alternative synthesis from 3-alkoxy-l8-methyl-3,5-estradien-l7-one derivatives: EP 201 452 Schering AG; appl.. medical w e for oral contraception in combination with ethynyl-estradiol:
Trang 1Gestodene G 961
1 methone-
sulfanyl
chloride
Reference(s):
BE 847 090 (Schering AG; appl 8.10.1976; D-prior 10.10.1975, 12.8.1976)
DOS 2 546 062 (Schering AG; appl 10.10.1975)
DE 2 636 404 (Schering AG; appl 12.8.1976)
DE 2 636 405 (Schering AG; appl 12.8.1976)
DOS 2 636 407 (Schering AG, appl 12.8.1979)
Hofmeister, H et al.: Arzneirn.-Forsch (ARZNAD) 36, 781 (1986)
alternative synthesis from 3-alkoxy-l8-methyl-3,5-estradien-l7-one derivatives:
EP 201 452 (Schering AG; appl 7.5.1986; D-prior 10.5.1985)
US4719 054 (Schering AG; 12.1.1988; appl 9.5.1986; D-prior 10.5.1985)
medical w e for oral contraception in combination with ethynyl-estradiol:
EP 148 724 (Schering AG; appl 18.12.1984; D-prior 22.12.1983)
US 4 621 079 (Schcring AG; 4.1 1.1986; appl 21.12.1984; D-prior 22.12.1983)
medical use for treatment of P-TGF dependent tumors:
EP 399 631 (Schering AG; appl 17.5.1990; D-prior 17.5.1989)
tramdermal delivery system:
EP 370 220 (Schering AG; appl 11.10.1989; D-prior 27.10.1988)
Formulation(s): drg and tabl 75 pg in combination with 30 pg ethynylestradiol
Trade Name(s):
D: Femovan (Schering; 1987)-
comb with ethynylestradiol
Minulet (Wyeth)-comb
Lederle)-comb with
ethynylestradiol
Meliane (&hering)-comb
with ethynylestradiol
Minulet (Wyeth-Leder1e)-
comb with ethynylestradiol
Moneva (&hering)-comb
with ethynylestradiol Phaeva (Schering)-comb I:
with ethynylestradiol Tri-minulet (Wyeth)-comb
with ethynylestradiol GB: Fernodene (Schering;
1987)-comb with ethynylestradiol Minulet (Wyeth; 1997)- comb with ethynylestradiol
Triadene (Schering)-comb with ethynylestradiol Ginoden (Schering; 1987)- comb with eth ynylestradiol Milvane (&hering)-comb wilh ethynylestradiol Minulet (Wyeth; 1988)- comb with ethynylestradiol Il-iminulet (Wyeth)-comb with ethynylestradiol
Trang 2962 G Gestonorone caproate
Gestonorone caproate
(Gestronol hexanoate)
Use: progestogen (for treatment of prostate hypertrophy
LD,,,: >10 glkg (M, p.0.);
>10 glkg (R, p.0.)
CN: 17-[(I -oxohexyl)oxy]-l9-norpregn-4-ene-3,20-dione
17-hydroxy-19-
norprogesterone
(from 38-hydroxy-20-0x0-5,16-
pregnodiene; cf pregnenolone
synthesis)
copraic anhydride Geslonorone coproote
DE 1 074 582 (Schering AG; appl 24.9.1958)
