Pharmaceutical Substances Syntheses, Patents, Applications - Part 69 docx

Fomulations: eye drops 1 mglml as hydrochloride Trade Names: D: D-EpifrinPharm-Allergan; Thilodigon Alcon; 1985- J: Pivalephrine Okami- Glaucothil Alcon; 1978 F: Propine Allergan Thil

Dipivefrine D 681

pivoloyl chloride

2-chloro-3'.4'- methylamine

dlhydroxy-

acetophenone

" c p o

H3C CH,

Dipivefrine

Hz, Pd-C

Dipivefririe

Reference(s):

a DOS 2 343 657 (Interx Res C o p ; appl 30.8.1973; USA-prior 31.8.1972)

US 3 809 714 (Interx; 7.5.1974; prior 3 1.8.1972) also racemate resolution

Hussain, A.; Truelove, J.E.: J Pharm Sci (JPMSAE) 65, 1510 (1976)

b DOS 2 152 058 (Klinge; appl 19.10.1971)

US 3 839 584

Fomulation(s): eye drops 1 mglml (as hydrochloride)

Trade Name(s):

D: D-Epifrin(Pharm-Allergan; Thilodigon (Alcon; 1985)- J: Pivalephrine (Okami-

Glaucothil (Alcon; 1978) F: Propine (Allergan)

Thiloadren (Alcon; 1980)- GB: Propine (Allergan; 1984)

682 D Dipotassiuni clorazepate

Dipotassium clorazepate

(Clorazepate dipotassium)

ATC: N05BA05 Use: tranquilizer RN: 57109-90-7 MF: C16HloClKN203 KOH MW: 408.92 EINECS: 260-565-6

LD,,,: 173 mglkg (M, i.v.); 700 mglkg (M, p.0.);

279 mglkg (R, i.v.); 880 mglkg (R, p.0.)

CN: 7-chloro-2,3-dihydro-2-oxo-5-phenyl-1 H-l,4-benzodiazepine-3-carboxylic acid monopotassium salt compd with potassium hydroxide

free acid

RN: 23887-31-2 MF: C16H,1ClN203 MW: 314.73 EINECS: 245-926-8

0 0

H 3 C f i O v O % 3 .HCI

c I C N diethyl aminomolonote

hydrochloride 2-amino-5- phenyl-

chlorobenzo- magnesium

nitrile bromide

a

Oipotossium clorazepate

US 3 516 988 (J Schmitt; 23.6.1970; F-prior 15.6.1964, 12.4.1965)

DE 1 518 764 (C M Industries S.A.; appl 14.6.1965; F-prior 15.6.1964, 12.4.1965)

DE 1 795 690 (C M Industries S.A.; appl 14.6.1965)

precursors:

DOS 1 795 832 (C M Industries S.A.; appl 14.6.1965; F-prior 15.6.1964, 12.4.1965)

Formulation(s): cps 5 mg, 10 mg, 20 mg; drops 5 mg; f c tabl 20 mg, 50 mg; lyo 50 mg, 100 mg

Trade Narne(s):

D: Tranxilium 50 (Sanofi Tranxtne (Sanofi J: Cephadol (Nippon

F: Noctran 10 (Menarini)- GB: Tranxene (Boehringer Ing.) USA: Gen-XENE (Alra)

Diprophylline

(Diprofyllin; Dyphylline)

ATC: R03DAOl Use: expectorant, bronchodilator RN: 479- 18-5 MF: CIoH,,N4O4 MW: 254.25 EINECS: 207-526-1

LDS,,: 1080 m g k g (M, i.v.); 1954 m g k g (M, p.0.);

860 mglkg (R, i.v.)

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

Dipyridamole D 683

+ C IOH ~ O H ,

3-chloro-1.2- Diprophylline proponediol

Diprophylline

0

glycidol

Reference(s):

a US 2 575 344 (State Univ Iowa; 195 1 ; prior 1946)

b Roth, H.J.: Arch Pharm Ber Dtsch Pharm Ges (APBDAJ) 292164, 234 (1959)

Formulation(s): drg 150 mg; suppos 200 mg, 400 mg; tabl 200 mg, 400 mg

Trade Name(s):

D: Neobiphyllin-Clys

(homrnsdorffl-comb

Ozothin (SmithKline

Beecham)

F: Ozothine Diprophylline

(SCAT)-comb

GB: Silbephylline (Berk); wfm

I: Cortinal Aerosol (Teofarma)-comb

Katasma (Bruschettini) J: Astmamasit (Showa) Corphyllin (Nippon Shinyaku)

Dihydrophylline (Tokyo Hosei)

Neophyllin-M (Eisai) Prophyline (Shionogi) Rominophyllin (Grelan) Theourin (Kanto) USA: Dilor (Savage) Dyline (Seatrace) Dylix (Lunsco) Lufyllin (Wallace)

Use: coronary vasodilator

RN: 58-32-2 MF: C , ~ H , ~ N , O ~ MW: 504.64 EINECS: 200-374-7

LD,: 150 mgkg (M, i.v.); 2150 mglkg (M, p.0.);

195 mg/kg (R, i.v.); 8400 mglkg (R, p.0.)

