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Pharmaceutical Substances Syntheses, Patents, Applications - Part 43 ppt

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numerous combination preparations F: Alodont Warner-Lambert- comb.. CCtylyre Oberlin GB: Calgel Warner-Lambert Fluprim Roche Gola Sella Golagamma Avantgarde J: Neocepacol Lepetit Neocor

Trang 1

Cetylpyridinium chloride C 421

k

2

1 Trade Name(s):

1 D: Cetrotide (ASTA Medica GB: Cetrotide (ASTA Medlca)

k

I AWD; 1999)

!

f Cetylpyridinium chloride

i

ATC: BO5CAO1; D08AJ03; D09AA07; R02AA06

Use: dls~nfectant, antisept~c

! RN: 123-03-5 MF: C,,H,,ClN MW: 340.00 EINECS: 204-593-9

i LD,,: 10 mglkg (M, i.v.); 108 rnglkg (M, p.o.),

E 200 mgkg (R, p.o.1

CN 1-hexadecylpyridinium chloride

pyridine cetyl chloride Cetylpyridinium chloride

Reference(s):

Budesinsky-Protiva, 53 1-532

Formulation(s): eff tabl 1.5 mg, 3 mg; lozenge 1.4 mg; sol 5 mg/lO rnl (0.01 %, 0.05 %); tabl 2 mg

Trade Name(s):

D: Dobendan (Cassella-med) Merocame (Seton)-comb Pcnaten (Johnson &

W~ilfing) I: Borocaina (Schiapparelli Ragaden (Ganassini)

Roland)-comb

numerous combination

preparations

F: Alodont (Warner-Lambert)-

comb

Broncorinol (Roche

Nicholas)-comb

CCtylyre (Oberlin)

GB: Calgel (Warner-Lambert)

Fluprim (Roche) Gola (Sella) Golagamma (Avantgarde) J:

Neocepacol (Lepetit) Neocoricidin (Schering-

Neoformitrol (Sandoz) Neogola (Sella) Noalcool (Sella)

numerous combination preparations

Colgen 123 (Kowa)-comb Pabron Troche (Taisho) Suprol (Iwaki) Cepacol (Lakeside)-comb.; wfm

Cobrex (Reid-Rowell)- comb.; wfrn

Chenodeoxycholic acid

(Chenodiol; Acide chenodtoxycholique;

Chenodesoxycholsaure)

ATC: AOSAAOI Use: choleretic, anticholethithogenic dissolution of cholesterol gallstones

RN: 474-25-9 MF: C24H4004 MW: 392.58 EINECS: 207-481-8

LD,: 100 mgkg (M, i.v.); 3 glkg (M, p.0.);

106 mdkg (R, i.v.); 4 glkg (R, p.0.);

> I d k g (dog, PO.)

CN: (3a,5P,7a)-3,7-dihydroxycholan-24-oic acid

Trang 2

422 C Chenodeoxycholic acid

0 0

0/CH3 H~cAo"XH,

+ HO-CH, -+ E Me ,,\+ - 1

Me H

'"OH H O."' H H

"'OH

methyl 3a,7a-diacetoxy- methyl 3 a 7 ~ - d i o c e t o x y

12a-hydroxycholonote (I) 12-oxocholonote (11)

1 H2N-NH2 H20 H O ~ O H , 200 O C

2 HCI

1 hydrozine hydrote

I Chenodeoxycholic ocid

~ i e s e r , L.F.; Rajagopalan, S.: J Am Chem Soc (JACSAT) 72,5530 (1950)

Hauser, E et a].: Helv Chim Acta (HCACAV) 43, 1595 (1960)

Hofmann, A.F.: Acta Chem Scand (ACHSE7) 17, 173 (1963)

Sato, Y.; Ikekawa, N.: J Org Chem (JOCEAH) 24, 1367 (1959)

purification:

DOS 2 302 744 (Union International; appl 20.1.1973; GB-prior 20.1.1972)

DE 2 404 102 (Schering AG; appl 25.1.1974)

DOS 2 613 346 (Diamalt; appl 29.3.1976)

US 4 163 017 (Diamalt; 31.7.1979; D-prior 29.3.1976)

