DE 2 500 110 (Lilly; appl. 3.1.1975; USA-prior. 10.1.1974). US 4 018 895 (Lilly; 19.4.1977; USA-prior. 10.1.1974). US 4 194 009 (Lilly; 18.3.1980; USA-prior. 15.9.1976). US 4 314 081 (Lilly; 2.2.1982; USA-prior. 10.1.1974). US 4 584404 (Lilly; 22.4.1986; USA-prior. 24.10.1983, 25.1.1978, 10.1.1974). b US 5 847 214 (Laporte Organics; USA-prior. 7.7.1997). c ES 2 103 680 (Lilly; appl. 3.8.1995). d US 2760 243 (Albemarle Corp.; USA-prior. 25.7.1997). e ES 210 654 (Lilly; appl. 24.7.1995). f EP 529 842 (Teva Pharm.; appl. 6.8.1992; IL-prior. 27.8.1991) EP391070 (Orion; appl. 1.3.1990; FI-prior. 3.3.1989). EP 380 924 (E. Magnone; appl. 8.1.1990; I-prior. 10.1.1989). W09 906 362 (Albemarle Corp.; appl. 4.8.1998; USA-prior. 4.8.1997). WO 9 856 753 (Albemarle Cop; appl. 12.6.1998; USA-prior. 12.6.1997). ES 2 120 368 (Almirall Prodesfarma; 16.10.1998; appl. 14.6.1996). EP529 842 (TevaPharm.; appl. 6.8.1992; IL-prior. 27.8.1991). EP 617 006 (Pliva D.; appl. 4.2.1994; HR-prior. 5.2.1993). E3 2 101 655 (Lilly; prior. 28.7.1995). E3 2 101 654 (Lilly; prior. 24.7.1995). ES 2 101 650 (Lilly; prior. 29.6.1995). W09 81 1 054 (Egis Gyogyszergyar; appl. 10.9.1997; HU-prior. 10.9.1996), US 5 760 243 (Albemarle Corp.; 2.6.1998; appl. 25.7.1996). ES2 103 680 (Lilly S. A,; 16.9.1997; appl. 3.8.1995). ES 2 103 681 (Lilly; 16.9.1997; appl. 19.9.1995). 1 synthesis of enantromers. 5 US4950 791 (H. C Brown, 21.8 1990; prlor. 12.6.1989, 30.3.1988). : US 4 918 242 (Aldnch, 17 4 1990, prlor. 12.6.1989, 30.3.1988). US4918 207 (Aldr~ch; 17.4.1990; prlor 12.6.1989, 30.3.1988). fluoxetine chiral process from benzoylpropionic acid: US 5 936 124 (Sepacor Inc.; appl. 22.6.1998). treatment of nicotine withdrawal symptoms: US 4 940 585 (W. E. Hapworth; 10.7.1990; appl. 17.2.1989). treatment of appetite and mood disturbances: WO 8 903 692 (MIT; appl. 21.10.1988; USA-prior. 15.9.1988; 22.10.1987). antidiabetic combination: EP294 028 (Lilly; appl. 29.4.1988; USA-prior. 4.5.1987). pharmaceutical formulation: EP693 281 (Lilly; appl. 17.7.1995; E-prior. 20.7.1994). memory improvement: US4647 591 (Lilly; 3.3.1987; prior. 7.10.1985, 21.6.1985). solid oral composition: ES 2 103 682 (Lilly; appl. 29.9.1995). analgesic compositions: EP 193 355 (Lilly; appl. 20.2.1986; USA-prior. 25.2.1985, 25.7.1986). EP 193 354 (Lilly; appl. 20.2.1986; USA-prior. 25.2.1985). treatment of anxiety: EP 123 469 (Lilly; appl. 6.4.1984; USA-prior. 8.4.1983) novel trarlsdemal formulations: W09 802 169 (Alza Corp.; appl. 15.7.1997; USA-prior. 15.7.1996). 902 F Fluoxymesterone phur~naceuticd formulations: EP 693 281 (Lilly; appl. 17.7.1995; E-prior. 20.7.1994). low dose tablet: US 5 830 500 (Pentech Pharm.; 3.1 1.1998; appl. 22.7.1996; USA-prior. 