Ceftazidime C 401 0 0 NoN02, CH3COOH 0 0 S02C12, CH2CI2 0 0 H3C IV10^CH3 H3cVO^CH3 - c'+O^CH, N'O~ chloride N'~~ ethyl acetoocetote ethyl 2-hydroxy- ethyl 4-chloro-2- irninoocetoocetote hydroxyirnino- ocetoacetote (I) thioureo H2NL -N 0 '+0^CH3 N'~ H ethyl (Z)-2-(2-amino- thiazol-4-yl)-2-hydroxy- irninoacetote 11 trityl chloride ethyl (2)-2-hydroxyimino- tert-butyl 2-(2-tritylorninothiozol-4- 2-bromo-2- y1)acetate (II) methyl- propionate 1. CH,OH. NoOH 2. HCI m . ethyl (2)-2-(1 -tert-butoxy- corbonyl- 1 -methylethoxyimino)- 2-(2-tritylominothiozol-4- yl)ocetote (111) (Z)-2-(1 -tert-butaxycarbanyl- 1 -rnethylethoxyimino)-2- (2-tritylaminothiozol-4-yl)- ocetic acid (IV) 402 C Ceftazidime cefoloridine (4. v.) 7(R)-ornino-3-(1- pyridiniomethy1)-3- cephem-4-carboxylic acid chloride monohydrochloride (V) ("0 1 Ceftazidime dihydrochloride Reference (s): DOS 2 921 3 16 (Glaxo; appl. 25.5.1979; GB-prior. 26.5.1978). US 4 258 041 (Glaxo; 24.3.1981; GB-prior. 26.5.1978). GB 2 025 398 (Glaxo; appl. 25.5.1979; GB-prior. 26.5.1978). US 4 525 587 (Eli Lilly; 25.6.1985; prior. 27.12.1982, 3.2.1984). intertnediate IV: US 4 497 956 (Glaxo; 5.2.1985; GB-prior. 13.11.1981). acid chloride of IV: EP 101 148 (Glaxo; appl. 28.4.1983; GB-prior. 29.4.1982). intermediate V: EP 135 258 (Eli Lilly; appl. 18.6.1984; USA-prior. 20.6.1983). EP 70 706 (Glaxo; appl. 16.7.1982; GB-prior. 17.7.1981). salts and crystal modiJications: crystalline dihydrochloride: US 4 467 086 (Glaxo; 21.8.1984; GB-prior. 2.10.1979). Ceftezole C 403 pentahydrate: DOS 3 037 102 (Glaxo; appl. 1.10.1980; GB-prior. 2.10.1979). GB 2 063 871 (Glaxo; appl. 1.10.1980; GB-prior. 2.10.1979). US 4 329 453 (Glaxo; 1 1.5.1982; appl. 9.9.1980; GB-prior. 2.10.1979). sesquihydrate: DOS 3 313 816 (Hoechst; appl. 16.4.1983). EP 122 584 (Hoechst; appl. 10.4.1984; D-prior. 16.4.1983). anhydrous crystal modification: DOS 3 313 818 (Hoechst; appl. 16.4.1983). EP 122 585 (Hoechst; appl. 10.4.1984; D-prior. 16.4.1983). pharmaceutical formulations: DOS 3 332 616 (Glaxo; appl. 9.9.1983; GB-prior. 10.9.1982). Formulation(s): vial 250 mg, 500 mg, 1 g, 2 g, 3 g Trade Name(s): D: Fortum (Cascan-Glaxo; Kefadim (Lilly) Starcef (Firma) 1984) I: Ceftim (Glaxo Allen) J: Modacin (Shin Nihon) F: Fortum (Glaxo Wellcome) Glazidim (Glaxo) USA: Ceptaz (Glaxo) GB: Fortum (Glaxo Wellcome; Panzid (Duncan) Fortaz (Glaxo; 1985) 1983) Spectrum (Sigma-Tau) Tazdime (Lilly; 1985) Ceftezole ATC: J01DA36 Use: antibiotic RN: 26973-24-0 MF: C,,H,,N,O,S, MW: 440.49 CN: (6R-trans)-8-0x0-7-[(I H-tetrazol- 1 -ylacetyl)amino]-3-[(1,3,4-thiadiazol-2-ylthio)methyl]-5-thia- 1 - azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 3. COOH O 3. 