100 mg Trade Names: D: Captimer Fresenius Thiola Coop.. 10 mg; vial 4 mg, 10 mg as hydrochloride Trade Names: D : Orbinamon Pfizer; wfm I: Navane Pfizer; wfm USA: Navane Pfizer; wfm G
Trang 1Tiopronin T 2051
Trade Name(s):
D: Emdabol (Merck); wfm Gerantabol (Merck)-comb.;
wfm
Tiopronin
(Mercamidum)
ATC: R05CB12 Use: detoxicant, liver therapeutic, hepatoprotectant, mucolytic RN: 1953-02-2 MF: C,H,NO,S MW: 163.20 EINECS: 217-778-4
LD,,,: 1733 mgkg (M, i.v.); 2330 mglkg (M, p.0.);
1300 mglkg (R, p.0.)
CN: N-(2-mercapto- 1 -oxopropy 1)glycine
monosodium salt
RN: 2015-25-0 MF: C,H,NNaO,S MW: 185.18
LD,,: 2 100 mgkg (M, i.v.)
2-bromo- glycine
propionyl
bromide
N-(2-brornopropionyl)- glycine
Reference(s):
FR 1491 204 (Santen; appl 10.8.1962; J-prior 2.1 1.1961)
FR-M 3 081 (Santen; appl 22.10.1962; J-prior 2.1 1.1961)
GB 1 023 003 (Santen; appl 14.9.1962)
use as mucolytic agent:
GB 1 482 651 (Lab Cassenne; appl 16.9.1974; USA-prior 14.9.1973)
US 3 857 951 (Lab Cassenne; 3 I I 2.1 974; appl 14.9.1973)
against nosotoxicosa:
US 3 897 480 (Santen; 29.7.1975; J-prior 3.10.1972, 11 S.1973)
sodium salt:
DOS 2 924 231 (P Gargani; appl 15.6.1979; I-prior 16.6.1978)
Formulation(s): amp 100 mg, 250 mg; drg 100 mg, 250 mg; gran 150 mg, 350 mg; tabl 100 mg
Trade Name(s):
D: Captimer (Fresenius) Thiola (Coop Farm.) USA: Thiola (Mission)
F: Acadione (Cassenne) Thiosol (Coop Farm.)
1: Mucolysin (Farmila) J: Thiola (Santen)
Tiotixene
(Thiothixene)
ATC: N05AF04 Use: neuroleptic RN: 3313-26-6 MF: C,,H,,N,02S2 MW: 443.64
LD,,: 100 mglkg (M, i.p.);
55 mgkg (R, i.p.)
CN: (~-N,N-dimethyl-9-[3-(4-methyl-l-piperazinyl)propylidene]-9H-thioxanthene-2-sulfonamide
Trang 22052 T Tiotixene
dihydrochloride dihydrate
RN: 221 89-3 1-7 MF: C,,H2,N,02S2 2HC1 2H20 MW: 552.59
1 SOCI,
2 FH3
H N , QJ"JJso3'" 1 thionyl 9H-thioxonthene OCid 9H-thioxonthene-2- chloride 2-dimethylominosuifonyl-
sulfonic acid " dimethy'- 9H-thioxanthene (U)
omine (1)
1 C4H9Li
2'H3c&,/c~3
I1
2 methyl acetate
9-ocetyl-2-dimethylomino- sulfonyl-9H-thioxonthene
barohvdride
1 -methyl-
piperozine
P0Cl3
phosphoryl
\ I I / 0
Reference(s):
US 3 310 553 (Pfizer; 21.3.1967; appl 26.4.1963; prior 25.9.1962)
DE 1 470 157 (Pfizer; appl 24.9.1963; ~ ~ ~ - ~ r i o r - 2 5 9 1 9 6 2 ; 26.4.1963)
Muren, J.F.; Bloom, B.M.: J Med Chem (JMCMAR) 13, 17 (1970)
Formulation(s): cps 1 mg, 2 mg, 4 mg, 5 mg, 10 mg; tabl 10 mg; vial 4 mg, 10 mg (as hydrochloride)
Trade Name(s):
D : Orbinamon (Pfizer); wfm I: Navane (Pfizer); wfm USA: Navane (Pfizer); wfm GB: Navane (Pfizer); wfm J: Navane (Taito Pfizer)
Trang 3Tioxolone T 2053
Use: antiseborrheic RN: 4991-65-5 MF: C7H,0,S MW: 168.17 EINECS: 225-653-0
CN: 6-hydroxy- 1,3-benzoxathiol-2-one
resorcinol ammonium
rhodanide
1 Tioxolone I
Reference(s):
US 2 332 418 (Winthrop; 1943; D-prior 1938)
use:
US 2 886 488 (Thomae; 12.5.1959; D-prior 2.7.1955)
Formulation(s): sol 200 mgllOO g in comb with 100 mg benzoxonium chloride
Trade Name(s):
D: Loscon (Ga1derma)-comb I: Wasacne (IFI); wfm J: Vikura (Eisai)
F: GBacnine (Lab du D'Furt); Wasacne (Wassermann);
Use: antitussive RN: 5169-78-8 MF: CI5Hl7NS2 MW: 275.44
LD,,: 55 mglkg (M, i.v.); 867 mglkg (M, p.0.);
44 mglkg (dog, i.v.)
