PF: FANSIDAR cp. continnd 500 mg sulfadoxina si 25 mg pirimetamina.

SULFAMIDE PIRAZINICE SULFAMETOXIPIRAZINA SULFAMETOXIPIRAZINUM (DCI)

NH2

H3 CO SO2 NH

N N

2-sulfanilamido-3-metoxi-pirazina Sinonime: SULFALEN, Sulfametopirazina. PF: LONGUM cp.; KELFIZINA.

1

 SULFACLOZINA SULFACLOZINUM (DCI)

NH2

N SO2 NH N Cl

2-sulfanilamido-6-cloro-pirazina
Sinonim: Sulfacloropirazina. PF: ESB3 pulbere de uz vet.
NH2

SULFAQUINOXALINA SULFAQUINOXALINUM (DCI)

SO2 NH N N

2-sulfanilamido-chinoxalina Sinonim: Sulfabenzpirazina.

2

SULFAMIDE PIRIDAZINICE SULFAMETOXIPIRIDAZINA SULFAMETHOXYPYRIDAZINUM (DCI)

NH2

SO2

NH N N

OCH3

3-sulfanilamido-6-metoxi-piridazina

preparare: prin reactia sulfanilamidei cu 3,6-dicloro-piridazina:

NH2
+

NH2 Cl N N Cl

HCl SO2 NH N N Cl

SO2

NH2 NH2 NaOCH3

-

NaCl SO2 NH N N OCH3

3,6-dicloro-piridazina se obtine din anhidrida maleica si hidrazina:

O O HC C HC C O O + NH2 NH2 HC C HC C NH NH HC C HC C N N OH POCl3 HC C N HC C N Cl

O 3,6-dicetotetrahidropiridazina

OH 3,6-dihidroxipiridazina

Cl 3,6-dicloropiridazina

 SULFACLORPIRIDAZINA SULFACHLORPYRIDAZINUM (DCI)

NH2

SO2

NH N N

Cl

3-sulfanilamido-6-cloro-piridazina

SULFAMIDE PIRIDINICE
SULFAPIRIDINA SULFAPYRIDINUM (DCI)
SO2 NH N NH2

2-sulfanilamido-piridina PF: DAGENAN cp.

5

SULFAMIDE N1-SUBSTITUITE, N4-ACILATE FTALILSULFATIAZOL PHTALYLSULFATHIAZOLUM (DCI)

HOOC NH C O N SO2 NH S

2-(N4-ftaloil)-sulfanilamido-tiazol Sinonim: Ftalazol. preparare: pornind de la anilina si anhidrida ftalica:

NH2 C + C

O C O - HOH O C

O N O + HOSO2Cl

anilina

anhidrida ftalica O C N C O SO2Cl - HCl C O

N H2N S

O C N SO2NH N S

HOOC NH C + HOH O N SO2 NH S

 PF: FTALILSULFATIAZOL cp. 500 mg; SUCCINILSULFATIAZOL SUCCYNYLSULFATHIAZOLUM (DCI)

NH C CH2CH2 O N SO2 NH S COOH

2-(N4-succinil)-sulfanilamido-tiazol

AZODERIVATI DE TIP ANALOG SULFAMIDELOR N1-SUBSTITUITE, N4ACILATE SULFASALAZINA

SULFASALAZINUM (DCI)

N N

OH COOH

SO2

NH

Acid 4-hidroxi-4-(2-piridil sulfamoil)-azobenzen-3-carboxilic

Sinonim: Salazosulfapiridina.
preparare: tratarea CAS-ului cu 2-amino-piridina:

NH C CH3 O +
H2 N N

NH C CH3 O - HCl + HOH - CH3COOH SO2 NH N

NH2

SO2 Cl

SO2

NH

+ NaNO2 + 2 HCl - NaCl - 2 HOH

N N] Cl

OH COOH

N N

OH COOH

SO2

NH

SO2 N

NH

2-Amino-piridina se obtine prin reactia Cicibabin, din piridina si amidura de sodiu:

+ HOH N NHNa - NaOH N NH2

+ N

NaNH2

PF: SALAZOPYRIN cp 500 mg

AZULFIDINE
10

SULFAMIDE CU STRUCTURI DIVERSE

MAFENID MAFENIDUM (DCI)

CH2

NH2

SO2

NH2

p-aminometil-benzensulfonamida Sinonim: Homosulfanilamida.

CH3 lumina 150o C toluen clorura de benzil CH2 Cl + H2N COCH3 acetamida - HCl acetilbenzilamina CH2 NHCOCH3

Cl2

CH2 + HOSO2Cl

NHCOCH3 HOH - CH3COOH

CH2

NH2

+ NH3
- HOH

- HCl

SO2

NH2

SO2

NH2

11

 PF: SULFAMYLON crema. ANTIMICOBACTERIENE ANTITUBERCULOASE (TUBERCULOSTATICE) ACID p-AMINOSALICILIC ACIDUM AMINOSALICYLICUM (DCI)
COOH OH

NH2

Acid 4-amino-2-hidroxibenzoic
Sinonim: PAS preparare: prin sulfonarea p-nitrotoluenului:

12

CH3 H2SO4 conc.

CH3 SO3H KMnO4/H2SO4

COOH SO3H 3 H2

(Zn + HCl) NO2 NO2 acid 2-metil-5-nitrobenzensulfonic COOH SO3H KOH 300 oC NH2 NH2 COOH OH NO2

PF: PASER pachet cu 4 g granule

IZONIAZIDA
ISONIAZIDUM (DCI, FR X)

CO NH NH2

Hidrazida acidului 4-piridincarboxilic Sinonim: HIN

13

 preparare: prin oxidarea -picolinei: CH3

KMnO4/H2SO4 N

COOH
+

COOCH3 CH3OH H2SO4 N

CO NH NH2 H2N NH2 . H2O - CH3OH N

PF: RIFAMPICINA I IZONIAZIDA capsule 300 mg rifampicina si 150 mg izoniazida.

CO NH NH3
+

COO .

PASINIAZIDA PASINIAZIDUM (DCI)

N NH2

OH

p-aminosalicilat de izonicotinoilhidrazida
14

IZONICOTINOILHIDRAZONE FTIVAZIDA
CO NH N CH OH OCH3 N

FTIVAZIDUM (DCI)

Vanilidenhidrazida acidului izonicotinic preparare: condensarea HIN-ului cu vanilina (4-hidroxi-3-metoxibenzaldehida):

CO NH NH2 + N OHC OH OCH3 N CO NH N CH OH OCH3

15

 CROTONIAZIDA CROTONIAZIDUM (DCI)

CO NH N CH CH CH CH3

2-butenilidenhidrazida acidului izonicotinic

preparare: condensarea HIN-ului cu aldehida crotonica:
CO NH N CH CH CH CH3

CO NH NH2 + N OHC CH CH CH3

16

 METAZIDA
CO NH NH CH2 NH NH CO

METAZIDUM (DCI)
N N

2,2-metilendihidrazida acidului izonicotinic

preparare: condensarea a 2 moli de HIN cu formaldehida:

CO NH NH2 2 N + CH2O N N CO NH NH CH2 NH NH CO

METANIAZIDA METHANIAZIDUM (DCI)

CO NH NH CH2

SO3H

izoniazid metansulfonat
17

DERIVAI TIOAMIDICI AI ACIDULUI IZONICOTINIC ETIONAMIDA ETHIONAMIDUM (DCI) (FR X)

N S C NH2

C2H5

2-etil-izonicotin-tioamida

Preparare: oxidarea cu perhidrol a 2-etil-piridinei:

NO2 + H2O2 N C2H5 CH3COOH N O S Br CuBr N C2H5 CuCN N C2H5 CN H2S N(CH2CH2OH)3 N C2H5 C NH2 C2H5 + HNO3 H2SO4 N Fe/H2SO4 C2H5 N C2H5 NH2

18

 PF: TRECATOR cp 250 mg. PROTIONAMIDA PROTIONAMIDUM (DCI)

N S C NH2

CH2

CH2

CH3

2-propil-tio-izonicotinamida PF: PROTIONAMIDA cp. 250 mg DERIVAI AI PIRAZINEI PIRAZINAMIDA PYRAZINAMIDUM (DCI)
N
1 2

C NH2 O

4 3

Amida acidului pirazin-2-carboxilic

19

 preparare: condensarea o-fenilen-diaminei cu glioxalul:

HC O HC O H2N + H2N -2 HOH N N chinoxalina + KMnO4 NaOH N N COOH COOH

O (CH3CO)2O N N C O C O NH3 N N C NH2 O N CH3OH N COOH

- CO2

COOCH3

N N

COOCH3

PF: RIFATER cp (120 mg rifampicina, 50 mg izoniazida si 300 mg pirazinamida).

20

 MORFAZINAMIDA MORPHAZINAMIDUM (DCI)

N N

C NH CH2 O

N-(morfolinometil)-pirazincarboxamida Sinonim: Morinamida

preparare: pirazinamida, formaldehida si morfolina:

N N N C NH2 O + CH2O + HN O - HOH N C NH CH2 O N O

DERIVAI DE TIOUREE TIOCARLID TIOCARLIDUM (DCI)

CH3 OCH2CH2CH CH3

CH3 OCH2CH2CH CH3

NH

C S

NH

4,4'-Bis(izopentiloxi)-tiocarbanilida
21

 Sinonim: izoxil.
OH + (CH3CO)2O OH + NH CO CH3 p-acetilaminofenol CH3 CH2CH2CH CH3 CH3 Br CH2CH2CH CH3

NH2

bromura de izoamil

p-amino-fenol
O CH3 CH2CH2CH CH3

O + HOH
-

CH3COOH NH2 p-izoamiloxianilina

NH CO CH3

CH3 CH2CH2CH CH3

CH3 OCH2CH2CH CH3 + CS2 - H2S

CH3 OCH2CH2CH CH3

2 NH2

NH

C S

NH

22

 ETOXID
AETHOXIDUM (DCI) H5C2O
NH C NH S OC2H5

4,4-bis-etoxi-tiocarbanilida preparare:
2 H5C2O NH2 . HCl + NH4SCN - NH4Cl H5C2O NH C NH S OC2H5

fenetidina
+ CS2 - H2S

Sau
H5C2O NH C NH S OC2H5

2 H5C2O

NH2

fenetidina

BUTOMELID
BUTOMELIDUM (DCI)

H3C N

NH C NH S

OC4H9

4-(n-butoxi)-4'(4''-metilpiperazino-1'')tiocarbanilida
23

TIOSEMICARBAZONELE ALDEHIDELOR AROMATICE TIOACETAZONA THIOACETAZONUM (DCI)

CH N NH C NH2 S

NH CO CH3

N-4-(carbamo-tioilhidrazin-iliden) metilfenilacetamida

HIDROXIALCHILDIAMINE
ETAMBUTOL ETAMBUTOLUM (DCI) (FR X)

HO CH2 CH NH CH2CH2 CH2 CH3 NH

CH2 CH CH2 CH3

OH

2-2-(1-hidroxibutan-2-ilamino)etilaminobutan-1-ol
24

CH2 CH2 CH2 Cl Cl + 2 CH2 CH3

OH

HO CH2 CH NH CH2CH2 CH2 CH3 NH

CH2 CH CH2 CH3

OH

CH NH2

dicloretan butanol
CH2 CH2 CH3 NO2

2-amino-1CH2 + CH2O NaHCO3 CH2 CH3 OH H2 CH2 CH2 CH3 OH

CH NO2

CH NH2

1-nitropropan formaldehida

ANTILEPROASE DIAFENILSULFONA DIAPHENYLSULFONUM (DCI)

H2N O S O NH2

4,4-diaminodifenil-sulfona
25

 Sinonim: Dapsona preparare:

O2N S S NO2

O2N

Cl

Na2S

p,p-dinitro-difenil-disulfura

p-clor-nitrobenzen
O2N S NO2

oxidare

p,p-dinitro-difenil-sulfura
O O2N S O NO2 O H2N S O NH2

red.

PF: DAPSONE cp. 25 mg si 100 mg; DISULONE cp. 100 mg.

26

 CLOFAZIMINA CLOFAZIMINUM (DCI)

Cl

N N

N CH(CH3)2 NH Cl

N-5-bis(4-clorofenil)-3,5-dihidro-3-(1-metiletil)imino-2-fenazinamina PF: LAMPRENE capsule a 50 mg clofazimina.

ALDESULFONA
ALDESULFONUM (DCI)
Na2OSH2C NH SO2 NH CH2SO2Na

Sarea de sodiu a acidului sulfonil bis (1,4-fenilenimino) bis-metansulfonic

27

 TIAMBUTOSINA

CH3 NH C NH S N CH3

THIAMBUTOSINUM (DCI) H9C4 O

N-(4-n-butoxifenil)-N-(4-dimetilaminofenil)tiouree ANTIMALARICE se clasifica in: antimalarice naturale (alcaloizi cu nucleu chinolinic chinina si chinidina) antimalarice de sinteza:

-derivati de 8-aminochinolina;
-derivati de 4-aminochinolina; -alti derivati de chinolina; -derivati acridinici;

-derivati biguanidici;
-derivati pirimidinici.

28

ANTIMALARICE NATURALE ALCALOIZI CU NUCLEU CHINOLINIC CHININA QUININUM (DCI)

H3CO N

OH CH N

CH CH2

nucleu chinuclidinic

}
4 3

nucleu chinolinic

2-etenil-4-azabiciclos2.2.2toct-5-il)- (6-metoxichinolin-4-il)-metanol

ANTIMALARICE DE SINTEZ
DERIVAI DE 8-AMINOCHINOLIN PAMACHINA
H3CO
6 7 8 1' 1 5

COOH OH
3' 4' +

PAMAQUINUM (DCI)

2 2'

CH2 OH COO
-

NH CH CH2 CH3

CH2

CH2

N(C2H5)2 H

Sarea 6-metoxi-8-(4-dietilamino-1-metil-butilamino)-chinolinei cu acidul 1,1-metilen-bis-(2-hidroxi-3-naftoic) 29

 Sinonim: Plasmochina

H3CO + N NH2 6-metoxi-8-aminochinolina 1-dietilamino-4-clor-pentan COOH H3CO N NH CH CH2 CH3 CH2 CH2
+ +

Cl

CH CH2 CH3

CH2

CH2

N(C2H5)2 - HCl

OH CH2 OH COOH

N(C2H5)2 H

pamachina embonat

30

 PRIMACHINA PRIMAQUINUM (DCI)

H3CO N NH CH CH2 CH3 CH2 CH2

+

NH3

H2PO4 sau Cl

6-metoxi-8-(4-amino-1-metil-butilamino)-chinolina fosfat (sau clorhidrat) PF: PRIMACIN cp. 13,2 mg fosfat echivalent cu 7,5 mg de primachina
OH

PLASMOCID PLASMOCIDUM (DCI) 3

H CO N NH CH2 CH2 CH2 CH2
+

COO

NH(C2H5)2 COOH OH

Sarea 6-metoxi-8-(3-dietilamino-propilamino)-chinolinei cu acidul metilendisalicili

31

H3CO + N NH2 6-metoxi-8-aminochinolina 1-dietilamino-3-clor-propan OH H3CO

+

Cl

CH2

CH2

CH2

N(C2H5)2 - HCl

COOH

N NH CH2 CH2 CH2 N(C2H5)2

CH2

COOH OH plasmocid

32

 Acidul metilen-disalicilic se obtine prin condensarea acidului salicilic cu formaldehida:

OH COOH OH COOH

CH2O - HOH

CH2

COOH OH OH

COOH

PENTACHINA PENTAQUINUM (DCI)

H3CO N NH (CH2)5 CH3 CH CH3 H2PO4

-

NH2

6-metoxi-8-(5-izopropilamino-pentametilenamino)-chinolina
33

 TAFENOCHINA TAFENOQUINUM (DCI)

O H3CO

CF3

CH3

N NH CH CH3

OCH3 CH2 CH2 CH2 NH2

N-[2,6-dimetoxi-4-metil-5-[3-(trifluorometil) fenoxi]chinolin-8-il]pentan-1,4-diamina DERIVAI DE 4-AMINOCHINOLIN

H3C CH
+

(CH2)3

NH(C2H5)2

NH2
4 3

CLOROCHINA DIHIDROGENOFOSFAT
CLOROQUINI
Cl

5 6 7

2 H2PO4

2 1

DIHYDROGENOPHOSPHAS (DCI) (FR X) Bishidrogenofosfat de 7-cloro-4-4-(dietilamino)1-metil-butilaminochinolina 34

Cl + Cl N H3C CH NH2 2-amino-5-dietilaminopentan (CH2)3 N(C2H5)2

4,7-diclorochinolina

H3C CH NH

(CH2)3

N(C2H5)2

+ 2 H3PO4 Cl N

clorochina

PF: NIVAQUINE cp. a 200 mg sulfat de clorochina; sirop; ARALEN cp. a 500 mg fosfat de clorochina.

35

 HIDROXICLOROCHINA HIDROXYCHLOROQUINUM (DCI)

CH2 H3C CH NH (CH2)3 N CH2

CH3 CH2 OH

Cl

7-cloro-4-(4-(N-etil-N--hidroxi-etilamino)1-metil-butilaminochinolina PF: PLAQUENIL comprimate filmate 200 mg sulfat de hidroxiclorochina. AMODIACHINA AMODIAQUINUM (DCI)
CH2 Cl N N CH2 CH3

NH

OH CH2 CH3

4-(7-clor-4-chinolinamino)-o-dietilamino-o-crezol Sinonim: Camochina.

36

H3C CO NH HO NHCOCH3 + CH2O + HN(C2H5)2

OH CH2 CH2 N CH2 CH3 CH3

3-dietilamino-metil-p-acetilaminofenol
Cl

HO

H2N

OH CH2 CH2 N CH2 CH3 CH3

Cl

4,7-diclorochinolina

amodiachina

PF: FLAVOQUINE cp a 200 mg clorhidrat de amodiachina.

CH2 CH3 CH3 CH3 CH3

CICLOCHINA CICLOQUINUM (DCI)

NH

CH2 OH

N CH2 CH2

CH2 Cl N

N CH2

4-(7-clor-4-chinolinamino-, -dietil-aminoxilenol)
37

 PROPACHINA PROPAQUINUM (DCI)

Cl NH OH CH2 N N

4-(7-clor-4-chinolinamino)--pirolidin-o-crezol

ALI DERIVAI DE CHINOLIN

MEFLOCHINA MEFLOQUINUM (DCI)
N H CH OH

2,8-bis((trifluorometil)chinolin-4-il)(2-piperidil)-metanol
N CF3

CF3

PF: LARIAM cp. a 250 mg clorhidrat de meflochina

38