Pharmaceutical Substances Syntheses, Patents, Applications - Part 32 pps

Butylscopolammonium bromide
B
3
1
1
Butylscopolammonium bromide
ATC: A03BBOI
(Butylscopolamine bromide; Scopolamine butyl bromide;
antispasmodic
Hyoscin butyl bromide)
RN: 149-64-4 MF: C,,H30BrN04 MW: 440.38 EINECS: 205-744-1
LD,,: 10.3 mg/kg(M,i.v.); 1170mglkg(M,p.o.);
24 mglkg (R,
i.v.);
1040 mglkg (R, p.0.)
CN:
[7(S)-(la,2~,4~,5a,7P)1-9-butyl-7-(3-hydroxy-1-oxo-2-phenylpropoxy)-9-methyl-3-oxa-9-
azoniatricyclo[3.3.1 .02"]nonane bromide
butyl bromide
(-)-scopolamine
I
Butylscopolommonium bromide
Reference(s):
DE 856 890 (Boehringer Ing.; appl. 1950).
Formulation(s):
amp. 20 mglml; drg. 10 mg;
f.
c. tabl. 10 mg; suppos. 7.5 mg, 10 mg; tabl. 20 mg;
vial 200 mg/lO ml
Trade Name(s):
D: Buscopan (Boehringer

1ng.)-comb.
F:
GCnoscopolamine (Amino)
Scopoderm (Novartis)
GB: Buscopan (Boehringer Ing.)
I:
Buscopan (Boehringer Ing.)
Buscopan compost0
(Boehringer 1ng.)-comb.
Tranquo-Buscopan
(Boehringer 1ng.)-comb.
J:
Antispasmin (Green Cross)
Bubusco-S (Sawai)
Buscopan (Boehringer-
Tanabe)
Buscoridin (Kanebo)
Buscote (Kotani)
Buspon
(Toyo Pharmar)
Butibol (Towa)
Butylpan (Hokuriku)
Butymide (Ohta)
Butysco (Kobayashi)
Diaste-M (Fukuchi-
Fujizoki)
Hyoscomin (Vitacain)
Hyospan (Toiyo)
Moryspan (Beppu)
Reladan (Isei)

Scobro (Ono)
Scobron (Mohan)
Scobutylamin (Horii)
Scordin-B (Ono)
Scorpan (Kanto)
Sparicon (Yamanouchi)
Spasmopan (Nichiiko)
Stibron (Iwaki)
312
C
Cabergoline
Cabergoline
ATC:
GO~CBO~
Use: doparnine D, receptor antagonist,
prolactin inhibitor for prevention
or
suppression of puerperal lactation
RN: 81409-90-7 MF: C,,H,,N,O, MW: 451.62
CN:
(8~)-N-[3-(Dirnethylamino)propyl]-N-[(ethylamino)carbonyl]-6-(2-propenyl)ergoline-8-carboxamide
1.
K2C03,
DMF
2.
NaOH.
CH30H
8p-methoxycarbonyl-
ergoline
(cf.

pergolide
synthesis)
ally1
bromide
THF
d
N-ethyl-Na-[3-(dirnethyl-
amino)propyl]corbo-
diirnide
6-allyl-88-ergoline-
carboxylic
acid
(I)
Cabergoline
0CNvCH3,
toluene
or
'33
H3CbN=c=Nq
CH3
@
CH2CIZ.
CuCl
(cot.),
PPh3
H3C
1-
3-dimethylamino-
ethyl
isocyanate

propylarnine.
diisopropylcarbo-
diimide
H
N~
6-allyl-N-[3-(dimethyl-
amino)propyl]-8p-
ergolinecorboxarnide
Reference(s):
a GB 2 074 566 (Farmitalia Carlo Erba S.p.A.; appl. 31.3.1981; GB-prior. 3.4.1980).
b
US 4 526 892 (Farrnitalia Carlo Erba S.p.A.; 2.7.1985; USA-prior. 3.3.1981).
BE 894 060 (Farmitalia Carlo Erba S.p.A.; appl. 9.8.1982; GB-prior. 11.8.1981).
b,c
WO
9
31 8 034 (Farmitalia Carlo Erba S.p.A.; appl. 15.2.1993; GB-prior. 12.3.1982).
Candiani; Cabri, W.; Zarini, F.; Bedeschi, A,: Synlett (SYNLES)
1995
(6), 605.
Cadexomer iodine
C
3
13
synthesis
and
nidation inhibitory activity of
a
new class of ergoline derivatrves:
Brambillh,

