formulation with penicillins and cephalosporins: DOS 2 559 41 1 Beecham; appl.. with amoxicillin Trade Names: D: Augmentan SmithKline Beecham; 1982-comb.. with amoxicillin Betabactyl S
Trang 1Hepasteril B compositum, Reducdyn (Nordmark)- F: Thioncycline (Merrel1)-
wfrn
Use: liver therapeutic RN: 372-75-8 MF: C6H,,N303 MW: 175.19 EINECS: 206-759-6
CN: fl-(aminocarbony1)-L-ornithine
malate (1:l)
RN: 70796-17-7 MF: C6H,,N303 C,H,O, MW: 291.26
@ by fermentation
o from Socchorornyces genus
L-arginine hydrochloride
b from orniihine
Citrulline
c from Arthrobaciel
Referencefs):
1 Fox, S.W.: J Biol Chem (JBCHA3) 123,687 (1938)
2a JP 52 143 288 (Kyowa; appl 20.5.1976)
2b JP 50 148 588 (Miura; appl 23.5.1974)
2c JP 53 075 387 ( ~ y o w a ; appl 13.12.1976)
alternative syntheses:
JP 122 48/67 (Ajinomoto; appl 1 1.9.1965)
JP 117 58/68 (Kyowa; appl 15.1 1.1965)
Fox, S.W et al.: J Org Chem (JOCEAH) 6, 410 (1 941)
crystallization:
JP 7 100 174 (Ajinomoto; appl 20.1 1.1968)
isolation from Citrullus vulgaris Schrad.:
Wada, M.: Biochem Z (BIZEA2) 224,420 (1930)
use as liver therapeutic:
FR-M 4 182 (Inst de Recherche Sci.; appl 9.3.1965)
FR-M 5 594 (Dimaphar; appl 1.7.1966)
FR-M 5 703 (Lab Carriere Carron; appl 30.8.1965)
FR-M 6 305 (Dimaphar; appl 15.12.1966)
use as digestant:
FR-M 5 695 (Lab Carriere Carron; appl 29.8.1966)
citrulline fumarate:
FR-M 6 306 (Dimaphar; appl 15.12.1966)
Trang 2492 C Cladribine
citrulline maleate:
FR-M 6 443 (Dimaphar; appl 21 A.1967)
Formulation(s): amp 60 mg/15 ml; drg 25 mg, 100 mg
Trade Name(s):
D: Polilevo (Taurus Pharma)- Perifago (Pharmacia & Citruplexina (Synthe1abo)-
F: Azonutril (Pharmacia & Stimol (Biocodex; as Ipoazotal (SIT)-comb
Epurarn (Pharmafarm)- I: Biotassina (UCM)-comb
comb
Cladribine
(NSC- 105014-F; RWJ-2625 1 ; 2-CdA)
RN: 4291-63-8 MF: C,,H,,CIN,O, MW: 285.69
CN: 2-chloro-2'-deoxyadenosine
ATC: LOlBB04 Use: antineoplastic
CH, 2.6-dichloro- 2-deoxy-3.5-di-O-p-
p u r i n e toluayl-a-D-erythro-
pentofuronosyl chloride
1 NH3, CH,OH 100 O C
2 chrornatogrophy
Clodribine
I
purine (I)
Trang 3guanosine
1 pyridine OMF k
1 pentyl nitrite, K2C03,
CH2C12 (C,H,),CCI
2 NH,OH, THF
OH OH
Z-chloro- odenosine
pyridine
111 1.3-dichloro- 1 l.3,3-tetro-
DMAP, ocetonitrile
+ c ' r O ~ -+
0-phenyi chloro- thioformote
1 Bu3SnH AIBN, benzene, A
2 Bu,N+F- THF
Clodribine
1 tributyltin hydride
2 tetrobutvlommonium fluoride E l
2-chloro-2'-0-phenoxy-
thiocorbonyl-3'.5'-0-
(tetroisopropyldisiioxonylene)-
Trang 4494 C Clavulanic acid
Refc?rence(s):
a Kazimierczuk, Z et al.: J Am Chem Soc (JACSAT) 106,6379-6382 (1984)
EP 173 059 (Univ Brigham Young; appl 17.7.1985; USA-prior 6.8.1984, 15.1.1987)
Christensen, L.F el al.: J Med Chem (JMCMAR) 15,735 (1972)
b US 5 208 327 (Ortho Pharm Corp.; appl 16.4.1992; USA-prior 18.12.1991)
compositions for treatment of rheumatoid arthritis:
US 5 310 732 (Scripps Res Inst.; appl 19.2.1992; USA-prior 3.2.1986)
Formulatiort(s): inj sol 10 mg/lO ml
Trade Name( s):
D: Leustatin (Janssen-Cilag) GB: Leustat (Janssen-Cilag)
F: Leustatine (Janssen-Cilag) USA: Leustatin (Ortho Biotech)
Use: P-lactamase inhibitor RN: 58001 -44-8 MF: C,H,NO, MW: 199 I6 EINECS: 261-069-2
LDS,,: 4 g/kg (M, i.v.); 4526 mg/kg (M, p.0.);
7936 rnglkg (R, p.0.)
