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Pharmaceutical Substances Syntheses, Patents, Applications - Part 82 pdf

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CN: 2-[[3-trifluoromethylphenyl]amino]benzoic acid 2-2-hydroxyethoxyethyl ester... flufenornic ocid 2-2-ch1oroethoxy- Etofenornate potossiurn salt ethanol 4, v References: DE 1 939 1

Trang 1

Etizolam E 81 1

Reference(s):

DE 1 493 533 (Chemie Griinenthal; appl 10.4.1964)

DAS 1 493 567 (Chemie Griinenthal; appl 7.10.1965)

US 3 930 017 (Chemie Griinenthal; 30.12.1975; D-prior 7.10.1965)

US 4 110 470 (Chemie Griinenthal; 29.8.1978; D-prior 7.10.1965)

Formulation(s): cps 20 mg

Tmde Name(s):

D: Skleronorm (Griinenthal);

w fm

Use: benzodiazepine tranquilizer, anxioly tic, sedative

RN: 40054-69-1 MF: CI,H,,ClN4S MW: 342.85

LD,: 4258-4358mgkg (M, p.0.); >5000 mglkg (M, LC.);

3619-3509 mgkg (R, p.0.); >5000 m g k g (R, s.c.)

CN: 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2[1,2,4]triazolo[4.3-a][1,4]diazepine

0

2 HBr, CH3COOH

1

1 N-benzyloxycarbonyl- 2'-chlom-2-cyono- butyr- 2-amino-3-(2- glycyl chloride

acetophenone aldehyde chlarobenzayl)-

5-ethylthiophene

CH3COOH, pyridine

-

NH2

1.3-dihydro- 7-ethyl-2H-thieno- [2.3-el-1,4-

Trang 2

8 1 2 E Etodolac

1 N2H4

II -b

1 hydrazine

0 H

Reference(s):

Nakanishi, M et al.: J Med Chem (JMCMAR) 16, 214 (1973)

Nakanishi, M et al.: Arzneim.-Forsch (ARZNAD) 22, 1905 (1972)

Tahara, T et al.: Arzneim-Forsch (ARZNAD) 28, 1153 (1978)

DOS 2 229 845 (Yoshitomi; appl 19.6.1972; J-prior 18.6.1971,21.6.1971, 30.6.1971, 8.7.1971, 10.7.1971, 13.7.1971)

US 3 904 641 (Yoshitomi; 9.9.1975; J-prior 18.6.1971, 21.6.1971, 30.6.1971, 8.7.1971, 10.7.1971, 13.7.1971)

Formulation(s): drops 0.05 %; tabl.0.5 mg, 1 mg

Trade Natne(s):

Etodolac

(Etodolic.acid; Etodolsaure)

ATC: MOlAB08 LJse: anti-inflammatory, analgesic RN: 41340-25-4 MF: C,,H,,NO, MW: 287.36

LD,,: 593 mgkg (M, p.0.);

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

CN: 1,8-diethyl- l,3,4,9-tetrahydropyrano[3,4-blindole-1 -acetic acid

2-ethyl-

aniline

2-ethylbenzene- diazonium chloride

2-ethylphenyl- hydrazine (I)

0 0

ethyl 3-oxopentanoate 4-hydroxy

butonal

KOH

Etodolac

Trang 3

Etodroxizine E 8 1 3

Referencefs):

US 3 939 178 (American Home Products; 17.2.1976; appl 15.9.1972)

US 3 843 681 (American Home Products; 22.10.1974; appl 1.6.1971)

GB 1 391 005 (American Home Products; appl 1.6.1972; USA-prior 1.6.1971)

DOS 2 226 340 (American Home Products; appl 30.5.1972; USA-prior 1.6.1971)

FR 2 140 154 (American Home Products; appl 1.6.1972; USA-prior 1.6.1971)

Demerson, C.A et al.: J Med Chem (JMCMAR) 18, 189 (1975)

Demerson, C.A et al.: J Med Chem (JMCMAR) 19, 391 (1976)

mcemate resolution:

US 4 520 203 (American Home Products; 28.5.1985; appl 16.8.1983)

US 4 544 757 (American Home Products; 1.10.1985; appl 16.2.1984)

Formulation(s): cps 200 mg, 300 mg; s r tabl 400 mg, 600 mg; tabl 100 mg, 200 mg, 400 mg, 500 mg

Trade Name(s):

F: Lodine (Wyeth) 1: Edolan (Lepetit; 1987) Ostelac (Wyeth)

GB: Lodine SR (Monmouth; Lodine (Wyeth; 1987) USA: Lodine (Wyeth-Ayerst) 1985) J: Hypen (Nippon Shinyaku)

Use: tranquilizer, hypnotic RN: 17692-34-1 MF: C,,H,,ClN,O, MW: 418.97

LD,: 70 mglkg (M, i.v.); 540 mglkg (M, p.0.);

58 mglkg (R, i.v.); 920 mglkg (R, p.0.)