CN: 3-(di-2-thienylmethy1ene)-1-methylpiperidine
4'-hydroxybenzophenone 2-carboxylate (1:l)
RN: 31139-87-4 MF: C,sH,7NS2 C,,H,,O, MW: 517.67 EINECS: 250-481-8
LD6 10 g/kg (M, p.0.);
10 g/kg (R, p.o.1 '
citrate
RN: 5169-77-7 MF: C l 5 H l 7 N S 2 ~ xC,H807 MW: unspecified
Z-thienyl-
bromide
Trang 42054 T Tiauizium bromide
Reference(s):
ES 272 195 (A Gallardo; appl 20.1 1.1961)
(also citrate)
further literature see under citrate below
4'-hydroaybenzopherrone-2-carboqlate (hibenzate):
JP 17 591 (62') (Tanabe Seiyaku; appl 27.10.1962; prior 19.10.1960)
GB 924 544 (Tanabe Seiyaku; valid from 7.12.1961; J-prior 19.12.1960)
citmte:
Ponomarev, A.A.; Martemjanova, N.I.: Khim Geterotsikl Soedin (KGSSAQ) 1957, 174
SU 176 903 (Ponomarev, Martemjanova; appl 27.10.1 962)
Formulution(s): powder 10 %; syrup 25 mg (as hibenzate); tabl 10 mg (as citrate)
Trade Name($):
I : Asverin (ISF); wfm Asverin-H (Tanabe; as Hustopan-Syr (0hta)-
J: Asvenne (Tanabe Seiyaku) Hustopan (0hta)-comb
Use: antispasmodic RN: 71731-58-3 MF: C,,H,,BrNS2 MW: 410.44
LD,,,: 10.3 mglkg (M, i.v.1; 578 mg/kg (M, p.0.);
11.4 mglkg (R, i.v.); 1177 mglkg (R, p.0.);
14.2 m g k g (dog, i.v.); 662 mgfkg (dog, p.0.)
CN: truns-3-(di-2-thienylmethylene)octahydro-5-methyl-2H-quinolizinium bromide
SOCI,
b I
thionyl 2-piperidine- ocrylonitrile 1 -(2-cyonoethyl)- chloride
Trang 5F
Tiracizine T 2055
_+
\ 2 methyl
-
bromide 2-thienyl-
magnesium
bromide
1 Tiquiiium bromide
US 4 205 074 (Hokuriku; 27.5.1980; appl 1.3.1979; prior 10.5.1978)
DOS 2 820 687 (Hokuriku Pharm.; appl 11.5.1978; J-prior 16.5.1977, 9.1 1.1977, 8.12.1977,21.12.1977, 28.2.1978)
Koshinaka, E et al.: Chem Pharm Bull (CPBTAL) 27, 1454 (1979)
Trade Name(s):
I: Thiaton (Hokuriku; 1984)
Use: antiarrhythmic RN: 83275-56-3 MF: C,,H2,N3O, MW: 367.45
CN: [5-[(dimethylamino)acetyl]-l0,1l-dihydro-5H-dibenz[b~azepin-3-yl]carbamic acid ethyl ester
monohydrochloride
RN: 78816-67-8 MF: C2,H2,N30, HCI MW: 403.91
LD,: 5.4 mglkg (M, i.v.); 48 mglkg (M, p.0.);
10.9 mglkg (R, i.v.); 78 mglkg (R, p.0.)
