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Pharmaceutical Substances Syntheses, Patents, Applications - Part 46 potx

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250 mg, 500 mg Trade Names: D: Paraflex Cilag-Chemie- comb.; wfm I: Biomioran Bioindustria; wfm Paraflex Cilag-Chemie; wfm J: Chlozoxine Sanko Chroxin Kanto Deltapyrin Kodama- comb.. CN

Trang 1

9 Chlortetracycline C 45 1 USA: Combipres (Boehringer Hygroton (Rh6ne-Poulenc Tenoretic (Zeneca)

SO 1 AA02 Use: antibiotic RN: 57-62-5 MF: C22H23ClN,08 MW: 478.89 EINECS: 200-341-7

LD,,: 134 mg/kg (M, i.v.); 1500 mglkg (M, p.0.);

1 I8 mgkg (R, i.v.);

150 &kg (dog, i.v.); 750 m a g (dog, p.0.)

CN: [4S-(4a,4aa,5aa,6~,12aa)]-7-chloro-4-(dimethyIamino)- l,4,4a,5,5a,6,ll,l2a-octahydro-3,6,lO, 12,12a- pentahydroxy-6-methyl- 1,11 -dioxo-2-naphthacenecarboxamide

RN: 64-72-2 MF: C,,H23ClN20, HCl MW: 515.35 EINECS: 200-591-7

LD,,: 100 mgkg (M, i.v.); 2314 mglkg (M, p.0.);

100 mglkg (R, i.v.)

I Chiortetracycline

From fermentation solutions of Streptomyces aureofaciens

Reference(s):

US 2 482 055 (American Cyanamid; 1949; prior 1948)

US 2 609 329 (American Cyanamid; 1949; prior 1948)

US 2 899 422 (American Cyanamid; 1959; prior 1956)

US 2 987 449 (American Cyanamid; 6.6.1961; prior 23.2.1960)

US 3 050 446 (American Cyanamid; 21.8.1962; prior 28.7.1960)

Duggar, B.M.: Ann N Y Acad Sci (ANYAA9) 51, 175 (1948)

Formulation(s): cream 10 mglg, 30 mglg, 3 %; eye ointment 10 mglg (1 %); ointment 30 mg/lO g (3 %); pastes

30 mg; pessaries 100 mg (as hydrochloride)

Trade Name(s):

D: Aureodelf (Leder1e)-comb GB: Aureocort (Wyeth)-comb Aureomix (SIT)-comb Aureomycin (Lederle) Aureomycin (Wyeth) J: Aureomycin (Lederle) F: Aur6omycine (Specia); Deteclo (Wyeth)-comb USA: Aureomycin (Lederle);

Tri-antibiotique Chibret comb

(Chibret)-comb.; wfm Aureomicina (Cyanamid)

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452 C Chlorthenoxazine

1Jse: anti-inflammatory, antipyretic, analgesic

RN: 132-89-8 MF: C,,H,,CINO, MW: 211.65 EINECS: 205-082-3

LD,,: 1 1.155 gfkg (M, p.0.);

10 @kg (R, p a ) CN: 2-(2-chloroethy1)-2,3-dihydro-4H- 1,3-benzoxazin-4-one

propionoldehyde

HCI, CH,COOH

acrolein

Referencets):

a DE 1 021 848 (Thomac; appl 1955)

I b DE 1 028 999 (Thomae; apyl 1956; addition to DE 1 021 848)

Formulation(s): tabl 200 mg

Trade Namets):

D: Cimporhin (Tomae)-comb.; Betix (Saha); wfm Ossipirina (Radiumfarrna);

Fiobrol (Geigy)-comb.; comb.; wfm Oxal (Saita); wfm

I: Atoss~pirina (Bonomeo)- Ossazone (Brocchieri); Reulin (Isola-Ibi); wfrn

Use: muscle relaxant RN: 95-25-0 MF: C7H4CIN02 MW: 169.57 EINECS: 202-403-9

LD,,: 440 mglkg (M, p.0.);