7-ominocepholo- H tetrozole-1- sparonic acid (cf. cefazolin) (I) acetic acid 2-mercopto- Ceftezole 1 -3.4-thiodiazole Reference(s): DE 1 770 168 (Fujisawa; appl. 10.4.1968; J-prior. 15.4.1967, 23.10.1967, 28.10.1967). US 3 516 997 (Fujisawa; 23.6.1970; J-prior. 15.4.1967, 24.10.1967, 28.10.1967). GB 1 206 305 (Fujisawa; appl. 11.4.1968; J-prior. 15.4.1967, 24.10.1967, 28.10.1967). combination with penicillins: DOS 2 508 443 (~ujisawa; appl. 27.2.1975; J-prior. 28.2.1974, 27.3.1974). 404 C Ceftizoxime Formularion(s): vial 250 mg, 500 mg, 1 g, 2 g (as sodium salt) Trade Name(s): I: Alomen (Benedetti) J: Ccloslin (Fujisawa) Falomesin (Chugai) Ceftizoxime ATC: J01DA22 Use: p-lactam antibiotic (cefalosporin derivative) RN: 68401-81-0 MF: C13H13N,0,S2 MW: 383.41 CN: [6R-[6a,7~(Z)]]-7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]a~in]-8-o~~-5-thia-l- azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid monohydrochloride RN: 68401-80-9 MF: C13H13NS05S2. HC1 MW: 419.87 monosodium salt RN: 68401-82-1 MF: Cl,HI,N,NaO,S, MW: 405.39 LD,,,: 5150 mgkg (M, i.v.); >I0 g/kg (M, p.0.); 5570 mglkg (R, i.v.); >lO glkg (R, p.0.) 4-nitrobenzyl 3-hydroxy-7(R)- phenylocetomido-3-cephem-4- corboxylate (cf. cefoclor synthesis) 4-nitrobenzyl 3-h~droxy-7(R)- phenylocetornidocephom-4- corboxylote (1) 4-nitrobenzyl 7(~)-~hen~l ocetornido-3-cephem-4- corboxylate (11) Ceftriaxone C 405 ? 1. N-(trimethylsilyl)ocetomide 2. 2-(2-formamido-4-thiozolyl)-2- methoxyiminoacetic acid Reference(s): US 4 427 674 (Fujisawa; 24.1.1984; GB-prior. 14.3.1977, 12.7.1977, 11.10.1977, 3.1.1978). US 4 463 002 (Fujisawa; 3 1.7.1984; J-prior. 21.5.198 I). Formula~ion(s): vial 0.25 g, 0.5 g, 1 g, 2 g (as sodium salt) Trade Name(s): D: Ceftix (Roche; 1983) GB: Cefizox (Wellcome); wfm J: Epocelin (Fujisawa) F: Cefizox (Bellon) I: Eposerin (Farmitalia) USA: Cefizox (Fujisawa; 1983) Ceftriaxone ATC: JOlDA13 Use: P-lactam antibiotic (cefalosporin derivative) RN: 73384-59-5 MF: CI8HI8N8O7S3 MW: 554.59 EINECS: 277-405-6 CN: [6R-[6a,7~(Z)J]-7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-X-oxo-3-[[(1,2,5,6-tetrahydro-2- methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid disodium salt . RN: 74578-69-1 MF: C18H,6N,Na,07S3 MW: 598.55 EINECS: 277-930-0 LD,: 2200 mgkg (M, i.v.); >10 glkg (M, p.0.); 1900 mgkg (R, i.v.); >I0 gkg (R, p.0.) d' "' N.N-dimethyl- '-y"O"CH3 ocetomide ethyl 2-(2-omino- chloro- 4-thiozalyl)-2-(meth- ocetyl oxyimino)ocetate chloride (cf. cefotoxime synthesis) ethyl 2-(2-chloroocet- omido-4-thiozolyl)-2- methoxyiminoocetote (I) 406 C Ceftriaxone KOH, H20. ''>NH CH2CIp N(C&,)3, CZH,OH 0 LN