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Pharmaceutical Substances Syntheses, Patents, Applications - Part 170 docx

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0.5 mg, 1 rng, 2 mg, 5 rng as hydrochloride Trade Names: D: Adversuten ASTA Medica Polypressl-forte Pfizer- GB: Hypovase Invicta; 1974 Duramipress durachernie ~razosin-ratiodharm wfrn E

Trang 1

Prednicarbate P 1 69 1

alternative synthesis:

US 3 935 213 (Pfizer; 27.1.1976; prior 5.12.1973)

DOS 2 457 911 (Pfizer; appl 4.12.1974; USA-prior 5.12.1973)

DOS 2731 737 (Pfizer; appl 11.7.1977; USA-prior 6.8.1976)

US 4 062 844 (Pfizer; 13.12.1977; appl 20.9.1976)

US 4 138 561 (Bristol-Myers; 6.2.1979; prior 30.9.1977)

BE 861 821 (Fermion; appl 14.l2.1977; SF-prior 15.1 2.1976)

BE 861 822 (Ferrnion; appl 14.12.1977; SF-prior 15.12.1976)

a-form:

US 4 092 315 (Pfizer; 30.5.1978; appl 1.3.1976)

DAS 2 708 192 (Pfizer; appl 25.2.1977; USA-prior 1.3.1976)

anhydrous crystalline form:

DE 3 429 415 (Orion; appl 9.8.1984; FL-prior 25.6.1984)

US 4 816 455 (Heumann Pharrna; 28.3.1989; appl 3.3.1987; EP-prior 21.3.1986)

Formuhtion(s): s r cps 1 rng, 2 rng, 4 rng, 6 rng; tabl 0.5 mg, 1 rng, 2 mg, 5 rng (as hydrochloride)

Trade Name(s):

D: Adversuten (ASTA Medica Polypressl-forte (Pfizer)- GB: Hypovase (Invicta; 1974)

Duramipress (durachernie) ~razosin-ratiodharm wfrn

Eurex (Sanofi Winthrop) (ratiopharrn) J: Minipress (Pfizer Taito; Minipress (Pfizer; 1977) F: Alpress LP (Pfizer) 1981)

Minipress (Pfizer; 1979) USA: Minipress (Pfi7er)

Prednicarbate

(Hoe 777)

ATC: D07AC18 Use: topical glucocorticoid, steroidal anti- inflammatory

RN: 73771-04-7 MF: C2,H3,0, MW 488.58 EINECS: 277-590-3

CN: (1 1 P)- 17-[(ethoxycarbonyl)oxy]-1 I-hydroxy-21-(I -oxopropoxy)pregna-1,4-diene-3,20-dione

prednisolone tetraethyl

( q v.1 orthocorbonote

prednisolone 17.21 -diethy1 orihocarbonote (I)

CH3COOH

CI

H H

0&Lc~3

Me NO 0-CH,

Me H

Trang 2

1692 P Prednimustine

Reference(s):

Stache, U et al.: Arzneim.-Forsch (ARZNAD) 35 (11), 1753 (1985)

EP 742 (Hoechst; appl 27.7.1978; D-prior 4.8.1977)

DE 2 735 110 (Hoechst; appl 4.8.1977)

US 4 242 334 (Hoechst: appl 21.2.1979; D-prior 4.8.1977)

Formulation(s): cream 2.5 mgll g; ointment 2.5 mgll g; sol (in aqueous ethanol, 20 %) 2.5 mgll g

Trade Name(s):

D: Dermatop (Hoechst) I: Dermatop (Hoechst Marion USA: Dermatop (Hoechst Marion

Use: antineoplastic RN: 29069-24-7 MF: C,5H45C12N0, MW: 646.65 EINECS: 249-410-3

LDs,,: 530 mglkg (R, p.o.)

CN: (1 1 ~)-21-[4-[4-[bis(2-chloroethyl)arnino]phenyl]-I-oxobutoxy]-l1,17-dihydroxypregna-1,4-diene-3,20-

dione

prednisolone

( 9 v.)

