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Pharmaceutical Substances Syntheses, Patents, Applications - Part 95 pps

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Tiêu đề Pharmaceutical Substances Syntheses, Patents, Applications - Part 95 Pps
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250 mg as sulfate Trude Names: D: Leukase SmithKline Beecham Sofra Tiill Albert-Roussel, Hoechst F: NComycine Diamant Diaman1-comb.. and more than 50 combination preparations GB: Sofrad

Trang 1

Framycetin F 941

H3cL0 CH3 0

+ C'mNco * o f i \ ki H sodium nitrite

0 7 CH3 formlc ocid

Reference(s):

EP 117 959 (ADIR; appl 16.11.1983; F-prior 17.11.1982)

US 4 567 169 (ADIR; 28.1 l986; F-prior 17.1 1.1982)

synthesis of a-aminoethylphosphonic acid diethyl cster:

Berlin, K.D et al.: J Org Chem (JOCEAH) 33,3090 (1968)

Kowalik, J.; Mastalerz, P.: Synthesis (SYNTBF) 1981, 57

Oleksyszyn, J.; Tyka, R.: Tetrahedron LeU (TELEAY) 22, 2823 (1977)

Formulation(s): amp 208 mg

Trade Namels):

F: Muphoran (Servier; 1990)

Fotemustine I

Framycetin

(Neomycin B)

ATC: ROlAXO8 Use: antibiotic

RN: 119-04-0 MF: C23H46N6013 MW: 614.65 EINECS: 204-292-2

idopyranosyl-(1+3)-~-~-ribofuranosyl-(l+5)]-2-deoxy-~-streptamine

sulfate (1:3)

RN: 4146-30-9 MF: C2,H,N60,3 3H2S04 MW: 908.88 EINECS: 223-969-3

I Fromycetin

From fermentation solutions of Streptomycesfradiae

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942 F Fumagillin

Reference(s):

lJS 2 799 620 (Rutgers Res Found.; 16.7.1957; prior 29.6.1956)

purification:

US 2 848 365 (Upjohn; 1958; appl 1950)

US 3 005 815 (Merck & Co.; 24.10.1961; prior 1955, 1957)

US 3 022 228 (S B Penick; 20.2.1962; appl 19.1.1960)

US 3 108 996 (Upjohn; 29.10.1963; appl 30.7.1962)

Formulatiort(s): cream 0.5 %; drops 1.25 %; eye drops 0.5 %; ointment 20 mglg; powder 20 mglg;

spray 500 mg1203.5 g; tabl 250 mg (as sulfate)

Trude Name(s):

D: Leukase (SmithKline

Beecham)

Sofra Tiill (Albert-Roussel,

Hoechst)

F: NComycine Diamant

(Diaman1)-comb

and more than 50

combination preparations

GB: Sofradex (F1orizel)-comb

Soframycin (Hoechst)

comb

Sofra-Tulle (Hocchst; as

sulfate)

1: Cheliboldo (Terapeutic0)- comb

Crisolax (Lifepharma)- comb

Sofra-tulle (Roussel) J: Dexmy (Takeda) Fradio (Nippon Kayaku) USA: Coly-Mycin (Parke Davis)- comb

Cortisporin (Monarch; as sulfate)

Lazersporin-C (Pedinol; as sulfate)

NeoDecadron (Merck; as sulfate)

Neomycin Sulfate (Roxane) Neomycin Sulfate (Teva) Neosporin (Glaxo Wellcome; as sulfate) Neosporin (Warner- Lambert)

Use: antibiotic RN: 231 10-15-8 MF: C,,H,,O, MW: 458.55 EINECS: 245-433-8

LD,,: 2 glkg (M, p.0.)

