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Pharmaceutical Substances Syntheses, Patents, Applications - Part 9 pot

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Arncinonide Formulations: cream 0.1 %; lotion 0.1 %; ointment 0.1 % Trade Narnes: D: Amciderm HermaVMerck; Penticort Neomycine USA: Cyclocort Fujisawa; 1979 F: Penticort Wyeth-Lederle

Trang 1

Amcinonide A 8 1

Amcinonide

(Triamcinolone acetate cyclopentanoide)

ATC: D07AC11; H02AB Use: topical glucocorticoid RN: 51022-69-6 MF: C,,H,,FO, MW: 502.58 EINECS: 256-915-2

LDs,: >5 @g (M, p.0.);

>2 glkg (R, p.0.)

CN: (1 1 P, 16a)-21-(acety1oxy)- 16,17-[cyclopentylidenebis(oxy)]-9-fluoro-ll-hydroxypregna-1,4-diene-3,20-

dione

triarncinolone cyclopentanone triarncinolone cyclopentanonide (I)

Reference(s):

GB 1 442 925 (American Cyanamid; USA-prior 17.8.1973)

ocetonhydride

DOS 2 437 847 (American Cyanamid; applT 6.8.1974; USA-prior 17.8.1973)

BE 818 929 (American Cyanamid; appl 16.8.1974; USA-prior 17.8.1973)

US 4 158 055 (American Cyanamid; 12.6.1979; USA-prior 6.6.1975)

Arncinonide

Formulation(s): cream 0.1 %; lotion 0.1 %; ointment 0.1 %

Trade Narne(s):

D: Amciderm (HermaVMerck; Penticort Neomycine USA: Cyclocort (Fujisawa; 1979)

F: Penticort (Wyeth-Lederle; I: Amcinil (Crosara)

Use: selective noradrenergic antihypotensive RN: 30578-37-1 MF: C,,H,,N,O CH,O,S MW: 313.33 EINECS: 250-248-0

LD,,: 28 m g k g (M, i.v.); 1330 mglkg (M, p.0.);

24 m g k g (R, i.v.); 1410 m g k g (R, p.0.);

60 m g k g (dog, i.v.); 100 mglkg (dog, p.0.)

CN: 4-amino-6-methoxy-1-phenylpyridazinium methyl sulfate

Trang 2

82 A Amfebutamone

chloride

RN: 51410-15-2 MF: CllH,,CIN,O MW: 237.69

2-butyne- rnucachloric

hydrazine C I

I

NH2 sulfate

pyridozinone (I)

Reference(s):

Reicheneder, F et al.: Arsneim.-Forsch (ARZNAD) 31 (11), 1.529 (1981)

DE 1 912 941 (BASF; appl 14.3.1969)

DOS 2 139 687 (BASF; appl 7.8.1971)

DOS 2 21 1 662 (BASF; appl 10.3.1972)

DOS 3 1 14 496 (BASF; appl 10.4.1981)

EP 63 267 (BASF; appl 31.3.1982; D-prior 10.4.1981)

precursors:

DE 2 100 685 (BASF; appl 8.1.1971)

Arneziniurn rnetilsulfote

Formulation(s): amp 5 mg; tabl 10 mg

chlaro-1- phenyl-6(1 H)-

phenyl-6(1H)- pyridazinone

pyridozinone

Trade Nanze(s):

D: Regulton (Knoll) Supratonin (Griinenthal)

Amfebutamone

(Bupropion)

ATC: N06AE Use: antidepressant RN: 34911-55-2 MF: C,,H,,ClNO MW: 239.75

LD,,: 544 mg/kg (M, p.0.)

CN: (+)- 1-(3-chloropheny1)-2-[(I ,1 -dimethylethyl)amino]-1 -propanone

hydrochloride

RN: 31677-93-7 MF: C,,H,,ClNO HCl MW: 276.21 EINECS: 250-759-9 LD,,,: 230 m g k g (M, i.p.); 575 m g k g (M, p.0.);

210 mg/kg (R, i.p.); 600 mglkg (R, p.0.)

