Pharmaceutical Substances Syntheses, Patents, Applications - Part 56 potx

Colirnune Fisons Colirnune s 1001s 200 Fisons Durachrornan durachemie lntal Fisons; Rh6ne- GB: Poulenc Rorer; 1970 Lomupren Fisons Opticrorn Fisons Pulbil Klinge Vividrin Mann generics C

C r o p r o p a m i d e C 5 5 1

Formulation(s): aerosol 1 mgl0.05 ml; cps 100 mg; gran 100 mg, 200 mg; nasal spray 2.8 mg1O 14 ml, 20 mgl

ml; ophthalmic drops 10 mg10.5 ml, 20 mglml (as disodium salt)

Trade Name(s):

Aarane (RhGne-Poulenc

Rorer; 1983)-comb

Allergochrom (Ursapharm)

Allergospasmin (ASTA

Medica AWD; 1983)-comb

Colirnune (Fisons)

Colirnune s 1001s 200

(Fisons)

Durachrornan (durachemie)

lntal (Fisons; Rh6ne- GB:

Poulenc Rorer; 1970)

Lomupren (Fisons)

Opticrorn (Fisons)

Pulbil (Klinge)

Vividrin (Mann)

generics

Crornedil (Europhta)

Crornoptic (Chauvin)

Intercron (Laphal) Lomudal (RhGne-Poulenc Rorer Specia)

Lomusol (RhGne-Poulenc Rorer Specia)

Nalcron (Rh6ne-Poulenc Rorer Specia)

Opticron (RhGne-Poulenc Rorer Specia)

Intal Syncroner (Rh6ne- Poulenc Rorer; 1968) Nalcrom (RhGne-Poulenc Rorer)

Opticrom (RhGne-Poulenc Rorer)

Rynacrom Spray (RhGne- Poulenc Rorer)

I: Cromantal (Nuovo Cons Sanit Naz.)

Frenal (Schiapparelli Searle)

Gastrofrenal (Schiapparelli Searle)

Lomudal (Fisons) Nalcrom (Fisons) Rinofrenal (Schiapparelli Seark-comb

Sificrom (SIFI) Visuglican (Merck Sharp & Dohme)-comb

J: Intal (Fujisawa; 1971) USA: Aarane (Syntex); wfm Intal (Fisons; 1973); wfm Nasalcrom (Fisons); wfrn Opticrom (Fisons); wfm

Use: respiratory tonic RN: 633-47-6 MF: C,3H24N202 MW: 240.35 EINECS: 2 1 1-193-8

CN: N-[1-[(dirnethylamino)carbonyI]propyl]-N-propyl-2-butenamide

propyl- 2-chloro-N.N-

ornine dimethylbutyr-

ornide

Reference(s):

US 2447 587 (Geigy; 1948; CH-prior 1942j,

Formulation(s): drops 15 % (comb with crotetarnide)

Trade Name(s):

D: Micoren (Geigy)-comb F: Micorkne (Ciba-Geipy)- GB: Micoren (Geigyj-comb with crotetamide; wfm comb with crotetamide; with crotetamide; wfm

with crotetarnide; wfrn

552 C Crotamiton

Crotamiton

RN: 483-63-6 MF: C,,H,,NO MW: 203.29

LD,,,: 1600 mglkg (M, p.0.);

1500 mglkg (R, p.0.)

crotonoyl chloride N-ethyl-2-

met hylaniline

ATC: P03A Use: antipruritic, scabicide EINECS: 207-596-3

Reference(s):

GB 615 137 (Geigy; appl 1946)

Formulation(s): cream 0.1 glg; gel 50 mg1100 g; ointment 100 rngllOO g; sol 10 %

Trade Name(s):

(gepepharni) GB: Eurax (Novartis Consumer) Fujisawa)

Euraxil (Novartis I: Eurax (Zyma) USA: Burax (Westwood-Squibb) Consumer Health) J: Dermarin (Taisho)

Use: respiratory tonic RN: 6168-76-9 MF: C,2H22N202 MW: 226.32 EINECS: 228-208-9

CN: N-[l-[(dimethylamino)carbonyl]propyl]-N-ethyl-2-butenamide

dimethylbulyr- amide

crotonoyl

chloride

Crotetamide

Reference(s):

US 2 447 587 (Geigy; 1948; CH-prior 1942)