E.;
Dlsalle, E.; Briatlco, G.; Mantegani,
S.;
temper ill^,
A.: Eur. J. Med. Chem. (EJMCAS)
24,
421
(1989)
'
Formulution(s):
tabl. 0.5 mg, 1 mg, 2 mg, 4 mg
Tmde Namefs):
:
D:
CABASERIL (Pharmacia GB: Cabaser (Pharmacla
&
&
Upjohn) Upjohn)
Dostinex (Pharmacia
&
Dostinex (Pharmacia
&
Upjohn) Upjohn)
Cadexomer iodine
ATC:
Use:
RN:
94820-09-4 MF: unspecified
MW:
unspecified

LD50:
>2
glkg
(R,
i.p.);
>2 glkg
(R,
LC.)
CN: cadexomer iodine
12,
acetone
drxtrin
+
Cl>

epichloro-
hydrin
I:
Dostinex (Pharmacia
&
Upjohn)
USA: Dostinex (Pharmacia
&
Upjohn)
D03AXO
1
;
D08AG
antiseptic for treatment of decubitus
and venous leg ulcers

Cadexorner iodine
I
Referencefs):
DE
2
533 159 (A.
0.
Johannson; appl. 24.7.1975).
US4010 259 (A.
0.
Johannson; 1.3.1977; appl. 17.7.1975).
FR
2
320 112 (A.
0.
Johannson; appl. 5.8.1975).
Formulation(s):
dry sterile powder, micropellets, sachet 3
g,
1
%
bioavailable iodine
Trade Namefs):
D: Iodosorb (Strathmann) F: Iodosorb (Millot; 1984);
wfm
3
14
C
Cadralazine
7

GB: Iodoflex (Perstorp) Iodosorb (Perstorp; 1983) I: Iodosorb (Valeas; 1989)
Cadralazine
ATC:
CO~DBO~
Use: antihypertensive, vasodilator
RN: 64241-34-5 MF: Cl,H,,N,O, MW: 283.33
LD,,,: 700 mg/kg (M, i.p.);
269 mg/kg (R, i.v.); 2060 mg/kg (R, p.0.)
CN:
2-[6-[ethyl(2-hydroxypropyl)amino]-3-pyndazinyl]hydrazinecarboxylic
acid ethyl ester
cCH3
-
Wc,
&
+
OH fCH3
-,
I
NH2
3.6-dichloro-
H3C
pyridozine
propylene ethylamine N-eth~i-2-h~droxY- (cf. azintarnide)
oxide propylornine
OH cCH3
H
+
CI
0

ethyl carbazate
(1)
Cadralazine
Reference(s):
US 4 002 753 (I.S.F.; 11.1.1977; I-prior. 7.3.1973).
alternative syntheses:
US 4 575 552 (I.S.F.; 11.3.1986; I-prior. 28.4.1983).
US 4 632 982 (I.S.F.; 30.12.1986; I-prior. 28.4.1983).
US 4 757 142 (I.S.F.; 12.7.1988; I-prior.
13.5.1985).
cf. also synthesis of pildralazine
Formulation(s):
cps. 10 mg, 15 mg, 29 mg
Trade Name(s):
I: Cadraten (SmithKline Cadrilan (Novartis)
Beecham)
J:
Cadral (Novartis)
Cafaminol
(Mecoffaminum; Methylcoffanolamine)
Use: rhinological therapeutic
RN: 30924-3 1-3 MF: C,,H,,N,O, MW: 267.29 EINECS: 250-390-3
LD,,,: 700 mg/kg (M, s.c.)
CN:
3,7-dihydro-8-[(2-hydroxyethyl)methylamino]-l,3,7-trimethyl-1H-purine-2,6-dione
Cafedrine
C
315
caffeine 8-chlorocaffeine Cofaminol
(4.

