2.5 mg, 5 mg, 15 mg as hydrochloride Trade Names: D: Tremarit Novartis Pharma Tremonil Sandoz; as F: Spasmenzyme Salvoxyl- hydrochloride hydrate; GB: Tremonil Wander; wfm I: Tremaril S
Trang 1Metixene M 131 1
2-methyl-L-
serine
1 PBr5
2 NoOH
-+
(from ethoxy- bromobenzene L-2-amino-2- sodium) methyl-3-bromo-
propionic acid
Reference(s):
a Stein, G.A eta].: J Am Chem Soc (JACSAT) 77,700 (1955)
US 2 868 818 (Merck & Co.; 13.1.1959; appl 15.12.1953)
b Potts, K.T.: J Chem Soc (JCSOA9) 1955, 1632
c DOS 1 543 763 (Merck & Co.; appl 25.5.1966; USA-prior 3.6.1965)
GB 1 105 103 (Merck & Co.; appl 1.6.1966; USA-prior 3.6.1965)
alternative syntheses:
enantioselective synthesis.from L-tyrosine via the reaction product from N,O-bis(carbobenzoxy)-L-tyrosine with benzaldehyde and its methylation:
US 4 508 921 (Merck & Co.; 2.4.1985; appl 28.6.1984)
DL-rnetirosine by reaction ?f ~ , ~ - d i m e t h ~ l - 4 - h ~ d r o x ~ b e n ~ ~ l a r n i n e with ethyl 2-nitropropionate:
Saari, W.S.: J Org Chern (JOCEAH) 32,4074 (1967)
combination with carbidopa:
US 4 389 415 (Merck & Co.; 21.6.1983; USA-prior 24.1.1978,5.10.1979,20.7.1981)
EP 3 353 (Merck & Co.; appl 24.1.1979; USA-prior 24.1.1978)
Formulation(s): cps 250 mg
Trade Name(s):
GB: Dernser (Merck Sharp & USA: Dernser (Merck Sharp &
Metixene
(Methixene)
ATC: N04AA03 Use: antiparkinsonian, antispasmodic RN: 4969-02-2 MF: C2,H2,NS MW: 309.48 EINECS: 225-610-6
LD,,,: 18rng/kg(M,i.v.);430rnglkg(M,p.o.)
CN: l-methyl-3-(9H-thioxanthen-9-ylrnethyl)piperidine
hydrochloride
RN: 1553-34-0 MF: C2,H2,NS HCI MW: 345.94 EINECS: 216-300-1
LD,,: 18 rngkg (M, i.v.); 346 rnglkg (M, p.0.);
24 rnglkg (R, i.v.); 1460 rnglkg (R, p.0.)
hydrochloride monohydrate
RN: 7081-40-5 MF: C2,H2,NS HCl H 2 0 MW: 363.95
Trang 213 12 M Metoclopramide
CI
thioxonthene 3-chloromethyl-
1 -methylpiperidine
y 3
N
333
Metixene
Reference(s):
Formulation(s): tabl 2.5 mg, 5 mg, 15 mg (as hydrochloride)
Trade Name(s):
D: Tremarit (Novartis Pharma) Tremonil (Sandoz; as
F: Spasmenzyme (Salvoxyl- hydrochloride hydrate);
GB: Tremonil (Wander); wfm I: Tremaril (Sandoz)
J: Atosil (Teisan) Cholinfall (Tokyo Tanabe)
Dalpan (Grelan) Methyloxan (Nippon Shoji- Kodama)
Thioperkin (Hokuriku) USA: Trest (Dorsey); wfm
Use: anti-emetic, gastric therapeutic RN: 364-62-5 MF: CJ4Hz2CIN302 MW: 299.80 EINECS: 206-662-9
CN: 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide
monohy drochIoride
RN: 7232-21-5 MF: C,4H22C1N,0, HCI MW: 336.26 EINECS: 230-634-5
