Pharmaceutical Substances Syntheses, Patents, Applications - Part 164 ppsx

Gallardo SA; appl.. and isolation as hydrochloride.. 17.12.1973, 31.10.1974 Formulations: eye drops 0.5 %, 1 %, 2 %, 3 %, 4 %; eye ointment 10 mg/g, 20 mg/g, 30 mglg; gel 40 mglg as hyd

Pifarnine P 1631

Picotarnide

I

Referencefs): , ,

FR 2 100 850 (Manetti Roberts; appl 30.6.197 I; I-prior 1.7.1970)

DE 2 506 209 (Manetti Roberts; appl 14.2.1975) -

US 3 973 026 (Manetti Roberts; 3.8.1976; prior 5.2.1975)

BE 851 967 (Manetti Roberts; appl 1.3.1977)

Selleri R et al.: Chim Ther (CHTPBA) 6, 203 (1971)

Formulation(s): tabl 300 mg (as hydrate)

Trade Name(s):

I: Plactidil (Samil)

Use: peptic ulcer therapeutic, gastric acid secretion inhibitor

RN: 56208-01-6 MF: C,7H,N,02 MW: 424.63

LD,: 500 mglkg (M, i.p.)

1 -piperonyl-

piperozine

Reference (s):

ES 452 269 (Boehringer Mannh.; appl 12.1 1.1976)

Bianchetti, A et al.: Eur J Med Chem (EJMCA5) 9,555 (1974); 10,585 (1975)

1-brorno-3.7.1 1 -trimethyl-

Trade Name(s):

I : Pifazin (Pierrel); wfm

Pifornine 2.6.10-dodecotriene

1632 P Pifoxime

Pifoxime

(Pixifenidurn)

ATC: MOlAB Use: anti-inflammatory

RN: 31224-92-7 MF: C,,H2,N203 MW: 276.34

LD,,: 1 g k g (M, P.o.)

chloroacetic 4'-hydroxy-

4-ocetylphenoxy- ocetic ocid

Reference(s):

U S 3 907 792 (A Mieville; 23.9.1975; CH-prior 31.1.1969, 28.8.1969)

Trade Name(s):

F: Flamanil (Salvoxyl-

Wander); wfm

Use: topical non-steroidal anti- inflammatory and analgesic, ketoprofen derivative RN: 60576-13-8 MF: C22H20N202 MW: 344.41

monohydrochloride

RN: 59512-37-7 MF: C,,H2,N202 HC1 MW: 380.88

rnethylpyridine ([I)

ketoprofen (1)

Pildralazine P 1633

1 PCIJ

2 1 0

n

1 phosphorous

trichloride

Reference(s):

a GB 1 436 502 (A Gallardo SA; appl 10.4.1974; E-prior 10.4.1973)

b BE 882 7 1 1 (Fordonal SA; appl 3 1.7.1980; E-prior 25.2.1980)

Formulation(s): aerosol 20 mglml

Trade Name(s):

E: Calmatel (Almirall; 1985)

Use: hypotensive, vasodilator RN: 64000-73-3 MF: C8H,,N,0 MW: 197.24

N-methyl- 3.6-dichloro-

2-hydroxy- pyridazine

propylamine

OH y H 3 2 O H- C ~

- 1

1 hydrazine

M I hydrate

hydroxypropyl)- methylomino]- pyridazine

Pildralazine

Pifferi, G.; Parravicini, F.; Carpi, C.; Dorigotti, L.: J Med Chern (JMCMAR) 18, 741 (1975)

DOS 2 154 245 (ISF; appl 30.10.1971; I-prior 15.12.1970)

Trade Name(s):

I: Atensil (ISF); wfm

1634 P Pilocarpine

Use: parasympathomimetic, miotic RN: 92-1 3-7 MF: C, ,H16N202 MW: 208.26 EINECS: 202- 128-4

LD,,,: 61.9 mglkg (M, i.v.); 119 mglkg (M, p.0.);

88.5 mglkg (R, i.v.); 402 mg/kg (R, p.0.)

monohy drochloride

RN: 54-7 1-7 MF: C , ,H,,N,O, HCI MW: 244.72 EINECS: 200-212-5

LD,,,: 150 mglkg (M, i.v.); 200 mglkg (M, p.0.)

borate

RN: 16509-56-1 MF: C,,H,&O, xBH303 MW: unspecified

mononitrate

RN: 148-72-1 MF: CllH16N20, HNO, MW: 271.27 EINECS: 205-723-7

LD,,,: 345 mglkg (M, i.v.);

91 l mglkg (R, p.0.)

