0.01 % Trade Names: D: Flucinar medphano Jellin Griinenthal Jellisoft Griinenthal Procto-Jellin Griinentha1- comb... with neomycin GB: Metosyn Zeneca USA: Dermacin Pedinol F: Topsync C
Trang 1Fluocinolone acetonide F 891
H3C-CO-NH-Br HCIO,
b
N-bromoacetamide
1
0 CH,
0
Se02, (H3C)3C-OH
selenium fluoride
i
fluocinolone (IV)
-
- Fiuacinolone acetonide
US 3 014 938 (Syntex; 26.12.1961, appl 23.8.1960; MEX-prior 7.9.1959)
US 3 124 571 (Syntex; 10.3.1964; appl 19.5.1960; MEX-prior 26.1.1960)
Djerassi, C et al.: 3 Am Chem Soc (JACSAT) 82, 3399 (1960)
starting material:
Julian, P.L et al.: J Am Chem Soc (JACSAT) 72, 5145 (1950)
alternative syntheses:
GB 933 867 (American Cyanamid; appl 5.12.1959; USA-prior 8.12.1958)
US 3 197 469 (Pharmaceutical Research Prod.; 27.7.1965; appl 6.8.1958)
Formulation(s): cream 0.025 9%; ointment 0.025 %: topical sol 0.01 %
Trade Name(s):
D: Flucinar (medphano)
Jellin (Griinenthal)
Jellisoft (Griinenthal) Procto-Jellin (Griinentha1)-
comb
Trang 2892 F Fluocinonide
F: Antibio-Synalar
(Cassennc)-comb
Synalar (Cassenne)
Synalar Neomycin
(Cassenne)-comb
GB: Synalar (Zeneca)
I: Alfabios (Biotekfarma)
Alfafluorone (Biotekfarma)
Boniderma (Boniscontro &
Gazzonc)
Coramide (Ottolenghi)
Cortanest Plus (Piam)-
comb with lidocaine
Dermobeta (Terapeutico
M.R.)
Dermolin (Lafare)
Doricum (Farmila)-comb
with neomycinc
Doricum Semplice (Farmila)
Esacinone (Lisapharma) Fluocit (CT)
Fluomicetina (Zoja)-comb
with kanamycin Fluomix Same (Savoma) Fluovitef (Italfarmaco) Lauromicina Pomata (Lafare)-comb with eritromycin Localyn (Recordati) Mccloderm (Schwa@- comb with meclocycline Meclutin (ABC-Torino)- comb with meclocycline Nefluan (Mo1teni)-comb
Neoderm (Crosara)
Omniderm (Face) Proctolin (Recordati)- comb with lctocaine Sterolone (Francia Farm.) Ultraderm (Ecobi) J: Benamizol (Mohan Yakuhin) Biscosal (Ohta Seiyaku) Cortiphate (Tokyo Tanabe) Flucort (Syntex-Tanabe) Fluvean (Kowa) Fluzon (Taisho Seiyaku) USA: Derma-Smoothe (Hill) Fluonid (Allergan)
FS Shampoo (Hill) Synalar (Medicis) Synemol (Medicis)
Use: glucocorticoid, anti-inflammatory RN: 356-1 2-7 MF: C,,H,,F,O, MW: 494.53 EINECS: 206-597-6
LD,,: >6 glkg (M, p.0.);
14 m g k g (R, p.0.)
CN: (6a,11~,16a)-21-(acetyloxy)-6,9-difluoro-l 1-hydroxy-16,17-[(l-~ethylethylidene)bis(oxy)]pregna-l,4-
diene-3.20-dione
Reference(s1:
GB 916 996 (Olin Mathieson; appl 21.7.1959; USA-prior 6.8.1958)
US 3 124 571 (Syntex; 10.3.1964; appl 19.5.1960; MEX-prior 26.1.1960)
fluocinolone ocetonide
Forrnulation(s): cream 0.5 mglg; ointment 0.5 mglg, sol 0.5 mg/g
Trade Narne(s):
D: Topsym (Grunenthal) Topsyne nkomycine J: Bestasone (Kodama)
comb with neomycin GB: Metosyn (Zeneca) USA: Dermacin (Pedinol)
F: Topsync (Cassenne) I: Flu 21 (Select Pharma) Lidex (Medicis)
Topsyn (Recordati) Lidex E Cream (Medicis)
Fluocinonide
1
Trang 3Fluocortin butyl F 893
Fluocortin butyl
(Fluocortin butyl ester)
ATC: D07AB04 Use: glucocorticoid RN: 41767-29-7 MF: C2,H3,F05 MW: 446.56 EINECS: 255-543-8
LD,: >5 g/kg (M, p.o.1;
>4 g/kg (R, p.0.);
>I &/kg (dog, p.0.)
