke Davis; appl. 29.12.1967; USA-prior. 30.12.1966,29.9.1967). dihydrogen phosphate: DOS 2 047 368 (Parke Davis; appl. 25.9.1970; USA-prior. 26.9.1969). US 3 703 507 (Parke Davis; 21.11.1972; prior. 26.9.1969). alternative synthesis from adenosine monophosphate: Kaneka, M. eta].: Chem. Pharm. Bull. (CPBTAL) 25,1892 (1977). total synthesis of vidarabine: Lee et al.: J. Am. Chem. Soc. (JACSAT) 82,2648 (1960). Reist et a].: J. Org. Chem. (JOCEAH) 27, 3274 (1962); 29,3725 (1964). Formulation(s): ointment 3 % Trade Name(s): D: Vidarabin 3 % Thilo Salbe F: Vira-MP (Pierre Fabre J: Arasena-A (Mochida) (Alcon) Dermatologie) Vitarabine (Ajinomoto) GB: Vira-A (Parke Davis) USA: Vira-A (Parke Davis); wfm 2166 V Vieabatrin Vigabatrin ATC: N03AG04 (y-Vinyl-Gaba) Use: anticonvulsant, irreversible inhibitor of GABA transaminase RN: 60643-86-9 MF: C6H1,N02 MW: 129.16 LDSo: 3 gfl<g (M, p.0.); 3 glkg (R, p.0.) CN: 4-amino-5-hexenoic acid (+_)-form RN: 68506-86-5 MF: C6H, ,NO2 MW: 129.16 EINECS: 270-929-6 LD,,,: >2500 mglkg (M, i.p.); >3000 mglkg (M, p.0.); 23000 mglkg (R, p.0.) l,4-dichloro- diethyl molonote 2-butene 3-corboxomido-5- vinyl-2-pyrrolidone (U) 1,1 -bis(ethoxycorbonyl)- 2-vinylcyclopropone (I) Vigobotrin 1. NoOC2H5 2. NoNH2 2. HOAc , A &o '"."-"+ I' ' H2C- H 5-vinyl-2- pyrrolidone Reference(s): DOS 2 607 620 (Richardson-Merrell; appl. 25.2.1976; USA-prior. 18.3.1975). DE 2 902 438 (Merrell-Toraude; appl. 23.1.1979; USA-prior. 30.1.1978). US 4 235 778 (Merrell-Toraude; 25.11.1980; appl. 14.1 .l980; prior. 4.6.1979, 30.1.1978). US 4 254 284 (Merrell-Toraude; 3 3.1981; appl. 14.1.1980; prior. 4.6.1979, 30.1 .l978). Wei, Z Y.; Knaus, E.E.: J. Org. Chem. (JOCEAH) 58, 1586 (1993). combination with glycine: EP 124 09 1 (Merrell-Toraude; appl. 26.4.1984; GB-prior. 29.4.1983). Formulafion(s): f. c. tabl. 500 mg; gran. 500 mg; powder 500 mg Trade Name(s): D: Sabril (Hoechst) GB: Sabril (Hoechst) F: Sabril (Hoechst; 1990) I: Sabril (Carnillo Corvi) Viloxazine V 2167 Viloxazine ATC: N06AX09 Use: antidepressant, psychostimulant RN: 468 17-91-8 MF: C,,H,,NO, MW: 237.30 EINECS: 256-281-7 LD,,,: 60 mgkg (M, i.v.); 552 mglkg (M, p.0.); 60 mglkg (R, i.v.); 2 glkg (R, p.0.) CN: 2-[(2-ethoxyphenoxy)rnethyl]morpholine hydrochloride RN: 35604-67-2 MF: C,,H,,NO, . HCI MW: 273.76 EINECS: 252-638-6 LD,,: 60 mgkg (M, i.v.); 480 mglkg (M, p.0.); 60 mglkg (R, i.v.); 2 gkg (R, p.0.) 