starting material: Plattner, P.A.. 5 mg, 25 mg Trade Names: D: Presomen Solvay Prothil Solvay I: Colprone Wyeth Arzneimitte1-comb... Clinovir Pharmacia & Upjohn Depo-Clinovir Pharmacia
Trang 1Medazepam M 1221 Pectite (Kissei)
Pelmain (Sawai)
Radcol (Nippon Universal) Thibrin (Kyowa-Hoei) Sekinin (Tokyo Hosei) Zeotin (Toa Eiyo)
Use: tranquilizer, anxiolytic RN: 2898-12-6 MF: Cl6H,JlN2 MW: 270.76 EINECS: 220-783-4
LD,,: 475 mgfkg (M, p.0.);
900 mglkg (R, p.0.)
CN: 7-chloro-2,3-dihydro-1-methyl-5-phenyl-1H-1,4-benzodiazepine
2-amino-5-
chloro-
benzophenone
1 NaH
2 H3C-I
LiAIH, lithium olanote
I Medazepam
glycine ethyl ester
2 methyl iodide
H ~ N - ~ ~ ~
MgBr nitrobenzene, K2C03
Cu(CH3COO),
2,5-dichloro- phenyl- 1 -(2,5-dichloro-
benzonitrile magnesium phenyl)-1-phenyl-
H,c/O\ /P
0//S'Oy~~3
dimethyl sulfote
Trang 21222 M Medibazine
diamine (111)
Reference(s):
a,bUS 3 109 843 (Roche; 5.1 1.1963; appl 21.6.1962; prior 28.7.1961)
US 3 131 178 (Roche; 28.4.1964; prior 28.7.1961,4.12.1961,21.6.1962)
Sternbach, L.H et al.: J Org Chem (JOCEAH) 28,2456 (1963)
c DAS 1 934 385 (Sumitomo; appl 7.7.1969)
d DAS 1 695 188 (Roche; appl 23.5.1967; USA-prior 3.6.1966)
DAS 1 795 81 1 (Roche; appl 23.5.1967)
alternative syntheses:
US 3 141 890 (Roche; 21.7.1964; prior 28.7.1961,4.12.1961, 21.6.1962)
US 3 144 439 (Roche; 11.8.1964; prior 28.7.l961,4.12.l96I, 21.6.1962)
DE 1 445 864 (Roche; appl 27.7.1962; USA-prior 28.7.1961)
DOS 2 204 484 (Sumitomo; appl 31.1.1972; J-prior 9.2.1971, 6.4.1971,28.5.1971)
DOS 2 217 301 (Sumitomo; appl 10.4.1972; J-prior 12.4.1971)
I-demethyl-derivative from 5-chloro-2-(2,3-dioxop~perazino)benzophenone:
DAS 1 906 254 (Sumitomo; appl 7.2.1969; J-prior 2.4.1968)
DAS 1 965 980 (Sumitomo; appl 7.2.1969; J-prior 2.4.1968)
Formulation(s): cps 5 rng, I0 mg; tabl 2.5 mg, 5 mg, 10 rng
Trade Name(s):
D: Medazepam AWD I: Debrum (Sigma-Tau)- Kobazepam (Nihon
Rudotel Tabletten (OPW) J: Azepamid (Taiyo) Narsis (Sumitomo) F: Nobriurn (Roche); wfm Cerase (Torii) Nobrium (Nippon Roche)
Use: coronary vasodilator RN: 53-31-6 MF: C,,H,,N202 MW: 386.50 EINECS: 200-168-7
LD,,,: 4 1 mgkg (M, i.v.)
CN: l-(1,3-benzodioxol-5-ylmethyl)-4-(diphenylmethyl)piperazine
Trang 3Medifoxamine M 1223
Reference(s):
US 3 119 826 (Science Union; 28.1.1964; F-prior 12.4.1961)
1-(3.4-methylenedioxy- benzhydryl
Trade Narne(s):
F : Vialibran (Servier); wfm
Medibozine
Medifoxamine
benzy1)piperozine chloride
ATC: N06A Use: antidepressant RN: 32359-34-5 MF: C1,H,,N02 MW: 257.33 EINECS: 251-01 1-4
LD,,: 750 mgikg (M, p.0.)
