3-2-thieny1- ocrylonitrile acrylamide I N-methvltri- methylenediomine propane sultone References: BE 658 987 Pfizer; appl.. 125 mg, 250 mg as pamoate Trade Names: D: Helmex Pfizer H
Trang 1Pvrantel P 1751
Tmde Name(s):
F: Norbiline (Bellon)-comb I: Norbiline (RhSne-Poulenc
Rorer)
Use: anthelmintic (nematodes) RN: 15686-83-6 MF: C,,H,,N,S MW: 206.31 EINECS: 239-774-1
LD,,: 175 mg/kg (M, p.0.);
170 mglkg (R, pa.);
2 d k g (dog, p.0.)
CN: (E)-1,4,5,6-tetrahydro-l-methyl-2-[2-(2-thienyl)ethenyI]pyrimidine
tartrate (1:l)
RN: 33401-94-4 MF: ClIHl4N,S C,H,O, MW: 356.40 EINECS: 251-501-8
LD,,: 2220 pg/kg (M, i.v.); 123 mglkg (M, p.0.);
170 mgkg (R, p.0.)
pamoate (1: 1)
RN: 22204-24-6 MF: CIIHl4N,S C,,H,,O, M W 594.69 EINECS: 244-837-1
LD,: 62Q mglkg (M, i.p.1;
535 mglkg (R, i.p.)
+ ,c-coo, CH3COONH,, pyridine
N H 2
thiophene-2- cyanoocetic
carboxaldehyde acid
3-(2-thienyl) 3-(2-thieny1)- ocrylonitrile acrylamide (I)
N-methvltri- methylenediomine propane
sultone
Reference(s):
BE 658 987 (Pfizer; appl 28.1.1965; GB-prior 28.1 l964, 13.8.1964, 26.9.1964)
US 3 502 661 (Pfizer; 24.3.1970; prior 14.2.1967, 5.6.1967, 9.11.1967)
CH 404 677 (Dr A Wander; appl 2.12.1960)
CH 398 620 (Dr A Wander; appl 16.8.1960)
GB 980 853 (Dr A Wander; appl 16.8.1961 ; CH-prior l6.8.l960,2.I2.l960)
NL 147 426 (Dr A Wander; appl 24.5.1963; CH-prior 25.5.1962, 8.6.1962, 5.12.1962, 15.2.1963)
DE 1 280 879 (Wander; appl 7.8.196 1; CII-prior 16.8.1960, 2.12.1960)
US3539573(Wander; 10.11.1970;CH-prior 16.8.1960,2.12.1960,20.7.1961,25.5.1962,5.12.1962,15.2.1963, 22.3.1967, 11.7.1967, 3.11.1967)
Hunziker, F et al.: Helv Chim Acta (HCACAV) 50, 1588 (1967)
Fomulation(s): chewing tabl 250 mg; sol 5 %; susp 250 mg/5 ml, 720 mg; tabl 125 mg, 250 mg (as
pamoate)
Trade Name(s):
D: Helmex (Pfizer) Helmintox (Innotech I: Combantrin (Pfizer)
F: Combantrin (Pfizer) International) J: Combantrin (Pfizer)
GB: Combantrin (Pfizer); wfm
Trang 21752 P Pvrazinamide
USA: Antiminth (Pfizer); wfm Antiminth (Roerig); wfm Combantrin (Pfizer); wlm
Use: tuberculostatic, antibacterial RN: 98-96-4 MF: C,H,N,O MW: 123.12 EINECS: 202-717-6
LD,,: 1680 m g k g (M, i.p.); 2793 mglkg (M, s.c.)
