Med Chem - Group 5

7/23/2019 Med Chem - Group 5

http://slidepdf.com/reader/full/med-chem-group-5 1/16

SEM 1 2015/2016

FAR 212 MEDICINAL CHEMISTRY

CEFOTAXIME (PDB CODE: 3HLW)

Group 5:

No. Name Matric No. I.C No.

1. T!" Y# F$# 123%55 %&0'1'1&5&&2

2. *+,$ S#$- S#!" S 123''2 %50123136&26

3. T+ #!" C# 123%&6 %512105&62

&. F+#! N+4#+ 4#!# A+! 123'6 %51210'500

5. M## A#$*+ 4#!# H+7# 1230%' %5025035200

6. C$,#-+!# +/8 S+"+$9+! 123'65 %506220'5600

. C*#7#!$ Y+8 Y$#! Y$#! 123'& %5010501612

'. A*#!+ 4#!# M N+#* 1230% %500025'26%. M++ F#*+7 4#! M

I4*+#

123%12 %5052'05115

SUPERVISOR : DR. AISYAH SAAD ABDU RAHIM

!a"#e o$ Co%te%t

1 ; P + " $



Co%te%t Pa&e %um"er A47*+, 1I!*,#! 23M+#! 4<:

P+* 1: D*" !$!,+*$ P+* 2: D*"P*$#! S*,*$

P+* 3: C8$*+#$ D*" D$7#"!

P+* &: P<7#,,$#,+ P*8$*#$7 = D*"

P+* 5: L$+ O8##7+#!

3&&5

56

6%

%11C!,7#! 12R$=$*$!,$ 1213

ABS!RAC!

C$=+>#$ #7 + 3* "$!$*+#! ,$8+78*#! + +7 + " +,#9#< +"+#!7

4 *+87##9$ +! *+ !$"+#9$ 4+,$*#+ -# =*$* $==$,#9$!$77 +"+#!7*+ !$"+#9$ 4+,$*#+. C$=+>#$ +,7 4< 4#!#!" 8$!#,##! 4#!#!" 8*$#!

2 ; P + " $



(PBP)? #!#4##!" ,*77#!@#!" = 8$8#$ 7#$ ,+#!. C$=+>#$ #7 + *" + 4$<7

$ L#8#!7@#7 R$ = F#9$ +! #7 -+$*74$ +,,*#!" L$@$7 F*+.

T$ 4$,#9$ = #7 +7@ #7 #=#,+#!7 ! $+ ,8! #8*9$ #7

8<7#,,$#,+ 8*8$*#$7. T$ =#*7 #=#,+#! -+7 !$ 4+7$ ! #88##,#<8*8$*<. M#=#$ ,$=+>#$ +7 + -$* " P 9+$ +! $ *#"#!+ #!,*$+7$

$ <*8##,#< = ,$=+>#$ 4< 747##!" 2+#!#+&< "*8 + $ +,<

+#! 7#$ ,+#! 1?3#+##!$2?&#!$. A *$ <*8##, *" - +9$

$>$!$ +,#9#< +"+#!7 *+ !$"+#9$ 4+,$*#+. S$,! #=#,+#! #!99$ $

*$8+,$$! = ##!$>< -# ##!#78*8<>< "*8. T$ 8*87$ = 7,

*$8+,$$! -+7 #!$* $ +88*+, = 4$+ +,++7$7 = 4+,$*#+ $

77,$8#4$ "*8. L+7<? #=#,+#! + 87##! 3 = ,$=+>#$ -+7 !$

#8*9$ #!#4##! +,#9#< = ,$=+>#$ -+*7 8$!#,##! 4#!#!" 8*$#! (PBP).E7$* "*8 -+7 747#$ -# $7<+$ "*8 4$,+7$ $7<+$ +7 + -$* 8+

+! $!,$ # #7 + 4$$* $+9#!" "*8.

