Norethandrolone N 1461 Norethandrolone ATC: A14AA09 Use: anabolic RN: 52-78-8 MF: C2,H3,02 MW: 302.46 EINECS: 200-153-5 norethisterone (9. v.) 1 Norethandrolone Reference(s): US 2 721 871 (Searle; 1955; appl. 1954). alternative synthesis: 17s 2 691 028 (Searle; 1954; prior. 1952). Colton, EB. et al.: J. Am. Chem. Soc. (JACSAT) 79, 1123 (1957). Formulation(s): tabl. 10 mg Trade Name(s): F: Nilevar (Laphal) GB: Nilevar (Searle); wfm USA: Nilevar (Coastal); wfm Norethisterone (Norethindrone) ATC: G03ACO1; G03DC02 Use: progestogen RN: 68-22-4 MF: C,H,O, MW: 298.43 EINECS: 200-681-6 LDso: 6 dkg (M, PO.) CN: (17a)-17-hydroxy-19-norpregn-4-en-20-yn-3-one 1. Li, NH3 2. Crop CH3COOH HA 1. lithium, ammonia 0 2. chromium(W) oxide O 3.1 7-dioxo- 1 %nor- 4-androstene (I) orthoformic acid triethyl ester 1462 N Norethisterone acetate 1. K tert-amylate 2. HCI + HCECH + acetylene Norethisterane I Reference(s): US 2 774 122 (Syntex; 1956; MEX-prior. 1951). US 2 774 777 (Syntex; 1956; prior. 1952). Djcrassi, C. et al.: J. Am. Chem. Soc. (JACSAT) 76,4092 (1954). alternative syntheses: US 2 849 462 (P. dc Ruggieri; 1958; appl. 1957). Ringold, H.J. et al.: J. Am. Chem. Soc. (JACSAT) 78,2477 (1956). Ringold, H.J. et a].: Ann. N. Y. Acad. Sci. (ANYAA9) 71,500 (1958). Ueberwasser, H. et al.: Helv. Chim. Acta (fICACAV) 34,344 (19631. Ullmanns Encykl. Tech. Chem., 4. Aufl., Vol. 13, 31. Onken, D.; Meublein, D.: Pharmazie (PHARAT) 25, 3 (1970). total synthesis of 3,17-dioxo- 19-nor-4-androstene: DE 1 958 600 (Hoffmann-La Roche; appl. 21.1 1.1969; USA-prior. 22.11.1968). Formulation(s): tabl. 0.35 mg, 0.5 mg (also in comb.) Trade Name(s): D: Conceplan (Grunentha1)- comb. Micronovum (Janssen- Cilag) TriNovum (Janssen-Ci1ag)- comb. numerous generics F: Norluten (SmithKline Beecham) Ortho-Novum 1135 (Janssen-Ci1ag)-comb. Triella (Ci1ag)-comb. GB: Micronor (Janssen-Cilag) Noriday (Searle) Primolut N (Schering) Utovlan (Searle) numerous combination preparations I: Trinovum (Janssen-Ci1ag)- comb. J: Norluten D (Shionogi) Primosiston Tab. (Nihon Schering)-comb. Sophia-A, C (Teikoku Zoki)-comb. USA: Brevicon (Sear1e)-comb. Micronor (Ortho-McNeil) Modxon (Ortho-McNei1)- comb. Nclova (Warner Chi1cott)- comb. Norinyl (Sear1e)-comb. Ortho-Novum (Ortho- McNci1)-comb. generic and combination preparations Norethisterone acetate (Norethindrone acetate) ATC: G03D Use: progestogen RN: 51-98-9 MF: C22H2,03 MW: 340.46 EINECS: 200-132-0 CN: (17a)- 17-(acetyloxy)-19-norpregn-4-en-20-yn-3-one Norethisterone enanthate N 1463 norethisterone acetic anhydride (4. v.) Norethisterone ocetote 19-norpregno-3,5-dien-20-yne- 3.1 78-diol diacetate (I) Reference (s): US 2 964 437 (Schering AG; 13.12.1960; appl. 11.6.1957; D-prior. 