Pharmaceutical Substances Syntheses, Patents, Applications - Part 109 pps

Iodamide
1
1081
I
locetomic ocid
I
HC
0
HZ. Roney-Ni
'?
CH3
gN3-c0o~
Lp
iodine
monochloride
NO2
NH2
Reference(s):
FR
5 997
M
(Dagra; appl. 23.11.1966; prior. 25.11.1965, 26.5.1966).
H3C O
I
7
CH3
#"%OOH
I
''4%
Fonnulation(s):
tabl. 500 mg, 750

mg
Trade Name(s):
D:
Cholebrine
F:
CholCbrine (Schering); USA: Cholebrine (Mallinckrodt);
(Mundipharma);
wfm wfm wfm
1:
Colebrin (Schering);
wfm
Iodamide
(Jodamid)
ATC: V08AA03
Use: X-ray contrast medium
RN: 440-58-4
MF:
C12H,,13N204
MW:
627.94 EINECS: 207-125-1
LD,,:
>7 glkg
(M,
p.0.);
>7 glkg
(R,
p.0.)
CN:
3-(acetylamino)-5-[(acetylamino)methyl]-2,4,6-triiodobenzoic
acid

meglurnine
salt
RN:
18656-21-8
MF:
C,,H,,13N204
.
C7H17N0,
MW:
823.16 EINECS: 242-480-6
COOH COOH
COOH
4-chloro- 2.2-dichloro-N-
benzoic hydroxymethyl-
acid acetomide
3-aminamethyl-
4-chlorobenzoic
ocid
(I)
COOH COOH
H
,
Pd-C KICI2
III
Z
b
dichlora-
0
NH2
potassium

H3CKN
0
I
iodate
1082
1
Iodoxamic acid
I
Iodornide
I
Reference(s):
US 3 360 436 (Eprova; appl. 12.1 1.1963; CH-prior. 23.1 1.1962,9.8.1963).
GB
1 002 344 (Eprova; appl. 3.10.1963; CH-prior. 23.1 1.1962,9.8.1963).
DE 1 273 747 (Eprova; appl. 24.9.1963; CH-prior. 23.1 1.1962).
Fornzulation(s):
amp. 300 mg, 380 mg, 420 mg (as meglumine salt)
Trade Name(s):
D: Uromiro (Heyden); wfm Opacist E.R. (Bracco)
J:
Conraxin (Takeda)
I: Isteropac E.R. (Bracco) Uromiro (Bracco)
Iodoxamic acid
ATC: V08ACOl
Use: X-ray contrast medium
(cholangiography)
RN: 31127-82-9 MF:
C26H2,1,N20,0 MW: 1287.92 EINECS: 250-478-1
LD,,,: 13.65g/kg(M,i.v.)
CN: 3,3'-[(I

,16-dioxo-4,7,10,13-tetraoxahexadecane-l,l6-diyl)diimino]bis[2,4,6-triiodobenzoic
acid]
meglumine
salt
(1:2)
RN: 51764-33-1 MF: C2,H2,16N20,0. 2C7HI7NO, MW: 1678.35 EINECS: 257-398-6
NC~CH~
+
HOO~+O~~~~
+
NC~OfiO-OfiO-CN
acrylonitrile triethylene glycol
4,7,10,13-tetrooxahexadecane-
dinitrile
(I)
1.
H2S0,,
C2H50H
2.
NaOH
,7
4,7,10,13-tetrooxahexadecanedioyl
chloride
(11)
dirnethyl-
COOH
ocetornide
3-amino-2.4.6-
triiodobenzoic
ocid

COOH
1
Iodoxarnic ocid
I
DE 1 937 21 1 (Bracco; appl. 22.7.9969).
Formulation(s):
amp. 3.66 g, 5.49
g,
8.06 g, 9.91 g, 12.09 g (as meglurnine salt)
Iofendylate
1
1083
Trade Name(s):
D:
Endomirabil
(Byk
Gulden);
I:
Endobil (Bracco)
wfm
J:
Cholegrafin (Takeda)
Iofendylate
(Iophendylate)
ATC: V08AD04
Use: X-ray contrast medium
(myelography)
RN: 99-79-6 MF: C,,H,,I02 MW: 416.34 EINECS: 202-787-8
LD,,,:
21 00 mglkg

(R,
p.0.)
CN:
4-iodo-t-methylbenzenedecanoic
acid ethyl ester
+
H2COcH
H3C
0-c~~
I
iodo- ethyl 10-undecylenate lofendylate
benzene
Reference(s):
US
2 348 23
1
(Eastman Kodak; 1944; appl. 1940).
Formulation(s):
inj. sol.
Trade Name(s):
GB:
Ethiodan (Allen
&
USA: Pantopaque (Lafayette);
Hanburys); wfm wfm
Ioglycamic acid
(Acide ioglycamique)
ATC: VO8ACO3
Use: X-ray contrast medium
RN: 2618-25-9 MF: C,,H,oI,N207 MW: 1127.71 EINECS: 220-048-8

