Canthaxanthin 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). Canthaxanthih 1 Forrnulation(s): gel 10 mgl600 mg; 15 mgl900 mg 332 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 A pyridine, 0% ____, OH OH OH OH doxifluridine (q ) 5'-deoxy-5-fluoro- cytidine (I) pentyl chloro- formote (In) ATC: LOlBC06 Use: anticancer, orally active prodrug of doxifluridine cytidine (11) Copecitabine I ,r- Capreomycin C 333 pyridine. CH2C12 __* 1. NaOH. CH30H. - 1 O0C 2. HCI olternative preporotion of intermediate 11 5-fluora- hexarnethyldisilozane 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.) 334 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 F: Capastat (Lilly); wfm sulfate) GB: Capastat (King; as sulfate) USA: Capastat (Dura) Captodiame ATC: eN05BB02 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.) 4-butylthiobenzophenane 4-butylthiobenzhydrol 4-butylthiobenz- (from butyl phenyl sulfide hydry chloride (I) and benzoyl chloride) S NaOC2H,. K 1. H~N NH, FH3 2. NaOH 1 + 1. thiourea SH 2-(dimethylami- no)ethyl chloride H3f' '-"-'-'-' 4-butyllhiobenz- Coptodiome hydryl mercaptan Captopril 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) Captopril ATC: C09AAO1 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~CI CH3 0 thionyl 0 chloride O 0 rnethacrylic thioacetic 3-acetylthio-2-methyl- (11) acid (I) acid propionic ocid L-proline (Ill) benzyl U N-benzyloxycorbonyl- chloroformote L-proline N-benzyloxycarbonyl-L- L-proline tert- proline tert-butyl ester (IV) butyl ester H3C 0yCH3 separation of the diastereorners vla the dicyclohexylarnine CF3COOH, anisole "9 salt in ethyl acetote trifluoroacetic ocib O cooH b 1-(3-ocetylthio-2- 1 -[(2S)-3-acetylthio- rnethylpropanay1)- l-methylpropa- noyll-L-proline (VI) 336 C Captopril 1. OH- nl + ,, 2. seporotion of the diostereorner NH,, CH,OH B VI rnicrobiolog., e.g. with Condido ruguso/FO-0750 Condido rugoso/FO-0591. Condido utilis H3C +OOH /F0-0396 or other bioreogents , HoJ;ooH D(-)-3-hydroxy- isobutyric ocid (VII) CH3 isobutyric ocid rnicrobiolog., in onology to isobutyric ocid CH3 NoOH ,,I1 + 11, , OF' 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). Carazolol C I 337 1 pur$cation of captopril (removal of disuljide): US 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). Fonulation(s): tabl. 6.25 mg, 12.5 mg, 25 mg, 50 mg 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) Carazolol ATC: CO~AA 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 4-hydroxy- epichloro- 4-(2.3-epoxyprop0xy)- corbozole hydrin corbazole (1) 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). ( Formulation(s): tabl. 5 mg 338 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 pgkg (M, i.v.); 15 mgkg (M, p.0.); 100 @/kg (R, i.v.); 40 mglkg (R, p.0.) CN: 2-[(aminocarbonyl)oxy]-N,N,N-trimethylethanarninium chloride 2-chloro- phosgene 2-chloroethyl 2-chloroethyl ethanol chloroformate carbamote (I) 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. Dory1 (Merck) - Boinot); wfm J: Calpinol (Tanabe) Isopto-Carbachol (Alcon) Impto Carbachol (Alcon); USA: lsopto Carbachol Solut. Jesytryl (Chauvin wfrn (Alcon) ankerpharm) GB: Isopto-Carbachol (Alcon)- comb. Carbamazepine ATC: NOSAFOI; N03AX 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 7 N-Carbamoyl-L-aspartic acid calcium salt C 339 5H-dibenz- phosgene [b,f]azepine (1) / Carbamozrpinr I + KOCN 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 0 1. potassium 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). 1 340 C Carbasalate calcium Trade Name(s): F: Cycluran (Salvoxyl- Cycluran (Salvoxyl- Pacilan (Syntex-Daltan); Wander); wfm Wander; as L-ornithine- wfm 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) COOH I / OvO-\ 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 Carbazochrome ATC: B02BX02 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). . 3-acetylthio-2-methyl- (11) acid (I) acid propionic ocid L-proline (Ill) benzyl U N-benzyloxycorbonyl- chloroformote L-proline N-benzyloxycarbonyl-L- L-proline tert- proline tert-butyl. trifluoroacetic ocib O cooH b 1-( 3-ocetylthio- 2- 1 -[ (2S )-3 -acetylthio- rnethylpropanay1 )- l-methylpropa- noyll-L-proline (VI) 336 C Captopril 1. OH- nl + ,, 2. seporotion of. EINECS: 26 0-9 4 5-1 CN: l-(9H-carbazol-4-yloxy )-3 -[ (l-methylethyl)amino ]-2 -propanol H 0 NaOH, dioxane @ + U,.P OH 4-hydroxy- epichloro- 4-( 2.3-epoxyprop0xy )- corbozole hydrin corbazole