PCI5, 0-5 "C O LN 0 I + s+coo~ s+cl N\O/CH3 2-(2-chloroocetomido- 4-thiozoly1)-2-methoxy- iminoocetyl chloride (11) H3C\N/NH2 NoOCH,, CH,OH H3C\N/NH2 + KSCN + A - H s NH~ dimethyl oxolate methyl- potassium N-omino- hydrozine rhodanide N-melhyl- thiourea 7-orninocephalo- sporonic ocid 7(R)-omino-3-[[(2,5-dihydro- 6-hydroxy-2-methyl-50x0- 1,2,4-triazin-3-yl)thio]methyl]- 3-cephem-4-corboxylic acid (N) I. , NoHC03 HZN NH, 2. HCOOH V b I. thiourea Ceftrioxone Reference(s): DOS 2 922 036 (Roche; appl. 30.5.1979; CH-prior. 30.5.1978, 8.3.1979). US 4 327 210 (Roche; 27.4.1 982; appl. 24.1 1 .l978; CH-prior. 30.5.1978). alternative synthesis,from cefotaxime and 2,5-dihydro-6-hydroxy-2-methyl-3-mercapto-5-oxo-l,2,4-triazine: US 4 431 804 (Roche; 14.2.1984; CH-prior. 17.2.1981). Formulation(s): inj. powder 250 mg, 1 g, 2 g Trade Name(s): D: Rocephin (Roche; 1983) F: RocCphine (Roche) GB: Rocephin (Roche) Cefuroxime C 407 [ I: Rocefin (Roche) USA: Rocefin (Roche Labs.; ": Rocephin (Roche) 1985) Cefuroxime ATC: JOlDA06 Use: antibiotic RN: 55268-75-2 MF: C,6H16N408S MW: 424.39 EINECS: 259-560-1 LD,,: 10.4 gkg (M, i.v.); >10 gkg (M, p.0.); >8 g/kg (R, i.v.); 10 glkg (R, p.0.) CN: [6R-[6a,7~(Z)]]-3-[[(aminocarbonyl)oxy]methyl]-7-[[2-furanyl(methoxyimino)acetyl]amino]-8-oxo-5- thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt RN: 56238-63-2 MF: C,,H15N4Na0,S MW: 446.37 qCH3 NaNOZ, conc. HCI 0-methylhyd;oxyl- , qcooH r\ 2. diphenylmethyl 7-amino- cephalosporanate 1. HZO, OH- or esterases 2. CIS0,-NCO, acetonitrile 3. H,O 4. F3CCOOH, anisole n 2. chlorosulfonyl isocyanate V omine hydrochloride 2-fury- glyoxylic ocid I Cefuroxime syn-2-methoxy- imino-2-(2-furyl)- acetic ocid (I) 1. PCI5. CH2C12. N,N-dimethyiacetamide 2. 3. HCI I b 2. 7-amino-3-aminocarbonyloxymethyl- 3-cephem-4-carboxylic acid 408 C Cefuroxime Reference(s): GB 1 453 049 (Glaxo; appl. 21.8.1973; valid from 13.8.1974). DAS 2 439 880 (Glaxo; appl. 20.8.1974; GB-prior. 21.8.1973). DOS 2 462 376 (Glaxo; appl. 20.8.1974; GB-prior. 21.8.1973). DOS 2 204 060 (Glaxo; appl. 28.1.1972; GB-prior. 29.1.1971, 1.10.1971 and 14.1.1972). DOS 2 223 375 (Glaxo; appl. 12.5.1972; GB-prior. 14.5.1971 and 1 .lO.l97 1). DOS 2 265 234 (Glaxo; appl. 12.5.1972; GB-prior. 14.5.1971 and 1.10.1971). US 3 966 717 (Glaxo; 29.6.1976; GB-prior. 14.5.1971, 1.10.1971, 21.8.1973). DOS 2 439 880 (Glaxo; appl. 20.8.1974; GB-prior. 21.8.1973). US 3 971 778 (Glaxo; 27.7.1976; GB-prior. 25.10.1972). US 3 974 153 (Glaxo; 10.8.1976; GB-prior. 14.5.1971, 1 .lO.l97l, 21.8.1973). cryslalline sodium salt: DOS 2 901 730 (Glaxo; appl. 17.1 .l979; GB-prior. 