5 mg Trade Narnes: Ornatos Rohm Pharma- comb.; wfrn Priamide-Eupharma Janssen; wfrn Stelabid Rohm Pharma- comb.; wfrn Enuretine vit.. Dignonitrat Sankyo Duranitrat durachemie isoket Sch
Trang 1Isoetarine 1 1 101
N Br2 CH30H
CI bromine CI imidozole
2'.4'-dichloro-
ocetophenone
2-bromo- 2',4'-dichloro- acetophenone
NaBH4 CH30H
1-(2.4-dichloro- phenyl)-2-(1H- imidazol-1 -yl)- ethonol
1 -(2,4-dichloro- phenocyl)irnidozole (I)
DOS 1 940 388 (Janssen; appl 8.8.1969; USA-prior 19.8.1968)
US 3 717 655 (Janssen; 20.2.1973; prior 19.8.1968,23.7.1969)
US 3 839 574 (Janssen; 1.10.1974; prior 19.8.1968, 23.7.1969, 19.7.1972)
Godefroi, E.F et al.: J Med Chem (JMCMAR) 12,784 (1969)
Forrnulation(s): cream 10 mglg (1 %); pessaries 100 mg,300 mg, 600 mg (as nitrate); spray 10 mglml
Trade Name(s):
D: Bi-Vaspit (Axhe)-comb F: Fazol (Bellon; RhBne- Travocort (Schering)-comb Travocort (Schering)-comb Poulenc Rorer; 1979) Travogen (Schering) Travogen (Schering; 1979) GB: Travogyn (Schering) J: Adestan (Schering)
I: Isogyn (Crosara)
Isoetarine
(Etyprenalinum; Isoetharine)
ATC: R03AC07; R03CC06 Use: bronchodilator, sympathomimetic
RN: 530-08-5 MF: C,,H2,N03 MW: 239.32 EINECS: 208-472-1
CN: 4-[l-hydroxy-2-[(l-methylethyl)amino]butyl]-1,2-benzenediol
hydrochloride
RN: 50-96-4 MF: C,,H2,N03 HCI MW: 275.78
LD,,: 57 m g k g (M, Lv.)
H3C
, I isopropylamine
T.4'-dibenzyloxy-
Trang 21102 1 Isoflupredone acetate
Reference(s):
DRP 638 650 (I G Farben; 1934)
lsoetorine
Formulation(s): amp 1 mg, 2.4 mg, 5 mg, 5.1 mg; sol for inhalation 0.125 %, 0.61 %, 1 % (as hydrochloride)
Trade Name(s):
D: Asthmalitan (Kettelhack- GB: Bronchilator (Sterling USA: Bronkometer (Sanofi)-
Numotac (Riker); wfm Bronkosol (Sanofi)-comb
Use: glucocorticoid RN: 338-98-7 MF: C2,H2$0, MW: 420.48 EINECS: 206-423-9
CN: (ll~)-21-(acetyloxy)-9-fluoro-11,17-dihydroxypregna-l,4-diene-3,20-dione
isotlupredone
RN: 338-95-4 MF: C2,H2,F0, MW: 378.44 EINECS: 206-422-3
Se02 (H3C)3C-OH, Roney-Ni
- selenium dioxide tert-butonol
fludrocortisone 21 -acetote
(cf fludrocortisone
synthesis)
Isoflupredone acetate
DE 1 096 900 (American Cyanamid; appl 1959; USA-prior 1958)
microbiological dehydrogenation with Corynebacterium simplex (A.T.C.C 6946):
US 2 837 464 (Schering Corp.; 1958; prior 1955)
alternative synthesis:
DE 1 159 947 (Merck & Co.; appl 1956; USA-prior 1955)
GB 826 364 (Merck & Co.; valid from 1956; USA-prior 1955)
Formulation(s): amp 10 ml
Trade Name(s):
I: Altaflor (1ntes)-comb.; wfm
Biorinil (Farmila)-comb.;
wfm
Cortifluoral (Schering); Dermaflogil (Nuovo Cons
Trang 3Isoflurane 1 1103
Fluoroinil (Farmila)-comb.; Menaderm simp USA: Predef 2x (Upjohn); wfm
Use: inhalation anesthetic RN: 26675-46-7 MF: C,H,CIF,O MW: 184.49 EINECS: 247-897-7
LD,,: 5080 yL1kg (M, p.0.);
4770 yLlkg (R, p.0.)
