Formebolone F 931 Formebolone (Fonnyldienolone) ATC: A14 Use: anabolic, anti-inflammatory RN: 2454-11-7 MF: C2,H2,04 MW: 344.45 EINECS. 219-523-2 LD,,: 187 mglkg (M, i.p.1; 293 mglkg (M, s.c.); 104 mglkg (R, i.p.); 270 mg/kg (R, s.c.) CN: (I l a, 178)- 1 1,17-dihydroxy-l7-methyI-3-oxoandrosta-l,4-diene-2-carboxaldehyde Ilo,l7fi-dihydroxy-17- ethyl forrnote methyl-3-0x0-4-ondrosiene OHC Me Formebolone Reference(s): DE 1618 616 (LPB Braglia; appl. 8.2.1967). GB 1 168 931 (LPB Braglia; valid from 20.1.1967). Formulation(s): amp. 2 m112 ml; tabl. 5 mg Trade Name(s): I: Esiclene (LPB) Formes tane (4-HAD; 4-DHA) RN: 566-48-3 MF: C19H2,0, MW: 302.41 CN: 4-hydroxyandrost-4-ene-3,17-dione ATC: L02B; G03BA Use: aromatase inhibitor (for treatment of breast cancer) Formestone I Reference(s): Marsh, D.A. et al.: J. Med. Chem. (JMCMAR) 28,788 (1985). 932 F Formocortal alternative synthesis: Mann, J.; Pietrzak B.: J. Chem. Soc., Perkin Trans. 1 (JCPRB4) 1983,2681. Burnett, R.O.; Kirk, D.N.: J. Chem. Soc., Perkin Trans. 1 (JCPRB4) 1973, 1830. Brodil, A.M. et al.: Endocrinology (ENDOAO) 100, 1684 (1977). micronised formestane: EP 346 953 (Ciba-Geigi; appl. 3 1.10.1985; CH-prior. 6.11.1984). stable suspension for injection: EP 181 287 (Ciba-Geigy; appl. 31.10.1985; CH-prior. 6.1 1.1984). US 5 002 940 (Ciba-Geigy; 26.3.1991; appl. 3 1.10.1985; CH-prior. 6.11.1984). medical use for treatment of breast cancer: WO 9 010 462 (Endorecherche; appl. 9.3.1990; USA-prior. 10.3.1989). medical useJur treatment of prostate hyperplasia: DOS 3 339 295 (Schering AG; appl. 15.1 1.1982). WO 9 100 73 1 (Endorecherche; appl. 5.7.1990; USA-prior. 7.7.1989). medical use for treatment of gynecomastia: US 4 895 715 (Schering Corp.; 23.1.1990; appl. 14.4.1988). method for inhibition of estrogen biosynthesis: US 4 235 893 (A. M. Brodic et al.; 25.1 1.1980; appl. 8.5.1978). Formulation(s): amp. 250 mgl2 ml Trade Name(s): D: Lentaron (Novartis F: Lentaron (Novartis GB: Lentaron (Novartis) Pharma) Pharma) Formocortal (Formocortol) ATC: SOIBAl2 Use: glucocorticoid RN: 2825-60-7 MF: C2,H3,C1F0, MW: 569.07 EINECS: 220-584-2 LD,,,: 537mg/kg(M,i.p.);490mg/kg(M,s.c.) CN: (1 1 ~,16a)-21-(acetyloxy)-3-(2-chloroethoxy)-9-fluoro-l 1-hydroxy-16,17-[(I- methylethylidene)bis(oxy)]-20-oxopregna-3,5-diene-6-carboxaldehyde triethyl orthoformote 21 -ocetaxy-3.20-dioxo- ethylene go-fluoro- 1 18- hydroxy- glycol 16a.17-isopropylidene- dioxy-4-pregnene Formoterol F 933 I b trichloro- phosphorus DMF ethylene oxychloride CHO Formocortol Reference(s): US 3 314 945 (Societa Farmaceutici; 18.4.1967; I-prior. 