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Pharmaceutical Substances Syntheses, Patents, Applications - Part 79 potx

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numerous generics I: Estraderm Ciba-Geigy Progynon Schering J: Ovahormon Pasta Teikoku Zoki Alora Procter & Gamble Climara Berlex Estraderm Novartis Estring Pharmacia & Upjohn Estro-Plus

Trang 1

Estradiol benzoate E 781 Vagifem (Novo Nordisk;

RhBne-Poulenc Rorer)

F: Estrofem (Novo Nordisk)

Oestrogel (Besins-

Iscovesco)

Prkmarin (Wyeth-Ayerst)-

comb

Trisequens (Novo

Nordisk)-comb

Estradiol benzoate

(Oestradiolbenzoat)

GB: Cycloprogynova (ASTA USA:

Medica) Hormonin (Shire) Trisequens (Nova)-comb

numerous generics I: Estraderm (Ciba-Geigy) Progynon (Schering) J: Ovahormon Pasta (Teikoku Zoki)

Alora (Procter & Gamble) Climara (Berlex)

Estraderm (Novartis) Estring (Pharmacia &

Upjohn) Estro-Plus (Rocky Mtn.)- comb

FemPatch (Parke Davis) Vivelle (Novartis)

ATC: G03CA Use: estrogen

RN: 50-50-0 MF: C25H2,0, MW: 376.50 EINECS: 200-043-7

eatmdiol

(9 v.)

benzoyl

Referencefs):

a US 2 054 271 (Schering Corp.; 1933; D-prior 1932)

GB 485 388 (Lab Franq de ChimiothCrapie; appl 1936)

b DRP 641 994 (Schering AG; appl 1932)

alternative synthesis:

US 2 225 419 (Schering Corp.; 1940; D-prior 1937)

US 2 156 599 (Ciba; 1939; CH-prior 1936)

Formulation(s): amp 2 mglml, 10 mglml, 50 mg12 ml; sol 5 mg1100 ml

Trade Namefs):

D: Alpicort F (Wo1ff)-comb

Jephagynon (Wo1ff)-comb

Ney Normin (vit0rgan)-

comb

Syngynon (Jenapharm)

I? Benzo-Gynoestryl

(Roussel)

Dermestril (Sanofi

Winthrop)

Estraderm (Novartis)

Estreva (ThCramex)

Estrofem (Specia)

Menorest (Specia)

Oesclim (Fournier)

GB: Benztrone (Paines &

Byrne); wfm I: Benztrone (Amsa) Duo-Ormogyn (Amsa)- comb

Menovis (Parke Davis)- comb

Progynon (Schering) J: Estradin Susp (Santen- Yamanouchi)

Femihormon (Tokyo Hosei) Follikelmon (Kyorin) Ovahormon Benzoat Susp

(Teikoku Zoki)

Pelanin Inj (Mochida) Profollior B (Schering) Progynon B (Nihon Schering)

USA: Gynetone Inj (Schering)- comb.; wfm

Testradiol (Consolidated Midland)-comb.; wfm Testradiol (Truxton)-comb.; wfm

Trimonal (Vitacine)-comb.; wfm

numerous generics; wfm

Trang 2

782 E Estradiol cypionate

Estradiol cypionate

(Oestradiol- 17-cyclopentylpropionat)

ATC: G03C Use: estrogen RN: 313-06-4 MF: C,,H,,O, MW: 396.57 EINECS: 206-237-8

LD,,: >I glkg (M, i.p.)

CN: (17P)-estra- 1,3,5(IO)-triene-3,17-diol 17-cyclopentanepropanoate

eslrodiol 3-benzoate 3-cyclopentyl-

(9 v.1 propionic acid

estrodiol

(9 v.1 3-cyc~opentyl-

propionyl chloride

Reference(s):

a FR 1 215 503 (Lab Rolland; appl 1955)

h US 2 61 1 773 (Upjohn; 1952; prior 195 1)

For-mulation(s): amp 10 mg (1 mglml), 25 mg (5 mglml), 50 mg (5 mglml)

Trade Nume(s):

D: Femovirin Amp (Albert- I: Cicloestradiolo (Farmigea); Neoginon Depositum

F: Oestradiol-retard Rolland Estradiolo Depositum

Trang 3

F

E s t r a d i d valerate E 783 J: Depo-Estradiol (Upjohn- USA: Depo-Estradiol (Upjohn);

Use: estrogen RN: 979-32-8 MF: C&& MW: 356.51 EINECS: 213-559-2

LD,,: 1224 mglkg (M, p.0.)

