Pharmaceutical Substances Syntheses, Patents, Applications - Part 78 potx

Erythromycin ethylsuccinate
E
77
1
CH3
erythromycin propionyl
chloride
CH3
erythromycin
monopropionate
(I)
I
CH,
loury1 sulfate Erythromycin estolate
Reference(s):
US
3 000 874 (Eli Lilly; 19.9.1961; prior. 8.4.1959).
DE 1 114 499 (Eli Lilly; 27.6.1959).
Formulation(s):
-
cleavable tabl. 125 mg, 250 mg; cps. 250 mg; susp. 125 mg15 rnl, 250 mg15 ml; syrup 250 mg
(base equivalent)
Trade Name(s):
D: Infectomycin Togiren (Schwarzhaupt);
I:
Ilosone (Lilly)
(Infectopharrn)
wfrn
Marocid (Lifepharrna)
Neo-Eryclnurn (Schering);
F: Propiocine (Roussel); wfm Stellamicina (Pierrel)

wfm
Rubitracine (Takeda).
J:
Ilosone (Shionogi)
Sanasepton (Pharbita)
comb.; wfrn USA: Ilosone (Dista)
GB:
Ilosone (Lilly)
Erythromycin ethylsuccinate
ATC:
D
10AF02; D10AF52;
JO1
FA01
;
SOlAA17
Use: antibiotic
RN:
1264-62-6 MF:
C,,H7SN0,,
MW: 862.06 EINECS: 2 15-033-8
LD,,,:
>10
gkg
(M,
p.0.)
CN:
erythromycin 2'-(ethyl butanedioate)
772
E

Erythromycin gluceptate
No2C0,
ocetone
___,
erythromycin ethyl succinyl
chloride
Reference(s):
DE
1
121 056 (Abbott; appl. 1957; USA-prior. 1956).
chewing tablets:
DOS 2 758 942 (Abbott; appl. 30.12.1977).
Erythromycin ethylsuccinote
Formulation(s):
f. c. tabl. 400 mg; powder 1 gl4.5 g; susp. 125 mg15 ml; syrup 100 mg15 ml, 200 mg/5 ml,
400
mg15 ml, 600 mg15 ml (base equivalent)
Trade Narne(s):
D: Dura Erythromycin 1000
Granulat (durachemie)
Durapaediat (durachemie) GB:
Erythrocin
Granulat/-
Ampullen (Abbott)
Erythromycin-ratiopharm
(ratiopharm)
I:
Monomycin (Griinenthal)
Paediathrocin (Abbott)
combination preparations

F: Abboticine (Abbott)
Ery 125 e 250
(Bouchara)
Erycocci (Pharmafarm)
Erythrocine (Abbott)
Erythrogram (Pharma
2000)
Arpimycin (Rozemont)
Erymin (Elan)
Erythrocin I. M. (Abbott)
Erythroped A (Abbott)
Eritrocina (Abbott)
Eritroger
bustine (Isnardi);
wfm
Neobalsamocetina sosp.
(Alfa Farm.)-comb.; wfm
Proterytrin (Proter); wfm
Proterytrin cps e
i.m.
(Proter); wfm
Rossomicina sosp.
(Pierrel); wfm
Eryromycen (Kissei)
Ery throcin (Abbott-
Dainippon)
Erythro ES
(Sankyo)
Erythromycin ES (Taito
Pfizer)

Esinol (Toyama)
Evesin (Torii)
USA: E.E.S. (Abbott)
Eryped (Abbott)
Eryzole (Alra)
Pediazole (Ross)
Erythromycin gluceptate
(Erythromycin glucoheptonate)
ATC: JOIFAOI; SOlAA17
Use: antibiotic
RN:
23067- 13-2 MF: C,,H,,NO,,
.
C7H,,08 MW: 960.12 EINECS: 245-407-6
LD,,,: 453 mglkg (M, i.v.);
288 mglkg (R, i.v.)
CN:
D-glycero-D-gulo-heptonic
acid compd. with erythromycin (1:l)
Erythromycin
lactobionate
E
773
erythromycin
COOH
CH3
Erythromycin gluceptote
Reference(s):
US
2