CN: 3.3'-[oxybis[(l -oxo-2,l
-ethanediyl)imino]]bis[2,4,6-triodobenzoic
acid]
meglumine
salt
(1:2)
RN: 14317-18-1 MF: CI,H,,I,N,07~ 2C,H,,NOS
MW:
1518.14
3-amino-2,4,6- diglycolic chloride loglycamic acid
triiodobenzoic
acid
1084
1
Iohexol
Reference (s):
US 2 776 241 (Schering AG; 1957; D-prior. 1952).
US 2 853 424 (Schering AG; 1958; D-prior. 1952).
DE 936 928 (Schering AG; appl. 1952).
DE 962 698 (Schering AG; appl. 1952).
DE 962 699 (Schering AG; appl. 1953).
DE 1 006 428 (Schering AG; appl. 1955).
Formulation(s):
amp. 0.17 g/ml (as rneglumine salt)
Trade Name(s):
D:
Biligram (Schering); wfm GB: Biligram (Schering Bilivison (Schering); wfm
Bilivistan (Schering); wfm Chemicals); wfm Bilivistan (Schering); wfm
F: Biligram (Schering); wfm
I:

Biligram (Schering); wfm
Iohexol
ATC: V08AB02
Use: X-ray contrast medium
RN: 66108-95-0 MF:
C,yH2613N30y MW: 821.14 EINECS: 266- 164-2
LD,,: 50 g/kg (M, i.v.); >20 g/kg
(M,
p.0.);
25.235 g/kg (R, i.v.); >20 gkg (R, p.0.);
>20 gkg (dog, i.v.)
CN:
5-[acetyl(2,3-dihydroxypropyl)amino]-~,~-bis(23-dihydroxypropy1)-24,6-trioo-1,3-
benzenedicarboxamide
dimethyl 5-nitro- 3-amino-
1,2-
5-nitro-N,N'-bis(2,3-
isophtholate propanediol dihydroxypropy1)-
(from glycide isophthalomide
ond ommonia)
5-amino-N,N8-bis(2.3- 5-amino-2.4.6-triiodo-
dihydroxyprapy1)- N,N'-bis(2,3-dihydroxy-
isophthalamide
(I)
propy1)isophthalamide
1.
NaOCH,
2.
HO/\~CI
OH

5-acetamido-2.4.6-triiodo-
N.Na-bis(2.3-dihydroxy-
Iohexol
propyl)isophtholamide (11)
Iopamidol
1
1085
Reference(s):
DE 2 726 196 (Nyegaard; appl. 10.6.1977; GB-prior. 11.6.1976).
US
4 250 113 (Nyegaard; 10.2.1981; GB-prior. 11.6.1976).
Fomularion(s):
amp. 240 mg, 300 mg, 350 mg
Trade Name(s):
D:
Accupaque (Nycomed) F: Omnipaque (Nycomed;
J:
Lumopaque (Winthrop)
Omnipaque (Schering; 1986)
Omnipaque (Daiichi)
1983) I: Omnipaque (Schering; USA: Omnipaque (Winthrop-
1985) Breon); wfm
Iopamidol
ATC: V08AB04
Use: X-ray contrast medium
RN: 60166-93-0 MF:
C,7H2213N308 MW: 777.09 EINECS: 262-093-6
LD,,,: 33 glkg (M, i.v.); >49 glkg (M, p.0.);
22.044 glkg
(R,

i.v.);
35 g/kg (dog, i.v.)
CN:
(S)-N,~-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxopropyl)amino]-2,4,6-triiodo-l
,3-
benzenedicarboxamide
COOH
ICI
Hz"4
chloride
I
10
5-orninoiso-
phtholic ocid
5-ornino-2.4.6-
triiodoiso-
phthalic acid
H,c,$cl
dirnethylacetornide,
I
+
0 CH,
K
0
L-2-acetoxy-
propionyl
chloride
(from L-lactic
acid)
1.