CN: [2R-(2a,3Z,5a)]-3-(2-hydroxyethylidene)-7-oxo-4-oxa-l-azabicyclo[3.2.0]heptane-2-carboxylic acid
monosodium salt
RN: 57943-81-4 MF: C,H,NNa05 MW: 221.14 EINECS: 261-032-0
LD,,,: 4 glkg (M, i.p.); 4500 rnglkg (M, LC.)
From cultures of Streptornyces clavuligerns
Reference(s);
US 4 529 720 (Beecham; 16.7.1985; GB-prior 2.4.1974)
US 4 367 175 (Glaxo; 4.1.1983; GR-prior 7.2.1975)
GB 1 508 977 (Beecham; appl 11.4.1975; GB-prior 2O.4.l974,2l.6.l974.9.lO.l974, 1 I 12.1974) DOS 2 517 316 (Beecham; appl 18.4.1975; GB-prior 20.4.1974, 21.6.1974,9.10.1974, 11.12.1974)
DE 2 560 074 (Beecham; appl 18.4.1975; GB-prior 20.4.1974, 21.6.1974.9.10.1974, 1 1.12.1974)
pure salts ( e g Nu-, Li- and other salts);
US 4 490 294 (Beecham; 25.12.1984; GB-prior 7.2.1975, 17.3.1975)
US 4 490 295 (Beecham; 25.12.1984; GB-prior 7.2.1975, 17.3.1975)
GB 1 543 563 (Glaxo; appl 7.2.1975, 17.3.1975; Compl Spect 6.2.1976)
tert-bu~lamine salt:
EP 26 044 (Beecham; appl 15.8.1980; GB-prior 24.8.1979)
US 4 454 069 (Beecham; 12.6.1984; GR-prior 24.8.1979)
various salts:
US 4 367 175 (Glaxo; 4.1.1983; GB-prior 7.2.1975, 17.3.1975)
esters:
Trang 5formularion with amoxicillin:
US 4 301 149 (Beecham; 17.1 1.1981; GB-prior 11 lO.I977)
EP 49 061 (Beecham; appl 6.9.198 1 ; GB-prior 27.9.1980)
EP 52 962 (Beecham; appl 2.1 1.1981; GB-prior 20.1 1.1980)
GB 2 084 016 (Beecham; GB-prior 27.9.1980)
formulation with penicillins and cephalosporins:
DOS 2 559 41 1 (Beecham; appl 18.4.1975; GB-prior 20.4.1974,21.6.1974,9.10.1974, 11.12.1974)
Fonnulution(s): drops 12.5 mglml; f c tabl 125 mg; tabl 125 mg; vial 0.1 g, 0.2 g, 0.275 g, 0.6 g, 1.2 g, 2.2 g
(as potassium salt)-comb with amoxicillin
Trade Name(s):
D: Augmentan (SmithKline
Beecham; 1982)-comb
with amoxicillin
Betabactyl (SmithKline
Beecham)-comb, with
t~carcillin
F: Augmentin (Sm~thKline
Beecham; 1984)
I
Ciblor (Inava)
Claventin (SmithKline
Beecham)
GB: Augmentin (SmithKline
Beecham; 1984)-comb
with amoxicillin
Timentin (SmithKline Beecham)-comb
I: Augmentin (SmithKLine
B Farm.)-comb
Clavucar (Smith Kline &
French)-comb with ticarcilline Clavulin (Carlo Erba)- comb
Neoduplamox (Smith Kline
& French)-comb:
Timentin (SmithKline Beecham)-comb with ticarcilline
all combination preparations with amoxicillin J: Augmentin (Beecham- Meiji)-comb with amoxicillin USA: Augmentin (SmithKline Beecham: 1984)-comb with amoxicillin Timentin (SmithKline Beecham)
Use: anti-emetic, specific antagonist of peripheral and central dopamine receptors, reversible MAO-inhibitor RN: 55905-53-8 MF: CzoHz4CIN,02 MW 373.88 EINECS: 259-885-9
LD,,: 260 mg/kg (M, i.m.); 40 mglkg (M, i.p.); 51 mglkg (M, i.v.); 490 mglkg (M, p.0.): 350 mglkg (M, s.c.):
1450 mg/kg (R, i.m.); 155 mglkg (R, i.p.); 39 mglkg (R, i.v.); 2540 mglkg (R, p.0.); 4850 mglkg (R, s.c.) CN: 4-amino-5-chloro-2-methoxy-N-[l-(phenylmethyl)-4-piperidinyl]benzamide
monohydrochloride
RN: 57645-39-3 MF: C2,H2,C1N30, HCI MW: 410.35
LD,,: >I @kg (M, p a )
malate (1:l)
RN: 57645-91-7 MF: C,,Hz4CIN,0z C4H,0S MW: 507.97 EINECS: 260-874-6
LD,: 51 mgtkg (M, i.v.); 490 mglkg (M, p.0.);
39 mgkg (R, i.v.); 2540 mglkg (R, p.0.);
>800 mg/kg (dog, p.0.)