CN: pyrazinecarboxamide
CHO
I
CHO
glyoxol o-phenylene- quinoxoline pyrorine-2.3- pyrozine-2-
corboxylic
methyl pyrazine- Pyrozinomide 2-corboxylote
Reference(s):
DRP 632 257 (Merck; 1934)
Hall, S.A et al.: J Am Chem Soc (JACSAT) 62, 664 (1940)
alternative synthesis via 2-cyanopyrazine (from 2-chloropyrazine):
EP 122 355 (Servipharm; appl 25.7.1983; CH-prior 21.3.1983)
Formulation(s): cps 500 mg; drg 300 mg in comb with rifapiam, isoniazide; f c tabl 500 mg; tabl 100 mg,
500 mg
Trade Name(s):
D: Pyrafat (Fatol) F: ' Pirilbne (Marion Merrell) I: Piraldma (Bracco) Pyrazinamid (Hefa Rifater (Marion Merrel1)- J: Pyramide (Sankyo)
Pyrazinamid "Lederle" GB: Rifater (Hoechst)-comb Merrel1)-comb
Rifater (Griinentha1)-comb Dohme)
Pyridinol carbarnate
(Pyricarbate)
ATC: C04AX49 Use: antiarteriosclerotic RN: 1882-26-4 MF: C,,HISN30, MW: 253.26 EINECS: 217-538-9
LD,,,: 3100 m g k g (M, p.0.);
1230 m g k g (R, p.0.);
1 gfkg (dog, p.o.1
CN: 2,6-pyridinedimethanol bis(methy1carbamate)
Trang 3- Pyridinol carbarnate P 1753
starting product:
dioicolinic acid 2.6-bis(hydroxymethyI)-
pyridine (I)
2.6-bis(acetoxyrnethyI)- pyridine
C12, H2S0,
azobisisobutyronitrile H ~ O / H +
2.6-bis(chloromethyl)- pyridine
final product:
Reference(s):
FR 1 396 624 (M Inoue; appl 13.4.1964; J-prior 13.4.1963)
AT 258 953 (M Inoue; appl 13.4.1964; J-prior 13.4.1963)
AT 258 954 (M Inoue; appl 13.4.1964; J-prior 13.4.1963)
AT 258 955 (M Inoue; appl 8.1 1.1965)
methyl
isocyanate
alternative syntheses Lfrom 2,6-bis(hydroxymethy1)pyridine and N,W-dimethylurea]:
DOS 2 263 812 (Rocador S A.; appl 28.12.1972; E-prior 28.12.1971)
Pyridinol carbamale
yl- and y,-modifications:
DOS 2 702 772 (Richter Gedeon; appl 24.1.1977; H-prior 24.1.1976)
GB 1 548 334 (Richter Gedeon; appl 2 1.1.1977; H-prior 24.1.1976)
2.6-bis(hydroxymethy1)pyridine:
a FR 1 396 624 (M Inoue; appl 13.4.1964; J-prior 13.4.1963)
b Bockelheide, V.; Linn, W.J.: J Am Chem Soc (JACSAT) 76, 1286 (1954)
c FR 1 394 362 (Merck & Co.; appl 3 I 3.1964; USA-prior 2.4.1963)
Trang 41754 P Pyridofylline
alternative syntheses:
DAS 2 460 039 (Richter Gedeon; appl 19.12.1974; H-prior 29.12.1973)
DAS 2 614 400 (Richter Gedeon; appl 2.4.1976; H-prior 2.4.1975)
Fortnulation(s): tabl 250 mg
Trade Name(s):
F: Angioxine (Roussel); wfm I: Cicloven (AGIPS) J: Anginin (Banyu)
Use: coronary vasodilator RN: 53403-97-7 MF: C9H,2N406S C8HIIN03 MW: 473.46 EINECS: 258-521 -6
LD,,: 1 glkg(M,i.v.); 1600mg/kg(M,p.o.)
CN: 3,7-dihydro- l,3-dimethyl-7-[2-(sulfooxy)ethyl]-1H-purine-2,6-dione compd with 5-hydroxy-6-methyl-
3,4-pyridinedimcthanol (1 : 1)
pyridoxine
CHC13 CIS03H
chlorosulfonic acid
CZHJOH
Reference(s):
FR-M 828 ( J Debarge; appl 23.12.1960)
Trade Name(s):
F: Atherophyllinc (Merrell);
wfm
0-[2-(7-theophyllinyl)ethyl]
hydrogen sulfote (I)
Pyridofyllinc
Use: parasympathomimctic (cholinesterase blocker), antiniyasthenic, vagotonic RN: 101-26-8 MF: CYH11BrN20Z MW: 261.12 EINECS: 202-929-9
LDs,,: 1500 pglkg (M, i.v.); 16 mglkg (M, p.0.)