CN: 2-chloro-2-(difluoromethoxy)- 1,1,1-trifluoroethane
2,Z.Z-trifluoro- dimethyl
HZF, SbCI,
1-
hydrogen fluoride F~C-O
antimony
pentochloride
DOS 1 814 962 (Air Reduction Comp.; appl 16.12.1968; USA-prior 15.1 2.1967, 22.5.1968)
US 3 535 388 (Air Reduction Comp.; 20.10.1970; prior 15.12.1967, 21.3.1969)
US 3 535 425 (Air Reduction Comp.; 20.10.1970; prior 15.1 2.1967, 18.12.1969)
alternative synthesis:
DOS 2 344 442 (Hoechst; appl 4.9.1973)
US 3 637 477 (Air Reduction Comp.; 25.1.1972; prior 20.2.1970, 22.5.1968)
Formulation(s): sol for inhalation 100 ml
Trade Narne(s):
D: Forene (Abbott; 1984) J: Forane (Dainabot) USA: Forane (Ohmeda; 198 1 )
Isoflurophate -
(Difluorophate)
ATC: SO3 Use: parasympathomimetic, miotic
RN: 55-91-4 MF: C,H,,FO,P MW: 184.15 EJNECS: 200-247-6
LD,: 3200 yg/kg (M, i.v.); 2 mglkg (M, p.0.);
5 mg/kg (R, p.o.1;
3430 yglkg (dog, i.v.)
CN: phosphorofluoridic acid bis(1-methylethyl) ester
Trang 41 104 1 Isometheptene
lsoflurophote
Reference(s):
US 2 409 039 (Monsanto; 1946; appl 1944)
Formulatiorz(s): eye drops 0.01 %; eye ointment 0.025 %
Trade Name(s):
F: Diflupyl (Labaz); wfm USA: Floropryl (Merck Sharp &
J: D F P Inj (Sumitomo) Dohme); wfm
Use: sympathetic antispasmodic for gut and urinary tract
RN: 503-01-5 MF: CYH,,N MW: 141.26 EINECS: 207-959-6
LD,,,: 34 m g k g (M, i.v.); 134 m g k g (M, p.0.)
CN: N,6-dimethyl-5-hepten-2-amine
hydrochloride
RN: 6168-86-1 MF: C,HlyN HC1 MW: 177.72 EINECS: 228-21 1-5
LD,,,: 18 mglkg (M, i.v.);
26 mglkg (dog, i.v.)
tartrate (1:l)
RN: 5984-50-9 MF: C,H,,N C,H,O, MW 291.34 EINECS: 227-795-9
LD,,: 130 mglkg (R, i.p.)
2-methy!-6-0x0- methylomine
2-heptene
Isometheptene
Reference(s):
US 1 972 450 (Knoll; 1934; D-prior 1931)
US 2 230 753 (E Bilhuber; 1941; D-prior 1937)
US 2 230 754 (E Bilhuber; 1941; D-prior 1937)
Formulation(s): amp 100 mg (as hydrochloride); drops 100 mg, 50 mg; tabl (as tartrate)
Trade Namefs):
D: Neopyrin (Nordmark)- GB: Midrid (Shire)-comb USA: Duradrin (Duramed; as
Neosal (Nordmark)-comb.; J: Cesal (Dainippon)-comb Midrin (Camrick; as
Trang 5Isoniazid 1 1105
Use: tuberculostatic RN: 54-85-3 MF: C,H,N,O MW: 137.14 EINECS: 200-214-6
LD,,: 149 mglkg (M, i.v.); 133 m g k g (M, p.0.);
365 m g k g (R, i.v.); 1250 mg/kg (R, p.0.);
50 mgkg (dog, p.0.)
