Title of Invention

"A NEW PROCESS FOR PREPARATION OF IMIPENEM."

Abstract Disclosed herein is a compound of Formula II below: OH wherein R1 is a p-nitrobenzyl or p-methoxybenzyl, group; and R2 and R3 may be identical to or different from each other and are each independently a C1-6 alkyl or aryl group, or a derivative thereof, and a process for preparing the compound of Formula II Further disclosed is a process for preparing imipenem of Formula I below: by using the compound of Formula II.
Full Text A NEW PROCESS FOR PREPARATION OP IMIPENEM
Technical Field
The present invention relates to a compound of Formula
II below:
(Figure Removed)
wherein
R1 is a p-nitrobenzyl or p-methoxybenzyl group; and R2
and R3 may be identical to or different from each other and
are each independently a C1-6 alkyl or aryl group,
or a derivative thereof, and a process for preparing
the compound of Formula II.
The present invention also relates to a process for
preparing imipenem of Formula 1 below:
(Figure Removed)
by using the compound of Formula II.
The imipenem of Formula I is a carbapenem antibiotic
as a member of beta-lactam antibiotics.
Background Art
The first carbapenem antibiotic to be discovered was
thienamycin, isolated from naturally occurring streptomyces
cattleya by Merck Co., U.S.A. in 1976.
Since thienamycin is highly chemically unstable despite
superior pharmacological effects, it has not been developed
into medicines - Many attempts have been made to overcome the
chemical instability of thienamycin while maintaining the
pharmacological effects of thienamycin. For example,
imipenem, which is a novel thienamycin derivative synthesized
toy Merck Co., is prepared by modifying the amlne group of
thienamycin into an N-formimicoyl group. Imipenem is a new
concept antibiotic with ensured stability. Imipenem has been
widely used as a therapeutic agent to date. Imipenem as a
carbapenem antibiotic is the first available compound among
new type beta-lactam antibiotics possessing a carbapenem ring
system, and shows high stability even in the presence of
beta-lactamase. Inaddition, imipenem exhibits an extremely
broad spectrum of antibiotic activity against gram-positive
and gram-negative aerobic and anaerobic species. Imipenem
is prepared only by chemical total synthetic, unlike
conventional cephalosporin antibiotics.
The first industrial synthetic of imipenem was reported
in 1981. Since 1989, improved syntheticprocesses of imipenem
preparing in-situ imipenem monohydrate by activating a
bicyclic keto ester, reacting the activated ester with an
amine-protected N-formimidoyl-2-aminoethanethiol compound,
followed by catalytic hydrogenation using platinum oxide as
a catalyst to remove the 2-carboxyl and the amine protecting
groups without isolation of any intermediate, as depicted
in Reaction Scheme 1 below:
Reaction Scheme 1
(Figure Removed)
wherein R is hydrogen or a protecting group; and X is
a leaving group.
However, this process has the disadvantages that: the
imipenem is prepared from the bicyclic keto ester in a yield
as low as 35% and the process further involves four stages
in the preparation of the protected N-formimidoyl
2-aminoethanethiol compound. In addition, another
disadvantage of the process is that large excesses of water
(660-fold amount of the starting material) and solvents are
necessary for extraction upon washing after the N-formimidoyl
economical disadvantage.
On the other hand, U.S. Patent Nos. 4,845,261 and
4, 894, 450 disclose a novel process for continuously preparing
imipenem from a bicyclic keto ester via four stages without
isolation and purification of any intermediates. The
procedure of the process is depicted in Reaction Scheme 2
below:
(Figure Removed)
wherein R1 is a p-nitrobenzyl group.
As depicted in Reaction Scheme 1, since the process
consisting of four stages proceeds in-situ without undergoing
any separation and purification, the final product inevitably
contains large amounts of impurities, which makes the
separation and purification of the final product difficult.
In addition, the process is accompanied by the use of costly
bis (dichlorophenyl)phosphorochloridate in order to activate
the bicyclic keto ester precursor.
Since expensive N-ethylpyrrolidinone used as a reaction
solvent in Reaction Scheme 2 is a highly polar organic solvent,
it is difficult to remove the solvent from the
aste* oompiiQtiion or tho
excessive use of the reaction solvent (200-fold amount of
the starting material) creates an economic burden in the
industrialization of the process.
U.S. Patent No. 4,313,712 proposes a semi-synthetic
process of imipenem monohydrate using thienamycin isolated
from streptorayces cattleya as a starting material. The
overall procedure of this process is depicted in Reaction
Scheme 3 below:
Reaction Scheme 3
(Figure Removed)
As depicted in Reaction Scheme 3, however, since the
chemically unstable thienamycin ia obtained in a small amount
from the microorganism, the process is disadvantageous in
terras of poor economic efficiency. In addition, the use of
an excess of water (214-fold amount of the starting material)
as a reaction solvent causes difficulties in reaction,
separation, and purification. Furthermore, the process has
the disadvantage that 5% or more of dirtier bis-thienamycin
forrnamidine is formed as an undesired reaction by-product
along with the desired product imipenem.
Dr. Ranbaxy filed an international PCT application {WO
02/36594) relating to a process for preparing imipenem. This
process is similar to the process of Merck Co., except that
1, 3-dimethyl-3,4,5,6-tetrahydro-(2H)-pyrimidinane is used
as a reaction solvent. However, the publication does not refer
to a hydrogenation catalyst. In addition, the final product
imipenem in a crystalline form is prepared in a very low yield
of 23% from a bicyclic keto ester as a starting material by
adsorption chromatography.
Disclosure of the Invention
As stated above, according to the conventional
processes for preparing imipenem, since the intermediates
are impossible to separate and purify or are unstable, the
product imipenem is prepared via continuous reaction stages
(in~situ reaction). As a result, the formation of large
amounts of impurities is inevitable.
For these reasons, the large amounts of impurities cause
difficulties in work-up, separation and purification, leading
to low yield and purity of the final product.
In other words, according to the conventional synthetic
processes of imipenem, since the overall reaction stages
continuously proceed without any separation of the
intermediates due to poor chemical stability of the
intermediates, the isolation and purification of imipenem
are performed in the presence of impurities- In addition,
the isolation by crystallization is difficult, due to the
presence of impurities, resulting in low yield and purity
the use of expensive reaction solvents and large excesses
of solvents (200-fold amounts of the starting materials),
they have problems in terms of poor economic efficiency and
industrial application.
Therefore, the present invention has been made in view
of the above problems, and it is an object of the present
invention to provide the novel amlne-protected thienamycin
compound of Formula II useful in the preparation of iraipenem
monohydrate of Formula I, and a process for preparing the
thienamycin compound of Formula II.
It is another object of the present invention to provide
a process for preparing imipenem using the amine-protected
thienamycin compound of Formula II.
As explained above, according to the compound of Formula
II or a derivative thereof of the present invention, different
protecting groups are effectively introduced into the
carboxyl group and amine group of thienamycin to obtain the
amine-protected thienamycin compound of Formula II as a
imipenem intermediate, which is used in the preparation of
the imipenem monohydrate of Formula I. According to the
process of the present invention, the problem of low yield
of imipenem monohydrate due to the presence of large amounts
of impurities, resulting from no isolation arid purification
of intermediates, can be solved.- in addition, the imipenem
monohydrate with a high purity can be prepared from the novel
intermediate compound of Formula II in a simple manner
of Formula I can be greatly improved.
Since the process of the present invention uses common
organic solvents and water,, the solvents are readily removed
after completion of the reaction. In addition, since a
palladium catalyst containing a large amount of water is used
in the hydrogenation for the removal of the protecting groups,
the danger upon handling is considerably reduced, allowing
the process of the present invention to proceed under mild
reaction conditions . Accordingly, the process of the present
invention is economically advantageous and enables the
preparation of imipenem with no difficulty.
Brief Description of the Drawings
The above and other objects, features and other
advantages of the present invention will be more clearly
understood from the following detailed description taken in
conjunction with the accompanying drawings, in which:
Fig. 1 is an LC chromatogram showing the purity of a
ketone compound;
Fig. 2 is an LC chromatogram showing the purity of an
imine compound;
Fig. 3 is an LC chromatogram showing
Merck-formimidation;
Fig. 4 is an LC chromatogram showing
Merck-hydrogenation;
Fig. 5 is an LC chromatogram showing CWP (Choongwae
Fig. 6 is an LC cromatogram showing cwp-nyarogenation.
Best. Mode for Carrying out- the Invention

Preparation of (5R,6S)
p-nitrobenzyl-3- (diphenylphosphono) -6-[(1R)-1-hydroxyeth
yl] -1-szabieyclo[3-2.0]hept-2~ene-7-one-2-carboxylate
20.Og of (5R,6S)
p-nitrobenzyl-6-[(1R)-1-hydroxyethyl]-1-azabicyclo [3.2.0
]hept-3,7-dione-2-earboxylate of Formula Ill below was
dissolved in a mixture solution of acetonitrile (100 ml),
and tetrahydrofuran (100 ml) . The reaction temperature was
lowered to 0°C ~ -10°c. To the reaction mixture were
sequentially added 11.1g of N,N-diisopropylethylamin 18 . 5g of diphenylchlorophosphate . The resulting mixture was
stirred for 1.5-2 hours while maintaining the reaction
temperature at -10°C, giving the enol phosphate of Formula
IV below. The enol phosphate of Formula IV was used in the
next step without further separation.
(Figure Removed)
wherein Rx is p-nitrobenzyl.
(Figure Removed)
wherein R1 is p-nitrobenzyl.

Preparation of (5R,6S) p-nitrobenzyl
6-[(1R)-1-hydroxyethyl]-3({2-[(1-isopropylidene)amino]et
hyl} thlo) -l-azabicyclo [3.2 .0]hept-2-ene-7-one-2-carboxyl
ate
A reaction solution of the enol phosphate derivative
of Formula IV prepared in Example 1 was lowered from-40°C
tc -60°C, and then 7.8g of 2-aminoethanethiol hydrochloride
and 11.1g of diisopropylamine were sequentially added
thereto. The reaction mixture was stirred for 0.5-1 hour at
the same temperature. A ketone type solvent wa? added to the
reaction mixture in the presence of a base, stirred, and
crystallized. The obtained precipitate was filtered, washed
with hescane, and dried under reduced pressure at room
temperature, affording 20.5g (yield: 80.0%) of the
amine-protected thienamycin of Formula IT.
1H-NMR (DMSO--d6, 300 MH", ppm) 5 1.14 (d, J ~ 6.3 Hz,
3H), l."78 (3, 3H), 1.90 (s, 3H) , 3.12 (m, 2H) , 3.28-3.32 (m,
g'H), 3.37'"3.'1Q 'fin/ "gH)> 'r'l (m, -I'M) , I'.lfr (ill y .7-.; -1 fl .1
"Hz", 1H) , 5.07 (d, J=5.1Hz, 1H) , 5.27 (d, J = 14.1 Hz, 1H) ,
5.43 (d, J = 14.1 Hz, 1H), 7.70 (d, J - 8.7 Hz, 2H), 8.22
(d, J = 8.7 Hz, 2H) .
Mass: 447.51
M.p.: 148~151°C
Color: Pale yellow.

Preparation of . (5R,6S)
p-nitrobenzyl-3-[ [2-[ (f ormimidoylandno) ethyl] thio] -6- [ (1
R)-l-hydroxyethyl]-l-azablcyclo[3-2.0]hept-2-ene-7-one-2
-carboxylate
After 20.0g of the intermediate compound of Formula
II prepared in Example 2 was added to a mixed solvent of
disti lied water and tetrahydrofuran, the reaction temperature
was lowered f rom 5°C to -5°C or lower. To the reaction mixture
were added 18 ml of N-methylmorpholine and 30.8g of
benzylformimidate hydrochloride . The resulting mixture was
stirred at 0-10°C for 2-3 hours, affording the compound of
Formula V, which was used in the next step without further
separation.
(Figure Removed)

Preparation of
(+) - (5R, 6S) -3-{ [2- (forTOimidoylamino)ethyl]thio}-6- [ (R}-1
-hydroxyethyl] ~7-oxo~l-azabicyclo [3 . 2 . 0 ] hept-2-ene-2-car
boxylic acid (imipenem)
To a reaction solution of the carboxyl-protected
N-formimidoyl thienarnycin of Formula V prepared in Example
3, 16g of N-methylmorpholine was added to adjust the pH to
7 . 0 - 8 . 0 . A water-containing palladium catalyst was added
to the reaction mixture to proceed a deprotection reaction
at 10~25°C. At this time, the reaction was continued for 3
hours while maintaining the hydrogen pressure at 4-6 kg/cm2,
and then the catalyst was removedby filtration . HPLC analysis
of the reaction solution indicated that imipenem waa prepared
in a yield of 82%. The reaction solution was washed several
tiroes with ethyl acetate, and evaporated under reduced
pressure to remove residual organic solvents. The resulting
aqueous solution was purified by reversed-phase column
chromatography, followed by concentration using a reverse
osmosis technique- Acetone was added to the concentrate,
stirred for 2-3 hours, and crystallized. The crystallized
imipenem monohydrate was filtered, washed, and dried under
reduced pressure, affording 8 , 6g of the desired imipenem
monohydrate of Formula I (yield: 60%, purity (by HPLC) : 99%) .
Hereinafter, the preparation process of imipenem
Co. (see, U.S. Patent Nos. 4,845,261 and 4,894,450,
hereinafter referred to as "Merck a process").

According to Merck's process, imipenem was prepared
without separation of any intermediates. In contrast,
according to the present process, the imine compound was
prepared from the carboxyl-protectedthienamycin, separated,
and used to prepare imipenem. Thereafter, the yield and
content of imipenem were compared.
Experimental procedvu:es>
In the case of Merck's process, imipenem was prepared
in accordance with the procedure described in U.S. Patent
Nos. 4,845,261 and 4,894,450, except that
bis (dichlorophenyl) phosphor ochlori date so Id by TCI was used.

In order to compare the experimental results of the
present process with those of Merck's process, the following
samples were used:
- Ketone compound(ForitmlallI)
- Imine compound (Formulall)
- Merck's process: Formimidation & imipenem
- The process of the present invention: fc'ormimidation
Apparatuses and conditions for LC analysis employee
for comparing the experimental results of the present process
with those of Merck's process, were as follows:
1) Analytical apparatus
- Alliance 2695 & 2996 PDA system
- Workstation: Empower
- Column: C18,ODS, 4.6 x 260 mm, 5 vim
2) Analytical conditions
HPLC
- Flow rate: 1.0 mL/min.
- Injection Volume: 5 μl
- Sampling: 1/10 dilutions (by mobile phase B)
- Run time: 50 min.
- Column temperature: Room temperature
- Auto sampler temperature: 4°C
- Detector: 254 ran
ii) Mobile phases
- Mobile phase A: (NH4) 2HP04 buffer
- Mobile phase B: MeOH/ACN =1:1
- The gradient conditions of the mobile phases are shown
in Table 1 below:
(Table Removed)
Experimental results>
1) Purity of ketone.compound
The ketone compound is a reaction compound used in both
Merck' s process and the present process . The ketone compound
prepared in the present process was used in Merck' s process.
The purity of the ketone compound is shown in Table 2 below.
(Table Removed)
An LC chromatogram showing the purity of the ketone
compound is shown in Fig. 1.
2) Purity of iMine compound:
The iMine compound separated in accordance with the
present process is a compound distinguishing the present
process from Merck's process, and is a key compound for the
present experimental purpose. Table 3 shows the purity of
the imine compound.
Table 3
Purity of imine compound
96.3 (%)
An LC chromatogram showing the purity of the imine
compound is shown in Fig. 1.
of Merck' s process and the present process
Table 4 shows the purities of the respective steps in
both processes
(Table Removed)
4) Comparison of yields based on the respective steps
of Merck's process and the present process {relative to
theoretical values)
Table 5 shows the yields of the respective steps in
both processes,
(Table Removed)
Since Merck's process does not include the step of
prepar ing the imine compound, the imine compound content could
not be calculated. The theoretical contents based on the
respective steps indicate contents obtained when the
corresponding yields were 100%.
c o n c i c o n e x factors were
excluded from the calibration (since the state was liquid,
the factor values could not be exactly calculated).
The imipenem content was obtained by comparing the
calculated peak area with the peak area of the USP standard
reagent.
Figs. 3 through 6 are LC chromatograms showing
Merck-formimidation, Merck-hydrogenation,
CWP-formimidation, and CWP-hydrogenation, respectively.
As is evident from the above experimental results, the
present process wherein the imine compound was separated to
prepare imipenem, was superior to Merck's process in the
contents of the compound obtained after the formimidation
and the final product imipenem.
In accordance with one aspect of the present invention,
the above objects can be accomplished by a compound of Formula
II below:
(Figure Removed)
wherein
R1 is a p-nitrobenzyl or p-methoxybenzyl group; and Rj
and R3 may be identical to or different from each other and
are each independently a Cj._6 alkyl or aryl group,
or a derivative thereof.
1 ••w4^-'"ii--^'OGOm'QiCft*^^ —W.A.rC"*J iiji'LH iLJ ItJ £ CrS-^ZPL« L^ .7S*f.,iei Sr,*,*-*—-'" AI ' • iiT'...^ .'.,
invention, tnere is provided a process for preparing tne
compound of Formula II by coupling a compound of (Figure Removed)
wherein Rx is a p-nitrobenzyl or p-methoxybenzyl group,
or a derivative thereof with 2-aminoethanethiol
*
hydrochloride in the presence of a base, followed by reaction
with a ketone.
The ketone is selected from the group consisting of
acetone, methylethylketone, diphenylketone, and mixtures
thereof .
The compound of Formula IV or a derivative thereof is
obtained by condensing a compound of Formula III below:
(Figure Removed)
wherein RI is a p-nitrobenzyl or p-methoxybenzyl group,
with dxphenylchlorophosphate in the presence of a base.
As the reaction solvent, a mixed solvent of acetonitrile
and tet rahydrofuran is used.
The reaction temperature is within the range of 0°C to
In accordance with yet another aspect of the present
invention, there is provided a process for preparing the
compound of Formula I below:
(Figure Removed)
by reacting the compound of Formula II with
isopropylformimidate or benzylformimidate in the presence
of a base to obtain a compound of Formula V below:
(Figure Removed)
wherein R1is a p-nitrobenzyl or p-methoxybenzyl group,1
hydrogenating the compound of Formula V in the presence of
a metal catalyst, separating the hydrogenated compound, and
crystallizing the separated compound in the presence of an
alcohol or ketone.
The hydrogenation is carried out in the presence of
a palladium catalyst containing an excess of water under a
hydrogen pressure of 4~6 kg/cm2.
As a solvent for the reaction, a mixed solvent of water
arid tetxahydrof uran is used.
The present invention will now be described in more
detail.
thienamycin compound of Formula II is prepared by coupling
the enol phosphate derivative of Formula IV with
2-aminoethanethiol hydrochloride, followed by reaction, with
an appropriate ketone. The amine-protected thienamycin
compound thus prepared is useful in the preparation of the
imipenem monohydrate of Formula I.
According to the present invention, different
protecting groups are effectively introduced into the
cartaoxyl and amine groups of the thienamycin derivative used
in conventional preparation processes of imipenem to prepare
the amine -protected thienamycin compound of Formula II as
a carbapenem intermediate. The amine-protected thienamycin
compound thus prepared is stable at room temperature and can
be stored at low temperature for a long period of time.
That is, according to the present invention, the
bicyclic keto . ester of Formula III is condensed with
diphenylchlorophosphate in the presence of a base to prepare
the enol phosphate compound of Formula IV.
The enol phosphate derivative of Formula IV is prepared
in a polar solvent selected from ethers, e.g.,
tetrahydrofuran, diisopropyl ether and dioxane and
acetonitrile, and then the enol phosphate derivative is
coupled with 2-aininoethanethiol hydrochloride in the presence
of a base to prepare the thienamycin derivative . Thereafter,
a common ketone, such as 'acetone, methylethyl ketone or
diphenylketone, is added to the thienamycin derivative to
Unlike conventional preparation processes of imipenem,
different protecting groups are effectively introduced into
the carboxyl and amine groups of thienamycin to prepare the
amine-protected thienamycin compound of Formula II as a
carbapenem intermediate. The compound of Formula II is a novel
compound in the form of a pale white crystal that is stable
at room temperature and can be stored at low temperature for
a long period of time. In addition, the compound of Formula
II is useful as an intermediate for the preparation of an
imipenem intermediate and in the preparation of other
carbapenem antibiotics.
Further, according to the present invention, the
amine-protected thienamycin compound as a novel intermediate
is effectively used in the preparation of the imipenem
monohydrate of Formula I.
Further, according to the present invention, the
compound of Formula II is reacted with isopropylforimidate
hyclrochloride or benzylforimidate hydrochloride in the
presence cf a base to prepare the carboxyl group-protected
imipenem of Formula V, hydrogenating the carboxyl
group-protected imipenem in the presence of a metal catalyst
to remove the protecting group, followed by appropriate
treatment, to obtain an aqueous solution, which is then
separatee by reversed-phase column chromatography and
crystallized in an appropriate alcohol or ketone to prepare
Industrial Applicability
As explained above, according to the compound of Formula
II or a derivative thereof of the present invention, different
protecting groups are effectively introduced into the
carboxyl group and amine group of thienamycin to obtain the
amine-protected thienamycin compound of Formula II as a
irnipenem intermediate, which is used in the preparation of
the irnipenem monohydrate' of Formula I. According to the
process of the present invention, the problem of low yield
of imipenem monohydrate due to the presence of large amounts
of impurities, resulting from no isolation and purification
of intermediates, can be solved. In addition, the imipenem
monohydrate with a high purity can be prepared from the novel
intermediate compound of Formula II in a simple manner.
Furthermore, the yield and quality of the imipenem monohydrate
of Formula 1 can be greatly improved.
Since the process of the present invention uses common
organic solvents and water, the solvents are readily removed
after completion of the reaction. In addition, since a
palladium catalyst containing a large amount of water is used
in the hydrogenation for the removal of the protecting groups,
the danger upon handling is considerably reduced, allowing
the process of the present invention to proceed under mild
reaction conditions. Accordingly, the process of the present









We Claim:
1. A compound of Formula II below:
(Formula Removed)
wherein
R1 is a p-nitrobenzyl or p-methoxybenzyl group; and R2 and R3 may be identical to or different from each other and are each independently a C1-6 alkyl or aryl group.
2. A process for preparing a compound of Formula II below:
(Formula Removed)
wherein
R1 is a p-nitrobenzyl or p-methoxybenzyl group; and R2 and R3 may be identical to or different from each other and are each independently a C1-6 alkyl or aryl group, by coupling a compound of Formula IV below:
(Formula Removed)
wherein R1 is a p-nitrobenzyl or p-methoxybenzyl group, with 2-aminoethanethiol hydrochloride in the presence of a base, followed by reaction with a ketone.
3. The process as claimed in claim 2, wherein the ketone is selected from the group consisting of acetone, methylethylketone, diphenylketone, and mixtures thereof.
4. The process as claimed in claim 2 or 3, wherein the compound of Formula IV is obtained by condensing a compound of Formula III below:
(Formula Removed)
wherein R1 is a p-nitrobenzyl or p-methoxybenzyl group, with diphenylchlorophosphate in the presence of a base.
5. The process as claimed in claim 4, wherein the reaction solvent is a mixed solvent of
acetonitrile and tetrahydrofuran.
6. The process as claimed in claim 4, wherein the condensation is carried out at a
temperature within the range of 0°C to -10°C.

