purification and recovery using porous absorbents: PO8 259 541 Kyorin Seiyaku; appl.. synthesis offluorine-labeled fleroxacin: Livni, E.. CN: 2-[[8-trifluoromethyl-4-quinolinyl]amino]
Trang 1Flecainide F 861
hydrochloride
RN: 3717-88-2 MF: C24H25N04 HCI MW: 427.93 EINECS: 223-066-4
LD,,: 28 mgkg (M, i.v.); 740 mgkg (M, p.0.);
25 mglkg (R, i.v.); 1040 mglkg (R, p.0.)
salicylic propiony! P-propionyloxy-
3-propionyl- salicylic acid (1)
, 1 8 0 - 1 9 0 O C SOC12
CH3
benzoote
benzoic anhydride
0
8-carboxy-3- methylflavone
Reference(s):
U S 2 921 070 (Recordati; 12.1.1960; CH-prior 5.1 1.1957)
8-chloroformyl- 1-(2-hydraxy-
alternative synthesis:
U S 3 350 41 1 (Seceph; 31.10.1967; I-prior 10.10.1963)
Flavaxate
Formulation(s): f c tabl 200 mg; tabl 100 mg (as hydrochloride)
3-methylflovone (11) ethy1)piperidine
Tmde Name(s):
D: Spasuret (Sanofi Winthrop) 1: Cistalgan (Recordat$ J: Bladderon (Nippon
GB: Urispas (Shire) Genurin (Recordati) USA: Urispas (SmithKline
Beecham)
Use: antiarrhythmic RN: 54143-55-4 MF: C17H,F,N,03 MW: 414.35
CN: N-(2-piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide
acetate
RN: 54143-56-5 MF: C17H20F,N203 C2H402 MW: 474.40
Trang 28 6 2 F Fleroxacin
H 0 + F ~ C /s\( o - ~ ~ c - 0 -I
pyridine
Reference(s):
DE 2 5 13 916 (Riker; prior 27.3.1975)
US 3 900 481 (Riker; 19.8.1975; prior 1.4.1974)
US 3 655 728 (Riker; 1 1.4.1972; prior 22.7.1970)
US 4 005 209 (Riker; 25.1.1975; prior 27.5.1975)
Bannit, E.H eta].: J Med Chem (JMCMAR) 18, 1130 (1975); 20, 821 (1977)
Fomiulation(s): amp 50 rng; tabl 50 rng, 100 rng (as acetate)
Trade Name(s):
D: Tarnbocor (3M Medica; GB: Tarnbocor (3M Health J: Tarnbocor (Eisai)
F: FlCcai'ne (3M SantC; 1984) I: Almarytrn (Synthelabo;
1986)
Fleroxacin
( A M 833; R o 23-6240; Megalocin)
ATC: JOlMAO8 Use: antibacterial RN: 79660-72-3 MF: C,,H,,F,N,O, MW: 369.34
LD,,,: 20.4 mglkg (R, i v.]; >4 glkg (R, p 0.);
21.7 rnglkg (M, i v.); >4 glkg (M, p 0.);
> I glkg (dog, p 0.)
CN: 6,8-Difluoro-l-(2-fluoroethyl)-l,4-dihydro-7-(4-rnethyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid
monohydrochloride
RN: 79660-53-0 MF: C,,H,,F,N,O, HCl MW: 405.80
corboxylic acid
6.7.8-trifluoro-l- (2-fluoroethy1)-1.4- dihydro-4-oxoquinoline
Trang 3Floctafenine F 863
Reference(s):
'
a BE 887 574 (Kyorin Pharm.; appl 19.2.198 1; BE-prior 19.8.1980)
1 ZA 8 502 065 (Kyorin Pharm.; appl 20.3 1985; ZA-prior 20.3.1985)
b ES 2 010 862 (Inke S A.; appl 13.2.1989)
purification and recovery using porous absorbents:
PO8 259 541 (Kyorin Seiyaku; appl 23.3.1995)
synthesis offluorine-labeled fleroxacin:
Livni, E et al.: Nucl Med Biol (NMBIEO) 20 (I), 883-897 (1993)
N-rnethyl-
Formulation(s): amp for inj 400 mg; f c tabl 200 mg, 400 mg; tab! 200 mg, 400 mg; v1al400 mg1100 ml
Fleroxocin
Trade Name(s):
D: Quinodis (Rochel
Griinenthal)
piperozine
Use: analgesic RN: 23779-99-9 MF: CmHl,F3N204 MW: 406.36 EINECS: 245-881-4
LD,,: 180 mglkg (M, i.v.); 1960 mglkg (M p.0.):
160 mglkg (R, i.v.); 535 mglkg (R, p.0.);
>1 glkg (dog, p.0.)
