formulation with increased stability: JP 06 100 447 Tanabe Seiyaku; appl.. composition for treatment of kidney diseases: JP 272 849 Tanabe Seiyaku; appl.. composition for treatment of
Trang 1Imidapril I 1051
Trade Name(s):
Imidapril
(TA-6366)
Use: antihypertensive (ACE inhibitor)
CN: [4S-[3[R*(R*)],4R*]]-3-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-I-oxopropyl]-l-methyl-2-oxo-4-
imidazolidinecarboxylic acid
munohydrochloride
RN: 89396-94- 1 MF: C,,H,,N,O, HC1 MW: 44 1.9 1
(25)-2-[(IS)-1 -ethoxy-
corbonyl-3-phenyl-
propy~omino]propionic
ocid
benzyl (4s)-I-methyl-
2-0x0-imidorolidine-
4-cahaxylate
DCC THF
(2s)-2-[(lS)-1-ethoxy- corbonyl-3-phenylpropyl- omino]propianic ocid succinimido ester (1)
KOC(CH,)~
T W -40 OC
benzyl (45)-1-methyl-3-[(lS)-
2-[(1S)-1-ethoxycarbonyl-3-phenyl
prapylomino]propionyI]-2-0x0- imidozolidine-4-corboxyl~te (11)
H Pd-C ethanol
u
lmidopril
Trang 21052 1 Imipenem
tert-butyl (4s)- 1 - (2R)-2-(p-toluene-
methyl-2-oxoimi- sulfonyloxy)pro-
dozolidine 4-corboxylote pionyl chloride
tert-butyl (4s)-1- methyl-3-[(2R)-2- (p- toluenesulfonyloxy)- propionyl]-2-oxoimida- zolidine-4-carboxylate (nl)
HCI, dioxane
ethyl (2s)-2-
amino-4-phenyl-
butyrate
Reference(s):
a EP 95 163 (Tanabe Seiyaku; appl 20.5.1983; J-prior 24.5.1982)
b EP 373 881 (Tanabe Seiyaku; appl 12.12.1989; J-prior 16.12.1988)
formulation with increased stability:
JP 06 100 447 (Tanabe Seiyaku; appl 24.9.1992; J-prior 24.9.1992)
composition for treatment of kidney diseases:
JP 272 849 (Tanabe Seiyaku; appl 10.12.1987; J-prior 12.12.1986)
composition for treatment of heart failure:
EP 274 230 (Tanabe Seiyaku; appl 8.12.1987; J-prior 9.12.1986)
Formulation(s): tabl 2.5 mg, 5 mg, 10 mg (as hydrochloride)
Trade Narne(s):
Imipenem
(Imipemide)
Use: p-lactam antibiotic
LD,,,: 1660 m g k g (M, i.v.); >5 glkg (M, p.0.);
1972 mglkg (R, i.v.); >5 glkg (R, p.0.)
CN: [5R-[5a,6a(R*)]]-6-(1-hydroxyethyl)-3-[[2-[(iminomethyl)amino]ethyl]thio]-7-oxo-l- azabicyclo[3.2.O]hept-2-ene-2-carboxylic acid
monohydrate
RN: 7443 1-23-5 MF: C,,H,,N,04S H 2 0 MW: 317.37
Trang 3Imipramine 1 1053
COOH
H O W S + H 3 C \ O ~ N H e H C I -+ pH 8.5
k
H3C H NH2
Reference(s):
Leanza, W.J et al.: J Med Chem (JMCMAR) 22, 1435 (1979)
US 4 194 047 (Merck & Co.; 18.3.1980; prior 21.11.1975)
DOS 2 652 679 (Merck & Co.; appl 19.1 1.1976; USA-prior 21.1 1.1975)
COOH
B7\N H
thienamycin methyl formimidate
production of thienamycin (by fermentation of S cattleya):
US 3 950 357 (Merck & Co.; 13.4.1976; appl 25.1 1.1974)
DOS 2 552 638 (Merck & Co.; appl 24.1 1.1975; USA-prior 25.11.1974)
lmipenem
combination with cilastatin:
EP 48 301 (Merck & Co.; appl 24.9.1980)
hydrochloride
Trade Name(s):
Use: antidepressant
LD,,,: 21 mglkg(M, i.v.); 188 mglkg (M,p.o.);
9300 pglkg (R, i.v.); 250 mglkg (R, p.0.)
CN: 10,11-dihydro-N,N-dimethyl-5H-dibenz[b~azepine-5-propanamine
monohydrochloride
LD,,: 27 m g k g (M, i.v.); 275 mglkg (M, p.0.);
18 m g k g (R, i.v.); 305 mglkg (R, p.0.)
2 CI N/CH3
I
1 sodium amide
2 3-dimethylamino- propyl chlaride
10,ll -dihydro-5H-
dibenz[b,f]azepine
Reference(s):
US 2 554 736 (Geigy; 1951; CH-prior 1949)
DE 829 167 (Geigy; appl 1950; CH-prior 1949)
Trang 41054 I Imiquimod
hydrochloride)
Trade Narne(s):
as hydrochloride)
Pryleugan (ASTA Medica
AWD; as hydrochloride)
Tofranil (Novartis Pharma;
as hydrochloride)
F: Tofranil (Navartis; as
hydrochloride)
GB: Torrani1 (Novartis; as hydrochloride)
Tofranil (Novartis) combination preparations
Efuranol (Taito Pfizer) Feinalmin (Sanko)
Imidol (Yoshitomi) Imilanyle (Takata) Meripramin (Kanebo Nakataki)
Tohanil (Novartis) Tofranil (Novartis; as pamoate)
generic
Use: immunornodulator, interferon alfa inducer, antiviral
CN: 1 -(2-Methylpropy1)- 1 H-imidazo[4,5-c]quinolin-4-amine
hydrochloride
RN: 9901 1-78-6 MF: C,,HI,N4 HCI MW: 276.77
2 oq NoOH
CH3 1 sodium ozide
o ~ o z i n e
4-nitrotetrozolo[l,5-a]-
quinolin-5-yl trifluoro- ocetote (111)
Trang 5isobutylomine (N)
diethoxymethyl
ocetate
triphenyl-
phosphine
1 aq HCI CH3OH
2 aq NoOH
6-(2-rnethylpropy1)-6H-
irnidozo[4.5-c]tetrozolo-
[1,5-alquinoline (VI)
&N , N N
1,2-dichloro- benzene
H 3 c ~ c H 3
&N
N NH,
lmiquirnod
4-hydroxy-3-
nitroquinoline (VIII)
4-chloro-3- nitroquinoline
Trang 61056 1 Imiquimod
H,C CH,
Y
HZ Pt-C
toluene
d
1 -(2-methylpropy1)-
1 H-imidozo[4.5-c]-
quinoline 5-oxide (X11)
1 H3C20407 (XI), 125OC
CH3
2 CH3COOH, HZOZ
1 triethyl orthoformate
2 ocetic ocid, hydrogen peroxide
(XI
POCI3 DMF, 2O0C
1 SOCl,, CHZCIZ, DMF (cot.) HNO,
2 N CH2CIz N(C,H,),
propionic 1 thionyl chloride
a c i d 2 isobutylomine
4-hydroxy-
quinoline
Hz Pt-C, MgSO, 1 HCOOH A
ethyl ocetote 2 H,C-CO-0-OH, CH,COOH
1 formic acid
2 peroxyocetic acid
H,C CH,
Y
benzoyl isocyonote
1 HN03, CH3COOH, 40°C
2 F,C-SO,-0-SO, CF3 CH2C12, N(C2H5),
0 2 trifluoromethonesulfonic anhydride
4-hydroxy-Z(1H)-
quinolinone ( X N )
Trang 7Imiquimod 1 1057
En:
0
sodium borohydride,
nickel chloride B~ or triethyl orthoformote
Hz Pd-C CzH50H
_, Imiquimod
- -
2 POCI3, pyridine or toluene, 50°C
xnr
2.4-dichloro-3- nitraquinoline (XVIII)
2-chloro-N4-(2-methyI- propyl)-3,4-quinoline- diomine (XK)
NH,, CH,OH 150°C
XI, BO°C skeel bomb
1 POCI3, DMF
2 IV, N(%C5)3 H2, Pt-C toluene
Trang 81058 1 Imolamine
2 CHSCOOH H202 2 NH3 CH30H 145OC
-1 triethyl orthoformate
2 hydrogen peroxide
Rejkrence(s):
a WO 9 748 704 (Minnesota Mining and Manufacturing Company; appl 22.10.1996; USA-prior 21.6.1996)
b EP 145 340 (Riker Lab.; appl 16.11 l984; USA-prior 18.11.1983)
c WO 9 215 581 (Minnesota Mining and Manufacturing Company; appl 13.2.1992; USA-prior 1.3.1991)
d WO 9 417 043 (Minnesota Mining and Manufacturing Company; appl 25.1 l994; USA-prior 29.1.1993)
e US 4 988 815 (Riker Lab.; 29.1.1991; USA-prior 26.10.1989)
f US 4 689 338 (Riker Lab.; 25.8.1987; USA-prior 18.1 1.1983)
Formulation(s): cream 5%
Trade Name(s):
Use: coronary vasodilator, antianginal
CN: N,N-diethyl-5-imino-3-phenyl- 1,2,4-oxadiazol-4(5H)-ethanamine
monohydrochloride
LD,,: 25 m g k g (M, i.v.); 475 mglkg (M, p.0.);
650 mglkg (R, p.0.)
