olurninurn N-chlaro- chloride succinimide ?ejerences: I Juby, P.F.. alternative synthesis described DOS 2 004 038 Bristol-Myers; appl.. 2.5 mg Trade Names: D: Librax Roche-comb.. I: L
Trang 1Clidinium bromide C 501
potassium
cyanide
1 AICI3 'if
2 H,, Pd-C
V -, 11
1 olurninurn N-chlaro-
chloride succinimide
?ejerence(s):
I Juby, P.F et al.: J Med Chcm (JMCMAR) 15,1297 (1972)
(alternative synthesis described)
DOS 2 004 038 (Bristol-Myers; appl 29.1.1970; USA-prior 3 1.1.1969)
US 3 565 943 (Bristol-Myers; 23.2.1971; prior 17.9.1969, 3 1.1.1969)
US 3 663 627 (Bristol-Myers; 16.5.1972; prior 1.6.1970)
lltemative synthesis:
10s 2 330 856 (Takeda; appl 16.6.1973; J-prior 19.6.1972, 21.1 1.1972)
" 'Name(s):
: Britai (Bristol-Banyu) Indanol (Takeda)
Use: anticholinergic
N: 3485-62-9 MF: C22H2,BrN0, MW: 432.36 EINECS: 222-471-3
,DS0: 16 mgkg (M, i.v.); 492 m g k g (M, p.0.);
26 mgkg (dog, i.v.)
!N: 3-[(hydroxydiphenylacetyl)oxy]-l-methyl-l-azoniabicyclo[2.2.2]octane bromide
methyl iso- ethyl bromo-
nicotinote acetate
2 HCI
b
" +
H2, PtO
3 - 0 x 0 - quinuclidine
3-hydroxy- quinuclidine (11)
Trang 2502 C Clindamycin
brnzilic
chloride
Clidinium bromide
Reference(s):
US 2 648 667 (Hoffmann-La Roche; 1955; prior 1951)
Formulation(s): drg 2.5 mg
Trade Name(s):
D: Librax (Roche)-comb with GR: Libraxin (Roche)-comb I: Librax (Roche)-comb with chlorodiazepoxide; wfm with chlorodiazepoxide; chlorodiazepoxide
F: Librax (Roche)-comb with wfm USA: Librax (Roche)-comb with
Use: antibiotic RN: 18323-44-9 MF: C,,H&1N,05S MW: 424.99 EINECS: 242-209-1
LDso: 2618 m g k g (R, s.c.)
CN: (2s-trans)-methyl 7-chloro-6,7,8-trideoxy-6-[[(I -methyl-4-propyl-2-pyrrolidinyl)carbonyl]amino]-l-thio- L-threo-a-D-gulucto-octopyranoside
monohydrochloride
RN: 21462-39-5 MF: C,,H&IN205S HCI MW: 461.45 EINECS: 244-398-6
LD,,,: 245 mglkg (M, i.v.); 2539 m g k g (M, p.0.);
2193 m g k g (R, p.0.)
Clindamycin I
Reference(s):
US 3 496 163
DE 1 795 740
US 3 418 414 (Upjohn; 24.12.1968; appl 31.8.1966)
US 3 475 407 (Upjohn; 28.10.1969; appl 22.12.1967)
US 3 509 127 (Upjohn; 28.4.1970; appl 30.4.1968)
use a s antimalarinl:
US 3 627 887 (Upjohn; 14.12.1971; appl 17.10.1969)
Trang 3Clinofibrate C 503
Rydon reagent:
Landauer, S.R.; Rydon, H.N.: 1 Chem Soc (JCSOA9) 1953,2224
Coe, D.G et al.: J Chem Soc (JCSOA9) 1954,2281
Rydon, H.N.; Tonge, B.L.: J Chem Soc (JCSOA9) 1956, 3043
Formulation(s): amp 300 mg12 ml, 600 mgl4 ml, 900 mg16 ml; cps 150 mg, 300 mg; gel 10 mglg;
sol 10 mglml (as hydrochloride or phosphate); vaginal cream 20 mg
Trade Namefs):
D: Sobelin (Upjohn; 1968) Clinamycina (Savoma) USA: Clcocin (Pharmacia &
generics Dalacin C (Pharmacia & Upjohn; 1970)
F: Dalacine (Pharmacia & Upjohn; 1969) Clinda-Derm (Paddock) Upjohn; 1972) I: Dalacin C (Upjohn) Clindets Pledgets (Stiefel) GB: Cleocin (Upjohn) 1: Dalacin (Upjohn; 197 1)
Use: antihyperlipidemic, clofibrate derivative
RN: 30299-08-2 MF: C2,H3,0, MW: 468.59
LD,,: 255 mglkg (M, i.p.); 1800 mglkg (M, p.0.); 410 mglkg (M, s.c.);
205 m a g (R, i.p.); A 0 0 0 mglkg (R, p.o.1; 2200 mglkg (R, s.c.)