JP-appl 52 153 955 (Tokyo Tanabe; appl 18.6.1976)

isolation from animal bile:

US 3 919 266 (Intellectual Property Dev Corp.; 11.1 1.1975; prior 21.9.1972, 19 - 1973)

US 4 014 908 (Intellectual property Dev ~ o r p ; 29.3.1977; prior 21.9.1972, 19.1 1.1973,7.5.1974, 30.5.1974, 20.2.1976)

US 4 072 695 (Intellectual Property Dev Corp.; 7.2.1978; prior 21.9.1972, 19.1 1.1973, 7.5.1974, 30.5.1974, 20.2.1976, 17.9.1976)

combination with hymecromone:

DOS 2 700 085 (Lipha; appl 4.1.1977; F-prior 13.7.1976)

Trade Nante(s):

D: Chenofalk (Falk) Hekbilin (Strathmann)- GB: Chendol (CP Pharrn.)

F: ChCnodex (Hoechst HoudC) Chenossil (Midy)

Trang 3

Chloral hvdrate C 423

Fluibil (Zambon Italia) Cholasa ('Tokyo Tanabe) USA: Chcnix (Reid-Rowell);

Use: hypnotic, scdative RN: 302-17-0 MF: C,H,CI,O, MW: 165.40 EINECS: 206-1 17-5

LD56 530 mglkg (M, i.v.); 1100 mglkg (M, p.o.1;

479 m a g (R, p.0.)

CN: 2,2,2-trichloro-1 ,l -ethanediol

ethanol trichloro- 1 Chlarol hydrate

acetaldehyde (1)

Reference(s1:

UUmanns Encykl Tech Chem., 4 Aufl., Vol 9, 377

Formulation(s): cps 250 mg, 500 mg

Trade Nume(s):

D: Chloraldurat (Pohl) GB: Welldorm elixir (S & N) USA: Noctec (Squibb); wrm F: numerous combination I: Cloral (Tariff Nazionale) generica

Chloralodol

(Chlorhexadol)

ATC: N05CC02 Use: hypnotic

RN: 3563-58-4 MF: C,HI,C1303 MW: 265.56 EINECS: 222-634-9

CN: 2-methyl-4-(2,2,2-trichloro-1-hydroxyethoxy)-2-pentanol

2-methylpentane- chloral hydrate

2,4-diol

Reference(s):

U S 2 931 838 (Det Danske Med.-& Kern.-Komp.; 5.4.1960; DK-prior 8.12.1956)

Fonnulation(s): tabl 400 mg, 800 mg

Trang 4

424 C Chlorambucil

Trade Narne(s):

GB: Medodorm (Medo); wfm

Use: antineoplastic RN: 305-03-3 MF: C,,H,,C12N02 MW: 304.22 EINECS: 206-162-0

LD,,,: 80 m g k g (M, p.0.);

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

CN: 4-[bis(2-chloroethyl)amino]benzenebutanoic acid

ocetanilide succinic 4-(4-ocetamidophenyl)-

anhydride 4-oxobutanoic ocid

oxide 4-(4-ominopheny1)-

Reference(s):

US 3 046 301 (Borroughs Wellcome; 24.7.1962; prior 29.10.1959)

1 POCI,

2 H 2 0

1 phosphorus ~ld

Formulation(s): drg 2 mg; tabl 2 mg, 5 mg

oxychlaride

Trade Narne(s):

D: Leukeran (Glaxo GB: Leukeran (Glaxo Linfolysin (Nuovo ISM)

F: Chloraminophtne (Techni- I: Leukeran (Glaxo Wellcome)

Chlorambucil

JOlBAOl; SOlAAOl; S02AAO1; S03AA08

Use: antibiotic RN: 56-75-7 MF: C, ,H12C12N20, MW: 323.13 EINECS: 200-287-4

LD,,,: 110 m g k g (M, i.v.); 1500 mglkg (M, p.0.);

171 mg/kg (R, i.v.); 2500 mg/kg (R, p.0.)