1 Fe NH,
2 KOH
+ '''fCH3 *NO3 *$SO4
O CH,
chlorotormate
I0,l 1-dihydro-5H- OCetyl 3-nitro-5-acetyl- 10.1 1 -
azepine (I)
Reference(s):
FR 2493 314 (VEB Arzneimittelwerk Dresden; appl 5.1 1.1980)
DD 258 224 (VEB Arzneimittelwerk Dresden; appl 5.3.1987)
Skoldinov, A.P et al.: Khim Farm Zh (KHFZAN) 24,51 (1990)
DD 267 630 (VEB Arzneimittelwerk Dresden; appl 25.5.1987)
chloride
Trang 62056 T Tirilazad mesilate
alternative synthesis of 3-amino-5-acetyl- l 0 , l I -dihydro-5H-dibenzlb flazepine:
US 3 056 774 (Geigy; 1962; appl 1959; CII-prior 1958)
Formulation(s): f c tabl 50 mg, 100 mg
Trade Nnme(s):
D: Bonnecor
(Arzneimittelwerk
Dresden; 1990); wfm
Tirilazad mesilate
(U-74006)
ATC: N07XXOl Use: lipid peroxidation inhibitor
RN: 110101 -67-2 MF: C3,HS2N6O2 CH,03S MW: 720.98
CN: (16a)-21-[4-(2,6-di-l-pyrrolidinyl-4-pyrimidinyl)-l -piperazinyl]-l6-methylpregna-l,4,9(11)-triene-3,20-
dione monomethanesulfonate
hydrate
RN: 11 1793-42-1 MF: C3RH52Nh02 CH403S H 2 0 MW: 739.00
tirilazad
RN: 110101-66-1 MF: C3,H5*Nh02 MW: 624.87
m l
CNH
piperozine
C I
2.4,6-trichloro- pyrrolidine
6
4-chloro-2.6-
pyrimidine
[ 1 K2C03 CH3CN 6 0 O C
,,,cH, -
N y N + 2 methanesulfanic acid
6
1-(2,6-dipyrrolidino- 21-iodo-16a-methyl-
,4-pyrimidiny1)- pregna-1,4,9(11)-
piperozine (I) triene-3.20-dione
CH,-SO,H
Tirilozod mesilote
Reference(s);
WO 8 701 706 (Upjohn Co.; appl 28.8.1986; USA-prior 29.7.1986, 12.9.1985)
Trang 7Tirofiban hydrochloride T 2 0 5 7
use in the treatment of ischemic diseases:
WO 9 412 185 (Upjohn Co.; appl 2.12.1993; J-prior 3.12.1992)
use for chemotherapy:
WO 9 21 8 089 (Upjohn Co.; appl 27.3.1992; USA-prior 9.4.1991)
use for treatment ophthalmic disorders:
WO 9 119 482 (Upjohn Co.; appl 26.12.1991; USA-prior 12.6.1990)
Formulafion(s): amp 45 mgl30 ml, 105 mgl70 ml; vial 45 mg, 105 mg (as hydrate)
Trade Name(s):
AU: Freedox (Pharmacia &
Upjohn)
Tirofiban hydrochloride
(L 700462; MK 383)
ATC: BOlAC17 Use: platelet aggregation inhibitor, GPIIbI IIIa receptor antagonist
RN: 142373-60-2 MF: C2,H3,N2OsS HCl MW: 477.07
CN: N-(Butylsulfonyl)-O-[4-(4-piperidinyl)butyl]-~-tyrosine hydrochloride
monohydrate
RN: 150915-40-5 MF: C2,H,,N2OsS HCl H,O MW: 495.08
base
RN: 144493-65-5 MF: C2,H,6N20sS MW 440.61
1 BSTFA, A CH3CN
2 0
\\SA/\cH3 , pyridine
c" \
HO 5 15% KHSO,
1 N.O-bis(trimethylsily1)-
trifluoroocetomide
2 butonesulfonyl L-tyrosine chloride N-(butylsulf0nyl)-
L-tyrosine (I)
KOH, KI,
- 'CH,
/s\;
= 0
<COOH 4-(4-pyridiny1)-
butyl chloride (U)
1 H2 Pd-C, CH,COOH
2 HCI
i Tirofibon hydrochloride
Trang 82058 T Tirofiban hydrochloride
@ synthesis of mterrnediote 11:
Br-CI , THF
BuLi, THF
3-brorno-1 -chloro-
Boc /N
4-pyridine-
ocetic acid
N-(tert-butyloxy- corbony1)-4-pipe- ridineocetic acid
2 (rnethoxycorbonylmethylene)-