v.1
Reference(s):
DE
1
085 530
(J.
Klosa; appl. 15.8.1958).
US
3 094 531 (Delmar Chemicals; appl. 30.4.1959).
Formulation(s):
drg. 50 mg
Trade Nanie(s):
D:
Rhinoptil (Promonta); wfm
I:
Katasma balsamic0
(Bruschettini)
Cafedrine
ATC: COlCA21
Use: circulatory analeptic
RN: 58166-83-9 MF: C,,H,,N,O,
MW:
357.41
CN:
3,7-dihydro-7-[2-[(2-hydroxy-l-methyl-2-phenylethyl)amino]ethyl]-1,3-dimethy-1
H-purine-2,6-dione
[R-(R*,S*)]-cafedrine
RN: 78396-34-6 MF: C,,H,,N,O, MW: 357.41
[R-(R*,S*)]-monohydrochloride
RN: 3039-97-2 MF: C,,H,N,O,. HCl MW: 393.88 EINECS: 221-243-0

LD,,:
525 mgkg
(M,
i.p.)
theophylline 1,2-dibramo- 7-(2 bramaethyl)-
ethane theophylline
(I)
L-norephedrine
I
Cafedrine
Reference(s):
DE
1 095 285 (Degussa; appl. 25.9.1956).
US
3 029 239 (Degussa; 10.4.1962; D-prior. 17.4.1954).
Formulation(s):
amp. 200 mg;
f.
c. tabl. 100 mg
316
C
Caffeine
Trade Name(s):
D: Akrinor (Homburg)-comb. F: Praxinor (Lipha SantC)- I: Akrinor (ASTA Medica; as
with theodrenaline comb. with thCodrCnaline hydrochloride)
Caffeine
(Cafkine; Coffein)
ATC: N06BCOl
Use: analeptic. diuretic
RN: 58-08-2 MF: CUH,,N4O2 MW: 194.19 EINECS: 200-362-1

LD,,,: 62 mglkg (M,
i.v.); 127 mglkg (M, p.0.);
105 mglkg (R, i.v.); 192 mglkg (R, p.0.);
140 mglkg (dog, p.0.)
CN:
3,7-dihydro-1,3,7-trimethyl-lH-purine-2,6-dione
O\\
0
-
+
H,C,~,S~
\CH,
OYN
0
CH3
theophylline
dirnethyl
sulfate
Caffeine
(9.
v.)
Reference(s):
DE 834 105 (Boehringer Ing.; appl. 1949).
Formulation(s):
tabl. 200 mg
Trade Name(s):
D: Coffeinum (Merck) GB:
Cefergot.(Novartis)-comb.
J:
Percoffedrinol N (Passauer) Doloxene (Lil1y)-comb.

numerous generics and
combination preparations
numerous combination Migril (Glaxo Wellcome)- USA: Darvon (Lilly)
preparations comb.
DHCplus (Purdue
F: Cafkine Aguettant
I:
.
Caffeina (Tariff. Nazionale; Frederick)
(Aguettant) as citrate) Esgic-plus (Forest)-comb.
PercutafCine (Fabre) numerous combination numerous combination
generics and combination preparations preparations
preparations
Caffeine acetyltryptophanate
(A
50;
Coftrinum)
ATC: N06BCOl
Use: psychotonic
RN: 60364-24-1 MF: Cl,H14N203. CuHloN402 MW: 440.46
CN:
1-acetyl-L-tryptophan compd. with
3,7-dihydro-1,3,7-trimethyl-lH-purine-2,6-dione
(1: 1)
"
8"
''
HN CH,
CH3
K

0
HN CH,
K
0
N-acetyl-
L-tryptophan
I
Caffeine
acetyltryptaphanate
Calcifediol
C
317
Reference(s):
FR-M
1
759 (A.
E.
C.; appl. 22.2.1962).
Trade Name(s):
F:
Adrifane (Adrian, Paris);
wfm
Calcifediol
ATC: A1 1CC06
Use:
calcium regulator
RN:
19356-17-3
MF:
C,,H,O,