852 429 (Lilly; 1958; appl. 1953).
DE
941 640 (Lilly
;
appl. 1954; USA-prior. 1953).
Formulation(s):
vial 1 g (base equivalent)
Trade Name(s):
D:
Erycinum Trockensubstanz USA: Ilotycin gluceptate (Dista)
(Schering);
wfm
Erythromycin lactobionate
ATC: JOlFAO1; SOlAA17
Use: antibiotic
RN:
3847-29-8 MF:
C37H67N013
.
C,2H22012
MW:
1092.23
EINECS:
223-348-7
LD,,:
735 mglkg (M, i.p.1
CN:
4-O-P-D-galactopyranosyl-D-gluconic
acid compd. with erythromycin (1:l)
COOH

erythromycin lactobionic acid
774
E
Erythromycin monopropionate mercaptosuccinate
COOH
Erythromycin loctobionote
Rej'ers~lce(s):
US
2 761 859 (Abbott; 1956; appl. 1953).
Fonnulntion(s):
vial 500
mg,
1000
mg
(base equivalent)
Trade
Narne(s):
D: Erythrocin
I.V.
(Abbott) I: Eritro (Forrnulario Naz.)
GB:
Erythrocin
I.V.
J:
Erythromycin (Santen)
Lactobionate (Abbott); USA: Erythrocin Lactobionate-
w fm
I.V.
(Abbott); wfrn
Erythromycin monopropionate

ATC:
JO~FA
mercaptosuccinate
Use: macrolide antibiotic
(RV-
I I
)
RN: 84252-06-2
MF:
C,oH,INO,,
.
C,H,O,S MW: 940.16
LD,,,: >3000 mglkg (M, p.0.)
CN:
erythromycin-2'-propanoate ~nercaptobutanedioate (I :I)
erythromycin Erythromycin monopropionate
mercaptosuccinate
EP 57 489 (Pierrel; appl. 2.1.1982; F-prior. 2.2. I98 I).
EP 174 395 (Pierrel; appl. 2.1.1982; F-prior. 2.2.1982).
US
4 476 120 (Refarmed; 10.9.1984; appl. 2.2.1982; I-prior: 2.2.1 98 1).
Fonnulation(s):
gran. 200 mg; tabl. 500 rng
F
Erythromycin stearate
E
775
Trade Name(s):
I:
Zalig (Pierrel; 1989)

Erythromycin stearate
ATC. ~07CC02
Use: antib~otic
RN: 97327-17-8 MF: C,,H,,,NO,, MW. 1000.41
LD5,: 31 12 mg/kg
(M,
pa)
CN: erythromycin 2'-octadecanoate
CH3
erythromycin
0
0
stearoyl chloride
CH3
Erythromycin stearate
Reference(s):
US
2 862 921 (Upjohn; 1958; appl. 1953).
Formulation(s):
f.
c. tabl. 250 mg, 500 mg
Trade Name(s):
Erythromycin steorote
I
D: Dura Erythromycin Emestid 500 (Abbott); wfm
J:
Erythrocin (Abbott-
(durachemie)
GB:
Erythrocin (Abbott) Dainippon)

Erythrocin Filmtabletten
I:
Eritrocina Cpr (Abbott) USA: Erythrocin Stearate
(Abbott) Lauromicina (Lafare) (Abbott)
F:
Abboticine (Abbott); wfm generic
776
E
Escin
Escin
(Aescin)
ATC: COSCX; C05CX01
Use: anti-inflammatory (inhibition of
edema formation and decrease of
vesscl fragility), vein therapeutic
RN: 6805-41-0 MF:
C,,H,,O,, MW: 1101.24 EINECS: 229-880-6
LD,,,: 6.7 mglkg
(M,
i.p.);
2
mgkg
(M,
i.v.); 165 mglkg (M, p.0.); 38.59
mglkg
(M, s.c.);
10.15 mglkg (R,i.p.); 16OOglkg (R,i.v.); 833 mglkg
(R,
p.0.): 150mg/kg(R, s.c.)
CN: 3,s-epoxypicene escin deriv.