Formulation(s): drops 15 % (comb with cropropamide)

Cyamemazine C 553

Trade Name(s):

D: Micoren (Geigy)-comb F: Micorkne (Ciba-Geigy)- GB: Micoren (Ge1gy)-comb with cropropamide; wfm comb with cropropamide; with cropropamide

with cropropamide

C yamemazine

(Cyamepromazine)

ATC: N05AA06 Use: neuroleptic, tranquilizer RN: 3546-03-0 MF: C,,H,,N,S MW: 323.46 EINECS: 222-594-2

CN: l0-[3-(dimethylamino)-2-methylpropyl]-10H-phenothiazine-2-carbonitrile

Z-chloropheno-

thiozine

P-cyanopheno- thiozine

1 NaNH2, xylene

2 cl&i:3

CH3

I

2 1 -chloro-3-dimethyl-

amino-2-methyl-

Cyamemazine propane

DE 1 056 61 1 (RhGne-Poulenc; appl 1956; F-prior 1955)

Formulation(s): amp 50 mg/5 ml; drops 4 %; sol 40 mg/ml; tabl 25 mg, 100 mg

Trade Name(s):

D: Neutromil (Farmita1ia)- F: Tercian (Specia)

comb.; wfm

Cyanocobalamin

(Vitamin B ,,)

ATC: B03BAO1 Use: antipernicious vitamin RN: 68-19-9 MF: C,,HxxCoN14014P MW: 1355.39 EINECS: 200-680-0

CN: cobinamide cyanide hydroxide dihydrogen phosphate (ester) inner salt 3'-ester with 5,6-dimethyl-1-a-D- ribofuranosyl- 1 H-benzimidazole

554 C Cvanocobalamin

HO-

-CH3

'CH,

Cyanocobolarnin

By fermentation with Streptotnycev griseus, S olivaceus, S aureofaciens, Bacillus megatherium or Propionobacterium freudenreichii Molasses is used generally as fermentation medium, CoC1, and 5,6-

dimethylbenzimidazole are added Various adsorption and extraction methods are used for isolation from the fermentation liquors

Reference(s):

review:

Ullmanns Encykl Tech Chem., 3 AuB., Vol 18,219

Kirk-Othmer Encycl Chern Technol., 2nd Ed (15SWA8), Vol 21, (1963-1971), 544

Bernhauer, K et al.: Angew Chem (ANCEAD) 75, 1 145 (1963)

fermentative preparation:

US 2 505 053 (Merck & Co.; 1950; appl 1948)

US 2 530 416 (Merck & Co.; 1950; appl 1949)

US 2 563 794 (Merck & Co.; 1951; appl 1949)

US 2 595 499 (Merck & Co.; 1952; appl 1948)

US 2 650 896 (Mcrck & Co.; 1953; appl 1950)

US 2 703 302 (Merck & Co.; 1955; appl 1952)

LJS 2 703 303 (Merck & Co.; 1955; prior 1948)

DE 1 046 258 (Soc Farmaceutici Italia; appl 1956; I-prior 1955)

DE 1 076 889 (Distillers; appl 1958; GB-prior 1957)

US 2 951 017 (Distillers; 1960; GB-prior 1957)

US 3 000 793 (Merck & Co.; I96 1 ; prior 1955)

US 3 01 8 225 (Merck & Co.; 23.1.1962; prior 1953)

DE 1 080 264 (Distillers; appl 1958; GB-prior 1957)

DE 1 09 1 705 (Roche; appl 1959)

DE 1 109 317 (Roche; appl 1959)

GB 1 451 694 (Richter Gedeon; appl 25.10.1974; H-prior 26.10.1973)

US 4 1 19 492 (Nippon Oil; 10.10.1978; J-prior 5.2.1976)

yield increasing by addition of betaine to the nutritive medium:

US 3 000 793 (Merck & Co.; 1961; appl 1957)

US 2 923 666 (Pabst Brewing Comp.; 1960; appl 1954)

isolationfrom liverpreparations:

US 2 609 325 (Merck & Co.; 1952; appl 1948)

pur$icatiotl and isolation:

US 2 607 717 (Merck & Co.; 1952; appl 1949)

US 2 626 888 (Merck & Co.; 1953; appl 1950)

US 2 628 186 (Research Corp.; 1953.: appl 1950)

