2 mg, 6 mg as acetate Trade Names: D: Monocortin Griinenthal; GB: Haldrate Lilly; wfm Paramezone Recordati F: Dilar Cassenne; wfm comb... Paroxetine P 1565 From fermentation solutions o
Trang 1Paramethasone P 1561
1 chrornium(\rl)
oxide
21 -0cetoxy-6p-fluoro-17-hydroxy- 6a-fluoro-17.21 -dihydroxy-
16o-methylpregn-4-ene-3.20-dione 16a-methylpregn-4-ene-
3.20-dione (M)
1 microbiological
hydroxylation
2 111
w1 -+
disodium phosphate:
SeOz
Xs
dioxide
1 Paromethosone acetate
Reference(s):
US 2 671 752 (Syntex; 1954; appl 1951)
Djerassi, C et al.: J Am Chem Soc (JACSAT) 82, 2318 (1960)
- '? r - 7
1 O d - \ - L O ,
o
pyridine
2 acidic ion exchanger,
"'CH3 p
0 ' = phosphinic chloride
F
paramethasone
starling material:
Marker, R.E.; Crooks, H.M.: J Am Chem Soc (JACSAT) 64, 1280 (1942)
NaO
F
Paramethosone 21-disodium phosphate
alternative syntheses:
US 3 557 158 (Upjohn; 19.1.1971; appl 22.1.1962; prior 4.8.1958)
Schneider, P et al.: J Am Chem Soc (JACSAT) 81,3167 (1959)
GB 850 263 (Organon; appl 30.4.1959; NL-prior 12.5.1958)
US 4 041 055 (Upjohn; 9.8.1977; appl 17.1 1.1975)
disodiwn phosphate:
DE 1 134 075 (Merck AG; appl 26.1 1.1959)
Fom~dation(s): amp 20 mglml (as acetate); tabl 2 mg, 6 mg (as acetate)
Trade Name(s):
D: Monocortin (Griinenthal); GB: Haldrate (Lilly); wfm Paramezone (Recordati)
F: Dilar (Cassenne); wfm comb
Trang 21562 P Parethoxycaine
Para~nesone (Syntex- USA: Haldrone (Lilly); wfm Stero-Darvon (Li1ly)-
Use: local anesthetic RN: 94-23-5 MF: C,,H,,NO, MW: 265.35
CN: 4-ethoxybenzoic acid 2-(diethy1amino)ethyl ester
hydrochloride
RN: 136-46-9 MF: C,,H,NO, HCI MW: 301.81 EINECS: 205-246-4
reference!^):
US 2 404 691 (Squibb; 1946; prior 1937, 1944)
Formulation(s): tabl 0.75 mg (as hydrochloridc)
Trade Nan~e(s):
F: Maxicaine (Synthtlabo)
O J H 3
Porethoxycaine
Use: MAO-inhibitor, antihypertensive RN: 555-57-7 MF: CllH,3N MW: 159.23 EINECS: 209-101-6
LD,,: 56 mgkg (M, i.v.); 680 mglkg (M, p.0.);
300 mg/kg (R, p.o.)
CN: N-methyl-N-2-propynylbenzenemethanamine
hydrochloride
RN: 306-07-0 MF: C,,H,,N HC1 MW: 195.69 EINECS: 206-175-1
LD,,: YY m g k g (M, i.v.); 680 mgkg (M, p.0.):
175 mglkg (R, i.v.); 250 mglkg (R, p.0.);
175 mglkg (dog, p.0.)
N-benzylmethyl- p r o ~ a r g y l
Reference(s):
US 3 155 584 (Abbott; 3.11.1964; prior 3.12.1962)
Trang 3Paricalcitol P 1563
Formulation(s): tabl 10 mg, 25 mg (as hydrochloride)
Trade Name(s):
Paricalcitol
(Paracalcin)
Use: vitamin D-analog, treatment for hyperparathyroidism
RN: 131918-61-1 MF: C,,H,O, MW: 416.65
25-hydroxyvitamin D2
(isolation from pig blood)
oso,,
pyridrne
+
osmium
tetroxide
1 Tos-CI
2 H3C-OH
3 H ~ c ~ o ~ ~ H , pyridine
b
la:25-dihydroxy-3,5-cydo-
vitamin D2 1-acetate
&methyl ether (1)
No104
,
sodium metaperiodate
111
+
Trang 41564 P Paromomycin
KOH CH30H _,
EP 387 077 (Wisconsin Alumni Res Found.; 12.9.1990; appl 9.3.1990; USA-prior 16.2.1990)
WO 9 729 740 (Wisconsin Alumni Res Found.; appl 5.9.1996; USA-prior 13.2.1996)
Paaren, H.E et al.: J Org Chem (JOCEAH) 45,3253-3258 (1980)
Paaren, H.E et al.: J Org Chem (JOCEAH) 48, 3819-3820 (1983)
treatment of osteoporosis in comb with growth hormone secretagogue:
WO 9 853 827 (Ramoz Univ.; appl 22.5.1998; IL-prior 30.5.1997)
Formulation(s): amp 5 pg/ml; 1 ml, 2 ml, 5 ml
Trade Name(s):
USA: Zemplar (Abbott; 1998)
Paromomycin
(Aminosidine)
ATC: A07AA06 Use: antibiotic RN: 7542-37-2 MF: C23H4SN50L4 MW: 61 5.63 EINECS: 23 1-423-0
LD,,,: 2.275 glkg (M, p.0.);
21.62 g/kg (R, p.0.)
P-D-ribofuranosyl-(1+5)]-2-deoxy-D-streptamine
sulfate
RN: 1263-89-4 MF: C,,H4,N,0,4~ xH,S04 MW: unspecified EINECS: 215-031-7
LD,,,: 90 m g k g (M, i.v.); 23.5 glkg (M, p.0.);
181 rng/kg (R, i.v.); 21.62 g/kg (R, p.0.)
Trang 5Paroxetine P 1565
From fermentation solutions of Streptomyces rimosus forma paromomycinus or Streptomyces krestomyceticus
N.C.I.B 8995
Reference(s):
U S 2 916 485 (Parke Davis; 8.12.1959; prior 12.1.1959)
GB 880 035 (Soc Farmaceutici Italia; appl 31.3.1959; valid from 18.2.1960)
Formulation(s): cps 250 mg; powder 1 g; syrup 125 mg15 ml
Trude Name(s):
D: Humatin (Parke Davis) GB: Humatin (Parke Davis); Paramicina (Ragiomeri)
Humatin (Parkc Davis); Gabbroral (Carlo Erba) Sankyo)
Humatin (Parke Davis) wtm
Paroxetine
(BRL 29060; FG 705 1)
ATC: N06ABOS; N06AE Use: antidepressant, selective 5-HT-uptake inhibitor
RN: 61869-08-7 MF: C,,H,,FN03 MW: 329.37
LD,,: 374 mglkg (R, p.0.)
hydrochloride
RN: 78246-49-8 MF: C,9H2,FN03 HCI MW: 365.83
LD,,: 42 m g k g (M, i.v.); 3 7 8 m g k g ( M , p.0.);
30 m g k g (R, i.v.); 415 m d k g (R, p.0.)
hydrochloride hydrate (2:l)
RN: 110429-35-1 MF: C,,HzoFNO, HCl 112H20 MW: 749.68
maleate
RN: 64006-44-6 MF: ClyH,,FN03 xC4H,0, MW: unspecified
LD,,: 500 mglkg (M, p.0.); 845 mglkg (M s.c.)
acetate
RN: 72471-80-8 MF: Cl9HzOFNO3, C2H40z MW: 389.42
Trang 61566 P Paroxetine
arecoline
methylnipecotayl
chloride (11)
y"' 1 NaOCH,
2 SOCI,
F
4-fluorophenyl- rnognesium bromide (I)
F
methyl &/trans-4- (4-fluoropheny1)-N- methylnipecotate
OH
H,cd,,,'b distillotion
CH3 7 H 3
2 HBr
3 UAIH4 ,
1 (-)-menthol
3 lithium aluminum hydride
CI
S, decolin A
/ cuprous
methyl 1,4-dihydra-1-ethoxy- 4-(4-fluoropheny1)-
nlcotinate carbanyl-4-(4-fluora- 3-methoxycarbonyl-
phenyl]-3-methoxy- pyridine (N)
carbonylpyridine
7 H 3 I NOOCH,
N 2 LiAlH,
3 racemate resolution with H2 Pt o " " f ~ 0 ~ C H 3 (-)-di-p-toluoyltartaric acid ,
F methyl
bromide
Trang 7Paroxetine P 1567
6;" +
F
4-fluora-
benz-
aldehyde
1 LiAlH,
2 rocernate resolution with (-)-di-p-toluoyl-
H
H3C 0 O
ethyl N-methyl-
malanomate
2 KOH
2 sodium 3.4-
pheny1)-3-((1.3-benzo- dioxol-5-yloxy)methyI]-1- rnethylpiparidine
ethyl p-fluorocinnomote ethyl cyono-
ocetote
Trang 81568 P Paroxetine
J-pyridine-
carbaraldehyde
Reference(s):
US 3 912 743 (Ferrosan, 14.10.1975; GB-prior 30.1.1973)
a,d US 4 007 196 (AIS Ferrosan; 8.2.1977; appl 23.7.1975; prior 21.1.1974; GB-prior 30.1.1973)
DE 2 404 1 13 (AIS Ferrosan; appl 29.1.1974; GB-prior 30.1.1973)
GB 1 422 263 (AIS Ferrosan; appl 30.1.1973)
b EP 219 934 (Beecham; appl 6.8.1986; GB-prior 10.8.1985)
c EP 223 334 (Beecham; appl 6.8.1986; GB-prior 10.8.1985, 23.5.1986)
e WO 9 853 824 (SmithKline Beecham; appl 29.5.1998; GB-prior 29.5.1997)
f WO 9 852 920 (Knoll; appl 1351998; GB-prior 17.5.1997)
g WO 9 724 323 (Chiroscience; appl 30.12.1996; GB-prior 29.12.1995)
alternative synthesis of 111:
EP 300 617 (Beecham; appl 17.6.1988; GB-prior 23.6.1987)
