SmithKline Beecham Fastjekt Allergopharma Suprarenin Hoechst numerous combination preparations F: Anahelp Stallergknes Anakit Dome-Hollister- S tier DyspnC-Inhal Augot Eppy 1 % Allergan
Trang 1Epinastine hydrochloride E 75 1
Formulation(s): tabl 5 mg
Trade Name(s):
D: Stimovul (Organon); wfm I: Stimovul (Organon Italia) J: Stimovul (Ravasm)
!
,t Epinastine hydrochloride
VAL-801CL)
ATC: R06AX24 Use: antihistaminic
RN: 108929-04-0 MF: CI,H1,N, HCl MW: 285.78
, LD,,,: 17 mgkg (R, I.v.); 192 mglkg (R, p.0.)
CN: 9,13b-dihydro-1 H-d1benz[c~imidazo[1,5-a]azep1n-3-amine monohydrochlor~de
epinastine
RN: 80012-43-7 MF: C,,H,SN, MW: 249.32
1 ethanol THF
2 NaOH
3 HCI
+ Br-CN b
-6-ominomethyl- cyonogen Epinostine hydrochloride
6,ll-dihydro-5H- bromide
dibenz[b,e]azepine (11)
2 N-methyl-
benzylamine
OMF HCI
- I Epina3tine hydrochloride I
Epinostine
Trang 2752 E Epinephrine
Reference (s):
a DE 3 008 944 (Bochringer Ing.; appl 5.3.1981; D-prior 8.3.1980)
starting material:
Hunziker, E et al.: Helv Chim Acta (HCACAV) 49/11, 1433 (1966); 5011, 245 (1967)
b EP 496 306 (Boehringer Ing.; appl 18.1 l992; D-prior 2.5.1.1991)
composition with PAF-antagonists:
WO 8 910 143 (Schering Corp.; appl 24.4.1989; USA-prior 27.4.1988)
Formulation(sJ: tabl 10 mg, 20 mg
Trade Name(s):
J : Alesion (Nippon
Boehringer Ing./Sakyo)
Epinephrine
(Adrenaline)
ATC: AOIADO 1; B02BC09; C01CA24; R03AAO1; SOlEAOl
Use: sympathomimetic, vasoconstrictor RN: 51-43-4 MF: C,H,,NO, MW: 183.21 EINECS: 200-098-7
LD,,,: 217 p g k g (M, i.v.);
I50 pgfkg (R, i.v.);
100 @kg (dog, i.v.)
CN: (R)-4-[I-hydroxy-2-(methylamino)ethyl]-1,2-benzenedi0l
hydrochloride
RN: 55-3 1-2 MF: C,H,,NO, HCl MW: 219.67 EINECS: 200-230-3
LD,,,: 140 wg/kg (M, i.v.);
24 m g k g (R, p.0.)
tartrate (1:l)
RN: 51-42-3 MF: C,HI,NO, C,H,O, MW: 333.29 EINECS: 200-097-1
LD,o: 1780 pglkg (M, i.v.); 4 m g k g (M, p.0.);
82 pg/kg (R, i.v.)