CN: 2,2'-[cyclohexylidenebis(4,1-phenyleneoxy)]bis[2-methylbutanoic acid]
cyclo- phenol
hexanone
u
1 l -bis(4-hydroxy- phenyl)cyclohexone (I)
Referencefs): -
US 3 716 583 (Sumitomo; 13.2.1972; appl 7.4.1970; J-prior 16.4.1969)
US 3 821 404 (Sumitomo; 28.6.1974; J-prior 16.4.1969)
DOS 2 017 331 (Sumitomo; appl 10.4.1970; 1-prior 16.4.1969,2.5.1969)
0 COOH
synthesis of 1,l-bis(4-hydroxyphenyl)cyclohexane:
DD46 281 (G Drefahl, E Littmann; appl 22.1.1962)
Formulation(s): tabl 100 mg, 200 mg
Trade Namefs):
I : Deslipoze (Kowa Yakuhin) Lipirate (Hishiyama) Lipofibrate (Taiyo) Lipaderin (Uji) Lipoclin (Sumitomo; 1981) Prinmate (Sawai)
Trang 4504 C Clioquinol
Clioquinol
(Chloroiodoquine; Iodochlorhydroxyquin)
ATC: D08AH30; D09AA10; GOlAC02;
PO I AA02; S02AA05 Use: wound- and bowel-antiseptic RN: 130-26-7 MF: C9HsC11N0 MW: 305.50 EINECS: 204-984-4
LD,,,: 69 m g k g (M, p.0.);
>5 g/kg (R, p.0.)
CN: 5-chloro-7-iodo-8-quinolinol
oxyquinoline 5-chloro-B-
(4- V-1 hydroxyquinoline
Reference(s):
DRP 1 17 767 (Ciba; 1899)
Formulation(s): cream 3 gI100 g; emulsion 0.5 g1100 g; ointment 3 g/100 g
Trade Name(s):
D: Linola-sept (Wolff)
Locacorten-Vioform
(Novartis Pharma)-comb
Millicorten-Viofoml I:
(Novartis Pharma)-comb
F: Diprosept (Schering-
Plough)-comb
GB: Betnovate-C (Glaxo
Wellcome)-comb
Locorten-Vioform
(Novartis)-comb
Synalar C (Zeneca)-comb
Vioform-hydrocortisone (Novartis)-comb
Dermadex Chino1 J:
(SmithKline Beecham)- comb
Diproform (Schering- Plough)-comb
Iodoclorossich TI (Tariff USA:
Integrativo) Locorten (Zy ma)-comb
Reticus (Farmila)-comb Viobeta (ID1)-comb Viocidina (IDI) Emaform (Tanabe) Entero-Vioform (Ciba- Geigy -Takeda) Mexaform (Ciba-Geigy- Takeda)-comb Racet (Lemmon)-comb.; wfm
Vioform (Ciba); wfm
Use: minor tranquilizer RN: 223 16-47-8 MF: CI6H,,C1N2O2 MW: 300.75 EINECS: 244-908-7
LD,,,: 5 10 m g k g (M, i.p.); 840 m g k g (M, p.0.);
>2000 mglkg (R, p.0.)
