Betalactam I-Dai Hoc-janvier 2012.SV

7/28/2019 Betalactam I-Dai Hoc-janvier 2012.SV

1/67

KHANG SINH -LACTAMIN (-LACTAM)

Azetidin = -lactamin


2/67


3/67

CAC THUOC CHNHPenicillin: (PENAM)

penicillin G; penicillin V

methicillin; oxacillinampicillin; amoxicillin;carbenicillin; ticarcillin

Cht c ch -lactamase: (OXAPENAM)acid clavulanic

CARBAPENEM: imipenem

N

S

O

N

O

O

NO


4/67

CAC THUOC CHNHCephalosporin (CEPHEM)

Th h I : cephalexin; cephalothinTh h II: cefoxitin; cefaclorTh h III: cefotaxime; cefoperazone; ceftriaxone

Th h IV: cefepimeTh h V: ceftobiprole

MONOBACTAM: aztreonam

NO

S

NHO


5/67

C CHE KHANG KHUAN


6/67

C CHE KHANG KHUAN

Transpeptidases = Penicillin-binding proteins (PBP)

= Protine de liaison aux pnicillines (PLP)


7/67

Drugs that inhibit the cross-linking of the peptidoglycan chains The final step in the

formation of the cell wall is the completion of the cross-links. This converts the water-soluble and therefore

mobile peptidoglycans into the insoluble stationary cell wall. Investigations using Staphylcoccus aureus

indicated that the cross-linking is brought about by a multistep displacement of the terminal alanine of the

peptide attached to one peptidoglycan chain and its replacement by the terminal glycine of the peptide

attached to a second peptidoglycan chain (Fig. 7.26). This reaction is catalysed by transpeptidases.


8/67


9/67

C CHE E KHANG

Vi khuan e khang lactamin theo cac c che sau:e khang enzym: VK sn xut -lactamase

e khang khong enzym:- thay oi tnh tham thau cua mang te bao- bien mat hoac bien oi cac PBP

- Efflux pumps Vd: multidrug resistance (MDR) pumps


10/67

Th d: S khng ca Staphylococcus aureus

- Sx penicillinases

- Thay i PBP: PBP 2a tm thy trong MRSA (Methicillin-resistant Staphylococcus aureus)


11/67

(A) Stereo view of the active site of

PBP 2a ofS. aureusdepicted as a

solvent-accessible surface (green).

The side chains of the active-site

serine and lysine are shown as

capped sticks and colored by atomtypes (carbon in gray, oxygen in

red, and nitrogen in blue). The

backbone of the loop that caps the

active site is shown as an orange

wire.

(B) Stereo view of the active site

from the same perspective shown

in panel A, except the loop is now

shown as a solvent-accessible

surface for both the backbone and

the side chain functionalities. The

presence of the loop blocks the

active-site access for molecules

the size of typicallactamantibiotics.

The development of newlactam antibiotics that inhibit PBP 2a is significant progress andoffers a glimmer of hope for the future treatment of MRSA infections, including those caused by

vancomycin-resistant and -intermediate strains.


12/67

HOAT TNH KHANG KHUAN

Quan he cau truc tac ong

N

O

COOHH

HN

O

O

RH H

12

3

4

56

7

Penicillin

N

NH

O

O

R1H H

1

3

4

5

67

S

COOH

R2

N

NH

O

O

RH R1

SO3H

R2

cephalosporin

monobactam


13/67

NHOM PENICILLIN

Benzyl penicillin = Penicillin G


14/67

N

S

COOHH

HN

O

O

R

H H

12

3

4

5

6

7

Penicillin

N

S

COOHH

H2N

O

H H

12

3

4

56

7

6-aminopenicillinic acid

Danh phap IUPAC

Amid- 6 cua acid (2S, 5R, 6R-amino-6-dimethyl-3,3-oxo-7-thia-4-aza-1-bicyclo [3.2.0]-heptan carboxylic).

Danh phap thong dung

Penicillin nh la nhng amid cua acid 6-amino penicillanic (6- APA).


15/67

IEU CHE

T nam Penicillium notatum.