763 mglkg (R, p.0.) CN: 5-chloro-2(3H)-benzoxazolone

2-amino-4- phosgene Chlorzoxozone I

chlorophenol

Reference(s):

US 2 895 877 (McNeil; 21.7.1959; prior 30.7.1956)

Trang 3

Cholestyramine C 453

Formulation(s): tabl 250 mg, 500 mg

Trade Name(s):

D: Paraflex (Cilag-Chemie)-

comb.; wfm

I: Biomioran (Bioindustria);

wfm

Paraflex (Cilag-Chemie);

wfm

J: Chlozoxine (Sanko)

Chroxin (Kanto)

Deltapyrin (Kodama)- comb

Framenco (Fuso) Kiricoron (Sampo)-comb

Mesin (Yamanouchi) Nichirakishin (Nichiiko) USA:

Pathorysin (Kowa Yakuhin) Rheumadex Comp

(Nakataki)-comb

Salinalon (Nippon Kayaku)-comb

Solaxin (Eisai) Sorazin (Toho) Trancrol (Mohan) Parafon Forte (Ortho- McNeil Pharmceutica1)- comb

Cholestyramine

(Colestyramine)

Use: antipruritic at biliary congestion

RN: 11041-12-6 MF: unspecified MW: unspecified EINECS: 234-270-8

LD5,: >7.5 g/kg (M, p.0.);

>4 glkg (R, p.0.)

CN: cholestyramine

Chloromethylation o i styrene-divinylbenzene-mixing polymerizate and following reaction with trimethylamine

Referencels):

"medical use"

US 3 383 281 (Merck & Co.; 14.5.1968; appl 22.9.1961; prior 15.7.1958)

Formulation(s): eff tabl 2 g; gran 4 g; powder 4 g

Trade Name(s):

D: Lipocol (Merz & Co.) GB: Questran (Bristol-Myers USA: Locholest (Warner Chilcott Quantalan (Bristol-Myers Squibb) Professional Products) Squibb) I: Cholestrol (Formenti) Questran (Bristol-Myers Vasocan (Felgentrager) Questran (Bristol It Sud; as Squibb)

F: Questran (Allard; Bristol- hydrochloride)

Myers Squibb)

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454 C Choline chloride

Use: choleretic RN: 67-48-1 MF: C5HI4ClNO MW: 139.63 EINECS: 200-655-4

LD,,,: 53 mgtkg (M, i.v.); 3900 mglkg (M, p.0.);

3400 mglkg (R, p.0.)

CN: 2-hydroxy-N,N,N-trimcthylethanan~inium chloride

trimethyl- 2-chloro-

amine (I) ethonol

Choline chloride

ethylene choline hydroxide

oxide ( q v.)

Reference(s):

Ullmanns Encykl Tech Chem., 4 AuA., Vol 9,586

US 2 623 90 1 (Nopco; 1952; appl 1950)

Formulation(s): emulsion 400 mgl5 ml

Trade Name(s):

D: Geriatrie-Mulsin (Mucos)- I: Betotal (Carlo Erba)-comb numerous combination

F: Desintex-Choline (M Integrativo)

Richard)-comb

Use: lipotropic

KN: 77-91-8 MF: C6H707 C5HI4NO MW: 295.29 EINECS: 201-068-6

LD,,,: >4800 mglkg (M, i.v.); >4800 mgtkg (M, p.0.);

>4800 mglkg (R, i.v.); A 8 0 0 mglkg (R, p.0.)

CN: 2-hydroxy-N,N,N-trimethylethanaminium salt with 2-hydroxy-l,2,3-propanetricarboxylic acid (1:l)

choline hydroxide citric ocid Choline dihydrogen citrate

Trang 5

Choline hydroxide C 455

Reference(s):

US 2 870 198 (Nopco; 1959; appl 1954)

Formulation(s): amp 300 mglml

D: Neurotropan (Phonix)- Hipagrume (SynthC1abo)- I: Ipocol (Arnaldi)-comb.;

F: Citrocholine (ThCrica)- Kalicitrine (Promedica)- Liverin (Perkins)-comb.;