15.7.1964). Baldratti, G. et al.: Experientia (EXPEAM) 22, 468 (1966). starting material: Holmund, C.E. et al.: J. Am. Chem. Soc. (JACSAT) 83,2586 (1961). Bemstein, S. et al.: J. Am. Chem. Soc. (JACSAT) 81, 1689 (1959). Fonulaiion(s): eye drops 0.05 %; ointment 0.05 %; susp. 0.05 % Trade Name(s): D: Deidral S (Montedison)- Deflamene (Farmi talia); comb.; wfm wfm GB: Deflamene (Carlo Erba); I: Formoftil (Farmigea) wfm Formomicin (Farmigea). comb. with gentamycin Formoterol ATC: R03AC13; R03CC Use: selective P2-adrenoceptor agonist RN: 73573-87-2 MF: C,,HZ4N2O4 MW: 344.41 LD,,,: 71 mgkg (M, i.v.); 8310 mglkg (Mf, p.0.); 6700 mglkg (Mm, p.0.); 98-100 mglkg (R, i.v.) CN: (R*,R*)-(~)-N-[2-hydroxy-5-[1-hydroxy-2-[[2-(4-methoxyphenyl)-1- methylethyl]amino]ethyl]phenyl]formamide fumarate (2:l) RN: 43229-80-7 MF: C,,HuN20, l/2C4H404 MW: 804.89 fumarate dihydrate RN: 183814-30-4 MF: ClyH,4N204 . 1/2C4H404 . 2H20 MW: 840.92 m0\~t43 CLQQ __* 6'2 8, "$3 GBr (I)-A-benifl-N-[I-methyl- ' 02N CH3 bromine 02N 0 0 2-(4-methoxyphenyl)- 934 F Formoterol NoBH4 sadium O2N borohydride Fe. HCI CH3 HCOOH , (CH,CO)20 11 + H,N - III formic acid Reference(s): US 3 994 974 (Yamanouchi; 30.11.1976; prior. 22.1.1973). DOS 2 305 092 (Yamanouch]; appl. 2.2.1973; J-prior. 5.2.1972). Hett, R. et al.: Org. Process Res. Dev. (OPRDFK) 2 96 (1998). preparation of enantiomers from (+)- or (-)-1-methyl-2-phenylethylamine: Kibura, R.; Nakahara, Y.: Biol. Pharm. Bull. (BPBLEO) 18 (12), 1694 (1995). Glennon, R.A.; Smith, J.D.; Ismaiel, A.M.; Ashmawy, M.; Bataglia, G.; Fisher, J.B.: 5. Med. Chem. (JMCMAR) 34 (3), 1094 (1991). Kerwin et al.: J. Am. Chern. Soc. (JACSAT) 72,3983,3986 (1950). preparation of 4'-benyloxy-3'-nitroacetophenone: Meglio, R de; Ravenna, F.; Gentili, P.; Manzardo, S., Riva, M.: Pharmaco, Ed. Sci. (FRPSAX) 38 (12), 998 (1 983). Oelschlaeger et al.: Arch. Pharm: Bet. Dtsch. Pharm. Ges. (APBDAJ) 296, 107 (1963). preparation of N-benzyl-N-[I-methyl-2-(4-rnethoxyphenyl)ethyl]aminc: Woodruff; Larnbooy; Bust: J. Am. Chem. Soc. (JACSAT) 62,922 (1940). EX 844 228 (Temmler-Werke; 1938). alternative syntheses: JP 7 5 12 040 (Yamanouchi; appl. 31.5.1973). JP 8 1 115 751 (Yamanouchi; appl. 1 1.6.1980). Formulation(s): cps. for inhalation 12 pg (as furnarate dihydrate); powder inhaler 6 pglpuff, 12 pglpuff Trade Nanze(s): D: Oxis Turbohaler (Astrd Foradil P (Novartis) J: Atock (Yamanouchi; 1986) pharma-stern) F: Foradil (Novartis) Foscarnet sodium F 935 Foscarnet sodium ATC: J05 Use: antiviral (for treatment of CMV retinitis) RN: 63585-09-1 MF: CNa305P MW: 191.95 LD,: 384 mdkg (M, i.p.) CN: dihydroxyphosphinecarboxylic acid oxide trisodium salt hexahydrate RN: 34156-56-4 MF: CNa3O5P . 