CN: (6a,11 P, 16a)-6-fluoro- 1 1 -hydroxy-16-methyl-3,20-dioxopregna-l,4-dien-21 -oic acid butyl ester
fluocortin
RN: 33124-50-4 MF: C22H27FOs MW: 390.45 EINECS: 251-383-8
F
fluocortolone
(9 v.)
MnOZ CW2CIZ
manganese
dioxide
Fluocortin butyl
DOS 2 150 268 (Schering AG; appl 4.10.1971)
DOS 2 204 361 (Schering AG; appl 27.1.1972)
DOS 2 260 303 (Schering AG; appl 6.12.1972)
GB 1 387 91 1 (Schering AG; valid from 19.3.1975; D-prior 4.10.1971,27.1.1972)
Laurent, H et al.: Arzneim.-Forsch (ARZNAD) 27 (II), 2187 (1977) (also other methods)
DOS 2 441 284 (Schering AG; appl 27.8.1974)
BE 823 682 (Schering AG; appl 20.12.1974; D-prior 21.12.1973, 27.8.1974, 16.9.1974)
Formulation(s): cream 7.5 mglg; ointment 7.5 mglg; powder 100 mgl4 g
Trade Narnefs):
D: Bi Vaspit (Asche)-comb Lenen (Alk-Scherax; Vaspit (Asche)
H02AB03; S01CA04 Use: glucocorticoid RN: 152-97-6 MF: CZ2H2,FO4 MW: 376.47 EINECS: 205-811-5
CN: (6a,11~,16a)-6-fl~oro-11,21-dihydroxy-l6-methylpregna-l,4-diene-3,20-dione
Trang 4894 F Fluocortolone
1 BrZ
2 Nal
3 KOwCH3
b I N-bromo-
succinimide
16a rnethylpregnenolone 21 -0cetoxy-3p-hydraxy-16-a-
3@-ocetote methyl-20-axo-5-pregnene fluoride
(cf flumetasone synthesis)
OH microbiological dehydrogenation
Fluocortolone
Referetrce(s):
DE 1 135 899 (Schering AG; appl 20.5.1960)
BE 614 196 (Schering AG; appl 21.2.1962; D-prior 22.2.1961)
Domenico, A et al.: Arzneh-Forsch (ARZNAD) 15,46 (1965)
Dl3 1 169 444 (Schering AG; appl 22.2.1961)
synthesis of starting cotnpound:
Petrov, V.; Williamson, D.M.: J Chem Soc (JCSOA9) 1959, 3595
alternative synthesis:
Kieslich, K ct a].: Justus Liebigs Ann Chem (JLACBF) 726, 168 (1969)
DOS 1 909 152 (Schering AG; appl 19.2.1969)
review:
Akhrem, A.A et al.: Russ Chem Rev (Engl Trans].) (RCRVAB) 34,926 (1965)
Formulation(s): cream 2.5 mglg; lotion 2.5 mglg; ointment 2.5 mglg; tabl 5 mg, 20 mg, 50 mg
Trade Name(s):
D: Ultralan (Schering) Ultralanum (Schering) Ultralanum oint
CB: Ullradil (Schering); wfm
Trang 5Fluocortolone caproate F 895 Ultraproct (Schering)- I: Ultralan (Schering)-comb Ultraproct (Schering)-
-F ~ u o c o ~ ~ o ~ o ~ ~ caproate ATC: C05AA08; D07AC05; H02AR03
Use: glucocorticoid RN: 303-40-2 MF: C2,H,,FOs MW: 474.61 EINECS: 206-140-0
CN: ( 6 a , l l P, 16a)-6-fluoro-1 l-hydroxy-l6-methyl-21-[(1-oxohexyl)oxy]pregna-1,4-diene-3,20-dione
fluocortolone c a p r o i c a n h y d r i d e Fluocortolone c o p r o a t e
Referencefs):
FR 1 561 884 (Schering AG; appl 10.5.1968; D-prior 13.5.1967)
Forrnulation(s): cream; lotion; ointment 2.5 mglg in comb with fluocortolone
Trade Narnefs):
D: Ultralan Creme (Schering)-
comb
Ultralan Salbe (Schering)-
Ultraproct (Schering)-
comb
F: Myco-Ultralan (Schering)-
comb
Ultralan (Schering)-comb Ultralanum (Schering Ultraproct (Schering)- Chemicals)-comb.; wfm
Ficoid (F1sons)-comb.; Chemicals)-comb.; wfm
Ultradil (Schering Ultraproct (Schering) Chemicals)-comb.; wfm comb
Fluocortolone trimethylacetate