CN: [3R-[3a,4a(2R*,3R*),5P,6P(all-E)]]-2,4,6,8-decatetraenedioic acid mono[5-methoxy-4-[2-methyl-3-(3- methyl-2-butenyl)oxiranyl~-1-oxaspiro[2.5]oct-6-yl] ester

dicyclohexylammonium salt (1: 1)

RN: 41567-78-6 MF: C,6H,40, C,,H,,N MW: 639.87

From fermentation solutions of Aspergillusfurnigutus

Reference(s):

US 2 803 586 (Abbott; 1957; prior 1953)

pur@cation:

Tarbell, D.S et al.: J Am Chem Soc (JACSAT) 77,5613 (1955)

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7

Furazabol F 943

structure and stereochemistry:

Chapman, D.D et al.: J Am Chem Soc (JACSAT) 82, 1009 (1960)

Chapman, D.D et al.: J Am Chem Soc (JACSAT) 83,3096 (1961)

Tarbell, D.S et al.: J Am Chem Soc (JACSAT) 77, 5610 (1955)

McCorkindale, N.J.; Sime, J.G.: Proc Chem Soc., London (PCSLAW) 1961, 331

' h e r ; Tarbell, D.S.: Proc Natl Acad Sci USA (PNASA6) 48,733 (1962)

total synthesis:

Corey, E.J.; Snider, B.B.: J Am Chem Soc (JACSAT) 94, 2549 (1972)

Trade Name(s):

USA: Fugillin (Upjohn); wfm Fumidil (Abbott); wfm

Use: anabolic RN: 1239-29-8 MF: C,,,H,,N,O, MW: 330.47 EINECS: 214-983-0

LD,,,: 1731 mglkg (M, p.0.);

>4 g h (R, p.0.)

CN: (5a,17~)-17-methylandrostano[2,3-c][1,2,5]oxadiazol-l7-01

HO-NH2 HCI, pyridine

hydrochloride

Reference(s):

U S 3 415 818 (Sterling; 10.12.1968; appl 8.7.1965)

1 .H3CkN/Br pyridine

H

2 PCIS

1 N-brornoocetornide

2, phosphorus pentachloride

further method:

H

US 3 245 988 (Daiichi; 12.4.1966; J-prior 10.4.1963, 15.7.1963, 5.12.1963, 12.2.1964)

Formulation(s): tabl 1 mg

Trade Name(s):

J: Miotolon (Daiichi Seiyaku)

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944 F Furazolidone

Use: topical anti-infective, topical antiprotozoal, chemotherapeutic (trichomonas)

RN: 67-45-8 MF: C,H,N,O, MW: 225.16 EINECS: 200-653-3

LD,,,: 1782 mglkg (M, p.0.);

2336 m g k g (R, p.0.)

CN: 3-[[(5-nitro-2-furanyl)methylene]amino]-2-oxazolidinone

N H 2

2-hydrozino-

ethonol

N H 2

diethyl 3-ornino-2- corbonote oxozolidone

Nb / NO,

5-nitrofurfurol 1 Furozolidone

Reference(s):

US 2 759 931 (Norwich Pharm Co.; 1956; prior 1953)

US 2 927 110 (Norwich Pharm Co.; 1.3.19h0; prior 23.1.1958)

Formulation(s): liquid 50 mg/15 ml; tabl 100 mg

Trade Name(s):

F: Furoxane (Oberval); wfm Furoxone (Formenti) J: Ginvel (Fujita) Tricofuron (Oberval); wfm Ginecofuran (Crosara)- Medaron (Yamanouchi)

I: Furadone (Vebi) Tricofur (Formenti)-comb USA: Furoxone (Roberts)

Furosemide

(Frusemide)

ATC: C03CAO1 Use: diuretic RN: 54-31-9 MF: CI2H,,ClN2O5S MW: 330.75 EINECS: 200-203-6

LD,,,: 308 mg/kg (M, i.v.); 2 g/kg (M, p.0.);

800 mglkg (R, i.v.); 2600 mglkg (R, p.0.);

>400 mglkg (dog, i.v.); 2 glkg (dog, p.0.)