sodium
salt
RN: 20977-05-3
MF:
unspecified MW: unspecified EINECS: 244-133-4
LD,,,: 8299 pglkg (M, i.p.); 4730 mgkg (M, i.v.); 134 mgkg (M, p.0.); 92.53 mglkg (M, s.c.);
91 80 pglkg (R, i.p.); 8131 pglkg
(R,
i.v.); 400 mglkg (R, p.0.); 131 mglkg (R, s.c.);
91 30 ~glkg (g. p., i.v.);
5 mglkg (rabbit, i.v.)
0
CH,
K
0
Escin
Extraction of
Aesculus hippocustunurn
L. (horse-chestnut) and purification on cation-exchanger (H+-form), resp.
precipitation with cholesterol.
Reference(s):
extraction and puri,fication:
DE 916 664 (Riedel-de Haen; appl. 1952).
DE 950 027 (Klinge; appl. 195 1).
DAS
1
034 816 (VEB Arzneimittelwerk Dresden; appl. 1955).
DAS 1 045 597 (Dr.
W.
Schwabe; appl. 1953).

GB 820 787 (Klinge; appl. 1956).
GB 820 788 (Klinge; appl. 1956).
DE
1
058 208 (Klinge; appl. 1953).
DAS 1 095 989 (Madaus; appl. 11.3.1959).
US 3 163 636 (Klinge; 29.12.1964; D-prior.
14.6.1960).
DAS
1
182 385 (Chem. Fabrik Tempelhof; appl. 29.1.1962).
US 3 238 190 (Madaus; 1.3.1966; prior. 31.1.1961, 23.10.1963).
DOS 1617 570
(J.
Klosa; appl. 13.4.1967).
DOS
1
617 581 (Knoll; appl. 11.8.1967).
DAS 1617 413 (Klinge; appl. 31.8.1967).
DE 1 667 884 (Knoll; appl. 20.1.1968).
DOS 1 902 608 (Nattermann; appl. 20.1.1969; A-prior. 31.5.1968).
DOS 2 339 760 (Klinge; appl. 6.8.1973).
DAS 2 733 204 (LEK; appl. 22.7.1977; YU-prior. 12.8.1976).
7
Esmolol
E
777
"water soluble" (X-ray amorphous)
escin:
DE 1 282 852 (Madaus; appl. 14.12.1962).

DOS 1 902 609 (Nattermann; appl. 20.1.1969).
DOS 2
257 755 (LEK; appl. 24.11.1972; YU-prior. 6.12.1971).
GB
1
550 845 (Madaus; appl. 7.7.1976; D-prior. 11.7.1975).
separation of
a-
and
p-escin:
DAS 1 125 117 (Klinge; appl. 14.6.1960).
US 3 110 71
1
(Klinge; 12.1 1.1963; D-prior. 14.6.1960).
conversion of
p-
into
a-escin:
US
3
450 691 (Klinge; 17.6.1969; appl. 7.6.1967).
Formulation(s):
amp.
5
mg (as sodium salt); cps. 2 mg; drg. 10 mg, 15 mg, 20 mg; gel 1 gI100 g-comb.; s. r.
drg. 40 mg
Trade Narne(s):
D: Essaven (Nattermann)
comb.
Galleb forte

