Pharmaceutical Substances Syntheses, Patents, Applications - Part 59 ppsx

Defibrotide
D
581
Formulation(s):
amp. 500 mg; inj. powder 500 mg; lyo. 500 mg, 2
g
Trade Name(s):
D:
Desferal (Ciba)
I:
Desferal (Ciba-Geigy) USA: Desferal (Novartis; as
F:
Desfkral (Ciba-Geigy)
J:
Desferal (Novartis-Takeda) mesylate)
GB:
Desferal (Novartis)
Defibrotide
RN: 8371 2-60-1
MF:
unspecified MW: unspecified
CN:
defibrotide;
polydeoxytibonucleotides
from bovine lung
Extraction from mammalian organs with aqueous solution of Zn salts.
Reference(s):
DE2 154278 (Crinos; appl. 3.11.1971; I-prior. 3.11.1970).
DE
2
154 277 (Crinos; appl. 3.1

1
.I97 1; I-prior. 3.11 1970).
US 3 829 567 (Crinos; 13.8.1974; I-prior. 3.1 1.1970).
US 3 899 481 (Crinos; 12.8.1975; I-prior. 3.1 1.1970).
EP 263 155 (Crinos; 10.4.1987; I-prior. 17.4.1986).
ATC: B0I AX01; B06A
Use: antithrombotic, cholinergic channel
modulator, stimulates
fibrinolysis
medical use for renal dialysis patients:
EP317 766 (Crinos; appl. 20.10.1988; I-ptior. 23.10.1987):
medical use for treatment of myocardial ischaemia:
EP 152 148 (Crinos; appl. 11.2.1985; I-prior. 16.2.1984).
medical use for treatment ~Jperipheral arterial disease:
EP 137 543 (Crinos; appl. 7.9.1984; I-prior. 12.9.1983).
medical use for treatment of acute renal in.~~~ficiency:
EP 137 542 (Crinos; appl. 7.9.1984; I-prior. 12.9.1983).
Formulation(s):
vial 200 rng
Trade Name(s):
I:
Dasovas (Carlo Erba) Noravid (Rousscl; 1986)
Prociclide (Crinos; 1986)
Deflazacort
ATC:
I
102~~ 13
(Azacort; Oxazacort) Use: glucocorticoid, anti-inflammatory
RN: 14484-47-0 MF: C2,H3,NO6 MW: 441.52 EINECS: 238-483-7
LD,,,:

5200 mgkg (M, p.0.)
CN:
(1
1P,16P)-21-(acety1oxy)-1
l
-hydroxy-2'-methyl-5'H-pregna-
1,4-dieno[17,16-dloxazole-3,20-dione
S
582
D
Dehydrocholic acid
0
'.
H2N\NKCHs
1.
AI[OCH(CH~)~I~,
H
cyclohexonone
2.
NaBH,
3.
Li2COs
I3.HCI
1.
semicorbozide
1.
aluminum
2.
bromine
3.

lithium
carbonate
nNPCH3
2.HsC-COOH
.HsC
1.
iodine,
2,2'-ozoisobutyronitrile
2.
triethylammonium
ocetate
I
Deflozocort
Keference(s1:
GB
1
077 393 (Lepetit; appl. 22.4.1965).
Nathansohn, G. et al.: J. Med. Chem. (JMCMAR) 10,799 (1967).
synthesis
of
I7~-azido-3P,16~-diacetoxy-5a-pregnane-
I
1,20-dione:
Nathansohn, G. et al.: Gazz. Chim. Ital. (GCITAY)
35,
1338 (1965).
ulternative synfhesis:
US 3 624 077 (Lepetit; 30.1 1.1971; GB-prior. 1 l.l.lY66).
Nathansohn, G. et al.: Steroids (STEDAM)
13,