22.7.1996). Fornzulation(s): cps. 1 1.2 mg, 22.4 mg; sol. 22.4 mg15 ml; tabl. 22.4 mg (as hydrochloride) Trade Nume(s): D: Fluctin (Lilly; 1990) GB: Prozac (Lilly; 1989) Prozac (Lilly; 1989) F: Prozac (Lilly; 1989) I: Fluoxeren (Menarini; 1990) USA: Prozac (Dista) Fluoxymesterone ATC: G03BAOl Use: androgen RN: 76-43-7 MF: C2,H2,F03 M W: 336.45 EINECS: 200-96 1 8 LD,,,: 2350 mglkg (M, i.p.) CN: (1 1 ~,17~)-9-fluoro-l1,17-dihydroxy-l7-methylandrost-4-en-3-one - 3,17-dioxo-l lg- pyrrolidine hydroxy-4-androstene (from 3,17-dioxo- 4-androstene) 1 H~C+~-CI & 2. base 1 H3C-CO-NH-Br 2 NaOH Me H P - I1 H H 1 p-toluenesulfonyl . 1. N-brorno- o/ chlor~de 0 acetarn~de (11) I Fluoxymesterone I Reference(s): US 2 793 218 (Upjohn; 1957; prior. 1955). US 2 813 881 (Upjohn; 1957; prior. 1955). US 2 837 517 (Upjohn; 1958; prior. 1956, 1955). US 3 029 263 (Upjohn; 10.4.1962; prior. 24.12.1959, 22.12.1958,6.6.1958). DAS 1 037 447 (Ciba, appl. 1955; CH-prior. 1954). Heyl, W.F.; Herr, M.E.: J. Am. Chem. Soc. (JACSAT) 75, 1918 (1953). Bernstein, S. et al.: J. Org. Chem. (JOCEAH) 19,41 (1954). Fried, J.; Sabo, E.F.: J. Am. Chem. Soc. (JACSAT) 75,2273 (1953); 76, 1455 (1954). Herr, M.E. et al.: J. Am. Chem. Soc. (JACSAT) 78, 501 (1956). Flupentixol F 903 - -alternative synthesis. US 3 118 880 (Ciba; 21.1.1964; CH-prior. 26.5.1954). Formulation(s): tabl. 1 mg, 2 mg, 2.5 mg, 5 mg, 10 mg Trade Name(s): D: Ultandren (Ciba); wfm I: Halotestin (Upjohn) Halotestin (Upjohn); wfm F: Halotestin (Pharmacla & J: Halolest~n (Kodama) Ora-Testryl (Squibb); wfm Upjohn) USA: Halodrin (Upjohn)-comb.; GB: Ullandren (Ciba); wfm wfm Flupentixol . (Flupenthixol) ATC: NOSAFOl Use: neuroleptic, antipsychotic RN: 2709-56-0 MF: C2,H,,F3N20S MW: 434.53 EINECS: 220-304-9 LD,: 150 mglkg (M, i.p.) CN: 4-[3-[2-(trifluoromethyl)-9H-thioxanthen-9-yliene]propyl]-I-piperazineethanol dihydrochloride RN: 241 3-38-9 MF: C,3H,sF3N,0S .2HCI MW: 507.45 ETNECS: 219-321-4 LD,,: 94 mgkg (M, i.v.); 423 mglkg (M, p.0.); 37 mglkg (R, i.~.); 791 mglkg (R, p.0.) decanoate RN: 30909-51-4 MF: C,,H,,F,N20S . C,oH,,O MW: 588.78 1 -(2-benzyloxyethyl) piperazine S0Cl2 2, &3 I S m thionyl 2. Z-trifluoromethyl- chloride 9-thioxanthane (11) 904 F Fluperolone acetate ollylmognesiurn bromide Reference(s): a GB 925 538 (Smith Kline & French; appl. 3.3.1961 ; USA-prior. 7.3.1960, 5.5.1960). US 3 282 930 (Smith Kline & French; 1.1 1.1966; prior. 7.3.1960, 5.5.1960). b US 3 116 291 (Kefalas; 3 1.12.1963; DK-prior. 4.12.1958). Kaiser, C. et a].: J. Med. Chem. (JMCMAR) 15,665 (1972). flupentixol decanoate: DAS 2 029 084 (Kefalas; appl. 12.6.1970; USA-prior. 20.6.1969). US 3 681 346 (Kefalas; 1.8.1972; prior. 20.6.1969). starting material: GB 925 539 (Smith Kline & French; appl. 3.3.1961; USA-prior. 