CN: (17P)-estra- 1,3,5(IO)-triene-3,17-diol 17-pentanoate

17P-estradiol valeric anhydride

(4 v.1

estrodiol divalerate (I) I &tradioI valerate

Reference(s):

US 2 205 627 (Ciba; 1940; CH-prior 1936)

US 2 233 025 (Ciba; 1941; CH-prior 1936)

use as antidepressant:

DOS 2 758 549 (Schering AG; appl 23.12.1977)

Formulafion(s): amp 5 mglml, 10 mglml; drg 1 mg, 2 mg; drops 2 mg10.5 ml; f c tabl 2 mg; tabl 2 mg, 4 mg

Trade Name(s):

Gynokadin (Kade)

Merimono (Novartis

Pharma) -

Progynon Depot (Schering)

Progynova (Schering)

numerous combination

preparations

Climkne (Schering)-comb

Divina (1nnothCra)-comb

Progynova (Schering)

Cyclo-Progynova (ASTA

Medica)-comb

Progynova (Schering)

Gravibinan (Schering)-

comb

Gynodian Depot

(Schering)-comb

Progynon Depot (Schering)

Progynova (Schering) J: Pelanin Depot (Mochida) Progynon Depot (Nihon Schering)

USA: Ardefem (Burgin-Arden);

wfm Atladiol (Atlas); wfm Delestrogen (Squibb); wfm Depogen (Hyrex); wfm Depogen (Sig); wfm Dioval (Keene); wfm Ditate DS (Savage); wfm Dura-Estate (Ries); wfm Dura-Estradiol (Myers- Carter); wfm

Dura-Estradiol (Ruckstuhl); wfm Duratrad (Ascher); wfm

Estate (Savage); wfm Estral-L (Pasadena Res.); wfm

Estraval (Kay); wfm Estravel-P.A (Tutag); wfm Feminate (Western Res.); wfm

Femogen L.A (Fellows); wfm

Repo-Estra (Central); wfm Repo-Estro Med (Medics); wfm

Reposo E (Canfield); wfrn Retestrin (Rocky Mtn.); wfm

Span-Est (Scrip); wfm Testaval (Legere); wfm Valergen (Hyrex); wfm

Trang 4

7 8 4 E Estradiol undecylate

numerous combination

preparations; wfm

Estradiol undecylate

(Oestradiolundecanoat)

ATC: G03CA Use: estrogen RN: 3571-53-7 MF: C2,H,03 MW: 440.67 EINECS: 222-677-3

CN: (1 7p)-estra- 1 ,3,S(IO)-triene-3,l'i'-diol 17-undecanoate

176-estrodiol undeconoyl estrodiol diundeconoote (1)

US 2 990 414 (Syntex; 27.1.1 961; appl 18.3.1948; MEX-prior 26.3.1957)

Fornzulation(s): amp 100 rnglml

Trade Name(s):

F: Oestradiol-Retard J : Depogin (Shionogi)

ThCramex (Thkramex) USA: Delestrec (Squibb); wfm

Use: antineoplastic RN: 489 1- 15-0 MF: C2,H,2C12N0,P MW: 520.39 EINECS: 225-5 12-3

RN: 52205-73-9 MF: C2,H&I,NNa,O6P MW: 564.35

0

ethy1)arnine

Trang 5

1 Estriol E 785

Reference(s):

GB 1 016 959 (Leo; appl 9.4.1963; valid from 24.3.1964)

US 3 299 104 (Leo; 17.1.1967; GB-prior 9.4.1963)

GB 1 523 035 (Leo; appl 10.3.1976; valid from 8.3.1977)

complex compounds with alcohols (for purification):

