4-tluorobenz- ethyl
aldehyde isobutyrylacetate
ethyl 3-amino-
4-methyl-2-
pentenoate
1.
DDO,
CH2C12
2. Red-Al, THF
11
-
1.
2,3-dichloro-
5.6-dicyano-p-
benzoquinone
2.
sadium bis(2-
methoxyethoxy)-
dihydridoaluminate
2.6-diisopropyl-
4-(4-fluoropheny1)-
5-methoxymethyl-
3-pyridine-
carboxaldehyde
(111)
ethyl 2-isobutyryl-
3-(4-fluoropheny1)-
acrylate (I)
CH3~ CH3
H3c~~~cH3

F
diethyl 1,4-dihydro-2,S-
diisopropyl-4-(4-fluoropheny1)-
pyridine-3.5-dicarboxylate
(11)
F
ethyl 2,6-diisopropyl-4-
(4-fluorophenyl)-5-hydroxy-
methylpyridine-3-carboxylate
H~C'
diethyl 2-
(cyclohexylamino)-
vinylphosphonate
1.
H3C-I, NOH, THF
2. LiAlk. THF
1.
methyl iodide
2. lithium aluminum
hydride
3. pyridinium
chlorochromate
NOH. THF. 25 OC
d
N
0 0
THF,
-65
OC
+

,
v
H3C
u~/CH3
2. triethylborane
methyl
acetoacetote
412
C
Cerivastatin
sodium
1.
THF,
50
"C
2.
chromotogrophic
separation of
O,
diosteromers
CH3
+
H2N
OH
F
methyl erythro-(E)-7-[2,6-diisopropyl- (+)-(~)-~hen~l-
4-(4-fluorophenyl)-5-methoxymethyl- glycinol
3-pyridyll-3,5-dihydroxy-hept-6-enoote
(V)
1

Cerivostotin sodium
1.
NoOH
chrornotogrophicseparotion
of enontiomers
2.
HCI
with chirol phase "Boychirol
PM'
v
-+
H,C'
b
(+)-VII
OH
F
Cerivostotin sodium
u
Reference(s):
a
DE 4 040 026 (Bayer; appl. 14.12.1990).
EP 325 130 (Bayer AG; appl. 9.1.1989; D-prior. 20.1.1988).
EP
491 226 (Bayer AG; appl. 3.12.1991; D-prior. 14.12.1990).
AU 9 189 615 (Bayer AG; appl. 11.12.1991; D-prior. 14.12.1990).
(R)-(+)-a-phenethylamine
can
be
used instead
ofS-(+)-phenylglycinol.

b
Drugs Future (DRFUD4) 19,537-541 (1994).
Formulation(s):
tabl. 0.1
mg,
0.2 mg, 0.3
mg
Trade Name(s):
D: Lipobay (Bayer) GB: Lipobay (Bayer)
USA:
Baycol (Bayer)
Ceruletide
C
413
Ceruletide
(Caerulein)
ATC: V04CC04; V04CK
Use: diagnostic (for pancreatic function),
stimulant of gastric secretory
RN: 17650-98-5 MF:
C5RH73N1302LS2
MW: 1352.42
LD,,:
1012 mgkg
(M,
i.v.)
CN:
5-oxo-~-prolyl-~-glutaminyl-~-a-asparty-O-sulfo-~-tyrosyl-~-threonylglycyl-~-tryptophyl-~-methionyl-
L-a-aspartyl-L-pheny lalanin amide
Boc-Tyr Boc-Tyr-NH-NH-Z Tyr-NH-NH-Z

.
HCI
(I)
0
Boc:
40&?H,
CH3
H
N
COOH
,
+
Boc'
-
4
-ifO\Bzl
0
1.
HCI
______,
2.
Boc-Gln
1.
HCI
Boc,
2.
Z-Pyr
Pyr-Gln-Asp-Tyr-N,
(N)
414