CN: 4-pyridinecarboxylic acid hydrazide
HZN-NHZ
b
hydrazine
H
ethyl
isonicotinate
lsoniozid
u
Reference(s):
Meyer, H.; Mally, J.: Monatsh Chem (MOCMB7) 33, 393 (1912)
US 2 596 069 (Roche; 1952; appl 1952)
US 2 830 994 (Distillers; 15.4.1958; GB-prior 29.6.1955)
DE 1 116 667 (BASF; appl 3.7.1956)
combination with protionamide and dapsone:
DAS 2 340 515 (Saarstickstoff-Fatol; appl 10.8.1973)
Formulation(s): amp 100 mg15 ml, 250 mg/5 ml; tabl 50 mg, 100 mg, 200 mg, 300 mg
Trade Name(s):
D: Isoprodian (Fato1)-comb
Isozid (Fatol)
Myambutol (Leder1e)-
comb
Tebesium (Hefa Pharma)
F: Dexambutol-INH
(LIArguenon)-comb
Rifater (Marion Merrel1)-
comb
Rifinah (Marion Merrel1)-
comb
Rimifon (Roche)
GB: Rifater (Hoechst)-comb
Rifinah (Hoechst)-comb
Rimactazid (Novartis)- comb
Rimifon (Roche); wfm
I: Emozide B6 (Piam)-comb
Etanicozid (Piam)-comb
Etibi (Zoja)-comb
Miazide (Cyanamid)-comb
Nicazide ( I n ) Nicizina (Pharmacia &
Upjohn) Nicozid (Piam) Rifanicozid (Piam)-comb
Rifinah (Lepetit)-comb
combination preparations J: Anteben (Dainippon)
Diazid (Nippon Shinyaku) Hycozid (Takeda) Hydra (Otsuka) Iscotin (Daiichi) Niazid (Sankyo) Niplen (Tanabe) Sumifon (Sumitomo) Tuberon (Shionogi) USA: Nydrazid (Apothecon) Rifamate (Hoechst Marion Roussel)
Rifater (Hoechst Marion Roussel)
generic
Isoprenaline
(Isoproterenol)
ATC: COlCA02; R03AB02; R03CBOI Use: bronchodilator, dermatic RN: 7683-59-2 MF: C, ,H,,NO, MW: 21 1.26 EINECS: 23 1-687-7
LD,,: 83 m g k g (M, i.v.); 450 mgkg (M, p.0.);
57 m g k g (R, i.v.); 355 mg/kg (R, p.0.);
50 m g k g (dog, i.v.); 600 mglkg (dog, p.0.)
CN: 4-[l-hydroxy-2-[(l-methylethyl)amino]ethyl]-l,2-benzenediol
Trang 61 106 1 Isopropamide iodide
bitartrate (1:l)
RN: 59-60-9 MF: C,,H,,NO, C,H,O, MW: 361.35 EINECS: 200-437-9
hydrochloride
RN: 51-30-9 MF: C,,H,,NO, HCI MW: 247.72 EINECS: 200-089-8
LD,,, 77 mglkg (M i.v.); 1260 mglkg (M, p.0.);
26.9 mglkg (R, i.v.); 2221 mglkg (R, p.0.);
50 mglkg (dog, i.v.); 600 m g k g (dog, p.0.)
sulfate ( 2 1 )
RN 299-95-6 MF: C,,H,,N03 112H2S04 MW: 520.60 EINECS: 206-085-2
LD,,,: 188 mglkg (M, i.v.); >3 glkg (M, p.0.);
96 mglkg (R, i.v.); 2230 mg/kg (R, p.0.);
50 mglkg (dog, i.v.); 600 mglkg (dog, p.0.)
2-chloro-3'.4'-di- isopropylarnine
hydroxyacctophenone
lsoprcnoline
I
Reference(s):
US 2 308 232 (Boehringer Ing.; 1943; D-prior 1939)
DRP 723 278 (Roehringer Ing.; appl 1939)
racemate resolution with (+)-tartaric acid:
US 2 715 141 (Delmar Chemicals; 1955; appl 1952)
Fornzulation(s): aerosol 0.1 mglpush; amp 0.2 mg, 2 mg (as hydrochloride); sol for inhalation 0.25 %, 0.5 %
(as sulfate); tabl 10 mg, 15 mg, 20 mg
Trade Narrre(s):
D: lngelan (Roehringer Ing.) J: Asthpul Sol (Nippon
Kattwilon (Kattwiga) Shoji)
I;: lsuprel (Abbott) Isomeny 1 (Kaken)
GB: Saventrine (Pharmax) Protemal (Nikken)
I: Aleudrin (Fher); wfm Proternol (Nikken)
generics
Sedansol "Iso" (Nippon Zoki)
Sooner (Kaken) Isuprel (Sanofi; as hydrochloride) Medihaler-Iso (3M; as sulfate)
IJse: anticholinergic, antispasmodic RN: 71-81-8 MF: C23H,,IN,0 MW: 480.43 EINECS: 200-766-8
LD,,,: 12.779 &/kg (M, i.v.); 1600 m g k g (M, p.0.)
CN: y-(aminocarbonyl)-N-methyl-N,N-bis(l-methylethyl)-y-phenylbenzenepropanaminium iodide
Trang 7Isosorbide dinitrate 1 1 107
H C CH3
' H C N
3 y -cl CH3
b
1 sodium ornide
2 2-diisopropylarnino-
diphenyl- ethyl chloride
acetonitrile
(1) methyl
iodide
Reference(s):
GB 772 921 (Janssen; appl 1955: NL-prior 1954)
DE 1 003 744 (Janssen; appl 1955; NL-prior 1954)
Janssen, P et al.: Arch Int Pharmacodyn Ther (AIPTAK) CIII, 82 (1955)
US 2 823 233 (Bristol; 1958; appl 1954)
Formulation(s): inj sol 3 mg12 ml; tabl 5 mg
Trade Narne(s):
Ornatos (Rohm Pharma)-
comb.; wfrn
Priamide-Eupharma
(Janssen); wfrn
Stelabid (Rohm Pharma)-
comb.; wfrn
Enuretine vit E
isoprapamide (Le
Marchand)-comb.; wfrn
Priamide (Delalande); wfrn
GB: Stelabid (S.K.F.)-comb.;
wfrn Tyrimide (Smith Kline &
French); wfrn
I: Fluvaleas (Valeas)-comb
Iodosan (SmithKline Beecham)-comb
Valtrax (Valeas) combination preparations
J: Marygin M (Sumitomo)
USA: Combid (Smith Kline & French); wfrn
Darbid (Smith Kline & French); wfrn
Ornade (Srnilh Kline & French); wfrn
Prochlor-lso (Schein); wfrn Pro-Iso (Zenith); wfrn
Use: coronary vasodilator RN: 87-33-2 MF: C,H,N20, MW, 236.14 EINECS: 201-740-9
LD,,: >40 mglkg (M, i.v.); 1050 mglkg (M, p.0.);
>40 mglkg (R, i.v.); 747 mglkg (R, p.0.)
CN: 1,4:3,6-dianhydro-D-glucitol dinitrate
D-sorbitol isosarbide I lsosorbide dinitrote (
Trang 81108 1 Isosorbide mononitrate
Referencefs):
Goldberg, L.: Acta Physiol Scand (APSCAX) 15, 173 (1948)
Krantz, J.C et a].: J Pharmacol Exp Ther (JPETAB) 67, 187 (1939)
aqueous solutions,for parenteral application:
DAS 2 623 800 (Sanol Schwarz-Monheim; appl 28.5.1976)
I;ormulation(s): r r cps 20 mg, 40 mg, 60 mg, 80 mg, 100 mg; tabl 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg,
40 mg
Trade Name(s):
D: Corovliss (Boehringer
Mannh.)
Dignonitrat (Sankyo)
Duranitrat (durachemie)
isoket (Schwarz)
Iso Mack (Mack, Illert.)
Isostenase (Aiuchemie)
May cor (Godecke; Parke
Davis)
Nitrosorbon (Pohl)
TD spray Iso Mack (Mack)
generic and numerous
combination preparations
F: Isocard (Bouchara) Langoran (Marion Merrell) Risordan (Specia)
GB: Cedocard retard (Phannacia & Upjohn) Isocard (Eastern) Isoket retard (Schwarz) Isordil (Monmouth) Sorbichew (Zeneca) Sorbid SA (Zeneca) Sorbitrate (Zeneca) 1: Carvasin (Wyeth) Diniket (Schwarz)
Nitrosorbide (Lusofarmaco) Stenodilate (Schwarz)- comb
J: Cardis (Iwaki) Carvanil (Banyu) Diretan (Ono) Nitroret (Hishiyama) USA: Dilatrate-SR (Schwarz) Isordil (Wyeth-Ayerst) Sorbitrate (Zeneca) generic
Isosorbide mononitrate
(Isosorbide 5-nitrate)
ATC: COlDA14 Use: coronary vasodilator RN: 16051-77-7 MF: C6H9N06 MW: 191.14 EINECS: 240-197-2
LD,,: 1820 mglkg (M, i.v.); 1771 m g k g (M, p.0.);
1750 mglkg (R, i.v.); 2010 mglkg (R, p.0.)
