Pharmaceutical Substances Syntheses, Patents, Applications - Part 36 docx

Carfecillin
C
351
Carfecillin
ATC: GOlAA08; JOlCA
Use: antibiotic
RN:
27025-49-6 MF: C23H22N206S MW: 454.50 EINECS: 248-1 71-2
LD,,: 728 mg/kg (M, i.v.); 3924 mglkg (M, p.0.)
CN:
[2S-(2a,5a,6~)1-6-[(1,3-dioxo-3-phenoxy-2-phenylpropyl)amino]-3,3-dimethyl-7-oxu-4-thia-1-
azabicyclo[3.2.0]heptane-2-carboxylic
acid
u
phenylrnalonic
acid
HOOC
COOH
X
SOC12,
DM.,
cl;)(;OO~
I'
OOH, phenol NaHC03,
rnonophenyl phenyl
malonote
(I)
COOH
.NaHCO,
6-ominapenicillanic
acid

Carfecillin
1
US 3 853 849 (Beecham; 10.12.1974; prior. 2.1
1
.I 967 and 29.5.1969).
US
3
881 013 (Beecham; 29.4.1975; CB-prior. 5.1
1
.I966 and 27.1.1967)
Formula~ion(s):
tabl. 500 mg
Trade Name(s):
I: Uricillirla (IBI)
J:
Gripenin-0 (Fujisawa)
Urocarf (SPA;
as
sodium Uticillin (SmithKline
salt) Beecham)
Carfenazine
(Carphenazine)
ATC: NO5AK
Use: neuruleptic
RN: 2622-30-2 MF: C2,H,,N3O2S MW: 425.60 EINECS: 220-072-9
CN:
1-[10-[3-[4-(2-hydroxyethyl)-l-piperazinyl]propy1]-1OH-phenothiazin-2-yl]-I-propanone
dimaleate
RN: 2975-34-0 MF: C2,H3,N302S 2C4H404
MW:

657.74 EINECS: 221-019-2
LD,,: 42 mgkg (M, i.v.); 156 rnglkg (M, p.0.);
162 mglkg
(R,
p.0.)
2-propionyl- chloropropane 10-(3-chloropropyl)-2-
phenothiozine prapionylphenothiazine
(1)
352
C
Carindacillin
Carfenazine
Reference(s):
US 2 985 654 (Schering Corp.; 1961; appl. 1956).
US 3 023 146 (American Home; 27.2.1962; appl. 6.6.1960; prior. 3.6.1959).
Formulation(s):
tabl. 25 mg, 400 mg
Trade Name(s):
USA: Proketazine (Wyeth); wfm
Carindacillin
ATC: JOlCAO5
(Indanylcarbenicilline; Carbenicillin Indanyl Sodium)
Use: antibiotic
RN: 3553 1-88-5
MF:
C2,H,,N20,S MW: 494.57
LD,,: 3600 mgkg (M, p.0.);
2 glkg (R, p.o.1;
>500 mglkg (dog, p.0.)
CN:

[2S-(2a,5a,6P)]-6-[[3-[(2,3-dihydro-
IH-inden-5-yl)oxy]-
1,3-dioxo-2-phenylpropyl]aminoJ-3,3-dimethyl-
7-oxo-4-thia-l-azabicyclo[3.2.0]heptane-2-carboxy1ic
acid
monosodium salt
RN: 26605-69-6
MF:
C26H,,N,Na06S MW: 5 16.55 EINECS: 247-845-3
LD,,,: 210mglkg(M,
i.v.);4400mg/kg(M,p.o.);
295 mglkg (R, i.v.); 4450 mglkg (R, p.0.);
>15.3 mglkg (dog, p.0.)
PCI5
phosphoru?
HOO:;'OOH
pento;.
5-indanol
'
chloride
phenylmalonic
phenyl(ch1ora-
-
phenylketene
(I)
COOH
COOH
Carindocillin
US
3

