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Pharmaceutical Substances Syntheses, Patents, Applications - Part 174 ppt

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Propiram P 1731 COOH COOH CI-CO-O-CH2-CHCH,2, NC2H53 isobulyl chloroformate, triethylamine 2-phenoxybutyric 6-arninopenicillanic References: GB 877 120 Beecham; appl... Trade Numes

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Propiram P 1731

COOH COOH

CI-CO-O-CH2-CH(CH,)2, N(C2H5)3

isobulyl chloroformate, triethylamine

2-phenoxybutyric 6-arninopenicillanic

Reference(s):

GB 877 120 (Beecham; appl 10.5.1960; USA-prior 25.5.1959,22.10.1959)

GB 899 199 (Pfizer; appl 7.1.1960; USA-prior 28.9.1959)

GB 904 576 (Bayer; appl 24.1 1.1960; D-prior 4.12.1959)

GB 958 478 (Beecharn; appl 28.2.1963; USA-prior 13.3.1962)

DE 1 143 817 (Beecharn; appl 25.5.1960; USA-prior 25.5.1959, 22.10.1959)

DE 1 154 805 (Bayer; appl 24.10.1961)

DE 1 159 449 (Griinenthal; appl 22.3.1961)

Fomulation(s): f c tabl 280 rng, 700 rng; syrup 70 rng; tabl 125 mg, 140 rng, 280 mg, 700 rng (as potassium

salt)

Trade Name(s):

F: Brocilline (Nativelle); wfm J: Oracillin (Takeda)

Use: analgesic

LD5": 290 mglkg (M, s.c.);

366 rng/kg (R, s.c.)

CN: N-[l-rnethyl-2-(l-piperidinyl)ethyl]-N-2-pyridinylpropanamide

fumarate (1:l)

RN: 13717-04-9 MF: C,,H,,N,O C4H404 MW: 391.47 EINECS: 237-270-6

LD,,: 48.2 rnglkg (M, i.v.); 874 mglkg (M, p.0.);

63.8 rnglkg (R, i.v.); 1289 mglkg (R, p.0.);

1 glkg (dog, p.0.)

Q

sodium

Q

CI amide HN Y N 9

2-amino- 2-chloro-l-

pyridine piperidino-

propane

2-(2-piperidino-l - rnethylethylornino)- pyridine (I)

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prapianic anhydride I propiram /

Reference(s):

US 3 163 654 (Bayer; 29.12.1964; D-prior 13.4.1961)

FR 1 492 761 (Bayer; appl 13.4.1962; D-prior 13.4.1961)

combinations:

US 4 479 956 (Analgesic Assoc.; 30.10.1984; appl 26.4.1983)

Trade Name(s):

I : Algeril (Bayer); wfrn

Yropiverine

(P4)

ATC: G04BD06 Use: anticholinergic, treatment of

incontinence RN: 60569-19-9 MF: C2,H,,N0, MW: 367.49

CN: a-Phcnyl-a-prupoxybenzeneacetic acid 1 -methyl-4-piperidinyl ester

hydrochloride

RN: 54556-98-8 MF: C,,H2,N0, HCl MW: 403.95

1 -methyl-4- piperidinol (11)

(cf benoctyzlne

synthesis)

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Propofol P 1733

COOH

11 SOC12 benzen; clpN isoproponol SOClp

-b 111 -+ N

\cH3 benzilic ocid

1 -methyl-4- chloropiperidine

alternative synthesis of ethyl benzilote (I):

bensaldehyde benzoin benzil

Reference(s):

a DD 106 643 (C Starke et al.; appl 12.7.1973; DD-prior 12.7.1973)

Laphin, 1.1 et al.: Khim Khim Tekhnol (SSAKAG) 30 (7), 27-36 (1987)

b Klosa, J.; Delmar, G.: J Prakt Chem (JPCEAO) 1 6 , 7 1-82 (1962)

pharmaceutical preparation:

DE 2 937 489 (C Starke, G Schubert; appl 17.9.1979; DD-prior 9.10.1978)

transdermal formulation:

JP04 266 821 (Rido Chem.; appl 22.2.1991)

Formulatior~(s): drg 5 mg, 15 mg (as hydrochloride)

Trade Narne(s):

Propofol

(Disoprofol; ICI-35868)

Use: anesthetic (injectible)

LD,,: 50mgkg (M, i.v.); 1100 mgfkg (M, p.0.);

42 mgkg (R, i.v.); 500 mg/kg (R, p.0.)

Reference(s):

US 2 831 898 (Ethyl Corp.; 1958)

Kolka, A.J et al.: J Org Chem (JOCEAH) 21,712 (1956); 22,642 (1957)

Kealy, T.J.; Coffman, D.D.: J Org Chem (JOCEAH) 26, 987 (1961)

Carlton, J.K.; Bradbury, W.C.: J Am Chem Soc (JACSAT) 78, 1069 (1956)

I

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1734 P Propoxycainc

Trade Name(s):

Use: local anesthetic

LD,,: 9 mglkg (M, i.v.)

