medical use for treatment of breast cancer: WO 9 010 462 Endorecherche; appl.. medical useJur treatment of prostate hyperplasia: DOS 3 339 295 Schering AG; appl... 0.05 % Trade Names:
Trang 1Formebolone 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 M e
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)
Trang 2932 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)
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-
Trang 3Formoterol F 933
trichloro- phosphorus DMF
ethylene oxychloride
CHO
Formocortol
Reference(s):
U S 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);
GB: Deflamene (Carlo Erba); I: Formoftil (Farmigea)
wfm
Formomicin (Farmigea) comb with gentamycin
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
GBr (I)-A-benifl-N-[I-methyl- '
02N CH3 bromine 0 2 N
Trang 49 3 4 F Formoterol
NoBH4
borohydride
formic acid
Reference(s):
U S 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)
E 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)
Trang 5Foscarnet sodium F 935
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
C H 3
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):
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
Trang 6936 F Fosfomycin
1 POCI3, pyridine
2 H20
b
1 phosphorus
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
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 g k g (M, p.0.);
>7 g k g (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)
Trang 7Fosinopril 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
Trang 8938 F Fosinopril
I CuBr, HsCACHs ' Et20,
b
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 4 N NaOH
2 - 1 0 OC 2-CI OH
CrO, HzSO,
I
2 b e z y c h a r o f o r a t (Ni
N-benzyloxy- carbonyl-4-0x0- L-praline (Vl)
CFsCOOH, CH2CI,
Li, liq NH,
NH,CI Hz PtO HCI C H OH
Trang 9b - x
/ \
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
Flucidine (Boehringer Ing.; GB: Staril (Bristol-Myers Tensogard (Bristol It Sud)
Trang 10940 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
phenytoin
silver dibenzyl
phosphate
1 benzene
Fosphenytoin sodium
I
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)
Use: antineoplastic, alkylating nitrosourea derivative
RN: 921 18-27-9 MF: CyH1yCIN305P MW: 3 15.69
LD,,: 6 0 m g k g (M, i.p.)
CN: [l-[[[(2-chloroethyl)nitrosoamino]carbonyl]amino]ethyl]phosphonic acid diethyl ester
ocetylphosphonic acetylphosphonic acid a-orninoethylphosphonic