Chlormadinone acetate C 43 1 Peridex (Procter & Periogard (Colgate Oral; as Gamble; as gluconate) gluconate) Chlormadinone acetate ATC: G03D Use: progestogen RN: 302-22-7 MF: C,,H,,ClO, MW: 404.93 EINECS: 206- 1 18-0 LD,,: >2 glkg (M, i.v.); >15 glkg (M, p.0.); >I0 gkg (R, p.0.) CN: 17-(acetyloxy)-6-chloropregna-4,6-diene-3,20-dione ___* p-chloranil acid 17-hydraxy- progesterone C I (not isolated) CI Chlorrnadinone ocetote Reference(s1: DE 1 075 114 (E. Merck AG; appl. 29.4.1958). Briickner, K. et al.; Chem. Ber. (CHBEAM) 94, 1225 (1961). Fortnulation(s): tabl. 2 mg, 5 mg Trade Name(s): D: Chlormadinon (Jenapharm) Menova (Merck)-comb. 1: Fisiosequil (Recordati); Gestafortin (Merck) Neo-Eunomin wfm Gestamestrol (Hermal- (Griinentha1)-comb. J; Lutoral (Shionogi) Chemie)-comb. F: Lutkran (SolymCs) 432 C Chlormerodrin Chlormerodrin ATC: C03 Use: diuretic RN: 62-37-3 MF: C5H,1CIHgN,02 MW: 367.20 EINECS: 200-530-4 LD,,: 215 mglkg (M, p.0.); 150 mglkg (R, p.0.) CN: [3-[(aminocarbonyl)amino]-2-rnethoxypropyl-C1,03]chlor~mercury Reference(s): US 2 635 982 (Lakeside Labs.; 1953; prior. 1951). Formulafion(s): amp.; tabl. 18 rng Trade Name(s): USA: Neohydrin (Lakeslde); wfm Chlormezanone ATC: ~03~~02 Use: muscle relaxant RN: 80-77-3 MF: C,,H&INO,S MW: 273.74 EINECS: 201-307-4 LD,,: 600 mgfkg (M, p.0.); 605 mgkg (R, p.0.); 500 mg/kg (dog, p.0.) CN: 2-(4-chlorophenyl)tetrahydro-3-methyl-4H-l,3-thiazin-4-one 1, I-dioxide 3-mercapto- methyl- 4-chloro- 2-(4-chloropheny1)- propionic amine benzoldehyde 3-methyltetm- acid hydro- 1.3-thiozin- 4-one Rejierence(s): GB 815 203 (Sterling Drug; appl. 3.7.1957; USA-prior. 20.7.1956). Surrey, A.R. et al.: J. Am. Chern. Soc. (JACSAT) 80,3469,3471 (1958). Formulation(sj: suppos. 200 mg; tabl. 100 mg, 200 mg, 400 mg Trade Name(s): D: Muskel Trancopal Muskel Trancopal cum (Winthrop); wfm codeino (Winthrop)-comb. Muskel Trancopal camp. with paracetamol and (Winthrop)-comb. with codeine phosphate; wfm 0 Chlormezanone Supotran (Winthrop); wfrn TrancogCsic (W1nthrop)- comb. with aspirine; wfm Trancopal (Winthrop); wfrn paracetamol; wfm F: Alinam (Lucien); wfm GB: Trancopal (Winthrop); wfm Chlormidazole C 433 Trancoprin (Winthrop)- Eblimon (Guidotti)-comb. Transanate (Teikoku comb. with aspirine; wfm numerous combination Hormone) I: Clormetadone (Nuovo preparations USA: Trancopal (Sanofi) Cons. Sanit. Naz.)