By extraction of Juborandi leaves (especially Pilocurpus microphvllus Stapf.) and isolation as hydrochloride

Reference(s):

Ullmanns Encykl Tech Chem., 3 Aufl., Vol 3,277

BIOS Final Reports No 766, 233

parnoate:

DAS 2 462081 (Merck & Co., appl 16.12.1974; USA-prior 17.12.1973, 31.10.1974)

Formulation(s): eye drops 0.5 %, 1 %, 2 %, 3 %, 4 %; eye ointment 10 mg/g, 20 mg/g, 30 mglg; gel 40 mglg

(as hydrochloride)

Trade Nume(s):

D: Isopto-Pilocarpin (Alcon)

Pilocarpol (Winzer)

Pilomann (Mann)

Spersa carpin (CIBA

Vision)

Vistacarpin (Pharm-

Allergan)

numerous generics and

combination preparations

F: Chibro-Pilocarpine (Merck

Sharp & Dohme-Chibret)

Isopto-Pilocarpine (Alcon) Pilo (Chauvin)

Pilocarpine Martinet (CIBA Vision Ophthalmics) GB: Isoptocarpin (Alcon) Minims Pilocarpine (Chauvin; as nitrate) Ocusert Pilo (Dominion) Pilogel (Alcon) Salagen (Chiron) Sno-Pilo (Chauvin)

I: Dropilton (Bruschettim) Liocarpina (SIFI) Pilocarpina Lux (Allergan) Pilogel (Alcon)

Pilotonina (Farmila) Salagen (Chiron Italia) generics

J: generic preparations USA Salagen (MGI)

Pilsicainide P 1635

Pilsicainide

(SUN- 1 165)

ATC: COlBC Use: class Ic antiarrhythmic RN: 88069-67-4 MF: C,,H,N,O MW: 272.39

LD,,): 17 m g k g (M, i.v.); 175 mglkg (M, p.0.);

I8 mglkg (R, i.v.); 255 mglkg (R, p.0.);

53 m g k g (dog, p.0.)

monohydrochloride

RN: 88069-49-2 MF: C,,H,N,O HCI MW: 308.85

LD,,): 222 mg/kg (M, p.0.); 410 mglkg (M, s.c.);

260 mglkg (R, p.0.);

87 m g k g (rabbit, p.0.);

50 mglkg (dog, p.0.)

H3cQ H2N

CH, ' + 2 2.6-dimethyl- '

1H-2.3.5.6- molonic 7a-carboxymethyl-

tetrahydro- acid pyrrolizidine

pyrrolizine

I Pihicainide I

Reference(s):

EP 89 061 (Suntory; appl 15.3.1983; J-prior 16.3.1982)

US 4 564 624 (Suntory; 14.1.1986; appl 10.3.1983; J-prior 16.3.1982)

JP9 167 591 (Suntory; appl 11.3.1983)

Formulation(s): cps 25 mg, 50 mg (as hydrochloride)

Trade Name(s):

J: Sunrythm (Suntory; Daiichi

Seiyaku; 199 1)

Use: vasodilator RN: 10001-43-1 MF: C,,H,8N,02 MW: 314.35

LD,,,: 402 mgkg (M, i.v.); 1900 mglkg (M, p.0.)

CN: 3,7-dihydro- 1,3-dimethyl-7-[2-[(3-pyridinylmethyl)amino]ethyl]- 1 H-purine-2,6-dione

1636 P Pimeprofen

nicotinate (1:l)

RN: 10058-07-8 MF: C,sH,8N602 C6HSN02 MW: 437.46 EINECS: 233-185-3 LD,,: 470 mglkg (M, i.v.); 2530 mglkg (M, p.0.);

3700 mgkg (R, p.o.1

theophylline 1,2-dibromo- 7-(2- bromoethyl)-

ethane theophylline (1)

Reference(s):

US 3 350 400 (Eprova; 31.10.1967; CH-prior 12.1.1965)

3-(aminomethyl)-

Trade Name(s):

wfm

Pirnefy\line

Pimeprofen

(Ibuprofen piconol)

pyridine

ATC: MOIAE; M02AA Use: anti-inflammatory

RN: 64622-45-3 MF: C,,H,,NO, - MW: 297.40 EINECS: 264-979-8

LD,,,: 1980 mglkg (M, p.0.);

1440 mgkg (R, p.0.);

7 4 glkg (dog, p.0.)

CN: a-methyl-4-(2-methylpropy1)benzeneacetic acid 2-pyridinylmethyl ester

ibuprofen sodium salt 2-chloromethyl- Pimeprofen

Pimobendan P 1637

triethyl-

2-(4-isobutylphenyl)- P-hydroxy-

propionyl chloride rnethyl-

(from ibuprofen) pyridine

Reference(s):

DOS 2 658 610 (Hisamitsu; appl 23.12.1976; J-prior 24.12.1975)

US 4 150 137 (Hisamitsu; 17.4.1979; J-prior 24.12.1975)

Formulation(s): cream 5 %; ointment 5 %

Trade Name(s):

Pimobendan

(UD-CG 1 15; UD-CG 1 15BS)

ATC: COlCE Use: cardiotonic, PDE 111-inhibitor, vasodilator

RN: 74150-27-9 MF: C,,H,,N402 MW: 334.38

LDso: >2 g/kg (M, p.0.);

72 m g k g (R, i.v.); 950 m g k g (R, p.0.)

hydrochloride

RN: 74149-75-0 MF: C19H18N402 xHC1 MW: unspecified

monohy drochloride

RN: 77469-98-8 MF: C,yH,8N402 HCl MW: 370.84

racemate

RN: 118428-36-7 MF: C,,HI,N4O2 MW: 334.38

LDS6 75 mgflcg (R, i.v.)