monohydrochloride monohydrate
RN: 54143-57-6 MF: CJ4H2,ClN3O2 HC1 H,O MW: 354.28
0 0
+ ,.-OH d 6"
0
, + H,c/O, /P C H ~ C I ~ CH,COOH
OP 'O CH3
HN CH,
0
dirnethyl methyl 4- methyl 4-acei-
sulfote ocetornido- omido-5-chloro-
2-methoxy- Z-methoxy-
Trang 3Metoclopramide M 13 13
isopropyiote
N.N-diethyi-
ethylenediornine
I Metocloprornide I
Reference(s):
DE 1 233 877 (Soc &Etudes Scientifiques et Industrielles de 1'Ile-de-France; appl 14.7.1962; F-prior
25.7.1961)
FR 1 313 758 (Soc &Etudes Scientifiques et Industrielles de 1'Ile-de-France; appl 25.7.1961)
US 3 177 252 (Soc dlEtudes Scientifiques et Industrielles de 1'Ile-de-France; 6.4.1965; F-prior 25.7.1961)
US 3 219 528 (Soc d'Etudes Scientifiques et Industrielles de 1'Ile-de-France; 23.11.1965; F-prior 25.7.1961, 5.8.1961,4.11.1961)
US 3 357 978 (Soc &Etudes Scientifiques et Industrielles de l'lle-de-France; 12.12.1967; F-prior 5.3.1963)
alternative syntheses:
DOS 1 932 512 (Huhtamaki; appl 26.6.1969; SF-prior 28.6.1968)
DAS 1 960 130 (Yamanouchi; appl 29.11.1969; J-prior 2.12.1968,9.12.1968,4.4.1969)
DAS 1 966 453 (Yamanouchi; appl 29.11.1969; J-prior 9.12.1968)
DAS 2 102 848 (Delmar; appl 21.1.197 1 ; USA-prior 21.1.1970)
DAS 2 119 724 (Teikoku Hormone Mfg.; appl 22.4.1971; ~ - ~ r i o i 24.4.1970)
DAS 2 162 917 (Soc &Etudes Scientifiques et Industrielles de 1 'Ile-de-France; appl 17.12.1971 ; J-prior 21.12.1970)
DAS 2 166 117 (Teikoku Hormone Mfg.; appl 22.4.197 1 ; J-prior 24.4.1970)
DAS 2 166 1 18 (Teikoku Hormone Mfg.; appl 22.4.1971 ; J-prior 24.4.1970)
DAS 2 342 934 (Delmar; appl 24.8.1973; GB-prior 25.8.1972, 13.12.1972, 16.4.1973)
DAS 2 365 988 (Heumann & Co.; appl 12.7.1973)
starting material:
DAS 2 335 439 (Heumann & Co.; appl 12.7.1973)
Formulation(s): amp 10 mg/2 ml, 50 mg1lO ml; cps 10 mg, 30 mg; drops 4 mg, 5 mg; liquid 4 mg;
s r cps 30 mg; sol 1 mglml, 15 mg115 ml, 5 mg/5 ml; suppos 10 mg, 20 mg;
tabl 10 mg (as hydrochloride hydrate)
Trade Name(s):
D: Cerucal (ASTA Medica
AW D)
Gastronerton (Dolorgiet)
Gastrosil (Heumann)
Gastro-Timelets (Temmler)
Paspertase (Solvay
Arzneimitte1)-comb
Paspertin (Solvay
Arzneimittel; 1965)
generics
F: Anausin Metoclopramide
(ASTA Medica)
CCphalgan (UPSA)-comb
Metoclopramide GNR
(GNR-pharma)
Primptran (Thera France;
1964) GB: Gastrobid Continus (Napp) Maxolon (Monmouth;
1967) Paramax (Lorex)-comb
I: Citroplus (Irbi) Clopan (Firma) Cronauzan (ASTA Medica) Ede (Teofarma)-comb
Eugastran (Piam)-comb
Geffer (Boehringer Mannh.)