Hepacholine Sortriol Romarine-choline Rybutol (Bergamon)- (SynthClab0)-comb (At%-ocid)-comb comb.; wfm

RN: 123-41-1 MF: CSH,,NO2 MW: 121.18 EINECS: 204-625-1

LD%: 21.4 mgkg (M, i.v.1

CN: 2-hydroxy-N,N,N-trimethylethanaminium hydroxide

Intermediate for choline salts

Reference (5):

Ullmanns Encykl Tech Chem., 4 Aufl., Vol 9,586

GB 379 260 (F Korner; appl 1932; D-prior 1931)

DRP655 882 (Prod AminCs S A., Briissel; appl 1931; B-prior 1931)

Renshaw, R.R.: J Am Chem Soc (JACSAT) 32, 128 (1910)

US 2 774 759 (American Cyanamid; 1956; appl 1955)

alternative synthesis from trimethylamine and 2-chloroethanol:

DE 801 210 (BASF; appl 1948)

US 2 623 901 (Nopco; 1952; appl 1950)

Pade Narnefs):

USA: Cholinellnoritol Tablets Lipo-C (Legere); wfm

(Solgar); wfm

Choline salicylate

(Salicylate d e choline)

ATC: N02BA03 Use: analgesic, anti-inflammatory, antipyretic

RN: 2016-36-6 MF: C5H14N0 C7Hs03 MW: 241.29 EINECS: 217-948-8

LD,,: 2690 mgkg (M, p.o.1

CN: 2-hydroxy-N,N,N-trimethylethanaminium salicylate (1: I)

Trang 6

456 C Choline stearate

salicylic acid choline chloride

sodium solt

Choline salicylate

Referertce(s):

US 3 069 321 (Labs for Pharmac Dev.; 18.12.1962; appl 4.4.1960)

BE 583 5 13 (Mundipharma; appl 12.10.1959)

Formulation(s): drops 200 mglml; gel 87.1 mglg; sol 500 mg1100 ml

Trade Name(s):

D: Audax (Mundipharma) F: Givalex (Norgine Pharma)- I:

Salicol (Sais); wfm

Satibon (Grelan) Mundisal (Mundipharrna)- Pansoral (1nava)-comb USA: Trilisate (Purdue Frederick) comb GB: Bonjela (Reckitt &

Co1man)-comb

Use: anti-inflammatory, liver therapeutic RN: 60154-01-0 MF: C18H,s02 CSHl4NO MW: 387.65

CN: 2-hydroxy-N,N,N-trimethylethanaminium octadecanoate (salt)

Reference(s):

US 2 774 759 (American Cyanamid; 1956; appl 1955)

choline hydroxide stearic acid

Formulation(s): ointment 2.95 gllOO g

Choline stearate

Trade Name(s):

D: Chomelanum (Schur)

(4 v.)

(Cholinophylline; Oxtriphylline; Oxytrimethylline) Use: bronchodilator

RN: 4499-40-5 MF: C7H7N402 C5H,,N0 MW: 283.33 EINECS: 224-798-7

CN: 2-hydroxy-N,N,N-trimethylethanaminium, salt with 3,7-dihydro-l,3-dimethyl-IH-purine-2,6-dione (1:l)

Trang 7

Chymopapain C 457

hydrogen carbonate

Reference(s):

US 2 776 287 (Nepera; 1957; appl 1954)

Fomulation(s): f c tabl 200 mg; s r tabl 400 mg, 600 mg

Trade Name(s):

D: Euspirax (Asche) Teofilcolina (Salfa); wfm Theophyl-Choline

GB: Choledyl (Warner); wfm Teofilcolina sedativa (Perkins)-comb with Sabidal (Zyma); wfm (Salfa)-comb.; wfm theophyllineacetate; wfm

Use: intervertebral disk damages therapeutic

RN: 9001-09-6 MF: unspecified MW: unspecified EINECS: 232-580-8

LD,,: 42.3 mgkg (M, i.v.);

36.1 mgkg (R, i.v.1

CN: chymopapain

Proteolytic enzyme from the latex of Carica papaya with an approximate molecular weight of 27000 It is

differentiated from papain in electrophoresis behavior, in solubility and in substrate specifity Isolation by acidify

of papaya-latex with HCl, salting out with NaCl and following chromatographic purification The formulation contains L-cysteine as reducing agent