6H20 MW: 300.04 CH3 triethyl phosphite ethyl chlorofarmate diethyl ethoxy- carbonylphosphonate Foscarnet sodium i Reference(s): ES 541 567 (Esp. Latinas Med. Universales; appl. 26.3.1985). ES 556 513 (Lab. Esp. Farm. Centrum; appl. 24.6.1986). CS 253 848 (V. Zikan, F. Roubinek; appl. 18.7.1986). Nylen, P.: Ber. Dtsch. Chem. Ges. (BDCGAS) 57b, 1023 (1924). synthesis and use for regulation of plant growth: US 4 018 854 (Du Pont; 19.4.1977; prior. 25.6.1975,30.5.1974,23.7.1973). DOS 2435 407 (Du Pont; appl. 23.7.1974; USA-prior. 23.7.1973, 17.9.1973, 30.5.1974). medical use for treatment of virus infections: US 4 339 445 (Astra; 13.7.1982; appl. 21.12.1978; S-prior. 1.7.1976). Formulation(s): cream 2 gllOO g; vial 6 g (24 mg/ml) (hexahydrate) Trude Name(s): D: Foscavir (Astra) F: Foscavir (Astra) Virudin (Bracco) Triapten Antiviralcreme GB: Foscavir (Astra; 1990) USA. Foscavir (Astra) (LAWIWy eth) I: Foscavir (Astra-Simes) Fosfestrol (Diethylstilbestrol diphosphate) ATC: L02AA04 Use: antineoplastic RN: 522-40-7 MF: C,,H2208P2 MW: 428.31 EINECS: 208-328-8 LD,,,: 630 mg/kg (M, i.v.); 2 glkg (M, p.0.); 425 mg/kg (R, i.v.); 3 &/kg (R, p.0.) CN: (E)-4,4-(1,2-diethyl-1.2-ethenediyl)bispheno] bis(dihydrogen phosphate) tetrasodium salt RN: 23519-26-8 MF: C,,H2,0,P2 . xNa MW: unspecified 936 F Fosfomycin 1. POCI3, pyridine 2. H20 b 1. phosphorus HO oxychloride Reference(s): US 2 234 31 1 (Ciba; 1941; CH-prior. 1938). US 2 802 854 (ASTA-Werke; 1957; D-prior. 1952). US 2 971 975 (Miles Labs.; 14.2.1961; appl. 30.8.1955) diethylstilbestrol Forrnulation(s): amp. 60 mg/5 ml; tabl. 120 mg (as tetrasodium salt) Fosf estrol Trade Natne(s): (4- v) D: Honvan (ASTA Medica I: Honvan (ASTA Medica) Stilphostrol (Miles AWD) J: Honvan (Kyorin) Pharm.); wfm F: ST-52 (ASTA Medica) USA: Stilphostrol (Dome); wfm generic GB: Honvan (ASTA Medica) Fosfomycin (Phosphonomycin) ATC: JOlXXOl Use: antibiotic RN: 23155-02-4 MF: C3H704P MW: 138.06 EINECS: 245-463-1 LD,,: 4 glkg (M, i.p.1 CN: (2R-cis)-(3-methyloxirany1)phosphonic acid calcium salt (1:l) RN: 26016-98-8 MF: C,H,Ca04P MW: 176.12 EINECS: 247-408-7 LD,,: >3.5 gkg (M, p.0.); >7 gkg (R, p.0.) disodium salt RN: 26016-99-9 MF: C,H,Na,O,P MW: 182.02 trometamol salt RN: 78964-85-9 MF: C3H,04P. C4H,,N03 MW: 259.20 From fermentation solutions of Srrepromycesfradiae (ATCC 21096). Reference (s): Hendlin et al.: Science (Washington, D.C.) (SCIEAS) 166, 122 (1969). BE 718 507 (Merck & Co., appl. 29.10.1968; USA-prior. 