eye drops containing loratadine metabolites: WO 9 848 803 Schering-Plough K.K.; WO-prior.. treatment of allergic rhinitis and asthma with desloratadine: WO 9 834 61 1 Sepracor; appl...
Trang 1Desipramine D 591
Use: ant~depressant RN: 50-47-5 MF: CIXH22NZ MW: 266.39 EINECS: 200-040-0
LD,: 22 mgkg (M, i.v.); 448 mglkg (M, p.o.),
29 mgkg (R, I.v.); 375 mglkg (R, p.0.)
CN: 10,l I-dihydro-N-methy1-5H-dibenz[b,flazep1ne-5-propanam1ne
monohydrochloride
RN: 58-28-6 MF: C,,H2,N2 HCI MW: 302.85 EINECS: 200-373-1
LDN: 37 mgkg (M, i.v.); 315 mglkg (M, p.0.);
19 mgkg (R, i.v.); 87 1 mgkg (R, p.0.);
25 mglkg (dog, I.v.)
10.1 1-dihydra-5H- prapane 5-(3-chloropropy1)-
dibtnz[b.f]ozepine (1) 10.1 1-d~hydro-5H-
d~benz[b.f]azep~ne
3-(benzylmethyl-
amino)propyl chloride
(from 1-bromo-3-chloro-
propone and benzylmethylomine)
I Desipramine
b
sodium
L ~ / C H ~ + cI ,R O-CH, 4
a23 L N I C H 3
I
imipramine ethyl
( q v.1 chloroformote
Reference(s):
a FR-M 796 (Geigy; appl 3.9.1960; CH-prior 4.9.1959)
GB 908 788 (Geigy; appl 1960; CH-prior 1959)
DE 1 I89 550 (Geigy; appl 1960; CH-prior 1959)
b US 3 454 698 (Colgate-Palmolive; 8.7.1969; prior 25.5.1960)
US 3 454 554 (Colgate-Palmolive; 8.7.1969; prior 25.5.1960)
c DE 1 288 599 (Geigy; appl 13.3.1962; CH-prior 14.3.1961)
DE 1 445 800 (Geigy; appl 2.3.1962; CH-prior 3.3.1961)
Desipramine
I
Formulation(s): drg 25 mg; tabl 25 mg
Trang 2592 D Desloratadine
Trade Name(s):
D: Pertofran (Novartis F: Pcrtofran (Novartis; as J: Pertofran (Fujisawa)
Petylyl (ASTA Mcdica GB: Pertofran (Geigy); wfm Marion Roussel; as
Desloratadine
(Sch-34117)
Use: non-sedating antihistamine metabolite of loratadine RN: 100643-71-8 MF: C,,H,,CIN, MW: 310.83
CN: 8-Chloro-6,11 -dihydro-1 1 -(4-piperidinylidene)-5H-benz[5,6]cyclohepta[l,2-blpyridine
laratadine (q v.)
YH3
BrCN
*
cyonogen bromide
I Desloratadine 1
Desloratadine
u
8-chloroazotadine
(cf lorotadine)
Reference(s):
a,b WO 8 503 707 (Schering Corp.; appl 8.2.1985; USA-prior 15.2.1984)
polymorphs:
WO 9 901 450 (Schering C o p ; appl 1.7.1998; USA-prior 2.7.1997)
eye drops containing loratadine metabolites:
WO 9 848 803 (Schering-Plough K.K.; WO-prior 25.4.1997)
treatment of allergic rhinitis and asthma with desloratadine:
WO 9 834 61 1 (Sepracor; appl 10.2.1998; USA-prior 11.2.1997)
WO 9 620 708 (Sepracor; appl 1 1.12.1995; USA-prior 30.12.1994)
transdermal dosage system:
DE 4 442 999 (Hexal Pharma; D-prior 2.1 2.1994)
Trade Name(s):
IJSA: DCL (Schering-Plough;
2000)
Trang 3Deslorelin D 593
precocious puberty)
RN:
CN:
57773-65-6 MF: CHH,,N,7012 MW: 1282.48
6-~-tryptophan-9-(N-ethyl-L-prolinamide)-lO-deglycinamide luteinizing hormone-releasing factor (pig)
Tos: Tosyl
Boc: tert-butoxycorbonyl
C12BzI: 2.4-dichlorbbenzyl
Bzl: benzyl
DNP: 2,4-dinitrophenyl
Boc-
Boc-
Boc OH H-
Boc
Boc- H H CI2BzI Boc
\CI,B~I -OH H
\BZI \ C I ~ B Z I
\ C 1 2 ~ z ~
\ C ~ I
*rq Pro Resin
Bac OH CI-
Boc
Boc- H H Tos Boc
\TOS
OH H
\TOS
\TOS
as
0s
Trang 4594 D Desmopressin
Rrj'irence(s):