7.3.1960,5.5.1960). Formulation(s): amp. 20 mglml, 100 mglml; drg. 0.5 mg, 1 mg, 5 mg; drops 50 mglml (as dihydrochloride); vial 200 mg (20 mglml) (as decanoate) Trade Name(s): D: Fluanxol (Bayer Vital) Fluanxol (Lundbeck); wfm J: Metamin (Takeda; 1973) F: Fluanxol (Lundbeck; 1976) I: Deanxit (Lusofarmaco)- GB: Depixol (Lundbeck; 1972); comb. wfm Siplarol (Erba); wfm Fluperolone acetate ATC: H02AB Use: glucocorticoid, anti-inflammatory RN: 21 19-75-7 MF: C,,H,,FO, MW: 434.50 EINECS: 218-327-4 CN: [I 1 P,l7a,l7(S)]- 17-[2-(acety1oxy)-1 -oxopropyl]-9-fluoro-11,17-dihydroxyandrosta-1,4-dien-3-one Fluphenazine F 905 fBr CH, I. yeast fermentation Reference(s): Agnello, E.J. et al.: J. Org. Chem. (JOCEAH) 28, 1531 (1963). Agnello, E.J. et al.: Experientia (EXPEAM) 16, 357 (1960). (also alternative syntheses) 1. H3C-S02CI, DMF, pyridine CH3 O 2. H,C-CO-NH-Br 4. HZF2. THF 1. methanesulfanyl chloride 2. N-bromoocetarnide 4. hydrogen fluoride Trade Namc(s); I: Alacortil (Pfizer); wfm USA: Methral (Pfizer); wfm (m) Fluphenazine Fluperolone acetate ATC: N05AB02 Use: neuroleptic, antipsychotic RN: 69-23-8 MF: Cz2H2,F3N30S MW: 437.53 EINECS: 200-702-9 LD,,: 51 mgkg (M, i.v.); 220 mgkg (M, p.0.) CN: 4-[3-[2-(trifluoromethyl)-lOH-phenothiazin-l0-yl]propyl]-l-piperazincethanol dihydrochloride RN: 146-56-5 MF: CZ2H2,F3N3OS. 2HC1 MW. 510.45 EINECS: 205-674-1 LD5,: 56 mgkg (M, i.v.); 220 mglkg (M, p.0.) decanoate RN: 5002-47-1 MF: C22H,6F3N30S . CloH,80 MW: 591.78 1-(3-hydroxypropy1)- methyl piperazine formate 4-(3-hydrouypropyl)- piperazine- 1 -corbox- aldehyde NOOH + 11 amide 4-(3-chlar0propyl)- Z-trifluoromethyl- piperazine-I -carbox- phenothiozine aldehyde (1) 906 F Flupirtine .CF- 2. oq. HCI ' H 1. 2-bromoethyl acetote 10-[3-(1 -piperazinyl)propyl]- 2-trifluoromethyl- phenothiazine (II) Fluphenazine I US 3 058 979 (Smith Kline & French; 16.10.1962; prior. 13.5.1957). DE 1 095 836 (Squihb; appl. 8.12.1956; USA-prior. 23.12.1955, 12.7.1956). alkanecarboxylic acid esters: DE 1 165 602 (Olin Mathieson; appl. 25.4.1962; USA-prior. 26.4.1961). US 3 194 733 (Oh Mathieson; 13.7.1965; prior. 26.4.1961,28.1.1963). US 3 394 131 (Squibb; 23.7.1968; prior. 26.4.1961,28.1.1963). Kurland, A.A. et al.: Curr. Ther. Res. (CTCEA9) 6, 137 (1964). Formulation(s): amp. 2.5 mglml, 5 mglrnl, 12.5 mgl0.5 ml, 25 mg/ml, 25 mg12 ml, 50 md0.5 ml, 100 mgml (as decanoate); drops 4 mglrnl; f. c. drg. 3 mg, 6 mg; f. c. tabl. 0.5 mg, 1 mg, 4 mg; sol. 2.5 mglml; tabl. 1 mg, 2.5 mg, 4 mg, 5 mg, 10 mg (as dihydrochloride) Trade Name(s): D: Dapotum (Bristol-Mycrs Squibb; Sanofi Winthrop) Lyogen (Promonta Lundbeck) Omca (Bristol-Myers Squibb) F: Modecate (Sanofi Winthrop) Moditen (Sanofi Winthrop) Motival (Sanofi Winthrop)- comb. GB: Modecate (Sanofi Winthrop) Moditen (Sanofi Winthrop) Motipress (Sanofi Winthrop)-comb. . Motival (Sanofi Winthrop)- comb. I: Anatensol (Bristol-Myers Squibb) Dominans (Recordati). comb. Moditen (Bristol-Myers Squibb) J: Anatensol (Showa) Fludecasine (Yoshitomi) Sevinol (Schering- Shionogi) IJSA: Pennitil (Schenng); wfm Pennitil (Schering-Plough); wfm Prolixin (Squibb); wfm Prolixin (Bnstol-Myers Squibb); wfm generics Flupirtine ATC: Iyl03B: N02BG07 Use: analgesic RN: 56995-20-1 MF: C,sH,7FN,02 MW 304.33 EINECS: 260-503-8 LD,,: 617 mglkg (M, p.0.); 1660 mgikg (R, p.0.) CN: [2-amino-6-[[(4-fluorophenyl)methyl]amino]-3-pyridinyl]carbamic acid ethyl ester monohydrochloride RN: 33400-45-2 MF: C,,H,,FN,O,. HC1 MW: 340.79 EINECS: 251-496-2 LD,,,: 432 mg/kg (M, s.c.) maleate (1:l) RN: 75507-68-5 MF: C,,HI,FN40, . C4H4O4 MW: 420.40 EINECS: 278-225-0 Fluprednidene acetate F 907 , , CI C I 4-fluoro- 2,6-dichloro- 2,6-dichloro- 2.0mina.6.chloro- benzylomine pyridine 3-nitropyridine 3-nitropyridine 1. Hz. Raney-Ni r I 2. ethyl chloroformate Referencers): DE I 670 522 (Degussa; appl. 12.5.1966). DE 1795 858 (Degussa; appl. 19.7.1968). US3 481 943 (Degussa; 2.12.1969; D-prior. 12.5.1966). US 3 513 171 (Degussa; 19.5.1970; D-prior. 12.5.1966). Bebenburg, W. v. et al.: Chern Ztg. (CMKZAT) 103, 387 (1979). Bebenburg, W. v. et al.: Chern Ztg. (CMKZAT) 105, 217 (1981). US 5 959 115 (ASATA Medica; 28.9.1999; appl. 23.4.1 998; D-prior. 23.4.1997). (1) Formularion(s): cps. 50 mg, 100 mg; suppos. 75 mg, 150 mg (as maleate) Flupirtine Trade Name(s): D: Katadolon (ASTA Medica Trancopal (Sanofi I: Katadolon (ASTA Medica) AWD) Winthrop) Fluprednidene acetate ATC: D07AB07; D07CB02; D07XB03 Use: topical glucocorticoid RN: 1255-35-2 MF: C,,H,,FO, MW: 432.49 EINECS: 215-013-9 CN: (1 1P)-21-(acety1oxy)-9-fl uoro-11,17-dihydroxy-l6-methylenepregna-1,4-diene-3,20-dione 0 CH, methane 1 6-dehydropregnenolone acetate 1. H20,. NaOH 2. 1 1 H,C 0 CH, 0 1. hydrogen peroxide 38-acetoxy-16-methyl-20- 0x0-5.16-pregnadiene (I) 908 F Fluprednidene acetate 1. I,. COO 2, 0 HCI. CH3COOCZHS H3CAOK I H3C-CO-CH3 I1 , IV 1. iodine (111) rnicrobiologicol dehydrogenotion [Flovobacterium dehydrogenons] 2. H;C-SO2-CI rnicrobiologicol hydroxylotion [Fusoriurn equiseti Soccordo] v , w 2. methonesulfonyl chloride 0 1.0-Br , HCIO,. H20 0 0 3. H,F2 1. N-brornosuccinimide 3. hydrogen fluoride rnicrobiologicol dehydrogenation - Fluprednidene ocetotc Refercnce(s): GB 1 230 671 (Merck Patent GmbH; appl. 10.7.1969). Irmscher, K. et al.: Arzneim Forsch. (ARZNAD) 18,7 (1968). (also other syntheses reviewed) synthesis of 16-dehydropregnenolone acetate: Wettstein, A.: Helv. Chim. Acta (HCACAV) 27, 1803 (1944). alternative syntheses: GB 946 860 (Merck & Co.; appl. 17.3.1960; USA-prior. 24.3.1959). US 3 068 226 (Merck & Co.; 11 .l2.1962; appl. 22.12.1961; prior. 