-comb. J: Myolespen (Dojin Iyaku) Condo1 (Maggioni- Relizon (Mochida) Winthrop)-comb. Trancopal (Daiichi) Chlormidazole (Clornidazolum) ATC: DO1 AC Use: fungistatic, antifungal RN: 3689-76-7 MF: C,,H,,CIN, MW: 256.74 EINECS: 222-998-9 CN: 1-[(4-chlorophenyl)methyl]-2-methyl-1H-benzimidazole hydrochloride RN: 54118-67-1 MF: C,,H,,ClN,. HC1 MW: 293.20 + H3C-COOH + Chlorrnidozole N-(chl0robenzyl)- acetic acid o-phenylenediamine 2. 4-chlorabenzyl bromide 2-methyl- benzirnidozale Referencefs): US 2 876 233 (Griinenthal; 3.3.1959; prior. 29.10.1956). Formulation(s): cream 5 %; ointment 5 % (as hydrochloride) Trade Name(s): D: Myco-Jellin (Griinentha1)- Polycid N (Griinentha1)- comb. with fluocinolone comb.; wfm acetonide; wfm Chlorobutanol ATC: A04AD04 Use: hypnotic, anesthetic RN: 57-15-8 MF: C,H,C1,0 MW: 177.46 EINECS: 200-317-6 CN: 1 ,l, 1 -trichloro-2-methyl-2-propanol 434 C Chloroprednisone acetate KOH H3C~CH3 + HCCI, + 0 acetone chloroform ( Chlorobutonol ( Rqfcrcnce(s): Budesinsky-Protiva, 235. Willgerodt, C,: Bes. Dtsch. Chem. Ges. (BDCGAS) 14, 2451 (1881). US 2 462 389 (Socony-Vac Oil; 1949; prior. 1946). Formzclation(s): sol. 250 mgI100 ml Trade Narne(s): D: Givalex (Norgine) F: Alodont (Warner-Lambeft)- comb. Angispray (Monot)-comb. Balsamorhinol (Jamsen)- comb. Ciella (RPR Cooper)-comb. Eludril (1nava)-comb. Givalex (Nagine Pharma)- comb. Liquifilm (Allergan)-comb. Optrex (Etris)-comb. GB: Cerumol (L.A.B.)-comb. Eludril (Chefam)-comb. Monphytol (L.A.B.)-comb. I: Abiostil (Deca)-comb. Antipulmina (Lisapharma) Cerumenex (ASTA Medics)-comb. Clorobutanolo (Tariff. Integrative) Corizzina (SIT)-comb. Desalfa (1ntes)-comb. Fialetta odontalg. Knapp (Montefannac0)-comb. Oftalzina (SIT)-comb. Respiru (Pierrel)-comb. Rinoleina (Grane1li)-comb. Chloroprednisone acetate ATC: HOZAB; D07AB Use: topical glucocorticoid RN: 14066-79-6 MF: C,,H,CIO, MW: 434.92 EINECS: 237-919-3 CN: (6a)-2 1-(acetyloxy)-6-chloro-17-hydroxypregna-l,4-diene-3,11,20-trione Chloroprednisone ocetate Reference(s): DE 1 079 042 (Syntex; appl. 1958; MEX-prior. 1957). FF-M 666 (Syntex; appl. 20.9.1960). alternative synthesis: US 3 130 21 1 (Upjohn; 21.4.1964; prior. 1957, 1958). pharmace~ctical,formulation: GB 955 89 1 (Organon; valid from 1962; NL-prior. 196 1). Formulation(s): cream; ointment Chloroprocaine C 435 Trade Narnefs): USA: Adremycin (Organon); Topilan (Syntex); wfm wfm Chloroprocaine ATC: NOlBA04 Use: local anesthetic RN: 133-16-4 MF: C13Hl,C1N202 MW: 270.76 CN: 4-amino-2-chlorobenzoic acid 2-(diethy1amino)ethyl ester monohydrochloride RN: 3858-89-7 MF: C13HI,C1N,0, . HCl MW: 307.22 EINECS: 223-371-2 LD,,: 266 mglkg (M, i.p.); 700 mglkg (M, LC.) 0 CI p 9" PI . HCI b 2-diethylamino- ethonol N"2 NH2 NH2 Chloroprocaine 4-amino-2- 4-amino-2- hydrochloride