US 4 115 414 (Leo; 19.9.1978; GB-prior 10.3.1976)

DE2710 293 (Leo; appl 9.3.1977; GB-prior 10.3.1976)

Formulation(s): cps 151.8 mg, 303.6 rng (as disodiurn salt); vial 621 rng (as meglumine salt)

Trade Name(s):

D: Cellmustin (cell pharm) F: Estracyt (Pharmacia & J: Estracyt (Nippon Shinyaku) Estracyt (Pharmacia & Upjohn) USA: Erncyt (Pharmacia &

Upjohn) GB: Estracyt (Pharmacia & Upjohn; as sodium salt)

Prostamustin (Azupharma) I: Estracyt (Farmitalia)

Use: estrogen RN: 50-27-1 MF: C,,HUO3 MW: 288.39 EINECS: 200-022-2

LD,,: >2 g k g (R, p.0.)

isopropenyl 3-rnethoxyestra-1,3.5(10).16-tetra- acetate en-1 7-01 acetate (I)

I - perbenzoic acid

olonote

16a.17~-epoxy-3-rnethoxy- Estriol estro-1,3.5(10)-trien-17-01

acetate

Reference(s):

Gallagher, T.F.: J Am Chem Soc (JACSAT) 76, 2943 (1954)

Trang 6

a

7 8 6 E Estriol succinate

alternative syntheses:

Butenandt, A.; Schaffler, E.L.: Z Naturforsch (ZNTFA2) 1, 82 (1946)

Huffmann, M.N et al.: Science (Washington, D.C.) (SCIEAS) 100,312 (1944)

Huffmann, M.N.; Lott, M.H.: J Am Chem Soc (JACSAT) 69, 1835 (1947)

US 1 967 351 (Pres and Board of Trustees of St Louis; 1934; appl 1930)

The Merck Index 12th Ed., 63 1 (Rahway 1996)

Formulnrion(s): cream 0.5 mg/g; drg 1 mg; f c tabl 2 mg; ovula 0.03 mg, 0.5 mg; tabl I mg, 2 mg

Trade Name(s):

D: Cordes (Ichthyol)

Estiol (Jenapharm)

Gynasan (Bastian-Werk)-

comb

Oekolp (Kade)

Ortho-Gynest (Janssen-

Cilag)

Ovestin (Organon)

Ovo-Vinces 200 (Wolff)

Synapause (Nourypharma)

Xapro (Jenapharm)

numerous combination

preparations

F: Gydrelle (Iprad) Physiogine (Organon) Trophicrkme (Sanofi J:

Winthrop) Trophigil (Sanofi Winthrop)-comb

GB: Hormonin (Shire)-comb

Ortho-Gynest (Janssen- USA:

Cilag) Ovestin (Organon) Trisequens (Novo Nordisk)-comb

I: Colpogyn (Angelini)

Ortho Gynest Depot (Cilag) Ovestin (Organon Italia) Climatol (Santen) Estriel (Mochida) Molin (Teikoku Zoki) Ovapause (Organon) Season (Teikoku Zoki) Estro Plus Tab (Rocky Mtn.)-comb.; wfm Hormonin (Camrick)- comb.; wfm

Use: estrogen RN: 514-68-1 MF: C2,H3,0, MW: 488.53 EINECS: 208-185-1

CN: (1 6 a , 17P)-estra- 1,3,5(10)-triene-3,16,17-trio1 16,17-bis(hydrogen butanedioate)

disodium salt

RN: 113-22-4 MF: C,,H,,,Na,O, MW: 532.50

Rejerence(s):

GB 879 014 (Organon; appl 26.5.1960; NL-prior 29.5.1959)

estriol succinic

Formulation(s): tabl 2 mg, 4 mg (as disodium salt); vial 20 mg (as disodium salt)

Estriol succinate

Trade Natne(s):

D: Orgastyptin (Organon Synapause (Nourypharma); F: Synapause (Organon); wfm

(4 v.) anhydride

Trang 7

Estrone E 787

Estrone

(Oestron)