IN!RODUC!ION

C$8+78*#! #7 7$#7<!$#, 4$+ +,+ +!#4##, $*#9$ =*

,+$ Cephalosporium +! # -+7 #7,9$*$ 4< #7$88$ B*. H$ #7,9$*$

3 ; P + " $



+ $ ,*$7 Cephalosporium acremonium #!#4#$ $ "*- = *+87##9$

+! *+!$"+#9$ 4+,$*#+.1

!# !-? $*$ +*$ =#9$ "$!$*+#!7 ,$8+78*#! + +7 4$$!

#7,9$*$. E+, "$!$*+#! +7 #=#$ 8*8$*#$7 = $ 8*$9#7 "$!$*+#! +7

47$*9$ #! $ 78$,* = +,#! +"+#!7 *+ !$"+#9$ 4+,$*#+ +! 4$+

+,++7$ *$7#7+!,$. C$=+>#$ #7 $ =#*7 3* "$!$*+#! = C$8+78*#!

$9$8$ +! +*@$$ 4< H$,7R77$ P+*+,$#,+ +*! 1%'07. T$*$

+*$ 7$9$*+ 4*+! !+$7 =* ,$=+>#$ 7, +7 C+=*+! ? I+>#$? C$=+>!$

$, 2 +! #7 INN #7 ,$=+>#$. I #7 #"< *$7#7+! 4$++,++7$ +! +7 4*+

78$,* = +,#9#<? +@#!" # $==$,#9$ +"+#!7 4 *+ 87##9$ +! *+

!$"+#9$ 4+,$*#+.

S##+* $ $* 3* "$!$*+#! ,$8+78*#!? ,$=+>#$ #7 7$ *$+

9+*#7 @#! = 4+,$*#+ #!=$,#!7 #!,#!" 7$9$*$ * #=$*$+$!#!" =*. I #7 +7

7$ 8*$9$! #!=$,#!7 #! 7*"#,+ 8+#$!. E>+8$7 = #!=$,#!7 + ,+! 4$

*$+$ 4< ,$=+>#$ +*$ #!=$,#! = 78#!+ ,* * 4*+#! $ $!#!",,,7 +!

4 #!=$,#!. C$=+>#$ +7 + 4*+ 78$,* = +,#9#< +"+#!7 *+ 87##9$

+! *+ !$"+#9$ 4+,$*#+ 4 # ,+!! 4$ 7$ +"+#!7 Pseudomonas aeruginosa.

O! 8 = +? ,$=+>#$ #7 7$= *$+ #!=$,#!7 + +*$ @!-! 4$ *$7#7+!

8$!#,##! $*#9+#9$7. I #7 4$#!" +#!#7$*$ #! $ 4< 9#+ #!*+9$!7#!$,#! * #!=7#! * #!*+7,+* #!$,#!. A7 $ #!*+7,+* #!$,#! +< 4$

8+#!=? #!*+9$!7 #!$,#! #7 7+< 8*$=$**$.3

T$ $,+!#7 =

,$8+78*#! #7 7##+* 8$!#,##!

(+7 7-! #! $ #+"*+ +49$)&. I $>$*7

4+,$*#,#+ +,#! 4<#!#4##!" ,$ -+

7<!$7#7 78$,#=#,+< $ 8$8#"<,+!

+<$*. C$=+>#$ +7 + #" +==#!#< =*

8$!#,##!4#!#!" 8*$#! (PBP). T$

,*77#!@+"$ = 8$8#$ 7#$ ,+#!7 4$-$$! 8$8#"<,+! 8*$,*7*7 #7 ,++<7$

4< PBP #! $ *$+,#! @!-! +7 *+!78$8#+#!. I! $ 8*$7$!,$ = ,$=+>#$?

,$=+>#$ #!$*=$*$7 -# $ ,*77#!@#!" 4< 4#!#!" $ PBP? 7 8*$9$!#!"4+,$*#+ ,$ -+ 7<!$7#7. O!,$ 4+,$*#+ ,$ -+ 7<!$7#7 #7 #7*8$? #"

& ; P + " $



#!$*!+ 7#, 8*$77*$ -# ,+7$ $ ,$ *8*$. T7? # #7 7+# +

,$=+>#$ +7 4+,$*#,#+ +,#!.5

A7 =* $ $+4#7 = ,$=+>#$? +*! 2036G = #!*+9$!7<

+#!#7$*$ 7$ = 1&C,$=+>#$ #7 $>,*$$ 4< $ @#!$< +7 8+*$! *". A!$* 1525G $>,*$$ +*$ = $7+,$< $*#9+#9$ -#, #7 $ +* $+4#$.6

D$7+,$< $+4#$ +7 4$$! 8*9$! ,!*#4$ $ 4+,$*#,#+ +,#9#<.