CN: 2-[[8-(trifluoromethyl)-4-quinolinyl]amino]benzoic acid 2,3-dihydroxypropyl ester
2-trifluoro- diethyl ethoxy-
methyl- methylenemalonote
Trang 4864 F Flomoxef
3-ethoxycarbonyl-4-
hydroxy-8-trifluoro-
methylquinoline (I)
4-hydroxy-8- trifluoromethyl- auinoline
H O T o O<CH, H3C NaH, toluene
4-chloro-8- methyl
trifuoromethyl- anthronilate
quinoline (11)
' 3 3 Floctatenine
DE 1 815 467 (Roussel-Uclal; appl 18.12.1968; F-prior 29.12.1967,29.3.1968, 23.8.1968)
US 3 644 368 (Roussel-Uclaf; 22.2.1972; F-prior 29.12.1967,23.8.1968)
US 3 818 090 (Roussel-Uclaf; 22.2.1972; prior 7.7.1971)
Trade Name(s):
D: Idarac (Roussel; 1978); F: ldarac (Roussel Diamant; I: Idarac (Roussel; 1977)
Flomoxef
(6315-S)
ATC: J0lC
RN: 99665-00-6 MF: C,,HlRF2N,O7S, MW: 496.47
CN: (6R-ci.~)-7-[[[(difluoromethyl)thio]acetyl]amino]-3-[[[l-(2-hydroxyethyl)-lH-tetrazol-5-yl]thio]methyl]-
7-methoxy-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Trang 5Flomoxef F 865
@ side choin I:
F F ~ s , , - ~ ~F ~S-COOH ~ ~ ~
F
chloro-
difluoro-
methane
ethyl (difluoro- rnethylthio)ocetate
(difluorornethyl- thio)acetic acid (I)
ethanalomine carbon
disufide
methyl N-(2-hydroxy- ethyl)dithiocorbornate (11)
1-(2-hydroxyethy1)-
1H-tetrozole-5-thiol (IV)
8 final product:
NoOCH,, DMF
N
diphenylrnethyl
7a-banzarnido-3-
chlorornethyl-1 -oxo-
3-cepkm-4-corboxylote
(cf latomoxef synthesis)
p-rnethyl-
benzyl
Trang 6866 F Flopropione
hypochlorite PI"?!;
1 PC15, pyridine 1 I, pyridine
2 NaHCO,
VII
CH3
~ s u j i , T et a].: J Antibiot (JANTAJ) 38, 466 (1984)
US 4 532 233 (Shionogi; 30.7.1985; J-prior 23.12.1982)
DOS 3 345 989 (Shionogi; appl 20.12.1983; J-prior 23.12.1982)
EP 128 536 (Shionogi; appl 7.6.1984; J-prior 14.6.1983)
purification:
DOS 3 503 303 (Shionogi; appl 31.1.1985; J-prior 2.2.1984)
Formulation(s): vial (dry substance for inj.) 500 mg, l g
Trade Name(s):
J: Flumarin (Shionogi)
Use: antispasmodic RN: 2295-58-1 MF: C,H,,O, MW: 182.18 EINECS: 218-942-8
LD,,,: 300 mglkg (M, i.v.); 2780 mglkg (M, p.0.);
246 mg/kg (R, i.v.); 2380 mglkg (R, p.0.)
