Pharmaceutical Substances Syntheses, Patents, Applications - Part 131 potx

6 mg, 24 mg, 60 mg Trade Narnes: Depo-Medrate Pharmacia & Upjohn Medrate Pharmacia & Upjohn Metypred Orion Pharma Urbason Hoechst & Upjohn Mtdrol Pharmacia & Upjohn Soh-MMrol Pharmacia

Methylprednisolone M 1301

hydrocortisone

( q v.)

ethylene glycol

1 H,C-MgBr

2 2n H2S0,

bromide

enzymotic dehydrogenation

[Septomyxo offinis (ATCC 6737)]

6a-methyl- hydrocortisone (111)

Methylprednisolone

L

U i 2 897 218 (Upjohn; 28.7.1959; appl 23.1 1.1956; prior 23.4.1956)

Speero, G.G et al.: J Am Chem Soc (JACSAT) 78,6213 (1956); 79, 1515 (1957)

alternative syntheses:

US 3 053 832 (Schering Corp.; 11.9.1962; prior 29.4.1957)

Fried, J.H et al.: J Am Chem Soc (JACSAT) 81,1235 (1959)

US 4 041 055 (Upjohn; 9.8.1977; appl 17.1 1.1975)

Formulation(s): amp 20 mg, 30 mg, 40 mg, 60 mg, 80 mg; cream 0.1 %; ointment 0.1 %; tabl 6 mg, 24 mg,

60 mg

Trade Narne(s):

Depo-Medrate (Pharmacia

& Upjohn)

Medrate (Pharmacia &

Upjohn)

Metypred (Orion Pharma)

Urbason (Hoechst)

& Upjohn) Mtdrol (Pharmacia &

Upjohn) Soh-MMrol (Pharmacia &

Upjohn) GB: Medrone (Pharmacia &

Upjohn)

Asmacortone (Nuovo Cons Sanit Naz.)

Avancort (Farmades) Depo Medrol (Upjohn) Emmetip (Zanoni) Esametone (Lisapharma) Firmacort (Firma)

Medrol (Upjohn) Urbason Retard (Hoechst) Dura-Meth (Foy); wfm

LD,,,: 1860mglkg (M, p.0.);

2500 m g k g (R, p.0.)

CN: ( 1 7P)-I 7-hydroxy-17-methylandrost-4-en-3-one

ondrostenolone methyl-

magnesium iodide

CrO,

oxide

0

Reference(s):

US 2 143 453 (Ciba; 1939; CH-prior 1935)

US 2 374 369 (Ciba; 1945; CH-prior 1939)

US 2 374 370 (Ciba; 1945; CH-prior 1939)

Ruzicka, L.: Helv Chim Acta (HCACAV) 18, 1487 (1935)

starting material:

The Merck Index, 2846 (Rahway 1976)

alternative syrztheses:

US 2 384 335 (Alien Property Custodian; 1945; NL-prior 1936)

US 2 386 331 (Ciba; 1945; CH-prior 1938)

US 2 435 013 (Ciba; 1948; CH-prior 1941)

Bharucha, K.R.: Expcrientia (EXPEAM) 14, 5 (1958)

Formulution(s): cps 5 mg, 10 mg, 25 mg

Trade Nume(s):

Methylthioninium chloride M 1303 Hormovitastan (ASTA)-

comb.; wfrn

Klimax Taeschner

(Taeschner); wfrn

Lipogeron 300

(Nattermann)-comb.; wfrn

Medigeron (Medice)-

comb.; wfrn

Pasuma (Cascan)-comb.;

wfrn

Primodian (Schering)-

comb.; wfm

Primogeron (Schering)-

comb.; wfrn

Reginol (Merz)-comb.;

wfrn

Testifortan (Promonta)- comb.; wfrn

Tropodil (Tropon)-comb.;

Viracton plus (Promonta)- comb.; wfrn

Glosso-StCrandryl (Roussel); wfrn TriphosadCnine Methyltestostkrone

wfm

Veinotrope MCthyltestostCron (Lobica); wfrn Mepilin (Duncan, Flockhart)-comb.; wfrn Perandren (Ciba); wfrn Testovis (SIT) Enarmon Tab (Teikoku Zoki)

Primodian (Nihon Schering)-comb

Sanstron (Sankyo) Android (ICN) Estratest (Solvay) Testred (ICN) Virilon (Star)

Methylthioninium chloride

(Methylenblau; Methylene blue)

Use: diagnostic (for gastric function test), antidote (cyanide poisonings)

LD,,: 77 m g k g (M, i.v.); 3500 mg/kg (M, p.0.);

1250 m g k g (R, i.v.); 1180 mglkg (R, p.0.)