O9$*7$ = ,$=+>#$ ,+7$7 +9$*7$ $==$,7 7, +7 !+7$+? 9##!"? #+**$+

+! 8$!#+< *$ 7$9$*$ ,+7$ 7, +7 S$9$!7!7! 7<!*$.

DRUG NOMENCA!URE

ATC ,$ =* $ *"? C$=+>#$? #7 01DD01. A,,*#!" ATC

C+77#=#,+#! S<7$? *$8*$7$!7 +!##!=$,#9$7 =* 7<7$#, 7$. F* 01? #7

"*8 ,8*#7$7 +!#4+,$*#+7 =* 7<7$#, 7$ $>,$8 =* <,4+,$*#+ -#, #7

!$* 0&. A!#4+,$*#+7 +*$ ,+77#=#$ +,,*#!" $#* $ = +,#! +!

,$#7*<. F*$**$? 01D *$8*$7$!7 $ "*8 =* $* 4$++,+

+!#4+,$*#+7 $* +! 8$!#,##!7. L+7<? 01DD ,!7#77 = #* "$!$*+#!

,$8+78*#!7 -#, +9$ +*@$ +,#9#< +"+#!7 "*+!$"+#9$ 4+,$*#+ 4

##$ +,#9#< +"+#!7 "*+87##9$ ,,,#.'

T$ ,$#,+ !+$ #7 (6R? R? ) 3(A,+><$<)(2(2

+#!#+&<)2($><##!)+,$+#)'>5#+1++4#,<,&?2?0J,

2$!$2,+*4><#, +,#.% C$=+>#$ #7$= #7 $ INN.

5 ; P + " $

Structure of desacetyl metabolite



T$ @$< =!,#!+ "*87 8*$7$! #! #7 *" +*$ 4$++,+ *#!"? +#$ +!

$7$*7.

T$ - ,$#,+ *$+,#!7 + ,+! $+ $ ,$#,+ $"*++#! +*$:

*8 = +#$7: <*"$!+#! = +#$7

*8 = $7$*7: <*<7#7 = $7$*7

PAR! ': DRUG(PRO!EIN S!RUC!URE+) O9$*+ (=* C#$*+) 4) L#"+! (*") +! 8,@$ (=*

C#$*+)

T$

+*"$

7*,*$ -# +*"$ $ #7 $ 8,@$ -$*$

#"+! 4#!7 #.

,) A +8 = L#"+! (D*") KP*$#! I!$*+,#!

6 ; P + " $

Ligan



The ligand interact

with another protein

through the dotted

line.

PAR! ): COMPU!ER(AIDED DRUG DESIGN

+) 2D 7*,*$

4) F* H<8$*C$

M#!##7+#! $!$*"<: &&'.122'03 @,+/

,)

; P + " $

Before minimization

After minimization



PAR! *: PHYSICOCHEMICA PROPER!IES O+ !HE DRUG

No. E#eme%t, S-m"o# Num"er pre,e%t i%

,tructure

Atomic ei&/t

0I%1i2i1ua#3

Atomic ei&/t

0o2era##3

1) S8* S 2 32.065 6&.13

2) N#*"$! N 5 1&.006 0.0335

3) H<*"$! H 1 1.00% 1.13&3

&) C+*4! C 16 12.010 1%2.112

5) O><"$! O 15.%%%& 111.%%5'

!ota# *55.*4*

a3 Mo#ecu#ar ei&/t

"3 HBA a%1 HBD10

' ; P + " $

3D structures in ball and stic!" 3D structures in space #olume

3D structures in stic!



c3 i. o& P: 67 0Sum o$ a## t/e $ra&me%t,388(8)