CN: N,N-dimethyl-2,2-diphenoxyethanamine
fumarate (1:l)
RN: 16604-45-8 MF: C,,H,,N02 C4H4O4 MW: 373.41 EINECS: 240-657-2
C I "'8
2 dimethylornine
rnethylocetomide
Reference(s):
FR 5 498 (Lab Gerda; appl 1966)
Brunet, M.A et al.: Bull Soc Chim Fr (BSCFAS), 2000 (1967)
additional synthesis:
FR 2 645 147 (Lab Rolland; appl 3.4.1989)
FR 2 601 004 (Lab Rolland; appl 7.7.1986)
FR 2 588 553 (Lab Rolland; appl 16.10.1985)
EP 226 475 (Lab Rolland; appl 22.7.1985)
synthesis of diphenoxyacetic acid:
Alphen, J van: Recl Trav Chim Pays-Bas (RTCPA3) 46, 144 (1927)
Scheibler, H.; Depner, M.: J Prakt Chem (JPCEAO) 7, 60 (1958)
DE 561 281 (Chem Fabrik von Heyden; appl 1930),
also EP 226 475, FR 2 601 004
Trang 41224 M Medrogestone
medical use for treatment of cerebral hypoxia and senility:
FR 2 589 357 (Lab Rolland; appl 5.11.1985)
FR 2 583 639 (Lab Rolland; appl 24.6.1985)
Formularion(s): tabl 50 mg
Trade Name(s):
F: ClCdial (Lipha SantC)
Use: progestogen RN: 977-79-7 MF: C,,H,,O, MW: 340.51 EINECS: 213-555-0
LD,,,: 850 mglkg (g.p., p.0.)
CN: 6,17-dimethylpregna-4,6-diene-3,20-dione
& M e ,,vCH3 \ ~ ' 3 H,C 1 O/ OH , CHCI3, 0 'C
peroxyocetic acid
methyl 3@-hydroxy-17a-
rnethyl-ondrost-5-ene-17-
corboxylote
Cr03 H,C-CO-CH3
chromium(VI) oxide
methylmagnesium
bromide
thionyl chloride
CI CI
nr
chloronil (N)*
C H ~
Medrogestone
Trang 5Medroxyprogesterone acetate M 1225
iodide
38-ocetoxy-6-methyl-
20-0x0-5.16-pregnodiene
(from dehydropregnenolone
onologously to o)
1 Oppenouer oxidation
2 IV
Reference(s):
a US 3 133 913 (American Home Products, 19.5.1964; appl 11.9.1961)
Deghenghi, R.; Gaudry, R.: J Am Chem Soc (JACSAT) 83,4668 (1961)
starting material:
Plattner, P.A et al.: Helv Chim Acta (HCACAV) 31,603 (1948)
b Deghenghi, R et al.: J Med Chem (JMCMAR) 6,301 (1963)
starting material:
Bum, D et al.: J Chem Soc (JCSOA9) 1957,4092
alternative syntheses:
US 3 170 936 (American Home Products; 23.2.1965; appl 7.8.1963)
US 3 210 387 (American Home Products; 5.10.1965; appl 6.5.1963; CDN-prior 28.1 1.1962)
Formulation(s): tabl 5 mg, 25 mg
Trade Name(s):
D: Presomen (Solvay Prothil (Solvay I: Colprone (Wyeth)
Arzneimitte1)-comb Arzneimittel) USA: Colprone (Ayerst); wfm
F: Colprone (Wyeth-Lederle)
Use: antineoplastic, progestogen RN: 71-58-9 MF: C2,H,,O4 MW: 386.53 EINECS: 200-757-9
LD,,,: >16 glkg (M, p.0.);
>6.4 g/kg (R, p.0.);
>5 glkg (dog, p.0.)