Trang 3

I Amfenac sodium A 83

3-chloro- ethylmagnesium 5'-chloro-

tert-butyl- amine

Rejerence(s):

DOS 2 059 61 8 (Wellcome; appl 3.12.1970; GB-prior 4.12.1969)

DOS 2 064 934 (Wellcome; appl 3.12.1970; GB-prior 4.12.1 969)

CA 977 778 (Wellcome; appl 15.1 1.1970)

I Formulation(s): s r tabl 100 mg, 150 mg (as hydrochloride); tabl 75 mg, 100 mg

Trade Name(s):

USA: Wellbutrin (Glaxo

Wellcome)

Zyban (Glaxo Wellcome)

Amfenac sodium

RN: 61941-56-8 MF: C,,H,,NNaO, MW: 277.26

LD,,: 550 m g k g (M, i.v.); 615 m g k g (M, p.0.);

277 m g k g (R, i.v.1; 31 1 mglkg (R, p.0.)

CN: 2-amino-3-benzoylbenzeneacetic acid monosodium salt

monohydrate

RN: 61618-27-7 MF: C,,H,,NNaO, H 2 0 MW: 295.27

amfenac

RN: 51579-82-9 MF: C15H,,N0, MW: 255.27

LD,,: 615 m g k g (M, p.0.);

31 1 mglkg (R, p.0.)

1 HZ Pd-C NoOH

2 N o N 0 2 HCI

ATC: MOlAB Use: non-steroidal anti-inflammatory, analgesic

3 tin(ll) chloride

Trang 4

84 A Amfepramone

Amfenoc sodium

u

Reference(s):

DOS 2 324 768 (Robins; appl 16.5.1973; USA-prior 17.5.1972)

US 4 045 576 (Robins; USA-prior 17.5.1972)

Welstead, W.J et a].: J Med hem (JMCMAR) 22, 1074 (1979)

1 -aminoindolin-2-one:

Lora Tamayo, M et al.: Org Prep Proced Int (OPPIAK) 8 , 4 5 (1976)

J: Fenazox (Meiji Seika)

Amfepramone

(Diethy lpropion)

ATC: A08AA03 Use: appetite depressant RN: 90-84-6 MF: C13H19N0 MW: 205.30 EINECS: 202-019-1

LD,,: 160 mglkg (M, p.0.);

>400 m g k g (R, p.0.)

CN: 2-(diethylamino)- l -phenyl- 1-propanone

hydrochloride

RN: 134-80-5 MF: C,3H19N0 HC1 MW: 241.76 EINECS: 205-156-5

LD,,,: 50 mglkg (M, i.v.); 385 mglkg (M, p.0.);

400 mglkg (R, p.0.)

propiophenone a-bromo-

propiophenone

I Amfepromone (

Reference(s):

US 3 001 910 (Temmler-Werke; 26.9.1961; D-prior 16.4.1958)

Trang 5

Amidephrine mesilate A 85

Formulafion(s): cps 25 mg, 75 mg; s r cps 375 mg; s r tabl 75 mg; tabl 25 rng, 7 5 mg

Trade Name(s):

D: Regenon retard (Tcmmler) GB:

Tenuate (Synomed)

F: Moderatan (ThCranol-

Deglaude)

PrCfamone (Dexo)

Tenuate-Dospan (Marion I:

Merrell)

Amidephrine mesilate

(Amidefrine mesilate)

Apisate (Wyeth)-comb.; USA: Tenuate (Merrcll-National);

Tenuate (Merrell); wfm Tepanil (Riker); wfm Tcnuate Dospan (Merrell);

wfrn Linea Valeas (Valeas) Tenuate Dospan (Lepctit)

ATC: R03A Use: rhinological therapcutic, vasoconstrictor, sympathomimetic RN: 1421-68-7 MF: CloH,6N203S CH403S MW: 340.42

LD,,,: 190 m g k g (M, i.v.); 2284 mglkg (M, p.0.);

13 m g k g (R, p.0);

1400 g k g (dog, Lv.)