C
Ceruletide
1.
HCI
3.
HCI
v
______*
Tcp:
bCl
CI
HCI
COOH CH3
Ac-Thr-Gly-Trp-Met-Asp-Phe-NH
.
HCI
(VI)
H
Pyr-Gln-kp
-Tyr(s03H)-Thr(Ac)-~ly-Trp-Met-Asp-Phe-NH
(W)
Ceruletide
DE
1
643 504 (Soc. Farmaceutici Italia; appl. 6.4.1972; I-prior. 9.8.1966).
US
3 472 832 (Soc. Farmaceutici Italia; I-prior. 9.8.1966).
Bernardi,
L.
et al.: Experientia (EXPEAM)

23,
700 (1967).
structure and isolation from Hyla caeruleu:
Anastasi,
A.
et al.: Experientia (EXPEAM)
23,
699 (1967).
Cetalkonium chloride
C
4
15
Formulation(s):
amp. 5 ~glml, 40 pgl2 ml; vial 20 kg, 30 kg, 40 kg
Trade Name(s):
D:
Takus (Pharmacia
&
J: Ceosunin (Kyowa Hakko)
Upjohn)
Cetalkonium chloride
ATC: SOlAA
Use: antiseptic, bactericide
RN: 122-18-9 MF:
C2,H4,C1N MW: 396.10 EINECS: 204-526-3
CN:
N-hexadecyl-N,N-dimethylbenzenemethanaminium
chloride
cetyl chloride dimethyl-
omine

N-cetyl-N,N-
dimethylomine
(I)
Reference(s):
FR
77
1
746
(I.
G. Farben; 1934).
Formulation(s):
sol.
13
g/100
g,
130 mg
Trade Narne(s):
benzyl chloride
D:
Baktonium (Bode) F: Pansoral (Pierre Fabre GB: Bonjela (Reckitt
&
Mundisal (Mundipharma)- SantC)-comb. Co1man)-comb.
comb. J: Lazal (Shionogi)
Cetalkonium chloride
Cethexonium bromide
ATC: DOSAX; R02AA20
Use: antiseptic
RN: 1794-74-7 MF:
C2,H,,BrN0
MW:

448.57
CN:
N-hexadecyl-2-hydroxy-N,N-dimethylcyclohexanaminium
bromide
chloride
RN: 58703-78-9 MF: CxHSoCINO MW: 404.12
2-amino- cetyl
cyclohexanol bromide
(1)
416
C
Cetiedil
(yH2)15-CH3
1.
anion exchanger.
,-
(OH- form)
Nap, 2. HCI
11
+
I-CH,
b
cethexonium iodide cethexonium chloride
Keference(s):
Winternitz,
F.
et al.: Bull. Soc. Chim. Biol. (BSCIA3)
33,
369 (1951).
cyclohexane dimethyl- 2-dimethyl-

Formulation(s):
collutorium 0.025 g1100 ml, 0.1 mgI0.4 ml, 0.3 gI100 ml; eye.drops 0.025
%
(bromide);
ointment 1 dl00 g; powder 1.5 gllOO g; sol 50 rng/100 ml
Cethexoniurn bromide
Trade Name(s):
F: Biocidan (Menarini)
oxide amine aminocyclo-
hexanol
Cetiedil
ATC:
C04AX26
Use: vasodilator (peripheral)
RN: 141 76- 10-4
MF:
C,,,H3,N0,S MW: 349.54 EINECS: 238-028-2
LD,,,:
1726
mg/kg
(M, p.0.)
CN:
a-cyclohexyl-3-thiopheneacetic
acid
2-(hexahydro-IH-atepin-1-y1)ethyl
ester
citrate
(1:l)
RN: 16286-69-4 MF: C2,,H3,N02S
.

C6HR0,
MW: 541.66 EINECS: 240-381-2
(C2~5)20.
-70
OC
COOH
3
cyclohexyl- 3-thienyl-
glyoxylic ocid lithium
(from 3-bromo-
thiophene and
butyllithiurn)
cyclohexyl- cyclohexyl-
(3-thienyl)- (3-thieny1)-
glycolic acid acetic acid (1)
1-(2-chloroethy1)- Cetiedil
hexohydro-
1H-
ozepine
Cetirizine
C
417
Referencefs):
FR
1
460 571 (InnothCra; appl. 10.6.1965).
FR-M 5 504 (Innothefa; appl. 10.6.1965).
Robba, M.; Guen,
Y.
Le: Chim. Ther. (CHTPBA)