Plasil (Lepetit; 1967)
Plasil enzimatico (Lepetit)- comb
Randum (Roussel) Viscal (Zoja) J: Donopon-GP (Sana) Peraprin (Taiyo Yakuko Takay ama)
Primperan (Fujisawa; 1970)
Putoprin (Mohan) Terperan (Teikoku Zoki) USA: Reglan (Robins; 1979)
Trang 41314 M Metolazone
Use: diuretic, antihypertensive RN: 17560-51-9 MF: C16H,6ClN103S MW: 365.84 EINECS: 241-539-3
LDso: >5 @kg (M, p.0.);
>5 @kg (R, p.o.1
CN: 7-chloro-l,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamide
5-chloro-2- ethyl chloro-
methyloniline forrnote
5-chloro-N-ethoxy- carbonyl-2-methyl- aniline (I)
2 NH3
I
acid 4-sulfomoyl-5-chloro-
N-ethoxycorbonyl-2- rnethyloniline
6-sulfarnoyl-7- chloro-isotoic anhydride
2-amino-5-sulf- acetaldehyde
ornoyl-4-chloro- dimethyl
N-(0-tolyl)- ocetal
benzarnide (111)
Metolozone
DAS 1 620 740 (Pennwalt; appl 24.12.1966; USA-prior 3.1.1966)
DOS 2 13 1 622 (Pennwalt; appl 25.6.1971; USA-prior 29.6.1970)
US 3 360 518 (Wallace & Tiernan; 26.12.1967; prior 3.1.1966)
US 3 557 11 1 (Wallace & Tiernan; 19.1.1971; prior 29.3.1968)
US 3 761 480 (Pennwalt; 25.9.1973; prlor 10.7.1968, 7.1 1.1969, 15.3.1972)
DOS 2 035 657 (Sumitomo; appl 17.7.1970; J-prior 22.7.1969, 25.2.1970, 27.3.1970)
Formulationfs): tabl 2.5 mg, 5 mg, 10 mg
Trade Namels):
D: Zaroxolyn (Hcumann) I: Zaroxolyn (SmithKline J: Normelan (Sandoz-
Trang 5Metopimazine M 13 15
USA: Mykrox (Medeva)
Zaroxoly n (Medeva)
Use: anti-emetic RN: 14008-44-7 MF: C2,H,N303S2 MW: 445.61 EINECS: 237-8 18-4
CN: 1-[3-[2-(methylsulfonyl)-10H-phenothiazin-l0-yl]propyl~-4-piperidinecarboxamide
2-methylsulfonyl-
phenothiozine
chloropropone 10-(3-~hloropropyl)-
2-methylsulfonyl- phenothiozine (I)
piperidine-4-
corboxomide
Metopimazine
DE 1 092 476 (RhGne-Poulenc; appl 14.4.1959; F-prior 24.4.1958)
Formulation(s): amp 10 mgll ml; cps 15 mg; drg 2.5 mg; sol 4 mg/ml, 5 mgI5 ml; suppos 5 mg;
tabl 2.5 mg
Trade Name(&
F: Vogalhe (Schwarz)
Use: beta blocking agent RN: 5 1384-5 1- 1 MF: C,,H2,N03 MW: 267.37 EINECS: 253-483-7
LD,,,: 62 m g k g (M, i.v.); 1050 m g k g (M, p.0.);
71.9 mglkg (R, i.v.); 3470 mg/kg (R, p.0.);
6 0 m g k g (dog, i.v.)
CN: 1-[4-(2-methoxyethyl)phenoxy]-3-[(l-methylethyl)amino]-2-propanol
tartrate (2:l)
RN: 56392-17-7 MF: C,,H2,NOv 1/2C4H,0, MW: 684.82 EINECS: 260-148-9
Trang 613 16 M Metrizamide
4-(2-melhoxy- epichloro
ethy1)phenol hydrin
0
1,2-epoxy-3-[4-(2- rnethoxyethy1)phen- oxylpropone (I)
Reference(s):
DAS 2 106 209 (AB Hassle; appl 10.2.1971; S-prior 18.2.1970)
US 3 873 600 (AB Hassle; 25.3.1975; S-prior 18.2.1970)
US 3 998 790 (AB Hassle; 21.12.1976; appl 15.1.1974; prior 19.3.1973)
isopropyl-
(S)-enantiomer:
US 5 034 535 (Astra; 23.7.1991 : S-prior 22.4.1988)
US 5 362 757 (Sepracor; 8.1 1.1994; appl 16.1 1.1992; prior 18.3.1991)
Metoprolol
Formulation(s): amp 5 mgI5 ml; s r f c tabl 200 mg; s r tabl 200 mg; tabl 50 mg, 100 mg (as tartrate)
