Alendronate sodium A 53 total synthesis: Johnson, P.S.. Blickenstaff, R.T.; Ghosh, A.C.; Wolf, G.C.: Total Synthesis of Steroids Organic Chemistry Vol.. 500 mg, 750 mg Trade Names: D:
Trang 1Alcuronium chloride A
Trade Name(s):
D: Delonal (Essex Pharma; GB: Modrasone (Dominion; J: Almeta (Shionogi)
\ F: Aclosone (Schering- I: Legederm (Schering- 1986)
Use: muscle relaxant RN: 15180-03-7 MF: C44H50CIZN402 MW: 737.82 EINECS: 239-229-8
LD,,: 610 pglkg (M, i.p.); 240 pglkg (M, i.v.); 38500 pglkg (M, p.0.); 610 pglkg (M, s.c.);
270 p g k g (R, i.p.); 27600 pglkg (R, p.0.); 280 pglkg (R, s.c.)
CN: [iR-(la,3aS*,lOa,l la~,12a,14aS*,19aa,20ba,21a,22a~,23E,26]-2,3,11,1 la,13,14,22,22a-octahydro-
23,26-bis(2-hydroxyethylidene)-l , 12-di-2-propenyl-1OH,19aH,20bH,21H-1,21: 10,12-diethano-
dipyrrolo[3,2-~3',2'-f1[1,5]diazocino[3,2,1-jk:7,6,5-j'k']dicarbazolium dichloride
iodide Wieland-Gumlich aldehyde
(degradation product of strychnine)
IRA-400 (CI form)
A
N(b)-ollyl-heminortoxi- ferine iodide (1)
diollylnortoxiferin diiodide (11)
Alcuronium chloride
Trang 252 A Aldosterone
Reference(s):
US 3 080 373 (Roche; 5.3.1963; F-prior 29.8.1960)
Karrer, P et al.: Angew Chem (ANCEAD) 70, 644 (1958)
Formulation(s): amp 5 ml, 10 ml(1 mg/ml); inj sol 10 mg/2 ml
Trade Name(s):
D: Alloferin Amp (Roche) GB: Alloferin (Roche); wfm USA: Alloferin (Roche); wfm F: Allofkrine (Roche); wfm J: Dialferin (Roche)
Use:
RN: 52-39-1 MF: C2,H2,0, MW: 360.45 EINECS: 200-139-9
CN: (1 1 p)- 11,21-dihydroxy-3,20-dioxopregn-4-en-18-a1
& nH3 -I, nitrosyl pyridine, & Me H 'cH3
0 / 0 /
21 -0-ocetyl-1 1-0-nitrosyl- corticosterone (I)
H02AAO1 mineralocorticoid
bosic soponificotion
-
21 -0-ocetyloldosterone (II)
Reference(s):
Aldosterone
Barton, D.H.R.; Beaton, J.M.: J Am Chem Soc (JACSAT), 82, 2641 (1960)
starting material:
The Merck Index, 25 13 (Rahway 1976)
alternative syntheses:
US 3 002 972 (Ciba; 3.10.1961; appl 28.1 1.1958; CH-prior 5.12.1957)
US 3 014 029 (Ciba; 19.12.1961; appl 16.6.1959; CH-prior 18.6.1958)
US 3 049 539 (Wisconsin Alumni Res Found.; 14.8.1962; appl 29.7.1957)
Wettstein, A et al.: Helv Chim Acta (HCACAV) 44, 502 (1961)
Reichstein, T et a].: Helv Chim Acta (HCACAV) 38, 1432 (1957)
review:
Fieser, L.F.; Fieser, M.: Steroide p 766 ff, Verlag Chemie, Weinheim 1961
Trang 3Alendronate sodium A 53
total synthesis:
Johnson, P.S et al.: J Am Chem Soc (JACSAT) 80,2585 (1958)
Blickenstaff, R.T.; Ghosh, A.C.; Wolf, G.C.: Total Synthesis of Steroids (Organic Chemistry Vol 30) p 187 ff, Academic Press, New York, London 1974
Formulation(s): tabl 500 mg, 750 mg
Trade Name(s):
D: Aldocorten (Ciba); wfm USA: Aldocortin (Burroughs
GB: Aldocorten (Ciba); wfm Wellcome); wfm
I: Sinsurrene Forte (Parke Electrocortin (Ciba-Geigy);
Use: treatment of osteoporosis RN: 121268-17-5 MF: C,H,,NNaO,P, 3H20 MW: 325.12
LD,,: >4 glkg (dog, p 0.)