DOS 2 830 629 (Salk Inst.; appl 12.7.1978; USA-prior 14.7.1977, 26.6.1978)
US 4 218 439 (Salk Inst.; 19.8.1980; appl 26.6.1978; prior 14.7.1977)
Formulation(s): vial 500 pg
Trade Name(s):
GB: Somagard (Monmouth; USA: Somagard (Roberts; 1990);
Use: antidiuretic RN: 16679-58-6 MF: C46HwN14012S2 MW: 1069.24 EINECS: 240-726-7 CN: I -(3-mercaptopropanoic acid)-8-D-argininevasopressin
RN: 16789-98-3 MF: C4,HwN,40,2S2 2C2H402 MW: 1189.34
Z-D-Arg(Tos)-OH Gly-OEt HCI Z-D-Arg(Tos)-Gly-OEt (1)
D-Arg(Tos)-GIy-OEt
Z-Pro-D-~rg(T0s)-GIy-OE~ (U) Z-Pr0-O-Arg(Tos)-Gly-~H~ (111)
Trang 5Desmopressin D 595
2-Asn-Cys(Bz1)-Pro-D-Arg(Tos)-Gly-NH (V)
Z-Cln-Asn-Cys(Bz1)-Pro-D-Arg(Tas)-Cly-NH (VI)
I
Tyr-Phe-OMe HCI Bzl-Mep-ONp BzI-Mep-Tyr-Phe-OMe (VII1)
Trang 6596 D Desogestrel
1 HBr CH,WOH
2 DMF N(C2HS),, pH 8.0.-15 "C
1 No, liq NH3, -40 O C
2 CH,COOH, pH 6.8
3 K3[WCN),l
4 purification on sephadex
Referenceis):
US 3 454 549 (Sandoz; 8.7.1969; CH-prior 17.7.1964)
US 3 497 49 1 (Ceskoslovenska Akad.; 24.2.1970; CS-prior 15.9.1966)
Huguenin, R.L.; Boissonas, R.A.: Helv Chim Acta (HCACAV) 49,695 (1966)
DOS 2 723 453 (Ferring; appl 24.5.1977; S-prior 24.5.1976)
DOS 2 749 932 (Ferring; appl 8.1 1.1977; S-prior 12.1 1.1976)
GB I 539 317 (Ferring; appl 20.5.1977; S-prior 24.5.1976)
GB 1 539 318 (Ferring; appl 4.1 1.1977; S-prior 12.1 1.1976)
Formulation(s): amp 4 kg; doses spray 0.1 mg; tabl 0.1 mg, 0.2 mg
Trade Namefs):
Minirin (Ferring) I: Minirin (Ferring) Rorer; as acetate) F: Minirin (Ferring; as J: Desmopressin (Kyowa
Use: progestogen, oral contraceptive (in combination with ethinylestradiol) RN: 54024-22-5 MF: C,,H,,O MW: 310.48 EINECS: 258-929-4
CN: (17a)-13-ethyl-] 1-methyIene-18,19-dinorpregn-4-en-20-yn-17-01
OH
+ & ii G Pb(OCOCti3)4, lead tetraacetate, I2 b I
1 lp-hydroxy-A4- ethylene
estrene-3.17-dime
Trang 7Desonide D 597
1.N2H4
0 2 CrOJ
b 11
bromide
) 111
1 1,2-ethanedithiol
2 sodium
(11) rnethylenetriphe- 11-rnethylene-18-methyl- borahydride
nylphosphorane b4-estrene-3.1 7-dione
oxide
Reference(s):
U S 3 927 046 (Akzona; 16.12.1975; appl 3.12.1973; NL-prior 9.12.1972)
DE2 361 120 (Organon; appl 7.12.1973; NL-prior 9.12.1972; 15.11.1973)
NL 7 411 607 (Akzo; appl 2.9.1974)
Broek, AS van den et al.: Recl Trav Chim Pays-Bas (RTCPA3) 9 4 , 3 5 (1975)
Formulation(s): tabl 150 pg (in combination with ethinylestradiol)
Trade Name(s):
D: Biviol (Nourypharma)-
comb
Cyclosa (Nourypharma)- F:
comb
Cydeane (Mansanto)-
comb
Lovelle (Organon)-comb
Marvelon (Organon; 198 1)- GB:
comb
Oviol (Nourypharma)- comb
Cydeane (Momanto)- comb
Mercilon (Organon)-comb
Varnoline (Organon; 1984)- comb
Marvelon (Organon)-comb
Mercilon (Organon; 1982)- comb
I: Mercilon (Organon)-comb Planum (Mer1arini)-comb Practil (Organon)-comb Securgin (Menarini)-comb USA: Desogen (Organon) Ortho-Cept (Ortho-McNeil Pharmaceutical)
Desonide
(Prednacinolone)
ATC: D07AB08; SOIBAI 1 Use: topical glucocorticoid RN: 638-94-8 MF: C,H,,O, MW: 416.51 EINECS: 21 1-351-6
LD,: 3710 m g k g (M, p.0.)