(Hoyer)-comb.
Heweven (Hevert)-comb.
Opino, Gel (Troponwerke)-
comb.
Opino retard
(Troponwerke)-comb.
Opino spezial
(Troponwerke)-comb.
Pe-Ce Ven (Terra-Bio-
Chemie)-comb.
Proveno (Madam)-comb.
Reparil (Madaus)
Revicain (Wiedemann)-
comb.
Veno Kattwiga (Kattwiga)-
comb.
Venoplant (Schwabe)-
comb.
Venostasin
(K1inge)-comb.
F: Flogencyl (Parke Davis)
Reparil (Madaus)
numerous combination
preparations
I:
Bres (Farmacologico
J:
Milanese)-comb.
Dermocinetic (1rbi)-comb.
Essaven (Nattermann)-

comb.
Etascin (Rorer)-comb.
Opino (Bayropharm)-
comb.
Premium (SIT)-comb.
Rectoreparil (IB1)-comb.
Reparil (1BI)-comb.
Somatoline (Manetti
Roberts)-comb.
Tioscina (Inverni della
Beffa)-comb.
Tochief (Ohta)
Tochikinon (Toho)
Yochimin (Choseido-
Seiyaku)
Esmolol
ATC: C07AB09
Use: anti-arrhythmic, P-adrenoceptor
antagonist, perioperative prophylactic
use in supraventricular tachycardia
RN: 81147-92-4 MF: C,,H,,NO, MW: 295.38
CN:
(f)-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]benzenepropanoic
acid methyl ester
hydrochIoride
RN: 81 161-17-3 MF: C,,H,sNO,. HCl MW: 331.84
LD,,:
93 mgkg (M, i.v.);
71 mgkg (R, i.v.);
32 mgkg (dog, i.v.)

methyl 3-(4-hydroxy- epichloro-
pheny1)propionote hydrin
methyl
3-[4-(2.3-epoxy-
propoxy)phenyl]propionate
(I)
778
E
Estazolam
Reference(s):
EP 41 491 (Hassle; appl. 27.5.1981
;
S-prior. 2.6.1980).
EP 53 435 (American Hospital Supply; appl. 29.10.1981; USA-prior. 28.1 1.1980).
Erhardt, P.W. et al.: J. Med. Chem. (JMCMAR)
25,
1408 (1982).
US 4 387 103 (American Hospital Supply; 7.6.1983; prior. 28.1 1.1980).
H C
NH2
1
+
3'7'
+
CH3
isopropylornine
injectable,formulation:
US 4 857 552 (Du Pont; 15.8.1989; prior. 8.6.1988).
US 4 593 119 (American Hospital Supply; 3.6.1986; prior. 28.1 1.1980).
OH

H~C~#,.)-,,O
CH3
Esrnolol
alternative synthesis:
ES 549 138 (Sune Coma; appl. 21.1 1.1985).
Formulation(s):
amp. 2.5 g110 ml; vial 100 mg/lO ml (as hydrochloride)
Trade Name(s):
D: Brevibloc (Baxter)
F:
Brevibloc (Isotec; 1989) USA: .Brevibloc (Ohmeda; 1987)
Estazolam
ATC: N05CD04
Use: hypnotic, sedative, tranquilizer
RN: 29975-16-4 MF:
C,,Hl1ClN4 MW: 294.75 EINECS: 249-982-4
LD,,,: 600 mglkg (M, p.0.);
2500 mglkg (R, p.0.)
CN:
8-chloro-6-phenyl-4H-[1,2,4]tnazolo[4,3-a][l,4]benzodiazepine
2-omino-5-chloro- ominooceto-
benzophenone
(I)
nitrile
formic
I
Estazo~am
I
acid
(Ill)

Estradiol
E
779
pyridine
I
+
H,N+O'-'~~~ OHCI
,
0
glycine ethyl ester
hydrochloride
d
phosphorus(V)
sulfide
hydro-lH-l.4-
benzodiozepine
Estozolam
1
US
3
701 782 (Upjohn;
3
1.10.1972; prior. 10.2.1972).
Hester,
J.B.
eta].:
J.
Med.
Chern. (JMCMAR)
14,