CN: 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoic acid

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Fursultiamine F 9 4 5

1 CIS03H

2 NH,

1 chlorosulfonic

acid

2,4-dichloro- 5-sulfomoyl-4.5

bcnzoic acid dichlorobenzoic

ocid

H,N,,fJ

A, diglyme

Reference(s):

US 3 058 882 (Hoechst; 16.10.1962; D-prior 28.12.1959)

DE 1 122 541 (Hoechst; appl 28.12.1959)

akernative syntheses:

DE 1213 846 (Hoechst; appl 13.4.1963)

DE 1 220 436 (Hoechst; appl 21.10.1 964)

DE 1 277 860 (Hoechst; appl 4.5.1966)

DE 1 295 566 (Hoechst; appl 23.3.1968)

DAS 1 806 581 (Hoechst; appl 2.1 1.1968)

review:

Sturm, K et al.: Chem Ber (CHBEAM) 99, 328 (1966)

Furosemide

Formulation(s): amp 80 mg, 500 mg; s r cps 30 mg, 60 mg, 120 mg; sol 20 mg, 40 mg, 50 mg, 250 mg (as

sodium salt); tabl 20 mg, 25 mg, 40 mg

Trade Narne(s):

D: Diurapid (Jenapharm)

durafurid (durachemie)

Furanthril (medphano) F:

Furesis (Bristol-Myers

Squibb)-comb

furo (ct-Arzneimittel)

Furo-Puren (Klinge-

Nattermann Puren) GB:

Furorese (Hexal)

Furosemid (ratiopharm;

Riker; Stadapharm) 1:

Fusid (GRY)

Hydro-Rapid-Tablinen

(Sanorania)

Lasix (Hoechst)

Odemase (Azupharma)

Osyrol (Hoechst)-comb

Sigasalur (Siegfried)

J:

generic and combination preparations

Aldalix (Momanto)-comb

Furos6mide (Biogal6nique) Lasilix (Hoechbt)

Logirkne (Pharmacia &

Upjohn)-comb

Lasix (Hoechst) numerous combination preparations

Fluss (Rousse1)-comb

Lasitone (Hoechst Italia Sud)-comb

Lasix (Hoechst) Lasix Reserpin (Hoechst)- comb

Spirofur (Lepetit)-comb

generics Accent (Toyama)

Arasemide (Arakawa) Diusemide (Nakataki) Diuzol (Wakamoto) Franyl (Seiko Eiyo) Fuluvamide (Kanto) Furfan (Nippon Roussel- Chugai)

Kutrix (Kyowa) Lasix (Hoechst) Lowpston (Maruko) Polysquall A (Tokyo Hosei) Profemin (Toa Eiyo- Yamanouchi) Protargen (Ohta) Radonna (Nippon Kayaku) Rasisemid (Kodamaj Urex (Mochida) USA: Lasix (Hoechst Marion Roussel)

Use: neurotropic analgesic RN: 804-30-8 MF: C,,H,,N,O& MW: 398.55 EINECS: 212-357-1

LDS,,: 430 m g k g (M, i.v.); 2200 mglkg (M, p.0.);

2200 mgkg (R, p.0.)

furanyl)methyl]dithio]-1-butenyllformamide

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946 F Fursultiamine

N CH,

NaOH

thiamine

sodium S-tetrahydro-

furfuryl thiosulfate

Fursultiarnine

US 3 016 380 (Takeda; 9.1.1962; J-prior 16.8.1957)

Forrnulation(s): amp 5 mglml; drg 50 mg; tabl 5 mg, 25 mg, 50 mg

Trade Narne(s):

D: Dolo-judolor (Woe1m)- judolor-Dragees (ICN); judolor Dragees (Woelm);

J: Alinamin F (Takeda)

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Gabapentin G 9 4 7

(GOE 2450; G o 3450; CI 945) Use: anticonvulsant

RN: 60142-96-3 MF: CyH17N02 MW: 171.24 EINECS: 262-076-3

CN: I-(Aminomethyl)cyclohexaneacetic acid

hydrochloride

RN: 60142-95-2 MF: CyH17N02 HC1 MW: 207.70 EINECS: 262-075-8

cyclo- ethyl cyanoacetate

hexonone (I)

1 1 -cyclohexane-

diacetic acid

NH,-OH - HCL

0

b

benzenesulfonyl

NaOH, H20, 100aC

(Lossen rearrangement)

I Gabapentin

1 , l -cyclahexane- diacetic anhydride (1U)

V

dimethyl malonate dimethyl cycla-

Trang 8

948 G Gabapentin

ethyl diethyl- phosphinylacetate

ethyl cyclo- hexylidene- acetate (VI)