4-[4-[bis(2-chloraethyl)amino]phenyl]- butyric anhydride

Prednimustine (I)

Reference(s):

DOS 2 001 305 (A B Leo; appl 13.1.1970; GB-prior 23.1.1969)

Formularion(s); cps 10 rng, 50 mg; tabl 10 mg, 100 mg

Trade Narne(s):

D: Sterecyt (Pharmaleo); wfm F: Sttrkocyt (Roger Bellon);

wfm

Use: glucocorticoid RN: 5626-34-6 MF: C2,H3,N06 MW: 473.61 EINECS: 227-064-4

CN: N,N-diethylglycine (1 1P)-I l,17-dihydroxy-3,20-dioxopregna-1.4-dien-21 -yl ester

Trang 3

Prednisolone P 1693

hydrochloride

RN: 17140-01-1 MF: C2,H3,N06 HCI MW: 510.07

-I

prednisalone

dieihyl-

amine

chloroacetyl chloride

GB 862 370 (Pfizer; valid from 1957; USA-prior 1956)

DE 1 037 451 (Schering AG; appl 1957)

*

alternative synthesis:

Pancrazio, G.; Sbarigia, G.: Farmaco, Ed Prat (FRPPAO) 16, 190 (1961)

Prednisolompte

Formulation(s): tabl 5 mg

Trade Name(s):

D: Deltacortril-intravenos

(Pfizer); wfm -

D07XA02; H02AB06; R01AD02; ROlAD52; SO1 BAO4; SOlCB02; S02BA03; S03BA02

Use: glucocorticoid RN: 50-24-8 MF: C21H280s MW: 360.45 EINECS: 200-021-7

LD,,: 180 mglkg (M, i.v.); 1680 mglkg (M, p.0.);

120 mgkg (R, i.v.)

CN: (1 1 ~)-11,17,21-trihydroxypregna-l,4-diene-3,20-dione

acetate

RN: 52-21-1 MF: C,,H3,06 MW: 402.49 EINECS: 200-134-1

LD5,,: 3500 m g k g (M, s.c.);

>240 mglkg (R, s.c.)

Trang 4

1694 P Prednisolone

hydrollostone

21 -ocetote

A, collidine

hydrocortisone

Br, CH,COOH

+ bromine

I Prednisolone 21 -oretole

microbiologicol dehydrogenation [Cotyneboctcrium haagii

/ H H

a US 2 897 216 (Schering Corp.: 1959; prior 1952)

starting material:

The Merck Index, 12th Ed., 815 (1996)

b US 3 134 718 (Schering Corp.; 26.5.1964; appl 12.12.1963; prior 1 1.8.1954)

Wettstein, A et al.: Helv Chim Acta (HCACAV) 39, 734 (1956)

Nobile, A et al.: J Am Chem Soc (JACSAT) 77,4184 (1955)

DAS 1 135 899 (Schering AG; appl 20.5.1960)

alternative synthesis:

US 4 041 055 (Upjohn; 9.8.1977; appl 17.1 1.1975)

Formulation(s): amp 10 mg/ml, 25 mglml, 50 mglml (as acetate); eye drops 1.2 mg/ml, 10 mglrnl (as acetate);

ointment 5 mglg, 100 mglg; suppos 100 mg (as acetate); syrup 15 mgl5 ml; tabl 1 mg, 5 mg,

20 mg

Trade Name(s):

D: Alferm (Schoning-Berlin)-

comb

Decaprednil (Orion

Pharma)

Decortin H (Merck)

Dontisolan (Hoechst)

Dura Prednisolon

(durachemie)

Hefasolon (Hefa Pharma) Prednabene (Merckle) Inflanefran (Pharm- Prednihexal (Hexal)

Preclal (Artesan; Cassella- Predni-POS (Ursapharm) med)