CN: ' (+)-N-[3-[l -hydroxy-2-(methylamino)ethyl]phenyl]mcthanesulfonamide monomethanesulfonate

amidephrine

RN: 37571-84-9 MF: C,,Hl,N,03S MW: 244.32

methonesulfonyl 3-orninooceto-

chloride phenone

3-methylsulfonylornino- acetophenone (I)

a-brorno-3-methyl- a-bcnzylrnethylomino-3-

sulfanylominoocetophenone rnethylsulfonylorninoacetophenone (II)

I Amidephrine mesilote J

FR-M 3 027 (Mead Johnson; appl 23.1.1963; USA-prior 24.1.1962, 14.12.1962)

For-mulation(s): sol 0.1 %

Trade Name(s):

GB: Dricol (Brislol); wfm

Trang 6

86 A Amidotrizoic acid

Amidgtrizoic acid

(Diatrizoic acid)

ATC: V08AAO1 Use: X-ray contrast medium RN: 117-96-4 MF: CllHyI,N204 MW: 613.92 EINECS: 204-223-6

LD,,,: 8900 mglkg (M, i.v.);

>12.3 glkg (R, i.v.)

CN: 3,5-bis(acety1amino)-2,4,6-triiodobenzoic acid

monosodium salt

RN: 737-3 1-5 MF: CllH,I,N2Na04 MW: 635.90 EINECS: 212-004-1

LD,,,: 14 glkg (M, i.v.); >7 g k g (M,R, p.0.);

11.4 glkg (R, i.v.);

13.2 g/kg (dog, i.v.)

meglumine salt

RN: 8064-12-8 MF: C,,H,13N,Na04 CllHyI,N,O,~ C,H,,NO, MW: 1445.03

LD,,: 11.5 g k g (M, i.v.);

29.2 mglkg (R, i.v.)

Hz Pd-C .6:", - KICIZ potossiumb

I

iodate 3.5-dinitrobenzoic acid 3,5-diaminobenzoic acid 3,5-diamino-2.4,6-

triiadobenzaic acid (I)

ocetic onhydride I Amidolrizaic acid I

I + H 3 C K o K C H 3 d

Reference (s):

Larsen, A.A et al.: J Am Chem Soc (JACSAT) 78, 3210 (1956)

GB 748 319 (Schering AG; appl 1954; D-prior 1953)

GB 782 3 13 (Mallinckrodt; appl 1955; USA-prior 1954)

US 3 076 024 (Sterling Drug; 29.1 l963; appl 19.2.1954)

DE 1 260 477 (Schering AG; appl 1954; USA-prior 1953)

C O O H

H 3 C 1 N

H I H

salts with amino acids:

DAS 2 261 584 (Dr F Kohler Chemie; appl 15.12.1972)

Formulation(s): amp 0.65 glml; inj sol 31 %-73 %

Tradv Name(s):

D: Angiografin (Schering)

Gastrografin (Schering)

Peritrast (Kohler; as lysine

salt)

Urografin (Schering)

Urovison (Schering)

F: Angiografine (Schering)

Gastrografine (Schering)

RadiosClectan (Schering)

GB: Gastrografin (Schering Chemicals); wfrn Hypaque (Winthrop); wfrn Urografin (Schering Chemicals); wfrn I: Gastrografin (Schering)- comb

Selectografin (Schering)- comb

J: Urografin (Schering- Nichidoku Yakuhin) USA: Cardiografin (Squibb); wfrn Cystografin (Squibb); wfrn Gastrografin (Squibb); wfrn Hypaque-Cysto

(Winthrop); wfrn Hypaque-Diu (Winthrop); wfrn

Trang 7

Amifostine A 8 7 Hypaque Sodium Reno-M-30 (Squibb); wfm Renovist (Squibb); wfm (Winthrop); wfm Reno-M-60 (Squibb); wfm Sinografin (Squibb)-comb Meglumine Diatrizoate Reno-M-DIP (Squibb); with adipiodon; wfm

(Eth~ophos; Gammaphos; NSC-296961; WR 2 7 2 1) Use: mucolytic agent, radioprotector,

reduction of cisplatin induced renal toxicity

RN: 20537-88-6 MF: CsHlsN203PS MW: 214.23

LD,,,: 557 mg/kg (M, i.v.); 842 mg/kg (M, p.0.);

826 mglkg (R, p.0.)

CN: 2-[(3-aminopropyl)amino]ethanethiol dihydrogen phosphate (ester)

t r ~ s o d ~ u m th~ophosphote dodecohydrate 2-(3-ominopropylamino)ethyl

Reference(s):

DD 289 448 (Amt fiir Atomsicherheit; appl 29.7.1982; DDR-prior 29.7.1982)

DD 289 449 (Amt fiir Atomsicherheit; appl 29.7.1983; DDR-prior 29.7.1983)

H

Amifastine

composition having improved stability:

WO 9 403 179 (US Bioscience; appl 30.7.1993; USA-prior 31.7.1992)

preparation of monohydrate:

JP54 046 722 (Yamanouchi; appl 12.4.1979; J-prior 21.9.1977)

preparation via 2-(3-aminopropy1amino)ethyI bromide:

SU 751 030 (Kortun; 30.6.1981; SU-prior 4.1.1979)

use forprotection during radio- and chemotherapy:

US 5 298 499 (Res Triangle Inst.; appl 5.7.1991; USA-prior 5.7.1991)

WO 8 907 942 (US Bioscience; appl 21.2.1989; USA-prior 23.2.1988)

US 5 167 947 (Southwest Res Inst.; appl 26.10:1989; USA-prior 26.10.1989)

US 3 892 824 (Southern Res Inst.; appl 16.12.1988; USA-prior 16.12.1988)

use for reducing side effects with azidothymidine:

WO 9 014 007 (US Bioscience; appl 9.5.1990; USA-prior 24.5.1989)

use for prevention of cytostatic alopecia:

DE 3 509 071 (ASTA-Werke; appl 14.3.1985; D-prior 29.3.1984)

Formulation(s): amp 500 mg; vial 500 mg dry substance for inj

Trade Name(s):

D: Ethyol (Essex Pharma; GB: Ethyol (Schering-Plough)

1995)

Trang 8

8 8 A Amikacin

Use: aminoglycoside antibiotic RN: 37517-28-5 MF: C22H43NJ013 MW: 585.61 EINECS: 253-538-5

LD5,: 280 m g k g (M, i.v.); >6 glkg (M, p.0.)

N1-(4-amino-2-hydroxy- l -0xobuty1)-2-deoxy-D-streptamine

sulfate ( 1 2 )

RN: 39831-55-5 MF: C,H,3NS0,3 2H2S0, MW: 781.76 EINECS: 254-648-6

LD,,: 18 1 mg/kg (M, i.v.); >I0679 g k g (M, p.0.);

234 mglkg (R, i.v.); >4 glkg (R, p.0.);

383 rnglkg (dog, i.v.)

kanarnycin A

(4 v.)

N H ~

~ ~ - ( b e n z ~ l a x ~ c a r b o n ~ I ) k a n a r n ~ c i n A (I)

I Arnikacin

LC-)- y-benzylaxycarbonylornino- a-hydroxybutyric acid succinirnido ester

GB 1 401 221 (Bristol Myers; appl 13.7.1972; USA-prior 13.7.1971)

DE 2 234 3 15 (Bristol-Myers; appl 12.7.1972; USA-prior 27.1.1972 13.7.1971)

US 3 781 268 (Bristol-Myers; 25.12.1973; prior 27.1.1972, 13.7.1971)

Kawaguchi, H et al.: J Antibiot (JANTAJ) 25, 695 (1972)

Trang 9

Amiloride A 89

alternative syntheses:

NL 7 401 517 (Bristol-Myers; appl 4.2.1974; USA-prior 7.2.1973)

NL 7 414 668 (Bristol-Myers; appl 11.11.1974; USA-prior 14.11.1973, 23.5.1974)

US 3 974 137 (Bristol-Myers; 10.8.1976; prior 23.5.1974)

DOS 2 432 644 (Takeda; appl 8.7.1974; J-prior 12.7.1973)

DOS 2 716 533 (Pfizer; appl 14.4.1977; GB-prior 14.4.1976)

DOS 2 818 822 (Bristol-Myers; appl 28.4.1978; USA-prior 28.4.1977, 20.3.1978)

DOS 2 818 992 (Bristol-Myers; appl 28.4.1978; USA-prior 28.4.1977; 20.3.1978)

disulfate pentahydrate:

FR 2 308 373 (Bristol-Myers; appl 22.3.1976; USA-prior 23.4.1975)

review:

Kawaguchi, H.; Hiroshi: Drug Action Drug Resist Bact (DADRBY) 2,45 (1975)

Formulation(s): cream 2.5 %, 5 %; eye drops 0.3 %, 0.5 %; gel 5.5; vial 100 mg/2 ml, 250 mgl2 ml,