CN: 4-amino-2-propoxybenzoic acid 2-(diethy1amino)ethyl ester

monohydrochloride

LD,,,: 7417 bglkg (M, i.v.)

methyl 4-nitro- propyl benzene-

solicylote sulfanote

COOH

H~C-N"+~' + , \ 0ficti3

4-nitro-2-propoxy- 2-diethylomino

benzoic acid (I) ethyl chloride

1 Prapoxycoine I

Rcfcrence(s):

US 2 689 248 (Sterling Drug; prior 1950)

Trade Nume(s):

comb.; wfm

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Propranolol P 1735

Use: beta blocking agent

LD,,: 28.1 mgkg (M, i.v.); 289 mgkg (M, p.0.);

23 mgkg (R, i.v.); 660 mgkg (R, p.0.)

hydrochloride

RN: 318-98-9 MF: C,,H,,N02 HCI MW: 295.81 EINECS: 206-268-7

LD,,: 18 mgkg (M,i.v.); 320mglkg (M,p.o.);

21 mgkg (R, i.v.); 466 mglkg (R, p.0.)

+

1 -naphthol (1)

@

1 11

2 NaOH

epichloro- 1 -chloro-3- ornine (111) hydrin (11) (1 -nophthoxy)-

2-proponol

3-(1 -naphkhoxy)- propylene oxide

Rejerence(s):

DE 1 493 847 (ICI; prior 18.1 1.1963)

US 3 337 628 (ICI; 22.8.1967; GB-prior 23.1 1.1962)

GB 994 918 (ICI; appl 23.11.1962; valid from 28.10.1963)

GB 995 800 (ICI; appl 23.1 1.1962; valid from 28.10.1963)

retard form:

US 4 138 475 (ICI; 6.2.1979; GB-prior 1.6.1977)

Propronolol

Formulation(s): amp 5 mgl5 ml; f c tabl 10 mg, 20 mg, 40 mg, 80 mg; s r cps 60 mg, 80 mg, 120 mg,

160 mg; tabl 10 mg, 25 mg, 40 mg, 80 mg (as hydrochloride)

Traa'e Name(s):

D: Beta-Tablinen (Sanorania)

Dociton (Rhein-Pharma;

Zeneca)

Efektolol (Brenner-Efeka)

Elbrol (Pfleger)

Indobloc (ASTA Medica

AWD)

Obsidian (Isis Pharma)

Probabloc-401-80

(Azupharma)

Propanur 20140180 (Henning Berlin) Prophylux (Hennig) Propranolol-Gry (Gry) Sagittol40/80/160 (Sagitta); wfm various generics and combination preparations

HCmipralon (Urpac-Astier) GB: Beta-Prograne (Tillomed)

Inderal LA (Zeneca; 1965) Inderetic (Zeneca)-comb lnderex (Zeneca)-comb Probeta LA (Trinity) Propanix LA (Ashbourne) I: Inderal (Zeneca; 1967)

Inderal (Sumitomo) Kemi (Otsuka) Pylapron (Kyorin)

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1736 P Proovlhexedrine

hydrochlorothiazide

Use: sympathomimetic, appetite depressant

hydrochloride

RN: 1007-33-6 MF: CloH21N HC1 MW: 191.75 EINECS: 213-753-7

(+)-base

(+)-hydrochloride

LD,,: 70 mglkg (M, i.p.)

N,a-dirnethyl-

benzeneethanornine

Reference(s):

DE 949 657 (Knoll; appl 1954)

DE 970 480 (Knoll; appl 1940)

Zenitz, B.L et al.: J A Chem Soc (JACSAT) 69, 11 17 (1947)

alternative synrhesis:

US 2 454 746 (Smith Kline & French; 1948; appl 1947)

Formularion(s): drg 25 mg

Trade Name(s):

D: Eventin (Minden); wfm GB: Benzedrex (Smith Kline & USA: Benzedrex (Smith Kline &

Use: X-ray contrast medium

LD,,: 300 mglkg (M, i.v.); >18 glkg (M, p.0.)

