HCI olternative preporotion of intermediate 11 cytosine 5-fluoro-2-0.4-N-bis- trirnethylsilylcytosine V References: a EP 602 454 Hoffmann-La Roche: appl... racemate resolution of DL
Trang 1Canthaxanthin C
retinal
(cf betacaratene synthesis)
0
4-ocetoxyretinol (I)
(4-ocetoxyretinyl)triphenyl-
phosphanium chloride (11)
trans-isozeoxanthin (111)
Reference(s):
US 3 31 1 656 (Roche; 28.3.1967; appl 12.5.1964)
Surmatis, J.D et al.: Helv Chim Acta (HCACAV) 53,974 (1970)
I
alternative syntheses:
DOS 2 037 935 (Roche; appl 30.7.1970; CH-prior 1.8.1969)
US 4 000 198 (Roche; 28.12.1976; appl 9.6.1975)
DOS 2 625 259 (Roche; appl 4.6.1976; USA-prior 9.6.1975)
Forrnulation(s): gel 10 mgl600 mg; 15 mgl900 mg
Trang 2332 C Capecitabine
Trade Name(s):
F: Phenoro "Roche" (Prod
Roche S.A.R.L.)-comb
with betacarotene
Capeci tabine
(Ro-09- 1978)
RN: 154361 -50-9 MF: C,5H22FN306 MW: 359.35
CN: 5'-Deoxy-5-fluoro-N-[(pentyloxy)carbonyl]cytidine
H C 0 CH3
,
doxifluridine
(q )
5'-deoxy-5-fluoro-
cytidine (I)
pentyl chloro-
formote (In)
ATC: LOlBC06 Use: anticancer, orally active prodrug of
doxifluridine
cytidine (11)
Trang 3,r-
pyridine
CH2C12
*
1 NaOH CH30H
- 1 O0C
2 HCI
olternative preporotion of intermediate 11
cytosine
5-fluoro-2-0.4-N-bis- (trirnethylsilyl)cytosine (V)
Reference(s):
a EP 602 454 (Hoffmann-La Roche: appl 1.12.1993; EP-prior 18.12.1992)
US 5 472 949 (Hoffmann-La Roche; 5.12.1995; EP-prior 18.12.1992)
b US 5 476 932 (Hoffmam-La Roche; 19.12.1995; USA-prior 26.8.1994)
compositions of interleukin and pyrimidine nucleosides:
WO 9 637 214 (Hoffmann-La Roche; appl 15.5.1996; EP-prior 26.5.1995)
Formulation(s): tabl 150 mg, 500 mg
Trade Name(s):
USA: Xeloda (Roche; 1998)
Copecitobine
I
Capreomycin
(Caprenomy cin)
RN: 11003-38-6 MF: C2,H,N,,08 MW: 668.72
LD,: 238 mglkg (M, i.v.)
CN: capreomycin (mixture of capreomycin IB, IA, IIA and IIB)
ATC: J04AB30 Use: tuberculostatic, peptide antibiotic
sulfate
RN: 1405-37-4 MF: H2S0, unspecificd MW: unspecified EINECS: 215-776-8
LD,,: 250 mgkg (M, i.v.);
325 mg/kg (R, i.v.)
Trang 4334 C Cautodiame
CH3
Capreomycin IB
From culture of Streptomyces capreolus by ion-exchange adsorption
Referertce(s):
US 3 143 468 (Eli Lilly; 4.8.1964; appl 25.5.1962; prior 2.1 1.1959)
Form~dation(s): vial 1 g
Trade Name(s):
D: Ogostal (Lilly); wfm J: Capastat (Shionogi; as
GB: Capastat (King; as sulfate) USA: Capastat (Dura)
Use: psychoregulant, sedative RN: 486-17-9 MF: C,,H,,NS, MW: 359.60 EINECS: 207-629-1
LD,,,: 72 mglkg (M, i.v.); 1630 mglkg (M, p.0.);
3800 mglkg (R, p.0.)
