Pharmaceutical Substances Syntheses, Patents, Applications - Part 67 pdf

10 mg; syrup 2.5 mglml Tmde Names: I: Gentus Gentili Tusben Benedetti J: Astomin Yamanouchi... 50 mg Trade' Names: D: Arlevert Hennig-comb.. Reisetabletten ratiopharm ratiopharm Rubie

Dimemorfan D 661

Dimozole

thiozole

Reference(s):

US 2 578 757 (Hoffmann-La Roche; 1951; prior 1949)

Formulation(s): topical 5 %

Tmde Name(s):

GB: Aster01 (Roche); wfm J: Aster01 "Roche" (Roche-

I: Aster01 (Roche); wfm S hionogi)

Use: antitussive, sedative

RN: 36309-01-0 MF: C,,H,,N MW: 255.41' EINECS: 252-963-3

CN: (9a,13a,14a)-3,17-dimethylmorphinan

phosphate

RN: 40678-33-9 MF: C,,H,,N xH,P04 MW: unspecified

ClMg

boronate

2-mothyl-5,6,7,8- 4-methylbenzyl- 2-methyl-1 -(4-methyl-

tctrahydroisoquino- mognesium chloride benzyl)-1.2.5.6.7,8-

(+)-2-methyl-1-(4- methylbenzy1)- 1.2.3,4,5,6.7,8-octo- hydroisoquinoline

I Dimemorfan

Formulation(s): drops 5 mglml; cps 10 mg; syrup 2.5 mglml

Tmde Name(s):

I: Gentus (Gentili) Tusben (Benedetti) J: Astomin (Yamanouchi)

662 D Dimenhydrinate

Use: anti-emetic RN: 523-87-5 MF: CL7H2,N0 C,H,CIN,O, MW: 469.97 EINECS: 208-350-8

LD,,,: 203 mglkg (M, p.0.);

200 mg/kg (R, i.v.); 1320 mg/kg (R, p.0.)

CN: 2-(dipheny1methoxy)-N,N-dimethylethanamine, compd with 8-chlorotheophylline

diphenhydromine 8-chlorotheophylline

(4 v.)

Reference(s):

US 2 499 058 (Searle; 1950; prior 1949)

US 2 534 813 (Searle; 1950; appl 1950)

Forrnulation(s): drg 10 mg, 20 mg, 50 mg, 150 mg, 200 mg (s r cps.); sol for inj 62 mgllO ml (i.v.),

100 mg12 ml (i.m.); suppos.40 mg, 70 mg, 80 mg, 150 mg; tabl 50 mg

Trade' Name(s):

D: Arlevert (Hennig)-comb

Dimen (Heumann)

Mandros (Dolorgiet)

Migraeflux (Henning)-

comb

Reisetabletten ratiopharm

(ratiopharm)

RubieMen (RubiePharm)

Superprepl-forte (Hermes)

Vertigo-Vomex

(Yamanouchi)

Vomacur (Hexal) Vomex (Yamanouchi) F: Dramamine (Monsanto) Mercalm (Lab Phygikne) comb

Nausicalm (Lab Brother

S A)

GB: Dramamine (Searle) I: Lomarin (Geymonat) Motozina (Biomedica Foscama)

Travelgum (ASTA Medica) Valontan (Recordati) Xamamina (SmithKline Beecham)

generics J: Dramamine (Dain~ppon) Vomiles (Fujisawa) USA: Dimenhydrinate (Wyeth- Ayerst)

(Di thioglycerin) Usc: antidote (heavy metal poisonings)

RN: 59-52-9 MF: C,H,OS, MW: 124.23 EINECS: 200-433-7

LD,,: 56 mgkg (M, i.v.); 217 mglkg (M, p.0.)

CN: 2,3-dimercapto-1-propanol

1 -propano1

US 2 402 665 (Du Pont; 1946; appl 1942)

US 2 432 797 (Minister of Supply of the United Kingdom; 1947; GB-prior 1942)

US 2 436 137 (Du Pont; 1948; appl 1944)

Stocken, L.A.; Thompson, R.H.S.: Biochem J (BIJOAK) 40,529,535,548 (1946)

Dimestrol D 663

~ynthesis via 2,3-dichloropropanol:

Ing, H.R.: J Chem Soc (JCSOA9) 1948, 1393

Fomulation(s): amp 100 mg

M e Name(s):

D: Sulfactin Homburg I: B.A.L Boots (Boots Italia) USA: BAL (Hynson Westcott &

F: B.A.L (L'Arguenon)

Dimestrol

(Dimethoxydiethylstilbene)