17.1 .l978). syn-2-methoxyimino-2-(2-fury1)acetic acid, resp. -acetyl chloride: US 4 017 515 (Glaxo; 12.4.1977; GB-prior. 14.5.1971, 1.10.1971, 12.5.1972 and 25.10.1972). 2-furylglyoxylic acid: GB I 503 649 (Glaxo; appl. 28.6.1974; valid from 27.6.1975). US 4 013 680 (Glaxo; 22.3.1977; prior. 18.6.1975). L-lysine salt of cefuroxime: US 4 128 715 (Glaxo; 5.12.1978; GB-prior. 28.4.1976). DOS 2 718 730 (Glaxo; appl. 27.4.1977; GB-prior. 28.4.1976). alternative melhods for 3-hydroxymethylcephalosporin derivatives: DE 1 545 915 (Glaxo; appl. 29.10.1965; GB-prior. 30.10.1964,27.1.1965, 19.10.1965). DOS 2 745 219 (Glaxo; appl. 7.10.1977; GB-prior. 8.10.1976). DAS 1 795 777 (Glaxo; appl. 29.10.1965; GB-prior. 30.10.1964, 27.1.1965, 19.10.1965). GB 1 474 519 (Glaxo; appl. 14.5.1973; valid from 6.5.1974). alternative methods for 3-carbamoylo~yme~hyl-ce~halosporin-derivativesfi.om the corresponding 3- hydroxyntethyl-derivatives (enzymatic with 0-transcarbantoylase): US 4 075 061 (Glaxo; 21.2.1978; GB-prior. 19.2.1976). US 4 164 447 (Glaxo; 14.8.1979; GB-prior. 19.2.1976). US 4 164 447 (Glaxo; 14.8.1979; GB-prior. 19.2.1976). (also reaction of the hydroxymethyl-compd. with chlorosulfonyl isocyanate corresponding at the cefoxitin- synthesis, q. v.). Fornzulation(s): amp. 250 mg, 500 mg, 750 mg, 1 g, 1.5 gl20 ml, 1-5 gl40 ml; gran. 125 mg (as sodium salt); tabl. 125 mg, 250 mg, 500 mg Trade Nante(s): D: Elobact (Glaxo Wellcome1 Cascan) Zinacef (Glaxo Wellcome; Hoechst; 1977) Zinnat (Glaxo Wellcome) F: Cepazine (Sanofi Winthrop) Zinnat (Glaxo Wellcome) GB: Zinacef (Glaxo Wellcome) I: Biociclin (Delsaz & Filippini) Biofurex (KBR) Bioxima (Kemyos) Cefamar (Firma) Cefoprim (Esseti) Cefumax (Locatelli) Cefur (Eurofarmaco) Cefurex (Salus Research) Cefurin (Magis) Coliofossim (Coli) Curoxim (Glaxo) Deltacef (Pulitzer) Duxima (Ecobi) Gibicef (Metapharma) Ipacef (IPA) Itorex (Biotekfarma) Kefox (CT) Kesint (Mendelejeff) Lafurex (Lafare) Lamposporin (Leben's) Medoxim (Medici) Polixima (Sifarma) Supero (Francia Farm.) J: Oracef (Shin Nihon-Glaxo) USA: Kefurox (Glaxo Wellcome; 1986) Zinacef (Glaxo Wellcome; 1983) Celecoxib C 409 Celecoxib (SC-58635; YM- 177) ATC: MOl AH01 Use: anti-inflammatory, cyclooxygenase-2 inhibitor RN: 169590-42-5 MF: C,,H,,F,N,O,S MW: 381.38 CN: 4-[5-(4-Methylpheny1)-3-(trifluoromethy1)-1 H-pyrazol-1-y l]benzenesulfonamide I CH3 ethyl trifluoroocetate 4'-methylaceto- phenone 4,4,4-trifluoro- 1 - (4-rnethylpheny1)- butane-1,s-diane (I) Celecoxib I WO 9 515 316 (Searle & Co.; appl. 14.11.1994; USA-prior. 30.1 1.1993,6.4.1994). WO 9 637 476 (Searle & Co.; appl. 23.5.1996; USA-prior. 25.5.1995). US 5 892 053 (Searle & Co.; 6.4.1999; USA-prior. 