CN: 2-[2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]ethoxy]ethanol

Reference(s):

GB 817 231 (UCB; appl 1957; B-prior 1956)

Formularion(s): tabl 50 mg

Trade Name(s):

D: Vesparax (UCB)-comb.; F: Drimyl (Cassenne); wfm

wfm

N(C2H5)3

+ C I ~ O P O ~ O H - triethylamine

CI

Etofenamate

y-O-o-OH

CI

Etodroxizine

ATC: M02AA06 Use: anti-inflammatory

(cf buclizine

synthesis)

RN: 30544-47-9 MF: C,,H,,F,NO, MW: 369.34 EINECS: 250-231-8

LD,: 75 mglkg (M, i.v.); 743 mglkg (M, p.0.);

139 m a g (R, i.v.); 292 mglkg (R, p.0.)

CN: 2-[[3-(trifluoromethyl)phenyl]amino]benzoic acid 2-(2-hydroxyethoxy)ethyl ester

Trang 4

814 E Etofibrate

+ CI- 0 -OH -

flufenornic ocid 2-(2-ch1oroethoxy)- Etofenornate

potossiurn salt ethanol

(4, v

Reference(s):

DE 1 939 1 12 (Troponwerke; appl 1.8.1969)

US 3 692 8 18 (Troponwerke; 19.9.1972; D-prior 1.8.1969)

Trade Narne(s):

D: Algesalona (Solvay Traumon (Bayer Vital;

Arzneimittel) 1984)

Rheumon (Bayer Vital; I: Bayrogel (Bayropharm;

Use: antihyperlipidemic, cholesterol depressant

RN: 3 1637-97-5 MF: C,,H,,ClNO, MW: 363.80 EINECS: 250-743- 1

CN: 3-pyridinecarboxylic acid 2-[2-(4-chlorophenoxy)-2-methyl-l-oxopropoxy]etl~yl ester

2-(4-chlorophenoxy)- ethylene

2-methylpropionic glycol

acid

Reference(s):

DOS 1 941 217 (Merz & Co.; appl 13.8.1969)

nicotinoyl

DOS 2 519 535 (Alter S.A.; Madrid; appl 2.5.1975; E-prior 29.5.1974)

DOS 2 53 1 254 (Merz & Co.; 12.7.1975; GB-prior 5.9.1974)

DOS 2 542 413 (Alter S.A.; appl 23.9.1975; E-prior 4.6.1975)

DOS 2 542 414 (Alter S.A.; appl 23.9.1975; E-prior 4.6.1975)

US 3 723 446 (Merz & Co.; 27.3.1973; appl 12.8.1970; D-prior 13.8.1969)

Etofibrote

chloride

Trang 5

Etofylline E 815

Trade Narne(s):

D: Lipo-Merz (Merz & Co.;

1974)

(Oxyethyltheophylline; Hydroxyathyltheophyllin) Use: cardiotonic, bronchodilator

RN: 519-37-9 MF: C,H12N403 MW: 224.22 EINECS: 208-269-8

LD,,: 344 mglkg (M, i.v.); 400 mglkg (M, p.0.);

486 mg/kg (R, i.v.); 710 mglkg (R, p.0.)

CN: 3,7-dihydro-7-(2-hydroxyethyl)-1,3-dimethyl-lH-purine-2,6-dione

ethylene

oxide

US 2715 125 (Cane's Chem Works; 1955; prior 1953)

Formuiation(s): drg 50 mg, 80 mg in comb

Trade Narne(s):

D: Coroverlan (Verla) F: Oxyphylline (Amido); wfm J: Oxyphylline (Sankyo) Eucebral (Siidmedica)- I: Teostallarid (SmithKline

Use: anesthetic, hypnotic

RN: 33125-97-2 MF: CI,H,,N2O2 MW: 244.29 EINECS: 251-385-9

LD,,,: 29.5 mglkg (M, i.v.); 650 mglkg (M, p.0.);

14.8 mglkg (R, i.v.)

