I: Sinequan Pfizer; wfm Mannh./AWD Mannh.; as hydrochloride USA: Sinequan Pfizer; as Sinquan Pfizer GB: Sinequan Pfizer; as hydrochloride Doxifluridine 5'-dFUR ATC: LOlBB Use: antineop
Trang 1Doxazosin D 71 1
1 sodium amide
chlorapyrrolidine
diphenyl-
acetonitrile
PBr3
I
phosphorus(l1l)
bromide
US 3 192 230 (A H Robins; 29.6.1965; prior 9.2.1961)
Lunsford, C.D et al.: J Med Chem (JMCMAR) 7, 302 (1964)
Formulation(s): amp 20 mglml
Trade Narne(s):
D: Dopram (Brenner); wfm I: Doxapril (Carlo Erba); wfm J: Dopram (Kissei)
F: Dopram (Martinet); wfm Doxapril (Farmalabor); USA: Dopram (Robins; as
Use: a,-receptor antagonist, antihypertensive RN: 74191-85-8 MF: C2,H2,N,05 MW: 451.48
LD,,: > 1000 mglkg (M, R, p.0.)
hydrochloride
RN: 70918-01-3 MF: C23H2sNsOs HCl MW: 487.94
mesylate
RN: 77883-43-3 MF: C2,HZ5N5O5 CH,03S MW: 547.59
LD,,: 2935 mglkg (M, p.0.);
>5 glkg (R, p.0.);
>1 g k g (dog, p.0.)
piperazine 1,4-benzodioxan-2- N-(1,4-benzodioxon-2-
Trang 2712 D Doxefazepam
4-amino-2-chloro-6,7-
dimethoxyquinozoline
(cf prozosine synthesis)
Doxozosin
DE 2 847 623 (Pfizer; appl 2.1 1.1978; GB-prior 5.1 1.1977)
US 4 188 390 (Piizer; 12.2.1980; GB-prior 5.1 1.1977)
E P 848 001 (Alfa Chem.; appl 17.10.1997; I-prior 13.12.1996)
WO 9 935 143 (Knoll; appl 18.12.1998; D-prior 6.1.1998)
medical use for treatment of atherosclerosis:
US 4 758 569 (Pfizer; 19.7.1988; appl 26.8.1987)
osmotic device:
US 4 837 11 1 (Alza; 6.6.1989; appl 21.3.1988)
~ r a d e Name(s):
D: Cardular (Pfizer; 1989 as I: Cardura (Roerig; 1989 as
Diblocin (Astra; 1989 as Dedralen (Lifepharma;
Normothen (Fisons Italchimici; 1989 as mesylate)
Cardenalin (Pfizer)
Use: hypnotic RN: 40762- 15-0 MF: C1,H,,C1FN20, MW: 348.76
LD,,: 274 mglkg (M, i.p.); 1500 mglkg (M, p.0.);
586 mglkg (R, i.p.1; 1500 m g k g (M, p.0.)
+ H 3 C 0 ~O N H ~ ' pyridine
H C I -b clg 31 H peracetic C ~ O ~ ~ H
2-amino-5-chloro- glycine ethyl ester
2'-fluorobenzo- hydrochloride
phenone
(cl flunitrozepom
synthesis)
Trang 3+ H O r v B '
Z-bromo- ethanol
I Doxefazepam I
M-1.4-benzod~azep~n-
2-one )-oxide (I)
Referencefs):
Wagnone, G.F et al.: Arzneim.-Forsch (ARZNAD) 25,720 (1975)
B'DOS 2 338 058 (Schiapparelli; appl 26.7.1973; E-prior 28.7.1972)
1 synthesis of 7-chloro- 1.3-dihydro-5-(2-fluoopheny1)-2 1 4 b e n z o d i a z e p i n - o n e 4-oxide:
? SA 6 802 239 (Hoffmann-La Roche; US A-prior 21.4.1967, 23.10.1967)
3
T d Namefs):
I: Doxans (Schiapparelli
Searle); wfm
Use: antidepressant, tranquilizer RN: 1668-19-5 MF: C,,H,,NO MW: 279.38
LD5,: 26 mgkg (M, i.v.); 135 m a g (M, p.0.);
16 m&g (R, i.v.); 147 mglkg (R, p.0.)
