Pharmaceutical Substances Syntheses, Patents, Applications - Part 32 pps

F: GCnoscopolamine Amino Scopoderm Novartis GB: Buscopan Boehringer Ing.. Buscopan compost0 Boehringer 1ng.-comb.. Tranquo-Buscopan Boehringer 1ng.-comb.. J: Antispasmin Green Cross Bubu

Butylscopolammonium bromide B 3 1 1

(Butylscopolamine bromide; Scopolamine butyl bromide; antispasmodic

Hyoscin butyl bromide)

RN: 149-64-4 MF: C,,H30BrN04 MW: 440.38 EINECS: 205-744-1

LD,,: 10.3 mg/kg(M,i.v.); 1170mglkg(M,p.o.);

24 mglkg (R, i.v.); 1040 mglkg (R, p.0.)

CN: [7(S)-(la,2~,4~,5a,7P)1-9-butyl-7-(3-hydroxy-1-oxo-2-phenylpropoxy)-9-methyl-3-oxa-9-

azoniatricyclo[3.3.1 02"]nonane bromide

butyl bromide (-)-scopolamine I Butylscopolommonium bromide

Reference(s):

DE 856 890 (Boehringer Ing.; appl 1950)

Formulation(s): amp 20 mglml; drg 10 mg; f c tabl 10 mg; suppos 7.5 mg, 10 mg; tabl 20 mg;

vial 200 mg/lO ml

Trade Name(s):

D: Buscopan (Boehringer

1ng.)-comb

F: GCnoscopolamine (Amino)

Scopoderm (Novartis)

GB: Buscopan (Boehringer Ing.)

I: Buscopan (Boehringer Ing.)

Buscopan compost0

(Boehringer 1ng.)-comb

Tranquo-Buscopan

(Boehringer 1ng.)-comb

J: Antispasmin (Green Cross)

Bubusco-S (Sawai)

Buscopan (Boehringer- Tanabe)

Buscoridin (Kanebo) Buscote (Kotani) Buspon (Toyo Pharmar) Butibol (Towa) Butylpan (Hokuriku) Butymide (Ohta) Butysco (Kobayashi) Diaste-M (Fukuchi- Fujizoki)

Hyoscomin (Vitacain)

Hyospan (Toiyo) Moryspan (Beppu) Reladan (Isei) Scobro (Ono) Scobron (Mohan) Scobutylamin (Horii) Scordin-B (Ono) Scorpan (Kanto) Sparicon (Yamanouchi) Spasmopan (Nichiiko) Stibron (Iwaki)

312 C Cabergoline

Use: doparnine D, receptor antagonist, prolactin inhibitor for prevention or

suppression of puerperal lactation RN: 81409-90-7 MF: C,,H,,N,O, MW: 451.62

CN: (8~)-N-[3-(Dirnethylamino)propyl]-N-[(ethylamino)carbonyl]-6-(2-propenyl)ergoline-8-carboxamide

1 K2C03, DMF

2 NaOH CH30H

8p-methoxycarbonyl-

ergoline

(cf pergolide synthesis)

ally1 bromide

THF

d

N-ethyl-Na-[3-(dirnethyl-

amino)propyl]corbo-

diirnide

6-allyl-88-ergoline-

carboxylic acid (I)

Cabergoline

0CNvCH3, toluene or

' 3 3 H3CbN=c=Nq

H3C

1

propylarnine

diisopropylcarbo-

6-allyl-N-[3-(dimethyl- amino)propyl]-8p-

ergolinecorboxarnide

Reference(s):

a GB 2 074 566 (Farmitalia Carlo Erba S.p.A.; appl 31.3.1981; GB-prior 3.4.1980)

b US 4 526 892 (Farrnitalia Carlo Erba S.p.A.; 2.7.1985; USA-prior 3.3.1981)

BE 894 060 (Farmitalia Carlo Erba S.p.A.; appl 9.8.1982; GB-prior 11.8.1981)

b,c WO 9 31 8 034 (Farmitalia Carlo Erba S.p.A.; appl 15.2.1993; GB-prior 12.3.1982)

Candiani; Cabri, W.; Zarini, F.; Bedeschi, A,: Synlett (SYNLES) 1995 (6), 605

Cadexomer iodine C 3 13

synthesis and nidation inhibitory activity of a new class of ergoline derivatrves:

Brambillh, E.; Dlsalle, E.; Briatlco, G.; Mantegani, S.; temper ill^, A.: Eur J Med Chem (EJMCAS) 24, 421 (1989)

' Formulution(s): tabl 0.5 mg, 1 mg, 2 mg, 4 mg

Tmde Namefs):

: D: CABASERIL (Pharmacia GB: Cabaser (Pharmacla &

& Upjohn) Upjohn)

Dostinex (Pharmacia & Dostinex (Pharmacia &

Use:

RN: 94820-09-4 MF: unspecified MW: unspecified

LD50: >2 glkg (R, i.p.); >2 glkg (R, LC.)