Documents:

123-DELNP-2006-Abstract-(16-04-2010).pdf

123-DELNP-2006-Abstract-(16-10-2009).pdf

123-delnp-2006-abstract.pdf

123-DELNP-2006-Claims (16-10-2009).pdf

123-DELNP-2006-Claims-(16-04-2010).pdf

123-delnp-2006-claims.pdf

123-DELNP-2006-Correspondence-Others (16-10-2009).pdf

123-DELNP-2006-Correspondence-Others-(16-04-2010).pdf

123-delnp-2006-correspondence-others.pdf

123-delnp-2006-description (complete).pdf

123-DELNP-2006-Drawings (16-10-2009).pdf

123-delnp-2006-drawings.pdf

123-DELNP-2006-Form-1-(16-04-2010).pdf

123-delnp-2006-form-1.pdf

123-delnp-2006-form-18.pdf

123-DELNP-2006-Form-2-(16-04-2010).pdf

123-delnp-2006-form-2.pdf

123-DELNP-2006-Form-3 (16-10-2009).pdf

123-delnp-2006-form-3.pdf

123-delnp-2006-form-5.pdf

123-DELNP-2006-GPA-(16-04-2010).pdf

123-delnp-2006-pct-210.pdf

123-delnp-2006-pct-304.pdf

123-DELNP-2006-Petition-138 (16-10-2009).pdf

123-DELNP-2006-Petition-138-(16-04-2010).pdf


Patent Number 244385
Indian Patent Application Number 123/DELNP/2006
PG Journal Number 50/2010
Publication Date 10-Dec-2010
Grant Date 06-Dec-2010
Date of Filing 06-Jan-2006
Name of Patentee CHOONGWAE PHARMA CO.
Applicant Address 698 SHINDAEBANG-DONG, DONGJAK-GU, SEOUL 156-757, REPUBLIC OF KOREA.
Inventors:
# Inventor's Name Inventor's Address
1 OH CHANG HOON 218-1801 SUPSOKMAEUL APT.
2 BAE HYUN SEOP 112-204 SAMIK APT., #5-13 SIHEUNG-DONG, KEUOMCHUN-GU, SEOUL, KOREA.
3 HWANG TAE SEOP 313-303 DONGSIN APT., YONGTONG-DONG, YONGTONG-GU, SUWON CITY, KOREA.
4 AHN CHAN YONG 514-103 JUGONG APT., GOJAN-DONG, DANWON-GU, ANSAN CITY, KOREA.
5 KIM MOO SUNG 301-204 SAMIK 3RD APT., KEUM-DONG, KEUONSUM-GU, SUWON CITY, KOREA.
PCT International Classification Number C07D 477/20
PCT International Application Number PCT/ KR2004/003224
PCT International Filing date 2004-12-09
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 10-2003-0088857 2003-12-09 Republic of Korea