Penicillin G (them vao moi trng acid phenylacetic )

Penicillin V (them vao moi trng acid phenoxyacetic )

60mg/L 20 g/L

Phng phap sinh hoc

N

S

O

HN

CH3

COO

HH

H

CH3

COCH2

R'

N

SNH

H COO

H H

O

C

OH2CO

R


16/67

IEU CHEBan tong hp

N

S

COOHH

HN

O

O

R

H H

12

3

4

56

7

Penicillin

N

S

COOHH

H2N

O

H H

12

3

4

56

7


B-condition = 1. Me2SiCl2 2. n-Bu-OH, -40oC 3. H2O, 0

oC

A- condition

B-condition

A-condition = Aclylase

N

S

COOHH

HN

O

O

R1

H H

12

3

4

56

7

Penicillin

N

S

COOHH

H2N

O

H H

12

3

4

56

7


R'COCl, Et3N


17/67

BAN TONG HPAMOXICILLIN

N

S

OCOOH

CH3

CH3H2N

6-APA

+ SiCl

CH3

CH3

CH3

trimethylclorosilon

N

S

OCH3

CH3H2N

OO Si

H3C

CH3

CH3

6-aminopenicillanic acidtrimethylsilyl ester

(I)

(I) +

HO

Cl

O

NH2

.HCl

D-(-)2-(4-hydroxyphenyl)-glycylclorid. hydroclorid

N,N-dimethylanilin N

S

OCH3

CH3HN

OO Si

H3C

CH3

CH3

O

NH2

HO

amoxiillin trimethylsilyl ester(II)

(II)H2O, pH 1,3-1,5

N

S

OCOOH

CH3

CH3HN

O

NH2

HO

Amoxcicillin

R


18/67

Tnh chat vat ly

Cac penicillin di dang muoi hoac dang acid la nhng bot trangkhong mui khi tinh khiet.

Pho UV

N

S

COOHH

HN

O

O

R

H H

12

3

4

56

7

Penicillin

Benzylpenicillin K

(BP 2007)

Absorbance (2.2.25)

Dissolve 94.0 mg in water R and dilute to 50.0 ml with the same solvent.

Measure the absorbance of the solution at 325 nm, 280 nm and at themaximum at 264 nm, diluting the solution, if necessary, for the

measurement at 264 nm. The absorb ances at 325 nm and 280 nm d o

no t exceed 0.10 and th at at the maxim um at 264 nm is 0.80 to 0.88,

calculated on the basis of the undiluted (1.88 g/l) solution. Verify the

resolution of the apparatus (2.2.25); the ratio of the absorbances is at

least 1.7.


19/67

Tnh chat vat ly

Pho IR: vung 1600-1800 cm-11760 va 1730 cm-11700 va 1650 cm-11600 cm-1


20/67

Tnh chat vat ly

Nng sut quay cc

Specific optical rotation (2.2.7)

Dissolve 0.500 g in carbon dioxide-free water R and dilute to 25.0 ml with the

same solvent. The specific optical rotation is + 270 to + 300, calculated with

reference to the dried substance.

Benzylpenicillin K (BP 2007)


21/67

Tnh acid Tao muoi natri va kali (bn)

Tan trong nc, pha tiem

Tnh chat hoa hoc

N

S

COOHH

HN

O

O

R

H H

12

3

4

5

6

7

Penicillin

Natri amoxicillinK Benzylpenicillin

R


22/67

Tnh acid Tao muoi vi cac amin:

Procain penicillin: tac ong keo dai 24-48 h,

Benethamin penicillin: tac ong keo dai 3-7 ngay,

Benzathin penicillin: tac ong keo dai 2-4 tuan.

Tnh chat hoa hoc

N

S

COOH

H

HN

O

O

H H

12

3

4

56

7

Penicillin

Procain benzylpenicillin

Benzathin benzylpenicillin

R

H H


23/67

Tnh acid

Tao thanh nhng este, tien chat cua PNC co kha nang phong thchtr lai cac khang sinh nay in vivo.

Tnh chat hoa hoc

HN

O

H2

N H

N

S

OCOOR

CH3

CH3

R = O CMe3

O

Pivampicillin

R = O

O

Talampicillin

R =O

Me

O Me

O

Bacampicillin

Tin dc ampicillin gip hp thu KS tt hn qua rut

N

S

COOHH

HN

O

O

H H

12

3

4

56

7

Penicillin


24/67

Penicillin

O

O O OMe3

O

Esterase

H

Penicillin

O

O OH

H

Penicillin

O

OH+ CH2O

C ch thy phn acyloxymethyl ester bi esterase

T h kh b b t l t


25/67

C NR2

O

R

: :

..

