Pharmaceutical Substances Syntheses, Patents, Applications - Part 69 docx

Dipivefrine
D
681
-
tl
,
pivoloyl chloride
2-chloro-3'.4'- methylamine
dlhydroxy-
acetophenone
"cpo
H3C
CH,
Dipivefrine
Hz,
Pd-C
Dipivefririe
Reference(s):
a
DOS 2 343 657 (Interx Res. Cop; 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-
1978)
comb. Santen)
Glaucothil (Alcon; 1978)
F:
Propine (Allergan)
Thiloadren (Alcon; 1980)-
GB:
Propine (Allergan; 1984)
comb.
I:
Propine (Allergan)
9
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
H3CfiOvO%3
.HCI
+
+
NH2
I
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
Winthrop) Winthrop) S hinyaku)
F: Noctran 10 (Menarini)-
GB: Tranxene (Boehringer Ing.) USA: Gen-XENE (Alra)
comb. I: Transene (Sanofi Winthrop) Tranxene (Abbott)
Diprophylline
(Diprofyllin; Dyphylline)
ATC: R03DAOl
Use: expectorant, bronchodilator
RN: 479-
18-5 MF: CIoH,,N4O4 MW: 254.25 EINECS: 207-526-1
LDS,,: 1080 mgkg (M, i.v.); 1954 mgkg (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
+
CI~OH

,
OH
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)
Dipyridamole
ATC: BOlAC07
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,
Sn
C12
or
No2S204
or
H2/Pd-C
,
rrr
b
N
thiourea
4-hydroxy-2-
rnercopto-6-
methylpyrimidine
684
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
Iw.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
2. 2-chloro- 2. 2-diisoprapylamino-
'
H3C~H:3~
pyridine phenyi- ethyl chloride
(1)
(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
Anneirnittel)
-
GB: Dirythrnin (Astra) phosphate)
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)
Disulfiram
ATC: P03AA04; V03AAOl
Use: alcohol deterrent
RN: 97-77-8 MF: C,,HzoN2S, MW: 296.55 EINECS: 202-607-8
LD,,: 1980 mgkg (M, p.0.);
500
mgkg (R, p.0.)
CN:
tetraethylthioperoxydicarbonic
diamide ([(H2N)C(S)I2S2)
diethyl-
carbon
amine
disulfide
H3C)
NoOH
H3C)
Ci2
or
NoN02/HCI
H,C,NH
+
"2
H C N SNa
3V~
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)
Tosse)
I:
Antabuse (Crinos) USA: Antabuse (Wyeth-Ayerst)
F:
Esperal (Sanofi Winthrop) Exiltox (Candioli)
T.T.D B,-B4 (AJC
J:
Antabuse "D" (Tokyo
Pharma)-comb.
Tanabe)

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 dl0 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)
Ditophal
ATC: DO8
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
Dixyrazine
ATC: NO5ABO1
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)
Dobutamine
ATC: COICA07
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
Wr.
CH3COOH
HO
(1)
Dobutamme
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
2
H2N
HCI.
NMM
aoH
HN
'f
CH,
b
H3c-s-r#
OH
O
1
N-hydraxysuccin~rnide,
HN CH,
d~cyclohexylcarbodiimide
If
(S)-N-ocetyl-
0
2
doparnine hydrochloride,
rnethionine
(I)
N-methylmorpholine
([I)
690
D

Docetaxel
6
(1
+
__*
CI
O~CH,
pyridine
ethyl
chloroformate
Docarpornine
COOH
NMM
.
1
.
0,s
~~0
COOH
N-methyl-
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
CN:
[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