Popper, A et al.: Arzneh-Forsch (ARZNAD) 19,352 (1969)
(also starting material)
Formulation(s): amp 200 mg
Trade Namefs):
Use: orally active progestogen (for treatment of endometriosis), antigonadotropin
R N : 16320-04-0 MF: C2,H2402 MW: 308.42
CN: ( l 7 a ) - 13-ethyl-17-hydro~y-18,19-dinorpregna-4,9,1 I-trien-20-yn-3-one
3 N-bromo- succinirnide
3.5.17-trioxo-1 1 -
brorno- 13-ethyl- 4.5-secogon-9-ene
Trang 3Gestrinone G 963
C H
(COOH),
0 ' 1 ethylene glycol
oxalic acid
2 methylrnognesiurn
4.9,l 1-triene- bromide, ocetylene (11) 13-ethyl-17@-hydroxy-
3.17-dione (I)
Gestrinone
'1' 1 P(OC,H5),
&OH
2 ~ 0 ; acetone .SO & HCOOW HCIO,
1 triethyl phosph~te
13-ethyl-? 7- ethynyl-11@,17@- dihydroxygano- 4.9-diene-3-one
Reference(s):
a DE 1 593 307 (Roussel-Uclaf; appl 1966; F-prior 1965)
b DE 1 618 810 (Roussel-Uclaf; appl 1967; F-prior 1966)
alternative synthesis:
DOS 2 212 589 (Roussel-Uclaf; appl 15.3.1972; F-prior 19.3.1971)
GB 1 069 709 (Roussel-Uclaf; appl 1966; F-prior 1964)
synthesis of 13P-ethyl-4,9,1l -gonatriene-3,17-dione:
FR 1 526 962 (Roussel-Uclaf; appl 6.1.1967)
alternative synthesis:
NL 6 517 141 (Roussel-Uclaf; appl 1965; F-prior 1964)
Trang 4964 G Gitaloxin
synthesis of 3,5-dioxo-13-ethyl-17~-hydroxy-4,5-secogon-9-ene:
NL 6 414 702 (Roussel-Uclaf; appl 1965; F-prior 1963, 1964)
GB 1 096 761 (Roussel-Uclaf; appl 1964; F-prior 1963)
synthesis of 13-ethyl-17-ethynyl-1 lP,17P-dihydroxygona-4,9-diene-3-one:
FR-M 5 435 (Roussel-Uclaf; appl 1966)
Formulation(s): cps 2.5 mg
Trade Name(s):
Gi taloxin
(1 6-Fonnylgitoxin)
Use: cardiac glycoside
LDso: 28.7 g/kg (M, p.0.);
29.960 mglkg (R, p.0.)
CN: (3P,5P, 1 6P)-3-[(O-2,6-dideoxy-P-D-ribo-hexopyranosyL(1 +4)-0-2,6-dideoxy-P-D-ribo-hexopyranosyl-
(1 +4)-2.6-dideoxy-P-D-ribo-hexopyranosy1)oxyl- 16-(fonny1oxy)- 14-hydroxycard-2q22)-enolide
+ HCOOH
OH
Reference(s):
DE 1 026 3 12 (Boehringer Mannh.; appl 1955)
extraction from Digitalis purpurea:
DOS 1 042 838 (Boehringer Mannh.; appl 1958)
mixed crystals with digitoxin:
DE 1 140 315 (Boehringer Mannh.; appl 1961)
injection solution:
BE 618 160 (Christians; appl 25.5.1962)
review:
Georges, A et al.: Therapie (THERAP) 18, 209 (1963)
Formulation(s): tabl 0.1 mg
Trade Name(s):
Trang 5r
Gitoformate
(Pentaforrnylgitoxin)
Use: cardiac glycoside
RN: 10176-39-3 MF: C4,HMOI9 MW 921.00 EINECS: 233-450-3
LD,: 23.9 mdkg (M, p.0.);
39.01 mglkg (R, p.0.)
