Pharmaceutical Substances Syntheses, Patents, Applications - Part 189 ppsx

CN: carbonic acid 1,2-ethanediylbis[2,6-dioxo-4,1-piperazinediylmethylene] bis2-methylpropyl ester 1,2-bis3,5-dioxo- piperazin-1 -yl- ethane from ethylenediomine 1.2-bis4-hydroxymeth

I Sobrerol S 1881 / Trade Name(s)

J: Son~filan (Ta~to Pfizer)

Sobrerol

(Pinolhydrat)

ATC: R05CB07 Use: respiratory stimulant, secretolytic, mucolytic

RN: 498-71-5 MF: C,,,H,,O, MW: 170.25 EINECS: 207-868-1

LD,,,: 580 mg/kg (M, i.v.)

CN: 5-hydroxy-a,a,4-trimethyl-3-cyclohexene-l-methanol

(+)-u-pinene (2)-a-pinene 1 S o b r e m

oxide

H3C peroxyacetic H3C

H3C acid H3C

Reference(s):

US 2 815 378 (Glidden; 3.12.1957; appl 12.6.1-953)

DE 1 096 348 (FMC; appl 26.10.1959)

DE 2 114 138 (C Corvi; appl 24.3.1971; I-prior 17.4.1970)

0 H

medical use:

DE 2 166 355 (Camillo Corvi; appl 24.3.1971; I-prior '17.4.1970)

GB 1 176 817 (C Corvi; appl 8.12.1967; NL-prior 9.12.1966)

Forrnulation(s): cps 200 mg; gran 100 mg, 300 mg; suppos 20 mg, 100 mg, 200 mg; syrup 0.8 %

Trade Name(s):

I: Fluental (Corvi)-comb Sobrepin (Roche)

Polimucil (Po1i)-comb Sopulmin (Scharper)

Sobuzoxane

(MST 16)

ATC: LO1 Use: antineoplastic, topoisomerase II- inhibitor

RN: 98631-95-9 MF: C22H74N4010 MW: 514.53

LD,,,: >I glkg (M, p.0.);

>5 g/kg (R, p.o.1;

>3 g/kg (dog, p.0.)

CN: carbonic acid 1,2-ethanediylbis[(2,6-dioxo-4,1-piperazinediyl)methylene] bis(2-methylpropyl) ester

1,2-bis(3,5-dioxo-

piperazin-1 -yl)-

ethane

(from ethylenediomine

1.2-bis(4-hydroxymethyl- 3,5-dioxopiperozin-1 -yl)- ethone (I)

1882 S Sodium aurothiomalate

Refercnce(s):

EP 140 327 (Zenyaku Koguo Co.; appl 23.10.1984; J-prior 3 1.10.1983)

isobutyl

chlaroformote

E-ondution(s): sachets containing gran 400 mg, 800 mg, 1200 mg, 1600 mg

Soburoxone

Trade Nume(s):

J : Perazolin (Zenyaku Koguo)

Sodium aurothiomalate

(Gold Sodium Thiomalate)

ATC: MOlCBOl Use: gold therapeutic (antirheumatic, antiarthritic)

RN: 12244-57-4 MF: C,H,Au04S xNa MW: unspecified EINECS: 235-479-7

CN: sodium [mercaptobutanedioato(2-)]aurate(2-)

free acid

RN: 24145-43-5 MF: C,H,Au04S MW: 346.14 EINECS: 246-034-1

HS COOH

gald(l) thiornolic

iodide ocid

Sodium aurothiornalote

I

Fonnulution(s): amp 10 mg, 20 mg, 50 mg

Trade Natne(s):

D: Tauredon (Byk Gulden; GB: Myocrisin (IHC) USA: Myochrysine (Merck)

(Dioctyl sodium sulfosuccina~e; Docusatc sodium) Use: laxative, detergent, emulgator,

cerumenoly tic RN: 577- 1 1-7 MF: C,,H,,NaO,S MW: 444.57 EINECS: 209-406-4

CN: sulfobutanedioic acid 1,4-bis(2-ethylhexyl) ester sodium salt

Sodium dioctyl sulfosuccinate S 1883

calcium salt

RN: 128-49-4 MF: C40H74CaO14S, MW: 883.23 EINECS: 204-889-8

potassium salt

RN: 7491-09-0 MF: C20H,7K0,S MW: 460.67 EINECS: 231-308-5

COOH

$ +

COOH

furnaric

acid

NaHSO,

sodium

hydrogen

sulfite

Reference(s):