2-eihoxy- epichloro- phenol hydrin 1-(2-ethoxyphenoxy)- 2,3-epoxypropane (I) hydride 2. NaOCH, b Ir 1. chloroaceiyl chloride. trieihylomine Viloxazine 2-ominoethyl hydrogen sulfate (from 2-amino- ethanol and H2S04) 2168 V Viminol Reference(s): a GB 1 138 405 (ICI; appl. 28.12.1966; valid from 13.1 1.1967). US 3 714 161 (ICI; 30.1.1973; GB-prior. 28.12.1966). US 3 876 769 (ICI; 8.4.1975; prior. 24.11.1967). DOS I 695 295 (ICI; appl. 24.1 1.1967; GB-prior. 28.12.1966). b US 3 857 839 (ICI; 31.12.1974; GB-prior. 20.6.1969, 13.10.1969). US 3 71 2 890 (ICI; 23.1.1973; GB-prior. 20.6.1969; 13.10.1969). Greenwood, D.T. et al.: J. Med. Chem. (JMCMAR) 18,573 (1975). Formulation(s): amp. 100 mg15 ml; f. c. tabl. 100 mg; s. r. tabl. 300 mg; tabl. 50 mg, 100 mg Trade Name(s): D: Vivalan (Zeneca; 1977) Vivalan LP (Zeneca) I: Vicilan (ICI-Pharma) F: Vivalan (Zeneca; 1977) GB: Vivalan (Zeneca; 1974) J: Vicilan (Jcpharma) Viminol (Diviminol) ATC: N06AX09 Use: analgesic RN: 21363-18-8 MF: C2,H,,ClN,0 MW: 362.95 EINECS: 244-347-8 LD,,,: 325 mglkg (M, p.0.) CN: cr-[[bis(l-methylpropyl)amino]methyl]-l-[(2-chlorophenyl)methyl]-lH-pyrrole-2-methanol p-hydroxybenzoate (1:l) RN: 23784- 10-3 MF: C,,H,,ClN20. C,H,O, MW: 501.07 LD,,,: 206 mglkg (R, i.p.) 1 -(2-chloro- oxolyl benzy1)pyrrole chloride Na[AIH2(OCH2-CH2-OCH3)2] sodium oluminum b bis(2-methoxyethoxy)- dihydride (1) I Viminol LNANvCH- lithium aluminum I I LJ s J CH, hydride Vinblastine V 2169 Reference(s): a BE 790 747 (Whitefin Holding; appl. 30.10.1972; I-prior. 4.7.1972; 3O.lO.l97l) b US 3 539 589 (Whitefin Holding; 10.11 .l97O; GB-prior. 17.5.1966). starting material: DAS 1 795 841 (Whitefin Holding; appl. 10.1 1.1970; F-prior. 12.11.1969). review: Chiarino, D. eta].: Arzneim Forsch. (ARZNAD) 28 (II), 1554 (1978). stereoisomers: BE 790 747 (Whitefin Holding; appl. 30.10.1972; I-prior. 3O.lO.1971; 4.7.1972). DOS 2 253 149 (Whitefin Holding; appl. 3O.lO.1972; I-prior. 30.10.1971). Formulation(s): tabl. 50 mg Trade Name(s): D: Lenigesial (Inpharzam); I: Dividol (Zambon Italia; as wfm hydrochloride) Vinblastine ATC: LO~CAO~ (Vincaleukoblastine) Use: antineoplastic RN: 865-21-4 MF: C4,HsnN40y MW: 810.99 EINECS: 212-734-0 LD5,,: 2 mgkg (R, i.v.) CN: [3aR-[3aa,4~,5~,5a~,9(3R*,5S*,7R*,9S*),10bR*,13aa]]-methyl4-(acetyloxy)-3a-ethyl-9-[5-ethyl- 1,4,5,6,7,8,9,1 O-octahydro-5-hydroxy-9-(methoxycarbonyl)-2H-3,7-methanoazacycloundecino[5,4- b]indol-9-yl]-3a,4,5,5a,6,11,12,13a-octahydro-5-hydroxy-8-methoxy-6-methyl- lH-indolizino[8,1- cdlcarbazole-5-carboxylate sulfate (1:l) RN: 143-67-9 MF: C46HSnN40y. H2S04 MW: 909.07 EINECS: 205-606-0 LD,,,: 9500 pglkg (M, i.v.); 423 mglkg (M, p.0.); 37 mglkg (R, i.v.); 305 mdkg (R, p.0.) sulfate monohydrate RN: 6449-03-2 MF: C4,Hs8N,O, . H,SO, . H20 MW: 927.08 I Vinblastine By extraction from leaves of Vinca rosea. 