MW:
400.65 EINECS: 242-990-9
CN:
(3~,5Z,7E)-9,l0-secocholesta-5,7,10(19)-triene-3,25-diol
25-hydroxycholesterol 3-ocetote acetic anhydride
dimethylhydantoin
2.
trirnethyl phosphite
3.
lithium aluminum
hydride
dirnethylhydontoin
2.
trimethyl phosphite
3.
rnethylmognesium
iodide
Reference(s):
a,bBlunt, J.W.; DeLuca, H.F.: Biochemistry (BICHAW) 8,671 (1969).
DeLuca,
H.F.:
Am. J. Clin. Nutr. (AJCNAC) 22,412 (1969).
Halkes,
S.J.;
Vliet, N.P. van: Recl.
Trav.
Chim. Pays-Bas (RTCPA3)
88,
1080 (1969).
alternative svntheses:

Sodano, Ch. S.: Vitamins, Synthesis, Product~on and Use, p. 131, 159 (New Jersey 1979).
US 4 001 096 (Upjohn; 4.1.1977; prior. 21.2.1975).
US
3
833 622 (Upjohn; 3.9.1974; prior. 17.3.1969).
structure and isolation:
DeLuca, H.F.: Am. J. Clin. Nutr. (AJCNAC) 22,412 (1 969).
Formulation(s):
drops 0.15 mglml, 0.45 mglml
Trade Nameis):
D: Dedrogyl (Albert-Roussel, F: DCdrogyl (Roussel)
I:
Didrogyl (Roussel)
Hoechst) Un-Alfa
(Lb)
USA: Calderol (Organon)
Calcipotriol
ATC: A1 1CC; D05AX02
Use: antipsoriatic, topical vitamin
D,-
analog
RN: 112828-00-9 MF: C,,H,,O,
MW:
412.61
CN:
(la,3~,5Z,7E,22E,24S)-24-cyclopropyl-9,1O-secochola-5,7,10(19),2~-tetraene-1,3,24-triol
'?3
CH3 CH3
-
I1

tert-butyld~methyl-
sflyl chlor~de
(I)
vitamin
D2
CH, CH,
Me
,NH
%
CH3 CH3 CH3 CH, CH3 CH, CH, CH,
triphenylphosphine
propane
NaOH
VI
d
1.
V,
A
2.
chrornotography
CH3 CH3 CH, CH,
(cyclapropylcarbo-
nylrnethy1ene)tri-
phenylphasphorane
320
C
Calcitriol
2.
chromotagraphy
m1

-
C H
cH cH
Li~o-&o-jiTcH3
'CH
cH
I
CH3 CH3 CH, CH3
(W
Bu4N+F-
b
tetrobutyl-
ammonium
fluoride
I
Calcipotriol
Reference(s):
EP 227 826 (Leo; appl. 14.7.1986; GB-prior. 2.8.1985).
WO 8 700 834 (Leo; appl. 14.7.1986; GB-prior. 2.8.1985).
Calverley,
M.J.:
Tetrahedron (TETRAB) 43,4609 (1987).
Fonmdation(s):
ointment 50 pglg
D: Daivonex (Leo) F: Daivonex (LCo)
I:
Daivonex (Formenti)
Psorcutan (Schering AG) GB: Daivonex (Leo; 1991)
Psorcutan (Schering)
Calcitriol

(la,25-Dihydroxy-vitamin
D,)
ATC: A 1 ICC04; DOSAX03
Use: calcium regulator
RN: 32222-06-3 MF: C,,H,O, MW: 416.65 EINECS: 250-963-8
LDS,,: 1350 pglkg (M, p.0.);
I05 pglkg (R, i.v.); 620 pgkg
(R,
p.0.)
CN:
(la,3~,5Z,7E)-9,10-secocholesta-5,7,10(19)-triene-l,3,25-triol
1
a.25-dihydroxycholesterol
acetic
anhydride