383 (1969).
Fornrulution(s):
tabl. 6 mg, 30 mg
Trade Nume(s):
D: Calcort (Albert-Roussel, I: Deflan (Guidotti)
Hoechst) Flantadin (Lepetit)
Dehydrocholic acid
(Acide dehy drocholique)
ATC: A05
Use: choleretic, liver protective drug
RN: 81-23-2 MF: C,,H3,0s MW: 402.53 EINECS: 201-335-7
LD,,,: 1492
mgkg (M, i.v.); 3100 mglkg (M, p.0.);
750 mglkg (R, i.v.); 4 gkg (R, p.0.)
CN:
(5P)-3,7,12-trioxocholan-24-oic
acid
cholic
ocid
Dehydrocholic
ocid
US2966499 (Merck
&
Co.: 27.12.1960; prior. 9.4.1958).
Formulation(sJ:
amp. for i.v. and i.m. inj. 1 g/5 ml H,O (as sodium salt); tabl. 250 mg
D:
Decholin (Cassella-Riedel) numerous combination Decholin (Miles); wfm
Eupond N (Ferring) preparations
Decholin Sodium (Dome);

Felacomp (Veda)-comb.
J:
Dehychol (Nippon Eiyo) wfm
numerous combination Dehydrochol (Kanto; Gastroenterase (Wallace)-
Sawai; Hokuriku) comb.; wfm
F:
Dycholiurn (ThCraplix); Hydrochol (Kyorin) Hepahydrin (Great
USA: Atrocholin (Glaxo); wfm Southern); wfm
GB:
Dehydrocholin (Duncan,
Bilax (Drug Industries)- Ketochol (Searle): wfm
Flockhart); wfm
comb.; wfm
Neocholan (Dow); wfm
I;
Certobil (Metapharma)- Cholan (Pennwa1t)-comb.;
Neolax (Central)-comb.;
wfm wfm
Debridat (Sigma-Tau)- Cholan-DH (Pennwalt); Sodium Dchydrocholate
wfm (City Chem.); wfm
Heparbil (Montefarmaco)- Cholan-HMB (Pennwa1t)- Sodium Dehydrocholate
comb.; wfm (Endo); wfm
Delavirdine mesilate
(U-90152s)
ATC: J05AG02
Use: antiviral, HIV-
I
reverse transcriptase
inhibitor
RN:

147221-93-0 MF: C22H2xN60,S
.
CH403S MW: 552.68
CN:
1-[3-[(I-Methylethyl)amino]-2-pyridinyl]-4-[[5-[(methysulfonyl)amino-1W-indol-2-yl]-
carbonyllpiperazine monornethanesulfonate
base
RN:
136817-59-9 MF: C22H28N603S MW: 456.57
Boc-0,
aceton~trile Boc
CI
NO2
H
N-'
di-tert-butyl
HN d~carbonote
2-chlom- piperozine
1
-(3-nitro-2-
3-nitropyridine pyridy1)piperazine
'.
-
Q
2.H3CKCH,
0
,
NoCN
.
BH3

,
CH30H
g
b
2. acetone, sodium cyonoborohydride
I
/
584
D
Demecarium bromide
5-nitroindole-
2-corboxylic ocid
3.
H3C-S03H
,
ocetonitrile
111
b
2.
methonesulfonyl chloride
.
H3C-S03H
Delovirdine rnesilote
~omero, D.L. et
al.:
J. Med. Chem. (JMCMAR)
36,
1505 (1993).
WO 9 109 849 (Upjohn; USA-prior. 28.12.1989).
Pedersen, O.S.; Pedersen, E.B.: Synthesis (SYNTBF), 2000,479.

water clathrates:
WO 9 422 836 (Upjohn
+
Co.; appl. 15.3.1994; USA-prior. 26.3.1993).
novel crystal form:
WO 9 528 398 (Upjohn
+
Co.; appl. 1.3.1995; USA-prior. 15.4.1994).
combination with HIV-protease inhibitors:
WO 9 726 880 (Pharmacia
+
Upjohn; appl. 10.12.1996; USA-prior. 26.1.1996).
WO 9 616 675 (Rega Inst.; appl. 29.1 1.1995; USA-prior. 30.11.1994).
combination and use with other reverse transcriptme inhibitors:
WO 9 409 781 (Upjohn
+
Co.; appl. 10.9.1993; USA-prior. 28.10.1992).
Fonnulation(s):
tabl. 100 mg
Trade Narne(s):
USA: Rescriptor (Pharmacia
&
Upjohn; 1997)
Demecarium bromide
ATC: SOlEB04
Use: cholinesterase inhibitor
RN: 56-94-0 MF: C,,H,,Br,N404 MW: 716.60 EINECS: 200-301-9
LD,,: 6490
pglkg
(M, p.0.)