CN: cadexomer iodine

12, acetone

drxtrin + Cl> -

epichloro-

hydrin

I: Dostinex (Pharmacia & Upjohn)

USA: Dostinex (Pharmacia & Upjohn)

D03AXO 1 ; D08AG antiseptic for treatment of decubitus and venous leg ulcers

Cadexorner iodine

I

Referencefs):

DE 2 533 159 (A 0 Johannson; appl 24.7.1975)

US4010 259 (A 0 Johannson; 1.3.1977; appl 17.7.1975)

FR 2 320 112 (A 0 Johannson; appl 5.8.1975)

Formulation(s): dry sterile powder, micropellets, sachet 3 g, 1 % bioavailable iodine

Trade Namefs):

D: Iodosorb (Strathmann) F: Iodosorb (Millot; 1984);

wfm

3 14 C Cadralazine 7

GB: Iodoflex (Perstorp) Iodosorb (Perstorp; 1983) I: Iodosorb (Valeas; 1989)

Use: antihypertensive, vasodilator RN: 64241-34-5 MF: Cl,H,,N,O, MW: 283.33

LD,,,: 700 mg/kg (M, i.p.);

269 mg/kg (R, i.v.); 2060 mg/kg (R, p.0.)

CN: 2-[6-[ethyl(2-hydroxypropyl)amino]-3-pyndazinyl]hydrazinecarboxylic acid ethyl ester

H 3 C

pyridozine

+

ethyl carbazate

Reference(s):

US 4 002 753 (I.S.F.; 11.1.1977; I-prior 7.3.1973)

alternative syntheses:

US 4 575 552 (I.S.F.; 11.3.1986; I-prior 28.4.1983)

US 4 632 982 (I.S.F.; 30.12.1986; I-prior 28.4.1983)

US 4 757 142 (I.S.F.; 12.7.1988; I-prior 13.5.1985)

cf also synthesis of pildralazine

Formulation(s): cps 10 mg, 15 mg, 29 mg

Trade Name(s):

I: Cadraten (SmithKline Cadrilan (Novartis)

Cafaminol

(Mecoffaminum; Methylcoffanolamine)

Use: rhinological therapeutic

RN: 30924-3 1-3 MF: C,,H,,N,O, MW: 267.29 EINECS: 250-390-3

LD,,,: 700 mg/kg (M, s.c.)

CN: 3,7-dihydro-8-[(2-hydroxyethyl)methylamino]-l,3,7-trimethyl-1H-purine-2,6-dione

Cafedrine C 315

caffeine 8-chlorocaffeine Cofaminol

(4 v.1

Reference(s):

DE 1 085 530 (J Klosa; appl 15.8.1958)

US 3 094 531 (Delmar Chemicals; appl 30.4.1959)

Formulation(s): drg 50 mg

Trade Nanie(s):

D: Rhinoptil (Promonta); wfm I: Katasma balsamic0

(Bruschettini)

Use: circulatory analeptic RN: 58166-83-9 MF: C,,H,,N,O, MW: 357.41

CN: 3,7-dihydro-7-[2-[(2-hydroxy-l-methyl-2-phenylethyl)amino]ethyl]-1,3-dimethy-1 H-purine-2,6-dione [R-(R*,S*)]-cafedrine

RN: 78396-34-6 MF: C,,H,,N,O, MW: 357.41

[R-(R*,S*)]-monohydrochloride

RN: 3039-97-2 MF: C,,H,N,O, HCl MW: 393.88 EINECS: 221-243-0

LD,,: 525 mgkg (M, i.p.)

theophylline 1,2-dibramo- 7-(2.-bramaethyl)-

ethane theophylline (I)

L-norephedrine I Cafedrine

Reference(s):

DE 1 095 285 (Degussa; appl 25.9.1956)

US 3 029 239 (Degussa; 10.4.1962; D-prior 17.4.1954)

Formulation(s): amp 200 mg; f c tabl 100 mg

316 C Caffeine

Trade Name(s):

D: Akrinor (Homburg)-comb F: Praxinor (Lipha SantC)- I: Akrinor (ASTA Medica; as with theodrenaline comb with thCodrCnaline hydrochloride)

Caffeine

(Cafkine; Coffein)

ATC: N06BCOl Use: analeptic diuretic RN: 58-08-2 MF: CUH,,N4O2 MW: 194.19 EINECS: 200-362-1

LD,,,: 62 mglkg (M, i.v.); 127 mglkg (M, p.0.);

105 mglkg (R, i.v.); 192 mglkg (R, p.0.);

140 mglkg (dog, p.0.)

