Cicletanine C 461 Cicletanine (Cycletanide) ATC: C03BX03 Use: diuretic, antihypertensive RN: 89943-82-8 MF: C14H,2ClN02 MW: 261.71 LD,,: 4500 mgkg (M, p.0.); 5000 mgkg (R, p.0.) CN: (~)-3-(4-chloropheny1)-1,3-dihydro-6-methylfuro[3,4-c]pyridin-7-ol hydrochloride RN: 82747-56-6 MF: C,4H,2ClN02~ HCl MW: 298.17 ~3~%~~ , OH + HIC CHI pyridoxine acetone 3,4a-0-iso- manganese dioxide propylidene- pyridoxine BrMg tJ C I 4-chlorophenyl- mognesium bromide I Cicletanine I Reference(s): DOS 3 204 596 (Soc. de Conseils de Recherche et d'Appl. Sci.; appl. 10.2.1982; GB-prior. 10.2.1981). US 4 383 998 (Soc. de Conseils de Recherche et d'Appl. Sci.; 17.5.1983; GB-prior. 10.2.1981). synthesis of 2,2,8-trimethyl-5-formyl-4H-pyrido[3,4-d]-1,3-dioxane: Koryntyk, W.; Wiedemann, W.: J. Org. Chern. (JOCEAH) 27,2531 (1962). Koryntyk, W.; Kris, E.J.; Singh, R.P.: J. Org. Chem. (JOCEAH) 29, 574 (1964). Sattsangi, ED.; Argoudelis, C.J.: J. Org. Chem. (JOCEAH) 33, 1337 (1968). Formulation(s): cps. 50 mg, 100 mg (hydrochloride) Trade Name(s): D: Justar (Intersan; 1989) F: Tenstaten (Ipsen-Beaufour; 1988) Ciclometasone ATC: D07AB; H02AB Use: glucocorticoid RN: 86022-88-0 MF: C32HuClN07 MW: 590.16 EINECS: 289-141-9 CN: [l 1~,16~,21(trans)]-21-[[[4-[(acetylamino)methyl]cyclohexyl]carbonyl]oxy]-9-chloro-l 1,17-dihydroxy- 16-methylpregna- l,4-dime-3,20-dione 462 C Ciclonium bromide troneromic ocid (9- v.) N(C2H&. THF I + _____* triethylornine beclometasone (9. v.1 Ciciometasone Reference(s): FR 2 280 384 (Rorer; appl. 1.8.1974). synthesis of 4-aminomethylcyclohexanecarboxylic acid: Levine, M.; Sedlecky, R.: J. Org. Chem. (JOCEAH) 24, 115 (1959). Trade Nurne(s): I: Cycloderm (Rottapharm) Telecort Sray (Rottapharm) Ciclonium bromide ATC: A03DA04 Use: antispasmodic, anticholinergic RN: 29546-59-6 MF: C22H3,BrN0 MW: 408.42 EINECS: 249-687-0 LD,,: 400 mglkg (M, p.0.); 1030 mgkg (R, p.0.) CN: 2-(1 -bicyclo[2.2.1 Ihept-5-en-2-yl- 1 -phenylethoxy)-N,N-diethyl-N-methylethanaminium bromide ocetophenone bicyclo[2.2.1]- hept-5-en-2-yl- rnognesium chloride chloride H3C-Br methyl '-CH, bromide Ciclonium bromide I Reference(s): DE 1 052 982 (ASTA; appl. 29.6.1957). Fnrmulatior~(s): amp. 10 mgl2 ml T Ciclopirox C 463 Trade Name(s): D: Dolo-Adamon (ASTA)- Tranquo-Adamon (ASTA comb.; wfm Medica)-comb.; wfm Ciclopirox ATC: DOlAE14; GOlAX12 Use: antifungal RN: 29342-05-0 MF: C,,H,,NO, MW: 207.27 EINECS: 249-577-2 CN: 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridinone cidopirox olamine