CN: 3-dibenz[b,e]oxepin- 1 1 (6H)-ylidene-N,N-dimethyl- 1 -propanamine
hydrochloride
13 mgkg (R, i.v.); 147 m a g (R, p.0.);
ethyl 2-bromo- phenol
methylbenzoate
(F,C-CO),O
b trifluoroacetic 2-phenoxymethyl- anhydride
benzoic acid (I)
ethyl Z-phenoxy- methylbenzoate
-N/CH3
C W I
3-dimethylaminopropyl- magnesium chloride
11 - o m - 6 , l l - dihydrodibenz-
Trang 4714 D Doxifluridine
HCI
Reference(s):
US 3 420 851 (Pfizer; 7.1.1969; appl 19.12.1962; prior 13.3.1962)
DE 1 232 161 (Boehringer Mannh.; appl 7.10.1961)
c tabl 25 mg, 50 mg, 75 mg, 100 mg
Trade Name(s):
D: Aponal (Boehringer F: Quitaxon (Boehringer I: Sinequan (Pfizer); wfm
Mannh./AWD) Mannh.; as hydrochloride) USA: Sinequan (Pfizer; as
Sinquan (Pfizer) GB: Sinequan (Pfizer; as
hydrochloride)
Doxifluridine
(5'-dFUR)
ATC: LOlBB Use: antineoplastic, antimetabolite RN: 3094-09-5 MF: C9HIIPNZOS MW 246.19 EINECS: 221-440-1
LD,,,: >2000 mg/kg (M, i.p.); >1 glkg (M, i.v.); ~ 5 0 0 0 m g k g (M, p.0.);
>2000 mglkg (R, i.p.); > I glkg (R, i.v.); 3390 m g k g (R, p.o.), 3471 mg/kg (Rm, p a ) ; 3390 mg/kg (Rf,
p.0.)
CN: 5'-deoxy-5-fluorouridine
0 0
x
H3C CH,
Trang 5Doxofylline D 715
(c,H,-O),P+CH, I- nZ ~ d - c
methyltriphenoxy-
phosphonium iodide
HO OH
Referencefs):
a,b DOS 2 756 653 (Hoffmann-La Roche; appl 19.1 2.1977; USA-prior 20.12.1976)
US 4 071 680 (Hoffmann-La Roche; appl 20.12.1976)
Cook, A.F et al.: J Med Chem (JMCMAR) 22, 1330 (1979)
additional synthesis:
EP 21 231 (Hoffmann-La Roche; appl 10.6.1980; CH-prior 15.6.1979)
Hrebabecky, H.; Beranek, J.: Collect Czech Chem Commun (CCCCAK) 43, 3268 (1978)
Kiss, J, et al.: Helv Chim Acta (HCACAV) 65, 1522 (1982)
Scott, J.W et al.: J Carbohydr., Nucleosides, Nucleotides (JCNNAF) 8, 171 (1981)
Ajmera, S.; Danenberg, V.: J Med Chem (JMCMAR) 25,999 (1982)
Rosowsky, A et al.: J Med Chem (JMCMAR) 25, 1034 (1982)
combination with purine nucleosides or nucleotides:
EP 189 755 (Hoffmann-La Roche; appl 9.10.1985)
1987)
Doxofylline
(ABC-I 213)
ATC: R03DA11 Use: antiasthmatic, bronchodilator
RN: 69975-86-6 MF: CllHI4N1O4 MW: 266.26 EINECS: 274-239-6
LD,,: 216 mglkg (M, i.v.); 841 m g k g (M, p.0.);
445 mglkg (R, i.p.); 315 rnglkg (R, i.v.); 966 mglkg (R, p.0.)
Trang 67 1 6 D Doxorubicin
theophylline 3-chloro-1.2- 7-(2,3-dihydroxy-
dihydroxypropane pr0pyl)theophylline
HO
C H 3
7-acetaldehyde (I) glycol
Reference(s):
DE 2 827 497 (ABC; appl 22.6.1978; I-prior 4.6.1978)
US 4 187 308 (ABC; 5.2.1980; I-prior 4.6.1978)
Avico, U eta].: Farmaco, Ed Sci (FRPSAX) 17,73 (1962)
synthesis of theophylline-7-acetaldehyde:
Maney, P.V.: I Am Pharm Assoc (JPHAA3) 35,266 (1946)
Toffoli, F et al.: Farmaco, Ed Sci (FRPSAX) 11, 516 (1956)
Trade Namc(s):
Doxorubicin
(Adriamycin)
ATC: LOlDBOl Use: antineoplastic, antibacterial RN: 23214-92-8 MF: C27H2,N0,1 MW: 543.53 EINECS: 245-495-6
LD,,,: 10 mglkg (M, i.v.); 570 mglkg (M, p.0.);
10.510 mglkg (R, i.v.);
2.4 mglkg (dog, i.v.)
hydrochloride
RN: 25316-40-9 MF: C2,H2,NO,, HC1 MW: 579.99 EINECS: 246-818-3
LD,,,: 1245 @,/kg (M, i.v.); 698 mgkg (M, p.0.);
12510 pglkg (R, i.v.)
Trang 7I
Doxycycline D 7 1 7
Doxorubicin
L
From culture of mutant F 1 106 of Streptomyces peucetius va,: caesius
Reference(s):
DE 1 770 204 (Soc Farmaceutici Italia; prior 13.4.1968)
US 3 590 028 (Soc Farmaceutici Italia; 29.6.1971; appl 18.4.1968; I-prior 18.4.1967)
GB 1 161 278 (Soc Farmaceutici Italia; appl 16.4.1968; I-prior 18.4.1967)
alternative syntheses:
partial synthesis from daunorubicin:
DOS 1 917 874 (Soc Farrnaceutici Italia; appl 8.4.1969; I-prior 12.4.1968)
partial synthesis from adriarnycinon:
US 4 058 519 (Soc Farmaceutici Italia; 15.1 1.1977; GB-prior 22.3.1974)
US 4 098 798 (Soc Farmaceutici Italia; 4.7.1978; GB-prior 22.3.1974)
daunorubicin (from cultures of Streptomyces peucetius F I 1762):
GB 1 003 383 (Soc Farmaceutici Italia; appl 11.11.1963; I-prior 16.11.1962)
doxombicin- 14-octanoate:
DOS 2 260 438 (Soc Farrnaceutici Italia; appl 11.12.1972)
US 3 803 124 (Soc Farmaceutici Italia; 9.4.1974: I-prior 12.4.1968,4.5.1971)
stable liposome composition:
WO 9 202 208 (Liposome Technology Inc.; appl 2.8.1991; USA-prior 8.8.1990)
Trade Name(s):
D: Adriblastin (Pharmacia & GB: Caelyx (Schering-Plough; USA: Adriamycin (Pharmacia &
Adrimedac (rnedac) I: Adriblastina (Farrnitalia; Doxil (Sequus)
Ribodoxo (ribosepharrn) J: Adriacin (Kyowa Hakko; Squibb)
F: Adriblastine (Pharmacia & 1975)
Upjohn; 1974)
Use: antibiotic
RN: 564-25-0 MF: Cz2H2,Nz0, MW: 444.44 EINECS: 209-27 1- 1
LD,: 241 m g k g (M, i.v.); 1870 rnglkg (M, p.0.);
228 m g k g (R, i.v.); >2 glkg (R, p.0.);
>lo0 mglkg (dog, i.v.); >SO0 mglkg (dog, p.0.)
CN: [4S-(4a,4aa,5a,Saa,6a,l2aa) J-4-(dimethylamino)- l,4,4a,S,Sa,6,ll, 12a-octahydro-3.5,10,12,12a-
pentahy droxy-6-methyl- I, 1 l -dioxo-2-naphthacenecarboxarnide
Trang 8718 D Doxycycline
monohydrochloride
RN: 10592- 13-9 MF: C2,H2,N20, HCI MW: 480.90 EINECS: 234-198-7 LD,,,: 290 mglkg (M, i.v.); 1890 mg/kg (M, p.0.);
137 mglkg (R, i.v.); 1700 mglkg (R, p.0.);
>500 mglkg (dog, p.0.)
monohydrate
RN: 17086-28- 1 MF: C22H24N20x H,O MW: 462.46
hyclate
RN: 24390-14-5 MF: CZ2Hz4N2O8 1/2C2H60 HCI 1/2H20 MW: 1025.89
-thiophenol
rnethacycline
H2, Roney-Ni
OH
Reference(s):
a US 3 019 260 (American Cyanamid; 30.1.1962; prior 13.5.1959)
DE 1 082 905 (American Cyanamid; appl 3.11.1958; USA-prior 5.1 1.1957)
b US 3 200 149 (Pfizer; 10.8.1965; prior 23.5.1960)
DAS 1 793 556 (Pfizcr; appl 19.5.1961; USA-prior 23.5.1960)
DE 1 298 522 (Pfizer; appl 23.5.1961 ; USA-prior 23.5.1960)
Blackwood, R.K et al.: J Am Chem Soc (JACSAT) 85,3943 (1963)
Trang 9bmreospecific hydrogenation of rnetacycl~ne with d~aceto(tr~phenylphosph~ne)rhod~um(II) complex to
{ doxycycline:
;DAS 2 554 524 (Pfizer; appl 4.1 2.1975, USA-prior 28.1.1975)
k
i
1 k d e Name($):
i-
g D: Azudoxat (Azuchemie)
t Clinofug (Wolff)
Mespafin 100 (Merckle)
a' Mucotectan (Boehringer
Iw.1
Neodox (Rosen Pharma)
i
1 Sigadoxin (Kytta-Siegfried)
Supracyclin 1001200
i (Griinenthal)
V~bramycin N (Pfizer)
t
r" Vibravenos (Pfizer)
i F: Doxycline Plantier (ASTA
ii Medica)
I
Doxygram (Pharma 2000)
I Doxylets (Galephar)
c G~anudoxy (Pierre Fabre)
: Monocline (Doms-Adrian)
Spanor (Blothempie)
Tolexine (Biorga) J:
Vibramy cine (Pfizer) Vibraveineuse (Pfizer) GB: Doxatet (Cox); wfm Doxy lar (Lagap); wfm USA:
Nordox (Norton); wfm Vibramycin Acne Pack (Trinity)-comb
I: Bassado (Ppli) Doxina (Ipfi) Farmodoxi (Lifepharma) Gram-Val (Polifarma) Miraclin (Farmacologico Milanese)
Monodoxin (Crosara) Ribociclina (Puropharma)- comb
Unacil (Firma)
I lydramycin (Sankyo) Liomycin (Daiichi) Roximycin (Kyorin) Vibramycin (Taito Pfizer) Doryx (Warner Chilcott Professional Products; as hydrate)
Monodox (Oclassen; as monohydrate)
Vibramycin (Pfizer; as calcium salt)
Vibramycin (Pfizer; as hydrate)
Vibramycin (Pfizer; as monohydrate)
Use: antihistaminic
LD,: 62 mgkg (M, i.v.); 470 mglkg (M, p.0.)
succinate (1:l)
RN: 562-10-7 MF: C17H2,N20 C4H604 MW: 388.46 EINECS: 209-228-7
LD,,: 62 mgkg (M, i.v.); 470 m g k g (M, p 0.)
I NaNHZ
2 FH3
-b
OH 1 sodium omide
H3C 2 2-(dimethylomino)- 2-acetyl- phenylmagnesiurn 1 -phenyl- 1 - ethyl chloride
pyridine bromide (2-pyridyl)-
ethanol
Reference(s):
Sperber, N et al.: J Am Chem Soc (JACSAT) 71,887 (1949)
Trade Name(s):
D: Gittalun (Boehringer Ing.) Mereprine (Cassella-med) Sedaplus (Rosen Pharma) Hewedomir forte (Hevert) Praedisup (Chephasaar)- Wick Formel 44 S (Wick
Trang 10720 D Drofenine
F: Donormyl (0berlin)-comb Nethaprin expect (Merrell Vicks Medinait (Procter &
GB: Nethaprin Dospan (Merrell comb.; wfm Aid (Pfizer; as succinate)
Dow)-comb.; wfm 1: Doxised (Corvi)
Drofenine
(Hexahydroadiphenine)
ATC: A03DA49 Use: antispasmodic
RN: 1679-76-1 MF: C2,H3,N02 MW: 317.47
LD,,,: 37 mglkg (R, i.v.)
CN: a-cyclohexylbenzeneacetic acid 2-(diethy1amino)ethyl ester
hydrochloride
RN: 548-66-3 MF: C2,H3,N02 HCI MW: 353.93 EINECS: 208-954-1
LD,,: 47 m g k g (M, i.v.); 3700 mg/kg (M, p a )
Referencefs):
CH 219 301 (Ciba; appl 1938)
odiphenine (q v.)
Drofenine
Trade Name(s):
D: Spasmo-Cibalgidcomp F: Spasrno-Cibalgine (Ciba)- I:
Dronabinol
(6-9-THC)
ATC: A04A Use: anti-emetic, active ingredient of marijuana
RN: 1972-08-3 MF: C2,H,,02 MW: 314.47
LD,,: 168 m g k g (M, i.p.); 42 m g k g (M, i.v.); 482 mg/kg (M, p.0.);
373 m g k g (R, i.p.); 29 mg/kg (R, i.v.); 666 m g k g (R, p.0.)
H3C ,;OH
/ boron trifluoride etherote
O H
H3cccH3
H3C CH,
p-menth-2-