CN: 1,4:3,6-dianhydro-D-glucitol 5-nitrate
HO H 1 H N 0 3 Ac20, AcOH
2 NaOH pH 7.0
0
isosorbide (I) Isosorbide
dinitrate synthesis)
0
CH3 pyridine, CH2CI2 AcOH A C ~ O H N O ~
0 0
isosarbide (olong with
Trang 9Isosorbide mononitrate 1 1109
isosorbide 2-acetate
5-nitrate (11)
Reference(s):
a US 3 886 186 (American Home; 27.5.1975; prior 29.4.1971, 30.8.1973)
EP 143 507 (Toshin Chemical; appl 13.7.1984; J-prior 25.1 1.1983)
DOS 2 221 080 (American Home Products; appl 28.4.1972; USA-prior 29.4.1971)
b DOS 2 751 934 (American Home Products; appl 21.1 1 l977; USA-prior 24.2.1977)
US 4 065 488 (American Home Products; 27.12.1977; appl 24.2.1977)
EP 45 076 (Boehringer Mannh.; appl 25.7.1981 ; D-prior 30.7.1980)
DOS 3 028 873 (Boehringer Mannh.; appl 30.7.1980)
US 4 431 829 (Boehringer Mannh.; 14.2.1984; D-prior 30.7.1980)
similar methods (via 2-acyloxy derivative):
DE 2 903 927 (Sanol-Schwarz; appl 2.2.1979)
EP 64 194 (Cassella; appl 16.4.1982; D-prior 5.5.198 1)
EP 57 847 (H Mack Nachf.; appl 26.1.1982; D-prior 29.1.1981)
DOS 3 102 947 (H Mack Nachf.; appl 29.1.1981)
EP 67 964 (H Mack Nachf.; appl 18.5.1982; D-prior 22.6.1981)
DOS 3 124 410 (H Mack Nachf.; appl 22.6.1981)
US 4417 065 (H Mack Nachf.; 22.1 1.1983; D-prior 22.6.1981)
preparation from isosorbide dinitrate:
EP 59 664 (SNPE; appl 25.2.1982; F-prior 27.2.1981)
formulations:
DOS 3 325 652 (Dr Rentschler; appl 15.7.1983)
Formulation(s): s r cps 40 mg, 60 mg; tabl 20 mg, 40 mg
Trade Name(s):
D: Coleb (AstraIPromed)
Corangin (Novartis
Pharma)
elantan (Synthelabo)
IS 5 mono-ratiopharm
(ratiopharm)
Ismo (Boehringer Mannh.)
Monit-Puren (Isis Puren)
Monoclair (Hennig)
Mono Mack (Mack, Illert.)
Monostenase (Azupharma)
Olicard (Solvay
Arzneimittel)
numerous generics
F: Monicor L.P (Pierre Fabre)
GB: Elantan (Schwarz)
Imdur (Astra) isib XL (Ashbourne) Ismo retard (Boehringer Mannh.)
MCR 50 (Pharmacia &
Upjohn) Monit (Lorex) Mono-Cedocard (Pharmacia & Upjohn) Monomax (Trinity) I: Duronitrin (Astra) Elan (Schwarz) Ismo (Boehringer Mannh.) Ismo Diffutab (Boehringer Mannh.)
Monocinque (Lusofarmaco) Monoket (Chiesi) Nitralfa (Malesci) Orasorbil (Rottapharm)
dinitrate:
Nltrosorbide (Lusofarmaco) Stenodilate (Schwarz)- comb
J: Itocol (Toa Eiyo- Yamanouchi) USA: Imdur (Key Pharm.) Ismo (Wyeth- Ayerst) Monoket (Schwarz)
Trang 1011 10 1 Isothipendyl
Use: antiallergic, antihistaminic RN: 482-15-5 MF: CI6HIyN3S MW: 285.42 EINECS: 207-578-5
LD,,: 222 mglkg (M, p.0.)
CN: N,N,~-trimethyl-lOH-pyrido[3,2-b][l,4]benzothiazine-lO-ethanamine
monohydrochloride
RN: 1225-60-1 MF: C16HlyN3S HC1 MW: 321.88 EINECS: 214-957-9
LD,,: 28 mglkg (M, i.v.); 222 mglkg (M, p.0.);
1220 mglkg (R, p.0.)
Reference(s):
DE 1 001 684 (Degussa; appl 1954)
US 2 974 139 (Degussa; 7.3.1961; D-prior 2.10.1954)
Formulation(s): drg 12 mg; gel 0.75 % (as hydrochloride)
Trade Name(s):
D: Andantol-fortel-Gelee GB: Nilergex (ICI); wfm J: Aczen NS (Kanebo) (Homburg); wfm I: Calmogel (RhGne-Poulenc Andantol (Sumitomo) F: SCdermyl (RPR Cooper) Rorer)
Use: keratolytic, acne therapeutic RN: 4759-48-2 MF: C2,H2,02 MW: 300.44 EINECS: 225-296-0
LD,,,: 3389 mglkg (M, p.0.);
>4 glkg (R, p.0.)
CN: 13-cis-retinoic acid
sodium salt
RN: 13497-05-7 MF: C2,H2,Na02 MW: 322.42
potassium salt
RN: 22232-80-0 MF: Ca,HZ7KO2 MW: 338.53
vinyl-8-ionol triphenyl-
(cf retinal synthesis phosphine
ond tretinoin