16.6.1956) Djerassi, C. et al.: J. Am. Chem. Soc. (JACSAT) 81,436 (1959). DE 1 017 166 (Schering AG; appl. 16.6.1956). alternative synthesis: DD 136 502 (VEB Jenapharm; appl. 1 1.5.1978). Formulation(s): f. c. tabl. 1 mg; tabl. 1 mg, 5 mg, 10 mg Trade Name(s): D: Gestakadin (Kade) Neorlest 21 (Parke Davis)- comb. Norethisteron (Jenapharm) Primolut-Nor (Schering) Primosiston (Schering)- comb. Prosiston (Schering)-comb. GB: Sinovula (Axhe)-comb. Sovel (Novartis Pharma)- comb. Trisequens (Novo Nordisk; RhBne-Poulenc Rarer)- comb. F: Kliogest (Specia)-comb. Milli-Anovlar (Schering)- comb. Milligynon (Schering) Miniphase (Schering)- comb. Primolut-Nor (Schering)- comb. Elleste Deret (Sear1e)- comb. Estra combi (Novartis)- comb. Evorel combi (Janssen- Ci1ag)-comb. Klimofem (Novo Nordisk)- comb. Loestrin (Parke Davis)- comb. S.H. 420 (Schering Chemicals) Trisequens (Novo Nordisk)-comb. I: Primolut-Nor (Schering) J: Anovlar (Nihon Schering)- comb. Norluten A (Shionogi) USA: Aygestin (ESI Lederle) Estrostep (Parke Davis)- comb. Norethisterone enanthate ATC: G03DB Use: progestogen RN: 3836-23-5 MF: C,,H,,O, MW: 410.60 EINECS: 223-326-7 CN: (17a)-17-[(l -oxoheptyl)oxy]-19-norpregn-4-en-20-yn-3-one 1464 N Noretynodrel C H III H,C~SO,H or pyridine , 0 0 norelhisterone enanthic anhydride (q v.) Norethisterone enontnate I Reference(s): DE 1 017 166 (Schering AG; appl. 16.6.1956) alt~rnative synthesis: FR 1 349 991 (Parke Davis; appl. 29.1 1.1962; GB-prior. 1.12.1961). use as progestogen depot preparation: DOS 2 548 413 (Schering AG; appl. 27.10.1975). Formulation(s): amp. 200 rng/ml Trade Name($): D: Noristerat (Schering) F: Noristerat (Schering) GB: Noristerat (Schering) Noretynodrel (Norethy nodrel) ATC: G03D Use: progestogen RN: 68-23-5 MF: C2,H260, MW: 298.43 EINECS: 200-682-1 CN: (17a)-17-hydroxy-19-norpregn-5(10)-en-20-yn-3-one Li, liq. NH, + 3-methoxy-17-am- 2.5(10)-estradiene (I) CH Ill KOC(CH,)ZC2H5. diethyl ether, toluene I + HCGCH b Noretynadrel L Norfenefrine N 1465 Reference(s): US 2 691 028 (Searle; 1954; prior. 1953, 1952). US 2 725 389 (Searle; 1955; prior. 1953). starting material: US 2 655 51 8 (Searle; 1953; appl. 1952). alterna~ive synthesis: FR 1 421 476 (Roussel-Uclaf; appl. 2.1 1.1964). Formulation(s): tabl. 2.5 mg, 5 mg, 9.85 mg in comb. with metranol Trade Name(s): D: Kontrazeptivum 63 I: Ebionel (Panther-Osfa USA: Enovid (Sear1e)-comb.; (ratiopharm)-comb.; wfm Chemie)-comb.; wfm wfm Zyklustabletten IB 2 (Ce- Elan (Valeas)-comb.; wfm Enovid E (Sear1e)-comb.; Ka-Ce)-comb.; wfm Singestol (Caber)-comb.; wfm GB: Enavid (Sear1e)-comb.; wfm wfm J: Enavid (Dainipponj-comb. Norfenefrine ATC: COICAOS Use: sympathomimetic, circulatory analeptic, adrenergic RN: 536-21-0 MF: CHHl,N02 MW: 153.18 EINECS: 208-626-8 LD,,: 4.9 mglkg (M, i.v.); 263 mgkg (M, p.0.); 17.4 mgkg (R, i.v.); 390 mglkg (R, p.0.) CN: a-(aminomethy1)-3-hydroxybenzenemethanol hydrochIoride RN: 4779-94-6 MF: C8HllN02.HC1 MW: 189.64 EINECS: 225-323-6 LD,,: 113 mglkg (M, i.v.); 3300 mglkg (M, p.0.); 17.4 mglkg (R, i.v.); 390 mgkg (R, p.0.) OK3 + .I% - 0g3 OH 3'-hydroxyaceto- benzoyl 0% 3'-benzoyloxy- phenone (I) chloride ocetophenone (11) NH, resp. hexomethylenetetromine n - OH 2-bromo-3'-benzoyloxy- ocetophenone 2-omino-3'-hydroxy ocetophenone (Ill) r 1466 N Norfloxacin Norfenefrine u H2. Roney-Ni I11 + I-C,H,, -0N0,. I isoomyl nitrite QoH HO &NH2 OH Reference (s): a FR 851 296 (R. Sachs; 1938). FR 866 569 (R. Sachs; 1939). b DE 2 130 7 10 (Godecke; appl. 21.6.1971). Formulation(s): amp. 50 mg15 ml; cps. 6 mg; drg. 15 mg, 45 mg; drops 6 mglml; sol. 6 mglml; s. r. tabl. 50 mg; tabl. 45 mg (as hydrochloride) Trade Nume(s): D: Energona (Maurer) Norfenefrin Zlethen Normetolo (Selvi); wfm Esbuphon (Schaper & (Ziethen) J: Coritat (Green Cross) Briimmer) Novadral (Godecke) Tonolift (Teisan) Norfenefrin retard forte- generic and numerous Zondel (Grelan; as ratiopharm (ratiopharm) combination preparations hydrochloride) I: Euro-Cir (Virgiliano); wfm Norfloxacin ATC: JOlMA06; SOlAX12 Use: antibiotic (gyrase inhibitor) RN: 70458-96-7 MF: C,,H,,FN30, MW: 319.34 EINECS: 274-614-4 LD,,,: 220 mglkg (M, i.v.); 4 glkg (M, p.0.); 245 mg/kg (R, i.v.); >4 gkg (R, p.0.) CN: 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(I-piperazinyl)-3-quinolinecarboxylic acid (CH3 H 0 C'DNH2 F + H3cvo~o,cH3 + :xX&o-cH3 0 0 H,C,O 0 3-chloro-4- diethyl ethoxy- (I) fluorooniline methylenemalonate 1. 8r-c~~ , N(c~H~), 2. NoOH I P * 11 0wCH3 1. ethyl bromide 0 0 Norgestimate N 1467 Referencefs): DE 2 804 097 (Kyorin; appl. 3 1.1.1978; J-prior. 16.5.1977) US 4 146 719 (Kyorin; 27.3.1979; J-prior. 16.2.1977). 1 -ethyl-6-fluoro-7- piperazine qnthesis of 1-ethyl-6-fluoro-7-chloro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid: Koga, H. et al.: J. Med. Chem. (JMCMAR) 23, 1358 (1980). Norfloxocin Fortnulation(s): eye drops 3 mglml; f. c. tabl. 400 rng chloro-1.4-dihydro- 4-oxoquinoline-3- carboxylic acid (U) Trade Nameis): D: Barazan (Dieckmann; Noroxine (MSD-Chibret; Sebercim (ISF) 1984) 1986) J: Baccidal (Kyorin) Chibroxin (Chibret) GB: Utinor (Merck Sharp &. USA: Chibroxin (Merck) F: Chibroxine (Merck Sharp Dohme) Noroxin (Merck; 1986) & Dohmc-Chibret) I: Fulgram (ABC) Noroxin (Roberts) Noroxin (MSD) Norgestimate ATC: G03AA Use: progestogen, oral contraceptive RN: 35189-28-7 MF: C,,H,,NO, MW: 369.51 CN: (17a)- 17-(acetyloxy)-13-ethyl-l8,19-dinorpregn-4-en-20-yn-3-one oxime :H3 ""2 , - , ,-' . " - - C=CH b C=CH hydroxylomine hydrochloride levonorgestrel acetate (cf. levonorgestrel) Reference(s): GB 1 123 104 (Ortho; appl. 2.9.1966; USA-prior. 