CN: 7-chloro-1 -methyl-5-phenyl- 1 H- 1.5-benzodiazepine-2,4(3H,SH)-dione
1 -3-dichloro-
benzene
5-chloro-2-
nitrodiphenyl-
Trang 5Clobenoside C 505
I
manoethyl
rnolonyl
chloride
1 -demethyl- clobazam (11)
Clabazam
L
DAS 1 793 837 (Roussel-Uclaf; appl 14.12.1967; I-prior 14.12.1966)
US 3 984 398 (Roussel-Uclaf; 5.10.1 976; I-prior 14.12.1966)
US 3 836 653 (Boehringer Ing.; 17.9.1974; D-prior 7.2.1967, 18.1
DOS 1 670 190 (Boehringer Ing.; appl 7.2.1967)
DOS 1 670 306 (Boehringer Ing.; appl 18.1.1968)
Weber, K.H et al.: Justus Liebigs Ann Chem (JLACBF) 756, 128
I-demethylclobazam:
DAS 1 668 634 (Roussel-Uclaf; appl 14.12.1967; I-prior 14.12.19
synthesis of 5-chloro-2-nitrodiphenylamine:
Laubenheimer: Ber Dtsch Chem Ges (BDCGAS) 9,771 (1876)
combination with nomifensine:
DOS 2 724 683 (Hoechst; appl 1.6.1977)
Formulation(s): cps 10 mg; tabl 10 mg, 20 mg
Tmde Name(s):
D: Frisium (Hoechst; 1977) GB: Frisium (Hoechst; 1979)
F: Urbanyl (SynthClabo; I: Frisium (Hoechst Italia
Use: anti-inflammatory, vasoprotective
RN: 29899-95-4 MF: C2sH,2C1,0, MW: 499.43 EINECS: 249-940-5
CN: ethyl 5,6-bis-0-[(4-chlorophenyl)methyl]-3-O-propyl-~-glucofuranoside
Trang 6506 C Clobenzorex
1.25.6-di-0-
isopropylidene-
a-0-glucofuronose
1 HCI CH30H
2 Hz Pd-C
I -*
NoOH
ally1 bromide
'3'3
1.2-0-isopropylidene- 3-O-propyl-a-O-
glucofuronose
HCI C2H50H
A
KOH
4-chlorobenzyl chloride
I Clobenoside
Reference(s):
DOS 1 793 338 (Ciba-Geigy; appl 3.9.1968; CH-prior 11.9.1967)
US 3 665 884 (Ciba-Geigy; 11.4.1972; CH-prior 1 1.9.1967) -
US 3 542 76 1 (Ciba-Geigy; 24.11.1970; appl 25.4.1968; CH-prior 1 1.9.1967)
synthesis of I ,2-O-isopropylidene-3-O-propy~-a-~-glucofuranose:
DOS 2 031 161 (Ciba; appl 24.6.1970; CH-prior 3.7.1969)
Cunningham, J et al.: Tetrahedron Lett (TELEAY) 19, 1191 (1964)
Corbettand, W.M.; McKay, J.E.: J Chem Soc (JCSOA9), 2930 (1961)
Fomulation(s): tabl 200 mg, gel
Trade Narne(s):
CH: Aglidin (Zyma)
Arvigol (Zyma)
Finocal (Zyma) Flogasol (Vifor)
Use: appetite depressant RN: 13364-32-4 MF: C,,H,,CIN MW 259.78 EINECS: 236-434-4
CN: (+)-N-[(2-chlorophenyl)methyl]-a-methylbenzeneethanamine
Trang 7Clobenztropine C 507
hydrochloride
RN: 5843-53-8 MF: C,,H,,ClN HCl MW: 296.24 EINECS: 227-434-5
LD,: 103 mg/kg (M, i.p.);
:: I03 mglkg (R, i.p.)
dexomphet- 2-chloro-
Clobenzorex
Reference(s):
FR 1 429 306 (S I F A,; appl 23.1 1.1964)
Formulation(s): cps 30 rng (as hydrochloride)
Trade Name(s):
F: Dinintel (Roussel Diarnant;
as hydrochloride)
Clobenztropine
(Chlorobenztropine)
ATC: R06 Use: antihistarninic RN: 5627-46-3 MF: C,,Hz4C1N0 MW: 341.88
CN: 3-[(4-chlorophenyl)phenylmethoxy]-8-methyl-8-azabicyco[3.2.l]octane
hydrochloride
RN: 14008-79-8 MF: C2,Hz4CINO HCI M W 378.34
LD,: 174 mglkg (M, p.0.);
364 mg/kg (R, p.0.)
xylene, 145-155 '
tropine 4-chlorobenz-
hydryl chloride I Clobenztropine I
Reference(s):
US 2 782 200 (Schenley Labs.; 1957; appl 1955)
alternative synthesis (with 4-chlorodiphenyldiazornethane):
US 2 799 680 (S Promer; 1957; appl 1954)
Trade Name(s):
USA: Teprin (Endo); wfm
Trang 8'I
508 C Clobetasol propionate
Clobetasol propionate ATC: D07ADO1
Use: topical glucocorticoid RN: 25122-46-7 MF: C2,H,,CIF0, MW: 466.98 EINECS: 246-634-3
LD,,: >3 g/kg (M, p.0.);
>3 d k g (R, p.0.)