CN: (4-Amino-1-hydroxybutylidene)bis[phosphonic acid] monosodium salt trihydrate
acid
RN: 66376-36-1 MF: C,H,,NO,P, MW: 249.10
anhydrous monosodium salt
RN: 1293 18-43-0 MF: C4HI2NNaO,P2 MW: 271.08
y-ominobutyric acid
1 140°C 50 psi 20h
Alendronote sodium
I
Reference(s):
WO 9 506 052 (Merck & Co.; USA-prior 25.8.1993)
WO 9 533 756 (Merck & Co.; appl 2.6.1995; USA-prior 6.6.1994)
US 5 510 517 (Merck & Co.; 2.3.1995; USA-prior 25.8.1993)
DE 3 016 289 (Henkel KG; D-prior 28.4.1980)
BE896 453 (1st Gentili s p a.; appl 14.4.1983; I-prior 15.4.1982, 16.2.1983)
BE903 513 (1st Ccntili s p a.; appl 25.10.1985; I-prior 29.10.1984)
EP 494 844 (1st Gentili s p a.; appl 2.1.1992; I-prior 8.1.1991)
US 4 621 077 (1st Gentili s p a,; 8.6.1984; I-prior 15.4.1982)
US 5 019 651 (Merck & Co.; 27.12.1991; USA-prior 20.6.1990)
US 4 922 007 (Merck & Co.; 1.5.1990; USA-prior 9.6.1989)
alternative process for the production of alendronate:
WO 9 834 940 (Apotcx Inc.; CA-prior 11.2.1997)
Formulation(s): amp 5 mg, 10 mg; tabl 5 mg, 10 mg, 40 mg (as sodium salt)
Trang 454 A Alfacalcidol
Trade Name(s):
D: Fosamax (Merck Sharp & Alendros (Gentili) 'Teiroc (Teijin)
Dohme) Dronal (Sigmatau) USA: Fosamax (Merck Sharp & GB: Fosamax (Merck Sharp & Fosamax (Merck Sharp & Dohme; 1993)
I: Adronat (Neopharmed) J: Onclast (Banyu)
(la-Hydroxycholecalciferol; la-Hydroxy-vitamin D,) Use:
vitamin D-derivative RN: 41294-56-8 MF: C,,H,O, MW: 400.65 EINECS: 255-297-1
LD,,: 440 g/kg (M, p.0.);
340 g/kg (R, p.0.)