CH3

2-ethyl- l -hexan01 bis(2-ethylhexyl) furnarate (1)

I Sodium dioctyl sulfosuccinote

US 2 028 091 (American Cyanamid; 1936; appl 1933)

US 2 176 423 (American Cyanamid; 1939; appl 1936)

calcium salt:

US 3 035 973 (Lloyd Brothers Inc.; 1962; appl 1958)

Formulation(s): drg 5 mg; drinking amp 50 mg, 100 mg; suppos 10 rng; syrup 20 mg/5 ml; tabl 2.5 mg, 5

mg, 50 mg

Trade Narnefs):

D: Agaroletten (Warner-

Lambelt)-comb

Florisan (Boehringer 1ng.)-

comb

Laxagetten (ct-

Arzneimitte1)-comb

Otowaxol (Norgine)-comb

Potsilo (Stark, Konstanz)-

comb

Tirgon (Woe1m)-comb

further combination

preparations

F: Jamylbne (Expanpharm)

Norgalax (Norgine Pharma) GB: Klyx (Ferring); wfm Solivax (Concept); wfm numerous combination preparations

I: Dorbantyl (Robins)-comb.;

wfm Fisiolax (Manetti Roberts)- comb.; wfm

Ikelax (1keton)-comb.; w f n ~ Lambanol (Zi1liken)- comb.; wfm

Sorbichs (Pharkos)-comb ; wfm

Tiplcol (Blomedica Foscama)-comb.; wfm J: Bulkosol (Elsai) USA: Colace (Roberts) Modane Plus (Savage) Modane Soft (Savage) Peri-Colace (Roberts) Senokot-S (Purdue

Frederick)

genencs and further combination preparations

1884 S Sodium picosulfate

(Natrium-picosulfat; Picosulfate sodium; Sodium Use: laxative

picosulphate)

RN: 10040-45-6 MF: C,,H,,NNa,O,S, MW: 481.41 EINECS: 233-120-9

LD,,,: 1600 mglkg (M, i.v.); 14.5 g/kg (M, p.0.);

1450 mg/kg (R, i.v.); 17 g/kg (R, p.0.)

CN: 4,4'-(2-pyridinylmcthy1ene)bisphenol bis(hydrogen sulfate)(ester) disodium salt

1 CIS03H, pyridine

2 NaOH _*

1 chlarosulfonic acid

0 H

2-(4.4'-dihydroxybenz-

hydly1)pyridine

(cf, bisacodyl)

US 3 528 986 (De Angeli; 15.9.1970; appl 22.8.1966)

alternative synthesis (with amidosulfonic acid or pyridine sulfur ~rioxide adducr)

DOS 1 904 322 (Dr K Thomae; appl 29.1.1969)

Formulution(.sJ: drg 5 mg; drops 7.5 mglml; tabl 1.25 mg, 5 mg

Trade Namc.(s):

D: Agiolax (Madaus) Regulax (Krewel

Dalcolax (Boehringer Ing.) Meuielbach)

Laxoberal (Boehringer GB: Laxoberal (Windsor)

Mandrolax Pico (Dolorgiet) I: Falquigut (Falqui)

Midro (Midro)

Gocce Antonetto (Antonetto) Gocce Lassative Aicardi (SIT)

Guttalax (Fher)

Sofalcone

(SU-88)

ATC: A02B Use: ulcer therapeutic RN: 64506-49-6 MF: C,,H,,,O, MW: 450.53

LD,,,: 131 mglkg(M,i.v.);>10g/kg(M, p.0.);

105 mglkg (R, i.v.); > I 0 g/kg (R p.0.);

>20 glkg (dog, p.0.)

CN: (5-[(3-methyl-2-butenyl)oxy]-2-[3-[4-[(3-methyl-2-butnyl)oxy]phenyl]-I-oxo-2-

propenyl]phenoxy]acetic acid

OH 0

KOH or K2C0,/acetone 2'.4'-dihydroxy- prenyl bromide

Sorbitol S 1885

ethyl bromo-

ocetote

2'-ethoxycorbonylmethoxy- 4'-(3-methyl-2-buienyloxy)-

ocetophenone (11)

Sofolcone

1

Reference(s):

DE 2 705 603 (Taisho; appl 10.2.1977; J-prior 13.2.1976)

US 4 085 135 (Taisho; 18.4.1978; appl 11.2.1977; J-prior 13.2.1976)

synthesis of intermediate I:

Kyogoku, K, et al.: Chem P h a m Bull (CPBTAL) 27, 2943 (1979)