2-chloro-3',4'- methylamine 7.4'-dihydroxy- DL-epinephrine (I)
dihydroxy- 2-methylomino-
acetaphenone acetophenone
(+)-tartaric acid
I _ _ _ _ _ ,
H
CH3
Trang 3Epirizole E 753
Reference(s):
DRP 152 814 (Hoechst; 1903)
DRP 157 300 (Hoechst; 1903)
DRP 222 451 (Hoechst; 1908)
lbllar, B.F.: J Am Chem Soc (JACSAT) 70, 2067 (1948)
Formulation(s): amp 0.05 m d 1 0 ml, 1 mgfml, 2.05 md2.05 ml (as hydrochloride); eye drops 2 mglml, 5 mg/
ml; eye ointment 1 mglg (as tartrate)
Trade Name(s):
D: Adrenalin 1:1000
JENAPHARMA
(Jenapharm)
Adrenalin Medihalcr
(Kettelhack-Riker)
Anaphylaxie-Besteck
Losung Z.J (SmithKline
Beecham)
Fastjekt (Allergopharma)
Suprarenin (Hoechst)
numerous combination
preparations
F: Anahelp (Stallergknes)
Anakit (Dome-Hollister-
S tier)
DyspnC-Inhal (Augot) Eppy 1 % (Allergan France)
Glaucadrine (Merck Sharp
& Dohme-Chibret)-comb
numerous combination preparations and generics GB: Accusite (Matrix)-comb
Epipen (ALK) Eppy (Chauvin) Simplene (Chauvin) combination preparations I: Adrenal (Lifepharma) Adrenalina Ism (Nuovo ISM)
Eppy (Merck Sharp & Dohme)
Rinantipiol (Antipio1)- comb
Xylocaina (Astra-Simes) Xylonor (0gna)-comb J: Vaponefrin (Tokyo M.I.) USA: Epi E-Z Pen (Dey) EpiPen (Dey) Sensorcaine with Epinephrine (Astra)-comb Sus-Phrine (Forest) Xylocaine with Epinephrine (Astra)-comb
Epirizole
(Mepirizole)
ATC: MO1 A; N02B; SOlB Use: analgesic, anti-inflammatory RN: 18694-40-1 MF: C l I H , 4 N 4 0 2 MW: 234.26 EINECS: 242-507-1
LD,,: 550 m g k g (M, i.v.); 740 m g k g (M, p.0.);
214 mglkg (R, i.v.); 445 mglkg (R, p.0.)
CN: 4-methoxy-2-(5-methoxy-3-methyl-lH-pyrazol-l-yl)-6-methylpyrimidine
hydmzine
CH3
hydrote 6-methyl- 2,4-dichloro- 2-chloro-4-
uracil 6-methyl- methoxy-6-
pyrimidine rnethylpyrim~dine
dimethyl sulfote
2-hydrazina-4- diketene Epirizole
methoxy-2-me-
thylpyrimidine (I)
Referencels):
FR-M 6 793 (Daiichi Seiyaku; appl 31.8.1967)
DAS 2237 632 (Daiichi Seiyaku; appl 31.7.1972; J-prior 31.7.1971, 5.8.1971)
Trang 4754 E Epirubicin
intermediates:
Vanderhaeghe, H ; Claesen, M.: Bull Soc Chim Belg (BSCBAG) 68, 30 (1959)
Formulation(s): tabl 50 mg, 100 mg
Trade N a m ( s ) :
Epirubicin
(Pidorubicin; 4'-epi-Adriamycin)
ATC: LOlDB03 Use: antineoplastic
RN: 56420-45-2 MF: C2,H2,N0,, MW: 543.53
LD,,,: 16.07 mglkg (M, i.v.);
14.27 mglkg (R, i.v.);
2 mgkg (dog, iv.)