RN: 41621-49-2 MF: C,,H,,N02 . C2H7N0 MW: 268.36 EINECS: 255-464-9 LD,: 71 mgkg (M, i.v.); 1740 mglkg (M, p.0.); 72 mgkg (R, i.v.); 2350 mglkg (R, p.0.) I CH3 pyridine '3'3 Ciclopirox NH20H. HCI, CH,COONo vLcH3 , hydroxylamine CH3 hydrochloride methyl 5-cyclohexyl- 3-methyl-5-0x0-2- pentenoote (mixture with the 3-pentenoote: from methyl 4-methyl- 2-butenoate) methyl 5-cyclohexyl- 3-methyl-5-hydroxyimino- 2-pentenoate (I) '33 Ciclopirox olarnine I a US 3 883 545 (Hoechst AG; 13.5.1975; appl. 16.1 1.1971; prior. 22.12.1972). US 3 972 888 (Hoechst AG; 3.8.1976; D-prior. 25.3.1972). b ZA 696 039 (Hoechst AG; appl. 12.8.1969; D-prior. 31.8.1968). DE 1 795 270 (Hoechst AG; appl. 31.8.1968). DOS 2 214 608 (Hoechst AG; appl. 25.3.1972). Formulation(s): cream 1 5%; powder 1 % (as olamine); sol. 10 mglml (as ciclopirox); vaginal cream 1 % (as olamine) Trade Name(s): D: Batrafen (Hoechst; 198 1) Brumixol (Bruschettini) Micoxolamina (Delalande Nagel-Batrafen (Hoechst) Dafnegin (Poli) Isnardi) F: Mycoster (Pierre Fabre; Miclast (Pierre Fabre Phar.) J: Batrafen (Hoechst) 1986) Miclast (Lifepharma) USA: Loprox (Hoechst Marion I: Batrafen (Hoechst) Micomicen (Synthelabo) Roussel; 1983) Ciclosporin (Cyclosporin A) ATC: L04AA01 Use: immunosuppressive RN: 59865-13-3 MF: C,,Hll,N,,O,, MW: 1202.64 CN: [R-[R*,S*-(E)]]-cyclic(~-alanyl-~-alanyl-N-methyl-~-leucyl-N-methyl-~-leucyl-N-methyl-~-valyl-3- hydroxy-N,4-dimethyl-~-2-amino-6-octenoyl-~-a-aminobutyryl-N-methylglycyl-N-methyl-~-leucyl-~- valyl-N-methyl-L-leucyl) Ciclosporin Cyclic peptide from 11 amino acids. Preparation by fermentation of Tolypoclndium injatum Gams with addition of DL-a-aminobutyric acid lo the fermentation medium. Isolation by homogenization of mycelium, extraction with 90 % methanol and column chromatographic purification. Reference(s): US 4 117 118 (Sandoz; 26.9.1978; priol. 29.11.1974, 15.8.1975,9.9.1976; CH-prior. 9.4.1976). DE 2 455 859 (Sandoz; appl. 26.1 1.1974; CH-prior. 6.12.1973,21.10.1974). Riiegger, A. et at.: Helv. Chim. Acta (HCACAV) 59, 1075 (1976). Kobel, H.; Traber, R.: Eur. J. Appl. Microbial. Biotechnol. (EJABDD) 14, 237 (1982). structure: Petcher, T.J. et al.: Helv. Chim. Acta (HCACAV) 59, 1480 (1976). total syntheses: Wenger, R.M.: Angew. Chem. (ANCEAD) 97, 88 (1985). EP 34 567 (Sandoz; appl. 13.2.1981; CH-prior. 14.2.1980). oral formulation: US 5 766 629 (Sangstat Med. Corp.; 16.6.1998; prior. 