KZC03, DMSO, 0JCH3 Hz Pd-C,

ethyl 1 -(nitro- methyl)cyclo- hexaneacetate

1 H3C-CN

2 KCN, HCN

1 acetanitrile

1 oq HCI

2 ion exchange

E l

CN HCI, ethanol,

toluene

1 -cyanacycla- hexoneacetonitrile

1 NaOH CHjOH Hz, Rh-Pd-C

2 HCI

1 -cyanocyclo- hexoneacetic

Trang 9

Gabexate G 949

LiCI H20, 1 . r " , KCN, toluene

Gabapentine

1 benzyl alcohol

ethyl (I-cyano-

Reference(s):

a DE 2 61 1 690 (Goedecke; D-prior 19.3.1976)

US 4 152 326 (Warner-Lambert; 1.5.1979; D-prior 19.3.1976)

b EP 358 092 (Lonza; appl 29.8.1989; CH-prior 1.9.1988)

c EP 414 274 (Goedecke AG; appl 24.8.1990; D-prior 25.8.1989)

d US 5 319 135 (Warner-Lambert; 7.6.1994; USA-prior 25.8.1989)

EP 414 262 (Warner-lambert; appl 24.8.1990; USA-prior 25.8.1989)

e CA 2 030 107 (I7.5.199l; appl 15.1 1.1990; CH-prior 16.1 1.1989)

preparation of alternale crystal forms:

W O 9 828 255 (Teva Pharm.; appl 24.12.1997; IL-prior 24.12.1996)

high-purity monohydrate:

EP 340 677 (Warner-Lambert; appl 28.4.1989; USA-prior 2.5.1988)

Formulation(s): cps 100 mg, 300 mg, 400 mg

Trade Name(s):

D: Neurontin (Parke Davis) GB: Neurontin (Parke Davis) USA: Neurontin (Parke Davis) F: Neurontin (Parke Davis) I: Neurontin (Parke Davis)

Use: protease inhibitor RN: 39492-01-8 MF: C,,H,,N,O, MW: 321.38

monomesylate

RN: 56974-61-9 MF: C,,H,,N,O, CH,O,S MW: 417.48

LD,,: 218mg/kg(M, i.v.); 8 glkg (M, p.0.);

4020 mgkg (R, I.v.); 6480 mg/kg (R, p.0.)

Y

o-guonidinocaproic acid

"

chloride

wguanidina- coproyl chloride (I)

ethyl 4-hydraxy- I Gabexote I

pyridine THF

*

0

Trang 10

950 C; Gallamine triethiodide

Reference(s):

DOS 2 050 484 (Ono; appl 14.10.1970; J-prior 14.10.1969)

US 3 751 447 (Ono; 7.8.1973; J-prior 14.10.1969)

Formi~lation(s): amp 100 mgI5 rnl (as mesylate)

Trade Name(s):

J : Foy (Ono; 1978)

Gallamine triethiodide ATC: M03

Use: muscle relaxant, ganglionic blocker RN: 65-29-2 MF: C,,,H,,I,N,O, MW: 89 1.54 EINECS: 200-605-1

LD,,,: 1800 ~ g l k g (M, i.v.); 425 mglkg (M, p.0.);

5100 pg/kg (R, i.v.); > I glkg (R, p.0.);

800 ~ g l k g (dog, i.v.)

CN: 2,2',2"-[1,2,3-benzenetriyltris(oxy)]tris[N, N,N-triethyethanaminium] triiodide

1 NoNH2

1 sodium omide

pyrogollol 2 2-diethylomino- 1,2,3-tris(2-diethylomino-

ethyl chloride

ethoxy)benzene (1)

ethyl

iodide

Gollomine triethiodide

Formulation(s): amp 20 mglml, 40 mgl2 ml, 40 mglml, 100 mg

Trade Name(s):

D: Flaxedil (Abbott); wfm J: Gallamine Inj "Teisan"

F: Flaxtdil (Specia); wfrn (Teikoku Kagaku-Nagase)

GB: Flaxedil (Concord) USA: Flaxedil (Lederle); wfm

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