22.10.1965). DE 1 620 102 (Ortho; appl. 9.9.1966; USA-prior. 22.10.1965). medical use for suppression of fertility: US 4 027 019 (Ortho; 3 1 S.1977; appl. 23.1.1976; prior. 24.7.1975). Formulation(s): tabl. 0.25 mg in comb. with ethinylestradiole Trade Name(s): D: Cilest (Janssen-Ci1ag)- F: Cilest (Janssen-Ci1ag)- GB: Cilest (Janssen-Ci1ag)- comb. comb. comb. Pramino (Janssen-Cilag)- Effiprev (Eflik)-comb. 1: Cilest (Cilag)-comb. comb. 1468 N Norgestrel USA: Ortho-Cyclen (Ortho- Ortho-Tri-Cyclen (Ortho- McNeil) McNeil) Norgestrel ATC: G03AA06; G03FAlO; G03FBO1 Use: progestogen RN: 6533-00-2 MF: C,,H,,O, MW: 3 12.45 EINECS: 229-433-5 LD,,: 5010 mglkg (M, p.0.); 5010 mglkg (R, p.0.) CN: (17a)-(&)-I 3-ethyl- 17-hydroxy- 18,19-dinorpregn-4-en-20-yn-3-one CH (CH,),COK. THF & + HC-CH H3C, 1 I H H potassium tert- H3C\ 0 butylate 0 (C)-3-methoxy-18-methyl- acetylene 17-0x0-2.5(10)-estradiene Reference (s): GB 1 041 279 (H. Smith; appl. 19.10.1961). GB 1 041 280 (H. Smith; appl. 19.10.1961). DOS 2 030 056 (Schering AG; appl. 13.6.1970). Buzby, G.C. et al.: J. Med. Chem. (JMCMAR) 9,782 (1966). starting material: Smith, H. et al.: J. Chem. Soc. (JCSOA9) 1964,4472. (+)-3-methoxy-18-methyl- 19-norpregna-2.5(10)- dien-20-yne-178-ol (I) total synthesis: NL-appl. 6 414 702 (Roussel-Uclaf; appl. 17.12.1964; F-prior. 17.12.1963). Smith, H. et al.: Experientia (EXPEAM) 19,394 (1963). Smith, H. et al.: J. Chem. Soc. (JCSOA9) 1963,5072. Blickenstaff, R.T.; Ghosh, A.C.; Wolf, G.C.: Total Synthesis of Steroids (Organic Chemistry Vol. 30) p. 270, Academic Press, New York, London 1974. Formulation(s): drg. 0.5 mg in comb. with ethinylestradiole Trade Name(s): D: Cyclo-Progynova Minidril (Wyeth-Leder1e)- GB: Cyclo Progynova (ASTA (Schering)-comb. comb. Medics)-comb. Stediril (Wyeth)-comb. Stediril (Wyeth-Leder1e)- Eugynon (Schering)-comb. F: Adepal (Wyeth-Lederle)- comb. Neogest (Schering) comb. Trinordiol (Wyeth- Prempak C (Wyeth) Microval (Wyeth-Lederle) Lederle)-comb. Schering PC4 (Schering)- comb. Norgestrienone N 1469 I: Eugynon (%hering)-comb. USA: LoIOvral (Wyeth-Ayerst)- Ovral (Wyeth-Ayerst)- J: Duoluton (Schering) comb. comb. Ovrette (Wyeth-Ayerst) - Norgestrienone ATC: GO~ACO~ Use: progestogen RN: 848-21-5 MF: C2,Hz2O2 MW: 294.39 EINECS: 212-698-6 CN: (17a)-17-hydroxy-l9-norpregna-4,9,11-trien-20-yn-3-one 1. NH,OH. NaOCOCH, & 2.00 Al[OCH(CH&l, b 1. hydroxylamine 0' 2. cyclohexonone, aluminum 17p-hydroxy-3-0x0- isopropylate 4.9,1 1 -estratriene 4.9.1 1 -eslrotrien-3.17-diane 3-axime (I) ethynylmognesium bromide 178-hydroxy-19-norpregna- 4,9,1 1 -trien-20-yn-3-one oxirne (11) 1 Norgestrienone I Reference(s): US 3 257 278 (Roussel-Uclaf; 21.6.1966; F-prior. 