CN: 3-[[(dimethylamino)carbonyl]oxy]-I-methylpyridinium bromide
Trang 5Pyridoxine P 1755
3-hydroxy- dimethyl- 3-(dimethylamino-
pyridine carbomoyl corbony1oxy)-
chloride pyridine
Reference(s1:
CH 246 834 (Roche; appl 1945)
US 2 572 579 (Roche; 1951; CH-prior 1945)
' 3 4 3 Pyridostigmine bromide
Fomulation(s): amp 1 mglml, 5 mglml; drg 60 mg; s r tabl 180 mg; syrup 6 0 mg15 ml; tabl 60 mg
Trade Name(s):
D: Kalymin (ASTA Medica F: Mestinon (Roche) J: Mestinon (Nippon Roche)
Pyridoxine
(Vitamin B,)
ATC:' A I I HA02 Use: vitamin (enzym co-factor)
RN: 65-23-6 MF: CsH,lN03 MW: 169.18 EINECS: 200-603-0
LD,: 545 mglkg (M, i.v.);
657 mglkg (R, i.v.); 4 glkg (R, p.0.)
CN: 5-hydroxy-6-methyl-3,4-pyridinedimcthanol
hydrochloride
RN: 58-56-0 MF: CsH1,NO, HCI MW: 205.64 EINECS: 200-386-2
LD,,: 660 mglkg (M, i.v.); 5500 mglkg (M, p.0.);
530 mglkg (R, i.v.); 4 glkg (R, p.0.);
>SO0 mgkg (dog, p.0.)
@ Marck + Co.:
u
H N 'f C H ~ + H O ~ C H ~ % H 2 ~ x ~ ~ c i 3 ~ c ~ oHc-NH2
DL-olanine (1) (11) DL-olonine ethyl
esler hydrochloride
N-formyl-DL-olanine ethyl ester (N)
5-ethoxy-4- (ocetol f r o m isobutyroldehyde Pyridoxine
+ 2-butene-1.4-diol) rnethyloxozole
Trang 61756 P Pyridoxine
cthyl 2-chloro-
acetoacetote
ethyl 4-methyl- 4-methyloxozole- 5-cyono-4- oxozole-5- 5-corboxomide methyloxozole (VII) corboxylote (VI)
dihydro- 1 -3-dioxepin
(ketol from ocetone +
2-butene-l,4-diol)
@ BASF:
0
1 NoOH
2 A @:S"'
3-methylsulfonyl-2,s-dihydro-
4-methyl-
oxoZolc (by addition of methonesulfonyl
bromide to 2,s-dihydrofuron and subsequent HBr elimination with NoOH)
0 COOH
COC12 (C&).+
I + 1 1 + I
'0 O ~ C H ~ omine
I NoOH
0 2 3.v HCI
ethyl 5-ethoxy-4-methyl-
oxozole-2-corboxylote (VIE)
Trang 7Pyridoxine P 1757
Reference(s):
review of pyridoxine syntheses:
Konig, H.; Boll, W.: Chem.-Ztg (CMKZAT) 100, 105 (1976)
a Harris, E.E et al.: J Org Chem (JOCEAH) 27, 2705 (1962)
DAS 1 470 022 (Merck & Co.; appl 10.5.1962; USA-prior 15.5.1961, 16.1.1962)
US 3 227 721 (Merck & Co.; 4.1.1966; prior 15.5.1961, 16.1.1962, 24.5.1965)
US 3 227 724 (Merck & Co.; 4.1.1966; prior 15.5.1961, 16.1.1962, 16.6.1964)
b US 3 222 374 (Roche; 7.12.1965; prior 22.5.1963, 20.1 1.1964)
US 3 250 778 (Roche; 10.5.1966; appl 29.11.1962)
US 4 026 901 (Roche; 31.5.1977; appl 30.4.1975)
DOS 2 616 349 (Roche; appl 14.4.1976; USA-prior 30.4.1975)
5-cyano-4-methyloxazole:
US 4 093 654 (Roche; 6.6.1978; appl 31.3.1977)
c DAS 2 143 989 (BASF; appl 2.9.197 1)
3-methylsulfonyl-2,5-dihydrofuran:
DOS 2 435 098 (BASF; 22.7.1974)
d Maeda, J et al.: Bull Chem Soc Jpn (BCSJA8) 42, 1435 (1969)
alternative syntheses:
from 5-ethoxy-4-oxazolylacetic acid:
DAS 2 008 854 (Roche; appl 25.2.1970; CH-prior 25.3.1969)
4-methyloxazol from formimino ester hydrochloride and hydroxyacetone:
GB 1 515 737 (BASF; appl 22.1 0.1975; D-prior 31.10.1974)
Formulation(s): amp 25 mg/2 ml, 50 mgl2 ml, 100 mgl2 ml, 300 mg; drg 100 mg, 300 mg; f c tabl 40 mg;
tabl 1 mg, 25 mg, 40 mg, 50 mg, 100 mg, 300 mg (as hydrochloride)
Trade Name(s):
D:
F:
GB:
I:
B,-ASmedic (Dyckerhofo
B,-Vicotrat (Heyl)
BYK (Roche Nicholas)-
comb
Bonasanit (Weimer]
Hexobion (Merck)
Vitamin B, ratiopharm
(ratiopharm)
generics and circa 500
combination preparations
Becilan (Specia)
Dermo-6
(PharmadCveloppement)
Pyridoxine Aguettant
(Aguettant)
Vitamine B, Richard
(Richard)
numerous combination
preparations
Complement Continus
(Napp); wfm
numerous combination
preparations
Acutil Fosforo (SmithKline
Beecham)
Adenoplex (Lepetit)-comb
Alcalosio (SIT)-comb
Antemesyl (Mo1teni)- comb
Antimicotico pom derm
(IF1)-comb
Benadon (Roche) Benexol (Roche)-comb
Coxanturenasi (Teofarma)- comb
Detoxergon (Ba1dacci)- comb
Dobetin (Ange1ini)-comb
Emoferrina B,, os (Piam)- comb
Etanicozid (Piam)-comb
Furanvit (SIF1)-comb
Memosprint (Po1i)-comb
Menalgon (Menarini)- comb
Miazide B, (Wyeth- Leder1e)-comb
Midium (Glaxo)-comb
Mionevrasi forte (Boehringer Mannh.)- comb
Neogeynevral (Geymonat)- comb
Neuraben (Bioindustria)- comb
Neurobionta (Bracco)- comb
Sustenium (Menarini)- comb
Triferon (Sa1us)-comb Trinevrina B, (Chidotti)- comb
Xanturenasi (Teofarma) J: Aderoxin (Sonybod-Torii) Pyridomin (Showa) Sandoxin (Sanko) numerous combination preparations
USA: Aminoxin (Tyson) Beelith (Beach)-comb Lurline (Fielding)-comb Marlyn Formula 50 (Marl yn)-comb
Mega-B (Arco)-comb
Trang 81758 P Pyrimethamine
Use: chemotherapeutic (toxoplasmosis and malaria), antimalarial
RN: 58-14-0 MF: CL2HI3C1N4 MW: 248.72 EINECS: 200-364-2
LDs,,: 92 mglkg (M, p.0.);
440 mglkg (R, p.0.)
CN: 5-(4-chloropheny1)-6-ethyl-2,4-pyrimidinediamine
orthoformote 4-chlorobenzyl
cyonide
methyl propionote
US 2 576 939 (Burroughs Wellcome; 1951; prior 1950)
US 2 602 794 (Burroughs Wcllcome; 1952; appl 1950)
US 2 680 740 (Rldne-Poulenc; 1954; F-prior 1951)
Formulation(s): tabl 25 mg
Trade Name(s):
D: Daraprim (Glaxo Fansidar (Roche)-comb USA: Daraprim (Glaxo
F: Fansidar (Roche)-comb I: - Metakelfin (Pharmacia & with sulfadioxine
GB: Daraprim (Burroughs J: Fansidar (Roche)-comb
Wellcomc)
Pyrithione zinc
(Zinc pyrithione)
ATC: D l l A X Use: antiseborrhoic, fungicide, bactericide RN: 13463-41-7 MF: C,,H,N,O,S,Zn MW: 317.71 EINECS: 236-671-3
LD,,,: 160 mg/kg (M, p.0.);
177 mglkg (R, p.0.);
600 mglkg (dog, p.0.)