(Fluocortolone 2 1 -pivalate)
ATC: C05AA08; D07AC05; H02AB03 Use: glucocorticoid
RN: 20380-10-3 MF: C2,H3,FO5 MW: 460.59
CN: 6a-fluoro-17,21-dihydroxy-l6a-methyl-pregna-l,4-diene-3,20-dione 21-pivalate
tl~ocortol~ne pivolic anhydride
F
Fluocortolone trimethylacetote
Referencefs):
FR 1561 884 (Schering AG; appl 10.5.1968; D-prior 13.5.1967)
Trang 6896 F Fluorescein
Formulatio~z(s): cream 20 mg/g; cream 2.5 mglg in comb with fluocortolone; emulsion 2.5 mglg in comb with
fluocortolone/-caproate; suppos 40 mg in comb with lidocain hydrochloride
Trade Name(s):
D: Doloproct (Schering)- Ultraproct (Schering)- Ultraproct (Schering
hydrochloride F: Ultraproct (Schering)- I: Ultralan (Schering)-comb Ultralan Creme (Schering)-
'jmb
Ultraproct (Schering)-
comb
Use: diagnostic RN: 2321-07-5 MF: CZoHj2O5 MW: 332.31 EINECS: 219-03 1-8
LD,,,: 300 mg/kg (M, i.v.)
CN: 3',6'-dihydroxyspiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one
disodium salt
RN: 518-47-8 MF: C20H,oNa20S MW: 376.28 EINECS: 208-253-0
' LD,,,: 1 glkg (M, i.v.); 4738 mglkg (M, p.0.);
1 glkg (R, i.v.); 6721 mglkg (R, p.0.);
1 glkg (dog, i.v.)
phthalic resorcinol
anhydride
Fluorescein
Reference (s):
Ullmanns Encykl Tech Chem., 4 Aufl., Vol 23,414
Formulation(s): amp 113.2 mglml (as disodium salt); eye drops 1.7 mg/ml
Trade Name(s):
D: Fluorescein-Losung 1 0 % Thilorbin (Alcon) I: Pancreolauryl Test intravenos 1nj.-Losung GB: Minims Fluorescein (Geymonat; as laurate)
Fluoreszein 0,15 % Thilo Minims lignocaine and Fluores (Showa Yakuhin) Augentropfen (Thilo) fluorescein (Chauvin)- Fluorescein sodium
DlOAAOl; SOlBA07; SOlCBO5 Use: glucocorticoid
RN: 426-13-1 MF: Cz2H2,F0, MW: 376.47 EINECS: 207-041 -5
LD,,,: 443 mglkg (R, i.p.)
CN: ( 6 a , 1 1 P)-9-fluoro- 1 1,17-dihydroxy-6-methylpregna-1,4-diene-3,20-dione
Trang 7Fluorometholone F 897
Ob ,CH3 pyridine
9-fluoro-6a-methyl- methane- (1)
hydrocortisone sulfonyl
chloride
Zn, CH3COOH
I
rnicrobiologicol dehydration
[Ssptomym offinis (ATCC 6737)]
I1
CH3
Fluorometholone
Referencets):
US 2 867 638 (Upjohn; 6.1.1959; appl 17.5.1967; prior 10.9.1956)
DE 1056 605 (Upjohn; appl 6.5.1959; USA-prior 10.9.1956)
starting material:
Spero, G.B el al.: J Am Chem Soc (JACSAT) 79, 1515 (1957)
Formulation(s): eye drops 1 mglml
Trade Namets):
D: Efflumidex (Pharm-
Efflumycin (Pharm- I:
Allergan)-comb
Ehrtolan (Albert-Rousse1)-
comb
Ejemolin (CIBA Vision)- J:
comb
Fluoropos (Ursapharm)
Isoptotlucon (Alcon) Ursnon (Nihon Yakuhin Flucon collyre (Alcon) K o g ~ o )
Efemoline (CIBA Vision) USA: FML Liquifilm (Allergan);
Fluaton (Allergan) Neo-Oxylone (Upjohn) Flumetol (Farmila)-comb comb.; wfm
Flu-Base (Kowa) Oxylone (Upjohn); wfm Flumetholon (Santen)
Okilon (Sumitorno)
Trang 8898 F Fluorouracil
Pluorouracil
(Fluracilum)
ATC: LOlBC02 Use: antineoplastic RN: 51-21-8 MF: C4H,FN202 MW: 130.08 EINECS: 200-085-6
LD,,,: 81 m g k g (M, i.v.); 115 mglkg (M, p.0.); !