CN: 3,3'-[I,
I0-decanediylbis[(methylimino)carbonyloxy]]bis[N,N,N-trimethybenzenaminium]
dibromide
Demeclocycline
D
585
phosgene
1
,lo-bis(rnethylorn~no]decane
3-dimothylarnlno-
phenol
sodlurn
salt
methyl
Dernecoriurn
bromide
bmrnide
Reference(s):
US
2789 891 (Osten: Stickstoffwerke; 1957; A-prior. 1954).
Fonnulation(s):
collyre 0.25
%,
0.5
%,
1
%
Tmde
Name(s):
D: Tosmilen (Lentia); wfm

GB:
Tosmilen (Astra): wfm
J:
Tosmilen (Chugai)
I?
Tomilhe (Chibret); wfm Tosmilen (Sinclair); wfm USA: Humorsol (Merck)
Demeclocycline
(Demethylchlortetracycline)
ATC:
D06AAOl: JOl AAOl
Use: antibiotic
RN: 127-33-3 MF: C2,H21CIN20,
MW:
464.86 EINECS: 204-834-8
LD,,: 79 mgkg
(M,
i.v.);
M.75 gkg
(R,
p.0.)
CN:
[4S-(&,4aa,5aa,6P,12aa)]-7-chloro-4-(dimethyamino)-l,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-
pentahydroxy-1
,l l-dioxo-2-naphthacene
carboxamide
monohydrochloride
RN: 64-73-3
MF:
C,,H,,CIN,O,
.

HCI
MW:
501.32 EINECS: 200-592-2
LD,: 275 mgkg
(M,
i.v.); 2150 mglkg (M, p.0.);
94 mgkg
(R,
i.v.); 2372 mglkg
(R,
p.0.)
586
D
Demegestone
From fermentation solutions of a
Streptomyces aureofuciens
mutant.
Reference(s):
US 2 878 289 (American Cyanamid; 17.3.1959; prior. 28.5.1956).
US 3 012 946 (American Cyanamid; 12. 12. 1961; appl. 16.11.1960).
US 3 019 172 (American Cyanamid; 30.1.1962; appl. 14.3.1960).
US 3 050 446 (American Cyanamid; 21.8.1962; appl. 28.7.1960).
US 3 154 476 (Olin Mathieson; 27.10.1964; appl. 29.4.1963).
DE 1 041
21
3 (American Cyanamid; appl. 24.5.1957; USA-prior. 28.5.1956).
McCormick, J.R.D. et al.: J. Am. Chem. Soc. (JACSAT) 79,4561 (1957).
Formulation(s):
tabl. 150 mg, 300 mg (as hydrochloride)
Trade Nante(s):

D:
Demebronc (Lederle)-
comb.
Ledermycin (Novalis
Arm)
Lederstatin (Novalis
Arm.)-comb.
F:
Ledermycine (Lederle-
Novalis); wfm
GB: Deteclo (Wyeth)-comb.
Ledermycin (Wyeth)
I:
Demebronc (Cyanamid)-
comb.
Dcmctraciclina (Libral);
wfm
Detracin (Sierochimica);
dm
Detravis (Vis); wfm
Dimeral (Panther-Osfa
Chemie); wfm
Diuciclin (Benvegna); wfm
Elkamicina (Biotrading);
wfm
Fidocin (Farmaroma); wfm
Isodemetil (Isola-Ibi); wfm
Latornicina (Farber-Ref);
wfm
Ledermicina (Cyanamid)

Lesten
(Serono)-comb.;
w fm
Magis-Ciclina (Tiber); wfm
Mirciclina
(Francia Farm.);
wfm
Neo-Cromacdin (Panther-
Osfa Chemre)
Oldem (Firma)-comb.
Tetradek (SIT)
Tollerclin (Scalari)
Varibiotic (Cyanamid)-
comb.
Veraciclina (Am)
numerous combination
preparations
J.
DemethylchlorTetracycline
(Kaken)
Ledermy cin (Lederle)
USA:
Declomycin (Lederle
Labs.; as hydrochloride)
Demeges
tone
ATC: G03DB05
Use: progestogen
RN: 101 16-22-0 MF: C2,Hz80z MW: 3 12.45 EINECS: 233-320-6
CN:

17-methyl-19-norpregna-4,9-diene-3,20-dione
3-rnethoxy-20-0x0-19-nor-
pregna-1,3.5(10).16-tetroene
(I)
(from estrone 3-methyl ether)
Denopamine
D
587
H0
CH3
1.
c~o,.
ocetone
O
CH,
1.
Li, NH,
2.
CH,COOH,
ocetone
1
&CH~
1
n
1,
chrornium(Vl)
1
oxide
Demegestone
u

Referencefs):
US
3
453 267 (Roussel-Uclaf; 1.7.1969; F-prior. 31.12.1964,25.2.1965, 24.3.1965, 14.6.1965. 3.9.1965,
17.9.1965).
US
3
547 959 (Roussel-Uclaf; 15.12.1970; F-prior. 27.12.1965).
Joly,
R.
et
al.: Bull.
Soc.
Chim.
Fr.
(BSCFAS)
1973,
2694.
starting material:
Bum,
D.;
Petrov, v.:
J.
Chem.
Soc.
(JCSOA9)
1962,364.
total synthesis:
Velluz,
L.

et al.: Tetrahedron (TETRAB)!
1966,
Suppl.
8,
part
11,
495
Formulation(s):
tabl. 500
mg
Trade Name(s):
F:
Lutionex (Roussel
Diarnant)
Denopamine
(TA-064)
ATC: COlCA
IJse: orally active cardiostimulant,
P,-
receptor agonist
RN: 71771-90-9
MF:
C,,H,NO,
MW:
317.39
LD,,:
198
mgkg
(hl,
i.v.); 5672

mglkg
(M,
p.0.);
9369
mglkg
(R, p.0.)
CN:
(R)-a-[[[2-(3,4-dimethoxyphenyl)ethyl]amino]methyl]-4-hydroxybenzenemethanol
hydrochloride
RN: 64299-19-0
MF:
CI,H,,NO,. HCI
MW:
353.85
2-chloro-4'-benzyloxy- 3,4-dimethoxy-
2-(3,4-dimethoxyphenevlylomino)-
ocetophenone phenethylomine
4'-benzyloxyocetophenone
(I)
1.
NoBH4
2.
rocemote resolution with
D(-)-acetylphenylolonine
3,
H,.
Pd-C
I
b
J3i3TO-CH3

HO
0-CH,
Denopamine
588
D
Deptropine
Reference(s):
DOS 2 542 881 (Tanabe; appl. 25.9.1975).
US 4 032 575 (Tanabe; 28.6.1977; appl. 1.10.1975).
US 4 072 759 (Tanabe; 7.2.1978; appl. 10.1 1.1976; prior. 1.10.1975).
Umino, N. et al.: Chem.
Pharm. Bull. (CPBTAL)
27,
1479 (1979).
enantioselective synthesis starting from optically active
4-hydroxyphenylglycine:
JP 85 009 702 (Tanabe; appl. 14.1 1 .l977).
JP 85 009 703 (Tanabe; appl. 14.1 1.1977).
Ikezaki, M. et al.: Yakugaku Zasshi (YKKZAJ) 106, 80 (1986).
Formulation(s):
gran. 5
%;
tabl. 5 mg, 10 mg
Trade Name(s):
J: Kalgut (Tanabe; 1988)
Deptropine
(Dibenzheptropine)
ATC: R06AX16
Use: antihistaminic, anticholinergic
RN: 604-51-3 MF:

C2,HZ7NO MW: 333.48 EINECS: 210-069-0
CN:
endo-3-[(l0,11-dihydro-5H-dibenzo[a,~cyclohepten-5-yl)oxy]-8-methyl-8-azabicyclo[3.2.l]octane
citrate
(1:l)
RN: 2169-75-7 MF: CZ3Hz7NO
.
C6H80, MW: 525.60 EINECS: 218-516-1
LD,,: 32 mgkg (M, i.v.); 300 mgkg (M, p.0.);
445 mgkg (R, p.0.);
75 mgkg (dog, p.0.)
methobromide
RN: 10139-98-7 MF: CZ4H3,BrNO MW: 428.41
LD,,: 1150 pgkg (M, i.v.); 680 mgkg (M, p.0.);
1200 pglkg (R, i.v.); 800 mglkg (R, p.0.);
71 mgkg (dog, p.0.)
methiodide
RN: 38146-43-9 MF: C,,H,,INO MW: 475.41
phthalic phenylacetic
anhydride ocid
2-(2-phenylethy1)-
benzoic ocid (1)
poiyphosphoric acid NaBH,
I
+
(y'$ J
(-J-Jy%"
0
OH
5-0x0-l0,11 -di- 5-hydroxy-l0,l