US 3 057 851 (Armour; 9.10.1962; prior 1955)

Cyclandelate C 555

Formulation(s): amp 0.1 mg, 1 mg; drg 1 mg; drops 0.05 mg; inj flask 0.5 mg, 1 mg 5 mg

D: B,, "Ankermann"

(Worwag)

B,,-Horfervit (Arteva

Pharma)

B ,, Rotexmedica

@otexmedica)

B,,-Steigerwald

(Steigerwald)

BIZ-Vicotrat (Heyl)

Biovital (Dr Schieffer)-

comb

Bryonon (Protina)-comb

Cervevit (Baxter)-comb

Cobidec (Warner-

Lambert)-comb

Cytobion (Merck)

Dodecatol (Heyl)-comb

Dolo-Neurobion

(Merck1e)-comb

Eryfer (Cassella-med)-

comb

Eukalasan (Steigerwaldl-

comb

Hamo-Vibolex (Anphasaar)

Lophakomb (Lomapharm)

Multibionta (Merckle)-

comb

Natabec (Warner-Lambert)

Neurotrat (Knoll)-comb

Vicapan R,, (Merckle)

Vitamin B 12 forte (Hevert)

Vitamin B,, (OTW)

Vitamin B 12 Injektionslosung (Wiedemann) Vitamin-B ,,-ratiopharm (ratiopharm)

numerous combination preparations

F: Alvityl (Sohay)-comb

Azedanit (Whitehall)- comb

B,, Mille Delagrange (SynthClabo) Berocca (Nicholas)-comb

Forvital (Whitehall)-comb

Pharmaton (Boehringer 1ng.)-comb

Soluvit (UCB)-comb

Synergil (Dakota) Vitamine B,, Aguettant (Aguettant)

Vitamine B,, Lavpisier (Chaix et du Marais) Vivamyne (Whitehall)

comb

numerous combination preparations

GB: Cytacon (Goldshield) Cytamen (Evans) I: Cobcquin (Casarini) Dobetin (Angclini) Efargen (Teofarma)-comb

Epargriseovit ( F a r m i t a h - comb

Eritrovit B 12 (Lisapharma) Mionevrasi (Boehringer Mannh.)-comb

Neoepari biol (Ecobi)- comb

Reticulogen (Lilly) Tonicum (SIT)-comb numerous combmation preparations

J: Actamin B,, (Yashima) Redisol (Merck-Banyu) numerous combination preparations

USA: Bevitarnel (Westlake) Chromagen (Savage) Cyanocobalamin (Elkins- Sinn)

Fetrin (Lunsco) Hemocyte-F (U.S

Pharmaceutical) Mega-B (Arco) Nascobal (Schwarz) Niferex (Schwarz) Nu-Iron-Plus Elixier (Merz)

Rubramin P C (Squibb) Trinsicon (UCB) numerous combination preparations

Use: antispasmodic RN: 456-59-7 MF: C,,HZ4O3 MW: 276.38 EINECS: 207-271-6

LD,: >10 g k g (M, p.0.);

5 glkg (R, p.0.)

CN: a-hydroxybenzeneacetic acid 3,3,5-trimethylcyclohexyl ester

acid cyclohexanol

Reference(s):

US 2 707 193 (Brocades-Stheeman; 1955; NL-prior 1949)

556 C Cyclizine

purification:

US 3 663 597 (American Home; 16.5.1972; appl 5.5.1970)

Trade Name(s):

D: Eucebral-N (Siidmedica)-

comb

Natil(3M Medica)

Spasmocyclon (3M

Medica)

F: Cyclergine (Poirier)

Cyclospasmol

(Yamanouchi)

Novodil (Augot)

Vascunormyl (A1con)-

comb

GB: Cyclobral (Norgine); wfm

Cyclospasmol (Brocades);

wfm

I: Ciclospasmol (Brocades) J: Anticen (Nippon Kayaku) Aposelebin (Hokuriku) Capilan (Takeda) Capistar (Kowa Yakuhin) Ceaclan (Mohan) Cepidan (Meiji) Circle-one (Funai) Circulat (Kotani) Cyclan (Ohta) Cyclan-Cap (Nichiiko) Cyclansato (SS) Cycleat Cap (Hishiyama) Cycralate (Kanto)