Reference(s):

Jansen, E.F.; Balls, A.K.: J Biol Chem (JBCHA3) 137,459 (1941)

US 2 313 875 (E F Jansen, A.K Balls; 1943; appl 1940)

US 3 558 433 (Baxter Labs.; 26.1.1971; appl 7.1 1.1967)

medical use:

US 4 439 423 (Smith Labs.; 27.3.1984; appl 13.5.1981)

US 3 320 131 (Baxter Labs.; 1967; prior 1963, 1964)

Formulation(s): vial 4 iu, 5 iu, 10 iullOOO iu

Trade Name(s):

D: Discase (Travenol); wfrn USA: Chymodiactin (Smith);

F: Chymodiactine (Knoll) wfm

Trang 8

a-Chymotrypsin

(Alphachymotrypsin)

ATC: B06AA04; SO1 KXOl Use: anti-inflammatory, proteolytic RN: 9004-07-3 MF: unspecified MW: unspecified EINECS: 232-671-2

LD,,,: 89 m g k g (M, i.v.); 2 6 g/kg (M, p.0.):

84 m g k g (R, i.v.); >4 glkg (R, p.0.)

CN: chymotrypsin

Isolation from homogenized bovine pancreas by

1 extraction with 0,25 normal H2S0,

2 Fractionated ammonium sulfate precipitaion of a-chymotrypsinogen (further fractions contain

deoxyribonuclease, chymotrypsinogen B, ribonuclease, trypsinogen)

3 Activation of a-chymotrypsinogcn by dissolution in 0,005 normal HCl, standardization to 0,l molar CaCI, and 0,l molar borate buffer pH 8.0; separation of inactive precipitate after 24 h; precipitation of CaZt as sulfate

4 Fractionated ammonium sulfate precipitation (twice)

5 Crystallization from borat buffer at pH 8.0 (twice)

6 Desaltmg by gel chromatography or dialysis

7 Sterile filtration

8 Lyophilization

Reference(s):

Ullmanns Encykl Tech Chem., 4 Aufl., Vol 10, 536

properties, review:

Niemann, C.: Science (Washington, D.C.) (SCIEAS) 143, 1287 (1964)

Formulation(s): amp ca 5 mg15 ml; ointment ca 5 mg/30 g

Trade Natne(s):

D: Alpha-Chymocutan

(Strathmann)

Alpha-Chymotrase

(Strathmann)

Enzym-Wied

(Wiedemann)-comb

Wobe-Mugos (Mucos)-

comb

F: Alphachymotrypsine

Choay (Sanofi Winthrop)

AlphacutanCe (Leurquin)

Cirkan (Sinbio)-comb

GB: Chymar (Armour); wfm Chymocy clar (Armour);

wfm Chymoral (Armour)-comb.;

wfm Deanase (Consolidated Chemicals); wfm

I: Ribociclina (Puropharma)- comb

Zonulasi (SmithKline Beecham)

J: Chymoral (Tokyo Tanabe) Chymotase (Mochida) Chymozym (Teikoku Hormone)

Kimopsin (Eisal) Zonolysine (Mochida) USA: Orenzyme (Merrell Dow); wfm

((+)-Catechin; (+)-Catechol; Cianidol; Cyanidanol; Use: liver therapeutic (inhibition of lipide

peroxidation) Cyanidol; Dexcyanidanol)

RN: 154-23-4 MF: C,5H,,0, MW: 290.27 EINECS: 205-825-1

CN: (2R-trans)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-I-benzopyran-3,5,7-triol

Trang 9

Cibenzoline C 459

Ingredient of various plants and trees ("catechu" from Uncaria gambir and Acacia catechu),

obtained by extraction w ~ t h water or ethyl acetate

Reference(s):

Freudenberg, K et al.: Ber Dtsch Chem Ges (BDCGAS) 54, 1204 (1 921)