2 CI2, FeCI,
b 1
1 , dimethyl sulfote
HN CH, I' 2 chlorine
0
Trang 6496 C Clemastine
CI CH3
HN CH3
K
0
methyl 2-methoxy-
4-aceiamido-5-
chlorobenzoate (I)
COOH
2-methoxy-4- amino-5-chloro- benzaic acid (11)
2 111
NH2
Clebopride
1-benzyl-4-amino- piperidine (In)
DE 2 513 136 (Anphar; appl 21.3.1975; GB-prior 21.3.1974)
US 4 138 492 (Anphar; 6.2.1979; appl 17.3.1975; GB-prior 21.3.1974)
Prieto, J et al.: J Pharm Pharmacol (JPPMAB) 29, 147 (1977)
alternative synthesis:
JP 63 295 558 (Asahi; appl 26.5.1987)
JP 63 295 557 (Asahi; appl 26.5.1987)
synthesis of intermediates:
JP 63 295 559 (Asahi; appl 26.5.1987)
transdermal patch:
EP 303 445 (Fordonal; appl 9.8.1988; J-prior 13.8.1987)
Formulation(s): amp 1 mg; sol 0.5 mg; syrup 0.5 mg; tabl 0.25 mg, 0.5 mg (as hydrogen maleate)
Trade Name(s):
I: Cleprid (Recordati; 1987) J: Amicos (Banyu; 1985)
Clemastine
(Meclastine)
ATC: D04AA 14; R06AA04 Use: antiallergic, antihistaminic RN: 15686-51-8 MF: CzIH,,CINO MW: 343.90
CN: [R-(R*,R*)]-2-[2-[1-(4-chlorophenyl)-l-phenylethoxy]ethyl]-l-methylpyrrolidine
hydrogen fumarate (1:l)
RN: 14976-57-9 MF: C2,H2,C1N0 C4H404 MW: 459.97 EINECS: 239-055-2
LD,,: 43 m g k g (M, i.v.); 730 mglkg (M, p.0.);
82 m g k g (R, i.v.); 3550 m g k g (R, p.0.)