CN: (la,3~,5Z,7E)-9,10-secocholesta-5,7,10(19)-triene-l,3-diol
potassium tert-butylote
0
3-0x0-1.4.6-cholestatriene 3-0x0-1.5.7-cholestotriene (I)
NoBH.,
sodium
borohydride
3-chloroper-
benzoic acid
lithium aluminum
Trang 5Alfadolone acetate A 55
Alfocolcidoi
Reference(s):
US 3 929 770 (Wisconsin Alumni Res.; 30.12 1975; J-prior 3.12.1973)
alternative syntheses:
Holick, M.F et al.: Science (Washington, D.C.) (SCIEAS) 180, 190 (1973)
Barton, D.H.R et al.: J Am Chem Soc (JACSAT) 95,2748 (1973)
Fiirst, A et al.: Helv Chim Acta (HCACAV) 56, 1708 (1973)
US 3 966 777 (Yeda Res & Devel.; 29.6.1976; IL-prior 22.10.1974)
DOS 2 259 661 (Wisconsin Alumni Res.; appl 1.12.1972; USA-prior 2.12.1971)
BE 877 356 (Wisconsin Alumni Res.; appl 28.6.1979; USA-prior 15.1.1979, 21.5.1979)
GB 1 553 321 (Merck & Co.; valid from 30.6.1977; USA-prior 1.7.1976)
DOS 2 923 953 (Upjohn; appl 13.6.1979; USA-prior 19.6.1978)
total synthesis:
Harrison, R.G et al.: Tetrahedron Lett (TELEAY) 1973, 3649
synthesis of intermediates:
US 4 046 760 (Merck & Co., 6.9.1977; prior 1.7.1976)
pharmaceutical formulation:
JP-appl 78 136 512 (Chugai; appl 28.4.1977)
US 4 164 569 (Chugai; 14.8.1979; J-prior 8.4.1977)
use a s anti-inflammatory:
FX 2 389 377 (J Brohult, appl 6.5.1977)
Formulation(s): amp 0.001 mg, 0.002 mg; cps 0.001 mg, 0.0025 mg, 1 mg; inj 2 yglml
Trade Name(s):
Eins Alpha (Leo) I: Dediol (Rhhe-Poulenc French) -
GB: Alfa D (Berk)
Alfadolone acetate
(Alphadolone acetate)
ATC: NOlA Use: anesthetic (intravenous) RN: 23930-37-2 MF: C23H3405 MW: 390.52 EINECS: 245-942-5
LD5,,: >30 mglkg (rabbit, i.v.)
CN: (3a,5a)-21-(acetyloxy)-3-hydroxypregnane-11,20-dione
alfadolone
RN: 14107-37-0 MF: C2,H320, MW: 348.48 EINECS: 237-961-2
LD,,,: 59 mgkg (M, i.v.)
Trang 656 A Alfaxalone
-
ride etherote
(4 v.)
Alfodolane ocetote
Br2.HBr CH,OH
Reference(s):
DE 2 030 402 (Glaxo; appl 19.6.1970; GB-prior 20.6.1969; 11.6.1970)
ZA 703 861 (Glaxo; appl 8.6.1970; GB-prior 20.6.1969)
(alternative synthesis)
Browne, P.A.; Kirk, D.N.: J Chem Soc (JCSOA9) 1969, 1653
Formulalion(s): amp 0.5 mglml
Trade Name(s):
D : Aurantex (Glaxo)-comb.; GB: Althesin (G1axo)-comb.;
F: Alfatesine (G1axo)-comb.; I: Althesin (G1axo)-comb.;
Alfaxalone
(Alphaxalone)
ATC: NOlAXO5 Use: anesthetic (intravenous) RN: 23930-19-0 MF: C2,H3,0, MW: 332.48
LDso: 430 m d k g (M, i.p.); 36.9 mglkg (M, i.v.); 880 mgikg (M, p.0.); 5220 mglkg (M, s.c.);
1 16 m d k g (R, i.p.); 19.4 mglkg (R, i.v.); 297 mglkg (R, p.0.); >2200 m g k g (R, s.c.);
9.36 m g k g (rabbit, i.v.)