CN: 2-[[[4-(butylthio)phenyl]phenylmethyl]thio]-N,N-dimethylethanamine
hydrochloride
RN: 904-04-1 MF: C,,H,,NS, HCl MW: 396.06 EINECS: 212-992-4
LD,,,: 44 mglkg (M, i.v.)
and benzoyl chloride)
K
2 NaOH
1 -+
no)ethyl chloride H3f' '-"-'-'-'
Trang 5Captopril C 335
Reference(s):
US 2 830 088 (O.H Hubner, P.V Petersen; 1958; DK-prior 1952)
Formulation(s): tabl 50 mg
Trade Name(s):
F: Covatine (Bailly)
Use: antihypertensive (ACE inhibitor) RN: 62571-86-2 MF: C9HI5NO3S MW: 217.29 EINECS: 263-607-1
LD,,: 663 mg/kg (M, i.v.); 2500 mg/kg (M, p.0.);
554 mglkg (R, i.v.); 4245 mglkg (R, p.0.)
CN: (S)-1-(3-mercapto-2-metl~yl-l-oxopropyl)-~-proline
CH3 H , C ~ S ~ C I C H 3
L-proline (Ill) benzyl
U N-benzyloxycorbonyl- chloroformote L-proline
N-benzyloxycarbonyl-L- L-proline tert-
proline tert-butyl ester (IV) butyl ester
H3C 0 y C H 3 separation of the diastereorners
vla the dicyclohexylarnine CF3COOH, anisole
"9 salt in ethyl acetote trifluoroacetic o c i b
O cooH
b
noyll-L-proline (VI)
Trang 6336 C Captopril
1 OH-
nl + ,, 2 seporotion of t h e diostereorner B VI NH,, CH,OH
rnicrobiolog., e.g with Condido ruguso/FO-0750
Condido rugoso/FO-0591 Condido utilis
H3C +OOH /F0-0396 or other bioreogents
D(-)-3-hydroxy-
isobutyric ocid (VII)
C H 3
isobutyric
ocid
rnicrobiolog., in onology to isobutyric ocid
CH3 NoOH
,,I1 + 11, , O F '
SOC12, DMF
VII
0
D-3-chloro-2-methyl-
propionyl chloride (Wl)
Reference ( s ) :
a,b DOS 2 703 828 (Squibb; appl 3 1.1.1977; USA-prior 13.2.1976; 21.6.1976, 22.12.1976)
US 4 046 889 (Squibb; 6.9.1977; appl 13.2.1976)
US 4 105 776 (Squibb; 8.8.1978; prior 13.2.1976, 21.6.1976,22.12.1976)
US 4 154 840 (Squibb; 15.5.1979; prior 13.2.1976,21.6.1976,22.12.1976,9.3.1977)
US 4 154 935 (Squibb; 15.5.1979; prior 21.2.1978, 1.9.1978)
c GB 2 065 643 (Kanegafuchi; appl 1 l2.1980; J-prior 13.12.1979,28.12.1979, 8.3.1980)
US 4 460 780 (Kanegafuchi; 17.7.1984; J-prior 20.1.1982)
microbiological production of D-(-)-3-hydroxyisobutyric acid:
US 4 310 635 (Kanegafuchi; 12.1.1982; J-prior 6.1 1.1979, 14.2.1980,7.7.1980)
similar methods with D- or DL-3-halogeno-2-methylpropionic acids as intermediates:
Nam, D.H et al.: J Pharm Sci (JPMSAE) 73; 1843 (1984)
DE 3 049 273 (Egyt; appl 29.12.1980; HU-prior 29.12.1979)
US 4 332 725 (Egy t; 1.6.1982; HU-prior 29.12.1979)
GB 2 066 252 (Egyt; appl 29.12.1980; HU-prior 29.12.1979)
US 4 399 144 (Wyeth; 16.8.1983; GB-prior 30.4.1980)
alternative syntheses:
via 3-mercapto-2-D-methylpropionic acid:
US 4 384 139 (Kanegafuchi; 17.5.1983; J-prior 20.8.1980)
GB 2 082 174 (Kanegafuchi; appl 7.8.1981 ; J-prior 20.8.1980)
via 3-acylthio-2-D-methylpropionic acids:
EP 8 831 (OcC-Andeno; appl 31.8.1979; NL-prior 7.9.1978)
racemate resolution of DL-3-acy1thio-2-methy1propionic acids:
EP 35 81 1 (OcC-Andeno; appl 26.2.1981; NL-prior 6.3.1980)
US 4 346 045 (OcC-Andeno; 24.8.1982; NL-prior 6.3.1980)
US 4 297 282 (Sumitomo; 27.10.1981; J-prior 2.3.1979, 13.3.1979, 28.6.1979,25.7.1979)
racemization of L-3-acylthio-2-methylpropionic acids:
US 4 41 1 836 (Sumitomo; 25.10.1983; J-prior 13.3.1979)
Trang 7Carazolol C
I 337 1
pur$cation of captopril (removal of disuljide):
U S 4 332 726 (Squibb; 16.1982; appl 25.8.1980)
medical use for treatment of glaucoma:
IEP 99 239 (Squibb; appl 6.7.1983; USA-prior 6.7.1982)
combination with diuretics:
DOS 2 854 316 (Squibb; appl 15.12.1978; USA-prior 27.12.1977)
controlled-release formulation:
US 4 505 890 (Squibb; 19.5.1985; appl 30.6.1983)
Trade Namefs):
D: Capozide (Bristol-Myers
Squibb; 1984)-comb with
hydrochlorothiazide
Lopirin (Bristol-Myers
Squibb; 1981)
Tensobon (Schwarz; 1983)
F: CaptCa (Bellon)-comb
Captolane (Bellon; 1984)
Ecazide (Bristol-Myers
Squibb)-comb
Lopril (Bristol-Myers Squibb; 1982) GB: Acepril (Ashbourne) Azecide (Ashbourne)- comb
Capoten (Biistol-Myers Squibb; 1981)
Capozide (Bristol-Myers Squibb)-comb
I: Acediur (Chidotti)-comb
Aceplus (Bristol-Myers Squibb)-comb
Accprcss (Guidotti) Capoten (Bristol-Myers Squibb; 1981)
J: Captoril (Sankyo; 1983) USA: Capoten (Bristol-Myers Squibb; 1981)
Capozide (Bristol-Myers Squibb; 1986)
Use: non-selective P-adrenoceptor blocker, antihypertensive, antianginal
RN: 57775-29-8 MF: C,,H2,N202 MW: 298.39 EINECS: 260-945-1
CN: l-(9H-carbazol-4-yloxy)-3-[(l-methylethyl)amino]-2-propanol
H
0 NaOH, dioxane
@ + U,.P
OH
Reference(s):
DOS 2 240 599 (Boehringer Mannh.; appl 18.8.1972)
GB 1 369 580 (Boehringer Mannh.; valid from 9.10.1974; D-prior 18.8.1972)
synthesis of 4-hydroxycarbazole:
DOS 2 928 483 (Boehringer Mannh., appl 14.7.1979)
Trang 8338 C Carbachol
Trade Narne(s):
D: Conducton (Klinge)
Carbachol
(Carbacholine)
ATC: N07ABOI; SOIEBO2 Use: parasyrnpathomimetic RN: 51-83-2 MF: C,H,,CIN2O2 MW: 182.65 EINECS: 200-127-3
LD,,: 300 p g k g (M, i.v.); 15 m g k g (M, p.0.);
100 @/kg (R, i.v.); 40 mglkg (R, p.0.)
CN: 2-[(aminocarbonyl)oxy]-N,N,N-trimethylethanarninium chloride
Reference(s):
DRP 539 329 (E Merck AG; appl 1930)
DRP 553 148 (E Merck AG; appl 1930)
DRP 590 3 11 (E Merck AG; appl 1932)
Hayworth, R.D et a].: J Chern Soc (JCSOA9) 1947 176
trirnethyl-
alternative syntllesis from choline chloride:
US 2 374 367 (Merck & Co.; 1945; prior 1943)
Corbachol
Fomulation(s): amp 0.25 mg; tabl 2 rng
ornine
Trade Name(s):
D : Carbarnann (Mann) F: Iricoline (Lernatte et I: Mios (1ntes)-comb
Isopto-Carbachol (Alcon) Impto Carbachol (Alcon); USA: lsopto Carbachol Solut
comb
Use: antiepileptic, anticonvulsant RN: 298-46-4 MF: C,SH,,N,O MW: 236.27 EINECS: 206-062-7
LD,,: 529 mgfkg (M, p.0.);
1957 rnglkg (R, p.0.);
5620 rngkg (dog, p.0.)