1-
[a.d]cycloheptene benzo[a,d]cycla-
heptene
Deptropine
I
tropine
er et al.:
J.
Med. Pharm. Chem. (JMPCAS) 4,335 (1961).
Formulation(s):
tabl. 1 mg
hde Name(s):
GB:
Brontina (Brocades); wfm Brontisol (Brocades)-
I:
Brontin (Forment~)
comb.; wfm
Dequalinium
chloride
ATC: DO8AHOI; GOlACO5; R02AA02
Use: bacteriostatic, antifungal
!"
RN:
522-51-0 MF: C,oH40CI,N4 MW: 527.58 EINECS: 208-330-9
LD,,:
1900
pglkg
(M, i.v.)
t
1;

CN:
I
,l'-(1
,l0-decanediyI)bis[4-amino-2-methyquinolinium]
dichloride
4-amlno-
quinaldine
A9cl
I
+
Dequaliniurn chloride
Referencefs):
GB 745 956 (Allen
&
Hanburys; appl. 1953).
dequoliniurn iodide
(I)
Formulation(s):
different tabl., creams, sol. and gels
590
D
Deserpidine
Trade Narne(s):
D: Dequafungan Hautspray
(Kreussler)
Dequavagyn (Kreussler)
Eriosept (Kreussler)
Evazol (Ravensberg)
Malty1 (Merckle)
Optipect (Thiemann)

Phylletten (Arznei Miiller-
Rorer)
Soor-Gel (Engelhard)
Sorot (Ravensberg)
Tonsillol (Merck1e)-comb.
numerous combination
preparations
F:
Humex Fournier Kinaldine
(Labs. Urgo)-comb.
Oroseptol (SmithKline
Beecham)-comb.
GB: Labosept (L.A.B.)
I: Aperdan (Tiber)-comb.
Decabis (Gazzoni)
Dequadin (Eurospital)
Dequadin (Importex)
Faringina (SIT)
Farmocillina (Zyma)
Golosan (Lifepharma)
Kinogen
(Geymonat).
comb.
Lariquin (Manetti Roberts)
Osangin (Antonetto)
Rinospray
(Midy)-comb.
S terox (Granel1i)-comb,
Transpulmina gola
(Sigurta)-comb.

J:
Almani S (Tanabe)-comb.
Dequadin Lozenges (Torii)
Honkon-N
(Zenyaku)-
comb.
Neues Troch (Toyo
Pharmar)
SP Troche
(Meiji Seika)
Deserpidine
(Desmethoxyreserpine)
ATC: C02AA05
Use: neuroleptic
RN:
13
1-01-1 MF: C,,H,,N,O, MW: 578.66 EINECS: 205-004-8
LD,,,: 500 mglkg (M, p.0.);
15 mglkg (R, i.v.)
CN:
(3~,l6~,l~a,l8~,2Oa)-l~-methoxy-l8-[(3,4,~-trimethoxybenzoyl)oxy]yohimban-
16-carboxylic acid
methyl ester
0
0/CH3
H3C\
I;,
d0-cp-~~3
,
N

N%
,,to
I
/
0-CH3
\
Deserpidine
a
By extraction of Rauwolfia serpentina (L.) Beuth. roots, separation of in greater quantity available reserpine
as heavy soluble thiocyanate and column chromatographic purification of the mother liquors.
b
By extraction of Rauwolfia canescens, R. hirsuta, R. tetraphylla, R. indecora, R. vornitoria Afz. or R
cubana
roots and purification by fractional crystallization andlor column chromatography on A1,0,.
Reference (s):
a
US 2 887 489 (Ciba; 1959; CH-prior. 1956).
b
US 2 982 769 (Ciba; 1961; appl. 1955).
Formulation(s):
tabl. 0.25 mg; tabl. 0.25 mg (comb. with 5 mg methyclothiazide)
Trade Name(s):
F: Enduronyl (Abbott)-comb.; Harmony1 (Abbott); wfm Oreticyl (Abbott)-comb.;
wfm USA: Enduronyl (Abbott)-comb.; wfm
GB: Enduronyl (Abbott)-comb.; wfm
wfm Harmony] (Abbott); wfm