25.8.1995, 21.3.1996). Formulation(s): cps. 25 mg, 50 mg, 100 mg; inj. sol. 250 mgf5 ml; oral sol. 100 mglml; sol. 100 mg Trade Name(s): D: Sandimmun (Novartis; F: Sandimmun (Novartis) Sandimmun (Novartis: 1983) GB: Neoral (Novartis) 1983) Cicloxilic acid C 465 1: Sandimmun (Sandoz) USA: Neoral (Novartis) 3: Sandimmun (Novartis; Sandimmune (Novartis; 1986) 1983) Cicloxilic acid ATC: AOSAX; A06AB Use: choleretic, hepatic protectant RN: 57808-63-6 MF: C,,H,,O, MW: 220.27 EINECS: 260-966-6 LD,: 2095 mgkg (M, p.0.); 1570 mgkg (R, p.0.) CN: cis-2-hydroxy-2-phcnylcyclohexanecarboxy1ic acid KMn04, No2C03 8 + HCHO 5 SOH perrnonganote 1-phenyl- form- cis-2-(hydroxy- cyclohexene aldehyde methyl)-1 -phenyl- cyclohexonol Rejerence(s): BE 848 143 (Guidotti Int.; appl. 9.12.1976; I-prior. 12.1 1.1975). alternative synthesis and use as choleretic: US 3 700 775 (L. Turbanti; 24.10.1972; I-prior. 29.4.1966). stereochemistry: Turbanti, L. et al.: Arzneim Forsch. (ARZNAD) 28 (II), 1449 (1978). Fomulation(s): amp. 60 mg; drg. 40 mg Trade Name(s): I: Plecton (Guidotti) Pleiabil (Guidotti)-comb. Cicrotoic acid (Acide cicrotoique) Use: choleretic RN: 25229-42-9 MF: CloH1,02 MW: 168.24 EINECS: 246-739-4 LD,: 1925 mglkg (M, p.0.); 2900 mglkg (R, p.o.1 CN: 3-cyclohexyl-2-butenoic acid ocatylcyclo- ethyl ethyl 3-cyclohexyl- hexane bromoocetate 3-hydroxybutanoote 466 C Cidofovir ethyl 3-cyclohexyl- I Cicrotoic acid I 2-butenoote (1) Reference(s): FR-M 4 665 (A. E. C. Soc. deChim. Organ. et Biol.; appl. 3.5.1965). Young et al.: J. Org. Chem. (JOCEAH) 28,928 (1963). Forrnulation(s): cps. 250 mg Trade Narne(s): F: Accroibile (Adrian- Marinier); wfm Cidofovir (HPMPC; GS-504; GS-0504) ATC: J05AB12 Use: antiviral RN: 1 13852-37-2 MF: C,H14N30,P MW: 279.19 CN: (S)-[[2-(4-amino-2-oxo-1(2H)-pyrimidinyl)-l-(hydroxymethyl)ethoxy]methyl]phosphonic acid dihydrate RN: 149394-66-1 MF: C8H,4N306P. 2H20 MW: 315.22 CsCO,, OMF, 100 OC A _______, 0 N H OH cesium carbonate COH \OH cytosine (R)-glycidol (2s)-4-amino-1- (2.3-dihydroxypropyi)- 1. (C2H50)3P-0 2. aq. NaOH 1 + 1. triethyl phosphate CI 2. oqueaus alkali metal hydroxide chloromethyl- 3. mineral acid Cidofavir phosphonic dichloride EP 253 412 (Ceskoslovenska Akademie Ved., Czech., appl. 20.1.1988; CS-prior. 18.7.1986). WO 9 624 355 (Astra; appl. 15.8.1996; WO-prior. 6.2.1995). WO 9 713 528 (Dumex-Alpharma; appl. 17.4.1997; prior. 