25.5.1995). Penning, T.D. eta].: J. Med. Chem. (JMCMAR) 40 (9), 1347 (1997). De Vleeschauwer, M.; Gauthier, J.Y.: Synlett (SYNLES) 1997 (4), 375. Formulation(s): cps. 100 mg, 200 mg Trade Name(s): USA: Celebrex (Pfizer; Searle; 1999) Celiprolol (ST- 1396) ATC: C07AB08 Use: cardioselective 0-receptor antagonist * RN: 56980-93-9 MF: C2,H3,N,O4 MW: 379.50 EINECS: 260-497-7 CN: h~-[3-acetyl-4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]phenyl]-N,N-diethylurea monohydrochloride RN: 57470-78-7 MF: C2,H,,N3O4 . HC1 MW: 415.96 EINECS: 260-752-2 LD,,: 42.3 mglkg (M, i.v.); 1362 mg/kg (M, p.0.); 68.3 mglkg (R, i.v.); 2157 mgkg (R, p.0.) 410 C Cerivastatin sodium 0 H3CHDNH, 0 + hydroxyoniline chloride 4-hydroxypheny1)ureo (I) 0 l.4~1 . NoOH 2. (H,C),C-NH, I b 1. epichlorohydrin 2. tert-butylamine Celiprolol DOS 2 458 624 (Lentia; appl. 11.12.1974; A-prior. 20.12.1973, 19.1 1.1974, 20.1 l.l974,25.ll.l974). US 4 034 009 (Chemie Linz 5.7.1977; appl. 17.12.1974; A-prior. 20.12.1973). purification: EP 229 947 (Lentia; appl. 2.12.1986; D-prior. 13.12.1985). synthesis of enantiomers: EP 135 162 (Chemie Linz; appl. 17.8.1984; D-prior. 19.8.1983). EP 155 518 (ChemieLinz; appl. 20.2.1985; D-prior. 21.3.1984). ophthalmic formulation: EP 366 765 (Alcon; appl. 26.4.1989; USA-prior. 26.4.1988). EP 109 561 (Rorer; appl. 20.10.1983; USA-prior. 27.10.1982). sustained release formulation: EP 285 871 (Lentia; appl. 16.3.1988; D-prior. 10.4.1987). EP 268 8 13 (Lentia; appl. 16.10.1987; D-prior. 24.10.1986). Formulation(s): f. c. tabl. 100 mg, 200 mg (as hydrochloride) Trade Namefs): D: Celipro Lich (Lichtenstein) F: CClectol (Bellon) Select01 (Pharmacia & GB: Celectol (Rh6ne-Poulenc Upjohn; 1986) Rorer) Cerivastatin sodium (Avastatin; Bay-W-6228; Rivastatin) Use: hyperlipidemic, HMG-CoA- reductase inhibitor, antihypercholesterolemic agent RN: 143201 -1 1-0 MF: C,,H,,FNNaO, MW: 481.54 CN: [S-[R*,S*-(E)J]-7-[4-(4-fluorophenyl)-5-(methoxymethyl)-2,6-bis(l-methylethyl)-3-pyridinyl]-3,5- dihydroxy-6-heptenoic acid monosodium salt . (2 )-2 -( 1 -tert-butoxy- corbonyl- 1 -methylethoxyimino )- 2-( 2-tritylominothiozol- 4- yl)ocetote (111) (Z )-2 -( 1 -tert-butaxycarbanyl- 1 -rnethylethoxyimino )-2 - (2-tritylaminothiozol-4-yl )-. methyl- potassium N-omino- hydrozine rhodanide N-melhyl- thiourea 7-orninocephalo- sporonic ocid 7(R)-omino- 3-[ [(2,5-dihydro- 6-hydroxy-2-methyl-50x 0- 1,2,4-triazin-3-yl)thio]methyl ]- 3-cephem-4-corboxylic. ethyl (Z )-2 -( 2-amino- thiazol-4-yl )-2 -hydroxy- irninoacetote 11 trityl chloride ethyl (2 )-2 -hydroxyimino- tert-butyl 2-( 2-tritylorninothiozol- 4- 2-bromo- 2- y1)acetate (II) methyl- propionate