CN: [R-(R*,R*)]-2,2-dichloro-N-[2-hydroxy-l-(hydroxymethyl)-2-(4-nitrophenyl)ethyl]aceta~de

Trang 5

Chloramphenicol C 425

2 HCI

1 hexamethylene- "."-"a OH.[

4'-nitro-

acetophenone

2-bromo-4'-nitro- ocetophenone

2-amino-4'-nitroaceto- phenone hydrochloride (I)

acetic anhydride 2-acetamido-4'-nitro-

acetophenone

D-camphorsulfonic ocid

1 Chloramphenicol I

H C CH,

cinnarnyl

alcohol

2 - b r o m o - l - phenyl-12- proponediol

5-bromo-2.2- dimethyl-4- phenyl-l,3- dioxane (IV)

DL-threo-5-

omino-2.2-

dirnethyl-4-

phenyl-

1.3-dioxone

D(-)-threo-5- amino-2,2- dirnethyl-4- phenyl-1,3- dioxane

D(-)-threo-5-di- chloroacetarnido- 2.2-dimethyl-4- phenyl-1.3-dioxane (V)

Trang 6

426 C Chloramphenicol

p h e n y l ) 1,3-propane-

dial dinitrate

Rqference(s):

Ehrhart-Ruschig IV, 398 ff

a Long, L.M.; Troutman, H.D.: J Am Chem Soc (JACSAT) 71,2469,2473 (1949)

US 2 483 871 (Parke Davis; 1949; appl 1948)

US 2 483 884 (Parke Davis; 1949; appl 1948)

US 2 483 885 (Parke Davis; 1949; appl 1949)

US 2 483 892 (Parke Davis; 1949; appl 1948)

US 2 687 434 (Parke Davis; 1954; appl 1953)

US 2 651 661 (Monsanto; 1953; appl 1950)

US 2 786 870 (Parke Davis; 1957; appl 1954)

Rebstock, M.C et al.: J Am Chem Soc (JACSAT) 71,2458-2468 (1949)

b BE 539 991 (Boehringer Mannh.; appl 1955; D-prior 1954)

DE 1 01 6 718 (Boehringer Mannh.; appl 1953)

BE 558 378 (Boehringer Mannh.; appl 14.6.1957; D-prior 27.6.1956,22.12.1956)

alternative synthesis (from benzaldehyde and nitromethane o r 0-nitroethanolvia 2-n~tro-1-phenyl- l,3- propanediol):

DE 862 302 (Parke D a m ; appl 1949; USA-prior 1948)

DE I 064 937 (Roehringer Mannh.; appl 1957)

DOS 2 708 301 (Egyt; appl 25.2.1977; H-pnor 25.2.1976)

0-3-monophosphate:

DAS 1 668 96 1 (Roussel-Uclaf; appl 20.2.1968; I-prior 20.2.1967, 18.5.1967)

Formulation(s): amp 1 g (as hydrogen succinate sodium salt); cps 250 mg, 500 mg; ear drops 5 g/100 ml,

50 mglg; eye drops 5 mg, 10 mg; ointment 1 % (10 mglg) Trade Name(s):

D: Aquamycetin (Winzer)

Chloramphenicol-PW

(Pharma Wernigerode)

Chloramsaar (Chephasaar)

Oleomycetin (Winzcr)

Paraxin (Boehringer

Mannh.)

Thilocanfol C (Alcon)

numerous combination

preparations

F: CCbtdexacol (Chauvin)-

comb

CCbCnicol (Chauvin)

numerous combination

preparations

GB: Chloromycetin (Goldshield) Kemicetine Succinate (Pharmacia & Upjohn) Minims Chloramphenicol (Chauvin)

SNO Phenicol (Chauvin) I: Chemicetina (Carlo Erba) Chloromycetin (Parke Davis)

Cloram (Formulario Naz.) Minims (Smith & Nephew) Mycetin (Farmigea) Sificetina (SIFI) Vitamfenicolo (Allergan)

numerous salts and combination preparations J: Antacin (Sumitorno) Chloromycetin (Sankyo) Kemicetine (Fujisawa) Myclocin (Takeda) Paraxin (Yamanouchi) Synthomycetine (Otsuka) numerous gcncrics and combination preparations USA: Elase-Chloromycetin (Fujisawa)

Trang 7

Chlorazanil C 427

Use: diuretic RN: 500-42-5 MF: C9HRC1N5 MW: 221.65 EINECS: 207-904-6

LD,,: 300 mglkg (M, p.0.);

16 mglkg (R, i.v.)