A,,*#!" SP? -+$* 74##< #7 $=#!$ +7 74##< "*$+$* +! 3.3G -#,

$+$7 +! +88*>#+#! = " P = 0.5. L" P 9+$7 $77 +! 0.5 +*$

,!7#$*$ 4$ -+$*74$ * <*8##, +! 9+$7 + +*$ *$ +! 0.5 +*$

-+$*#!74$. 1& H$!,$? ,$=+>#$ #7 + <*8##, ,8!.

ii. Mo#ar re$racti2it-:

M+* *$=*+,#9#< #7 + ,! $ 7$ ,+,+$ $ 7$*#, 4@ = + $,$

4< +88<#!" $ ,!,$8 = $,$ 8+*#7+#! (*$=*+,#9$ #!$>)? $!7#< +!

$,+* -$#" = $ $,$. I7 $+#! ,+! 4$ -*#$! +7 4$-:15

MR n2−1

n2+2

MW

d

MR (1.78 )2

−1

(1.78 )2+2 455.465

1.80

106.16 31

Iii. p9a a%1 io%i,atio% at pH .*

A,,*#!" D*"4+!@? $ 8+ + $ 7*!"$7 +,##, ,!##! #7 3.1' -$*$+7 +

$ 7*!"$7 4+7#, ,!##!? $ 8+ #7 &.15.

% ; P + " $

-$*$ $!7#<

MW $,+* -$#"

MR +* *$=*+,#9#<

! *$=*+,#9$ #!$>

+ra&me%t, ; 0$ra&me%t, 2a#ue3 Source,

1.% C$A>!

0.55 C$A>!

0.61 C$A>!

67 (8.<8



A 7*!"$7 +,##, ,!##! A 7*!"$7 4+7#, ,!##!

8+ 8H "[unionised][ ionised]

3.1' .& "

[unionised]

[ ionised]

&.22 "[unionised][ ionised]

10−4.22

[unionised]

[ ionised]

[unionised][ ionised]

6.026×10−5

1

G = #!#7+#!

−5

6.026×10

¿

¿1+¿1

¿

×100

G = #!#7+#! %%.%%G

8+ 8H "[ionised ][unionsed ]

&.15 .& "

[ ionised]

[unionised]

3.25 "[ ionised]

[unionised]

10−3.25

[ ionised]

[unionised]

[ ionised][unionised]

5.623×10−4

1

G = #!#7+#!

5.623×10−4

1+(5.623×10−4)

×100 G = #!#7+#!

0.0562G

H$!,$? ,$=+>#$ #7 +47*4$ + 4+7#, ,!##! +7 !#!#7$ =* + 8H.&.

D3 em=e>, empirica# approac/

W+$* 74##< = + $,$ ,+! 4$ 8*$#,$ 4< @#!" + $ ,+*4! 74###!"

8$!#+ = $ =!,#!+ "*8 = $ $,$. T$ $,$ #7 ,!7#$*$

#!74$ #= $ 74###!" 8$!#+ ! $>,$$ $ + !4$* = ,+*4! 8*$7$!

#! $ $,$ +! 9#,$ 9$*7+.16

em=e>, Empirica# So#u"i#it-

C$=+>#$ #7 + 8<=!,#!+ $,$ -# + + !4$* = 16 ,+*4!7.

F!,#!+ "*87 #!99$:

1) 2 $!$: 2 > 2 & C+*4!72) 3 A#!$ : 3 > 3 % C+*4!7

10 ; P + " $



3) 1 C+*4><#, A,#: 3 C+*4!7&) 1 E7$*: 3 C+*4!7

T7? + 74###!" 8$!#+:

& % 3 3

1%? "*$+$* +! $ + ,+*4! +7 !4$* (16)

t/e mo#ecu#e i, ater(,o#u"#e

E3 ipi%,=i>, Ru#e o$ 5 ,tate, t/at t/e 1ru& mu,t /a2e:8

+) A $,+* -$#" !$* 500 4) A 8+*##! ,$==#,#$! " P (+ $+7*$ = #88##,#<) = $77 +! 5 ,) N *$ +! =#9$ <*"$! 4! !*7 (HBD) ) N *$ +! 10 <*"$! 4! +,,$8*7 (HBA) (S*,$: R<+ S,#$< = C$#7*<)

C8!7 + 4$< $7$ *$7 +*$ #@$< 4$ *+< +,#9$ +! #7 -+$*74$$ - " P 9+$. C$=+>#$ 4$<7 $ L#8#!7@#7 R$ = F#9$.

PAR! 5: EAD OP!IMISA!ION

+. M#=#,+#! 4+7$ ! #88##,#< (L" P)

L" P #!#,+$7 $ #88##,#< = $ *" -#, #7 !$ = $ 7 #8*+!

8<7#,,$#,+ =+,*7 + +==$, $ *" +47*8#!. T$ *$ #88##, + *"?

$ +*"$* $ " P 9+$ # +7 +! $!,$ $ $+7#$* =* # 8$!$*+$ 8+7+

$4*+!$ +! 747$$!< 4$ +47*4$.

1'

H-$9$*? #!=> = *" #! *+!$"+#9$ 4+,$*#+ #==$*7 =* $ +49$ =+,.

*+!$"+#9$ 4+,$*#+ +7 + !#$ =$+*$ -#, #7 #7 $* $4*+!$ -#, #7

78+!!$ 4< 8*#!7. T$*$ +*$ - 8+-+<7 =* +!##,*4+,$*#+ +"$! $!$* +

,$ *" $* $4*+!$. F* <*84#, *"7? $< ,+! $!$* 9#+ #8#

$#+$ 8+-+< "$!$*+ #==7#! 8*#!7 =* <*8##, ,8!7.1% A"

$* $4*+!$ #7 +$ = #88<7+,,+*#$ +! #7 #8$*$+4$ ,+*"$ +!

+*"$ $,$7? *"7 #!=> #7 7# +*"$< ,!*$ 4< 8*#!7 -#, +- 8+77#9$

#==7#! = <*8##, $,$7 $ 8$*#8+7#, 78+,$.1'?1%

11 ; P + " $

L" P = #=#$ ,$=+>#$ L" P = *#"#!+ ,$=+>#$



I! *$* 4$ +4$ 8+77 *" 8*#!7 4$$*? $ ,8! #7 +$ *$ 8+*

4< #=<#!" $ 2+#!#+&< "*8 1?3#+##!$2?&#!$ (+7 7-! #!

+49$ =#"*$). T$ #=#$ *" 7-$ $,*$+7$ " P 9+$ -#, $+!7 + #

#7 *$ <*8##, +! $ *#"#!+ *". T$*$=*$? $ #=#$ *" 7

8$!$*+$ *+ !$"+#9$ 4+,$*#+ 4$$* +! $!,$ - +9$ +! #8*9$ *"

+,#9#<. L#8#!7@#7 R$ = 5 #7 4$<$.

L$@$ F*+

T+ !4$* = ,+*4!7 16C

1 COOH 1 > 3 3C

3 A#!$ 3 > 3 % C

& $!$ & X 2 ' C

1 E7$* 1 > 3 3 CT+ 74###!" 8$!#+ 23? "*$+$* +! +

!4$* = ,+*4! +7 (16)

∴ Modified cefotaximeis water soluble .

"3 Impro2eme%t "a,e1 o% Steric

+actor

T$ *#"#!+ ,$=+>#$ -# ##!$>< + 87##! #7 ,+!"$

##!#78*8<><. T#7 #7 4$,+7$ $ $< "*8 +7 + -$* 7$*#, $==$,

,8+*$ #78*8< "*8. W$ ,7$ 747#$ -# #78*8< "*8 #!7$+ =

t 4< "*8 4$,+7$ 4< +< 4$ 4@< "*8 +! $!,$ 8*$9$! $ *"

=* 4#!#!" +*"$ *+!78$8#+7$ $!<$. B< +#!" #78*8< "*8? # +4$

#!$* *$ $==$,#9$< +! $< "*8 $ +88*+, = 4$+ +,++7$7 =

4+,$*#+ $ 77,$8#4$ "*8.

12 ; P + " $



T#7 !$- +88*+, +7 4$<7 L#8#!7@# R$ = 5.