CN: 3,7-bis(dimethy1amino)phenothiazin-5-ium chloride

trihydrate

RN: 7220-79-3 MF: C,,H,p,CIN,S 3H20 MW: 373.91

4-ornino-N,N-di-

rnethyloniline

HCI, 85 O C

E3c-bi - iH 1 , -+

CH3

Reference(s):

Ullmanns Encykl Tech Chem., 4 Aufl., Vol 8, 237

H C \ry a;&CH3 I

CH3 CI- CH3

(1) N.N-dimethyl-

Formulation(s): amp 10 mg/ml, 50 mg/ml, 100 mg/ml; tabl 65 mg

Methylthioniniurn chloride

Trade Name(s):

Calmante(Chauvin)-comb

Mictasol Bleu (Martin- Johnson & Johnson-MSD)- comb

1304 M Methylthiouracil

Use: thyroid therapeutic

LD,,: 1500 mglkg (R, p.0.)

CN: 2,3-dihydro-6-methyl-2-thioxo-4(lH)-pyrimidinone

ocetoocetote

1 Methylthiourocil

Reference (s):

List, R.: Justus Liebigs Ann Chem (JLACBF) 236, 1 (1886)

Anderson, G.W et al.: J Am Chem Soc (JACSAT) 67,2197 (1945)

Formulation(s): tabl 0.025 g, 0.1 g

Trade Name(s):

LD,,,: 275 mglkg (M, i.v.); 890 mglkg (M, p.0.);

380 mglkg (R, i.v.); 860 mglkg (R, p.0.);

300 mglkg (dog, p.0.)

CN: 3,3-diethyl-5-methyl-2,4-piperidinedione

ethyl 2.2-di- methyl

ethylaceto- formote (I)

ocetote

ethyl 2,2-di- ethyl-4-(hydroxy- methylene)- ocetoocetote

Methysergide M 1305

ethyl 5-omina- 3,3-diethyl- 3,3-diethyl-

1,2.3.4-tetm- hydropyridine- 2.4-dione

piperidine- 2.4-dione (In)

0

Methypryton

Reference(s):

US 2 680 116 (Hoffmann-La Roche; 1954; CH-prior 1951)

DRP 634 284 (Hoffmann-La Roche; 1935)

US 2 151 047 (Hoffmann-La Roche; prior 1938)

Formulation(s): tabl 200 mg

Trade Narne(s):

-

Use: serotonin antagonist, antimigraine agent

LD,,,: 185 mglkg (M, i.v.); 440 mgkg (M, p.0.)

CN: [8~(S)]-9,10-didehydro-N-[l-(hydroxymethyl)propyl]-l,6-dimethylergoline-8-carboxamide

hydrogen maleate (1:l) -

1 KNH2, liq NH,

H3c'3s-ll"&NH -

N =

I H

(4 v.1

Reference(s):

US 3 113 133 (Sandoz; 3.12.1963; CH-prior 18.5.1956)

US 3 218 324 (Sandoz; 16.1 1.1965; ~ H - ~ r i o r 18.5.1956,20.3.1957, 16.4.1957,7.3.1958, 11.3.1960)

DE 1 076 137 (Sandoz: appl 7.5.1957; CH-prior 18.5.1956,20.3.1957)

Formulation(s): s r tabl 3 mg; tabl 1 mg, 2 mg (as hydrogen maleate)

1306 M Metiazinic acid

Trude Name($):

Metiazinic acid

(Acide metiazinique)

LD,,,: 350 mglkg (M, i.v.); 800 mglkg (M, p.0.);

495 mglkg (R, p.0.);

2 glkg (dog, p.0.)