CN: 2,2',2",2"'-[(4,8-di-1-piperidinylpyrimido[5,4-6]pyrimidine-2,6-diyl)dinitrilo]tetrakis[ethanol]

urco (I) ethyl 2.4-dihydroxy- 5-nitroorotic

acetoacetote (11) 6-methylpyrimidine acid (111)

HNO, , rrr S n C12 or No2S204 o r H2/Pd-C b N

thiourea 4-hydroxy-2-

rnercopto-6-

6 8 4 D Dipyridamole I

6

OH

I or KOCN OH

P0Cl3, PCI5

A

cyanate OH

5-arninoorotic 2,4,6,8-tetro-

ocid (IV) hydroxypyrirnido-

r5.4-dlpyrirnidine

' diethanolornine

piperidine 2.6-dichloro-4.8-

dipiperidinopyri-

rnido[5.4-dlpyri-

rnidine

CI

2,4,6.8-tetro-

chloropyrirnido-

[5,4-dlpyrirnidine (V)

rot-

Dipyridornole

Reference(s):

DE 1 116 676 (Thomae; appl 1955)

GB 807 826 (Thomae; appl 1956; D-prior 1955)

US 3 03 1 450 (Thomae; 24.4.1962; D-prior 1959)

2.4.6.8-tetrahydroxypyrimido[5,4-dlpyrimidine:

DE 845 940 (Dr G F Fischer; appl 1950)

Fischer, F.G.; Roch, J.: Justus Liebigs Ann Chem (JLACBF) 572,216 (1951)

catalytic hydrogenation of 5-nitroorotic acid with Pd-C:

DOS 2 600 542 (Lonza; appl 8.1.1976; CH-prior 13.1.1975)

2,4,6,8-tetrachloropyrimido[5,4-dlpyrimidine:

Fischer, F.G.; Roch, J.; Neumann, W.P.: Justus Liebigs Ann Chem (JLACBF) 631, 147 (1960)

alternative syntheses:

GB 799 177 (Thomae; appl 1955; D-prior 1954)

DE 1 093 801 (Thomae; appl 1954)

DE 1 15 1 806 (Thomae; appl 30.4.1959)

DAS 1 962 261 (Yamanouchi; appl 12.12.1969; J-prior 25.1.1969)

combination with acetylsalicylic acid (thrombocyte aggregation inhibitor):

FR-appl 2 368 280 (ThCramex; appl 20.10.1976)

FR-appl 2 368 272 (ThCramex; appl 20.10.1976)

Formulation(s): amp 10 mgl2 ml; cps 75 mg; drg 25 mg, 75 mg; f c tabl 75 mg

Trade Name(s):

D: Asasantin (Boehringer Ing.)

Curantyl (Berlin-Chemie)

Persantin (Boehringer Ing.)

F: Cleridium 150 (Euro

Generics)

Perkod (BiogalCnique)

Persantine (Boehringer

I w 1

Protangix (Expanpharm) GB: Persantin retard (Boehringer Ing.)

I: Corosan (Farmacologico Milanese)

Coroxin (Malesci) Novodil (OFF) Persantin (Boehringer Ing.)

Persumbrax (Boehringer 1ng.)-comb

J: Anginal (Yarnanouchi) Permiltin (Zensei) Persantine (Boehringer- Takeda)

USA: Persantine (Boehringer Ing.)

ATC: COlBA03 Use: antiarrhythrnlc

Ibt 3737-09-5 MF: C2,H2,N30 MW: 339.48 EINECS: 223-110-2

H)%: 30 mgkg (M, i.v.); 352 rngtkg (M, p.0.);

39.1 mgkg (R, i.v.); 333 rnglkg (R, p.0.)

CN: a-[2-[bis(l-rnethylethyl)arnino]ethyl]-a-phenyl-2-pyrid1neacetarnide

phosphate (1:l)

RN: 22059-60-5 MF: C2,H2,N30 H3P04 MW: 437.48 EINECS: 244-756-1

B,: 81 mgkg (M, i.v.); 820 mgtkg (M, p.0.);

41 mgkg (R, i.v.); 880 rnglkg (R, p.0.)