Trang 5

Prednisolone sodium phosphate P 1695 Prednisolon "Ferring"

(Ferring)

Prednisolon "Lentia"

(Lentia)

Prednisolon Augensalbe

Jenapharm (Jenapharm)

Prednisolut (Jenapharm)

Soh-Decortin (Merck)

Ultracortenol (CIBA

Vision)

combination preparations

F: Deliproct (Schering; as

caproate)-comb

Dtrinox (Thtrabel Lucien

pharrna)-comb

combination preparations

GB: Deltacortril (Pfizer)

Deltastab (Knoll) Hydrocortancyl cp stc (Roussel)

Hydrocortancyl susp inj (Roussel)

Precortisyl forte (Hoechst) Pred forte (Allergan) Scheriproct (Schering; as hexanoate)-comb

1: Biodeltacortilen (SIFT)- comb

Meticortelone (Schering- Plough)

Solprene (Farmigea) J: Codelcortone (Merck- Banyu)

Deltacortil (Taito Pfizer)

Delta Prenin (Sumitomo) Donisolone (Sankyo) Lavine (Tatsumi) Prednisolone Cream (Toho) Prednisolon Ophthalmic Oint (Nilten)

Predonine (Shionogi) Scherisolon Inj (Nihon Schering)

Scherisolon Tab (Nihon Schering)

numerous combination preparations

USA: Predniso (Roxane) Prelone (Muro)

Use: glucocorticoid RN: 125-02-0 MF: C2,H2,Na20,P MW: 484.39 EINECS: 204-722-9

LDS,: 360 mglkg (rabbit, i.v.)

CN: (1 1 P)-ll,l7-dihydroxy-21-(phosphonooxy)pregna- 1,4-diene-3,20-dione disodium salt

free acid

RN: 302-25-0 MF: C,,H2,0,P MW: 440.43 EINECS: 206-120-1

prednisolone

( q v.)

- 8 -

1 O d - F ; - U , pyridine

Cl

2 ocidic ion exchonger NoHCO,

b

1 dimorpholinophosphinic chloride

prednisolone 21 -phosphate

(monosodium solt) (1)

Prednisolone sodium phosphote 1

Reference(s):

DE 1 134 075 (Merck AG; appl 26.1 1.1959)

Trang 6

1696 P Prednisolone sodium succinate

alternurive synrheses:

US 2 789 1 17 (Merck & Co.; 1957; appl 1957)

US 2 870 177 (Merck & Co.; 1959; appl 1954)

US 2 932 657 (Merck k Co.; 12.4.1960; appl 30.7.1957)

US 2 936 313 (Glaxo; 10.5.1960; appl 18.11.1958; GB-prior 19.1 1.1957)

Forrnulation(s): amp 33.6 mg/5 ml, 53.75 mg15 ml; eye drops 0.5 g1100 ml; oral sol 6.7 mg15 ml

Trade Narne(s):

D: Hefasolon (Hefa Pharma) Phortisolone (Fumouze); Prednesol (Glaxo

Injektionslosung (Merckle) Solucort (Merck Sharp & Predsol (Evans)

F: Colicort (Merck Sharp & Dohme-Chibret) I: Solprene (Farmigea)-comb Dohme-Chibret)-comb GB: Minims Prednisolone J: Prozorin (Takeda) Deturgylone (SynthC1abo)- (Chauvin) USA: Optimyd (Medeva)-comb comb

Use: glucocorticoid RN: 1715-33-9 MF: C25H31NaOR MW: 482.51 EINECS: 216-995-1

LD,,: 1125 m g k g (M, i.v.);

770 mgkg (R, i.v.)

