alternative synthesis by reaction of 2-diethylan~inoethyl chloridc with 7-chloro-5-2-fluoropheny1-2-oxo-2,3- dihydro-1 H- l,4-benzodiazepine: GB 1 O4O 548 Roche; appl.. alternative synt
Trang 1Flurbiprofen F 91 1
Flurazeporn
Reference(s):
US 3 567 710 (Hoffmann-La Roche; 2.3.1971; prior 3.6.1968)
alternative synthesis by reaction of 2-diethylan~inoethyl chloridc with 7-chloro-5-(2-fluoropheny1)-2-oxo-2,3-
dihydro-1 H- l,4-benzodiazepine:
GB 1 O4O 548 (Roche; appl 1.3.1963; USA-prior 2.3.1962)
Formulation(s): cps 1 0 mg, 15 mg; tabl 27.42 mg (as base); cps 15 mg, 30 mg; tabl 30 mg (as
monohydrochloride); cps 15 mg, 30 mg; s r cps 20 mg (as dihydrochloride)
Trade Narne(s):
D: Dalmadorm (Roche) Felison ( ~ a ~ r o ~ h & n ) J: Benozil (Kyowa)
Flurazepam 15130 Riker Flunox (Boehringcr Dalmate (Nippon Roche)
Staurodorm Neu Mldorm A.R (Piarn) USA: Dalmane (Rochc)
I: Dalmadorm (Roche) Valdorm (Valeas)
Use: anti-inflammatory, analgesic RN: 5104-49-4 MF: ClsH13F0, MW: 244.27 EINECS: 225-827-6
LDsU: >385 mg/kg (M, i.v.); 640 m g k g (M, p.0.);
117 rngkg (R, p.0.);
10 mglkg (dog, p.0.)
CN: 2-fluoro-a-methyl[l , 1'-biphenyl]-4-acetic acid
sodium salt
RN: 56767-76-1 MF: C,,H,,FNaO, MW: 266.25
bromobenzene 4'-brorno-3'- 4-acetyl-2-nitra- 4-ocetyC2-ornino-
Trang 2912 F Flurbiprofen
A
HO''CH~
HzS04
COOH
0-CH,
0
4-ocetyl-2-fluoro-
biphenyl (1)
2-fluoro-4-biphe- nylylocetic ocid
ethyl 2-fluoro-4- biphenylylocetote (U)
1 NoOC,H,
2 H~c'O\
H3C O O CH3 2 dimethyl sulfotc
CH3
4-bromo-2-
fluorobiphenyl
2-(2-fluoro-4-biphenylyl)- 2-hydroxypropionic acid (111)
polyphosphoric acid
C H 2
2-(2-fluoro-4-bi- phenylyl)ocrylic acid
Reference ( s ) :
a DAS 1 518 528 (Boots; appl 19.1.1965; GB-prior 24.1.1964)
US 3 755 427 (Boots; 28.8.1973; GB-prior 24.1.1964)
US 3 793 457 (Adams Sectal; 19.2.1974; GB-prior 24.1.1964)
b GB 1 5 14 8 12 (Boots; appl 4.4.1975; valid from 31.3.1976)
similar method:
US 3 959 364 (Boots; 25.5.1976; GB-prior 24.5.1973)
alternative syntheses:
DOS 2 646 792 (Mitsubishi Petrochemical; appl 16.10.1976; J-prior 23.10.1975, 31.7.1976)
racemate resolution:
DOS 2 809 794 (Boots; appl 7.3.1978; GB-prior 8.3.1977, 18.1.1978)
Formulation(s): amp 50 mg; cps 200 mg; drg 50 mg, 100 mg; eye drops 0.3 mglml (as sodium salt
dihydrate); plaster 40 mg; s r cps 200 mg; suppos 100 mg; tabl 50 mg, 100 mg
Trade Name(s):
D: Froben (Kanoldt; 1980) Ocufen (Allergan) J: Froben (Kakenyaku)
Ocuflur (Pharm-Allergan) GB: Froben (Knoll; 1977) USA: Ocufen (Allergan; 1987)
F: Antadys (Theramex) Ocufen (Allergan)
Cebutid (Knoll; 1979) I: Froben (Boots Italia)
Trang 3Flurotyl F 913
Flurotyl
(Flurothyl)
RN: 333-36-8 MF: C4H,F,0 MW: 182.06
LDs0: 46 mgkg (M, i.v.)
