Trade Names: D: Conceplan Grunentha1- comb.. Micronovum Janssen- Cilag TriNovum Janssen-Ci1ag- comb.. GB: Micronor Janssen-Cilag Noriday Searle Primolut N Schering Utovlan Searle numero
Trang 1Norethandrolone N 1461
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 d k g (M, PO.)
CN: (17a)-17-hydroxy-19-norpregn-4-en-20-yn-3-one
1 Li, NH3
2 Crop CH3COOH
0 2 chromium(W) oxide O
3.1 7-dioxo- 1 %nor- 4-androstene (I)
orthoformic acid
triethyl ester
Trang 21462 N Norethisterone acetate
1 K tert-amylate
2 HCI
+ H C E C H -+
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
Trang 3Norethisterone 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
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
Trang 41464 N Noretynodrel
C H
H , C ~ S O , 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
-+
3-methoxy-17-am- 2.5(10)-estradiene (I)
CH Ill
KOC(CH,)ZC2H5 diethyl ether, toluene
Noretynadrel
L
Trang 5Norfenefrine 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.;
Zyklustabletten IB 2 (Ce- Elan (Valeas)-comb.; wfm Enovid E (Sear1e)-comb.;
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 m g k g (R, p.0.)
O K 3 + .I% - 0g3
OH
3'-hydroxyaceto- benzoyl
0%
3'-benzoyloxy-
NH, resp
hexomethylenetetromine
2-bromo-3'-benzoyloxy- ocetophenone
2-omino-3'-hydroxy ocetophenone (Ill)
Trang 6r
1466 N Norfloxacin
Norfenefrine
u
H2 Roney-Ni
I11 -+
I-C,H,, -0N0,
I
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):
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 g k g (R, p.0.)
CN: 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(I-piperazinyl)-3-quinolinecarboxylic acid
0
+ H 3 c v o ~ o , c H 3 + :xX&o-cH3
fluorooniline methylenemalonate
1 8 r - c ~ ~ , N ( c ~ H ~ ) ,
2 NoOH
0wCH3 1 ethyl bromide
Trang 7Norgestimate 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)
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):
Chibroxin (Chibret) GB: Utinor (Merck Sharp & USA: Chibroxin (Merck)
& Dohmc-Chibret) I: Fulgram (ABC) Noroxin (Roberts)
Noroxin (MSD)
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- , - , ,-' " - -
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)-
Pramino (Janssen-Cilag)- Effiprev (Eflik)-comb 1: Cilest (Cilag)-comb comb
Trang 81468 N Norgestrel
USA: Ortho-Cyclen (Ortho- Ortho-Tri-Cyclen (Ortho-
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 -
(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 , 7 8 2 (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):
Stediril (Wyeth)-comb Stediril (Wyeth-Leder1e)- Eugynon (Schering)-comb
comb
Trang 9Norgestrienone N 1469 I: Eugynon (%hering)-comb USA: LoIOvral (Wyeth-Ayerst)- Ovral (Wyeth-Ayerst)-
Ovrette (Wyeth-Ayerst)
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 0 0 Al[OCH(CH&l, b
1 hydroxylamine
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
Trang 101470 N Normethadone
Trade Nume(s):
Use: antitussive, analgesic RN: 467-85-6 MF: C2,H2,NO MW: 295.43 EINECS: 207-401-1
LD,,: 31 m g k g (M, i.v.)
CN: 6-(dimethylamino)-4,4-diphenyl-3-hexanone
hydrochloride
RN: 847-84-7 MF: C2,,Hz5NO HCI
LD,,: 45 m g k g (M, i.v.)
2-(dimethylomino)ethyl diphenyl-
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