T ,+,+$ $ -+$* 74##< = $ $,$? -$

$8<$ L$@$7 E8#*#, F*+.

T$ -+$* 74###!" 8$!#+ = *"+!#, =!,#!+ "*87 8*$7$!:

2 $!$: 2> 2 &C+*4!7

3 A#!$ : 3 > 3 % C+*4!7

1 C+*4><#, A,#: 3 C+*4!7

1 E7$*: 3 C+*4!7T7? + 74###!" 8$!#+:

& % 3 3

1%? "*$+$* +! $ + ,+*4! +7 !4$* (1')

t/e mo#ecu#e i, ater(,o#u"#e

T#7 $+!7 + $ !$- +88*+, $!+4$7 $ *" 8$!$*+$ $ $4*+!$ +!

$+7#< +47*4$ 4< $ 4<.

c3 Mo1i$icatio% ma1e to impro2e

i%/i"itio% acti2it-

13 ; P + " $

M#=#$ ,$=+>#$

+) A $,+* -$#" !$* 500 (&'3.5+)

4) A ,+,+$ " P (2.05) $77 +! 5

,) N *$ +! 5 <*"$! 4! !*7 (HBD)

) N *$ +! 10 <*"$! 4! +,,$8*7 (HBA)



E7$* "*8 + 87##! 3 747#$! #7 747#$ -# $+!$7=!+$ *

,!< @!-! +7 $7<+$ "*8. I #7 + ,!"+$ 4+7$ = $+!$7=!#, +,#?

+ 7*!" +,# -# 8+ 1.2.20 O! $ $* +!? $ 8+ = +,$#, +,# #! $ *#"#!+

,$=+>#$ #7 &.6. T#7 $+!7 + $+!$7=!#, +,# +7 + #"$* +,##< +!

+,$#, +,#. T$ 7*!"$* $ +,#? $ -$+@$* #7 ,!"+$ 4+7$ +! $!,$ $

4$$* $ $+9#!" "*8. T$*$=*$? $7<+$ #7 + " $+9#!" "*8 -$! $ 4$+

+,+ *#!" #7 ++,@$ 4< !,$8#$? *$7#!" #! $$,*! $,+#7+#! $7<+$

"*8. A 4$$* $+9#!" "*8 #! $ #=#$ ,8! 7 +9$ +! #8*9$

#!#4##! $,+!#7 +! $ *#"#!+ ,8!.

A,,*#!" L#8#!7@#7 R$ = 5:

L" P ! *$ +! 5 N$- ,L" P : 3.12

T+ HBA ! *$ +! 10 T+ 10 HBA

T+ HBD ! *$ +! 5 T+ 2 HBD

M$,+* -$#" ! *$ +! 500 N$- $,+* -$#" : &%1.5+

T#7 !$- ,8! 4$<7 L#8#!7@#7 R$ = 5 7 # 7 4$ *+< +,#9$ +!

7 4$ +4$ 8$*$+$ *" $4*+!$. L" P 9+$ #!#,+$7 + #7

,8! - +9$ #88##,#<.

L$@$ E8#*#,+ S4##<:

T+ !4$* = ,+*4! +7: 15

2 $!$: 2 > 2 & C+*4!7

3 A#!$ : 3 > 3 % C+*4!7

1 C+*4><#, A,#: 3 C+*4!7

N$- + 74##7#!" 8$!#+ & % 3

16C ("*$+$* +! $ + !4$* = ,+*4!7)

T$*$=*$? $ #=#$ ,8! 7 4$ -+$*74$.

CONCUSION

D$ $ 8*8$*#$7 = *+!$"+#9$ 4+,$*#+? ,$=+>#$ !$$7 +9$ #"$*

<*8##,#< *+$* +! #"$* #88##,#< =* $ *" 4$ $==$,#9$. I! *$*

+,#$9$ #7? $ ,8! #7 +$ 4$ *$ 8+* 4< #=<#!" $ 2

+#!#+&< "*8 1?3#+##!$2?&#!$. B< #=<#!" #7 7*,*$? $

" P ,+,+$ #7 *$,$ =* 1.%1 2.'0 -#, $+!7 + $ *" #7 !-

-+$* 74$ +! 7 7 #8*9$ $ 8$!$*+#! = $ *" #! *+

!$"+#9$ 4+,$*#+. N$>? #!,*$+7$ 7$*#, =+,* ! $ ,8! =* #!,*$+7$

*$7#7+!,$ +"+#!7 4$++,++7$? ##!$>< + 87##! #7 ,+!"$ #!

1& ; P + " $



##!#78*8<><. T$ #78*8< "*8 #7 =+9*$ 4$,+7$ = $ 4@#!$77 #! $

7*,*$ -#, 8*$9$!7 4$++,++7$ =* 4#!#!" *" +! $+ *"

$"*++#!. O! $ $* +!? 4< *$8+,#!" $7$* #$< + 87##! 3 747#$!

-# $7<+$ "*8 7 ,!*#4$ +! #8*9$ #!#4##! +,#9#< -+*7 PBP.

T#7 #7 4$,+7$ $7<+$ #7 + 4$$* $+9#!" "*8 +! $7$*? $!,$ # - $+9$

$+7#< -$! 4$++,+ *#!" #7 ++,@$ 4< + !,$8#$. A = $ #=#$

,8!7 4$< L#8#!7@#7 R$ = 5 +! 7 4$ -+$*74$ +,,*#!"

L$@$7 E8#*#,+ S4##<.

RE+ERENCE

1. A$>+!$* S? A*,#+$#7 B +! L+!+ R (1%%%) P+*+,$#,+ I!!9+#!:

R$9#!##!" H+! H$+. P$!!7<9+!#+: C$#,+ H$*#+"$ F!+#!.

2. D*"7., (!.) C$=+>#$ 8://---.*"7.,/#!$*!+#!+/,$=+>#$.D+$ +,,$77$: 20 S$8 2015

3. D*"7., (2015) C$8+78*#!7. 8://---.*"7.,/*"

,+77/,$8+78*#!7. D+$ +,,$77$: 20 S$8 2015

&. $!$ E (200') P$!#,##! M$,+!#7 = A,#!.87://---.<4$.,/-+,9BY!RW, D+$ +,,$77$: 2& N9 2015

5. S$ SD +! S$ Q (200%) T$>4@ = P+*+,"< 3/$. C$8+78*#!7:

M$,+!#7 = +,#!. E7$9#$*.

6. L$F*,@ L? P*#!,$ RA +! L$== RD (1%'2) M$,+!#7 = +,#!? +!##,*4#++,#9#<? 8+*+,"<? +9$*7$ $==$,7 +! ,#!#,+ $==#,+,< = ,$=+>#$.

Pharmacotherapy ? 2(&): 1&'&

. N9+*#7 N$- $++! L##$ (201&) C$=+>#$ S+!.

8://---.$7+=$."9.!/8*=7/++7$$/,/C$=+>#$4#,$#$#!.8= D+$

+,,$77$: 5 N9 2015

'. W* H$+ O*"+!#7+#!? WHO (2013) WHO ,+4*+#!" ,$!*$ =* *"