w
benzaldehyde omine
Reference(s):
FR 2 023 M (J Marcel, D Aron-Samuel, J.-J Sterne; appl 10.10.1962; GB-prior 12.6.1962, 11.7.1961)
Formulation(s): inj sol 50 mg/5 ml; tabl 30 mg
Trade Name(s):
Irrigor Aron (Spemsa); wfm
Trang 9Improsulfan ATC: LO1
Use: antineoplastic
CN: 3,3'-iminobis[l -propanoil dimethanesulfonatc (ester)
R R I1 II
HOr\/'RwOH + H3C-S-0-S-CH,
oceto-
nitrile
Reference(s):
Sakurai, J ; El-Merzabani, M.M.: Chem Pharm Bull (CPBTAL) 12, 954 (1964)
bis(3-hydroxypropy1)- rnethonesulfonic
sulfonic acid salts:
DOS 2 059 377 (Yoshitomi; appl 2.12.1970; J-prior 2.12.1969, 12.8.1970)
GB 1 272 497 (Yoshitomi; appl 25.12.1970; J-prior 2.12.1969, 12.8.1970)
lrnprosulfon
Formulation(s): tabl 10 mg
ornine anhydride
Trade Name(s):
J : Protecton (Yoshitomi; as
tosylate)
Incadronic acid 'use: bone resorption inhibitor, antiarthritic
agent
CN: [(Cycloheptylarnino)methylene]bis[phosphonic acid]
disodium salt monohydrate
RN: 183808-97-1 MF: CxH,,NNa20,P2 H 2 0 MW: 349.17
disodium salt
CH3
cycloheptyl- triethyl diethyl phosphite
m i n e orthaformate
Trang 101060 1 Indalpine
conc HCI
_*
tetroethyl (cyclo-
heptylamino)methylene-
bis(phosphanate) (I)
Reference(s):
EP 325 482 (Yamanouchi Pharm Co.; appl 20.1.1989; J-prior 20.1.1988)
Takeuchi, M.; Sakamoto, S.; Yoshida, M.; Abe, T.; Isomura, Y.: Chem Pharm Bull (CPBTAL) 41 (4), 688 (1 993)
oral pharmaceutical compositions:
EP 550 385 (Ciba-Geigy A G.; appl 11.12.1992; CH-prior 19.12.199 1)
pharmaceutical compositions:
EP 693 285 (Eli Lilly & Co.; appl 20.7.1995; USA-prior 22.7.1994)
Trade Name(s):
1997)
Use: antidepressant, selective serotonin- uptake inhibitor
CN: 3-[2-(4-pipendiny1)ethyll-1 H-indole
monohydrochloride
RN: 63845-42-1 MF: C,,HzONz HC1 MW: 264.80
LD,,,: 60 m g k g (M, i.v.); 600 m g k g (M, p.0.)
4-piperidine- benzyl
0'
N-benzyloxycarbonyl- acetic acid chloroformate 4-piperidineacetic acid
1 CH3-MgI
2 HCI
1 methyl- H : r c
magnesium iodide
3-indolyl 4-piperidylmethyl