CN: N-(4-chloropheny1)- 1,3,5-triazine-2,4-diamine

monohydrochloride

RN: 2019-25-2 MF: C,HRC1N5 HC1 MW: 258.1 1 EINECS: 21 7-962-4

1-(4-chlaropheny1)- formic I C ~ o r a z a n i l

biguonide hydrochloride acid

Reference(s):

DE 1 008 303 (Heumann & Co.; appl 1955)

Formulation(s): tabl 150 mg

Trade Name(s):

D: Orpidan-150 (Heumann);

wfm

Use: anticholinergic RN: 522-18-9 MF: C,,H,,ClN,O MW: 435.01 EINECS: 208-323-0

CN: I-[2-[(2-chlorophenyI)phenylmethoxy]ethyl]-4-[(2-methylphenyl)methyl]piperazine

dihydrochloride

RN: 5576-62-5 MF: C,,H,,ClN,O 2HCl MW: 507.93 EINECS: 226-951-3

LD,,: 1400 mglkg (M, p.0.);

66 mgkg (R, i.v.); 3350 mglkg (R, p.0.)

Reference(s):

BE 549 420 (H Morren; appl 10.7.1956),

2-chlarobenz- 1 -(2-hydroxyethyl)-

Formulation(s): tabl 30 mg (as dihydrochloride)

Chlorbenzoxamine hydlyl chloride 4-(2-methylbenzy1)-

piperazine

Trang 8

4 2 8 C Chlorcyclizine

n a d e Name(s):

D: Libratar (UCB); wfm Gastomax (Brocchieri); Libratar (UCB-Smith)

Chlorcy clizine

(Histachlorazine)

ATC: R06AE04 Use: antihistaminic RN: 82-93-9 MF: ClxH2,CIN2 MW: 300.83 EINECS: 201-446-0

CN: 1-[(4-chlorphenyl)phenylmethyl]-4-methylpiperazine

monohydrochloride

RN: 14362-3 1-3 MF: C,,H2,CIN2 HCI MW: 337.29

dihydrochloride

RN: 129-71-5 MF: ClxH2~C1N2 2HCI MW: 373.76

4-chlorobenz- 1 -methyl- / Chlorcyclizine 1

hydryl chlaride piperazine

Reference(s):

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

Formulation(s): tabl 50 mg (as hydrochloride)

Trade Name(s):

F: Di-ParalCne (Abbott); wfm I: Clorciclizina (Tariff USA: Mantadil (Burroughs

Di-Paralene (Abbott); wfm hydrocortisone; wfm

Use: tranquilizer RN: 58-25-3 MF: C,,H,,ClN,O MW: 299.76 EINECS: 200-371-0

LD,,,: 95 m g k g (M, i.v.); 200 m g k g (M, p.0.);

165 mg/kg (R, i.v.); 392 mglkg (R, p.0.)

CN: 7-chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-amine 4-oxide

2-arnino-5-

chlorobenzo-

phenone

6-chloro-2-chloromethyl 4-phenylquinazoline 3-oxide (I)

Trang 9

Chlorhexidine C 429

g

Chlordiazepoxide

f

:: Referencefs):

US 2 893 992 (Hoffmann-La Roche; 7.7.1959; prior 15.5.1958)

1 ,DE 1096 363 (Hoffmann-La Roche; appl 24.4.1959; USA-prior 15.5.1958)

P Stembach, L.H et al.: J Org Chem (JOCEAH) 26, 11 11 (196 1)

1

? Formulation(s): drg 10 mg; f c tabl 5 mg; tabl 5 mg, 10 mg, 25 mg

D: Limbatril (Roche)-comb

Multum (Rosen Pharma)

Radepur (ASTA Medica

AWD)

F: Librax (Roche)-comb

GB: Librium (Roche)

1: Diapatol (Teofarma)-comb

Librium (Roche)