245 mglkg (R, i.v.); 230 m g k g (R, p.0.);
30 mglkg (dog, p.0.)
CN: 5-fluoro-2,4-pyrimidinediol or 5-fluoro-2,4(1H,3H)-pyrimidinedione
ethylate H 0
ethyl fluoroocetote ethyl formate (1)
S-methylthiouronium
sulfote
5-fluoro- fluorourocil 2-methyl-
thiouracil
F2 or CF30F
b
fluorine
H
trifluoromethyl
urocil
hypofluorite
Refewnce(s):
a US 2 802 005 (C Heidelberger, R Duschinsky; 6.8.1957; prior 26.9.1956)
Duschinsky, R et al.: J Am Chem Soc (JACSAT) 79,4559 (1957)
b US 3 682 917 (I L Knuniants et al.; 8.8.1972; appl 25.3.1970)
US 3 846 429 (S A Giller et al.; 5.1 1.1974; appl 22.9.1971)
US 3 954758 (PCR, Inc.; 4.5.1976; prior 7.8.1967, 1.3.1968,27.5.1970,4.10.1971)
DOS 2 149 504 (Research Inst f Med and Chem.; appl 4.10.1971; USA-prior 5.10.1970)
DOS 2 719 245 (Daikin Kogyo; appl 29.4.1977; J-prior 29.4.1976)
DOS 2 726 258 (Daikin Kogyo; appl 10.6.1977; J-prior 11.6.1976)
synthesisfiom orotic acid by fluorination and following decarboxylation:
DOS 2 826 496 (Asahi Glass; appl 16.6.1978; J-prior 17.6.1977)
Formulation(s): cream 5 %; ointment 50 mglml, 1 g/20 g; plaster 96 ~ g l l l 3 cm2; vial 50 mglml, 250 mg15 ml,
500 mg/lO ml, 1000 mg120 ml
Trade Name(s):
D: Actino-Hermal Pflaster Verrumal (Herma1)-comb GB: Accusite (Matrix)
Efudix Roche (ICN) combination preparations Fluoro-Urac~le (Roche) Fluroblastin (Pharmacia & F: Efudix (Roche) generic
Trang 9Fluoxetine F 899
Carzonal (Tobishi) Timadin (Torii) USA: Efudex (Roche)
Efudix (Roche) Ulosagen (Kyowa Yakuhin Fluoroplex (Allergan)
inhibitor
f
RN: 54910-89-3 MF: C,,HlnF3NO MW: 309.33
LD,: 464 mgkg (M, p.o.1;
825 mgkg (R, p.0.)
CN: (~)-N-methyl-y-[4-(trifluoromethyl)phenoxy]benzenepropanamine
monohydrochloride
RN: 59333-67-4 MF: C17HlnF3N0 HC1 MW: 345.79
acelophenone paraform- dimethyl- 3-dimethylamino-
aldehyde amine propiophenone (1)
1 B,H,
2 S0Cl2
F 3 c ~ 0 H , NaOH
I 11
CH3 4-trifluoromethyl-
1.BrCN
2 KOH
NNCH3 1 cyanagen bromide
(*)-N,N-dirnethyl-3-phenyl-3-
(4-trifluoromethylphenoxy)-
pmpylamine (11)
NaOH, DMF
Fluoxetine
(*)-I -phenyl-3-(methyl- 1 -chloro-4-(tri-
omino)propan- 1-01 (111) fluoromethyl)-
Trang 10900 F Fluoxetine
bentyl 4-(tri- fluoromethyl)- phenyl ether
1 o3
2 H2N-CH,
3 NaCNBH3
_*
3 sodium cyano-
Fluoxetine
borohydride
N-methyl-
hydroxyl-
omine
N-methyl- nitrone
2-methyl-5-
phenylisoxo- zolidine (VI)
H Pd-C N
VI 2 111 - ( Fluoxetine (
2 NaH, OMS0
cyanomethyl
phenyl ketone
(?)'-3-phenyl-3- hydroxy-l- proponarnine
0 LIAIH,, THF
+ C I , k O P ' 3
diborone
I - - - +
methyl chloroformoie
Fluoxetine
El
1 CIC02C2H5
2 NaOH
1 ethyl