24.3.1959). US 3 163 760 (Merck & Co.; 9.7.1964; appl. 24.3.1959). US 3 309 272 (Merck & Co.; 14.3.1967; appl. 24.4.1961; prior. 24.3.1959). Formulation(s): cream 1 mdg; ointment 0.05 g1100 g, 1 mj& sol. 0.025 gI100 g, 0.15 g1100 g, 1 mglml Fluprednisolone acetate F 909 Trade Name(s): D: Candio-Hermal (Herma1)- Decoderm (Hermal) Sali-Decoderm (Herma1)- comb. Decoderm (Herma1)-comb. comb. Fluprednisolone acetate Use: glucocorticoid RN: 570-36-5 MF: C,,H,,FO, MW: 420.48 EINECS: 209-330- 1 CN: (6a,11 P)-21-(acety1oxy)-6-fluoro- 1 1,17-dihydroxypregna- l,4-diene-3,20-dione fluprednisolone RN: 53-34-9 MF: C2,H2,FOS MW: 378.44 EINECS: 200-170-8 acid cis-methyl 3,3- ethylenediaxy-1 1 -am- 5.1 7(20)-pregnadiene- 21-carboxylate 1. LIAIH, 2. O O , pyridine H~CWTH~ b 1. lithium alanote 2. acetic anhydride 2. H2S04. acetane b 1. N-methylmorpholine hydrogen peroxide osmium(Wll) oxide 1. CHCIS, HCI 2. microbiological dehydrogenation [Septomyxa affinis (ATTC 6737)] or Se02 rn b Fluprednisolone acetote Reference(s): US 2 841 600 (Upjohn; 1958; prior. 1957, 1955). DE 1 079 042 (Syntex; appl. 1958; MEX-prior. 1957). 910 F Flurazepam starting material: US 2 707 184 (Upjohn; 1955, prior. 1953, 1952). alternative synthesis: US 4 041 055 (Upjohn; 9.8.1977; prior. 17.1 1.1975) Formulation(s): tabl. 1.5 mg, 2 mg, 16 mg Trude Name(s): D: Isopredon (Hoechst); wfm I: Etadrol (Carlo Erha); wfm F: Decoderme (Merck- Etadrol (Farmitalia); wfm CICvenot); wfm USA: Alphadrol (Upjohn); wfm Flurazepam ATC: NOSCDOI Use: hypnotic, sedative RN: 1761 7-23-1 MF: C,,H,,ClFN,O MW: 387.89 EINECS: 241-591-7 LD,,,: 59.1 mgfkg (M, i.v.); 500 mgkg (M, p.0.); 38.7 mglkg (R, i.v.); 980 mgkg (R, p.0.) CN: 7-chloro- 1 -[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro-2H-l,4-benzodiazepin-2-one dihydrochloride RN: 1 172-18-5 MF: C,,H,,C1FN30 .2HC1 MW: 460.8 1 EINECS: 214-630-0 LD,,,: 59.1 rng/kg(M, i.v.); 596mg/kg(M, p.0.); 38.7 mglkg (R, i.v.); 879 mglkg (R, p.0.) hydrochloride RN: 36105-20-1 MF: C,,H,,CIFN,O~ HCl MW: 424.35 / cl%F 2-amino-5-chlaro P-fluorobenzo- phenone (cf, flunitrozeporn synthesis) bromaocetyl chlaride LiAlH 0 \ 00 \ NH , H2N-NH2 . H20 n lithium OH phtholirnidoocetyl hydrozine alonote chloride 0 hydrate . CN: 7-chloro- 1 -[ 2-( diethylamino)ethyl ]-5 -( 2-fluorophenyl )-1 ,3-dihydro-2H-l,4-benzodiazepin-2-one dihydrochloride RN: 1 17 2-1 8-5 MF: C,,H,,C1FN30 .2HC1 MW: 460.8 1 EINECS: 21 4-6 3 0-0 LD,,,:. glucocorticoid RN: 125 5-3 5-2 MF: C,,H,,FO, MW: 432.49 EINECS: 21 5-0 1 3-9 CN: (1 1P )-2 1-( acety1oxy )-9 -fl uoro-11,17-dihydroxy-l6-methylenepregna-1,4-diene-3,20-dione 0 CH, methane 1 6-dehydropregnenolone. EINECS: 20 9-3 3 0- 1 CN: (6a,11 P )-2 1-( acety1oxy )-6 -fluoro- 1 1,17-dihydroxypregna- l,4-diene-3,20-dione fluprednisolone RN: 5 3-3 4-9 MF: C2,H2,FOS MW: 378.44 EINECS: 20 0-1 7 0-8 acid cis-methyl