CN: 1,l'-oxybis[2,2,2-trifluoroethane]
No
F ~ ' O H -+ F ~ C - O N ~
2,2,2-trifluoro- (n)
ethanol (I)
Use: CNS stimulant convulsant
Reference(s):
US 3 363 006 (Pennwalt; 9.1 l968; prior 29.12.1955,20.6.1960)
Formulation(s): 2 ml in special inhalation device
Tmde Name(s):
USA: Indoklon (Ohio Med.);
wfm
Use: inhalation anesthetic
RN: 406-90-6 MF: C4H5F30 MW: 126.08 EINECS: 206-977-1
LD,,: 5600 mgkg (R, i.p.)
CN: (2,2,24rifluoroethoxy)ethene
ethanol (I)
montmorillonite 2 4 0 - 2 8 0 OC
ocetoldehyde
Reference(s):
a US 2 830 007 (Air Reduction Cornp.; 1958; appl 1953)
b US 2 870 21 8 (Air Reduction Cornp.; 1959; appl 1955)
Fonnulation(s): liquid for inhalation 125 rnl
Trang 4914 F Fluspirilene
Trade Name(s):
USA: Fluorornar (Ohio Med.);
wfm
Use: neuroleptic KN: 1841 -19-6 MF: C,,H,,F,N,O MW: 475.58 EINECS: 217-418-6 LD,,: 106 mg/kg (M, i.m.);
>I46 mg/kg (R, i.m.)
CN: 8-[4,4-bis(4-fluorophenyl)butyl]-l-phenyl-l,3,8-triazaspiro[4.5]decan-4-one
NH2
1 -benzyl- aniline potassium
4-onilino- 1 -benzyl-
4-corbomoylpiperidine (I)
spiro[4.5]decane (11) 4,4-bis-(4-fiuaro-
phenyl)butyl bromide
Reference(s):
Fluspirilene
BE 633 914 (Janssen; appl 20.6.1963; USA-prior 22.6.1962)
US 3 238 216 (Jansscn; 1.3.1966; prior 22.6.1962, 20.6.1963)
DAS 1 470 125 (Janssen; appl 21.6.1963; USA-prior 22.6.1962)
Formulation(s): amp 1.5 mg10.75 ml, 2 mgl ml, 12 mg16 ml; vial 12 mg (2 mglml)
Trade Name(sJ:
D: Fluspi (Neuro Hexal) GR: Redeptin (Smith Klinc &
Kivat (Honnosan) USA: Imap (McNeil); wfm
Trang 5Flutamide F 915
Use: antiandrogen, antineoplastic (hormonal)
RN: 133 11-84-7 MF: CllHl1F3N2O3 MW: 276.21 EINECS: 236-341-9
>2 glkg (dog, p.0.)