557 090 (Pfizer; 19.1.1971; appl. 5.1.1968).
US
3 574 189 (Pfizer; 6.4.1971
;
appl. 5.1.1968).
US
3
679 801 (Pfizer; 25.7.1972; prior. 5.1.1968,4.6.1969, 19.5.1970).
DAS
1
967 024 (Pfizer; appl. 3.1.1969; USA-prior. 5.1.1968).
Carisoprodol
C
353
allernative synthesis:
DOS
1 959 569 (Pfizer; appl. 27.1 1.1969; USA-prior. 23.1.1969).
Formulalion(s):
tabl. 500 mg
Trade Name(s):
D: Carindapen (Pfizer; 1973);
J:
Geopen-U (Taito Pfizer;
wfm 1976)
1: Geopen orale (Pfizcr; 1973) USA: Geocillin (Pfizer; 1972)
Carisoprodol
ATC: M03BA02
Use: muscle relaxant
RN:
78-44-4

MF:
C,,H,N,O, MW: 260.33 EINECS: 201-118-7
LDS{ 165 mglkg (M,
i.v.);
1800 mglkg
(M,
p.0.);
450 mgkg (R,
i.v.);
1320 mgkg (R, p.0.)
CN:
(1-methylethy1)carbamic acid
2-[[(aminocarbonyl)oxy]methyl]-2-methylpenty
ester
0
CH,
+
isopropyl-
H
CH3
CI
0
arnine
CH3
2-methyl-2- phosgene
(1)
propylpropane-
1,3-diol
(cf.
meprobamate

synthesis)
ethyl corbamate
I
Carisoprodol
I
Reference( s):
US
2 937 119 (Carter Products; 17.5.1960; prior. 11.6.1959).
Formulation(s):
tabl. 350 mg
Trade Name(s):
D:
Sanoma (Heilit) Flexartal (Clin-Midy); wfm numerous combination
F:
Flexagit (Clin-Midy)-
GB:
Carisoma (Pharmax) preparations
comb.; wfm
I:
Flexidone (Pierrel)-comb.
J:
Myobutazolidin (Ciba-
Flexalgit (Clin-Comar- Soma Complex Geigy-Fujisawa)-comb.
Byla)-comb.; wfm
(Teofarma)-comb. Somanil (Banyu)
Flexartal
(Clin-Comar- Teknadone (Teknofarma)- USA: Soma (Wallace)
Byla); wfm
comb.
354

C
Carmofur
Carmofur
(HCFU)
ATC: LOlBC04
Use: antineoplastic, orally active
fluorouracil derivative
RN:
61422-45-5 MF: C,,HI,FN303 MW: 257.27
LD,,: 1129 mgkg (M, p.0.);
268 mglkg (R, p.0.);
65 mgkg (dog, p.0.)
CN:
5-fluoro-N-hexyl-3,4-dihydro-2,4-dioxo-
l(2H)-pyrimidinecarboxamide
5-fluoro- phosgene
uracil
(I)
(4.
v.1
n-hexyl isocyanate
Reference(s):
a
JP
531098 977 (Mitsui; appl. 2.8.1977).
b
DOS 2 639 135 (Mitsui; appl. 31.8.1976; USA-prior. 5.1 1 .l975).
US 4 071 519 (Mitsui; 31.1.1978; prior. 5.11.1975).
Formulation(s):
tabl. 100 mg

Trade Name(s):
J:
Mifurol (Mitsui; 1981) Yamaful (Yarnanouchi;
1981)
Carmustine
(BCNU)
ATC: LOlADOl
Use: antineoplastic
RN:
1
54-93-8 MF: C5H9C12N302 MW: 2 14.05 EINECS: 205-838-2
LD,,,: 26 mgkg (M, i.p.); 45 mgkg (M, i.v.); 19 mg/kg (M, p.0.); 24 mgkg (M, s.c.);
13.8 mglkg (R, i.v.); 20 mg/kg (R, p.0.)
CN:
N,W-bis(2-ch1oroethyl)-N-nitrosourea
I
Carmustine
I
Rqference(s):
DOS 2 528 365 (The Government of US; appl. 25.6.1975; USA-prior. 13.11.1974).
Carnitine
C
355
nitmation with
NaNO,,
Johnston,
T.P.
et al.: J. Med. Chem. (JMCMAR) 6, 669 (1963).
synthesis of
N,N1-bis-(2-chloroethy1)urea:

Bastian,
H.:
Justus Liebigs Ann. Chem. (JLACBF) 566, 210 (1950).
review:
Carter, S.K. et al.: "Advances in Cancer Research"
(Ed.
G. Klein, S. Weinhouse) 16,273 (1972)
Formulation(s):
tabl. 7.7 mg
Trade Name(s):
D: Carmubris (Bristol-Myers GB: BICNU (Bristol-Myers USA: BICNU (Bristol-Myers
Squibb) Squibb) Squibb)
F:
BICNU (Bristol-Myers I: Nitrumon (Astra-Simes) Gliadel (RhGne-Poulenc
Squibb) Rorer)
Carnitine
(Levocarni tine)
ATC: A12AX; Al4B; AIIJC
Use: appetite stimulant, antiarrhythmic,
cardiomyopathy therapeutic
RN: 541-15-1 MF: C7HI5NO3 MW: 161.20
LD,,:
9
g/kg (M, s.c.);
7 glkg (dog, route unreported)
CN:
(R)-3-carboxy-2-hydroxy-N,N,N-trimethyl-1-propanaminium
hydroxide inner salt
L-hydrochloride
RN: 6645-46-1 MF: C7H15N03

.
HCl MW: 197.66 EINECS: 229-663-6
DL-carnitine
RN: 406-76-8 MF: C7H15N03 MW: 161.20 EINECS: 206-976-6
DL-hydrochloride
RN: 461-05-2 MF: C7H15N03
.
HCI MW: 197.66 EINECS: 207-309- 1
LD,,: 6 glkg (M, s.c.);
10 gkg (R, s.c.)
epichloro-
hydn'n
(I)
4-chloro-3-
hydroxy-
butyronitrile
cornitinenitrile
chloride
(IV)
I
DL-Cornitine hydrochloride
I
356
C
Carnitine
(2.3-epoxypropy1)-
trimethylornmonium
chloride
ethyl 4-chloro
ocetoocetote

I
DL-Carnitii hydrochloride
-
I
cornitine ethyl ester chloride (V)
DL-carnitinomide chloride
H,C COOH
&CH,
isopropanol
VI
+
CH3
COOH
DL-cornitinomide hydroxide (VI)
microbiologicolly
044
K74
H3C
1.
H20,
A
H3C\
/
OH
0
CI- 2. oxolic acid
NU
-
NH2
H~C/

L-cornitinomide chloride (VII)
DL-cornitine crotonobetaine
(WI)
1
L-Cornitine
H C
H3C\
3
OH
CI-
,N&~~~~
H3C
L-Cornitine hydrochloride
0

rn~crob~olog~colly
e.g. with Acinetobocter lwoffi (ATCC 9036)
or Proteus mirobilis (ATCCF 15290)
VIll
Reference(s):
la
US 3 135 788 (Nihon Zoki Seiyaku; 2.6.1964; J-prior. 28.9.1959).
hydrolysis of
carnitinenitrile chloride
with conc.
HCI:
DAS 1 090 676 (Labaz; appl. 24.10.1958).
b
US 4 070 394 (Ethyl Corp.; 24.1.1978; appl. 11.3.1977; prior. 23.1.1976).
c

CH 588 433 (Lonza; appl. 25.9.1974).
similar process from
y-chloroacetanilide:
CH 589 604 (Lonza; appl. 26.4.1974).
241
DOS 2 927 672 (C. Cavazza; appl. 9.7.1979; I-prior. 10.7.1978).
US 4 254 053 (C. Cavazza; 3.3.1981; I-prior. 10.7.1978).
electrolytic methods for release of base:
DOS 3 342 713 (Sigma-Tau; appl. 25.11.1983; I-prior. 25.1 1.1982).
US 4 521 285 (Sigma-Tau; 4.6.1985; I-prior. 25.1 1.1982).
b
EP 148 132 (Sigma-Tau; appl. 31.10.1984; DDR-prior. 3.1 1.1983).
c
EP 122 794 (Ajinomoto; appl. 13.4.1984; J-prior. 13.4.1983).
enzymatic methods from
y-butyrobetaine
and
2-ketoglutaric acid
with
y-butyrobetaine hydroxylase
from
Neurospora crassa:
GB 2 078 742 (Sigma-Tau; appl. 23.6.1981; I-prior. 24.6.1980).
synthesis from
~-mannitol:
US 4 413 142 (Anic; 1.1 1.1983; I-prior. 18.3.1981).
use as antiarrhythmic:
US 3 830 931 (S. L. De Felice; 20.8.1974; appl. 6.1 1.1972).
US 3 968 241 (S.
L.