Limbitryl (Roche)-comb

Psicofar (Terapeutico) USA: Librax (Roche Products; as Reliberan (Geymonat) hydrochloride)

Sedans (Ganassini)-comb Librium (Roche Products; Seren Vita (Synthelabo) as hydrochloride) J: Balance (Yamanouchi) Limbitrol (Roche Products)

Sophiamin (Kyowa Yakuhin)

Trakipearl (Hishiyama)

D09AA12; R02AA05; SO1 AX09; S02AA09; S03AA04

Use: antiseptic RN: 55-56-1 MF: C22H,oC12Nlo MW: 505.46 EINECS: 200-238-7

LD,: 24 mgkg (M, i.v.); 25 15 nig/kg (M, p.0.);

21 mgkg (R, i.v.); 9200 pL/kg (R, p.0.)

CN: N,N'-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide

diacetate

RN: 56-95-1 MF: C22H30C12Nlo 2C2H,02 MW: 625.56 EINECS: 200-302-4

dihydrochloride

RN: 3697-42-5 MF: C22H~oC12N~o~2HCI MW: 578.38 EINECS: 223-026-6

LD,,: >5 g/kg (M, s.c.)

di-~.glW~nate

RN: 18472-51-0 MF: C22H30C12NLo 2C6H1207 MW: 897.77 EINECS: 242-354-0

24.2 mglkg (R, i.v.); 2 @kg (R, p.0.)

Trang 10

430 C Chlorhexidine

hexornethylenebis- 4-chlorooniline

(dicyonodiornide) hydrochloride

I Chlorhexidine I

hexornethylenediornine (4-chlorophenyl)-

dihydrochloride dicyonodiomide

Reference(s):

GB 705 838 (ICI; appl 1951; valid from 1952)

1

$

I Formlclation(s): gel 1 g1100 g; powder 1 g1100 g; sol 0.1 g/100 g, 0.2 g1100 g, 1 g/50 ml (as digluconate)

D: Chlorhexamed (Blend-a- Hibidil (Zeneca; as Hibidil (Zeneca)

C hlorhexidindigluconat Hibiscrub (Zeneca; as Hibitane (Zeneca) (Engelhard)

Corsodyl (SmithKline Beecham OTC Medicines) Frubilurgyl (Boehringer Mannh.)

Hansamed (Beiersdorf) numerous combination preparations

F: Antalyre (Boehringer Ing.;

as g1uconate)-comb

Collunovar (Dexo; as gluconate)

Collupressine (SynthClabo;

as g1uconate)-comb

Collustan (Oberlin; as dig1uconate)-comb

Corsadyl (SmithKline Beecham; as digluconate) CytCal (Sinbio; as g1uconate)-comb

Dacryne (Johnson &

Johnson) Diseptine (Nicholas; as g1uconate)-comb

Eludril (Inava; as

digluconate) Hibitane (Zeneca; as gluconate)

Merfene (Novartis; as

- gluconate) Plurexid (Evans; as gluconate) Prexidine (Pred; as gluconate) SepCal (Sinbio; as digluconate) Thiovalone (Eurorga; as diacetate)-comb

GB: Bactigras (Smith &

Nephew) Chlorhexitulle (Hoechst) Corsodyl (SmithKline Beecham)

numerous preparations I: Clorex (Formulario Naz.) Contact (Vaas; as

Lenixil (Eurospital) Neomercurocromo (SIT) Neoxene (Ecobi) Odontoxina (Ipfi) Oramil (Ganassini) Plak Out (Byk Gulden) Sanoral (Kemiprogress) Savlodil (Zeneca)-comb Savlol (Zeneca)-comb Vaxidina (Vaas) Vidermina (Ganassini) J: Hexad01 (Green Cross) Hibiscrub (ICI) Hibitane Digluconate (Sumitorno) Maskin (Maruishi) Pabron (Taisho Seiyaku) White Go1 (Tamagawa Eizai)

White Rive (Eisai) USA: Betasept (Purdue hydrochloride) Frederick; as gluconate) Corsodyl (SmithKline Hibiclens (Zeneca; as

Effetre (Farma3 Medicalex) Hibistat (Zeneca; as

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