CN: (6cr)-17-(acetyloxy)-6-methylpregn-4-ene-3,20-dione
5a.17~-dihydroxy-
3,20-dioxo-6P-methyl-
HCI CHCIJ
-
C H 3 17-hydroxy-6~- methylprogesterone (I)
Trang 6I226 M Medroxv~rogesterone acetate
ocetic
anhydride (11)
CH3 Medroxyprogesterone ocetote
progesterone glycol
Referenceis):
a US 3 147 290 (Upjohn; I 9.1964; appl 17.5.1961; prior 23.1 1.1956)
Ellis, B et a].: J Chem Soc (JCSOA9) 1957, 4092
starting material: c f literature cited under a
b US 3 061 616 (~ocleta Farmaceutici Italia; 30.10.1962; appl 17.9.1958; GB-prior 24.4.1958)
DE 1 097 986 (Syntex; appl 29.8.1957; MEX-prior 8.9.1956)
Babcock, J.C et al.: J Am Chem Soc (JACSAT) 80,2904 (1958)
starting material:
Bernstein, S et al.: J Am Chem Soc (JACSAT) 76, 5674 (1954)
The Merck Index, 4756 (Rahway 1976)
alternative syntheses:
DE 1 081 456 (British Drug Houses; appl 21.8.1958; GR-prior 13.8.1957)
DE 1 101 415 (Searle; appl 24.9.1958; USA-prior 27.9.1957)
US 3 043 832 (Ormonoterapia Richter; 10.7.1962; appl 28.4.1961; I-prior 27.2.1961)
review:
Ehrhardt, Ruschig 111,352,
Trang 7Medrylamine M 1227
Formulation(s): amp 500 mg, 1 g; susp 500 mg; susp 150 mglml, 500 mglml; tabl 2.5 mg, 5 mg, 10 mg, 100
mg, 200 mg, 250 mg, 400 mg, 500 mg
Trade Name(s):
D: Clinofem (Pharmacia &
Upjohn)-comb
Clinovir (Pharmacia &
Upjohn)
Depo-Clinovir (Pharmacia
Farlutal (Pharmacia &
Upjohn)
MPA (Hexa1)-comb
F: Depo-Prodasone
(Pharmacia & Upjohn)-
comb
Depo-Provera (Pharmacia
Divina (1nnothCra)-comb
Farlutal (Pharmacia &
Upjohn) Gestoral (Novartis) Prodasone (Pharmacia &
Upjohn) GB: Depo-Provera (Pharmacia
Farlutal (Pharmacia &
Upjohn) Provera (Pharmacia &
Upjohn) combination preparations I: Depo-Provera (Upjohn)
Farlutal (Farmitalia) Lutoral (Midy) Provera (Upjohn) J: Hysron (Kyowa) Provera (Upjohn) USA: Amen (Carnrick) Depo-Provera (Pharmacia
Premphase (Wyeth-Ayerst) Prempro (Wyeth-Ayerst) Provera (Pharmacia &
Upjohn)
Use: topical antihistaminic RN: 524-99-2 MF: C1,H2,N02 MW: 285.39 EINECS: 208-368-6
CN: 2-[(4-methoxyphenyl)phenylmethoxy]-N,N-dimethylethanamine
hydrochloride
RN: 6027-00-5 MF: C I ~ H 2 , N 0 2 HC1 MW: 321.85 EINECS: 227-888-4
LD,,,: 148 mglkg (M, i.p.)
chlor~de
Reference(s):
US 2 668 856 (UCB; 1954; appl 1948)
Formulation(s): ointment 20 mglg (2 %) (as hydrochloride)
Trade Name(s):
D: Corti-Postafen (UCB)- Postafen Salbe (UCB);
Use: glucocorticoid RN: 2668-66-8 MF: C,,H,,O, MW: 344.50 EINECS: 220-208-7
LD,,,: 338 mglkg (R, i.p.)
CN: (6a, 11 P)- 11 -hydroxy-6-methylpregn-4-ene-3,20-dione
Trang 81228 M Mefenamic acid
1 ethylene glycol, p-toluene-
CH, 2 lithium alanate
6a-methyl-l l -oxo-
progesterone
Medrysane
I
Reference(s):
US 2 864 837 (Upjohn; 1958; prior 1958)
US 2 968 655 (Upjohn; 1961; prior 1956)
starting material:
Spero, G.B et al.: J Am Chem Soc (JACSAT) 78, 6213 (1956)
US 2 968 655 (Upjohn; 1961; prior 1956)
Formulation(s): eye drops 10 mg; eye ointment 10 mg
Trade Name(s):
D: Ophtocortin (Winzer) generic
Spectramedryn (Pharm- I: Medramil (Farmigea)-
F: Medryson Faure (CIBA USA: HMS Liquifilm (Allergan);
Medrocort (Upjohn); wfm
Use: anti-inflammatory, antirheumatic, analgesic
RN: 61-68-7 MF: ClsHl,NO, MW: 241.29 EINECS: 200-513-1
LD,,,: 96 mglkg (M, i.v.); 525 mglkg (M, p.0.);
112 m g k g (R, i.v.); 740 m g k g (R, p.0.)