5.7.1963,4.10.1963, 15.5.1964, 14.8.1964, 1.6.1965). FR-M 3 060 (Roussel-Uclaf; appl. 4.10.1963). NL 6 401 555 (Roussel-Uclaf; appl. 20.2.1964; F-prior. 20.2.1963,5.7.1963,4.10.1963). NominC, G. et a].: C. R. Hebd. Seances Acad. Sci. (COREAF) 260,4545 (1965). starting material: BE 631 298 (Roussel-Uclaf; appl. 19.4.1963; F-prior. 20.4.1 962). NL 6 414 702 (Roussel-Uclaf; appl. 17.12.1964; F-prior. 17.12.1963, 14.1.1964, 20.2.1964). NL6 517 141 (Roussel-Uclaf; appl. 30.12.1965; F-prior. 31.12.1964,26.2.1965,24.3.1965, 14.6.1965,3.9.1965, 17.9.1965). Velluz, L. et al.: C. R. Hebd. Seances Acad. Sci. (COREAF) 257,569 (1963). total synthesis: Ullmanns Encykl. Tech. Chem., 4. Aufl., Vol. 13, 34. Velluz, L. et al.: C. R. Hebd. Seances Acad. Sci. (COREAF) 257,3086 (1963). Formulation(s): tabl. 0.35 mg 1470 N Normethadone Trade Nume(s): F: Ogyline (Roussel) Planor (Rousse1)-comb. Normethadone ATC: R05~~06 Use: antitussive, analgesic RN: 467-85-6 MF: C2,H2,NO MW: 295.43 EINECS: 207-401-1 LD,,: 31 mgkg (M, i.v.) CN: 6-(dimethylamino)-4,4-diphenyl-3-hexanone hydrochloride RN: 847-84-7 MF: C2,,Hz5NO . HCI LD,,: 45 mgkg (M, i.v.) 2-(dimethylomino)ethyl diphenyl- chloride ocetonitrile ethy lmogneslum bromide Reference(s): DE 865 314 (Hoechst; appl. 1941). MW: 33 1.89 EINECS: 212-694-4 NONH2 sodium ornide nitrile (1) Normethadone DE 870 700 (Hoechst; ap& 1942). Bockmiihl, M.; Ehrhart, G.: Justus Liebigs Ann. Chem. (JLACBF) 561, 52 (1948). Formulation(s): drops 10 mg/ml Trade Name(s): D: Ticarda (Hoechst); wfm Normolaxol RN: 18831-34-0 MF: C,,H,,NO, MW: 327.38 CN: 4,4'-(2-quinolinylmethylene)bis[phenol] ATC: A06A Use: laxative hydrochIoride RN: 19035-45-1 MF: C22H,7N02 . HCl MW: 363.84 . (17a )-( &)-I 3-ethyl- 17-hydroxy- 18,19-dinorpregn-4-en-20-yn-3-one CH (CH,),COK. THF & + HC-CH H3C, 1 I H H potassium tert- H3C 0 butylate 0 (C )-3 -methoxy-18-methyl-. progestogen RN: 6 8-2 3-5 MF: C2,H260, MW: 298.43 EINECS: 20 0-6 8 2-1 CN: (17a )-1 7-hydroxy-19-norpregn-5(10)-en-20-yn-3-one Li, liq. NH, + 3-methoxy-17-am- 2.5(10)-estradiene (I) CH. US 4 146 719 (Kyorin; 27.3.1979; J-prior. 16.2.1977). 1 -ethyl-6-fluoro- 7- piperazine qnthesis of 1-ethyl-6-fluoro-7-chloro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid: Koga, H. et al.: