magnesium salt zinc salt choline orotate L-lysine orotate ocetyl chloride I Orotic ocid I 1.. glyoxylic acid ominoaceto- sodium cyon0te hydantoic acid... Behrend: Justus Liebigs
Trang 1Ornipressin 0 1501
CN: 8-L-ornithinevasopressin
Z OH H
Tos
Z
Tos
Z
R
0
NP:
Ornipressin
FR 1 396 607 (Sandoz; appl 3.4.1964; CH-prior 5.4.1963)
Huguenin, R.L.; Boissonnas, R.A.: Helv Chim Acta (HCACAV) 46, 1669 (1963)
Bodanszky, M et al.: J Am Chem Soc (JACSAT) 86,4452 (1964)
Trang 21502 0 Orotic acid
Formulation(s): amp 2.5 iu10.5 ml, 2.5 iu/5 ml
Trade Name(s):
Pharma)
Orotic acid
(Acide orotique)
Use: metabolic therapeutic, electrolyte carrier
LD,,,: 770mg/kg(M, i.v.);2g/kg (M.p.0.)
potassium salt
LD,,,: 10.9 g/kg (R, p.0.)
magnesium salt
zinc salt
choline orotate
L-lysine orotate
ocetyl chloride
I Orotic ocid I
1 OHC-COOH NoOH
0 2 HCI
H 1 glyoxylic acid ominoaceto- sodium cyon0te hydantoic acid
Trang 3Orotic acid 0 1503
H
Orotic acid
rnaleic acid rnonoureide 5-brornodihydro-
orotic ocid
11 , CH3COOH H
trichloroocetyl 0 0
Reference(s):
a DAS 1 770 117 (Diamalt; appl 2.4.1968)
DAS 2 025 247 (Lonza; appl 23.5.1970; CH-prior 28.5.1969)
b DAS 2 502 951 (Diamalt; appl 24.1.1975)
US 4 113 950 (Diamalt; 12.9.1978; D-prior 24.1.1975)
c CH 595 351 (Lonza; appl 7.5.1975)
d US 4 064 126 (Lonza; 20.1 2.1977; CH-prior 1 1.8.1975)
DOS 2 540 275 (Lonza; appl 24.2.1977; CH-prior 11.8.1975)
alternative syntheses:
j b m oxalacetic acid ester a n d urea:
Miiller: J Prakt Chem (JPCEAO) 56, 488 (1897)
Behrend: Justus Liebigs Ann Chem (JLACBF) 378, 165 (1910)
US 2 937 175 (RhBne-Poulenc; 17.5.1960; F-prior 18.1.1956)
DE 1 034 640 (RhBne-Poulenc; appl 1956)
from aspartic acid:
Nye, F et al.: J Am Chem Soc (JACSAT) 69, 1382 (1947)
from glyoxylic acid and hydantoin:
US 4062 847 (Diamalt; 13.12.1977; D-prior 24.1.1975)
fermentatively:
US 3 086 917 (Kyowa Hakko; 23.4.1963; J-prior 15.6.1960)
lithium orotate:
DOS 2 410 181 (Nadrol-Chemie; appl 4.3.1974)
Formulation(s): cps 250 mg (as hydrochloride); cps 60 mg in comb with a-tocopherol acetate; tabl 20 mg
(as zinc salt), 40 mg (as zinc salt), 500 mg (as choline orotate)
Trade Narne(s):
D : Vigodana N (Loges)-comb numerous combination Orolyl (Porcher-Lavril);
Trang 41504 0 Orphenadrine
Vita-thirteen (Sumitomo) generic
Use: antiparkinsonian, muscle relaxant
LD,,,: 33 mgkg(M,i.v.); 125mg/kg(M,p.o.)
hydrochloride
LD,,,: 20 m g k g (M, i.v.); 100 mglkg (M, p.0.);
27.5 mglkg (R, i.v.); 255 m g k g (R, p.0.)
citrate (1:l)
2-methylbenzhydryl Z-dimethylamino-
chloride ethanol
Orphenadrine
Reference(s):
US 2 567 351 (Parke Davis; 1951; prior 1946)
US 2 991 225 (~rocades-~theema;; 4.7.1961; NL-prior 1952)
Bijlsma, U.G et al.: Arzneim.-Forsch (ARZNAD) 5 , 7 2 (1955)
Formulation(s): amp 60 mgl2 ml; s r tabl 100 mg; tabl 100 mg (as citrate)
Trade Name(s):
Freyssinge)-comb.; wfm
Oseltamivir
(GS 4104)
Use: antiviral, anti-influenza, neuramidase inhibitor
CN: (3R,4R,5S)-4-(Acetylamin0)-5-amino-3-(1 -ethylpropoxy)-1 -cyclohexene- 1-carboxylic acid ethyl ester
phosphate
RN: 2042.55-1 1-8 MF: C,,H2,N2O4 H304P MW: 410.40
hydrochloride
citrate
Trang 5Oseltamivir 0 1505
HO COOH
QOH
+ H3C-0 0 - C H 3 Tos-OH, ocetone
OH H 3 C C H 3 p-toluenesulfonic
ocid
(-)-quinic acid 2.2-dirnethoxy-
propone
3.4-0-isopropylidene- 1,5-quinic loctone (I)
SO2CI2 -20°C
pyridine CH2CI2
sulfuryl chloride
ethyl 3.4-0-isopropylidene- 3-pentonone (111) ethyl 3.4-0-(1 -ethylpropylidene)-
5-0-(methonesuIfonyl)-
shikimate (11)
5-0-(methonesulfonyl)- shikimate (N)
1 ~ ~ 3 ~ - ~ - ~ - B F ~ ~ - ~n3c/ 'cn3 ~ 3
CH, 0
2 KHC03 aq C2H50H
1v
1 trimethylsilyl triflote
ethyl (3R,4R,5S)-4.5- epoxy-3-(1 -ethylpropoxy)-
1 -cyclohexene- 1 -corboxylote (V)
1 sodium ozide I
2 triphenylphosphine
1 NoN3, NH,CI D M F
2 0 0
H 3 c J - o K c H 3 ,
2 ocetic anhydride
0 C 0 , 3
1 Hz Roney-Ni C2HSOH
Aoc:H3 2 8% H3PO+ ,
N 3
Trang 61506 0 Otilonium bromide
H ~ C - O H
_*
H 3 C - 0 ~ 0 - C H 3
OH 2.2-dimethoxy-
isopropylidene- shikirnote (VII)
R
H3C-S-CI , TEA
11
0
V l l b 11 -b V -+
sulfonic ocid
Reference(s):
a RohlofP, J.C et al.: J Org Chem (JOCEAH) 63, 4545-4550 (1998)
WO 9 626 933 (Gilead Sciences; appl 26.2.1996; USA-prior 27.2.1995)
US 5 886 213 (Gilead Sciences; 23.3.1999; USA-prior 22.8.1997)
US 5 859 284 (Gilead Sciences; 12.1.1999; USA-prior 23.8.1996)
b Federspiel, M et al.: Org Process Res Dev (OPRDFK) 3 (4) 266-274 (1999)
Tmde Nurne(s):
CH: Tami flu (Roche; 1999)
LD,,,: 46.5 mglkg (M, i.v.); > I 500 mglkg (M, p.0.);
14.1 mg/kg (R, iv.); >I650 mglkg (R, p.0.)
diaxone, pyridine
- 1
N H 2
4-(2-octyloxybenzoyl-
ornino)benzoic acid (I)
4-(2-octyloxybenzoylornino)- benzoyl chloride
Trang 7Oxaceprol 0 1507
methyl bromide
Otilonium bromide
Reference(s):
DOS 1 643 458 (Menarini; appl 15.9.1967; I-prior 17.9.1966)
US 3 536 723 (Menarini; 27.10.1970; I-prior 27.9.1966)
Ghelardoni, M et a].: J Med Chem (JMCMAR) 16, 1063 (1973)
Formulation(s): amp 150 mg; drg 4 0 mg; suppos 20 mg; tabl 40 mg
Trade Narne(s):
Oxaceprol ATC: D 1 I A X O ~ ; MO I ~ ~ 2 4
(Aceprolinum; N-Acetyl-4-hydroxy-L-proline) Use: connective tissue therapcutic,
antirheumatic
CN: trans- 1-acetyl-4-hydroxy-L-proline
trans-L-hydroxy- ocetic anhydride
proline
H
CH,COOH
D coo,
HO 0 0 -
Oxaceprol
u
?-
HO
Reference(s):
GB 1 246 141 (P and B Coirre; appl 30.8.1968; F-prior 14.9.1967, 16.5.1968)
DAS 1 795 327 (S.A.R.L Franco-Chimie; appl 13.9.1968; F-prior 14.9.1967, 16.5.1968)
DOS 2 139 476 (P and B Coirre; appl 6.8.1971)
For~nulation(s): f c tabl 200 mg
Trade Narne(s):
Trang 81508 0 Oxacillin
Use: antibiotic
LD,,,: 1490 m g k g (M, i.v.); 6500 mgkg (M, p.0.)
azabicyclo[3.2.0]heptane-2-carboxylic acid
monosodium salt monohydrate
RN: 7240-38-2 MF: C,yHIRN3Na0,S H 2 0 MW: 441.44
benzoldehyde benzoldoxime benzhydroxirnic
acid chloride (I)
aceloacetic m i d ethyl 5-methyl-3-phenyl- 5-methyl-3-phenylisoxo-
ethyl ester isoxorale-4-corbaxylate zale-4-carbaxylic acid (Il)
11
thionyl
chloride
5-methyl-3-phenyl-
isoxazole-4-carbonyl
chloride
Oxacillin
Refermce(s):
US 2 996 501 (Beecham; 15.8.1961; GB-prior 31.3.1960)
GB 905 778 (Beecham; appl 3 1.3.1960; valid from 14.3.1961)
GB 958 478 (Beecham; appl 28.2.1963: USA-prior 13.3.1962)
Formularion(s): cps 250 mg, 500 mg; vial 0.5 g, 1 g (as sodium salt)
Trade Name( s):
Use: antidepressant
Trang 9Oxaflumazine 0 1509
hydrochloride
LD,,: 80 mglkg (M, i.v.); 365 mglkg (M, p.0.)
CI+O*%
bromine
2-chloroethyl
vinyl ether
1 -brorno-2-(2-chloro-
ethoxy)-2-(3-trifluoro-
rnethylpheny1)ethone (I)
phenylrnognesiurn (2-ch1oroethoxy)- bromide 1.2-dibrornoethone
toluene, A
isopropylarnine ( Oxoflozane
DOS 1 910 477 (CERM; appl 1.3.1969; F-prior 4.3.1968, 29.5.1968 18.6.1968,27.8.1968, 15.1 1.1968,
19.2.1969)
US3637680(CERM; 25.1.1972;F-prior.4.3.1968,29.5.1968, 18.6.1968,27.8.1968, 15.11.1968, 19.2.1969) Busch, N et a].: Eur J Med Chem.-Chim Ther (EJMCAS) 11, 201 (1976)
Formulation(s): drops 2 %
Trade Narnefs):
Use: psychosedative
hydrogen succinate (1:l)
RN: 41761-40-4 MF: C26H32F,N,02S C4H604 MW: 625.71
10-(3-pipera2inopropyl)- 2-(2-chloroethy1)-
2-trifluorornethyl- 1,3-dioxone
phenothiozine (from acrolein, 1.3-
(cf fluphenozine propanediol ond HCI)
synthesis)
Trang 101510 0 Oxaliplatin
Reference(s):
DAS 1 620 281 (Roussel-Uclaf; appl 28.6.1965; F-prior 29.6.1964,28.9.1964)
Ratouis, R.; Boissier, J.R.: Bull Soc Chim Fr (BSCFAS) 1966, 2963
alternative synthesis:
DOS 1 9 11 719 (S.I.F.A.; appl 7.3.1969; F-prior 8.3.1968)
Trade Narne(s):
wfm
Oxaliplatin
( I -0HP; NSC-266046; RP-54780)
LD,,,: 19.8 mg/kg (M, i.p.);
14.3-15.6 mglkg (R, i.p.)
1 (R),P(R)-di-
aminocyclohexone
Oxaliplatin
Reference(s):
Kidani, Y et al.: J Clin Hematol Oncol (JCHODP) 7, 197 (1977)
JP 53 03 1 648 (Kidani; appl 25.3.1978; J-prior 6.9.1976)
JP 09 132 583 (Tanaku Kihinzobo Kogyo; appl 20.5.1997; J-prior 10.11.1995)
as stable aqueous formulation:
WO 9 604 904 (Dehiopharm SA; appl 22.2.1996; CH-prior 8.8.1994)
in combination with cisplatin:
WO 9 412 193 (Debiopharm SA; appl 9.6.1994; CH-prior 24.1 1.1992)
Formulation(s): vial 50 mg, 100 mg
Trade Narne(s):
Use: anti-inflammatory, analgesic
LD,,,: 92 mglkg (M, p.0.);
78 mglkg (R, p.0.)