CN: 2-[(2,3-dimethylphenyl)amino]benzoic acid
copper(l1) acetate
benzoate
Reference($):
US 3 138 636 (Parke Davis; 23.6.1964; appl 23.6.1960)
DE 1 163 846 (Parke Davis; appl 22.6.1961; USA-prior 23.6.1960)
alternative syntheses:
DAS 1 186 073 (Parke Davis; appl 30.4.1963; CDN-prior 18.9.1962)
DAS 1 186 074 (Parke Davis; appl 30.4.1963; CDN-prior 18.9.1962)
DAS 1 186 870 (Parke Davis; appl 30.4.1963; CDN-prior 18.9.1962)
DAS 1 186 871 (Parke Davis; appl 30.4.1963; CDN-prior 18.9.1962)
Formulation(s): cps 250 mg; powder 500 mg, 1 g; suppos 125 mg, 500 mg; susp 50 mg
Trang 9Mefenorex M 1229
Trade Narne(s):
D: Parkemed (Parke Davis) J: Baphameritin M USA: Ponstan (Parke Davis);
F: Ponstyl (Parke Davis) Bonabol (Sawai) Ponstel (Parke Davis) GB: Meflam (Trinity) Pontal (Parke Davis-
Use: appetite depressant RN: 17243-57-1 MF: C,,H,,ClN MW: 21 1.74 EINECS: 241-279-0
CN: N-(3-chloropropy1)-a-methylbenzeneethanamine
hydrochloride
RN: 5586-87-8 MF: CI2H&lN HCl MW: 248.20 EINECS: 226-985-9
LD,,: 49 m g k g (M, i.v.); 230 mglkg (M, p.0.);
35 mglkg (R, i.v.); 410 mglkg (R, p.0.)
1 -proponol
Referencefs):
DE 1 210 873 (Hoffmann-La Roche; appl 18.3.1959)
Formulation(s): drg 40 mg (as hydrochloride)
Trade Narnefs):
D: Rondimen (ASTA Medica F: Incital (Pierre Fabre SantC)
AWD; as hydrochloride) USA: Anexate (Roche); wfm
Use: psychoanaleptic, CNS stimulant RN: 1227-61-8 MF: C,SH24N,0, MW: 280.37 EINECS: 214-963-1
LD,,: 168 mglkg (M, i.v.); 1500 ~ g l k g (M, p.0.)
CN: N-[2-(diethylamino)ethyl]-2-(4-methoxyphenoxy)acetamide
monohydrochloride
RN: 3413-64-7 MF: C,,H,N203 HCl MW: 316.83 EINECS: 222-304-4
Trang 101230 M Mefloquine
R+rence(s):
Thuillier, G ; Rumpf, P.: Bull Soc Chim Fr (BSCFAS) 1960, 1786
N,N-diethyl-
For~nulation(s): amp 150 mg; tabl 150 mg
Mefexomide
Trade Narne(s):
F: MCfCxadyne (Anphar); Timodyne (Anphar); wfm
ethylenediomine
Use: antimalarial RN: 53230-10-7 MF: C,,H,$,N,O MW: 378.32
CN: (R*,S*)-(+)-a-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol
monohydrochloride
RN: 51773-92-3 MF: C,,H,,F,N,O~HCl MW: 414.78 EINECS: 257-412-0 LD,,,: 880 mglkg (R, p.0.)
n-CIHo-Li
butyl-
2,&bis(trifIuoro- 2,8-bis(trifluoro- pyridine) methyl)-4-lithio- methyl)-4-quinoline-
quinoline (Ill) corboxylic acid (N)