CN: 1 -(2,4,6-trihydroxypheny1)- 1-propanone
Trang 7Florantyrone F 867
phloroglucinol propionitrile Flopropione
Reference(s):
Canter et al.: J Chem Soc (JCSOA9) 1931, 1245
Shinoda, K.: Yakugaku Zasshi (YKKZAJ) 35,235 (1927)
Howells et a].: J Am Chem Soc (JACSAT) 54, 2451 (1932)
pharmacology:
Cahen, R.; Boucherie, A,: C R Seances Soc Biol Ses Fil (CRSBAW) 157, 112 (1963)
Formukztion(s): cps 40 mg; gran 80 mg/g, 160 mg/g
Trade Name(s):
J: Chlonarin (Kanebo) Cospanon (Eisai)
Colenfupan (Nichiiko) Pasmus (Daiichi)
generic
Use: choleretic RN: 519-95-9 MF: C2,H1,O3 MW: 302.33 EINECS: 208-279-2
CN: y-0x0-8-fluoranthenebutanoic acid
succinic fluoronthene
Reference(s):
US 2 560 425 (Miles Labs.; 195 1; prior 1948)
Trade Name(s):
I: Bilyn (Janus); wfm Idroepar (Beolet); wfm USA: Zanchol (Searle); wfm Cistoplex (Borromeo); wfm J: Zanchol (G.D.-Dainippon)
Use: coronary vasodilator RN: 53731-36-5 MF: Cl,H2,N0, MW: 295.38
CN: 4-[2-(3,5-diethoxyphenoxy)ethyl]morpholine
Trang 88 6 8 F Flosequinan
Reference (s):
DOS 2 020 464 (Orsymonde; appl 27.4.1970; GB-prior 29.4.1969)
Fnrmulation(s): cps 200 mg
Trude Name(s):
F: Carfonal (Lafon); wfm
Flosequinan
ATC: COlDBOl Use: vasodilator, antihypertensive
RN: 76568-02-0 MF: CllH,oFN02S MW: 239.27
CN: 7-Fluoro- 1 -methyl-3-(methylsulfiny1)-4(1H)-quinolinone
COOH
2-chloro-4-fluoro
benzoic ocid
4-fluoro-N- methylonthranilic ocid
7-fluoro-1 -methyl- trirnethyl-
3.1 -benzoxozine- sulfoxonium
trimethyl
dirnethyloxosulfonium 4-fluoro-2-(methylomino)- benzaylmethylide (11)
Trang 9Fluanisone F 869
111
0 - Fq3,cH3 0 0 -
dirnsyl sodium 1 -[4-fluoro-2-
(methylomina)phenyl]- 2-(methylsulfinyl)- ethanone
"Q"" +
3-fluoro-
aniline
phxO-ph
diphenyl
ether
Reference (s):
methyl (methylthi0)-
acetate
methyl 3-(3-fluoro-
aniline)-2-(methylthb-
acrylate (IV)
?\
1 H3C, ,S/O'CH~
0 \b
2 MCPBA CHZCIZ
1 dimethyl sulfate
0 2 3-chloroperbenzoic
acid
a DE 3 011 994 (Boots; appl 27.3.1980; GB-prior 27.3.1979)
b,cBirch, A.M et al.: J Chem Soc., Perkin Trans 1 (JCPRB4) 1994, 387
EP317 149 (Boots; appl 7.1 1.1988; GB-prior 18.11.1987)
Formulation(s): tabl 50 mg, 100 mg
Trade Name(s):
GB: Manoplax (Boots)
Use: neuroleptic RN: 1480-19-9 MF: C2,H2,FN202 MW: 356.44 EINECS: 216-038-8
LDg: 25 mgikg (M, i.v.); 550 mglkg (M, p.0.);
20 mgkg (R i.v.)
CN: l-(4-fluorophenyl)-4-[4-(2-methoxyphenyl)-l-piperazinyl]-l-butanone
I -(2-rnethoxy- 4-chloro-4'-fluoro- Fluonisone
Trang 10870 F Fluazacort
Reference(s):
DAS 1 185 6 15 (Janssen; appl 25.3.1960; USA-prior 26.3.1959)
US 2 997 472 (Janssen; 22.8.1961; prior 26.3.1959)
Trade Name(s):
D: Sedalande (Delalande); F: Saalande (Delalande);
Fluazacort
(Azacortid)
ATC: D07AB Use: topical glucocorticoid, anti- inflammatory
RN: 19888-56-3 MF: C,sH,oFNO, MW: 459.51 EINECS: 243-400-2
LD,,,: 54 m g k g (M, s.c.);
580 rnglkg (R, s.c.)
CN: (1 1~,16~)-21-(acetyloxy)-9-fluoro-11-hydroxy-2'-methyl-5'H-pregna-1,4-dieno[l7,16-d]oxazole-3,20-
dione
3p-ocetoxy-11.20-
dioxo- 16-pregnene
(from hecogenin
cf olfoxolone
synthesis)
pyridine
-+ I
1 NoBH,
2 HCI, CHJOH
CH3S02CI,
, ,, MXN+'HJ collidine