500 mg/2 ml

Trade Name(s):

D: Biklin (Bristol-Myers

Squibb; 1976)

F: Amiklin (Bristol-Myers

Squibb)

GB: Amikin (Bristol-Myers

Squibb; 1976)

I: Amicasil (Biotekfarma)

Bb-k8 (Bristol; 1978)

Chemacin (CT) Pierami (Pierrel; 1980) Likacin (Lisapharma; Sifamic (SIFI)

Lukadin (San Carlo) Biklin (Banyu-Bristol- Migracin (SmithKline Myers Squibb)

Mikavir (Salus Research;

1986)

Use: diuretic, antihypertonic RN: 2609-46-3 MF: C,HuClN70 MW: 229.63 EINECS: 220-024-7

CN: 3,5-diamino-N-(aminoiminomethyl)-6-chloropyrazinecarboxamide

monohydrochloride

RN: 2016-88-8 MF: C6HuC1N70 HC1 MW: 266.09 EINECS: 217-958-2

YHO +

CHO

glyoxal 5.6-diaminouracil lumazine 3-aminopyrazine-

2-carboxylic acid (1)

methanol methyl 3-omino- methyl 6-chloro-

pyrazine-2-carboxylote 3.5-diaminopyrazine-

Trang 10

90 A Amineptine

guonidine I Arniloride I

Reference(s):

DE 1 470 053 (Mercle & Co.; appl 28.10.1963; USA-prior 30.10.1962)

US 3 313 813 (Merck & Co.; 11.4.1967; prior 30.10.1962,7.10.1963)

GB 1 066 855 (Merck & Co.; appl 24.10.1963; USA-prior 30.10.1962,7.10.1963)

Bicking, J.B et al.: J Med Chem (JMCMAR) 8,638 (1965)

Cragoe, E.J et al.: J Med Chem (JMCMAR) 10, 66 (1967)

improved method for 5,6-diaminouracil:

DOS 2 831 037 (Lonza; appl 14.7.1978; CH-prior 20.7.1977)

combination with etacrynic acid:

US 3 781 430 (Merck & Co.; 25.12.1973; prior 30.10.1962,7.10.1963,7.2.1966, 18.2.1969, 21.12.1971) Fomulation(s): tabl 2.5 mg, 5 mg, 10 mg in comb with hydrochlorothiazide (as hydrochloride)

Trade Name(s):

D: Amiduret (Trommsdorff;

1985)-comb

Diaphal (Pierre Fabre

Pharma)-comb

Diursan (TAD)-comb

Esmalorid (Merck)-comb

Moducrin (MSD; 1978)-

comb

Moduretik, -mite (Du Pont

Pharma; 1973)-comb

Rhefluin, -mite (Kytta-

Siegfried)-comb

F: LogirCne (Pharmacia &

Upjohn SA)-comb

Modamide (Merck Sharp &

Dohme; 1973)

Moducren (Merck Sharp &

Dohme-Chibret; 1979)- comb

Modurktic (Merck Sharp &

Dohme; 1973)-comb

GB: Amilco (Baker Norton;

1983)-comb with hydrochlorothiazole Burinex A (Leo)-comb I:

FruCo (Baker Norton)-

Frumil (RhGne-Poulenc Rorer; 1983)-comb

Kalten (Zeneca; 1985)- comb

Lasoride (Hoechst; 1987)- comb

Moducren (Morson; 198 1)- comb

Moduret-25 (Du Pont; 1984)-comb

Moduretic (Du Pont; 1970) Navispare (Novartis)-comb Moduretic (Merck Sharp & Dohme; 1975)-comb Midamor (Merck Sharp & Dohme; 1981)

Moduretic (Merck Sharp & Dohme; 1981)-comb

Use: psychoanaleptic, CNS stimulant RN: 57574-09-1 MF: C22H27N02 MW: 337.46 EINECS: 260-818-0

LD,,,: 1 15 mglkg (M, i.p.)

CN: 7-[(10,1 l-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)amino]heptoic acid

hydrochloride

RN: 30272-08-3 MF: C2,HZ7NO, HCI MW: 373.92 EINECS: 250-107-3

LD,,: 405 mglkg (M, p.0.)

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