C

R

O..: :

NR

R

Comparison of tertiary amide and -lactam carbonyl groups

Tnh khong ben cua vong beta lactam

T h kh b b t l t


26/67

Tnh khong ben cua vong beta lactam(OH- hay penicillinase)

- Chu y tng k vinhng chat co tnh kiem

penicillin

OH

N

S

O

HHNR

O

H

CO2H

HN

S

COOH

C

O

HO

H HR

O

acid penicilloic

S

N COOHROCHN

OHO

- CO2

S

NH

COOHROCHNS

NH

ROCHN CO2H

acid penilloic

ROCHNO

H

penilloaldehyd

HS

COOHH2N+

D-penicillamin

-Phn ng d ng

-nh lng


27/67

S alcol phan va amino phan

N

S

O

NH

CH3

COOH

H

CH3

CR

O

N

S

CO

NH

CH3

COOH

H

CH3CR

O

DD

Tac nhan ai nhan san pham

alcol R'OH R'O ester penicilloic

amin R'-NH-R'' R'-N-R'' amid penicilloic

hydroxylamin NH2OH NH-OH d/c a. hydroxamic


28/67

HN

S

CH3

CH3

COOH

HNCR

O

O NH

OH

N

S

CH3

CH3

COOH

HNCR

O

O

NH2OH

HN

S

CH3

CH3

CO

HNCR

O

ONH

O

Cu2+

Cu O

(xanh ngoc)


29/67

S m vng -lactam c xc tc bi cc ion kim lai(Phc to thnh vi ion kim lai hat ha s tn cng i nhn)

N

S

CH3

CH3

OO

O M

2 +

HNAc

N

OO

O M

2 +

HNAc

H H H HS

X

Ch : vng -lactam b m, KS mt tc dng

T h kh b b t l t


30/67

Tnh khong ben cua vong beta lactam(acid mnh, nng hoc HgCl2)

N

S

O

N H H

CH2O2H

R

O

H

H

HN

SN H H

CO2H

R

O

H

O

N

HSN H

CO2H

R

O

O

HN

HSN

CO2H

R

O

O

HN

S

HN

CO2H

R

O

OHO

H H

acid penicilloic

ROCHNO

H

penilloaldehyd

HS

COOHH2N+

D-penicillamin

S

N

H

ROCHN CO2H

acid penilloic

Peni G bn pH= 6-7.Hat tnh KS gim rt nhanh

pH


31/67


32/67

X = NH2, Cl, PhOCONH, heterocyles


33/67

N

S

H

CO NH

COO

C

H

NH2

O

H H

Na

Ampicillin

Na

N

S

H

CO NH

COO

C

H

NH2

O

H HHO

Amoxicillin

N

S

O

HN

CH3

COO

HH

H

CH3

COCH2

R'

N

SNH

H COO

H H

O

C

OH2CO

R

Peni G Peni V


34/67

Kiem nghiem

nh tnh:

- Pho IR- Sac ky lp mong

- Phan ng vi hydroxylamin, sau o vi CuSO4

- Phan ng mau vi acid H2SO4

- Phan ng mau vi dd formaldehyd trong H2SO4

N

S

O

HN

CH3

COO

HH

H

CH3COCH2

R'

Kiem nghiem


35/67

Kiem nghiem

Kiem tinh khiet

- hp thu UV

- pH

- Nang suat quay cc

- Cac tap chat thong thng: Th du kim loai nang

- Cac tap chat lien quan: Th du N,N-dimethylanilin (trongampicillin hoac amoxicillin) bang sac ky kh.

N

S

H

CO NH

COO

C

H

NH2

O

H H

Na

Ampicillin

Na

N

S

H

CO NH

COO

C

H

NH2

O

H H

HO

Amoxicillin

Kiem nghiem


36/67

Kiem nghiem

nh lng

1. PHNG PHAP OXY HOA KH

2. PHNG PHAP HPLC

3. PHNG PHAP VI SINH VAT

(Xac nh hoat lc cua khang sinh)

Penicilinphan huy

D-penicillamin + acid penaldic


37/67

Cac khang sinh nhom penicillin rat t oc,

Tai bien chu yeu do d ng,

D ng nhe gay nga, noi me ay D ng nang gay shock phan ve

OC TNH VA TAI BIEN


38/67

PENICILLIN NHOM IPenicillin thien nhien

Penicillin G (benzyl penicillin)Dang tac dung nhanh: Na/K benzyl penicillin

Dang tac dung cham: procain PNC, benethamin PNC, benzathin PNC

Penicillin V (phenoxy methyl penicillin)

N

S

O

HN

CH3

COO

HH

H

CH3COCH2

R'

N

SNH

H COO

H H

O

C

OH2CO

R

Peni G Peni V


39/67

Ben trong moi trng acid,hap thu tot hn, hoat chattrong huyet thanh cao hn,T1/2 dai hn.