1 sodium amide

' H 3 C ~ H : 3 ~

(2-pyridy1)- acetonitrile

Reference(s):

US 3 225 054 (Searle; 21.12.1965; appl 3.7.1962; prior 17.5.1961)

DE I 470 216 (Searle; appl 16.5.1962; USA-prior 17.5.1961)

Fonnulation(s): cps 128.8 mg, 193.2 rng, 257.6 rng; s r cps 161.25 mg, 193.2 rng, 322.5 mg (as dihydrogen

phosphate)

Tmde Name(s):

D: Diso-Duriles (Astra) F: Isorythm (Lipha SantC) J: Rythrnodan (MR) Disonorm (Solvay Rythrnodan (Roussel) USA: Norpace (Searle; as

Norpace (Heurnann) Norpace (Searle)

Rythmodul (Albert- Rythmodan (Roussel)

Roussel, Hoechst) I: Ritmodan (Roussel)

Distigmine bromide

(Hexamarium bromide)

ATC: N07AA03 Use: parasympathomimetic

RN: 15876-67-2 MF: C2,H,,Br2N404 MW: 576.33 EINECS: 240-013-0

LDSo: 300 pgkg (M, i.v.); 10.5 mglkg (M, p.0.);

740 pglkg (R, I.v.); 10 mglkg (R, p.0.)

CN: 3,3'-[1,6-hexanediylbis[(methylimino)carbonyl]oxy]bis[l-methylpyridin~um] dibrornide

686 D Disulfiram

CH3

N.N,N'.N'-tetra- phosgene

rnethylhexomethy-

lenediomine

methyl

bromide

Distigmine bromide

US 2 789 981 (0sterr Stickstoffwerke; 1957; A-prior 1954)

Formulation(s): amp 0.5 mg; tabl 5 mg

Trade Nnme(s):

D: Ubretid (Nycomed) GB: Ubretid (RhBne-Poulenc I: Ubretid (Torii)

Rorer)

Use: alcohol deterrent RN: 97-77-8 MF: C,,HzoN2S, MW: 296.55 EINECS: 202-607-8

LD,,: 1980 m g k g (M, p.0.);

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

CN: tetraethylthioperoxydicarbonic diamide ([(H2N)C(S)I2S2)

diethyl- carbon

amine disulfide

H ,

C ,

s

I Disulfirom

bC) S

H3C-NKS\sKN-CH3

S

<CH3

Reference(s):

US 1 782 11 1 (Naugatuck; 1930; appl 1925)

US 1 796 977 (Roessler & Hasslacher; 1931; appl 1928)

US 2 375 083 (Monsanto; 1945; prior 1943)

US 2 464 799 (Sharples Chemicals; 1949; prior 1945)

Dithranol D 687

Formularion(s): tabl 100 mg, 200 mg, 500 mg

Trade Name(s):

D: Antabus (Byk Gulden; Byk GB: Antabuse (Dumex) Nocbin (Tokyo Tanabe)

F: Esperal (Sanofi Winthrop) Exiltox (Candioli)

T.T.D.-B,-B4 (AJC J: Antabuse "D" (Tokyo

Dithranol

(Anthralin)

ATC: DOSACOI Use: antipsoriatic

r RN: 1143-38-0 MF: C,4H,~)03 MW: 226.23 EINECS: 214-538-0

i CN: 1,8-dihydroxy-9( 1 OH)-anthracenone

1,8-anthmquinone-

disulfonic acid

1.8-dihydroxy- onthraquinone (I)

/ Dithranol I

Referenctfs):

DRP 296 091 (Bayer; appl 1915)

Zahn, K.; Koch, H.: Rer Dtsch Chem Ges (BDCGAS) 71, 172 (1938)

Foimularion(s): cream 0.5 mglg, 1 mglg, 2 mglg; ointment 0.5 %, 1 %, 2 %, 3 %; pencils sticks 0.2 g110 g,

0.5 d l 0 g

Trade Name(s):

D: Psoradexan (Herma1)-

comb

Psoralon (Herma1)-comb I:

F: Anaxeryl (Bai1ly)-comb

GB: Dithrocream (Dermal) USA:

Micanol (Evans) Drithocreme (Dermik) Psorin (Thames)-comb Micanol (Bioglan) Pentagamma (1BP)-comb.;

wfm Dritho-Scalp (Dermik)

Use: chemotherapeutic (leprosy) RN: 584-69-0 MF: C,,H,,02S2 MW: 254.37

CN: 1,3-benzenedicarbothioic acid S,S-diethyl ester

688 D Dixyrazine

,S H diethyl sulfote

I

isophtholoyl dithioiso-

chloride phthalic acid

Reference(s):

GB 791 734 (ICI; appl 1954)

Formulation(s): cream 96 %

Trade Natne(s):

GB: Etisul (ICI); wfm

1 Ditophol I

Use: neuroleptic, antihistaminic RN: 2470-73-7 MF: C24H33N302S MW: 427.61 EINECS: 219-591-3

LDS,,: 37.5 mg/kg (R, i.v.); 400 mg/kg (R, p.0.)