ATC: GO3 Use: estrogen

RN: 130-79-0 MF: C2,H,,O2 MW: 296.41 EINECS: 204-994-9

CN: (E)-1,l'-(l,2-dlethyl- l,2-ethenediyl)bis[4-methoxybenzene]

diethylstilbestrol methyl

chloride

4'-rnethoxy-

pmpiophenone (1)

I +

H3C

phosphorus

664 D Dimetacrine

Reference(s):

a Reid, E.E.; Wilson, E.: J Am Chem Soc (JACSAT) 64, 1625 (1942)

b Sisido, K.; Nozaki, H.: J Am Chem Soc (JACSAT) 70,776 (1948)

c GB 584 253 (B.T Bush; appl 1943; USA-prior 1941)

GB 584 705 (B.T Bush; appl 1943; USA-prior 1941)

DE 897 559 (Bayer; appl 1938)

alternative synthesis:

DE 824 043 (Boehringer Ing.; appl 1949)

review:

Solmssen, U.V.: Chem Rev (Washington, D C.) (CHREAY) 36,481 (1945)

Trade Name(s):

D: Depot-Oestromon (Merck);

wfm

Use: antidepressant, thymoleptic RN: 4757-55-5 MF: C20H2,N2 MW: 294.44

LD,,,: ,39600 ~ g / k g (M, i.v.); 1293 mglkg (M, p.0.);

1850 m g k g (R, p.0.)

CN: N,N,9,9-tetramethyl- 1 O(9H)-acridinepropanamine

tartrate (1:l)

RN: 3759-07-7 MF: C20H2,N2.C,H60, MW: 444.53 EINECS: 223-166-8

LD,,,: 40.9 mglkg (M, i.v.); 755 m g k g (M, p.0.);

38 m g k g (R, i.v.); 1671 mglkg (R, p.0.)

diphenylomine

9-methyl- acridine

9.9-dimethyl-

9 , l O-dihydro- ocridine (I)

2 C,-N/CH3

I

'3'3

2 3-dimethylomino- I

Rej'erencels):

DE 1 224 315 (Kefalas; appl 7.9.1961; GB-prior 16.9.1960)

GB 933 875 (Kefalas SIA; appl 16.9.1960; valid from 13.9.1961)

US 3 284 454 (Siegfried; 8.1 1.1966; CH-prior 18.12.1961, 3.8.1962)

Molnar, I.; Wagner-Jauregg, T.: Helv Chim Acta (HCACAV) 48, 1782 (1965)

Fortnulation(s): drg 100 mg (as hydrochloride)

Dimethadione D 665

[ D: Istonil (Siegfried); wfm J: Istonyl (Nippon

I

L

!

1 RN: 695-53-4 MF: C,H,NO, MW: 129.12 EINECS: 211-781-4

$ LD,: 850 m a g (M, i.p.)

' CN: 5,5-dimethyl-2,4-oxazolidinedione

gaseous HCI H3C O H

+ HO/'CH, - H , C ~ O " C H ~

ethyl a-hydroxy- isobutyrate

ATC: A09A

Use: antacid, antiflatulant

dimethyldichlorosilane, e g.:

007 063 (General Electric; appl 1956; USA-prior '1955)

2 148 669 (Wacker-Chemie; appl 29.9.1971)

DOS 2 521 742 (Wacker-Chemie; appl 15.5.1975)

666 D Dimethisterone

Forrnulation(s): cream 4 02.; lotion 4 oz

Trade Name(s):

D: Absorber HFV (Arteva

Pharma)

Aegrosan (Opfermann)

Busala (Pharma Selz)

Ceolat (Solvay

Arzneimittel)

Dimeticon-ratiopharm

(ratiopharm)

Espumisan (Berlin-

C hemie)

ILIO-Funktion

Kautabletlen (Robugen)

Meteosan (Novartis)

sab simplex (Parke Davis)

Symadal (Chauvin

ankerpharm)

F: Castrobul (Lab Cuerbet)-

comb

CB:

I:

J:

Gel de polysilane (Labs

UPSA) Rennie Deflantine (Labs

Roche Nicholas SA)-comb

numerous combination preparations

Infacol (Pharmax) numerous combination preparations

Mylicon (Parke Davis) Olio Silic (Tariff

Integrative) Polisilon (Midy)-comb

Silisan (Lipha)-comb

Aeropax (Green Cross) Ganatone (Hokuriku) Gasace (Kanto) Gascon (Kissei)

USA:

Gasless (Hishiyama) Gaspanon (Kotani) Gas tee1 (Fuso) Gaszeron (Nichiiko) Gersmin (Kowa) Harop (Toyo Pharmar) Magarte (Mohan) Poly silo (Toa) Silies (Nippon Shoji)

Sili-Met-San S (Nippon

Shoji) Spalilin (Maruishi) Eucerin (Beiersdorf) Moisture1 (Westwood- Squibb)

Use: progestogen RN: 79-64-1 MF: C,,H,202 MW: 340.51 EINECS: 201-215-4

CN: (6a,17~)-17-hydroxy-6-methyl-17-(1-propynyl)androst-4-en-3-one

3,3-ethylenedioxy-

6-rnethd-17-0x0-

5-ondrostene

[from 3p.17p-diocetoxy-

5-ondrostene (I)]

17o-ethynyl-68-methyl-

3p.5a.178-trihydroxy-

ondrostone

[from Jp-hydroxy-17-

0x0-5-androstene (IT)]

F H 3

+ E

F

MgBr

1 -propynyl- mognesium bromide

Dimethinterone

u

Ill

2 H,C-l Li NH, 1 CrO,, pyridine

3 (COOH)

2

2 methyl iodide lithium

ammonio

3 oxalic acid

a US 2 927 119 (British Drug Houses; 1.3.1960; appl 15.5.1958; GB-prior 21.5.1957)

Petrov, V et al.: J Chem Soc (JCSOA9) 1957,4105; 1960, 3676

US 2 939 819 (British Drug Houses; 7.6.1960; GB-prior 25.1.1957)

Petrov, V et al.: J Chem Soc (JCSOA9) 1959, 1957

Petrov, V et al.: J Chem Soc (JCSOA9) 1957,4099

Ruzicka, L.; Hofman, K.: Helv Chim Acta (HCACAV) 20, 1280 (1937)

' Fbrmulation(s): tabl 5- 15 mg

Eade Namefs):

GB: Secrosteron (Duncan, J: Secrosteron (Santen- USA: Oracon (Mead Johnson);

1 RN: 477-93-0 MF: C1yH22N203S MW: 358.46 EINECS: 207-520-9

CN: 10H-phenothiazine-10-carboxylic acid 2-[2-(dimethylamino)ethoxy]ethyl ester

$ monohydrochloride

RN: 518-63-8 MF: ClyH22Nz03S HCI MW: 394.92 EINECS: 208-255-1

1 LD,,: 580 mgkg (M, p.o.1;

1500 mgkg (R, p.0.)

i

OYCl

pyridine

2-(2-dimethylomino- phenothiozine- ethoxy)ethonol

1 0-corbonyl chloride

Referencefs):

DE 1 036 259.(Ayerst; appl 1955; USA-prior 1955)

L

' Formulation(s): syrup 12.5 mg15 ml

! Trade Namefs):

i: F: Cotrane (Clin-Midy); wfm I: Cothera (Ayerst); wfm Tussizid (Beolet); wfm

Cotrane (Midyfarm); wfm Perlatos (Farm Mil.); wfm

RN: 33335-58-9 MF: C,,H4,CI2N20, MW: 723.74 EINECS: 25 1-46 1 - 1

CN: 6,6',7',12'-tetramethoxy-2,2,2',2'-tetramethyltubocuraranium dichloride

t'

iodide

$ RN: 7601-55-0 MF: C40H4812NZ06 MW: 906.64 EINECS: 231-510-3

1 LDe: 230 @ k g (M, i.v.);

35 ~ g l k g (R, i.v.)

6

668 D Dimetindene

row tubocurore

(or tubocurore iodide)

H,C-CI or H,C-I, 60 "C

b

methyl chloride or methyl iodide fesp

I Dimethyltubocurarinium chloride

Reference(s):

US 2 581 903 (Eli Lilly; 1952; prior 1949)

Formulation(s): vial 2 mg/ml (20 ml)

Trade Name(s):

D: Methyl Curarin HAF USA: Mecostrin (Squibb); wfm

(Ethicon); wfm Metubine Jodide (Lilly)

Dimetindene

(Dimethindene)

ATC: D04AA13; R06AB03 Use: antihistaminic, antipruritic RN: 5636-83-9 MF: C&,N2 MW: 292.43 EINECS: 227-0834

LD,,: 27 mgkg (R, i.v.); 618 m g k g (R, p.0.);

45 mgkg (dog, i.v.)