ATC: G03CA07; G03CC04 Use: estrogen

RN: 53-16-7 MF: Cl,HzzOz MW: 270.37 EINECS: 200-164-5

CN: 3-hydroxyestra-1,3,5(10)-trien-17-one

oxide

androatenolone

3.17-dioxo-1.4- ondrostadiene (n)

$17-dioxo-1.4.6-

ondrostatnene

(from 3,17-dioxo-

1,4-androstadiene)

3-ocetoxy-19-hydroxycholesterol

(from cholesterol)

microarganism

CSD-I 0

H , C ~ S O , H

lithium, biphenyl

ethylene

glycol

Reference(s):

a,b Ehrhart, Ruschig, 111, 3 15

c Sih, Ch et al.: J Am Chem Soc (JACSAT) 87, 2765 (1965)

Trang 8

788 E Etacrvnic acid

starting material:

Kalvoda, J et al.: Helv Chim Acta (HCACAV) 46, 1361 (1963)

d Dryden, H.L et al.: J Am Chem Soc (JACSAT) 86,742 (1964)

production of conjugated estrogens:

US 2 565 115 (Squibb; 1951; prior 1948)

US 2 720 483 ( O h Mathieson; 1955; prior 1951)

US 4 154 820 (Akzona; 15.5.1979; prior 26.9.1977, 23.2.1976)

toral syntheses:

EP 37 973 (Hoechst; appl 2.4.1981; D-prior 12.4.1980)

Morand, P.; Lyall, J.: Chem Rev (Washington, D C.) (CHREAY) 68, 85 (1968)

Veliuz, L et al.: Angew Chem (ANCEAD) 72,725 (1960)

Velluz, L et al.: Angew Chem (ANCEAD) 77, 185 (1965)

Smith, 13 et al.: J Chem Soc (JCSOA9)1963,5072

Smith, H et al.: Experientia (EXPEAM) 19, 177 (1963)

Anachenko, S.N.; Torgov, J.V.: Tetrahedron Lett (TELEAY) 1963, 1553; 1964, 171

Blickenstaff, R.T.; Ghosh, A.C.; Wolf, G.C.: Total Synthesis of Steroids (Organic Chemistry Vol 30) p 58-63, 142-145, Academic Press, New York, London 1974

Formulation(s): e g 1.4 mg in comb.; amp 20 mg; drg 0.625 mg, 1.25 mg, 2.5 mg; vial 20 mg

Trade Narne(s):

D: Coniugen (K1inge)-comb.;

wfrn

G T 50 B (Gewo)-comb.;

Menrium (Roche)-comb.; USA:

wfrn

Oestro-Feminal (Mack,

Illert.; as estrogen

conjugate)-comb.; wfm

Ovaribran (Thomae; as

estrogen conjugate)-comb.;

wfrn

Ovowop (Hor-Fer-Vit)-

comb.; wfrn

F: Colpormon (Lipha SantC)

PrCmarin (Wyeth-Lederle)

Synergon (Lipha Sant6)-

comb

GB: Hormonin (Shire)-comb

I: Emopremarin (Wyeth; as

estrogen conjugate)

Premarin (Wyeth; as estrogen conjugate) Prempak (Wyeth)-comb

Estropan (Mochida)-comb

Di-Genik (Savage)-comb.;

wfrn Di-Met (0rganon)-comb.;

wfrn Duogen (Smith, Miller &

Patch)-comb.; wfrn Estro-V (Webcon); wfrn Estrus01 (Smith, Miller &

Patch); wfrn FolleStrol (Blue Line); wfrn Foygen (Foy); wfm Hormestrin (Smith, Miller

& Patch)-comb.; wfrn Mal-0-Fem (Fellows)- comb.; wfm

Menagen (Parke Davis);

wfrn

Menformon (Organon); wfm

Natural Estrogenic Substance (Legere); wfm Nestronaq (Noyes); wfm Ogen (Abbott; as estropipate); wfrn Prinn (Scirp); wfrn Propagon-S (Spanner); wfrn

Spanestrin (Savage)-comb.; wfrn

Theelin (Parke Davis); wfm Wynastron (Wyeth); wfm further combination preparations and generic; wfrn

Etacrynic acid

( ~ t h a c r y n s a u r e ; Acide etacrynique)