CN: 3,7-dihydro-1,3,7-trimethyl-lH-purine-2,6-dione

O\\ 0

CH3

(9 v.)

Reference(s):

DE 834 105 (Boehringer Ing.; appl 1949)

Formulation(s): tabl 200 mg

Trade Name(s):

D: Coffeinum (Merck) GB: Cefergot.(Novartis)-comb J:

Percoffedrinol N (Passauer) Doloxene (Lil1y)-comb

numerous generics and combination preparations numerous combination Migril (Glaxo Wellcome)- USA: Darvon (Lilly)

F: Cafkine Aguettant I: Caffeina (Tariff Nazionale; Frederick)

PercutafCine (Fabre) numerous combination numerous combination

preparations

Caffeine acetyltryptophanate

(A 50; Coftrinum)

ATC: N06BCOl Use: psychotonic RN: 60364-24-1 MF: Cl,H14N203 CuHloN402 MW: 440.46

CN: 1-acetyl-L-tryptophan compd with 3,7-dihydro-1,3,7-trimethyl-lH-purine-2,6-dione (1: 1)

" 8 " ' '

H N CH,

0

N-acetyl-

Calcifediol C 317

Reference(s):

FR-M 1 759 (A E C.; appl 22.2.1962)

Trade Name(s):

F: Adrifane (Adrian, Paris);

wfm

Use: calcium regulator

RN: 19356-17-3 MF: C,,H,O, MW: 400.65 EINECS: 242-990-9

CN: (3~,5Z,7E)-9,l0-secocholesta-5,7,10(19)-triene-3,25-diol

25-hydroxycholesterol 3-ocetote acetic anhydride

dimethylhydantoin

2 trirnethyl phosphite

3 lithium aluminum

hydride

dirnethylhydontoin

2 trimethyl phosphite

3 rnethylmognesium

Reference(s):

a,bBlunt, J.W.; DeLuca, H.F.: Biochemistry (BICHAW) 8,671 (1969)

DeLuca, H.F.: Am J Clin Nutr (AJCNAC) 22,412 (1969)

Halkes, S.J.; Vliet, N.P van: Recl Trav Chim Pays-Bas (RTCPA3) 88, 1080 (1969)

alternative svntheses:

Sodano, Ch S.: Vitamins, Synthesis, Product~on and Use, p 131, 159 (New Jersey 1979)

US 4 001 096 (Upjohn; 4.1.1977; prior 21.2.1975)

US 3 833 622 (Upjohn; 3.9.1974; prior 17.3.1969)

structure and isolation:

DeLuca, H.F.: Am J Clin Nutr (AJCNAC) 22,412 (1 969)

Formulation(s): drops 0.15 mglml, 0.45 mglml

Trade Nameis):

D: Dedrogyl (Albert-Roussel, F: DCdrogyl (Roussel) I: Didrogyl (Roussel)

Use: antipsoriatic, topical vitamin D,-

analog RN: 112828-00-9 MF: C,,H,,O, MW: 412.61

CN: (la,3~,5Z,7E,22E,24S)-24-cyclopropyl-9,1O-secochola-5,7,10(19),2~-tetraene-1,3,24-triol

'?3

CH3 CH3

tert-butyld~methyl- sflyl chlor~de (I)

vitamin D2

Me ,NH

%

triphenylphosphine

propane

NaOH

1 V, A

2 chrornotography

CH3 CH3 CH, CH,

(cyclapropylcarbo-

nylrnethy1ene)tri-

phenylphasphorane

320 C Calcitriol

2 chromotagraphy

C H

c H c H Li~o-&o-jiTcH3 'CH c H

I

(W

Bu4N+F-

b

tetrobutyl- ammonium fluoride

I Calcipotriol

Reference(s):

EP 227 826 (Leo; appl 14.7.1986; GB-prior 2.8.1985)

WO 8 700 834 (Leo; appl 14.7.1986; GB-prior 2.8.1985)

Calverley, M.J.: Tetrahedron (TETRAB) 43,4609 (1987)

Fonmdation(s): ointment 50 pglg

Psorcutan (Schering AG) GB: Daivonex (Leo; 1991) Psorcutan (Schering)

Calcitriol

(la,25-Dihydroxy-vitamin D,)

ATC: A 1 ICC04; DOSAX03 Use: calcium regulator RN: 32222-06-3 MF: C,,H,O, MW: 416.65 EINECS: 250-963-8

LDS,,: 1350 pglkg (M, p.0.);

I05 pglkg (R, i.v.); 620 p g k g (R, p.0.)

CN: (la,3~,5Z,7E)-9,10-secocholesta-5,7,10(19)-triene-l,3,25-triol

1 a.25-dihydroxycholesterol acetic anhydride