N-(tert-butyloxy-
triphenylphosphorone methyl 4-[N-(tert-butyl-
1 Hz P I C ,
4-[N-(tert-butyloxy- carbony1)piperidin- 4-yl]butyl bromide
PPh3, THF 1 Hz Pd-C
yoH + 1 - 1 -
N /
Reference($):
a US 5 206 373 (Merck+ Co.; 1.9.1993; USA-prior 28.2.1992)
Chung, J.Y et al.: Tetrahedron (TETRAB) 49 (26), 5767 (1993)
b EP 478 363 (Merck+ Co.; appl 27.9.1991; USA-prior 30.8.1990)
Egbertson, M S et al.: J Med Chem (JMCMAR) 37,2537 (1994)
c WO 9 316 994 (Merck + Co.; appl 24.2.1993; USA-prior 28.2.1992)
Trang 9Tiropramide T 2059
alternative synthesis:
US 5 292 756 (Merck + Co.; 8.3.1994; USA-prior 30.8.1991, 27.9.1990)
pharmaceutical compositions:
US 5 733 919 (Merck + Co.; 31.3.1998; USA-prior 23.10.1996)
WO 9 715 328 (Merck + Co.; appl 23.10.1996; USA-prior 27.10.1995)
Formulation(s): sol for inj 0.05 mglml, 0.25 mglml; vial 50 ml, 0,25 mglml
Trade Name(s):
D: Aggrastat (Merck Sharp & USA: Aggrastat (Merck Sharp &
Use: antispasmodic RN: 55837-29-1 MF: C,,H,,N,O, MW: 467.65
LD,,: 40.5 mglkg (M, i.v.); 550 m g k g (M, p.0.);
33.9 mgkg (R, i.v.); 800 mg/kg (R, p.0.)
CN: (+_)-a-(benzoylamino)-4-[2-(diethylamino)ethoxy]-N,N-dipropylbenzenepropanamide
hydrochloride
RN: 57227-16-4 MF: C,,H,,N,O, , xHC1 MW: unspecified EINECS: 260-634-0
LD,,: 28 mglkg (M, i.v.); 639 mglkg (M, p.0.);
32 mglkg (R, i.v.); 1074 m g k g (R, p.0.)
0
HO
DL-tyrosine benzoyl (+)-0,N-dibenzoyltyrosine (I)
chloride
I acetone, N ( c ~ H ~ ) , , C I C O O C ~ H ~ H3CeN-CH3
2 H J C ~ N - C H J
H
1
2 dipropyiornine
(11)
I N NaOH CH,OH
6 h ambient temp
N-benzoyi-DL-tyrosine-
Trang 102060 T Tixocortol ~ i v a l a t e
Reference(s):
DOS 2 503 992 (Rotta Research; appl 31.1 l975; I-prior 1.2.1974)
US 4 004 008 (Rotta Research; 18.1.1977; I-prior 1.2.1974)
2-diethylomino-
ethyl chloride
Formulation(s): amp 50 mgl3 ml; s r cps 200 mg; suppos 200 mg; tahl 100 mg (as hydrochloridc)
Tiroprornide
Trade Name(s):
D: Alfospas (Opfermann) I: Alfospas (Rottapharm) Maiorad (Rotta Research)
(Tiocortisol pivalate; Tixocortol trimethylacetate) Use: glucocorticoid
RN: 55560-96-8 MF: Cz6H,,0sS MW: 462.65 EINECS: 259-706-4
CN: (1 1 P)-2 1-[(2,2-dimethyl-l -oxopropyl)thio]- I1 ,I 7-dihydroxypregn-4-ene-3.20-dione
tixocortol
RN: 61951-99-3 MF: Cz,H3004S MW: 378.53
dioxo-21 -iodo-4-pregnene propanethioic
(cf hydrocortisone ocid
2 1 -phosphate synthesis)
Reference(s):
DOS 2 357 778 (Jouveinal; appl 20.1 1.1973; F-prior 30.5.1973)
synthesis of tixocortol:
Schaub, R.E.; Weiss, M.J.: J Org Chem (JOCEAH) 26, 1223 (1961)
Formulation(s): clysma 250 mg; nasal spray lg1100 g; susp 1 gllOO g
Trade Name(s):
D: Tiovalon (Intersan; 1986); Oropivalone-Bacitracine Pivalone NComycine
I? Dontopivalone (Jouveina1)- Pivalone Nasale (Jouveinal; Rectovalone (Jouveinal)
comb