ATC: CO3CCO1 Use: diuretic RN: 58-54-8 MF: C,,HI2Cl2O4 MW: 303.14 EINECS: 200-384-1

LD,,,: 176 mglkg (M, i.v.); 600 mglkg (M, p.0.);

1 glkg (R, p.0.)

sodium salt

RN: 6500-81-8 MF: C,,H,,CI,NaO, MW: 325.12

Trang 9

Etafenone E 789

1 hutyry chloride 2.3-dichlorophen-

4-butyryl-2,3-dichloro- phenoxyacetic acid (I)

form- dimethyl-

aldehyde amine

I Etocrynic ocid

BE 612 755 (Merck & Co appl 17.1.1962;USA-prior 19.1.1961)

US 3 255 241 (Merck & Co.; 7.6.1966; prior 19.1.1961, 6.12.1961)

alternative synthesis:

DE 1 276 030 (Merck & Co.; appl 18.12.1964; USA-prior 23.12.1963)

Formulation(sJ: tabl 25 rng, 50 mg (as free acid); vial 53.6 mg (as sodium salt)

Trade Name(s):

D: Hydromedin (Merck Sharp GB: Edecrin (Merck Sharp & Reomax (Bioindustria)

F: Edecrine (Merck Sharp & I: Ac Etacr (Formulario Naz.) USA: Edecrin (Merck Sharp &

Dohme)

Use: coronary vasodilator RN: 90-54-0- MF: C2,H2,N02 MW: 325.45 EINECS: 202-002-9

hydrochloride

RN: 2192-21-4 MF: C2,H2,NO2 HCl MW: 361.91 EINECS: 218-587-9

LD,,: 28 mgkg (M, i.v.); 352 mglkg (M, p.0.);

20.8 mgkg (R, i.v.); 71 6 mgkg (R p.0.);

50 mgkg (dog, p.0.)

Trang 10

790 E Etamiphylline

2'-hydroxy-3- 2-diethylomino-

phenylpropio- ethyl chloride

phenone

I Etofenone I

R<ference(s):

DAS 1 265 758 (S p A Lab Guidotti; appl 25.5.1960)

Formulation(s): amp 25 mg; drg 75 mg; s r cps 50 mg (as hydrochloride)

Trade Name(s):

D: Baxacor (Helopharm); wfrn

Baxacor (Mack, Illert.);

wfrn

Digi-Baxacor (Mack,

1llert.)-comb.; wfrn

Iso Baxacor (Helopharm)-

comb.; wfrn

Pagano-Cor (Helopharm);

wfrn Seda-Baxacor (Helopharm)-comb.; wfm Seda-Baxacor (Mack

1llert.)-comb.; wfm I: Dialicor (Guidotti) J: Asamedel (Maruko)

Cardilicor (Uji) Corodilan (Meiji) Dialicor (Kissei) Esanthin-S (Kyoritsu Yakuhin)

Etafenarin (Taiyo) Korofenon (Nissin)

Etamiphylline

(Dietamiphylline)

ATC: R03DA06 Use: cardiotonic, diuretic

RN: 314-35-2 MF: C13H2,N,02 MW: 279.34 EINECS: 206-244-6

LD,,,: 1237 m g k g (M, p.0.)

monohydrochloride

RN: 17140-68-0 MF: CI3H2,N,O2, HCI MW: 315.81 EINECS: 241-204-1

LD,,,: 127 mglkg (M, i.v.1

camphersulfonate (1 : 1)

RN: 19326-29-5 MF: C13H?IN50? C10Hlh04S MW: 51 1.64 EINECS: 242-962-6

LD,,,: 604 mglkg (M, s.c.)

1 NoOH

C I ~ N - C H ,

A

O Y 2 2-diethylomino-

Reference(s):

GB 669 070 (A J.-M Moussalli et al.; appl 1949; F-prior 1948)

Klosa, J.: Arch Pharm Ber Dtsch Pharm Ges (APBDAJ) 288160, 301 (1955)

Formulation(s): 75 mg in comb.; suppos 200 mg, 500 mg; tabl 100 mg (as camphersulfonate)

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