Formulation(s): cps 50 mg, 100 mg; gran 10 %

Trade Name(s):

I: Solon (Taisho; 1984); wfm

Sorbitol

(D-Glucitol)

RN: 50-70-4 MF: C6H& MW: 182.17

CN: ~-glucitol

ATC: A06Ati07; B05CX02; V04CCO1 Use: osmotic, laxative

EINECS: 200-061-5

OH

Sorbitol

~llmanns Encykl Tech Chem., 4 Aufl., Vol 24,772

Formulation(sj: sol 13.4 gl67.5 ml, 400 gll0OO ml; clysma 200 gllOO0 ml; susp 48 gll20 ml, 96 g1240 ml

Trade Name($ j:

D: 1 x klysma Sorbit Klistier Sorbitol-Infusionslosung numerous combination (Pharmacia & Upjohn) 40 (Braun Melsungen) preparations

Mikroklist (Pharmacia & Yal (Trommsdorff) F: Arnilose (ATC Pharma) Upjohn)-comb

1886 S Sorivudine

HCpagrume (Rosa-

Phy topharma)

HCpargitol (ElertC)

Sorbitol Aguettant

(Aguettant)

Sorbitol Delalande

(S ynthelabo)

numerous combination

preparations

GB: Glandosane (Fresenius)- comb

Relaxit (Crawford)-comb

combination preparations only

I: Sorbilande (Delalande) numerous combination preparations

J: Sorbit Inj (Nikken Kagaku)

D-Sorbitol Solution (Maruishi) Sorbit TS Inj (Termo) USA: Actidose (Paddock)-comb Sorbitol Sodium

(Pharmaceutical Associates)

Sorivudine

(BVAU)

Use: antiviral

RN: 77 181-69-2 MF: C,,H,,BrN,O, MW: 349.14

LD,,,: >8 glkg (R, p 0.); >2 glkg (R, s c.);

>10 glkg (M, p 0.); >5 glkg (M, s c.);

>5 glkg (dog, p o.)

CN: (~)-l-~-~-Arabinofuranosyl-5-(2-bromoethenyl)-2,4(1H,3H)-pyrimidinedione

I

0 H

1 -8-D-orabino- parafarrn-

furanosyluracil (I) aldehyde (11)

HCI or NaOH

)

I

OH

5-(hydroxyrnethy1)-

1 -8-D-arabinofuranosyl-

uracil (In)

HCI, dioxone

2 BuLi, 11

1 triphenyl- phosphine

2 butyllithiurn

paraform- 0 H

aldehyde

Br2 DMF

IV -*

I Sorivudine

Sorivudine S 1887

1 11, HCI

2 o2

OH

5-formyl-l-p-D- arobinafuronosyl- uracil (V)

2 NaOH, H20, dioxane

N

-co2

pyridine

, DMSO

2 NaOH H20, dioxone

r

bromine

1.2-dichlaroethane

Reference{s):

a EP 031 128 (Yamasa Shoyu; appl 1.7.1981; J-prior 19.12.1979)

b JP 59 163 39.5 (Yamasa Shoyu Co.; appl 14.9.1984; J-prior 8.3.1983)

c J P 58 062 195 (Yamasa Shoyu Co.; appl 14.4.1983; J-prior 8.10.1981)

d DD 280 763 (Akademie der Wissenschaften der DDR; appl 18.7.1990; DD-prior 4.8.1981)

nurleic acid related compounds:

Robins, M.J., Manfredini, S.: Tetrahedron Lett (TELEAY) 31 (39), 5633 (1990)

.facile uccess to 2'-0-acetylprodrugs of l-(~-~-arabinofuranosyl)-.5(E)-(2-bromovinyl)uracil:

Baraldi, P.G.; Bazzanini, R.; Manfredini, S.; Simoni, D.; Robins, M.J.: Tetrahedron Lett (TELEAY) 34 (19),

3177 (1993)

.rynrhesis and antiviral activity of(@-5-(2-bromoviny1)uracil:

De Clercq, E et a].: J Med Chem (JMCMAR) 29,213 (1986)

Formulation{s): tabl 50 mg

Trade Nume(s):

J: Usevir (Nippon Shoji

KaishdEisai; 1993); wfm

Use: beta blocking agent, anlianginal, antihypertensive

RN: 3930-20-9 MF: CI,H,,N2O3S MW: 272.37

LD,,,: 166 mglkg (M, 1.v.)