CN: (3o?,5a)-3-hydroxypregnane-l1,20-dione
acetate
RN: 51267-69-7 MF: C23H3404 MW: 374.52
Rhizopus nigricans
Trang 7Alfaxalone A 57
Cr03 HOAc
I la-hydroxy-5a-pregnone-
H2lrCI6, P(OCH3)3 (CH&HOH
(Henbest reduction)
acid
Alfoxalone
1 1 -oxotigogenin
(from hecogenin)
1 TOSCI , pyridine
OK , DMF
1 HZ Pd-C
2 NoOH
_*
1 1 -20-dioxo-3p-hydroxy- 5a-pregnane (V)
a Browne, P.A.; Kirk, D.N.: J Chem Soc C (JSOOAX) 1969, 1653
b Naaata W et al.: Helv Chim Acta (HCACAV) 42 1399 (1959)
Trang 85 8 A Alfentanil
medical use:
DE 2 030 402 (Glaxo; appl 19.6.1970; GB-prior 20.6.1969, 11.6.1970)
Formulation(s): amp 5 ml, 10 ml, 0.3 %
Trade Natne(s):
J: Alphadione (Shin Nihon
Jitsugyo)
Use: analgesic, short-time anesthetic (for basal narcosis)
RN: 71195-58-9 MF: C2,H32N,03 MW: 416.53
CN: N-[1-[2-(4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-l-yl)ethyl]-4-(methoxymethyl)-4-pipe~dinyl]-N-
phenylpropanamide
monohydrochloride
RN: 69049-06-5 MF: C21H32N,03 HCl MW: 452.99 EINECS: 273-846-3
monohydrochloride monohydrate
RN: 70879-28-6 MF: C2,H32N,0, HC1 H 2 0 MW: 471.00
chloroethone
(1)
0
propionic
Trang 9Alfuzosin A 59
Alfentonil
L
Reference(s):
GB 1 598 872 (Janssen; appl 3.5.1978; USA-prior 5.5.1977)
DOS 2 819 873 (Janssen; appl 5.5.1978; USA-prior 5.5.1977, 13.3.1978)
17s 4 167 574 (Janssen; 11.9.1979; appl 25.10.1978; prior 13.3.1978)
Forrnulution(s): amp 500 pglml; inj sol I mgl2 ml, 5 mg/lO ml; intensive care inj 5 mgtml
Trade Nutne(s):
D: Rapifen (Janssen-Cilag; GB: Rapifen (Janssen-Cilag;
F: Rapifen (Janssen-Cilag) USA: Alfenta (Janssen; 1987)
Use: antihypertensive, a,-antagonist, treatment 6f benign prostatic hypertrophy
RN: 81403-80-7 MF: C,,HnN504 M W 389.46
CN: (+)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazalinyl)methylamino]propyl]tetrahydro-2-furancarboxamide
monohydrochloride
RN: 81403-68-1 MF: C19H27N504 HCI M W 425.92
3 NH,
OHCaO-CH~ *No3 , OHC~~'~~: , , I 1 2 N ~ - ~ ~ 3
perrnongonate
3,4-dirnethoxybenz-
aldehyde
(veratroldehyde)
Fe, CH,COOH b H2N%-"3
2-amino-4.5-di-
rnethoxybenzomide
Trang 1060 A Algestone acetophenide
CI
POCI,
4-amino-2-chloro- 6,7-dimethoxy- quinazoline (111)
triethylarnine 0 0 ' "i
3-(methylomino)- tetrohydrofuran- ethyl
2-corboxylic acid chloroformote
proponenitrile
N-tetrahydrofuroyl-
ethylomine (N)
hydrofuroyl-trime- thylenediomine (V)
Reference(s):
US 4 315 007 (Synthelabo; 9.2.1982; F-prior 6.2.1978, 29.12.1978)
DE 290 445 (Synthelabo; appl 16.8.1979; F-prior 6.2.1978,29.12.1978)
Manoury, P.M et al.: J Med Chem (JMCMAR) 29, 19 (1986)
isoomyl alcohol
synthesis of 6,7-dimethoxyquinazoline-2,4-dione:
Althuis, T.H.; Hess, H.J.: J Med Chem (JMCMAR) 20, 146 (1977)
C " 3 Alfuzosin
Formulation(s): tabl 2.5 mg (as hydrochloride)
Trade Name(s):
D: Urion (Byk Gulden) Xatral (SynthClabo; 1989) Xatral (Synthelabo) Uroxatral (Synthelabo) GB: Xatral (Lorex)
F: Urion (Zambon) I: Mittoval (Schering)
Algestone acetophenide ATC: DlOAX; G03DA
(Alfasone acetophenide; Alphasone acetophenide) Use: antiacne, progestogen RN: 24356-94-3 MF: C2,H3,04 MW: 448.60 EINECS: 246-195-8
CN: [16a(R)]-16,17-[(l-phenylethylidene)bis(oxy)]pregn-4-ene-3,2O-dione
dgestone
RN: 595-77-7 MF: C2,H3,0, MW: 346.47 EINECS: 209-869-2