CN: SH-dibenz[bJlazepine-5-carboxarnide
Trang 97
N-Carbamoyl-L-aspartic acid calcium salt C 339
5H-dibenz- phosgene
[b,f]azepine (1)
/ Carbamozrpinr
potassium
cyanate
Reference(s):
US 2 948 718 (Geigy; 9.8.1960; CH-prior 20.12.1957)
alternative synthesis:
DD 133 052 (R Miiller; appl 8.9.1977)
Formulation(s): s r tabl 200 mg, 400 mg; susp 100 mg;.tabl 200 mg
Trade Name(s):
D: Finlepsin (ASTA Medica Timonil (Desitin) J: Tegretol (Fujisawa) AWD; Boehringer Mannh.) F: Tegrttol (Novartis) USA: Epitol (Teva)
Sirtal (Merck Generika) GB: Tegretol (Novartis) Tegretol (Novartis) Tegretal (Novartis Pharma) I: Tegretol (Novartis)
N-Carbamoyl-L-aspartic acid calcium salt Use: psychoenergetic, tranquilizer (Calcii carbaspartas)
RN: 16649-79-9 MF: C5H,CaN,0, MW: 214.19 EINECS: 240-698-6
CN: N-(aminocarbony1)-L-aspartic acid calcium salt (1:l)
N-carbamoyl-baspartic acid
RN: 13 184-27-5 MF: CsHRN20s MW: 176.13 EINECS: 236-134-3
LD,,: >I g/kg (M, p.0.)
potassium L-aspartate
I KOCN
2 HCI
0 NH 3 CaCI,
KoK1;O~ b
cyanate
N-Carbamayl-L-aspadic
acid calcium salt
W
Jy,$?z cop+
- 0
0
Referencefs):
FR-M 6 376 (Roussel-Uclaf; appl 18.4.1967)
Trang 101
340 C Carbasalate calcium
Trade Name(s):
salt); wfm
Carbasalate calcium
(Calcium carbaspirin)
ATC: BOlAC08; N02BA15 Use: analgesic
RN: 5749-67-7 MF: Cl,Hl4CaO8 CH,N,O MW: 458.44 EINECS: 227-273-0
CN: 2-(acetyloxy)benzoic acid calcium salt compd with Urea (1 :1)
Reference(s):
Parrott, E.L.: J Pharm Sci (JPMSAE) 51, 897 (1962)
acetylsaiicylic
acid
calcium acetylsalicylate:
US 2 003 374 (Lee Labs.; 1935; appl 1932)
Carbasalate calcium
Formulation(s): tabl 500 mg
Trade Name(s):
D: Iromin (Omegin); wfm USA: Fiogesic (Sandoz); wfm
F: Solupsan (UPSA)
Ursinus Inlay-Tabs (Dorsey); wfm
Use: antihemorrhagic, hemostatic RN: 69-81-8 MF: CloHI,N4O3 MW: 236.23 EINECS: 200-717-0
LD,,,: >35.832 glkg (M, p.0.);
>17.280 glkg (R, p.0.)
CN: 2-(1,2,3,6-tetrahydro-3-hydroxy-1-methyl-6-oxo-5H-indol-5-ylidene)hydrazinecarb0xamide
epinephrine
(9 v.)
Carbazochrome
Reference(s):
US 2 506 294 (Soc Relge de 1'Azote et des Prod Chim.; 1950; B-prior 1943)
GB 806 908 (Labaz; appl 1957; USA-prior 1956)
US 3 244 591 (Endo Labs.; 5.4.1966; appl 10.8.1960)
oxidation of adrenaline with persulfate:
DOS 2 713 652 (Nippon Gohsei; appl 28.3.1977; J-prior 31.3.1976)