CN: (1 1 P)-2 1 -(3-carboxy- 1 -oxopropoxy)-l 1 ,17-dihydroxypregna-1,4-diene-3,20-dione monosodium salt

free acid

RN: 2920-86-7 MF: C2,H,,0, MW: 460.52 EINECS: 220-861-8

prednisolone

( 9 v.)

quinoline

succinic anhydride

( Prednisolone sodium succinate

DAS 1 045 400 (Pfizer; appl 1956; USA-prior 1955)-withdrawn

continuation of DE 1 013 648

Forrnularion(s): amp 10 mg, 25 mg, 100 mg (as free acid); amp 10 mglml, 25 mglml, 50 mg/ml, 100 mglml,

250 mgl5 ml, 250 mg/lO ml, 500 mgl5 ml, 500 mgllO ml, 1000 mg1.5 ml, 1000 mgll0 ml

Trang 7

Prednisolone sodium sulfobenzoate P 1697

Trade Name(s):

D: Aquapred (Winzer)-comb Solo-Decortin H (Merck) J: Predonine, water sol

Hostacortin H sol I: Endoprenovis (Vister) (Shionogi)

(Hoechst) Ibisterolon Iniett (IBI) IJSA: Meticortelone sol

Realin Supp (Geigyl Policort (Lepetit)-comb (Schering); wfm

Use: glucocorticoid RN: 630-67-1 MF: C,,H,,Na09S MW: 566.60 EINECS: 21 1-141-4

CN: (1 1 ~)-ll,l7-dihydroxy-21-[(3-sulfobenzoyl)oxy]pregna- 1,4-diene-3,20-dione monosodium salt

prednisolone methonesulfonyl

(9 v.1 chloride

sodium 3-sulfo-

benzoate

Prednisolone sodium 21-sulfobenzoote

Reference(s):

US 3 037 034 (Roussel-Uclaf; 29.5.1962; appl 21.4.1960; F-prior 24.4.1959)

alternative synthesis:

US 3 032 568 (Roussel-Uclaf; 1.5.1962; appl 15.3.1961; prior 13.4.1959)

Formulation(s): collutorium 22.5 mgl3 m1;clysma 20 mg; eye ointment 30 mgl4 g; foam 20 mg

Trade Name(s):

comb.; wfm F: DCsocort (Chauvin)-comb GB: Predenema (Pharmax)

Prednisolone steaglate

(Prednisolone stearoylglycolate)

ATC: H02AB06 Use: glucocorticoid RN: 5060-55-9 MF: C4,H,O8 MW: 684.96 EINECS: 225-763-9

CN: (1 1 P)- 11 ,l7-dihydroxy-21-[[[(1-oxooctadecyl)oxy]acetyl]oxy]pregna-1,4-diene-3,20-dione

Trang 8

1698 P Prednisolone tebutate

0 dioxane pyridine

+ C,&~y(CH2)16-CH3 0 -

prcdnisolone steoroylglycoloyl

(9 v.) chloride

Prednisolone steoglote

Reference(s):

US 3 171 846 (Carlo Erba; 2.3.1965; I-prior 10.7.1962)

Girardi, P.N et al.: Arzneim.-Forsch (ARZNAD) 16, 162 (1966)

Formulation(s); nasal drops 0.25 %

Trude Name(s):

F: Rollsone (Bellon); wfm Estilsona (Erba); wfm Siutisane (Erba); wfm GB: Sintisone (Farmitalia Carlo Glistelone (Erba); wfm Verisone (Tiber); wfm

I: Erbacort (Erba); wfm Prenisei (Cifa); wfm

Use: glucocorticoid RN: 7681 -14-3 MF: C,,H,,O, MW: 458.60 EINECS: 23 1-661-5

CN: (1 10)-21-(3,3-dimethyl-1 -oxobutoxy)-l 1,17-dihydroxypregna-1,4-diene-3,20-dione

pyridine

CI CH3

prednisolone tert-butyl-

( q v.) acetyl chloride

Reference(s):

US 2 736 734 (Merck & Co.; 1956; prior 1955)

Prednisolone tebutotc

DE 1 135 904 (Merck & Co.; appl 1956; USA-prior 1955)