synthesis of arecoline:
The Merck Index, 1 lth Ed., 803 (Rahway 1989)
optically pure precursors:
US 52 582 5 17 (Sepracor; 2.11.1993; appl 6.8.1992)
ctys!alline hydrochloride hemihydrate:
EP 223 403 (Beecham; appl 14.10.1986; GB-prior 25.10.1985)
US 4 721 723 (Beecham; 26.1.1988; appl 23.10.1986; GB-prior 25.10.1985)
medical use for treatment of pain:
EP 269 303 (Beecham; appl 9.1 1.1986; GB-prior 11.1 1.1985)
medical use for treatment of obesity:
EP 188 08 1 (Ferrosan; appl 2.12.1985; GB-prior 4.12.1984)
preparation of easily soluble paroxetine:
WO 9 831 365 (SmithKline Beecham; appl 12.1.1998; GB-prior 15.1 l997)
new polymorph of anhydrous paroxetine:
CA 2 187 128 (Brabtfort Chem.; appl 4.10.1996)
method of producing amorphous paroxetine:
EP 810 224 (Asahi Glass; appl 30.5.1997; J-prior 30.5.1996)
US 5 672 612 (Pentech Pharm; USA-prior 9.9.1996)
controlled-release pharmaceutical compositions:
WO 9 703 670 (SmithKline Beecham; appl 19.7.1996; GB-prior 20.7.1995)
Formulation(s): tabl., 20 mg, 30 mg (as hydrochloride)
Trade Name(s):
D: Seroxat (SmithKline F: Dexorat (SmithKline GB: Seroxat (SmithKline
Tagonis (Janssen-Cilag)
Trang 9Parsalmide f' 1569
1: Sereupin (Ravizza) Seroxat (SmithKline USA: Paxil (SmilhKline
Use: anti-inflammatory RN: 30653-83-9 MF: Cl,H1,N202 MW: 246.3 1 EINECS: 250-274-2
LDS,,: 148 mglkg (M, i.v.); 428 mgtkg (M, p.o.);
864 mg/kg (R, p.0.)
CN: 5-amino-N-butyl-2-(2-propyny1oxy)benzamide
2 NoOH
chloride
5-ocetamido-0-ocetyl- 5-ocetomido-0-ocetyl-
5-acetomido-N-butyl- proparw
Porsolmide
Reference(s):
DOS 2 029 991 (E.R.A.S.M.E.; appl 18.6.1970; GB-prior 20.6.1969)
US 3 739 030(E.R.A.S.M.E.; 12.6.1973; GB-prior 20.6.1969)
Pedrazzoli, A et al.: Chim Ther (CHTPBA) 3, 200 (1968)
ulternative synthesis:
GB 1 539 007 (C M Ind.; valid from 26.10.1977; F-prior 8.11.1976)
Fortnulution(s): drg 200 mg, 400 mg; f c tabl 600 mg; s r tabl 800 mg
Trade Name(s):
1: Parsal (Midy); wfm
Use: tuberculostatic antibacterial RN: 2066-89-9 MF: C7H,N0, C,H,N,O MW: 290.28 EINECS: 218-183-2
CN: 4-pyridinecarboxylic acid hydrazide mono(4-amino-2-hydroxybenzoate)
Trang 101570 P Pecazine
$ +
CII OH 60 "C
_F ,
,NH2
0 N NH2
(9 v.)
Reference(s):
CH 303 085 (Roche; appl 1952)
Fonnulation(s): tabl 100 mg
Trade Name(s):
1): Dipasic (Gewo); wfm Pasiniazide Rolland
F: Paraniazide (L'HCpatrol); (L'HCpatrol); wfm
Pecazine
(Mepazine)
ATC: N05A IJse: neuroleptic
RN: 60-89-9 MF: C,,H,N,S MW: 310.47 EINECS: 200-490-8
LD,,: 70 m g k g (M, i.v.)
monoacetate
RN: 24360-97-2 MF: Cl9HZ2N2S C2H40, MW: 370.52 EINECS: 246-207-1
monohydrochloride
RN: 2975-36-2 MF: C19H2zN2S HCl MW: 346.93 EINECS: 221-020-8 LD,,,: 62mg/kg(M,i.v.); 155mg/kg(M,p.o.);
20 m g k g (R, i.v.); 1 glkg (R, p.0.)
FH3
sodium
Reference(s):
US 2 784 185 (Promonta; 1957; D-prior 1953)
Forrnulafion(s): tabl 50 rng, 400 mg (as hydrochloride)
Trade Name(s):
D: Pacatal (Promonta); wfrn