CN: 3,5-diiodo-4-0x0-l(4H)pyridineacetic acid propyl ester

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Propylthiouracil P 1737

iodine I chloroocetic acid I 1

4(1H)-pyridone 3.5-diiodo-4(1 H)-

pyridone

I Propyliodone

Reference(sJ:

GB 517 382 (ICI; appl 1938)

BE 5 16 687 (Glaxo; appl 1953; GB-prior 1952)

Formulation(s): susp 10 g120 ml, vial 50 %

Trade Name(s):

0

3.5-diiodo-4-0x0- 1.4-dihydropyridino- acetic ocid (I)

Chemie); wfm

Use: antithyroid drug

LD,,: 1250 mgikg (R, p.0.)

ethyl 3-oxocoproote thioureo I Propylthiouiocil I

Reference(s):

Anderson, G.W et al.: J Am Chem Soc (JACSAT) 67,2197 (1945)

Formularion(s): tabl 25 mg, 50 mg

Trade Name(s):

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1738 P Propyphenazone

Propgphenazone

(Isopropylantipyrin)

Use: analgesic, antipyretic RN:

LD,,,:

CN:

960 mglkg (M, p.o.1;

860 mglkg (R, p.0.)

1,2-dihydro- 1,s-dimethyl-4-(I -methylethyl)-2-phenyl-3H-pyrazol-3-one

pyrozolone

4-isopropyl-3- methyl- 1 -phenyl- 5-b2-pyrozolone (1)

Reference(s):

D R P 565 799 (Hoffmann-La Roche; appl 1931)

D E 962 254 (Riedel-deHaen; appl 1954)

Formulntion(s): cps 400 mg; suppos 100 mg, 200 mg, 300 mg, 400 mg; tabl 500 mg

Trade Name(s):

AWD)

Demex (Berlln-Chemie)

Eufibron (Berlin-Chemie)

Isoprochin (Mcrckle)

Saridon (Roche Nicholas)-

comb

and circa 150 more

generics and combination

preparations

F: Polypirine (Lehning)-

comb

I: Caffalgina (Home)-comb

Flexidone (Po1i)-comb

Influvit (Recordati)-comb

Micranet (0gna)-comb

Mind01 (Merck-Bracco)- comb

Neo-Optalidon (Novartis)- comb

Omniadol (Montefarrnaco)- comb

Optalidon confetti (Novartis)-comb

Ribelfan (Pharmacia &

Upjohn)-comb

Saridon (Roche)-comb Spasmocibalgina (Novanis)-comb Spasmoplus (Novartis)- comb

Uniplus (Ange1im)-comb Veramon (Sofar)-comb, Vit~algin (Boots H.M

VIT1)-comb

LD,,,: 8 0 mg/kg (M, i.p.)

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Proquazone P 1739

phenothiozine 2 2-bromopropionyl

bromide

(1) methyl I Propyromozine bromide

bromide

Referencefs):

US 2 615 886 (Astra; 1952; prior 1951)

Formulation(s): tabl 25 mg; vial 10 mglml

Trade Name(s):

F: Diaspasmyl (Diamant);

wfm

Use: analgesic, anti-inflammatory

LD,,: 930 mgkg (M, p.0.);

759 mglkg (R, p.0.)

H3C

NH2

_,

2-amino-4-methyl-

benzophenone

P-isopropylomino- 4-methylbenzo- phenone

Reference(s):

US 3 723 432 (Sandoz-Wander; 27.3.1973; prior 29.8.1966,4.5.1967,4.10.1967,26.2.1968, 1.7.1968,

12.11.1968)

DE 1 805 501 (Sandoz; appl 26.10.1968; USA-prior 30.10.1967, 26.2.1968, 1.7.1968)

alternative synthesis:

US 3 549 635 (Sandoz-Wander; 22.12.1970; prior 26.2.1968, 1.7.1968)

DOS 1 909 110 (Sandoz; appl 24.2.1969; USA-prior 26.2.1968, 1.7.1968)

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1740 P Proscillaridin

2-isopropylamino-4-methylbenzophenone:

US 3 845 128 (Sandoz; 29.10.1974; prior 30.10.1967, 5.8.1970)

DOS I 81 8 01 2 (Sandoz; appl 26.10.1968; USA-prior 3O.lO.l967,26.2.1968, 1.7.1968)

US 4 071 557 (Sandoz; 31.1.1978; appl 29.1.1976)

Formulation(s): cps 200 mg, 300 mg; suppos 300 mg

Trade Name(s):

D: Biarison (Sandoz); wfm

Proscillaridin

(Proscillaridin A)

ATC: COlABOl Use: cardiac glycoside RN: 466-06-8 MF: C,,H,,O, MW: 530.66 EINECS: 207-370-4

LD,,: 4.7 mglkg (M, i.v.); 30.5 mg/kg (M, p.0.);

9 mg/kg (R, i.v.); 56 mglkg (R, p.0.)

enzymatic hydralysis (p-glucosidose)

_*

glucoscilloren A

(from Scillo moritimo L.)

enzymatic hydrolysis (scillorenose or strophonthobiore or Coronillo enzymes or fungo1 enzymes)

OH OH

scllloren A (I)

I Proscilloridin

@ from Urgineo burkei Baker

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