Trade Natne(s):
D: Azumetop (Azupharma)
Beloc (Astra; 1976)
Lopresor (Novartis Pharma;
1976)
Prelis (Novartis Pharma;
1982)
Sigaprolol (Kytta-
Siegfried)
Treloc (Astra)-comb
generics
F: Logimax (Astra)-comb
Logroton (Novartis Pharma SA)-comb
Lopressor (Novartis Pharma SA; 1980) Seloken (Astra; 1980) GB: Betaloc (Astra: 1975) Co-betaloc (Astra; as tartrate)-comb
Lopresor (Novartis; 1975)
I: Igroton Lopresor (Novartis)-comb
Lopresor (Novartis; 1978) Seloken (Astra; 1978) Selozide (Astra)-comb J: Lopresor (Ciba-Geigy) Seloken (Fujisawa; 1983) USA: Lopressor (Novartis; 1978)
Use: X-ray contrast medium RN: 55 134- 1 1-7 MF: C,,H2,13N30, MW: 789.10
CN: 2-[[3-(acetylamino)-5-(acelylmethylamino)-2,4,6-triiodobenzoyl]amino]-2-deoxy-~-glucopyranose
rnetrizoic acid rnetrizoyl chloride (I)
Trang 7Metrizoic acid M 13 17
I Metrizamide
US 3 701 77 1 (Nyegaard; 31.10.1972: GB-prior 27.6.1969,9.2.1970)
DOS 2 03 1 724 (Nyegaard; appl 26.6.1970; GB-prior 27.6.1969,9.2.I97O)
Formularion(s): amp 3.75 g, 6.75 g (12.5 %, 13.5 %, 18.75 %)
Trade Name(s):
D: Amipaque (Schering; F: Amipaque (Sterling USA: Amipaque (Wjnthrop-
Arnipaque (Schering); wfrn J: Amipaque (Schering; 1981)
Use: X-ray contrast medium RN: 1949-45-7 MF: Cl2HI1I3N2O4 MW: 627.94 EINECS: 217-761-1
LD,,: 10 g/kg (M, i.v.); >46.8 mg/kg (M, p.0.);
14.3 glkg (R, i.v.); 38.1 mglkg (R, p.0.)
CN: 3-(acetylamino)-5-(acetylmethylamino)-2,4,6-triiodobenzoic acid
monosodium salt
RN: 7225-61-8 MF: C1,Hlo13N2Na04 MW: 649.92 EINECS: 230-624-0
arnidotrizoic acid dirnethyl
(4 v.1 sulfate
Metrizoic acid
Reference(s):
GB 973 881 (Nyegaard; appl 5.12.1960; N-prior 8.12.1959)
GB 987 796 (Nyegaard; appl 26.2.1962; N-prior 28.2.1961)
US 3 178 473 (Nyegaard; 13.4.1965; appl 2.3.1962)
Formulafion(s): amp 100 mg, 150 mg, 260 mg, 350 mg, 370 mg, 440 mg (as Ca-, Mg-, Na- and meglumine
salt)
Trang 813 18 M Metronidazole
Trade Name(s):
D: Ronpacon (Cilag-Chemie); F: Isopaque (Winthrop); wfm USA: Isopaque (Winthrop); wfrn
JOIXDOI; POlABOl Use: chemotherapeutic (trichomonas) RN:
LD,,,:
CN:
443-48-1 MF: C6HyN303 MW: 171.16 EINECS: 207-136-1
3800 m g k g (M, p.0.);
3 glkg (R, p.o.1
2-methyl-5-nitro- 1 H-imidazole-1-ethanol
2-methyl- 2-methyl-5-
irnidozole nitroirnidozole (I)
I Metronidazole
ethylene
oxide
Formularion(s): cps 250 mg, 375 mg; f c tabl 250 mg, 400 mg; suppos 100 mg (vaginal); tabl 250 mg,
400 mg; vaginal tabl 100 mg; vial 5 g11000 ml
Trade Name(s):
Canesten-Clont-
Kombipack (Bayer)
Clont (Bayer Vital)
Flagyl (Rhbne-Poulenc
Rorer)
Fossyol (Merckle)
generics
Rodogyl (Specia)-comb
Rozagel (Biorga)
Tergynan (Bouchara)-
comb
Anabact (ASTA Medica AWD)
Elyzol (Dumex) Flagyl (Rhbne-Poulenc Rorer)
Metrogel (Novartis) Rozex (S tafford-Miller) Zidoval(3M)
Deflamon (SPA) Flagyl (Farmitalia) Metronid (Formulario Naz.)