chlorobenzoic chlorobenzoyl acid chloride hydrochloride Reference (s): US 2460 139 (Wallace & Tiernan; 1949; appl. 1945). Formulation(s): multiple-dose vial 1 %, 2 %; single-dose vial 2 %, 3 % (as hydrochloride) Trade Narne(s): .I: Piocaine (Teikoku Kagaku- USA: Nesacaine (Astra) Nagase) Nesacaine (Pennwalt) Chloropyramine (Halopyramine; Chlortripelennamine) ATC: D04AA09; R06AC03 Use: antihistaminic RN: 59-32-5 MF: CI6H2,CIN3 MW: 289.81 EINECS: 200-421-1 LD,,: 24.1 mglkg (M, i.v.); 354 mgkg (M, p.0.); 32.5 mglkg (R, i.v.); 920 mglkg (R, p.0.) CN: N-[(4-chlorophenyl)methyl]-hr,hr-dimethyl-N-2-pyridinyl-1,2-ethanediamine monohy drochloride RN: 6170-42-9 MF: C,,H2,C1N3 . HCl MW: 326.27 EINECS: 228-216-2 ocI + H~N-~/~~~ Hz. Raney-Ni b Pc1 OHC CH3 HN-~/~~~ I 4-chloro-benz- CH3 N.N-dimethyl- N'-(4-chlorobenzyl) aldehyde ethylenediamine N,N-dimethyl- ethylenediarnine (1) 436 C Chloropyrilene Reference(s): US 2 569 3 14 (American Cyanamid; 195 1 ; appl. 1947). Vaughan, J.R. et al.: J. Org. Chem. (JOCEAH) 14,228 (1949). 2-bromo- Formulation(s): amp. 20 mg; cream 1 %; tabl. 25 mg Chloropyramine Trade Name(s): D: Synpen (Geigy); wfm I: Sinopen (Geigy); wfm pyridine Chloropyrilene (Chlorthenylpyramine) ATC: R06AC Use: antihistaminic RN: 148-65-2 MF: C,,H,,ClN,S MW: 295.84 LD,,,: 105 mg/kg (M, i.p.) CN: N-[(5-chloro-2-thienyl)methyl]-A~,h~-dimethyl-N-2-pydinyl-1,2-ethanediamine citrate (1:l) RN: 148-64-1 MF: C,4H,,ClN3S . C6H,07 MW: 487.96 EINECS: 205-720-0 monohy drochloride RN: 135-35-3 MF: C,,H,,ClN,S . HCl MW: 332.30 LD,,,: 438 mg/kg (M, p.0.) 5-chloro-2- N.N-dimethy1-N'- chloromethyl- (2-pyridyl)ethylene- thiophene diarnine I Chloropyrilene I Reference(s): (cf. thenyldiamine, methapyrilene) US 2 581 868 (Monsanto; 1952; prior. 1946). Clapp, R.C. et al.: J. Org. Chem. (JOCEAH) 14,216 (1949). Clapp, R.C. et al.: J. Am. Chem. Soc. (JACSAT) 69, 1549 (1947). Formulation(s): tabl. 25 mg Trade Name(s): I: Brevirina (Prodatti Erma)- Panta-Valeas (Valeas); wfm Tagathen (Lederle; as comb.; wfm USA: Tagathen (Lederle); wfm citrate); wfm Chloroquine C 437 Chloroquine ATC: POlBAOl Use: antirheumatic, antimalarial RN: 54-05-7 MF: CI8H2,C1N3 MW: 319.88 EINECS: 200-191-2 LD,,: 21.6 mglkg (M, i.v.); 3 1 1 mglkg (M, p.0.); 60 rnglkg (R, i.v.); 330 mg/kg (R, p.0.) CN: N4-(7-chloro-4-quinolinyl)-~1,~'-diethyl-l,4-pentanediamine diphosphate RN: 50-63-5 MF: C18H2hC1N3 . 2H3P04 MW: 515.87 EINECS: 200-055-2 LD,: 500 mg/kg (M, p.0.) sulfate (1: 1) RN: 132-73-0 MF: C18H&lN3 . H2S04 MW: 417.96 EINECS: 205-077-6 sulfate (1:l) monohydrate RN: 6823-83-2 MF: C,8H26CIN,. H204S. H20 MW: 435.97 dihydrochloride RN: 3545-67-3 MF: C,8H2,CIN3. 