2170 V Vinburnine Reference(s1: Svohoda, G.H. eta].: J. Pharm. Sci. (JPMSAE) 51,707 (1962). US 3 097 137 (CDN-P. and Dev.; 9.7.1963; appl. 19.5.1960; prior. 2.12.1958). US 3 225 030 (Eli Lilly; 21.12.1965; appl. 15.2.1965; prior. 25.8.1958). US 4 070 358 (Richter Gedeon; 24.1.1978; H-prior. 28.10.1975). DOS 2 648 284 (Richter Gedeon; appl. 25.10.1976; H-prior. 28.10.1975). DOS 2 823 46 1 (Richter Gedeon; appl. 30.5.1978; H-prior. 3 1.5.1977). synthesis,from catharanthin: DOS 2 614 863 (Dr. Rahman; appl. 6.4.1976). Fonnulation(s): amp. 10 mgIl0 ml (as sulfate); vial 10 mg (as sulfate monohydrate) Trade Nands): D: cellblastin (cell pharm) Vinblastinesulfat-GRY I: Velbe (Lilly) Velbe (Lilly) (Gry) J: Exal (Shionogi) Vinblastin R.P. (RhBne- F: Velbe (Lilly) USA: Velban (Lilly) Poulenc) GB: Velbe (Lilly) Vinburnine (Vincamon) ATC: C04AX17 Use: cerebral vasodilator RN: 474-00-0 MF: CI,H2,N20 MW: 294.40 EINECS: 207-476-0 CN: cburnamenin- l4(15H)-one MnO,/cellite, toluene ______, (cf. vincarnine synthesis) Reference(s): GB 1 440 634 (Richter Gedeon; valid from 7.12.1973; H-prior. 8.12.1972). starting material: DOS 2 93 1 295 (Richter Gedeon; appl. 1.8.1979; H-prior. 1.8.1978). alternative syntheses: DOS 2 323 423 (Richter Gedeon; appl. 9.5.1973; H-prior. 17.5.1972). US 3 888 865 (Richter Gedeon; 10.6.1975; appl. 14.3.1973). FR 2 268 016 (Omnium; appl. 17.4.1974). isolation,from Hunteria eburnea: DOS 1 932 245 (L. Olivier; appl. 25.6.1969; F-prior. 25.6.1968). total synthesis: Bartlett, M.F.; Taylor, W.I.: J. Am. Chem. Soc. (JACSAT) 82,5941 (1960). Werkert, E.; Wickberg, B.: J. Am. Chem. Soc. (JACSAT) 87, 1580 (1965). BE 776 337 (Roussel-Uclaf; appl. 7.12.197 1 ; F-prior. 6.1.1971). BE 802 9 13 (Roussel-Uclaf; appl. 27.7.1973; F-prior. 3 1.7.1972). Hugel, G. et al.: Tetrahedron Lett. (TELEAY) 1974, 1597. . O-octahydro-5-hydroxy- 9-( methoxycarbonyl )-2 H-3,7-methanoazacycloundecino[5, 4- b]indol-9-yl ]-3 a,4,5,5a,6,11,12,13a-octahydro-5-hydroxy-8-methoxy-6-methyl- lH-indolizino[8, 1- cdlcarbazole-5-carboxylate. EINECS: 24 4-3 4 7-8 LD,,,: 325 mglkg (M, p.0.) CN: cr-[[bis(l-methylpropyl)amino]methyl]-l-[(2-chlorophenyl)methyl]-lH-pyrrole-2-methanol p-hydroxybenzoate (1:l) RN: 2378 4- 1 0-3 MF: C,,H,,ClN20 CN: 1-( 3,4-dimethoxybenzoyl )-4 -[ 1,2,3,4-tetrahydro-2-oxo-6-quinolinyl]piperazine HzN pethoxyacryloyl p-nitro- aniline p-aminoacet- chloride anilide 1. H,SO, H 2. bis(pbromoethyl )- amine