dirnethylacetarnide,
tributylornine
2-ornino-1.3-
propanediol
I
loparnidol
DE 2 547 789 (Savac; appl. 24.10.1975; CH-prior. 13.1 2.1974).
US
4 001 323 (Savac; 4.1.1977; CH-prior. 13.12.1974).
1086
1
Iopanoic acid
Fortnulution(s):
amp. 200 mg, 300 mg, 370 mg
Trade Narne(s):
D: Solutrast (Byk Gulden;
GB: Niopam (Merck; 1982); J: Iopamiron (Nippon
1981)
wfm
Schering)
F: Iopamiron (Schering; 1982)
I:
Giastromiro (Bracco) USA: Isovue (Squibb); wfm
Iopamiro (Bracco)
Iopanoic acid
(Acidum iopanoicum)
ATC: V08ACO6
Use: X-ray contrast medium
RN: 96-83-3 MF:
C,,H,,I3NO2 MW: 570.93 EINECS: 202-539-9

LDs,,: 320 mglkg (M, i.v.); 6600 mglkg
(M,
p.0.);
280 mglkg (R, i.v.); 1540 mglkg (R, p.0.)
CN:
3-amino-a-ethyl-2,4,6-triiodobenzenepropanoic
acid
monosodium
salt
RN: 2497-78-1
MF:
Cl1H,,I,NNaO2 MW: 592.92 EINECS: 219-683-3
LD,,,: 296 mgkg
(M,
i.v.); 1602 mglkg
(M,
p.0.);
332 mgikg (R, i.v.); 2986 mglkg (R, p.0.)
0
0
sodium butyrote
qCHO
+
(U-OJ-CH3
-
NO2 CH3 NO2
3-nitro- butyric anhydride a-ethyl-3-nitro-
benzoldehyde cinnornic acid
(I)
2-(3-orninobenzy1)-

butyric ocid
HZ.
Roney-Ni ICI
NH2 monochloride
Reference(s):
US 2.705 726 (Sterling Drug; 1955; prior. 1949).
I
I
NH2
For~nulation(s):
cps. 500 mg (as sodium salt); powder 375 mglg (as calcium salt)
Trade Name(s):
D:
Telepaque (Winthrop); wfm I: Cistobil (Bracco) Molpaque (Tokyo Tanabe)
F: TClCpaque (Winthrop); Telepaque (Winthrop); wfm Telepaque (Kodama)
wfin J: Ace-Line (Maruishi) USA: Telepaque (Winthrop); wfm
GB: Telepaque (Winthrop);
wfm Leabar (Toyo S Ono)
Iophenoic acid
1
1087
Iophenoic acid
(Acidum iophenoicum; Iophenoxic acid)
RN: 96-84-4 MF: Cl,Hl,1303 MW: 571.92
LD,,:
374 mglkg (M, i.v.); 1850 mglkg (M, p.0.);
2 glkg
(R,
p.0.);
203 mgkg (dog, i.v.)

CN:
a-ethyl-3-hydroxy-2,4,6-triiodobenzenepropoic
acid
ATC: V08AD
Use: X-ray contrast medium
3-hydroxy- butyric anhydride a-ethyl-3-hydroxy-
benzaldhyde cinnamic acid
(1)
sodium arnalgorn
ICI
1-
Tic-'
OH
monochloride
2-(3-hydroxybenzyl)-
butyric acid
Iophenoic ocid
Reference(s):
US 2 931 830 (Sterling Drug; 5.4.1960; appl. 20.3.1952).
GB
726 987 (Sterling Drug; appl. 1953; USA-prior. 1952).
Trade Name(s):
USA: Teridax (Schering); wfm
I0p
yd0l
ATC: V08AD02
Use: X-ray contrast medium
RN: 5579-92-0 MF:
C,H91,N0, MW: 420.97 EINECS: 226-968-6
CN:

1-(2,3-dihydioxypropyl)-3,5-diiodo-4(1H)-pyridinone
3.5-diiodo-4(1
H)-
glycide
I
lopydol
pyridone
(I)
I
(cf. diodone
synthesis)
1
-chloro-2.3-
propanediol
1088
1
Iotalamic acid
Reference(s):
DRP 579 224
(I.
G. Farben; appl. 1930).
Formulation(s):
vial 20 mg
3,5-diiodo-4(1H)-pyridonelml
in comb. with iopydol
Trade Name(s):
D: Hydrast (Byk Gulden); I: Hytrast (Byk Gulden)- J: Hydrast (Guerbet-
wfm comb. with iopydone; wfm Kodama)-comb. with
F:
Hydrast (Guerbet)-comb. iopydone