De Felice; 6.7.1976; prior. 6.1 1.1972, 2.7.1974).
paren feral use for improvement of myocard function:
US 4075 352 (S. L. De Felice; 21.2.1978; appl. 28.4.1976).
use for reduction of cardiotoxicity of cytostatics, e. g.
daunomycin:
US 4 320 110 (S. L. De Felice; 16.3.1982; appl. 4.10.1979).
US 4400 371 (S. L. De Felice; 23.8.1983; appl. 12.5.1981).
use as appetite stimulant:
US 3 810 994 (Ethyl Corp.; 14.5.1974; appl. 1.6.1972).
additive to parenteral feeding:
DOS 3 032 300 (A. Lohninger, Wien; appl. 27.8.1980).
US 4 320 145
(C.
Cavazza; 16.3.1982; I-prior. 5.10.1979).
EP59 775 (Leopold
&
Co.; appl. 1.6.1981; YU-prior. 9.6.1980).
use as antihyperlipidemic:
US4 315 944 (Sigma-Tau; 16.2.1982; I-prior. 21.9.1979).
use as geriatric for improvement of mental ability:
US 4 474 812 (Sigma-Tau; 2.10.1984; I-prior. 29.10.1982).
treatment of lung diseases:
DE 2 360 332 (Otsuka; appl. 4.12.1973; J-prior. 7.12.1972).
Formulation(s):
drinking sol. 1 g/10 ml; inj. sol. lg15 ml; syrup 1 g13.3 ml
Trade Name(s):
D: Biocarn (Medice)
L-Carn (Sigma-Tau)
F:
Uvoearnil (Sigma-Tau)

1: Anetin (Ibirn)
Biocarnil (Gentili)
Briocor
(Farge)
Cardimet (Errekappa
Euroter.)
Cardiogen (Chemil)
Carnitene (Sigma-Tau)
Carnitolo (Recordati
Farma)
Carnitop (Virginia Farmac.)
Carnovis (Duncan)
Carnum (Firma)
Carrier (Chiesi)
Carvit (AGIPS)
Eucar (Salus Research)
Eucarnil (Pulitzer)
Kernit (CT)
L-Carnitina
Coli (Coli)
Lefcar (Glaxo)
Levocarvit (Mitim)
Medocarnitin (Medosan)
358
C
Caroxazone
Metina (Pierrel)
Transfert (Piam) USA: L-Carnitine (Tyson)
Miocardin
(Magis)

J:
Abedine (Nippon Zoki) Carnitor (Sigma-Tau)
Miocor (Ecobi) Entomin (Maruko)
Miotonal (Caber)
Monocamin (Tanabe)
Caroxazone
ATC: N06A
Use: antidepressant
RN: 18464-39-6 MF: C1,Hl0N2O3 MW: 206.20 EINECS: 242-345-1
LD,,,: 728 mglkg (M. p.0.)
CN:
2-oxo-2H-1,3-benzoxazine-3(4H)-acetamide
NaHC03,
HZO.
CH2C12
NH3,
H20
COCI,
'
adNH2
phosgene
b
ethyl
(2-hydroxy-
benzyl0mino)acetate
NH2
Caroxazone
Reference(s):
CH 586 687 (Farmitalia; appl. 26.4.1974).
ZA 742 435 (Farmitalia; appl. 17.4.1974).

alternative synthesis:
US 3 427 3 13 (Farmitalia; 11.2.1969; I-prior. 23.12.1965, 14.9.1966).
Bernardi, L. et al.: Experientia (EXPEAM) 24,774 (1968).
Trade Narne(s):
I: Timostenil (Carlo Erba); Timostenil (Farmi talia);
w
fm
w
fm
Carpipramine
(Carbadipimidine)
ATC: N06B
Use: antidepressant
RN: 5942-95-0 MF: C2,H3,N,0 MW: 446.64 EINECS: 227-700-0
LD,,,: 28 mglkg (M, i.v.); 2180 mglkg (M, p.0.);
37 mgkg (R, i.v.); 1025 mglkg (R, p.0.)
CN: 1'-[3-(10,11
-dihydro-SH-dibenz[b~azepin-5-yl)propyl][l,4'-bipiperidine]-4'-carboxamide
dihydrochloride monohydrate
RN: 7075-03-8 MF: C,,H,,N,O. 2HC1
.
H,O MW: 537.58 EINECS: 230-372-1
LD,,,: 136 mglkg (M, i.p.); 28 mglkg (M, i.v.); 2180 mglkg (M, p.0.);
76 mglkg (R, i.p.); 37 mglkg (R, i.v.); 1025 mgkg (R, p.0.);
18 mgkg (rabbit, i.v.)
maleate
(1:l)
RN: 100482-23-3 MF: C2,H3,N,O
.
C,H,O, MW: 562.71