CN: (8S-cis)-l0-[(3-amino-2,3,6-trideo~y-a-~-alnbino-hexopyranosyl)oxy]-7,8,9,1O-tetrahydro-6,8,11- trihydroxy-8-(hydroxyacety1)- I methoxy-5,12-naphthacenedione
hydrochloride
RN: 56390-09-1 MF: C2,H,,N0,, HCI MW: 579.99
F C 0 CF3
0 rutheniurn(N) K
0
methyl 2,3,6-tri- trilluoroocetic oxide (11)
deoxy-3-amino- onhydride (I)
pyranoside
I1
sodium
HN CF3
0
2.3,6-trideoxy-3-trifluoro-
acetamida-4-0-trifluoro-
acetyl-a-L-arabino- hexopyranosyl chloride ( N )
Trang 5Epitiostanol E 755
odriomycinone 2,Z-dimethoxy-
propane
I Epirubicin
1 HgO HgBr2
2 NaOH
Reference(s):
Arcamone, F et al.: J Med Chem (JMCMAR) 18,703 ( 1 975)
DOS 2 510 866 (Farmitalia; appl 20.3.1975; GB-prior 22.3.1974)
HO
CH3
US 4 058 519 (Farmitalia; 15.1-1.1977; appl 19.3.1975; GB-prior 22.3.1974)
alternative synthesis:
DOS 2 618 822 (Farmitalia; appl 29.4.1976; GB-prior 30.4.1975)
purijication:
Formulation(s): vial 10 mg, 20 mg, 50 mg (as hydrochloride)
Trade Name(s):
D: Farmo~blcin (Pharmacia GB: Pharmarubicin (Pharmacia J: Farmorubicin (Farmitalia)
& Upjohn; 1984) & Upjohn; 1985)
F: Farmorublcine (Pharmacia I: Farmorubicina (Farmitalia;
Epitiostanol
(Epithioandrostanol; Epithiostanol)
ATC: G03B; L02BA Use: antiestrogen, antineoplastic RN: 2363-58-8 MF: C19H,oOS MW: 306.51
LD,,: 1160 mgkg (M, i.p.)
CN: (2a,3a,5a,l7P)-2,3-epithioandrostan-17-01
R H3C-S-CI ,
0
+ HSCN
HO
chloride
H
178-ocetoxy-2.3-epoxy- thiocyonic
Sa-ondrostone acid
Trang 6756 E Epitizide
Reference(s):
GB 977 599 (Shionogi; valid from 19.12.1962; J-prior l9.12.I96l)
NL 6 400 226 (Shionogi; appl 15.1.1 964)
Takeda, K et al.: Tetrahedron (TETRAB) 21,329 ( I 965)
Formulation(s): vial 10 mg
Trade Namefs):
J : Thiodrol (Shionogi)
Epitizide
(Epithiazide)
ATC: C021, Use: antihypertensive, diuretic
RN: 1764-85-8 MF: C,oH,,CIF,N,O,S, MW: 425.86 EINECS: 217- 18 1-9
CN: 6-chloro-3,4-dihydro-3-[[(2,2,2-trifluoroethyl)thio]methyl]-2H-l,2,4-benzothiadiazinc-7-sulfonamide
mercaptoocet- 2,2,2-tri-
oldehyde fluoroethyl
dirnethyl iodide
ocetol
1.2-dimethoxyethone, HCI
CI
5-chloro-2.4-di-
ominosulfonyl-
aniline
(cf chlorothiozide
synthesis)
(2.2.2-trifluoroethyl- thio)ocetoldehyde dirnethyl ocetol (I)
Epitizide
US 3 009 911 (Pfizer; 21.11.1961; prior 3.6.1960, 14.9.1960,4.1.1961)
Trade Name(s):
GB: Thiavcr (Riker); wfm
Trang 7Epoprostenol E 757
Epoprostenol
(PGI,; Prostacyclin)
ATC: BOlAC09 Use: anticoagulant, platelet aggregation inhibitor
RN: 35121-78-9 MF: C,H,,Os MW: 352.47
CN: (5Z,9a,l la,13E,15S)-6,9-epoxy-11,15-dihydroxy-prosta-5,13-dien-l-oic acid
RN: 61849-14-7 MF: C,H,,NaO, MW: 374.45 EINECS: 263-273-7
prostoglandin F2,, 11.1 5-bis-
(tetrahydropyran-2-yI) ether
(cf dinoprost synthesis)
1 CH3COOH
2 KOC(CH,),
2 potassium
tert-butylote
1 Epoprostenol
I ,7 '
OH 2 sodium ethylate
I -
prostaglandin F2,
methyl ester
Epoprostenal sodium
Reference(s):
Corey, E.J et al.: J Am Chem Soc (JACSAT) 99, 2006 (1976)
Nicolaou, K.C et al.: Lancet (LANCAO) 1977, 1058
review:
The Merck Index, 12th Ed., 1352 (Rahway 1996)
Formulation(s): vial (lyo.) 0.5 mg (as sodium salt)
Trade Narne(s):
G B : Flolan (Glaxo Wellcome) USA: Flolan (Glaxo Wellcome;
as sodium salt)
Trang 8758 E Eprazinone
Use: antitussive RN: 10402-90-1 MF: C2,H3,N20, MW: 380.53 EINECS: 233-873-3
LD,,,: 1 l 1 mglkg (M, i.p.); 246 mglkg (M, s.c.)