25.7.1967, 30.10.1967,9.5.1968,2.10.1968, 25.10.1968). synthesis and separation of isomers: BE 723 072 (Merck & Co., appl. 24.7.1968; USA-prior. 30.10.1967, 15.5.1968). BE 723 073 (Merck & Co., appl. 29.10.1968; USA-prior. 30.10.1967, 15.5.1968, 30.8.1968). Gliimkowski, E.J. et al.: J. Org. Chem. (JOCEAH) 35, 3510 (1970). Fosinopril F 937 Formulation(s): cps. 1 g; vial (lyo.) 2640 mg, 3960 mg, 6600 mg (as sodium salt); gran. 5.63 I g/8 g (as trometamol); tabl. 1 g (as calcium salt); tabl. 1 g (as calcium salt monohydrate) Trade Narne(s): D: Fosfocin pro infusione (Boehringer Mannh.) Monuril (Madaus) F: Fosfocine (Sanofi Winthrop) Monuril (Zambon) Uridoz (Therabel Lucien Pharma) 1: Afos (Salus Research) Biocin (Ibirn) Biofos (Leben's) Fosinopril (Fosenopril ; SQ-28555) Faremicin (Lafare) Foce (Medici)-comb. Fonofos (Pulitzer) Fosfobiotic (Bergamon) Fosfocin (Crinos) Fosfogram (Firma) Fosfolexin (Lifepharma)- comb. Fosforal (Farmasister) Foximin (Caber) Francital (Francia Farm.) lpamicina (IPA) Lancetina (Farma Uno) Lofoxin (Locatelli) Monuril (Zambon Italia) Neofocin (Medici) Priomicina (San Carlo) Ultramicina (Lisapharma) Vastocin (Coli) J: Fosmicin S (Meiji Seika) USA: Fosfocina (Merck Sharp & Dohme); wfm ATC: C09AA09 Use: antihypertensive (ACE inhibitor) RN: 98048-97-6 MF: C3,H4,N07P MW: 563.67 CN: [1[S*(R*)],2a,4~]-4-cyclohexyl-l-[[[2-methyI-l-(l-oxopropoxy)propoxy](4- phenylbutyl)phosphinyl]acetyl]-L-proline sodium saIt RN: 88889-14-9 MF: C3,H4,NNa07P MW: 585.65 trans-4-hydroxy- di-tert-butyl N-tert-butoxy- L-praline (1) dicarbonate carbonyl-trons- 4-hydraxy-L-proline 938 F Fosinopril I. CuBr, HsCACHs ' Et20, e~i 0 2. CFSCOOH HCI. C2H50H b H N HN ~oc/ COOH COOH COOH N-tert-butoxy- carbonyl-trons- 4-tosyloxy- L-proline (IU) trans-4- phenyl- L-proline (N) trons-4- cyclohexyl- L-proline (V) 2. alternative route 1.4N NaOH 2. -10 OC. 2-CI OH CrO,. HzSO, I 2. bezy charoforat (Ni Z' COOH 4 fN COOH N-benzyloxy- carbonyl-4-0x0- L-praline (Vl) CFsCOOH, CH2CI, Z/ COOH COOH Li, liq. NH,. NH,CI Hz. PtO . HCI. C H OH b 1v zz v sodium phosphite 4-phenylbutyl- phosphonous acid (WI) Hz. Pd-C resolution of diastereomers b -x / \ - CH3 I Fosinopril Reference(s): a1)DE 3 434 121 (Squibb; appl. 17.9.1984; USA-prior. 19.9.1983). Thottathil, J.K. et a].: Tetrahedron Lett. (TELEAY) 27, 151 (1986). similar process: US 4 912 231 (Squibb; 27.3.1990; prior. 