(-)-enantiomer

RN: 118428-37-8 MF: C,,H,,N402 MW: 334.38

LD,: 100 mglkg (R, i.v.)

(+)-enantiomer

RN: 118428-38-9 MF: C,,HI,N4O2 MW: 334.38

LD,,: 75 m g k g (R, i.v.)

4-anisoyl methyl 3-(4-amino-

chlon'de 3-nitrobenzayl)-

methyl 3-[4-(4-methoxy- benzoylarnino)-3-nitro-

1638 P Pimozide

hydrozine hydrate

,- A ,

Reference (s):

EP 8 39 1 (Thomae GmbH; appl 3.2.1980; D-prior 25.8.1978, 1.6.1979)

separatiun of enanliomers:

oral formulalion:

DE 4 001 622 (Thomae GmbH; appl 20.1.1990; D-prior 20.1.1990)

use for treatment of aslhma:

DE 4 001 623 (Thomae GmbH; appl 20.1.1Y90; D-prior 20.1.1990)

combination with P-blockers:

EP 387 762 (Thomac GmbH; appl 12.3.1990; D-prior 16.3.1989)

use for trealing erectile dysfunction:

DE 4 338 948 (J Carlen; appl 15.1 1.1993; D-prior l 5 l l 1 ~ 9 3 )

Formulalion(s): cps 1.25 mg, 2.5 rng

Trade Nameis):

J: Acardi (Nippon

Boehringer)

Use: neuroleptic RN: 2062-78-4 MF: C28H29F,N,0 MW: 461.56 EINECS: 218-171 -7

LD,,,: 14 mglkg (M, i.v.); 228 mglkg (M, p.0.);

90 mglkg (R, i.v.); 1 I00 mg/kg (R, p.0.);

32 mglkg (dog, i.v.); 40 mglkg (dog, p.0.)

CN: 1 -[I -[4,4-his(4-fluorophenyl)butyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

Pinacidil P 1639

4-lluorophenyl- cyclopropane-

magnesium corboxylic ocid

bromide ethyl ester

4.4-bis(4-fluoro-

phenyl)butyl

chloride

bis(4-(luorophenyl)- 1 , l -bis(4-fluorophenyl)- cyclopropylcorbinol 4-chioro-l -butene (1)

_*

1 -(4-piperidyl)-2-benz- imidozolonc (cf benperidol synthesis)

I Pimozide

US 3 196 157 (Janssen; 20.7.1965; appl 11.6.1963)

DD 243 284 (VEB Arzneimittelwerk Dresden; appl 13.12.1985)

Formulation(s): tabl 1 mg, 2 mg, 4 mg

Trade Name(s):

D: Antalon (ASTA Medica F: Orap (Janssen-Cilag) J: Orap (Fujisawa)

Orap (Janssen-Cilag) I: Orap (Jansscn-Cilag)

Pinacidil

(P-1134)

ATC: C02DGOl Use: antihypertensive, vasodilator, potassium channel activator RN: 60560-33-0 MF: C,,H,,N, MW: 245.33 EINECS: 262-294-9

155 mgkg (R, i.v.); 210 mg/kg (R, p.0.)

monohydrate

RN: 8537 1-64-8 MF: C,,H,,N, H 2 0 MW: 263.35

570 mg/kg (R, p.0.)

1640 P Pinacidil

4-pyridyl 1.2.2-trimethyl-

isothiocyonote propylornine

N-(4-pyridy1)-N'- (1.2.2-trirnethylpr0pyl)- thloureo (I)

(CHI DCC H,CyNyCH3

CH3CH3

I + H2N-CN

dicyclohexylcorbodiirnide

ethyldiisopropylarnine

cyanamide (11)

(CH3

COCIZ H C N CH3

= Y Y

CH3CH3

phosgene ethyldi-

isopropyl-

Reference(s):

DE 2 557 438 (Leo; appl 19.12.1975; GB-prior 20.12.1974)

DE 2 560 633 (Leo; appl 19.12.1975; GB-prior 20.12.1974)

GB 1 489 879 (Leo; appl 20.12.1974)

Petersen, H.J et al.: J Med Chem (JMCMAR) 21,773 (1978)

Hansen, E.T.; Peterscn, H.J.: Synth Commun (SYNCAV) 14, 537 (1984)

medical use for treatment of asthma:

EP 207 606 (Lilly; appl 15.5.1986; USA-prior 17.5.1985)

medical use for treatment of peripheral vuscular disease:

EP 223 81 1 (Beecham; appl 20.5.1986; GB-prior 29.5.1985, 22.5.1985)

combination with ACE inhibitors:

EP 271 271 (Beecham; appl 30.1 1.1987; GB-prior 24.12.1986,6.12.1986)

combination with P-blocker:

EP 323 745 (Beecham; appl 23.12.1988; CB-prior 6.1.1988)

sustained release formulation:

DOS 3 404 595 (Leo; appl 9.2.1984; DK-prior 11.2.1983)

Fonnulation(s): cps 12.5 mg, 25 mg

Trade Nume(s):

D K : Pindac (Leo)