formyl-P-D-ribo-hexopyranosyl-(1 +4)-2,6-dideoxy-3-0-formyl-~-~-ribo-hexopyranosyl)oxy]-l6-
(formy1oxy)- 14-hydroxycard-20(22)-enolide
HCOOH
formic acid
Rtference(s):
BE 625 447 (Manufacture de Produits Pharmaceutique; appl 28.1 1.1962)
Formulation(s): tabl 0.04 mg, 0.06 mg
Trade Name(s):
wfm
Use: analgesic, anti-inflammatory
RN: 3820-67-5 MF: Cl,H,,ClN2O, MW: 372.81 EINECS: 223-315-7
LD,,: 1486 mgkg (M, p.0.);
2300 mgkg (R, p.o.1
CN: 2-[(7-chloro-4-qu1nolinyl)amino]benzoic acid 2,3-dihydroxypropyl ester
? chloride 4-hydroxymethyl-
Trang 6966 G Glaziovine
quinoline
Rr;ference(s):
US 3 232 944 (Roussel-Uclaf; 1.2.1966; F-prior 20.8.1962)
FR-M 2 41 3 (Roussel-Uclaf; appl 20.1 1.1962; prior 20.8.1962)
anthranilic acid monoglyceride,from isatoic anhydride:
E-appl 678 (Pierre Fabre; appl 18.7.1978; F-prior 26.7.1977)
F;irmulatiort(s): suppos 500 mg; tabl 200 mg
Trude Name(s):
wfm
Use: tranquilizer
CN: (i)-2',3',8',8'a-tetrahydro-6'-hydroxy-5'-metloxy-1'-methylspiro[2,5-cyclol~exadiene-l,7'(1'H)-
cyclopent[ij]isoquinolin]-4-me
CH3
, I
rneihoxyrneihylene- triphenylphosphorane 6.7-dirnethoxy-2-methyl-
1.2.3.4-tetrahydroisoquino-
line- 1 -acetic acid
~ ~ ~ " v -.cH3 - , c - s o , H.0 3 ' HO 9- H , C , ~ ~ ~ , Koc(cH,),
rnethanesulfonic CH3 methyl vinyl potassium ' I'
H3C
Trang 7Glibenclamide G 967
1 pyridine
2 Br2 tier CH3CooH H3cKy$\ CH3
B r
0
Reference(s):
DOS 2 363 53 1 (Siphar; appl 20.12.1973; CH-prior 22.12.1972)
GB 1 459 210 (Siphar; valid from 18.12.1973; CH-prior 22.12.1972)
alternative syntheses:
U S 3 886 166 (Siphar; 27.5.1975; CH-prior 22.12.1972, 26.2.1973)
DOS 2 363 529 (Siphar; appl 20.12.1973; CH-prior 22.12.1972,26.2.1973)
Kametani, T et al.: Tetrahedron Lett (TELEAY) 1973, 4219
DOS 2 363 530 (Siphar; appl 20.12.1973; CH-prior 22.12.1972)
isolation from the leaves of Ocorea glaziovii:
Gilbert B et al.: J Am Chem Soc (JACSAT) 86, 694 (1964)
Formulation(s): tabl 200 mg
Trade Name(s):
I: Suavedol (Simes); wfm
Glibenclamide
(Gly buride)
Use: antidiabetic
RN: 10238-21-8 MF: C2,H2,CIN,0sS MW: 494.01 EINECS: 233-570-6
LDs,: 3250 m g k g (M, p.0.);
>20 g k g (R, p.0.);
>10 g k g (dog, p.0.)
CN: 5-chloro-N-[2-[4-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxybenzamide
2-phenyl-
5-chloro-2-meth-
oxybenzoic ocid
Trang 8968 G Glibornuride
I -*
1 chlorc- "'eH cyclohexyl
sulfonic
0-CH,
acid
isocyanote
I Glibenclarnide
Aumiiller, W et al.: Arzneim.-Forsch (ARZNAD) 16, 1640 (1966)
DE 1 283 837 (Hoechst; appl 13.7.1967; CDN-prior 21.7.1966)
DE 1 301 812 (Hoechst; appl 27.7.1965)
BE 684 652 (Hoechst; appl 27.7.1966; D-prior 27.7.1965)
US 3 454 635 (Hoechst; 8.7.1969; appl 13.7.1966; D-prior 2.12.1965)
Fortnulation(s): tabl 1.75 mg, 2.5 mg, 3.5 mg, 5 mg
Trade Name(s):
Bastiverit (Bastian-Werk)
duraglucon (durachemie)
Euglucon N (RocheIHMR;
1969)
Gluconorm (Wolff)
Glucoreduct (Sanofi
Winthrop)
Glucoromed (Lichtenstein)
Gluco Tablinen (Sanorania)
Glycolande (Synthelabo)
Humedia (APS)
Maninil (Berlin-Chemie) I:
Praeciglucon (Pfleger) Semi-Euglucon N (Rochel HMR)
Semi-Gliben-Puren N (Isis Puren)
Daonil (Hoechst) Euglucan (Boehringer Mannh.)
Hemi-Daonil (Hoechst) Miglucan (Boehringer Mannh.)
Daonil (Hoechst) Euglucon (Hoechst) Semi-Daonil (Hoechst) Daonil (Hoechst)
Euglucon (Boehringer Mannh.)