1967
(No. 2), 120.
synthesis of starting materials:
Robba, M.; Guen,
Y.
Le: Chim. Ther. (CHTPBA)
1966
(No. 4), 238.
FR-appl. 2 260 575 (Innothefa; appl. 11.2.1974).
FR-appl. 2 260 576 (ImothQa; appl. 11.2.1974).
synthesisfrom
3-thienylacetonitrile:
US
4
108 865 (Labaz; 22.8.1978; prior. 29.8.1974, 1.3.1976).
Formulation(s):
cps. 100 mg (as citrate)
Trade Name(s):
F:
Stratene (Gerda)
Vasocet (Cipharm)
I:
Stratene (Sigma-Tau);
wfm
Cetirizine
ATC: R06AE07
Use: non-sedative antihistaminic
RN:
83881-51-0
MF:

C21H25C1N203 MW: 388.90
CN:
(~)-[2-[4-[(4-chlorophenyl)phenylmethyl]-I-piperazinyl]ethoxy]acetic
acid
dihydrochloride
RN: 83881-52-1 MF: C21H25CIN203 .2HCI
MW:
461.82
LD,:
365 mg/kg (R, p.0.);
>320 mgkg (dog, p.0.)
Q+-CH~
H
0+LCH3
&
+
(;I
No2COJ
HCI
___,
(;I
___,
[;I
CI
H
cfoC,
dnc,
4-chlorobenzhydryl N-corbethaxy-
ethyl 4-(4-chlorabenzhydryI)-
1 -(4-chl~radi~henyl-

chlo"de piperorinc piperazine-
1
-carbarylate methyl)piperozine
(I)
0
0
Cl-~JoA+3
9
Na2C03
I
b
methyl 2-(2-chloroethoxy)-
acetate
.
sodium
carbonate
methyl
2-[Z-[4-(4-
Cetiririne
chlarodiphenylmcthyl)-
1
-piperazinyl]ethoxy]ocetate
Referencefs):
EP
58 146 (UCB; appl. 5.2.1982; GB-prior. 6.2.1981, 8.4.1981).
alternative synthesis (also enantiomers):
GB
2 225 321 (UCB; appl. 23.11.1988).
EP
801 064 (UCB; appl. 9.4.1997; BE-prior. 10.4.1996).

WO 9 737 982 (UCB;-~~~I. 28.3.1997; ~~-~rior. 4.10.1996).
WO 9 802 425 (Apotex; appl.
1
1.7.1997; CA-prior. 11.7.1996).
418
C
Cetrimonium bromide
synthesis of
1-(4-chlorodipheny1methyl)piperazine:
US 2 8 19 269 (Abbott; 1958).
HU 17 343 (Richter Gedeon; appl. 26.5.1977).
US 2 709 169 (UCB; 1952).
4
Formulatlon(s).
drops 10 mg, sol 0
1
%,
tab1 10 mg (as dihydrochloride)
1
4
Trade Name(s)
D. Zyrtec (UCB, Rodleben, GB Zlrtek (UCB) USA. Zyrtec (Pfizer, as
Vedim) I.
Formlstln (Formenti, 1990) h ydrochlonde)
F Vlrllx (SynthClabo) Vlrllx (Chemil)
Zyrtec (UCB) Z~rtec (UCB; 1990)
Cetrimonium bromide
(Cetrimide)
ATC: R02AA17
Use: antiseptic

RN: 57-09-0 MF: C,,H,,BrN MW: 364.46 EINECS: 200-311-3
LD,,,: 32mgkg(M,i.v.);
44
mgkg (R, i.v.); 410 mgkg (R, p.0.)
CN:
N,
N, N-trimethyl- 1 -hexadecanaminium bromide
hydroxide
RN: 505-86-2 MF: C,,H,,NO MW: 301.56 EINECS: 208-022-4
cetyl bromide trimethylamine
Cetrirnonium bromide
I
Shelton, R.S. et al.: J. Am. Chem. Soc. (JACSAT) 68,753 (1946).
Formulation(s):
sol. 117 mg1100 g; tabl. 4 mg
Trade Name(s):
D: Lemocin (Novartis Buccawalter (SmithKline GB:
Consumer Health)
Beecham)-comb.
Xylastesin (Espe)
CCtavlon (Zeneca)
numerous combination
DCrinox (ThCrabel Lucien)- I:
preparations comb.
F: Aseptit (Riom) Rectoquotane (Evans J:
Medical)-comb.
Ceanel
Conc. (Quinodem)-
comb.
Cetavlex (Zeneca)