Metronidazolo Same (Savoma)
Vagilen (Farmigea)
.I: Asuzol (Fuji) Flagyl (Shionogi) Nida (Toyo Pharmar) Takimetol (Nakataki) Trichocide (Green Cross) Wagitran (Nakataki) USA: Flagyl (SCS) Flagyl (SCS; as hydrochloride) Flagyl (Searle) Helidac (Procter &
Gamble)
Use: adrenocorticostatic RN: 54-36-4 MF: CI4HI4N,O MW: 226.28 EINECS: 200-206-2
CN: 2-methyl-l,2-di-3-pyridinyl-1-propanone
Trang 9Mexazolam M 1319
cathodic reduction
3-ocetyl-
pyridine
[Hg-cathode - 2 4 V,
-A
- HU
Reference(s):
Chart, J.J et a].: Experientia (EXPEAM) 14, 151 (1958)
Allen, M.J.: J Org Chern (JOCEAH) 15,435 (1950) - (pinacol-synthesis)
Bencze, W.L.; Allen, M.J.: J Am Chern Soc (JACSAT) 81,4015 (1959)
0
as intermediate mentioned in:
US 2 923 710 (Ciba; 2.2.1960, prior 14.7.1958)
US 2 966 493 (Ciba; 27.12.1960; appl 10.3.1958)
Forntulation(s): cps 250 mg
Trade Name(s):
D: Metopiron (Ciba); wfrn GB: Metopirone (Novartis) J: Metopiron (Ciba-Geigy-
F: Metopirone (Novartis I: Metopiron (Ciba); wfm Takeda)
Use: tranquilizer, anxiolytic RN: 31868-18-5 MF: C,8H,6C12N202 MW: 363.24
LD,,: 4571 rngkg (M, p.0.);
4500 rngkg (R, p.0.)
CN: 10-chloro-l l b-(0-chloropheny1)-2,3,7,ll b-tetrahydro-3-rnethyloxazolo[3,2-6][1,4]benzodiazepin-6(5H)-
one
O L ~ r
2 - a m i n o - 2 ' 5 bromoacetyl (I)
dichlorabenzo- chloride
phenone
2-amino-1 -
proponol
I Mexozalam
Heference(s):
Migadera, T et al.: J Med Chem (JMCMAR) 14,520 (1971)
JP 4 941 439 (Sankyo; appl 21.12.1970)
Trang 101320 M Mexenone
Formulation(s): 0.5 mg, 1 mg
Trade Name(s):
J : Melex (Sankyo)
Use: ultraviolet screen RN: 1641-17-4 MF: C,SH1403 MW: 242.27 EINECS: 21 6-691-9
CN: (2-hydroxy-4-methoxyphenyl)(4-methylphenyl)methanone
/C"3
AICI, DMF
H3C
4-rnethylbenzoyl 1,3-dirneth-
chloride oxybenzene
Reference(s):
US 2 773 903 (American Cyanamid; 1956; prior 1955)
Formulation(s): cream 4 %
Trade Name(s):
GB: Uvistat (WB
Pharmaceuticals); wfm
Mexenone
Use: anticonvulsant, antiarrhythmic RN: 3 1828-71-4 MF: C, ,Hl,NO MW: 179.26 EINECS: 250-825-7
LD,,,: 23 mglkg (M, i.v.); 320 mglkg (M, p.0.);
41 mglkg (R, i.v.)
CN: 1-(2,6-dimethy1phenoxy)-2-propanamine
hydrochloride
RN: 5370-01-4 MF: C,,H,,NO HCl MW: 215.72 EINECS: 226-362-1
LD,,: 21 mglkg(M,i.v.); 272mglkg(M,p.o.);
27 mglkg (R, i.v.); 330 mglkg (R, p.0.);
19 mglkg (dog, i.v.); 356 mglkg (dog, p.0.)
sodium 2.6-di- chloroocetone 1 -(2.6-dimethyl-
methylphenolate phenoxy)-2-propanone (I)
H2N-OH Hz Roney-Ni
I
hydroxyl-
amine