CN: (1 1 P, 16P)-21-chloro-9-fluoro- 16-methyl-17-(1 -oxopropoxy)pregna-1,4-diene-3,20-dione
clobetasol
RN: 25122-41-2 MF: C2,H28ClF0, MW: 410.91 EINECS: 246-633-8
belamethasone 17-propianate
(cf betomethasone dipropionate
synthesis)
lithium acetone
chloride
methonesulfonyl chloride
Clobetasol propianate
DE 1 902 340 (Glaxo; appl 17.1.1969; GB-prior 19.1.1968)
US 3 721 687 (Glaxo; 20.3.1973; GB-prior 4.4.1968)
Formulation(s): cream 0.05 %; ointment 0.05 %; sol 0.5 mglg (0.05 %)
Trade Name(s):
D: Dermoxin (Glaxo
WellcomelCascan; 1976)
Dermoxinale (Glaxo
WellcomelCascan; 1977)
Karison (Dermapharm)
F: Dermoval (Glaxo
Wellcome)
GB: Dermovate (Glaxo
Wellcome; 1973)
I: Clobesol (Glaxo Myalore (Ohta)
J: Betaleston (Nihon Solvega (Hisamitsu) Yaku hin) USA: Cormax (Oclassen) Delspart (Kodama) Temovate (Glaxo Dermovate (Glaxo; 1979) Wellcome; 1986) Entyfluson (Taiyo)
Glydil (Shinshin) Mahady (Wukamoto)
Clobetasone butyrate ATC: D07ABO1; SOlBA09
Use: topical glucocorticoid RN: 25 122-57-0 MF: C2,H3,C1FOS MW: 478.99 EINECS: 258-953-5
LD,,,: >6 glkg (M, p.0.);
>6 glkg (R, p.0.)
CN: (16~)-21-chloro-9-fluoro-16-methyl-17-(1-oxobutoxy)pregna-1,4-diene-3,11,20-trione
Trang 9Clobetasone butyrate C 509
*
dobetasone
$ RN: 54063-32-0 MF: CzzH2,ClF0, MW: 408.90
betamethasane 17-butyrote methone-
sulfonyl chloride
I Clobetosone butyrote I
Reference(s):
DE 1 902 340 (Glaxo; appl 17.1.1969; GB-prior 19.1 l968)
US 3 721 687 (Glaxo; 20.3.1973; GB-prior 4.4.1968)
cf, synthesis of betamethasone- 17-butyrate
Formulation(s): eye drops 0.1 %; cream, ointment 0.5 mg/g (0.05 %)
Tmde Name(s):
D: Emovate (Glaxo; 1980) Trimovate (Glaxo Visucloben (Merck Sharp
GB: Clobuvate (Dominion) Wellcome)-comb & Dohme)
Eumovate (Glaxo I: Eumovate (Glaxo; 1983) J: Kindavate (Glaxo; 1984) Wellcome; 1975)
Trang 10510 C Clobutinol
Use: antitussive RN: 14860-49-2 MF: C14H22CIN0 MW: 255.79 EINECS: 238-926-4
LD,,: 53 mglkg (M, i.v.); 334 rnglkg (M, p.0.);
63 mg/kg (R i.v.); 802 mglkg (R, p.0.);
45.3 mglkg (dog, i.v.)
CN: 4-chloro-a-[2-(dimethylamino)-l-methylethyl]-a-rnethylbenzeneethanol
hydrochIoride
RN: 1215-83-4 MF: CI,H,,CINO~ HC1 MW: 292.25 EINECS: 214-931-7
LD,,,: 40.9 mglkg (M, i.v.); 334 mglkg (M, p.0.);
63 mglkg (R, i.v.); 802 rnglkg (R, p.0.);
45.3 mglkg (dog, i.v.)
4-chlorobenzyl- 4-dimethylomino- I Clobutinol
magnesium chloride 3-methyl-2-butanone
Refereta(s):
DE 1 146 068 (Thomae; appl 21.3.1959)
DE 1 150 686 (Thomae; appl 12.5.1960)
US 3 121 087 (Thomae; 11.2.1964; prior 18.3.1960, 28.6.1961)
Engelhorn, R.: Arzneh-Forsch (ARZNAD) 10,794 (1960)
alternative synthesis:
DE 1 153 380 (Thomae; appl 21.5.1959)
Formulation(s): amp 20 mg12 rnl; drg 40 mg; cps 40 mg, 80 mg; drops 40 mg10.67 rnl; syrup 40 mg/lOml (a
hydrochloride)
Trade Name(s):
D: Mentopin (Hermes) Silomat (Boehringer Ing.) Silornat cornpos~turn Nullatuss (Pharma Tussamed (Hexal) (Fher)-comb
Wernigerode) F Silomat (Boehringer Ing.) J: S~lomat (Morishita) Rotafuss (MIP Pharrna) I: Silomat (Fher)
Use: thyrnoleptic RN: 47739-98-0 MF: C2,H,,CIN,0 MW: 481.08
CN: I'-[3-(3-chloro-10,11-dihydro-SH-d1benz[bJlazepin-5-yl)propyl][1,4'-bipiperidine]-4'-carboxamide
hydrochloride hydrate
RN: 28058-62-0 MF: C2,H3,C12N,0 HC1 H 2 0 MW: 572.02