CN: N-[4-[l-hydroxy-2-[(1-methylethyl)amino]ethyl]phenyl]methanesu1f011amide

monohydrochloride

RN: 959-24-0 MF: C,2H20N20$ HCI MW: 308.83 EINECS: 213-496-0

LD,,,: 2600 m g k g (M p.0.);

3450 mglkg (R, p.0.)

methonesulfonyl aniline methanesulfon-

Refc.rence(s):

Uloth, R.H el a].: J Med Chem (JMCMAR) 9, 8 8 (1966)

Sparfloxacin S 1889

Tmde Name(s):

D: CorSotalol (durachemie)

Darob (Knoll)

Gllucor (Solvay

Arzne~mlttel)

Sotalex (Brlstol-Myers

Squ~bb)

Sotazlden (Bristo1)-comb

Tachytalol (ASTA Medlca

AWD)

various generics Tolerzide (Bristol-Myers)- F: Sotalex (Bristol-Myers comb.; wfm

GB: Beta-Cardone (Evans) Sotalex (Bristol-Myers Sotacor (Bristol-Myers Squibb)

Squibb) USA: Betapace (Berlex; as Sotazide (Rristol-Myers)- hydrochloride) comb.; wfm

(AT-4140; Ci-978; CP 103826; PD-13 1501; RP-64206) antlbacterla'

RN: 110871-86-8 MF C,9H22F2N40, MW: 392.41

LD, >5 glkg (R, p 0.); >2 glkg (R, s c.);

>2 glkg (M, p 0.); >2 glkg (M, s c.);

> 600 mglkg (dog, p 0.)

CN: ns-5-Amino-I-cyclopropyl-7-(3,s d1methyl-l-piperaz1nyl)-6,8-difluoro-1,4-dihydr~-4-~~~-3-

qulnolinecarboxylic acid

, , HJC-OyO-CH3 O-CH,

2 D - ~ ' ' 2 diethyl ether

'kOVcH,

F - 1 ethyl orthoformote

F O O 2 cyclopropylornine

pentofluoro- molonote ethyl pentofluoro-

benzoic ocid benzoylacetote

K,C03 CH,CN

2 HS Pd-C C2H50H

0uCH3 1 benrylomine

(1) ethyl 5.6.7.8-tetrafluoro-

corboxylote

5-omino- lcyclopropyl- 6,7,8-trifluoro-4-0x0- 1,4-dihydroquinoline-

cis-2,6-dimethyi- I Sparfloxacin

H N q

Ill +

pyridine

H3C Ad+

HN v

H ~ ~ F ~ ~ ~ J COOH ) ,

H,N 0

Ref~rence(s):

Miyamoto, T et al.: J Med Chem (JMCMAR) 33, 1645.1656 (1990)

EP 221 463 (Dainippon; appl 23.10.1986; J-prior 29.10.1985)

synthesis of ethyl pentafluorobenzoylacetate:

Clay, R.J.; Collom, T.A.; Karride, G.L.; Wemple, J.: Synthesis (SYNTBF) 3 , 2 9 0 (1993)

Forntulution(s): f c tabl 200 mg; tabl 100 mg, 150 mg

Trade Nante(s):

D: Zagam (Rhhe-Poulenc J: Spara (Dainippon) USA: Zagam (Rh8ne-Poulenc

F: Zagam (Specia)

Spectinomycin

(Actinospectacin)

A X : JOIXXO4 Use: antibiotic RN: 1695-77-8 MF: C,,H,N2O7 MW: 332.35 EINECS: 216-91 1-3

LDio: 2 glkg (M, i.v.);

>5 glkg (R, p.0.)

CN: [2R-(2a,4afi,5afi,6fi,7fi,8fi,9a,9aa,I0afi)]-decahydro-4a,7,9-trihydroxy-2-methyl-6,8-bis(methylamino)~

4H-pyrano[2,3-b][1,4]benzodioxin-4-one

dihydrochloride pentahydrate

RN: 22189-32-8 MF: C,,Hz4N20,, 2HCI 5H20 MW: 495.35

LD,,,: > I 0 mglkg (M, p.0.); -

>5 glkg (R, p.0.)

Spectinomycin

Froin culture of Streptontyces spectubilis

Reference(s):

US 3 206 360 (Upjohn; 14.9.1965; prior 18.6.1962)

US 3 234 092 (Upjohn; 8.2.1966; prior 20.10.1959)

US 3 272 706 (Upjohn; 13.9.1966; prior 2.8.1961)

US 3 819 485 (Abbott; 25.6.1974; appl 3.7.1972)