CN: (R)-1-(I-phenylethy1)-1 H-imidazole-5-carboxylic acid ethyl ester

Trang 6

816 E Etoperidone

(R)-1 -phenyl- ethyl

ethylamine chloroocetate

(R)-N-(ethoxycarbo- ny1methyl)- 1 -phenyl- ethylamine

1 NaOC2H5 HCOOC2H5 THF

H ~ c > , , D 2 XSCN HCI

1 sodium ethylate, ethyl formote

( ~ ) - ~ - ( ~ t h ~ ~ ~ ~ ~ ~ b ~ - 2 potassium rhodanide (R)-5-ethoxycar-

imidazole (11)

Keference(s):

US 3 354 1'73 (Janssen; 21.1 1.1967; prior 16.4.1964)

DAS 1 545 988 (Jansscn; appl 14.4.196s; USA-prior 16.4.1964)

Janssen, P.A.J et al.: Arzneim.-Forsch (ARZNAD) 21, 1234 (1971)

injection solution:

DOS 2 937 290 (Janssen; appl 14.9.1979; USA-prior 14.9.1978)

For~nulation(s): amp 2 mglml, 20 mgIlO ml

Trade Name(s):

D: Hypnomidate (Janssen- F: Hypnomidate (Janssen-

Radenarcon (ASTA Medica GB: Hypnomidate (Janssen)

AW D) USA: Amidate (Abbott); wfm

Use: antidepressant

RN: 52942-3 1-1 MF: C,9H28CINS0 MW: 377.92

CN: 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-4,5-diethyl-2,4-dihydro-3H-1,2,4-triazol-3-one

4,5-diethyl- 1 -bromo-3- 2-(3-chloropropyl)-

b5-1 ,2.4- chloropropane 4,5-diethyl-A5-

Trang 7

Etopophos E 817

H ~ C " ~ ~ ' N " - " N >

N-(5-chlorophenyl)-

piperozine

Etoperidone

No, dioxone

Reference(s):

DOS 2 351 739 (Angelini Francesco; appl 15.10.1973; I-prior 16.10.1972)

US 3 857 845 (Angelini Francesco; 3 1.12.1974; I-prior 16.10.1972)

use as anriparkinsonian:

US4 162 318 (Angelini Francesco; 24.7.1979; I-prior 5.5.1976)

US 4 132 79 1 (Angelini Francesco; 2.1.1979; I-prior 5.5.1976)

combinarion with L-dopa a s anriparkinsonian:

US4 131 675 (Angelini Francesco; 26.12.1978; prior 9.2.1978)

Formulation(s): cps 25 mg, 50 mg

Trade Name(s):

I: Staff (Sigma-Tau); wfm

Etopophos

(BMY-4048 1-30)

ATC: LOlCB Use: antineoplastic (podophyllotoxin derivative)

RN: 122405-33-8 MF: C2yH31Na20,6P MW: 712.51

CN: [5R-[5a,5a~,8aa,9~(R*)]]-5-[3,5-dimethoxy-4-(phosphonooxy)phenyl]-9-[(4,6-O-ethylidene-~-~- glucopyranosyl)oxy]-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d]- 1,3-dioxol-6(5aH)-one disodium

salt

hexahydrate

RN: 151062-35-0 MF: C2,H3,Na2016P 6H20 MW: 820.60

free acid

RN: 117091-64-2 MF: C2,H3,O1,P MW: 668.54

Trang 8

1 P O C I ~ S H3CYNyCH3 ,

CH3CH3

2 NoHC03 H 2 0 )-

1 N,N-diisoprapyl-

ethylornine

0 H

Etopofos

CB 2 207 674 (Bristol-Myers Squibb; appl 3.8.1988; USA-prior 27.5.1988,4.8.1987)

synthesis of'etoposide-4'-phosphate:

EP 51 1 563 (Bristol-Myers Squibb; appl 16.4.1992; USA-prior 29.4.1991, 20.2.1992)

EP 567 089 (Nippon Kayaku; appl 21.4.1 993; J-prior 24.4.1992)

preparation of'etoposide without extensive purification:

EP 652 226 (Bristol-Myers Squibb; appl 3.11.1994; USA-prior 4.11.1993)

stable hemhydrate with improved storage stability:

EP 548 834 (Bristol-Myers Squibb; appl 18.1 2.1992; USA-prior 23.12.1991)

Formulation(s): vial 100 mg

Trade Name(s):

USA: Etopophos (Bristol-Myers)

Etoposide

(VP- 16-21 3)

ATC: LOlCBOl Use: antineoplastic, podophyllotoxin derivative

RN: 33419-42-0 MF: C2,H320,3 MW: 588.56 EINECS: 251-509-1

LD,,,: 15.07 m g k g (M, i.v.); 215 mglkg (M, p.0.);

75 m g k g (R, i.v.); 1784 mglkg (R, p.0.)