12.10.1995). svnthesis of (2s)-4-amino- 1 -(2,3-dihydroxypropy1)- 1 H-pyrimidin-Zone: Holy, A,: Collect. Czech. Chem. Commun. (CCCCAK) 58 (3), 649 (1993). Holy, A,: Collect. Czech. Chem. Commun. (CCCCAK) 43, 2054 (1978). Martin, J.C. et al.: Nucleosides Nucleotides (NUNUD5) 8 (5-6), 923 (1989). Cilastatin C 467 1 Fonnulation(s): vial 375 mg (75 mglml anhydrous) for I.". mfusion b Trade Name(s): D: VISTIDE (Pharmacia & USA: Vistlde (Gilead Science) Up~ohn) Cilastatin ATC: JOlDHSl Use: dehydropeptidase inhibitor (for combination with imipenem) RN: 82009-34-5 MF: C16Hz6Nz05S MW: 358.46 EINECS: 279-875-8 LDso: 8 glkg (M, route unreported); 8 gkg (R, route unreported) CN: [R-[R*,S*-(2)]]-7-[(2-amino-2-carboxyethyl)thio]-2-[[(2,2-dimethylcyc1opropyl)carbonyl]amino]-2- heptenoic acid monosodium saIt RN: 81129-83-1 MF: C16H,,N2Na0,S MW: 380.44 EINECS: 279-694-4 LD,,: 6786 mgkg (M, i.v.); >I 0 glkg (M, p.0.); 5027 mgkg (R, i.v.); >I0 glkg (R, p.0.) n oMF. NOH, toluene . + Br-Br t B~- n S S ethyl 1.3- 1.5-dibromo- dithione-2- pentane carboxylote ocetonitrile. H20 HBr. CH COOH 1- "-'If 3 , N-bromosuccinimide COOH 0 0-CH, ethyl 7-bromo-2- oxoheptanoote 11 + HzN &W3 0 CH3 d toluene Br>fi:~3 cyclopropane- dimethylcycloproponecorbox- corboxamide amido)-2-heptenoic acid (El) 7-bromo-2-0x0- heptonoic acid (11) NoOH 111 + H2Ny's~ , COOH L-cysteine COOH Cilastotin 468 C Cilazapril Rcference(s): EP 10 573 (Merk & Co.: appl. 24.7.1979; USA-prior. 24.7.1978). EP 48 301 (Merck & Co.; appl. 24.9.1980). Formulation(s): amp. 250 mg, 500 mg, 750 mg (as sodium salt) Trade Name(s): D: Zienam (MSD; 1985)- I: Imipem (Neopharmed) Tienam (MSD)-comb. comb. with imipenem comb. J: Tienam (Banyu; 1987)- F: Tienam (Merck Sharp & Tenacid (Sigma-Tau)- comb. Dohme-Chibret)-comb. comb. USA: Primaxin (Merck; 1985) Cilazapril ATC: C09AA08 Use: antihypertensive (ACE inhibitor) RN: 88768-40-5 MF: C22H,,N,0, MW: 417.51 CN: [1S-[la,9a(K*)]]-9-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]octahydro-l0-oxo-6H-pyridazino[1,2 a][l,2]diazepine- 1-carboxylic acid monohydrate RN: 92077-78-6 MF: C22H,,N,0s. H20 MW: 435.52 toluene. A PCI5 0 7-benzyl phtholic L-glutornote anhydride (1) tert-butyl 1 -(benzyl- axycorbony1)-hexo- hydro-3-pyridazine- corboxylate 1. Hz. Pd-C 2. recrystollizotion from 0 0 0 \tBu PCIv EtOAc/Et20 phth~+,,,$~~ N-ethylmorpholine n - III COOH 0 0 PhthN; 0 't~u BH, . THF '3 0 tart-butyl octohydro- 6,lO-dioxa-9(S)-phthol- imido-6H-pyridazo[l.2-01- [I ,Z]diozepine- 1 (S)- carboxylote (111) 1. NoBH, 2. recrystollizotion 3. CF3COOH or HBr/CH,COOH + tart-butyl 9(S)-ornino- actahydro-10-axo-6H-pyri- dozo[l,2-o][l ,2]diazepine- l(S)-corboxylote (N) I Cilozopril Reference(s): US 4 512 924 (Hoffmann-La Roche; 23.4.1985; GB-prior. 