T PNC-G: azidocillin,clometocillin

T PNC-V: pheneticillin,propicillin, phenbenicillin

PENICILLIN NHOM IPenicillin ban tong hp

X

X

CH

Z

CO HN

N

S

O

H H

CH3

CH2

COOH

Z = N3- ; X = H : azidocillin

Z = OCH3- ; X = Cl : clometocillin

O CH

Z

COHN

N

S

O

H H

CH3

CH2COOH

Z = CH3- : pheneticillin

Z = C2H5- : propicillinZ = C6H5- : phenbennicillin

PENICILLIN NHOM I


40/67

Pho khang khuan hep, chu yeu tren gram (+):

Cau khuan gram (+): tu cau khong tietpenicillinase, lien cau, phe cau

Cau khuan gram (-): lau cau (khuynh hng tang

MIC va xuat hien nhng chung e khang). Xoan khuan: xoan khuan giang mai, leptospira

va Borelia burgdorferi.

Trc khuan gram (+): trc khuan gay benh bach

hau, benh than, listeria(viem mang nao),erysipelothrix (viem quang).

PENICILLIN NHOM IPho khang khuan

KHONG TAC DUNG TREN TRC KHUAN GRAM (-)


41/67

PENICILLIN NHOM IIMeticillin, oxacillin, cloxacillin, dicloxacillin,

Pho hep gan giong penicillin nhom I, nhng co kha nangkhang lai penicillinase do S. aureustiet ra.

N

S

O

HN

CH3

COO

HH

H

CH3CO

O CH3

O CH3

NaMeticillin

PENICILLIN NHOM II


42/67

N

S

O

HN

CH3

COO

HH

H

CH3COCC

N

O

C CH3

X

Y

Naisoxazolylpenicillin

PENICILLIN NHOM IIMeticillin, oxacillin, cloxacillin, dicloxacillin,

X Y

-------------------------------------------------------------

Oxacillin (Bristopen) H HCloxacillin (Orbenin) Cl H

Dicloxacillin (Dicloxil) Cl Cl

Fluocloxacillin (Floxapen) Cl F

Chu y: s a thay the lam giam hoat tnh khang sinh


43/67

Ph KK ca mt penicillin ph thuc vo:- Cu trc- Kh nng xuyn mng VK gram m-Tnh nhy cm vi betalactamse

-i lc vi enzym mc tiu transpeptidase- Tc b bm ra ngai VK gram m

M mm (trial and error) tm kimpenicillin ph rng

Mt lng ln cht tng ng c tng hp vi nhng thay i nhnh bn, vi nhng nhn xt SAR nh sau:- Nhm hydrophobic (peni G) tt trn gram + nhng khng tt trn gram _- S gia tng trn gram m tm thy tt nht vi nhng nhm hydrophylic carbon alpha (iu ny c cho l tr gip nhng penicillin ny bngqua porin outercell membrane ca VK gram m)

N

S

O

HN

CH3

COO

HH

H

CH3COCH2

R'


44/67

N

S

O

HN

CH3

COO

HH

H

CH3COCH2

R'

The tren C cua chc carboxamid (PNC- G):

amin, hydroxyl, carboxylic, sulfonilic

M rong hoat pho sang vi khuan gram am

PENICILLIN NHOM III


45/67

PENICILLIN NHOM III

S

O

NH

COOH

C

ONH

2

HOOC

penicillin N

Dch nuoi cayCephalosporium acremonium

(yeu hn peni G tren gramdng,

nhng co tac ong tren gram am)

PENICILLIN NHOM Ampicillin

1945


46/67

Nhom III: gom co 2 phan nhom IIIA va III B:

III-A: khong co nhom the tren amin (NH2):

Ampicillin, Amoxicillin

III-B: co nhom the tren amin (NH2):

Azlocillin, Mezlocillin, Piperacillin

PNC NHOM III-A Ampicillin, Amoxicillin


47/67

PNC NHOM III-A Ampicillin, Amoxicillin

2S,5R,6R)-6-[[(2R)-2-amino-2-phenylacetyl]amino]-3, 3-dimethyl-7-oxo-

4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

(2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-

dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid,

- Bn vi acid- Nhng nhy cm vi lactamse.- Hp thu km qua rut


48/67

Pho cua penicillin G cong them mot so vi khuangram am nh Haemophilus, Escherichia, Proteusmirabilis, Salmonella, Shigella.