Gliben (Gentill) Glibomet (Guidotti)-comb Gliboral (Guidotti) Glucomide (Lipha)-comb combination preparat~ons
Euglucon (Yamanouchi) USA: Diabeta (Hoechst Marion Roussel)
Glynase (Pharmacia &
Upjohn) Micronase (Pharmacia &
Upjohn)
Use: antidiabetic
LDso: >20 glkg (M, p.0.);
18 glkg (R, p.o.1
CN: [1S-(endo,endo)]-N-[[(3-hydroxy-4,7,7-trimethylbicyclo[2.2.l]hept-2-yl)amino]carbonyl]-4-
methylbenzenesulfonamide
Trang 9Gliclazide G 969
,,,\J H 2
4 ,,,,,,, +
pyridine
_*
O H
C H 3 CH3
Reference (s):
DE 1 695 201 (Hoffmann-La Roche; appl 21.9.1967; CH-prior 28.10.1966,24.4.1967, 17.7
US 3 654 357 (Roche; 4.4.1 972; CH-prior 26.4.1968)
US 3 787 491 (Hoffmann-La Roche; 22.1.1974; prior 29.9.197 1)
US 3 860 724 (Hoffmann-La Roche; 14.1.1975; prior 29.9.197 1)
C H 3
C H 3
3endo-amino- ethyl 4-toluenesulfonyl-
Formulation(s): tabl 25 mg
Glibornuride
Trade Naine(s):
0-borneol corbarnote
Use: antidiabetic RN: 21 187-98-4 MF: Cl,H,,N303S MW: 323.42 EINECS: 244-260-5
LD,: 295 mglkg (M, i.v.); 3 g/kg (M, p.0.);
382 mgkg (R, i.v.); 3 glkg (R, p.0.)
CN: N - [ [ ( h e x a h y d r o c y c l o p e n t a [ c ] p y r r o l - 2 ( 1 H ) - n a m i d e
3-amino-3- ozabicyclo- [3.3.0]octone (I)
ethyl 4-toluene-
Referencefs):
US 3 501 495 (Science Union; 17.3.1970; GB-prior 10.2.1966)
FR 1 510714 (Science Union; appl 9.2.1967; GB-prior 10.2.1966)
Formulation(s): tabl 40 mg, 80 mg
Trade Name(s):
Trang 10970 G Glimepiride
Glimepiride
(Hoe 490)
Use: insulin-sparing sulfonylurea, antidiabetic
CN: 1ratzs-3-ethyl-2,5-dihydro-4-methyl-N-[2-[4-[[[[(4-
methylcyclohexyl)amino]carbonyl]amino]sulfonyl]pheny1]ethyl]-2-oxo- 1 H-pyrrole-1-carboxamide
, I
1 chlorosu-
3-ethyl-4- 2-phenylethyl
methyl-A'- isocyanate
pyrrolin-2-one
H
OCN
(1) trans-4-methyl-
cyclohexyl isacyonate
Glimepiride
DE 2 951 135 (Hoechst AG; appl 25.6.1981; D-prior 19.12.1979)
preparation oj'3-ethyl-4-methyl-A3-pyrrolin-2-one
Siedel: Justus Liebigs Ann Chem (JLACBF) 554, 144, 155 (1943)
Plleninger; Decker: Justus Liebigs Ann Chem (JLACBF) 598, 198,205 (1956)
Bishop, J.E.; Nagy, J.O.; O'Connell, J.F.; Rapoport, H.: J Am Chem Soc (JACSAT) 113 (21), 8024 (1991) Schoenleber, R.W.; Kim, Y.; Rapoport, H.: J Am Chem Soc (JACSAT) 106 (9), 2645 (1984)
Tipton, A,; Ligthner, D.A.: Monatsh Chem (MOCMB7) 130 (3), 425 (1999)
for treatment of'arteriosclerosis:
EP 604 853 (Hoechst Japan; appl 6.7.1994; J-prior 28.12.1992)
jbrmulation:
EP 649 660 (Hoechst AG; appl 26.4.1995; D-prior 26.1.1993)
controlled release:
DE 4 336 159 (Hoechst AG; appl 27.4.1994; D-prior 22.1.1993)
Jbr trmtnlent of'obesiiy:
WO 9 303 724 (Upjohn Co.; appl 4.3.1993; USA-prior 26.8.1991)
Formulation(s): tabl 1 mg, 2 mg, 3 mg, 4 mg
Trade Name(s):