Trang 7d CI
benzophenone chloride
4'-chloro- phenylmognesium
OcetoDhenone bromide
1 NaH, aylene
(+)-2-(2-chloro-
ethyl)-1 -methyl-
pyrrolidine
1 froctionol crystollizotion of rnoleotes
2 resolution with
(-)-dibenzoyl-L-tllrtoric acid
c'l
mixture of
4 isomers (U)
Clemostine
1
Reference(s):
Ebnijther, A.; Weber, H.-P.: Helv Chim Acta (HCACAV) 59, 2462 (1976)
GB 942 152 (Sandoz; appl 14.12.1960; CH-prior 19 I l96O, 3.8.1 960, 27.9.1960)
FR-M 1 313 (Sandoz; appl 13.7.1961)
preparation of 2-(2-chloroethy1)- 1-methylpyrrolidine enantiomers:
Vemier, J.M et al.: I Med Chern (JMCMAR) 42 (10) 1684 (1999)
Formul~ion(s): amp 2 rngl5 ml; gel 300 mglg (as hydrogen furnarate); syrup 0.5 mg/lO ml; tabl 1 mg
Trade Namr(s):
Corto-Tavegil (Novartis
Pharma)-comb
Tavegil (Novartis
Consumer Health)
Tavkgil (Sandoz); wfm
Tavegil (Nnvartis; as
hydrogen furnarate)
Tavegil (Sandoz)
Anhistan (Nippon Zoki) Fulurninol (Tatsumi) Antriptin (Nippon Yakuhin) Fumalestine (Hishiyama)
Kinotomin (Toa Eiyo)
Trang 8498 C Clemizole
Lacretin (Tokyo Tanabe) Natarilan (Nippon Telgin G (Takata)
Maikohis (Nihon Yakuhin) Piloral (Nippon Kayaku) Xolamin (Sanko)
Masletenc (Shioe) Tavegyl (Sandoz-Sankyo) Travist (Sandoz); wfrn
Use: antihistaminic, antiallergic RN: 442-52-4 MF: C,,H,,CIN, MW: 325.84 EINECS: 207-133-5
CN: l-[(4-chlorophenyl)methyl]-2-(l-pyrrolidinylmethyl)-1H-benzi~dazole
monohydrochloride
RN: 1163-36-6 MF: C19H2,CIN, HCI MW: 362.30 EINECS: 214-605-4
LDso: 75 m g k g (M, i.v.); 837 m g k g (M, p.0.);
7 4 m g k g (R, i.v.); 1950 mgfkg (R, p.0.)
1 -chloro- 4-chloro-
2 - n i t r o - benzylamine
benzene
Reference(s):
US 2 689 853 (Schering AG; 1954; D-prior 1950)
alternative syntheses:
D E 980 644 (Schering AG; appl 1950)
D E 901 649 (Schering AG; appl 1951)
Formulation(s): cream 10 mgl40 g; suppos 5 mg
Trade Name(s):
D: Megacillin (Grunentha1)- F Deliproct (Schering)- Ultraproct (&hering)-
Scheriproct (Scherax)- Ultralan (Schering); wfm I: Ultraproct (Schenng)-
comb.; wfm GB: - Scheriproct (Schering)-
comb.: wfm
Trang 9Clenbuterol ATC: R03AC14;R03CC13
IJse: bronchodilator
LD5,: 27.6 mgkg (M, i.v.)
CN: 4-amino-3,5-dichloro-a-[[(1,1-dimethylethyl)amino)methyl]benzenemethanol
hydrochloride
RN: 21898-19-1 M E C,2H,8C12N20 HCI MW: 313.66
4'-nitro- 2-brorno-4'-nitro-
acetophenone acetophenone
Hz, Raney-Ni 0 H
0
CI
I Clenbuterol 1
Trang 10500 C Clidanac
Reference(s):
Keck, J et al.: Arzneim.-Forsch (ARZNAD) 22, 861 (1972)
a DOS 1 793 416 (Thornae; appl 5.9.1967)
BE 704 213 (Thornae; appl 22.9.1967; D-prior 22.9.1966, 15.2.1967, 2.6.1967)
US 3 536 7 12 (Boehringer Ing.; 27.10.1970; D-prior 22.9.1966, 15.2.1967, 2.6.1967)
b DOS 2 157 040 (Thornae; appl 17.1 1.1971)
DE 1 543 928 (Thornae; appl 22.9.1966)
alternative syntheses:
DAS 2 354 959 (Thomae; appl 2.1 1.1973)
Fort?zulation(s): drops 0.059 mg/ml, 15 mg12 ml; syrup 0.005 rnd5 ml; tabl 0.01 mg, 0.02 rng (as
hydrochloride)
Trade Name(s):
D: Contraspasrnin (ASTA I: Broncodil (Leben's) Prontovent (Salus
Spasrno-Mucosolvan Contrasrnina (Falqui) J: Spiropent (Teijin-Kissei) (Boehringer 1ng.)-comb Monores (Valeas)
Use: non-steroidal anti-inflammatory, antipyretic
RN: 34148-01-1 MF: Cl,Hl,CI02 MW: 278.78
LD,,,: 41 mglkg (R, p.0.)
CN: 6-chloro-5-cyclohexyl-2,3-dihydro-1H-indene-l-carboxylic acid
1 Li, ?I
1 AICI, & ~ H ~ c - & ~ H
2 H,SO, 3 HCI CH ,COOH
1.3-dithiane phenylcyclo- J-chloro-
h e x o n e (I) propionyl
chloride
5-cyclohexyl-l- indonane
F'
_*
N-chloro- succinimide 5-cyclohexyl- 1 -indon-
corboxylic acid (11)
Clidonoc
L
TiCI,
CI 0,
1 + Y CH, -+ A