12.5.1982, 28.2.1983). US 4 658 024 (Hoffmann-La Roche; 14.4.1987; GB-prior. 12.5.1982). Attwood, M.R. et al.: FEBS Lett. (FEBLAL) 165, 201 (1984). let?-butyl l-(benzyloxycarbonyl)-hexahydro-3-pyridazinecarboxylate: Hassall, C.H. et al.: J. Chem. Soc., Perkin Trans. 1 (JCPRB4), 1451 (1979). Formulation(s): f. c. tabl. 0.5 mg, 1 mg, 2.5 mg, 5 mg Trade Narnefs): D: Dynorm (MercWRoche) GB: Vascace (Roche) F: Justor (Jacques Logeais) 1: Inibace (Roche) Initiss (Carlo Erba) Cilnidipine (FRC-8653) Use: antihypertensive, calcium antagonist RN: 132203-70-4 MF: C27H28N207 MW: 492.53 LD,< >5 g/kg (M, ~'0.1; 4412 mgkg (R, p.0.); >2 glkg (dog, p.0.) CN: (E)-(?)-I ,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 3- phenyl-2-propen yl ester unspecified stereochemistry RN: 102106-21-8 MF: Cz7Hz,Nz07 MW: 492.53 (+)-enantiomer RN: 132338-87-5 MF: C27H,RN,07 MW: 492.53 (-)-enantiomer RN: 132295-21-7 MF: C,,H,,N,O, MW: 492.53 Reference(s): EP 16 1 877 (Fujirebio; appl. 2.5.1985; J-prior. 4.5.1984, 20.6.1984). Drugs Future (DRFUD4) 21(3), 249-253 (1996). 2-methoxyethyl cinnamyl 2-(3- Formulation(s): tabl. 5 mg, 10 mg Cilnidipine Trade Narnefs): 3-aminocrotonate nitrobenzy1idene)- ocetoocetote J: Atelec (AjinomotolNippon- Cinalong (Fujirebio) HMR) Ciscard (Nippon Boehringer Inp.) Cilostazol (OPC- 1301 3) ATC: BOlAC Use: platelet aggregation inhibitor, cerebral vasodilating activity RN: 73963-72- 1 MF: C2,,HZ7N,O2 MW: 369.47 LD,,,: 25 glkg (M, p.0.); >5 g/kg (R, p.0.); >2 g/kg (dog, p.0.) CN: 6-[4-(I-cyclohexyl-1H-tetrazol-5-yl)b~1~xy]-3,4-dihydro-2(1H)-quinolinone cyclohexyl- 5-chloropento- amine noyl chloride H HO bicyclo- [5.4.0]undec- 1 -cyclohexyl-5-(4- 6-hydroxy-3,4- 5-ene Cilostozol chlorobutyl)tetrozole (1) dihydrocarbo- styril (cf. corteolol synthesis) . 5986 5-1 3-3 MF: C,,Hll,N,,O,, MW: 1202.64 CN: [R-[R*,S *-( E)]]-cyclic(~-alanyl-~-alanyl-N-methyl-~-leucyl-N-methyl-~-leucyl-N-methyl-~-valyl- 3- hydroxy-N,4-dimethyl- ~-2 -amino-6-octenoyl-~-a-aminobutyryl-N-methylglycyl-N-methyl-~-leucyl- ~-. hydrochloride methyl 5-cyclohexyl- 3-methyl- 5-0 x 0-2 - pentenoote (mixture with the 3-pentenoote: from methyl 4-methyl- 2-butenoate) methyl 5-cyclohexyl- 3-methyl-5-hydroxyimino- 2-pentenoate (I). RN: 2954 6-5 9-6 MF: C22H3,BrN0 MW: 408.42 EINECS: 24 9-6 8 7-0 LD,,: 400 mglkg (M, p.0.); 1030 mgkg (R, p.0.) CN: 2-( 1 -bicyclo[2.2.1 Ihept-5-en-2-yl- 1 -phenylethoxy)-N,N-diethyl-N-methylethanaminium