with iopydone; wfm
Iotalamic acid
(Iothalamic acid; Acide iotalamique)
ATC: V08AA04
Use: X-ray contrast medium
RN: 2276-90-6 MF: CllH913N204 MW: 613.92 EINECS: 218-897-4
CN:
3-(acetylamino)-2,4,6-triiodo-5-[(methylamino)carbonyl]benzoic
acid
monosodium salt
RN: 1225-20-3 MF: C,,H,13N2Na04 MW: 635.90 EINECS: 214-955-8
LD,,,: 19.2g/kg(M,i.v.)
meglumine salt
RN: 13087-53-1 MF: C,,H,13N204
.
C7H17N0, MW: 809.13 EINECS: 235-998-9
LD,,,: 8.1 glkg (M, i.v.);
10.5 glkg (R, i.v.)
dimethyl 5-nitro-
isophtholote
monomethyl
5-nitroisophtholote
Hz,
Pd-C ICI
I
*
H2N
iodine
0
CH3

manochloride
Reference(s):
Hoey, G.B. et al.: J. Med. Chem. (JMCMAR) 6,24 (1963).
US 3 145 197 (Mallinckrodt; 18.8.1964; appl. 26.6.1961; prior. 25.8.1960).
GB 994 215 (Mallinckrodt; appl. 18.8.1961; USA-prior. 25.8.1960).
acetyl
Formularion(s):
sol. 17
%,
24
%,
36
%,
43
%,
60
%,
66.8
%,
80
%
(as meglumine salt)
lotolomic acid
chloride
Iotrolan
I
1089
Trade Name(s):
D:
Conray (Byk Gulden); wfm

I:
Angio-Conray 80 (Bracco) Conray (Mallinckrodt);
F:
Contrix 28 (Guerbet); wfm Conray (Bracco) wfm
GB: Conray (May
&
Baker);
J:
Angio-Conray (Daiichi) Cysto-Conray
wfm
Conray (Daiichi)
(Mallinckrodt); wfm
Gastro-Conray (May
&
USA: Angio-Conray
Vascoray (Mallinckrodt);
Baker); wfm
(Mallinckrodt); wfm wfm
-
-
I0tr0lan
ATC: V08AB06
(DL-31
17;
Iotrol)
Use: X-ray contrast medium (water
soluble, non-ionic, for myelography
and contrast enhancement
in
CT)

RN: 79770-24-4
MF:
C3,H,,I,N,0,0 MW: 1626.24
LD,,:
>
26
g/kg (M,
i.v.);
12.7 g/kg
(R,
i.v.)
CN:
5,5'-[1,3-dioxo-1,3-propanediylbis(methylimino)]bis[N,N'-bis[2,3-dihydroxy-1-(hydroxymethyl)propyl]-
COOH OVCl
S0CI2
HOOC
OIH
2.4.6-triiodo-5-
methylomino-
isophtholic acid
01'
I
I
0
5-amino-6-hydroxy
CH, CH,
1,3-dioxepane
(11)
1090
1

Iotroxic acid
90% aq.
CFxCOOH
111
*
preparotion of
11:
2.2-dimethoxy- 1.2-dihydroxy- 2.2-dimethyl-
propane 2-butene 4.7-dihydro-1.3-
dioxepin
(N)
H3C-CN,
CH,OH,
30%
H202.
40
OC.
5
h
liq.NH3,
120
"C,
4
h
IV
acetonitrile, hydrogen peroxideb
H3C
0
octone
The epoxidation step can also be performed with m-chloroperoxybenzoic acid in CH2C12.

Reference(s):
US 4 341 756 (The Regents of the Univ. of Calif.; 27.7.1982; prior. 3 1.1.1980, 17.4.1980).
EP 33 426 (The Regents of the Univ. of Calif.; appl. 30.12.1980; USA-prior. 3 1.1.1980, 17.4.1980).
preparation of
trans-2,2-dimethyl-5-amino-6-hydroxy-l,3-dioxepane:
US 4 439 613 (The Regents of the Univ. of Calif.; 27.5.1984; prior. 31.1.1980, 17.4.1980,5.4.1982).
review:
Dawson, P.; Howell, M.: Br. J. Radiol. (BJRAAP) 59,987 (1986).
Fortnulation(s):
vial 10
ml
and 20 ml(513 mglml), 10 ml (641 mglml)
Trade Name(s):
D:
Isovist (Schering; 1988)
J:
Isovist (Nihon Schering;
I: Isovist (Schering) 19 87)
Iotroxic acid
ATC: V08AC02
Use: X-ray contrast medium
RN: 51022-74-3 MF:
C22H,,I,N20, MW: 1215.82 EINECS: 256-917-3
LD,,: 2820 mglkg (M, i.v.); >9 g/kg
(M,
p.0.);
4190 mg/kg (R, i.v.);
>9
g/kg
(R,

p.0.)
CN:
3,3'-[oxybis[2,I-ethanediyloxy(l-oxo-2,l-ethanediyl)imino]]bis[2,4,6-triiodobenzoic
acid]
tetroethylene glycol
3.6.9-trioxaundecanedioic
ocid