CN: 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide
Qc,
w
trifluoro-
msthylbenzene
1-nitro-3-tri- fluoromethyl- benzene
3-trifluoromethyl- aniline (I)
3'-trifluoromethyl- acetonilide
4-nitro-3-trilluoro
methylaniline (11)
isobutyryl
chloride (Ill)
Flutornide
pyridine
1 + UI d H 3 C ' ) ( 4 0 C F 3
C H , ~
3'-Lrifluorornethyl- isobutyronilide
Reference(s):
J Med Chem (JMCMAR) 10,93 (1967)
a DOS 2 130 450 (Scherico; appl 19.6.1971)
US 4 144 270 (Scherico; 13.3.1979; appl 26.6.1974)
b US 4 302 599 (Schering Co.; 24.11.1981; prior 10.9.1979)
synthesis of 4-nitro-3-trifluoromethylaniline:
Jones, R.G.: J Am Chem Soc (JACSAT) 69,2346 (1947)
medical use:
US 3 995 060 (Scherico; 30.11.1976; appl 11.9.1974)
US 4 139 638 (Schcring Corp.; 13.2.1979; appl 3.10.1977)
US 4 161 540 (Schering Corp.; 13.2.1979; appl 3.10.1977)
US 4 329 364 (Schering Corp.; 11.5.1982; appl 23.9.1976)
US 4 474 813 (Schering Corp 2.10.1984; appl 24.5.1982)
Formulation{s): cps 125 mg; tabl 250 mg
Trang 6916 F Flutazolam
Trade Name(s):
D: Apimid (Apogepha)
Cytamid (esparma)
Flumid (Hexal)
Fluta GRY (GRY-Pharma)
Winthrop)
Fugerel (Essex Pharma; GR:
1984)
Flutazolam
Eulexine (Schering-Plough; J: Odyne (Nippon Kayaku)
Chimax (Chiron)
ATC: NOSBA Use: benzodiazepine anxiolytic, tranquilizer
RN: 27060-91-9 MF: CI9HIRC1FN2O3 MW: 376.82
LD,,,: 19 10 m g k g (M, p.0.);
>6 @kg (R, p.o.1
CN: 10-chloro- l l b-(2-fluoropheny1)-2,3,7,1 1b-tetrahydro-7-(2-h~droxyethyl)oxazolo[3,2-
d][l,4]benzodiazepin-6(5H)-one
2-amino-5-chloro- glycine ethyl estel
2'-fluorobenzo- hydrochloride
phenone
(cf flunitrozepom
synthesis)
U
o l ~ r n i n ~ m chloride
ethylene
oxide
Flutozolorn
u
7-chloro-5-(2- f1uorophenyl)- 1.3-dihydro-2H- 1,4-benzodioze- pin-2-one (I)
Rcference(s):
DOS 1 952 486 (Hoffmann-La Roche; appl 17.10.1969; USA-prior 18.10.1968)
synthesis of 7-chloro-5-(2-fluoropheny1)- 1,3-dihydro-2H- 1,4-henzodiazepin-2-one:
US 3 109 843 (Hoffinann-La Roche; 5.1 1.1963; prior 21.6.1962)
Formulation(s): tabl 4 mg
Trade Name(s):
J : Coreminal (Mitsui)
Trang 7Fluticasone propionate F 9 17
Use: locally active glucocorticosteroid RN: 80474-14-2 MF: C,,H,,F,O,S MW: 500.58
CN: (6a,1 1j3,16a,17a)-6,9-Difluoro- l l-hydroxy-l6-methyl-3-oxo-l7-(1-oxopropoxy)androsta-1,4-diene-17-
carbothioic acid S-(fluoromethyl) ester
0
H,IO,, THF
-, 1
chloride
(cf diflucortolone
volerate)
2 H,S, DMF
q0*cH3 3 HCI H 2 0
~ ~ ~ C H , H0v-4
b - Me
or
1, arcl DMA, NaHC03
2 AgF CH&N
I1 . -,
F
Fluticasone propionate I
Reference(s):
BE 887 518 (Glaxo Group; appl 13.2.1981; GB-prior 15.2.1980)
L 109 656 (Chemagis LTD.;IL-prior 15.5.1994)
Phillipps, G.H et al.: 5 Med Chem (JMCMAR) 37,3717 (1994)
Formulation(s): aerosol for inh 44 pg, 110 pg, 220 pg; cream 0.05%; ointment 0.005%; nasal spray 0.05%
Trade Name(s):
D: Atemur (ASTA Medica Viani (Cascan; Glaxo I: Flixotide (Glaxo
Wellcome) GB: Cutivate (Glaxo Wellcome) USA: Cutivate (Glaxn Wellcome) Flutivate (Cascan; Glaxo Flixonase (Allen & Flonase (Glaxo Wellcome)
Flixotide (Allen &
Hanburys)
Trang 8918 F Flutoprazepam
U s e : long a c t i n g b e n z o d i a z e p i n e anxiolytic
RN: 25967-29-7 MF: C,,H,,CIFN,O MW: 3 4 2 8 0
LD,,,: 2 1 1 0 mglkg (M, i.p.); 2 4 3 0 mgkg (M, p.0.);
2 2 3 0 mglkg (R, i.p.); 1 0 0 6 g/kg (R, p.0.);
I000 mgkg (rabbit, p.0.);
> I 0 glkg (dog, p.0.)
CN: 7 - c h l o r o - l -(cyclopropylmethyl)-5-(2-fluoropheny1)- 1 3 - d i h y d r o - 2 H - l , 4 - b e n z o d i a z e p i n - 2 - o n e
1 Brz
* 0 0
r
2-fluoro-
toluene
ethyl a-(2-fluoro-
benzyl)ocetoocetate
2 KOH
1 cyclopropylmethyl bromide
-,
LI
benzy1)-a-(4-chloro-
phenyloza)oceto-
ethyl 5-chloro-3-
(2-fluoropheny1)-
indole-2-corbo~ylote (11)
acetate (I)
propylrnethyl-3-
(2-fluoropheny1)-
indole-2-corbou-
I Flutoprozeporn
Trang 9Flutrimazole F 919
CN 2 LiAIH,
CI
- CI -v
\ /
5-chloro-3- (2-fluoropheny1)- indole-2- carbonyl chloride
Referencefs):
DE 1 795 372 (Sumitomo; appl 20.9.1968; J-prior 22.9.1967)
DE 1 795 771 (Sumitomo; appl 20.9.1968; J-prior 2.1 1.1967)
US 3 925 364 (Sumitomo; 6.8.1974; appl 16.9.1968; J-prior 22.9.1967)
additional synthesis:
DOS 2 151 540 (Sumitomo; appl 15.10.1971; J-prior 17.10.1970)
DOS 2 113 122 (Sumitomo; appl 18.3.1971; J-prior 19.3.1970)
Formulation(s): tabl 2 mg
Trade Narnefs):
J : Restas (Banyu; 1985)
Flutrimazole
(UR-4056)
ATC: DOlA Use: topical antifungal RN: 119006-77-8 MF: C,,H,,F,N, MW: 346.38
CN: l-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H-imidazole
Trang 10920 F Flutropium bromide
2.4'-difluoro-
benzophenone
(2-fluorophenyl)- Flutrimazole (4-fluoropheny1)-
phenylchloro- methane
Refewnce(s):
EP 352 352 (J Uriach &Cia.; appl 31.1.1990; prior 28.7.1988)
Formulation(s): cream 1 %
Trade Name(s):
E: Micetal (Uriach)
Flutropium bromide
ATC: R03BB Use: anticholinergic, bronchodilator RN: 635 16-07-4 MF: C,H,,BrFNO, MW: 478.40
LD,,: 53 m g k g (M, i.p.1; 11 m g k g (M, i.v.); 760 mgikg (M, p.0.); 228 mglkg (M, LC.);
77 mglkg (R, i.p.); 12.5 mglkg (R, i.v.); 740 m g k g (R, p.0.); 615 mgikg (R, s.c.)
CN: (endo,syn)-8-(2-fluoroethyl)-3-[(hydroxydiphenylacetyl)oxy]-8-methyl-8-azoniabicyclo[3.2.l]octane
bromide
1 PCI,
H
/ \ 2 N-carbobenzyloxynortropine
-
benzilate (Il)
I N a p J
2 H3C-Br
I1 -b *
nortropine benzilote bromide (N) 1 Flulropium bramide