15.6.1987, 17.6.1988). a2)Krapcho, J. et al.: J. Med. Chem. (JMCMAR) 31, 1148 (1988). alternative route from L-pyroglutamic acid: Thottathil, J.K. et al.: J. Org. Chem. (JOCEAH) 51, 3140 (1986). US 4 588 819 (Squibb; 13.5.1986; appl. 19.1 1.1984). EP 183 390 (Squibb; appl. 25.10.1985; USA-prior. 19.1 1.1984). b US 4 337 201 (Squibb & Sons; appl. 16.6.1982; USA-prior. 4.2.1980). Krapcho, J. et al.: J. Med. Chem. (JMCMAR) 31, 1148 (1988). Fomulation(s): tabl. 5 mg, 10 mg, 20 mg, 40 mg (as sodium salt) Trade Name(s): D: Dynacil (SchwarzISanol) F: FozirCtic (Lipha SantC)- I: Eliten (Bristol-Myers Fasinorm (Bristol-Myers comb. Squibb) Squibb) Fozitec (Lipha SantC) Fosipress (Menarini) Flucidine (Boehringer Ing.; GB: Staril (Bristol-Myers Tensogard (Bristol It. Sud) Leo) Squibb) USA: Monopril (Bristol-Myers Fucithalmic (Alcon) Squibb) 940 F Fos~henvtoin sodium Fosphenytoin sodium (ACC 9653; CI-982) ATC: N03AB Use: anticonvulsant, prodrug of phenytoin RN: 92134-98-0 MF: C,,H,,N2Na20,P MW: 406.24 CN: 5,5-diphenyl-3-~(phosphonooxy)methyl]-2,4-imidazolidinedione disodium salt 1. K2C0,, H20 2. PCI,, CH2CI2 yo + HCHO -b N H N-CI phenytoin silver dibenzyl phosphate 1. benzene Tm ;:;zo;-c 1 + Ag0-P=O - 6s Fosphenytoin sodium I $yo ONa '0 N-0, Pao NaO Reference (s): Varia, S.A. et al.: J. Pharm. Sci. (JPMSAE) 73(8), 1068 (1984). stable injection formulation: US 4 925 866 (Du Pont; appl. 25.5.1989; USA-prior. 25.5.1989). use for treatment of stroke: EP 427 925 (Warner-Lambert; appl. 8.8.1990; USA-prior. 10.8.1989, 25.6.1990). Formulation(s): amp. 50 mg/ml Trade Name(s): USA: Cerebyx (Parke Davis) Fotemustine ATC: LOlADO5 Use: antineoplastic, alkylating nitrosourea derivative RN: 921 18-27-9 MF: CyH1yCIN305P MW: 3 15.69 LD,,: 60 mgkg (M, i.p.) CN: [l-[[[(2-chloroethyl)nitrosoamino]carbonyl]amino]ethyl]phosphonic acid diethyl ester ocetylphosphonic ocid diethyl ester acetylphosphonic acid a-orninoethylphosphonic diethyl ester oxime ocid diethyl ester (I) . methylethylidene)bis(oxy) ]-2 0-oxopregna-3,5-diene-6-carboxaldehyde triethyl orthoformote 21 -ocetaxy-3.20-dioxo- ethylene go-fluoro- 1 1 8- hydroxy- glycol 16a.17-isopropylidene- dioxy-4-pregnene Formoterol. COOH N-tert-butoxy- carbonyl-trons- 4-tosyloxy- L-proline (IU) trans- 4- phenyl- L-proline (N) trons- 4- cyclohexyl- L-proline (V) 2. alternative route 1.4N NaOH 2. -1 0 OC. 2-CI. mg/kg (R, s.c.) CN: (I l a, 178 )- 1 1,17-dihydroxy-l7-methyI-3-oxoandrosta-l,4-diene-2-carboxaldehyde Ilo,l7fi-dihydroxy-1 7- ethyl forrnote methyl- 3-0 x 0-4 -ondrosiene OHC Me Formebolone