Mot so vi khuan gay nhiem trung mac phai tai benhvien khong nhay cam vi nhom khang sinh nay:Enterobacter, Serratia, Proteus indol dng,Providencia, Bacillus pyocyanic.

Pho khang khuan III-AAmpicillin, Amoxicillin


49/67

PNC NHOM III-BAzlocillin, Mezlocillin, Piperacillin

Tac ong tren cac mam e khang vi ampicillin nh:Klebsiella, Enterobacter, Serratia, Pseudomonas

Piperacilin phoi hp vi aminosid hoac vi chat c chebetalactamase

PENICILLIN NHOM IV (-carboxy-PNC)


50/67

Na

N

S

H

HN

COOO

H HCOC

H

COO

Ar

Z

S

Z

Na

Na

Ar

Carbenicillin

Carindacillin

Ticarcillin

PENICILLIN NHOM IV (-carboxy-PNC)Carbenicillin, ticarcillin, carindacillin

Z=phenyl : Carfecillin

N

SHNH H

O

OC

HC

SO3H

COO Na

Sulbenicillin

Ben ve mat hoa hoc

Hoat tnh KK tng t cac

-carboxy-PNC

- Hoat tnh tren trc khuan mu xanh- ong van vi aminosid- Ticarcillin hoat tnh 2 lan manh

hn carbenicillin.


51/67

PENICILLIN NHOM VI (Amidino-PNC)

N

S

O

N

CH3

COO

HH

H

CH3CHN

R' Ten hoa hoc

Na+

CH2 O CO C(CH3)3(HCl)

Mecillinam

Pivmecillinam(Selexid)

Amidinopenicillin R'

Pho KK hep, tap trung chu yeu tren VK gram am.

Rat nhay cam: Escherichia coli.

Nhay cam: Yersinia, Salmonella, Shigella, Enterobacter, Citrobacter,

Klebsiella (khong san xuat hoac san xuat yeu penicillinase).

Khong e khang cheo vi ampicillin

N

azepan-1-ylmethanimine

CH NH

(nhn azepin gn trn lin kt amidine)

CHAT C CHE LACTAMASE


52/67

CHAT C CHE -LACTAMASE

AI CNG

Nhieu loai vi khuan co kha nang tiet ra cac enzym betalactamase phan huy cac khang sinh ho beta lactamine.

S san sinh cac enzym nay co the la t nhien hay tiepnhan c. Men beta lactamase bao gom penicilinase va

cephalosporinase.


53/67

Chat c che beta lactamase + cac penicillin: m rongpho khang khuan cua nhng chat nay len cac vikhuan tiet men penicillinase.

Sau khi gan vi men penicillinase, cac chat nay se bphan huy.

C CHE TAC ONG


54/67

Acid clavuclanic (suicide inhibitor)


55/67

Acid clavuclanic (suicide inhibitor)

Thu c t Streptomyces clavuligerusCau truc clavam (oxapenam)

c s dung dang muoi kali clavuclanat

Cac phoi hp: acid clavuclanic amoxicillin,

acid clavuclanic ticarcilinclavulanate meropenem (ang nghin cu)

NO C

HH

H

O

CH2OH

HH COOH


56/67

Cai thien tren nhng mam nhay cam san xuat betalactamase nh Neiserria gonorhoeae, Haemophilus,E. coli, Salmonella.

A. clavuclanic ticarcillin

Phoi hp nay gia tang tac ong tren Staphylococcus(95% Streptococcus nhay cam vi phoi hp acidclavuclanic ticarcillin so vi 49% neu ch s dungmot mnh ticarcillin).