Hacosan (Sanko) Hi-Cyclane Cap (Vama) Mandelic (Seiko) Marucyclan (Maruko) Mitalon (Toyo Pharmar) Newcellan Cap (Kowa) Saiclate (Morishita) Sancyclan (Santen) Sepyron Cap (Sankyo) Spadelate Cap (Zeria) Venalal (Mochida) Zirkulat (Nippon Shoji) USA: Cyclospasmol (Ives); w h generics; wfm

Use: antihistaminic, anti-emetic RN: 82-92-8 MF: C,,Hz2N2 MW: 266.39 EINECS: 201-445-5

LD,,: 147 mglkg (M, p.0.)

CN: 1-(diphenylmethy1)-4-methylpiperazine

monohydrochloride

RN: 303-25-3 MF: Cl,Hz,Nz , HCI MW: 302.85 EINECS: 206- 136-9

LD,,,: 165 mglkg (M, p.0.)

lactate (1:l)

RN: 5897-19-8 MF: Cl,H,2N2 C,H60, MW: 356.47

CH3

Cyclizine

US 2 630 435 (Burroughs Wellcome; 1953; prior 1948)

Trade Name(s):

D: Migrane-Kranit spezial GB: Diconal (Glaxo Wellcome)- I: Marzine (Wellcome; as

F: Migwell (Glaxo Wellcome; Migril (Glaxo Wellcome)- J: Cleamine (Kodama)-comb

Valoid (Glaxo Wellcome) Wellcome); wfm

Cvclnbarbital C 557

Marezine (Burroughs

Wellcome; as

hydrochloride); wfrn

Cyclobarbital

(Hexemal; Cyclobarbitone)

ATC: N05CA10 Use: hypnotic

RN: 52-31-3 MF: C,,H,,N,O, MW: 236.27 EINECS: 200-138-3

LDG 840 mg/kg (M, p.0.)

CN: 5-(1 -cyclohexen- 1-yl)-5-ethyl-2,4,6(1 H,3H,SH)-py rimidinetrione

calcium salt

RN: 5897-20-1 MF: C,,H,,N,O, xCa MW: unspecified EINECS: 227-590-4

calcium salt (2: 1)

RN: 143-76-0 MF: C,,H,,CaN,O, MW: 5 10.60 EINECS: 205-610-2

bromide

cyanoocetote

2-(I -cyclohexenyl)- butyrate (1)

dicyano-

diamide

Cyclobarbital

u

DRP 442 655 (Bayer; 1924)

GB 231 150 (Bayer; 1924)

Fonulation(s): cps 75 mg; tabl 100 mg, 200 mg (as calcium salt)

Trade Name(s):

D: Dormopan (Bayropharm)-

comb.; wfrn

Gastripan (Merck1e)-

comb.; wfrn

Itridal (Homburg)-comb.;

wfrn

Medinox (Pfleger)-comb.;

wfrn

Phanodorm (Bayer); wfrn

Somnubene (Merck1e)- comb.; wfrn

Somnupan C (Merckle);

wfrn Stodinox (Lorenz)-comb.;

wfrn Tcmpidorm N (Roland)- comb.; wfrn

generics; wfrn

F: Dormopan (Bayer- Pharma)-comb.; wfrn GB: Phanodorm (Winthrop); wfrn

Rapidal (Medo) I: Cyclobarbitalum (Sale di calcio)

J: Adorm (Shionogi)

5 5 8 C Cyclobenzaprine

Use: muscle relaxant, psychosedative RN: 303-53-7 MF: C2,,H2,N MW: 275.40 EINECS: 206-145-8

LD,,,: 36 tnglkg (M, i.v.); 250 mglkg (M, p.0.)