CN: [5R-[5a,5a~,8aa,9~(R*)]]-9-[(4,6-0-ethylidene-~-~-glucopyranosyl)oxy]-5,8,8a,9-tetrahydro-5-(4- hydroxy-3,5-dimethoxyphenyl)furo[3',4':6,7]naphtho[2,3 1,3-dioxol-6(5aH)-one

Trang 9

Etoposide E 8 19

4'-benzyloxycarbonyi-

4'-demethylepipodo-

phyllotoxin

(cf teniposide

synthesis)

4.6-0-(R)-ethylidene- 2,3-di-0-acetyl-8-D-

glucopyronose

1 Zn(OCDCH3), NaOCH,

2 Hz Pd-C

1 zinc acetote

Etoposide

Reference(s):

DE 1 643 521 (Sandoz; prior 9.12.1967)

US 3 524 844 (Sandoz; 18.8.1970; CH-prior 21.6.1965)

CH 514 578 (Sandoz; appl 27.2.1968)

Keller-Juseen, C et a].: J Med Chem (JMCMAR) 14,936 (1971)

US 5 637 680 (Nippon Kayaku; 10.6.1997; J-prior 24.4.1992)

EP 778 282 (Nippon Kayaku; appl 3.12.1996; J-prior 4.12.1995,8.12.1995)

Allevi, P et al.: J Org Chem (JOCEAH) 58,4175 (1993)

Formulation(s): cps 50 mg, 100 mg; vial 100 mg15 ml, 150 mgl7.5 ml, 500 mg125 ml, 1 g150 ml

Trade Narne(s):

D: Etomedac (medac) Etoposide Pierre Fabre J: Lastet (Nippon Kayaku; Vepesid (Bristol-Myers (Pierre Fabre) 1987)

Squibb; 1980) Vepeside (Novartis) Vepesid (Bristol Squibb;

F: Celltop (ASTA Medica) GB: Vepesid (Bristol-Myers 1987)

Etopophos (Bristol-Myers Squibb; 1981) USA: Ve Pesid (Bristol-Myers Squibb) I: Vepesid (Bristol It Sud; Squibb; 1983)

1982); wfm

Trang 10

820 E Etozolin

Use: diuretic RN:

LDso:

CN:

7"

73-09-6 MF: CI3H2,N2O3S MW: 284.38 EINECS: 200-794-0

8670 mglkg (M, p.0.);

10250 m g k g (R, p.0.)

[3-methyl-4-oxo-5-(l-piperidinyl)-2-thiazolidinylidene]acetic acid ethyl ester

O\\ / O - ~ ~ s

H ~ c ~ / ~ * ~

h-0 f N n o V C H 3 - I

ethyl 3-methyl-

4-oxothiozolidin-

2-ylideneacetate

Rejerence(s):

US 3 072 653 (Warner-Lambert; 8.1.1963; appl 6.3.1961)

DE 1 160 441 (Warner-Lambert; appl 21.10.1961; USA-prior 6.3.1961)

GB 1 022 047 (Warner-Lambert; appl 23.1 1.1962)

GB 1 022 048 (Warner-Lambert; appl 23.1 1.1962)

Satzinger, G.: Justus Liebigs Ann Chem (JLACBF) 665, 150 (1963)

ethyl 5-bromo-3-

Formulation(s): tabl 200 mg, 400 mg

Etozolin

Trade Name(s):

D: Elkapin (Godecke); wfm I: Elkapin (Parke Davis)

lidin-2-ylideneacetate

Use: antipsoriatic RN: 54350-48-0 MF: C,,H,,03 MW: 354.49 EINECS: 259-119-3

LD,,: 1176 m g k g (M, i.p.); >2000 mgkg (M, p.0.);

>2000 m g k g (R, i.p.); >4000 (R, p.0.)

CN: (all-E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid ethyl ester

1 HCI

methyl

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