7+#7#, $"<. 8://---.-,,.!/+,#!$>/

,$01DD017-$7,*#8#!<$7 D+$ +,,$77$: 22 S$8 2015

%. D*" 4+!@ 8://---.*"4+!@.,+/*"7/DB00&%3 D+$ +,,$77$: 25 S$8 2015

10. D*" 4+!@ (201&). P*8$*#$7: H<*"$! +,,$8* ,! +! <*"$! !*

,!. 8://---.*"4+!@.,+/*"7/DB00&%3 .D+$ +,,$77$: 2% O,4$* 2015

11. C$#,+#$.*" 4< C$A>! (2015) P*8$*#$7 Q#$-$*: " P = C$=+>#$

8://---.,$#,+#$.*"/7*,*$/U,$=+>#$7*,$,+,+$.D+$

+,,$77$: 6 N9$4$* 2015

12. C$#,+#$.*" 4< C$A>! (2015) P*8$*#$7 Q#$-$*: " P = 2

$metho%yimino&acetamide 8://---.,$#,+#$.*"/7*,*$/U

G2'$><##!G2%+,$+#$7*,$=8. D+$ +,,$77$: 6 N9$4$* 2015

15 ; P + " $

https://books.google.com/books?id=IH4lPs6S1bMC&pg=PA169&lpg=PA169&dq=cefotaxime+discovery++development&source=bl&ots=Qc0rTbbCjp&sig=ECyDVGzYHaadLIGFr1PqxsWL8FI&hl=en&sa=X&ei=QOG6VKDzCY-QyAS_4YLwDw&ved=0CEIQ6AEwBzgU#v=onepage&q=cefotaxime%20discovery%20%20development&f=false


http://www.drugs.com/international/cefotaxime.html

http://www.drugs.com/drug-class/cephalosporins.html



https://www.youtube.com/watch?v=qBdYnRhdWc

http://www.medsafe.govt.nz/profs/datasheet/c/Cefotaximebiochemieinj.pdf

http://www.whocc.no/atc_ddd_index/?code=J01DD01&showdescription=yes


http://www.drugbank.ca/drugs/DB00493


http://www.chemicalize.org/structure/#!mol=cefotaxime&source=calculate

http://www.chemicalize.org/structure/#!mol=(methoxyimino)acetamide&source=fp


http://www.drugs.com/international/cefotaxime.html



https://www.youtube.com/watch?v=qBdYnRhdWc

http://www.medsafe.govt.nz/profs/datasheet/c/Cefotaximebiochemieinj.pdf





http://www.chemicalize.org/structure/#!mol=cefotaxime&source=calculate







13. C$#,+#$.*" 4< C$A>! (2015) P*8$*#$7 Q#$-$*: " P = 2+#!1?3

#+&< http'((www.chemicalize.org(structure()*mol+c,-Bc-Dnc

-/0s,-/12source+fp. D+$ +,,$77$: 6 N9$4$* 2015

1&. L$@$ TL +! W##+7 DA (2013) P*$#,#!" W+$* S4##<: A!+<#,+/

V+!#+#9$ A88*+,. I!: F<$7 P*#!,#8$ = M$#,#!+ C$#7*< $. W$*7

-$* H$+.

15. L$+, AR +! #$ Q (200) A! #!*,#! ,$#!=*+#,7. M$,+*

$7,*#8*7: 2.3 M+* *$=*+,#9#<. S8*#!"$*

16. L$@$ TL +! W##+7 DA (200'). P*#!,#8$7 = *" #7,9$*<: W+$* 74##<

= *"7. I!: F<$7 8*#!,#8$7 = $#,#!+ ,$#7*<? 6 $. W$*7 -$* H$+.

1. H! S (200') B*$+@#!" $ R$7.

8://---.*7,.*"/,$#7*<-*/I77$7/200'/!$/B*$+@#!"T$R$7.+78 D+$

+,,$77$: 1 N9 2015.

1'. A+9#$ MS? C#7< M? V+#7$* M +! P+$* AM (2005) N$*R>. D*"M$+4#7 +! P+*+,@#!$#,7? $ BB*+#! B+**#$*? +! C$!*+ N$*97

S<7$ D*" D#7,9$*<. 2(&): 55&K51

1%. *+<7! ML (2010) ,$*7 T$ 7$ = A!#4##,7 S#> E!. T$ 8*$7$!,$ =

8*#! 8*$#! ,+7$7 <*8##, *" 8$!$*+$. CRC P*$77

20. D$-#,@ PM (2006) S=*#, A,# D$*#9+#9$: E77$!#+ = O*"+!#, C$#7*<: F* S$!7 = P+*+,<? M$#,#!+ C$#7*< +! B#"#,+ C$#7*<. W#$<

16 ; P + " $

http://www.chemicalize.org/structure/#!mol=c1%5Bc%5Dnc(s1)N&source=fp


http://www.rsc.org/chemistryworld/Issues/2008/June/BreakingTheRules.asp



http://www.rsc.org/chemistryworld/Issues/2008/June/BreakingTheRules.asp

Med Chem - Group 5

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