Formulation(s): susp 20 mglml

Trade Name(s):

USA: Hydeltra-TBA (Merck

Sharp & Dohme)

Trang 9

Prednisolone 2 1-trimethvlacetate P 1699

Prednisolone 214rimethylacetate

(Prednisolon 2 1 -pivalate)

ATC: H02ABO6 Use: glucocorticoid RN: 1107-99-9 MF: C2,H,,0, MW: 444.57 EINECS: 214-172-1

CN: (1 1 P)-21-(2,2-dimethyl- l-oxopropoxy)-l 1 ,17-dihydroxypregna-I,4-diene-3,20-dione

0'

prednisolone trirnethylocetyl

(4 v.1 chloride

I Prednisolone 2 1 -trirnethylocetote

Reference(s):

CH 398 585 (Ciba; appl 1956)

Formulation(s): ophthalmic ointment 5 mglml (0.5 %)

Trade Name(s):

D: Ultracortenol (Ciba); wfm Varecort (Zyma-Blaes)-

comb.; wfm

Use: glucocorticoid RN: 53-03-2 MF: C2,H2,0, MW: 358.43 EINECS: 200-160-3

LD,,: 600 mg/kg (M, i.m.); 135 mglkg (M, i.p.); 101 mglkg (M, s.c.)

CN: 17.21-dihydroxypregna-l,4-diene-3,11,20-trione

dihydrocortisone 21 -ocetote

(cf cortisone synthesis)

1 collidine 3% 3.5-lutidine

2 KHCO,

Trang 10

1700 P Prednival acetate

microbiological dehydrogenation

Reference(s):

a US 2 897 216 (Schering Corp.; 1959; prior 1952)

Applezweig, N.: Steroid Drugs, Vol 1, 66 (New York, London, Toronto 1962)

starting material:

Applezweig, N.: Steroid Drugs, Vol 1 , 6 6 (New York, London, Toronto 1962)

b US 3 134 718 (Schering Corp.; 26.5.1964; appl 12.12.1963; prior 11.8.1954)

Wettstein, A et al.: Helv Chim Acta (HCACAV) 39, 734 (1956)

review:

Ullmanns Encykl Tech Chem., 4 Aufl., Vol 13, 54

Formulation(s): cream 5 mglg; eye drops 2 mg/g in comb with chloramphenicole; suppos 5 mg, 10 mg,

30 mg, 100 mg; syrup 5 mgl5 ml, 25 mglml, 50 mglml; tabl 1 mg, 5 mg, 20 mg, 50 mg

Trade Name(s):

D: Decortin (Merck)

Oleomycetin-Prednison

Augentropfen (Winzer)-

comb

Prcdnison "Dorsch" (Orion

Pharma)

Prednison "Ferring"

(Pharmagalen)

Prednison "Sanhelios"

(Borner) Predni-Tablinen (Beiersdorf-Tablinen) Predni-Tablinen (Sanorania) Rectodelt (Trommsdorff) F: Cortancyl (Roussel) GB: Decortisyl (Roussel); wfm

Delta-Butazolidin (Geigy) comb.; wfm

J: Delta-Butazolidin (Ciba- Geigy-Fujisawa)-comb USA: Liquid Pred (Muro) Lisacort (Fellows) Sterapred (Merz) generics

Prednival acetate

(Prednisolone 17-0-valerate)

ATC: H02AB Use: glucocorticoid RN: 72064-79-0 MF: C,,H3,0, MW: 486.61 EINECS: 276-312-8

LDs(,: >3 &/kg (M, p.0.);

>4 g/kg (R, p.0.)

CN: (1 1P)-21-(acety1oxy)-1 l-hydroxy-17-[(l-oxopentyl)oxy~pregna-1,4-diene-3,20-dione

prednival

KN: 15 180-00-4 MF: C,,H3,0, MW: 444.57 EINECS: 239-228-2

LD,,,: 490 mg/kg (M, s.c.)

orthovolerate

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