CN: (T-4)-bis(l-hydroxy-2(1H)-pyridinethionato-O,S)zinc I
Trang 9Pyrithyldionc P 1759
2-chloro- ocetic acid
2-chloro- 2-mercopto- 1 -hydroxy-2- pyridine pyridine pyridine pyridinethione (I)
/ Pyrithione zinc 1
Reference(s):
GB 761 171 (Olin Mathieson; appl 19.5.1954; USA-prior 29.5.1953)
pyrithione:
US 2 745 826 ( O h Mathieson; 15.5.1956; appl 16.12.1953)
Shaw, E et al.: J Am Chem Soc (JACSAT) 72,4362 (1950)
use:
US 3 236 733 (Procter & Gamble; 22.2.1966; prior 5.9.1963, 1.4.1965)
US 3 281 366 (Procter & Gamble; 25.10.1966; prior 25.8.1964.4.1 1.1965)
Formulation(s): cream 1 gI100 g; shampoo 1 %, 2 %
Trade Name(s):
D: de-squaman hermal Ultrex antipelliculaire (Lab USA: DHS Zinc (Person RL
F: Fonderma (Doms); wfm GB: Polystar AF (Stiefe1)-comb Head & Shoulders (Procter
Use: hypnotic, sedative
RN: 77-04-3 MF: C,H,,NO, MW: 167.21 EINECS: 201-000-5
LD,,: 780 mgkg (R, p.0.)
CN: 3,3-diethyl-2,4(1 H,3H)-pyridinedione
methyl ethyl 2.2-diethyl- ethyl 2.2-diethyl-
formote ocetoocetate y-(hydroxymethy1ene)-
ocetoacetote
Trang 101
1760 P Pyritinol
Keference(s):
US 2 090 068 (Hoffmann-La Roche; 1937; D-prior 1935)
Trade Name(s):
D: Perscdon Roche (Roche): I: Hibersulfan (Ecobi)-comb.;
Pyritinol
(Pyrithioxine)
ATC: N06BX02 Use: neurotropic, nootropic RN: 1098-97-1 MF: C,,H20N20,S, MW: 368.48 EINECS: 214- 150- 1
CN: 3,3'-[dithiobis(methylene)]bis[5-hydroxy-6-methyl-4-pyridinemethanol]
dihydrochloride monohydrate
RN: 10049-83-9 MF: Cl6HmN2O4S2 2HCl H20 MW 459.42 EINECS: 233-178-5
LD,,,: 221 mg/kg (M, i.v.); 5786 mglkg (M, p.0.);
300 mglkg (R, i.v.); 6 g/kg (R, pa.)
3.4- bis(bromomethy1)-
5-hydroxy-6-methyl-
pyridine hydrobromide
(from pyridoxine)
potassium ethyl- xonthogenote
HO
Pyritinol
US 3 010 966 (E Merck AG; 28.1 1.1961; D-prior 21.3.1958)
DE 1 135 460 (E Merck AG; appl 21.3.1958)
DE 1 197 455 (E Merck AG; appl 27.8.1960)
alternative syntheses:
DAS 1 210 429 (E Merck AG; appl 3.8.1963)
DE 1 222 062 (E Merck AG; appl 8.2.1964)
DE 1 227 908 (E Merck AG; appl 8.2.1964)
DOS 1 695 402 (E Merck AG; appl 25.3.1967)
Fomulation(s): amp 200 mg; drg 100 mg, 200 mg; susp 80.5 mgf5 ml, 100 mg; syrup 100 mg (as
hydrochloride)
Trade Name(s):
D: Ardeyceryl P F: Biontabol (Merck- I: Encefabol (Bracco)
ClCvcnot); wfm Divalvdn (Nippon Kayaku)