CN: 3-(5H-dibenzo[a,~cyclohepten-5-ylidene)-N,N-dimethyl-l -propanamhe

hydrochloride

RN: 6202-23-9 MF: C,,,H,,N HCI MW: 31 1.86 EINECS: 228-264-4

LD,,,: 36mg/kg(M,i.v.);250mglkg(M,p.o.)

dibenzo[o,d]cyclo- J-dimethylornino-

chloride

HCI, CHJCOOH

Reference(s):

US 3 272 864 (Merck & Co.; 13.9.1966; appl 19.4.1962)

US 3 409 640 (Schering Corp.; 5.1 1.1968; appl 22.7.1 959)

medical use:

US 3 882 246 (Merck & Co.; 6.5.1975; prior 3 1.1.1973,21.5.1971,9.4.1974)

Ebrmdation(s): cps 10 mg; tabl 10 mg, 30 mg (as hydrochloride)

Trade Name(s):

1: Flexiban (Neopharmed) USA: Flexeril (Merck; as

hydrochloride)

Use: choleretic RN: 512-16-3 MF: C,,H,,03 MW: 186.25 EINECS: 208-138-5

LD,,,: 2900rng/kg(M,i.v.);>lOg/kg(M,p.o.);

1760 mglkg (R, i.v.); 4820 mglkg (R, p.0.)

CN: a-ethyl-1-hydroxycyclohexaneacetic acid

monosodium salt

RN: 11 30-23-0 MF: C,,H,,Na03 MW: 208.23 EINECS: 214-458-6

calcium salt

RN: 40043-69-4 MF: C,,H,,O,~ xCa MW: unspecified

betaine salt (1:l)

RN: 23579-12-6 MF: CI,,H1703 CSHl2NO2 MW: 303.40 EINECS: 245-750-1

:

Cyclofenil C 559

Reference(s):

DE 1094 254 (Lab J Logeais; appl 14.2.1959; F-prior 19.2.1958)

US 3 065 134 (Lab J Logeais; 20.1 1.1962; F-prior 19.2.1958)

Maillard, J et a].: Bull Soc Chim Fr (BSCFAS) 1958, 244

Formulation(s): amp 200 mg; tabl 250 mg (as sodium salt)

Trade Name(s):

D: Benestan (Kar1spharma)- Trommgallol I: Epa-Bon (Sifarma) comb.; wfm (Trommsdorff)-comb.; wfm J: Lipotrin (Eisai)

F: HCbucol (J Logeais) Riphole N (Nichiiko)

Use: gonadotropin stimulant (against infertility)

RN: 2624-43-3 MF: C,,H,O, MW: 364.44 E~NECS: 220-089-1

LD,,: >12.5 g k g (M, p.0.);

>12 g/kg (R, p.0.)

CN: 4-[[4-(acetyloxy)phenyl]cyclohexylidenemethy]phenol acetate

ethyl cyclo-

hexonecorboxylote

4-methoxyphenyl- magnesium bromide (from 4-bromoonisole)

u

4,C-dimethoxy- benzhydrylidene- cyclohexane (1)

1 -, 0 - ocetic anhydride

4.4'-dihydroxy- benzhydrylidene- cyclohexane

Cyclofenil

Reference(s):

U S 3 287 397 (K.G Olsson et a].; 22.11.1966; GB-prior 22.1 1.1960)

Formulation(s): tabl 100 mg, 200 mg, 400 mg

Trade Name(s):

D: Fertodur (Schering); wfrn GB: Ondonit (Roussel); wfrn I: Fertodur (Schering) F: Ondogyne (Roussel); wfm Rehibin (Thames); wfm Neoclym (Poli)

560 C Cyclomethycaine

J: Sexovid (Teikoku Zoki)

Use: local anesthetic RN: 139-62-8 MF: C2,H3,NO3 MW: 359.51

CN: 4-(cyclohexy1oxy)benzoic acid 3-(2-methyl-1-piperidiny1)propyl ester

sulfate (2:l)

RN: 6202-05-7 MF: C2pH,,NOv 112H,S04 MW: 817.10

sulfate (1:l)

RN: 50978-10-4 MF: C2,H,,N0, H,SO, MW: 457.59

4-cyclohexyloxy-

benzoic acid

Reference(s):

U S 2 439 818 (S M McElvain, T P Carney; 1948; appl 1946)

McElvain, S.M.; Carney, T.P.: J Am Chem Soc (JACSAT) 68, 2592 (1946)

Formulation(s): cream 0.5 % - 1 %; ointment 0.5 - 1%; spray 0.25 %

Trade Name(s):

USA: Surfacainc (Lilly); wfrn

Use: sympathornirnetic RN: 102-45-4 MF: CyH,,N MW: 141.26

CN: N,a-dirnethylcyclopentaneethanamine

cyclopentylidene- acetonitrile

cyclopentyl- acetonitrile (I)

Cyclopentamine

L