CN: 10-methyl-1OH-phenothiazine-2-acetic acid

2-acetyl-10-methyl-

phenothiazine

n

f " 0

N> KOH_

rnorpholine

I Metiorinic acid FH3

Reference(s):

GR 1 048 680 (Rhhe-Poulenc; appl 27.10.1965; F-prior 29.10.1 964, 30.10.1964, 28.12.1964,24.9.1965) ester derivatives:

US 3 424 748 (Rhhe-Poulenc; 28.1.1969; F-prior 22.10.1965,25.8.1966)

Forrnulation(s): cps 125 mg, 250 mg

Trade Narntfs):

Meticillin

(Methicillin)

Use: antibiotic

LD,,,: 3720 mglkg (M, i.v.)

CN: [2S-(2n,5a,6~)]-6-[(2,6-dimethoxybenzoyl)amino]-3,3-dimethy-7-oxo-4-thia-1-

azabicyclo[3.2.0]heptane-2-carboxylic acid

RN: 7246- 14-2 MF: C17H,,N2Na06S H 2 0 MW: 420.42

S0CI2

*

chloride

2.6-dirnethoxy-

benzoic acid

N(C2H5)3 ,

6-orninopeni- cillanic acid

Meticillin I

Meticrane M 1307

Reference(s):

US 2 951 839 (Beecham; 6.9.1960; GB-prior 15.7.1959)

Trade Name(s):

Use: diuretic

LD,,: 325 mg/kg (M, i.v.); >20 glkg (M, p.0.);

445 mglkg (R, i.v.); > I 6 glkg (R, p.0.)

CN: 3,4-dihydro-6-methyl-2H-1-benzothiopyran-7-sulfonamidc 1,l-dioxide

(C,H9),Nt OH-

HOOC

H3C

0

6-methyl- thiochroman

6-methyl- thiochromon

CIS03H

I1 -+

chlorosul-

fonic acid

Meticrone

L

Reference(s):

FR 1 365 504 (S.1.F.A; appl 24.5.1963)

Trade Namefs):

1308 M Metildigoxin

Metildigoxin

(Medigoxin; P-Methyldigoxin)

Use: cardiac glycoside

CN: (3~,5~,12~)-3-[(0-2,6-dideoxy-4-O-methyl-~-~-ribo-hexopyranosyl-(1~4)-0-2,6-dideoxy-~-~-ribo-

hexopyranosyl-(I +4)-2,6-dideoxy-P-D-ribo-hexopyranosyl)oxy]- 12,14-dihydroxycard-20(22)-enolid~

H ~ C / O \ //' Ba(OH),, AI2O3 DMF

+ s b

-OQ \O CH3

DE 1 643 665 (Boehringer Mannh.; appl 20.9.1967)

DOS 1 961 034 (Boehringer Mannh.; appl 5.12.1969)

US 3 538 078 (Boehringer Mannh.; 3.1 1.1970; D-prior 7.5.1968)

methylation with methyl mesylate:

DOS 2 734 401 (LEK; appl 29.7.1977; YU-prior 20.8.1976)

US 4 145 528 (LEK; 20.3.1979; YU-prior 20.8.1976)

Formulation(s): amp 0.2 mg; tabl 0.1 mg, 0.15 mg

Metipranolol M 1309

Trade Nante(s):

Use: beta blocking agent

CN: 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxyJ-2,3,6-trimethylphenol 1-acetate

4-acetoxy-2.3.5- epichloro-

trimethylphenol (I) hydrin

Metipranolal

Rejerence(s):

DOS 1 668 964 (Spofa; appl 1968; P-prior 1967)

CS 1 150 020 (L Blaha; appl 26.11.1970)

synthesis oj4-acetoxy-2,3,5-trimethylphenol:

DOS 2 314 600 (Teijin; appl 23.3.1973; J-prior 25.3.1972)

Forrnulation(s): drg 20 mg; eye drops 1 mglml, 3 mglml, 6 mglml (0.1 %, 0.3 %, 0.6 %); tabl 20 mg

Trade Name(s):

Metirosine

(Metyrosine; a-Methyltyrosine)

Use: antihypertensive (at phcochromocytoma)

CN: a-methyl-L-tyrosine

phenyl- (1)

acetone

a-methyl-DL-phenyl- alanine hydrochloride (11)

1 NaOH

11 . ,

2 dichloro-

chloride

N-dichloroacetyl- O 2 N a-methyl-DL-

phenylolanine

1 H,SO,, NaNO, racemate

resolution

a-methyl-Dl- tyrasine (N)

HO

Metirosine

(4-methaxypheny1)-

acetone

racernate resolution