CN: 3-[4-(2-ethoxy-2-phenylethyl)-1-piperazinyl]-2-methyl-I-phenyl-l-propanone
dihydrochloride
RN: 10402-53-6 MF: C,,H3,N202 2HCl MW: 453.45 EINECS: 233-872-8
LD,,,: 20 mgikg (M, i.v.); 286 mglkg (M, p.0.);
763 mglkg (R, p.0.)
Br-O-C(CH,)3
+
aldehyde
Reference(s):
DAS 1 695 43 1 (Mauvernay; appl 9.6.1967; GB-prior 27.6.1966)
JP-appl 540 22-379 (Asahi; appl 21.7.1977)
JP-appl 540 22-380 (Asahi; appl 21.7.1977)
JP-appl 540 22-381 (Asahi; appl 21.7.1977)
JP-appl 540 22-382 (Asahi; appl 21.7.1977)
Formulation(s): tabl 5 mg, 20 mg, 50 mg; cps 100 mg; suppos 50 mg, 100 mg (as dihydrochloride)
Trade Namefs):
D: Eftapan (Merckle) I: Mucitux (Recordati); wfm
F: Mucitux (Riom) J: Resplen (Chugai)
Eprosartan
ATC: C09CA02 Use: antihypertensive, angiotensin 11
antagonist RN: 133040-01-4 MF: C,3H,4N,0,S MW: 424.52
CN: (E)-a-[[2-Butyl-1-[(4-carboxyphe11yl)methyl]-1H-imidazol-5-yl]methylene]-2-thiophenepropanoic acid
rnesylate
RN: 144143-96-4 MF: C,3H,4N,04S CH40,S MW: 520.63
Trang 9Eprosartan E 759
imidazole triethyl orthoformate 1 -diethaxymethyl
imidozole (I)
1 12 No2C03 dioxone, H20
2 benzyl chloromethyl ether
butyl iodide 2-butyl-
imidozole
N-methyl-
~ - ( ~ - p ~ r i d ~ l ) - forrnomide
1 HCI (deprotection)
O C H 2 K2C03 DMF
methyl (4-bromo-
rnethy1)benzoote (N)
methyl 4-[(2-butyl-5- formyl-4-iodoimidozol-
1 -yl)methyl]benzoote (V)
"c\$
1 , LOA, THF
Hz, Pd-C
CH,OH
I
1 methyl 3-(2-thienyl)propionate (VII)
methyl 4-[(2-butyl-
5-formyl-lH-imidozol-
1-yl)methyl]benzoote (VI)
0 2 NoOH ethanol, H,O
Trang 10760 E Eprosartan
2-butyl-4-chloro
imidozole-5-
corboxoldehyde
methyl 4-[(Z-butyl-4- chloro-5-formylimidozol-
1 -yl)methyl]benzoote (M)
Hz, Pd-C piperidine/pyridine
monomethyl 2-(24hienylmethyl)- molonote (X)
KOH, ethonol
,
1 liq NH3
Eprosorton
I
1.3-dihydroxy-
acetone
pentonomidine 5-(ocetoxymethyl)-
1 -ocetyl-2-butyl- imidazole (XII)
(CH3
H C N CH
3 Y Y 3 (CF,CO),O CH3CH3 XI1 +
HO trifluoroocetic
anhydride, DlPEA
methyl 4-(hydroxy- methyl 4-[[5-acetoxymethy1)-
methy1)benzoate Z-butylimidazol-1 -yl]methyl]-
benzoate (XI11)