Freudenberg, K ct al.: Ber Dtsch Chem Ges (RDCGAS) 55, 1737 (1922)

Freudenberg, K et al.: Justus Liebigs Ann Chem (JLACBF) 444, 135 (1925)

absolute configuration:

Hardegger,E et al.: Helv Chim Acta (HCACAV) 40, 1819 (1957)

new crystal modifications:

US 4 5 15 804 (Zyma; 7.5.1985; GB-prior 24.2.1982)

salts with basic amino acids:

US4285 964 (Continental Pharma; 25.8.1981; appl 30.8.1979)

GB 2057 437 (Continental Pharma; appl 19.8.1980; USA-prior 30.8.1979)

US 4507 314 (Midit, Soc Fiduciaire; 26.3.1985; appl 20.7.1983)

Fomulation(s): tabl 750 mg

Trade Name(s):

D: Catergen (Zyma); wfm Catergen (Zyma); wfm Transepar (DompC); wfm

F: Caterghe (Zyma); wfm DrenoliveR (Biochimica J: Catergen (Kanebo-Sankyo)

I: Ausoliver (Ausonia); wfm Zanardi); wfm

Use: class I antiarrhythmic

RN: 53267-01-9 MF: C,,H,,N, MW: 262.36 EINECS: 258-453-7

CN: 2-(2,2-diphenylcy clopropy1)-4,5-dihy dro-1 H-imidazole

2 H ~ O or with H,c-?"

0-OH

0 2 mercury oxide or with

N 2

1 -cyano-2,2- ethylenediamine

I Cibenzoline I

Trang 10

460 C Ciclacillin

Reference(s):

DOS 2 359 795 (Hexachimie; appl 30.9.1973; GB-prior 30.1 1.1972,6.2.1973)

DOS 2 359 816 (Hexachimie; appl 30.9.1973; GB-prior 30.1 1.1972,6.2.1973,2.8.1973)

US 3 903 104 (Hexachimie; 9.1975; GB-prior 30.11.1972, 6.2.1973, 2.8.1973)

US 3 905 993 (Hexachimie; 16.9.1975; GP-prior 30.1 1.1972, 6.2.1973)

synthesis of diphenyldiazomethane:

Staudinger, H et al.: Chem Ber (CHBEAM) 49 (1916), 1932

Adamson, J.R et al.: J Chcm Soc., Perkin Trans 1 (JCPRB4) 1975, 2030

Formulation(s): cps 130 mg; tabl 130 mg; vial 100 mg

Trade Name(s):

F: Cipralan (UPSA; 1985) Exacor (Monsanto)

Ciclacillin

(Cyclacillin)

ATC: JOlCA Use: antibiotic RN: 3485-14-1 MF: C,sH23N304S MW: 341.43 EINECS: 222-470-8

LD,,: 5010 mgkg (M, p.0.);

5010 mgkg (R, p.0.);

2500 mgkg (dog, p.0.)

CN: [2S-(2a,5a,6~)]-6-[[(1-aminocyclohexyl)carbonyl]amino]-3,3-dimethyl-7-0~0-4-thia-1-

azabicyclo[3.2.0]heptane-2-carboxylic acid

Ciclacillin I

Reference(s):

US 3 194 802 (American Home; 13.7.1965; appl 7.2.1963; prior 26.2.1962)

US 3 553 201 (American Home; 5.1 l9i'l; appl 3.10.1967; prior 13.5.1966)

alternative synthesis:

DOS 2 755 903 (Dobfar; appl 15.12.1977; I-prior 16.12.1976)

enzymatic:

DAS 2 050 982 (Kyowa Hakko; appl 16.10.1970; J-prior 24.10.1969)

via silyl-derivatives:

US 3 478 018 (American Home; 11.1 1.1969; appl 2.10.1967)

Formulation(s): gran 10 %; tabl 250 mg, 500 mg

Trade Name(s):

D: Ultracillin (Griinenthal); Teejel (Napp)-comb.; wfm Vastcillin (Takeda)

GB: Calthor (Ayerst); wfm Citosarin (Toyo Jozo) USA: Cyclapen (Wyeth); wfm

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