LDSo:
147 mglkg (M, i.p.); 2055 mglkg (M, p.0.);
169 mglkg (R, i.p.)
Carprofen
C
359
iminodibenzyl 1,3-dibrarna-
propane
b~
r
3-(10.11 -dihydra-
5H-dibenz[b.f]ozepin-
5-yl)propyl bromide
(I)
Reference(s):
JP
66
006 572 (Yoshitomi; appl. 29.6.1963).
Nakanishi, M. eta].: J. Med. Chem. (JMCMAR)
13,
644 (1970).
(1 ,4'-bipiperidine)-
medical use as anxiolytic, hypnotic:
Carpipromine
EP 374 042 (~h6ne-~oulenc; appl. 13.12.1989; F-prior. 16.12.1 988).
4'-corboxomide
(cf. piparnperone
synthesis)
Formulation(s):
powder

10
%;
tabl. 25 mg, 50 mg
Trade Nante(s):
F:
Prazinil (Pierre Fabre) J: Defekton (Yoshitomi)
Carprofen
ATC: MOlAE
Use: non-steroidal anti-inflammatory
RN: 53716-49-7 MF: C,SHI,C1N02 MW: 273.72 EINECS: 258-712-4
LD,,:
400
mglkg (M, p.0.)
CN:
(?)-6-chloro-a-methyl-9H-carbazole-2-ace
acid
1.
HCI
H
H,C-
0
CH3
+
H~c-o~,,cH~
s,
03:)
3. C2H,0H, HCI
b
I
0 0

sad~um
2.
4-chloraphenyl-
ethylate LCH3 hydrazine
2-cyclo- diethyl methyl-
hexen- malonate
1 -one
diethyl methyl-
(3-oxocyclohexyl)
rnalonote
360
C
Carteolol
H
2.
NaOH
CI
MoLcH3
,
ethyl
B-chloro-a-methyl-
1.2.3.4-tetrahydro-9H-
carbazole-2-acetate
(I)
Carprofen
Rej'erence(s):
US 3 896 145 (Hoffrnann-La Roche; 22.7.1975; prior. 17.5.1973, 24.7.1972).
Formulution(s):
tabl. 150 rng
Trade Name(s):

USA: Rirnadyl (Roche); wfrn
Carteolol
ATC: C07AA15; S01ED05
Use: beta blocking agent
RN: 51781-06-7 MF: C,,H,N,O, MW: 292.38
LD,,: 810 rnglkg (M, p.0.);
830 rnglkg (dog, p.0.)
CN:
5-[3-[(1,1-dirnethylethyl)arnino]-2-hydroxypropoxy]-3,4-dihydro-2(1~-quino1inone
monohydrochloride
RN: 51781-21-6 MF: C,6H,,N,0,
.
HC1 MW: 328.84 EINECS: 257-415-7
LD,,:
54.5rng/kg(M,i.v.);810n1g/kg(M,p.o.);
153 rnglkg (R, i.v.); 1330 rnglkg (R, p.0.);
830 rnglkg (dog, p.0.)
HOOC~CH~
Pd-C,
195
"C,
140
OC,
3h
~O
Ng
aNH2
-
decaline.3h
-1

acrylic
acid
0
0
0
cyclohexane-
3-amino-2-
1.3-dione
cyclohexenone
5-hydroxy- epichloro- 5-(2.3-epoxypropoxy)-
Corteolol
1,2.3.4-
hydrin
1.2.3.4-tetra-
tetrohydro-
hydroquinolin-2-one
quinolin-
2-one
(I)
Rej'erence(s):
Winkler, W.: Arzneirn Forsch. (ARZNAD) 33,279 (1983).
DOS 2 302 027 (Otsuka; appl. 16.1.1973; J-prior. 13.4.1972).
US 3 910 924 (Otsuka; 7.10.1975; appl. 19.1.1973; J-prior. 13.4.1972).