2HCl MW: 392.80 EINECS: 222-592-1 2,s-dihydroxybenzoate RN: 16510-14-8 MF: C,,H,CIN, . xC,H,O, MW: unspecified EINECS: 240-578-3 diorotate RN: 16301-30-7 MF: C18H2,CIN, . 2C,H,N2O4 MW: 632.07 EINECS: 240-389-6 LDS,: 1130 mg/kg (M, p.0.) atorting products: 1. 4.7-Dichloroquinoline H H3C-0 100 OC 'loNH2 + H3cvoAo,cH3 + 250 oc 0 0 c'a&o,cH3 + 11 H3Cv0 0 3-chlorooniline (1) diethyl ethaxymethylene- molonate CI m0,CH3 OH 0 0 H OH ethyl 7-chloro-4- . 7-chloro- hydroxy-3-quinoline- 4-hydroxy- carboxylate (11) quinoline (111) P0CI3 Ill , CI 4.7-dichloro- quinoline (N) diethyl oxaloacetate 438 C Chloroquine I ethyl 5-chloro-4- ethyl 7-chloro-4- hydroxy-2-quinoline- hydroxy-2-quinoline- carboxylate (V) carboxylate (VI) (removal by crystallization from acetic acid) 270 OC mineral ail POCI, W Ib Ill b N CHO 250 "C I + H3c-od - c'~] mineral ail POCI, b 111 -+ N 0 H3C-0 ethyl farmyl- acetate 2. Navaldiamine ethylene diethyl oxide (VIII) amine (K) 2-diethylamina- ethanol Z-diethylamino- ethyl chloride (X) ethyl ocetoacetote (XI) - C02 H . NH Raney-Ni , OYN-CH~ 2, Hfl'f"'~A~~3 CH3 <CH3 CH3 (CH, navaldiarnine (XIV) I -brama- 4-pentanane (XV) H,. NH3, Raney-Ni XV + IX + XI11 4 XIV Chlorothiazide C 439 final product: Chloroquine I Chloroquine Reference(s): US 2233 970 (Winthrop; 1941; D-prior. 1937). DRP 683 692 (I. G. Farben; appl. 1937). Drake, N.L. et al.: J. Am. Chem. Soc. (JACSAT) 68, 1214 (1946). la Price, C.C.; Roberts, R.M.: J. Am. Chem. Soc. (JACSAT) 68, 1204 (1946). DD 53 065 (S. Schwarz et al.; appl. 1966). b Surrey, A.R.; Hammer, H.F.: J. Am. Chem. Soc. (JACSAT) 68, 113 (1946). c US 2 478 125 (American Cyanamid; 1949; appl. 1944). 2a DRP 486 079 (1. G. Farben; appl. 1924). b Elderfield, R.C. et al.: J. Am. Chem. Soc. (JACSAT) 68, 1579 (1946). alternative syntheses ofnovoldiamine: US 2 365 825 (Monsanto; 1944; appl. 1942). GB 1 157 637 (Sterling Drug; appl. 1966; USA-prior. 1965). arninating hydrogenation of novolketone, continuous method: DOS 2 923 472 (Bayer; appl. 9.6.1979). alternative synthesis of 4.7-dichloroquinoline from 3-chloroaniline and acrylic acid ester: FR 1 514 280 (Roussel-Uclaf; appl. 10.1.1967). EP 56 765 (RhGne-Poulenc; appl. 15.1.1982; F-prior. 16.1.1981). alternative synthesis of chloroquine from 7-chloro-4-0x0-l,2,3,4-tetrahydroquinoline and novoldiamine: EP 56 766 (RhGne-Poulenc; appl. 15.1.1982; F-prior. 