1078 (1971).
US
4
116 956 (Takeda; 26.9.1978; J-prior. 5.1 1.1968, 17.12.1968,25.12.1968, 13.2.1968).
DOS 1 955 349 (Takeda; appl. 4.1 1.1969; J-prior. 5.1 1.1968).
DOS 1 965 894 (Takeda; appl. 4.1 1.1969; J-prior. 5.1 1.1968, 17.12.1968,
25.12.1968, 13.2.1969).
DOS
2
012 190 (Upjohn; appl. 14.3.1970; USA-prior. 17.3.1969).
US
3
987 052 (Upjohn; 19.10.1976; prior. 17.3.1969, 29.10.1969).
DOS
2
114 441 (Takeda; appl. 25.3.1971; J-prior. 27.3.1970, 23.4.1970,28.5.1970).
US
4
102 881 (Takeda; 25.7.1978; J-prior. 27.3.1970, 23.4.1970,28.5.1970).
DOS 2 302 525 (Upjohn; appl. 19.1.1973; USA-prior. 31.1.1972).
review:
Schulte,
E.:
Dtsch. Apoth. Ztg. (DAZEA2)
115,
1253, 1828 (1975).
Formulation(s):
tabl. 1 rng,
2
mg

Trade Narnefs):
F:
Nuctalon (Cassenne; 1978)
I:
Esilgan (Cyanamid; 1983); J: Eurodin (Takeda; 1975)
wfm
USA: ProSom (Ahbott)
Estradiol
(Oestradiol)
ATC: G03CA03
Usc: estrogen
RN:
50-28-2 MF:
CL8H2,02
MW: 272.39
EINECS:
200-023-8
CN:
(17P)-estra-1,3,5(10)-triene-3.17-dial
estrons Estradiol
780
E
Estradiol
w
1.
H,,
Pt
1.
H,.
Raney-Ni

2.
benroyl chloride
2.
KOH.
CH,OH
3.
Cr0,.
CH,COOH
4.
KOH
I *
Br2
___,
bromine
collidine
d
11
Reference(s):
a
Ehrhart, Ruschig,
111,
317.
US 2 096 744 (Schermg Corp.; 1937; D-prior. 1932).
DRP 698 796 (Schering AG; appl. 1932).
b
lnhoffen, H.H.; Zuhlbdorff,
G
Ber. Dtsch. Chcm. Ges. (BDCGAS)
74,
1911 (1941).

US 2 361 847 (Schering Corp. 1944; D-prior. 1937).
Ullmanns Encykl. Tech. Chem.,
3.
Aufl., Vol. 8,657.
starring material:
The Merck Index, 12th Ed., 630 (1996).
alternative syntheses:
GB 485 388 (Lab. Franq. de Chimiothtrapie; appl. 1936).
US 2 225 419 (Schering Corp.; 1940; D-prior. 1937).
US
3
128 238 (Lilly; 7.4.1974; appl. 14.9.1962).
total synthesis:
Eder,
U.
et al.: Chem. Ber. (CHBEAM)
109,
2948 (1976).
Formulation(s):
gel 0.5 mglg, 1 mglg; tabl.
2
mg, 4 mg; transdermal plaster 0.75 mg, 1.5 mg, 2 mg, 3
mg,
4 mg, 8 mg; vaginal tabl. 0.025 mg
Trade
Name(s):
D: Aknefug Emulsion (Wo1ff)-
comb.
Cerella (Asche)
Crinohermal fem.

(Herma1)-comb.
Cutanum (Jenapharm)
DERMESTRIL
(Opfermann)
Estracomb
7TS (Novartis
Pharma)-comb.
Estraderm (Novartis
Pharma)
Estramon (Hexal)
Estrifam I-forte (Novo
Nordisk; RhGne-Poulenc
Rorer)
ESTRING (Pharmacia
&
Upjohn)
Evorel (Janssen-Cilag)
Fem7 (Merck)
Kliogest (Novo Nordisk;
Rh6ne-Poulenc Rorer)-
comb.
Linoladiol
(Wo1ff)-comb
Linoladiol-H (Wo1ff)-
comb.
Menorest (Novo Nordisk;
RhBne-Poulenc Rorer)
Osmil (Novartis Pharma)-
comb.
Sandrena (Organon)

Sisare Gel
(Nourypharma)
Tradelia (Sanofi Winthrop)
Trisequens (Novo Nordisk;
Rh6ne-Poulenc
Rarer)-
comb.