Pho khang khuan cua phoi hpB. clavuclanic amoxicillin

Sulbactam


57/67

Dan chat cua penam, ban tong hp t 6 APA

Cau truc tng t penicillin nhng khong co nhom the C6 (mat C*),

S v tr 4 c oxy hoa thanh SO2, Cau hnh C2 va C5 giong penicillin

Sulbactam(2S,5R)-3,3-Dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic

acid 4,4-dioxide

Phoi hp sulbactam-ampicillin

N

SHH

H

O H COOH

CH3

CH3

O O


58/67

- Dan chat este i t sulbactam va ampicillin

- Hoat tnh tren cau khuan gram dng, gram am; trckhuan gram dng, gram am

- c dung trong tai-mui-hong, ho hap, sinh duc, datren nhng mam nhay cam

Sultamicillin

N

S

CH3

CH3

O

OO

O

N

S

O

H3C

H3C

OO

O

H

N

O

NH2

Sultamicillin


59/67

Dan chat cua sulbactam ma mot nhom methyl mangnhom the triazolyl

Chat c che betalactamase khong thuan nghch phorong

S dung di dang phoi hp tazobactam - piperacillin

Tazobactam

N

SHH

H

O H COOH

CH2

CH3

O O

NNN

CARBAPENEM


60/67

NO

Carbapenem

N

HO

H3C

OCOOH

S

NH2

Thienamycin (1977)

Thienamycin :

- trch t moi trng nuoi cay Streptomyces cattleya.- hoat tnh khang khuan rong- hoat tnh tren Pseudomonas

- khang lai -lactamase

SNH2

SNH CH NH


61/67

NO

CO2

S

R

Me

OHHH

Plays a role in

lactamase resistance

Double bond leading tohigh ring strain and increase

in lactam reactivityThienamycin R = NH3

Imipenem R = NH-CH=NH


62/67

IMIPENEM

Acid [hydroxy-1 ethyl (R) ]6[[(iminomethylamino-2)ethyl]thio]-3-oxo-7-aza-1bicyclo [3.2.0]hepten-2

carboxylic-2 (5R,6S).

N

HO

H3C

OCOOH

S

NH2

Thienamycin (1977)

N

HO

H3C

OCOOH

S

NHNH

Imipenem

benzyl formimidat

IMIPENEM


63/67

Pho khang khuan

Ben vng vi men beta lactamase, pho khang khuan rat rong, bao gom:

-Cau khuan gram dng: Staphylococcus nhay meticillin (Staphylococcus khangmeticillin e khang vi imipenem), Strepococcus (ke ca nhom D),Pneumococcus, Enterococcus.

-Cau khuan gram am: Neisseria

-Trc khuan gram dng: Clostridium, Listeria monocytogenes

- Trc khuan gram am: H. influenzae, E. coli, Klebsiella, Proteus mirabilis,Enterobacter, Citrobacter, Serratia, Proteus vulgaris, Bacteroides fragilis,Acinetobacter, P. aeruginosae.

N

HO

H3C

OCOOH

S

NH

NH

IMIPENEM


64/67

- IV cham.

- De b phan huy bi dehydropeptidase ong than khi s dung thng

ket hp imipenem vi cilastin (chat c che enzym dehydropeptidase) e gii

han s chuyen hoa nay.

cilastin

N

HO

H3C

OCOOH

S

NH

NH

4-Methyl carbapenem


65/67

N

HO

OCO2H

S

HN

NH

Imipenem

Bn hn i vi s thy gii ca dehydropeptidase

NO

CO2

S

Me

OHHH CH3

HN

C

O

N

R2

R1

Meropenem R1= R2 = Me

Ertapenem R1= H; R2 =

CO2

Ni chung, carbapenem c ph khng khun rngnht trong tt c cc KS lactames.


66/67

ME1036. ME1036 (CP5609; developed by Meiji Seika, licensed

by Forest) is a broad-spectrum carbapenem that binds

with a high affinity to PBP 2a of MRSA (IC50 0.13 to 0.73

g/ml) and that exhibits potent in vitro inhibitory

activity against MRSA .

A series of 4-methyl carbapenems having structural similarityto ME1036 showed potent activities against MRSA and PRSP, as

well as against the gram-negative organism ampicillin-resistant,

-lactamase-negative Haemophilus influenzae

N

HO

OCO2H

S

HN

NH

Imipenem


67/67

PZ-601 (Razupenem). PZ-601 (formerly known as SMP-

601; licensed from Dainippon Sumitomo Pharma Co., Ltd.,

Osaka, Japan) is a new carbapenem currently being developed

by Protez Pharmaceuticals (now Novartis) that has

demonstrated a high degree of potency against MRSA.

N

HO

OCO2H

S

HN

NH

Imipenem

Documents

Betalactam I-Dai Hoc-janvier 2012.SV