CN: N,N-dimethyl-3-[1-(2-pyridinyl)ethyl]-lH-indene-2-ethanamine

maleate (1:l)

RN: 3614-69-5 MF: C2,HZ4N2 C,H404 MW: 408.50 EINECS: 222-789-2

LDSo: 26.8 mglkg (R, i.v.); 618 mglkg (R, p.0.)

1 NOH

2 C I - ~ / ~ ~ ,

0 7 1 sodium hydride

c H 3 2 2-(dimethylomino)

ethyl chloride

polyphosphoric acid

-*I

diethyl benzyl-

malonate

H3C

F H 3

w N \ C H 3

H+

1 phenyllithium or

butyllithium

H3C -

2 2-ethylpyridine

L -l

Dimetotiazine D 669

Reference(s):

US 2947 756 (Ciba; 2.8.1960; appl 5.5.1959; prior 12.8.1958, 3.1 1.1958, 10.2.1959)

US2970 149 (Ciba; 31.1.1961; appl 3.11.1958)

Formulation(s): amp 4 mg; drg 1 mg; drops 1 mglml; gel 1 mg/g; s r drg 2.5 rng; s r tabl 2.5 mg; syrup

0.122 mg/ml

Trade Name(s):

D: Fenistil (Zyma-Blaes) Vibrocil (Zyma)-comb.; J: Foristal (Ciba-Geigy-

GB: Fenostil (Zyma); wfm I: Fengel (Zyma) USA: Forhistal (Ciba); wfm Fenostil-Retard (Zyma); Fenistil (Zyma) Triten (Marion); wfm

Dimetotiazine

(Dimethothiazine; Fonazine)

ATC: N02CX05 Use: antiallergic, antihistaminic, antimigraine agent RN: 7456-24-8 MF: C1yH2SN302S2 MW: 391.56 EINECS: 231-229-6

LD,: 100 mg/kg (M, i.v.); 740 mg/kg (M, p.0.)

CN: 10-[2-(dimethylamino)propyl]-N,N-dimethyl-lOH-pknothiazine-2-sulfonamide

mesylate

RN: 7455-39-2 MF: C,,H2,N3O2S, CH,03S MW: 487.67

1 N0NH2

b

1 sodium omide

2 2-dimethylomino- propyl chloride

sulfonylphenoihiozine

Reference(s):

GB 814 512 (RhBne-Poulenc; appl 15.7.1957; F-prior 1.8.1956, 18.12.1956)

FR 1 179 968 (RhBne-Pou1enc;-appl 1.8.1956)

Formulation(s): cps 20 mg (base); suppos 50 mg; tabl 25 mg (mesylate)

Trade Name(s):

D: Migristene (Rhodia I: Alius (Roussel)

Pharma); wfm J: Bistermin (Toyo Shinyaku)

F: Migristhe (Specia); wfm Calsekin (Kanto-Isei)

GB: Banistyl (May & Baker); Demethotiazine (Mohan)

Neomestin (Taiyo) Serevirol (Fuji Zoki)

Dimoxyline

(Dioxyline)

ATC: A03 Use: antispasmodic, vasodilator RN: 147-27-3 MF: CZ2H2,NO, MW: 367.45

CN: I-[(4-ethoxy-3-methoxyphenyl)methyl]-6,7-dimethoxy-3-methylisoquinoline

phosphate (1:l)

RN: 5667-46-9 MF: C2,H2,N0, H,PO, MW: 449.44 EINECS: 227-126-0

4-(2-aminopropyl)- 1.2-dimethoxybenzene (I)

COOH phosphorus

oxychloride

4-ethoxy-3-

rnethoxyphenyl-

ocetic acid

Reference(s):

US 2 728 769 (Eli Lilly; 1955; prior 1949)

Formulation(s): tabl 100 mg

Trade Namefs):

I: Paverona (Lilly); wfm USA: Paveril (Lilly); wfm

Dinoprost

(Prostagladin F,,)

ATC: G02ADOl Use: oxytocic, abortifacient RN: 551-1 1-1 MF: C,,H,,O, MW: 354.49

LD,,,: 56 m g k g (M, i.v.); 1300 mglkg (M, p.0.);

106 mglkg (R, i.v.); 1170 mglkg (R, p.0.);

2.5-5.0 mglkg (rabbit, i.m., i.v.)

CN: (5Z,9a,l la,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-l-oic acid

trometharnine salt (1:l)

RN: 38562-01-5 MF: C,,H,,O, C,H,,NO, MW: 475.62 EINECS: 254-002-3 LD,,: 33 1 mglkg (M, i.v.); 71 1 rnglkg (M, p.0.);

101 mglkg (R, i.v.); 665 mglkg (R, p.0.)