CN: (1 lP,l6a)-ll,2l-dihydroxy-l6,l7-[(l-methylethylidenc)bis(oxy)]pregna-l,4-diene-3,20-dione
Trang 8598 D Desoximetasone
OJH microbiolqical hydroxylation and dehydration 0JH
[S roseochromogenes ond A simplex] , &OH
H H
( q v.)
HCI
Desonide
Reference(s):
US 3 536 586 (Squibb; 27.10.1970; prior 25.1.1968)
US 2 990 401 (American Cyanamid; 27.6.1961; prior 18.6.1958, 11.3.1958)
Bernstein, S et al.: J Am Chem Soc (JACSAT) 81, 4573 (1959)
synthesis of hydrocortisone:
Allen, W.S.; Bernstein, S.: J Am Chem Soc (JACSAT) 78, 1909 (1956)
Bernstein, S.: Recent Prog Horm Res (RPHRA6) 14, 1 (1958)
alternative synthesis:
US 3 549 498 (Squibb; 22.12.1970; prior 2.4.1968)
Formulation(s): cream 1 mg/g
Trade Name(s):
F: Locapred (Pierre Fabre) (Farmacologico Milanese) Reticus Antim~cotico Locatrop (Pierre Fabre) -Desonix (Usar)-comb (Farmila)-comb
TridCsonit (Dome- PR 100 (Farmacologico J: Tridesonit (Miles)
GB: Tridesilon (Lagap); wfm Prenacid (SIFI) Tridesllon (Bayer)
Desoximetasone
(Desoximethasone)
ATC: D07AC03; D07XC02 Use: topical glucocorticoid RN: 382-67-2 MF: C2,H2,F0, MW: 376.47 EINECS: 206-845-3
CN: (1 1 ~,16o1)-9-fluoro-11,21-dihydroxy-l6-methylpregna-l,4-diene-3,20-dione
Trang 9d Desoximetasone D 599
3a-ocetoxy-16-pregnene-
- 11,20-dione
(fmm deoxychol~c ac~d)
H,C-MgBr, LiBr
v
methylmognesium bromide
3n-hydroxy-lea-methyl- pregnane- 1 1,20-dione (I)
OMF Li2C03 LiBr
sernicorbazide hydrochloride
21 -ocetoxy-l6a-methyl- pregno- 1.4-diene-3.11.20- trione
0
:: ~ ~ ~ o c o o H , o&:ir H3C-SO2-CI, DMF, pyridine b V
H N N
21 -ocetoxy-1 lp-hydroxy- 16-methyl-1,4-pregno- diene-3.20-dione
Trang 10600 D Desoxycortone acetate
N-Br , HCIO+ D M F
perchlor~c o c ~ d 21-acetoxy-16u-methyl-
1,4.9(1 l)-pregnatriene-
3,20-dione (V)
1 AczO, pyridine
2 HZF2 DMF
3 2 hydrogen NoHC03, CH30H
fluoride
Reference(s):
US 3 099 654 (Roussel-Uclaf; 30.6.1963; F-prior 17.8.1960)
DOS 1 159 441 (Roussel-Uclaf; appl 4.8.1961; F-prior 17.8.1960)
FR 1 296 544 (Roussel-Uclaf; appl 17.8.1960)
Joly, R et al.: Arzneim.-Forsch (ARZNAD) 24, 1 (1974)
synthesis of 21-acetoxy-1 l~-hydroxy-16a-methyl-l,4-pregnadien-3,20-dione:
DOS 1 205 096 (Roussel-Uclaf; appl 12.5.1961; F-prior 14.5.1960, 16.5.1960)
alternative synthesis:
B E 614 196 (Schering AG; appl 21.2.1962; D-prior 22.2.1961)
US 3 232 839 (Schering AG; 1.2.1966; D-prior 22.2.1961, 27.6.1963)
Formulation(s): cream 0.25 %, 0.05 %; lotion 0.25 %; ointment 0.35 %
Trade Name(s):
D: Topisolon (Hoechst) Topifram (Roussel USA: Topicort (Hoechst Marlon
F: Topicorte (Roussel GB: Stiedex LP (Stiefel)
(Deoxycorticosterone acetate; Deoxycortone acetate) Use: mineralocorticoid
RN: 56-47-3 MF: C23H3204 MW: 372.51 EINECS: 200-275-9
desoxycortone
RN: 64-85-7 MF: C2,H3,,O3 MW: 330.47 EINECS: 200-596-4
LD,,,: 1 g/kg (M, route unreported)