16.1.1981). chlorination of 7-chloro-4-hydroxyquinoline with benzotrichloride: DOS 3 112415 (Dynamit Nobel; appl. 28.3.1981). Formulation(s): amp. 250 mgl5 ml; syrup 15 mg; tabl. 50 mg, 155 mg, 300 mg (as phosphate) Trade Name(s): D: Resochin (Bayer Vital) GB: Avloclor (Zeneca) USA: Aralen (Sanofi; as F: Nivaquine (RhGne-Poulenc Nivaquine (RhGne-Poulenc hydrochloride) Rorer Specia) Rorer) Aralen (Sanofi; as Savarine (Zeneca Pharma)- I: Cloroc (Formulario Naz.) phosphate) comb. Clorochina (Bayer) Chlorothiazide ATC: C03AA04 Use: diuretic RN: 58-94-6 MF: C7H6C1N304S2 MW: 295.73 EINECS: 200-404-9 LD,,: 940 mg/kg (M, i.v.); 8 g/kg (M, p.0.); 200 mgkg (R, i.v.); 10 glkg (R, p.0.); 1 gkg (dog, i.v.) CN: 6-chloro-2H- 1,2,4-benzothiadiazine-7-sulfonamide I, 1 -dioxide sodium salt RN: 7085-44-1 MF: C7H,C1N3Na0,S2 MW. 317.71 440 C Chlorotrianisene : i + OHC-NH2 + forrnornide Chlorothiozide 4-omino-6-chloro- 1.3-berizenedisulfarnide (I) Reference(.r): US 2 809 194 (Merck & Co.; 8.10.1957; prior. 2.5.1956). US 2 937 169 (Merck & Co.; 17.5.1960; prior. 25.9.1958). Novello, E.C.; Sprague, J.M.: J. Am. Chem. Soc. (JACSAT) 79,2028 (1957). alternatwe synthesis of 4-amino-6-chloro- 1,3-benzenedlsulfamide (chlorosu&onation of 1,3-dichlorobenzeneand subsequent reaction with ammonia): i DE 1 119 290 (Hoechst; appl. 7.1 1.1959). i t Formulatton(s): amp. 500 mgl20 ml (as sodium salt); tabl. 250 mg, 500 mg Trade Name(s): D: Chlotride (Sharp & I: Dohme); wfm F: Diupreskal (Th6raplix)- comb.; wfm Diurilix (Thtrap1ix)-comb.; J: wfm GB: Saluric (Merck Sharp & Dohme) Clotride (Merck Sharp & USA: Aldochlor (Merck) Dohme); wfm Diupres (Merck) Saluren (Croce Bianca); Diuril (Merck) wfm Diuril (Merck; as sodium Aldoclor (Merck Sharp & salt) Dohme)-comb. with generics methyldopa Chlotride (Merck-Banyu) Chlorotrianisene ATC: G03CA06 Use: synthetic cstrogen RN: 569-57-3 MF: C23H21C103 MW: 380.87 EINECS: 209-318-6 CN: 1, I',lU-(1-chloro- 1-ethenyl-2-ylidene)tris[4-methoxybcnzene] 4.4'-dimethoxybenrophenone 4-methaxybenzy- rnognesium chloride . 2-( 4-chlorophenyl)tetrahydro-3-methyl-4H-l,3-thiazin-4-one 1, I-dioxide 3-mercapto- methyl- 4-chloro- 2-( 4-chloropheny1 )- propionic amine benzoldehyde 3-methyltetm- acid hydro- 1.3-thiozin- 4-one Rejierence(s): GB. antihistaminic RN: 14 8-6 5-2 MF: C,,H,,ClN,S MW: 295.84 LD,,,: 105 mg/kg (M, i.p.) CN: N-[(5-chloro-2-thienyl)methyl]-A~,h~-dimethyl-N-2-pydinyl-1,2-ethanediamine citrate (1:l) RN: 14 8-6 4-1 MF: C,4H,,ClN3S. EINECS: 23 7-9 1 9-3 CN: (6a )-2 1-( acetyloxy )-6 -chloro-17-hydroxypregna-l,4-diene-3,11,20-trione Chloroprednisone ocetate Reference(s): DE 1 079 042 (Syntex; appl. 1958; MEX-prior. 1957). FF-M 666