CN: 2-[2-[4-[2-methyl-3-(1OH-phenothiazin-1O-yl)-propyl]-1-piperazinyl]ethoxy]ethanol

2 1-bromo-3-chloro- phenothiazine 10-(3-chlaro-2-methyl-

2-methylpropane

prapyl)phenothiazine (1)

Oixyrozine

Reference(s):

GB 861 420 (UCB; appl 17.4.1959; B-prior 19.4.1958)

Formulation(s): amp 10 mg; drops 22 mg; tabl 10 mg, 25 mg

Trade Nanie(s):

D: Esuco (UCB); wfm F: Esucos (Uckpha); wfm I: Esucos (SIT)

Use: cardiotonic

RN: 34368-04-2 MF: C,RH,3N03 MW: 301.39

CN: (+)-4-[2-[[3-(4-hydroxyphenyl)-1-methylpropyl]amino]ethyl]- I ,2-benzenediol

Docarpamine D 689

1

hydrochloride

1 RN: 49745-95-1 MF: C,8H,N0,.HCl MW: 337.85 EINECS: 256-464-1

I

W r CH3COOH

HO

f

L Reference(s):

; DOS 2 317 710 (Lilly; appl 9.4.1973; USA-prior 12.4.1972)

US 3 987 200 (Lilly; 19.10.1976; prior 12.4.1972, 15.1.1975)

Fonnulation(s): vial (lyo.) 280 mg (as hydrochloride)

Traa'e Name(s):

/ D: Dobutamin (ASTA Medica Dobutrcx (Lilly; 1978) I: Dobutrex (Lilly)

AWD; Fresen~us; Hexal; F Dobutrex (El1 Lilly) J: Dobutrex (Shlonogi; 1982)

Parke Davis) GB: Dobutrex (Lilly; 1977) USA: Dobutrex (Lllly; 1978)

Docarpamine

(TA-870; TA-8704)

ATC: CO2LX Use: cardiotonic, diuretic

RN: 74639-40-0 MF: C21H30N208S MW: 470.54

LD,: 2800 mgkg (M, i.v.)

CN: (9-carbonic acid 4-[2-[[2-(acetylamino)-4-(methylthio)-l-oxobutyl]amino]ethyl]-l,2-phenylene diethyl

ester -

(RS)-form

RN: 143289-50-3 MF: C2,H,,N,O8S MW: 470.54

H3C/SQyC"H

O 1 N-hydraxysuccin~rnide, H N CH,

2 doparnine hydrochloride, rnethionine (I) ([I)

690 D Docetaxel

6

CI O ~ C H , pyridine

ethyl

chloroformate

Docarpornine

1 0,s ~~0

rnorpholine

3.4-bis(ethoxycarbanyloxy)-

phenethylomine oxalate hernihydrate

Reference(s):

EP 7 441 (Tanabe Seiyaku; appl 6.2.1980; J-prior 30.6.1978)

JP 4 112 858 (Tanabe Seiyaku; appl 14.4.1992; J-prior 30.8.1990)

JP 7 165 684 (Tanabe Seiaku; appl 27.6.1995; J-prior 22.7.1994)

oral pharmaceuticals containing dopamine derivatives:

JP 06 183 964 (Tanabe Seiyaku; appl 5.7.1994; J-prior 24.12.1992)

Formulation(s): gran 75 mglg

Trade Name(s):

J: Tanadopa (Tanabe Seiyaku)

Docetaxel

(NSC-628503; RP-56976)

ATC: LOlCD02 Use: antineoplastic, microtubule inhibitor

RN: 114977-28-5 MF: C4,H,,NOI4 MW: 807.89

C N : [2aR-[2aa,4P,4ap,6P,9n(aR*,PS*), 1 la,12a,l2aa,12ba]]-~-[[(1,l-dimethylethoxy)carbonyl]amino]-a-

hydroxybenzenepropanoic acid 12b-(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,-12b- dodecahydro-4,6,1l-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11 -methano-l H-cyclodeca[3,4]benz[l,2-

bloxet-9-yl ester