Cetavlon (Zeneca)
Xylonor
(0gna)-comb.
Cetavlon (Sumitorno
Chem.)
Cetrorelix
(SB-75; D-20761)
ATC: HOlCC02
Use: LHRH-antagonist
RN: 120287-85-6 MF: C,,H,,ClN,,O,, MW: 143 1 .O6
CN:
N-Acetyl-3-(2-naphthalenyl)-~-alanyl-4-choro-~-phenyaanyl-3-(3-pyridinyl)-~-alanyl-~-seryl-~-
tyrosyl-~-(aminocarbonyl)-~-ornithyl-~-leucyl-~-arginy~-~-prolyl-~-alaninamide
Cetrorelix
C
419
acetate
RN:
145672-81-7 MF: C70Hy2ClN,7014
.
xC2H402 MW:
unspecified
diacetate
RN: 130143-01-0 MF: C70Hy2ClN,70,4~2C2H402 MW: 1551.17
trifluoroacetate
RN: 130289-71-3 MF: C70Hy2ClN17014
.
C2HF,0, MW: 1545.09
pamoate
RN: 132741 -85-6 MF: C70Hy2ClN170,4

.
C2,H,,0, MW: 1819.44
@
solid-phom synthesis:
0-(p-C1)Phe 0-Pol
Ssr
TY~ 0-Cit
Leu
Pro 0-Ala
Cit:
Pal:
Nal:
(p-CI)Phe:
Boc:
BZL:
2-Br-2:
Ac:
Tos:
LBZL
'-
Boc
OH
H-
7p
BZL
BZL
citrulline (N~-~arbamo~lornithine)
3-pyridylalanine
2-naphthylalanine
4-chlarophenylolonine

tert-butoxycarbonyl
benzyl
2-bromabenzyloxycarbonyl
acetyl
tosyl
Bos
NH-R
Boc
NH-R
NH-A
,2-Br-Z
,2-Br-Z
.2-Br-Z
NH-R
,2-Br-Z
NH-R
,2-Br-2
I I
v
I I
NH-R
,2-Br-Z
To*
,
NH-R
,2-Br-Z
To*
NH-R
NH2
polystyrene-

divinylbenzene
CH3 (MBHA-resin)
After cleovoge from the resin the crude peptide is dissolved
in aqueous acetic
acid and purified via prep. HPLC.
420
C
Cetrorelix
Cetrorelix
@
clossicol,
liquid-phose
synthesis:
Cetrorelix
u
obbreviotions
see
method
a
Reference(s):
a
Bajusz, S. et al.: Int J. Pept. Protein Res. (IJPPC3) 32,425 (1988).
EP 299 402 (ASTA Medica; appl. 11.7.1988; USA-prior. 17.7.1987).
a,b
Kleemann, A. et al.: Proc. Akabori Conf.: Ger Jpn. Symp. Pept. Chem., 4th, 1991,96-101.
b
Kunz, F.R. et al.: Proc. Akabori Conf.: Ger Jpn. Symp. Pept. Chem., Sth, 1994, 15-16.
long-acting injection suspension with pamoate salt:
US 773 032 (ASTA Medica; 10.6.1996; ~-~rior. 9.12.1993).
sterile acetate formulation:

EP 61 1 572 (ASTA Medica; D-prior. 19.2.1993).
use in fertility control:
EP 788 799 (ASTA Medica; USA-prior. 7.2.1996).
use for
BPH
or prostate cancer:
WO
9 810 781 (ASTA Medica; USA-prior. 12.9.1996).
Formulation(s):
vial 0.25 mg, 3 mg (as acetate)