methyl Trade Names: D: Pelerol Sandoz-comb.; F: Palerol Salvoxyl-Wander; Tropenziline bromide bromide... CN: la,3~,5a-3-[hydroxydiphcnylacetyloxy]spiro[8-azoniabicyclo[3.2.1]octane-8,1
Trang 1Tromantadine T 213 1
Trade Name(s):
D: Angitrit (Nordmark); wfm Etamin (Zeria) USA: Metamine (Pfizer); wfm
J: Amitolen (Hokuriku) Sedalis (Kayaku)
Use: antiviral RN: 53783-83-8 MF: C,6H28N202 MW: 280.41 EINECS: 258-770-0
CN: 2-[2-(climethylamino)ethoxyl-N-tricyclo[3.3.1 l3z']dec- 1-ylacetamide
monohydrochIoride
RN: 41544-24-5 MF: C,,H,,N,O, HC1 MW: 316.87 EINECS: 255-434-5
FH3
0
1 -amino- chloro- 1 -(2-chloroocet-
odamontone ocetyl amido)adamontane
chloride
Tromantodine
Reference(s):
DOS 1 941 218 (Merz & Co.; appl 13.8.1969)
Peteri, D.; Sterner, W.: Arzneim.-Forsch (ANCEAD) 23,577 (1973)
Formula~ion(s): cream 10 mg, 100 mg/lO g; gel 10 mg, 100 mg/lO g; ointment 1 % (as monohydrochloride)
Trade Name(s):
D: Vim-"Merz" (Merz & Co.) Viru-"Merz" Serol (Merz & I: Viruserol (Novartis
RN: 77-86-1 MF: C,H,,NO, MW: 121.14 EINECS: 201-064-4
CN: 2-amino-2-(hydroxymethy1)-1.3-propanediol
HZ Raney-Ni 02N-CHI + H C H O + H ~ ~ o O H H -,
nitro- farm- 2-(hydroxymethy1)-
methane aldehyde 2-nitro-1 ,3-
propanedial
Reference(s):
U S 2 174 242 (Purdue Res Found.; 1939; appl 1937)
electrolytic reduction:
US 2 485 982 (Commercial Solvents Corp.; 1949; appl 1944)
Trometamol
El
Formu/ation(s): amp 7.3 gl20 ml, sol 34.36 gI100 ml
Trang 22 132 T Tropenziline bromide
Trade Name(s):
D: Elektrolyt-Konzentrat Tris TRIS 36.34 % Braun (BI Thamacktat (Bellon;
Use: antispasmodic, parasympathomimetic RN: 143-92-0 MF: C,H,oBrNO, MW: 476.41 EINECS: 205-612-3
CN: 3-[(hydroxydiphenylacetyl)oxy]-6-methoxy-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide
methoxy- methyl- dimethyl
succinoldehyde omine ocetonedi-
corboxylote
N o
H ~ C ~ 0 rn H ~ c ' ~ Hz Roney-Ni -+ - 11
ethyl benrilote
H ~ C ~ 0 rn H ~ c ' ~ Hz Roney-Ni ,,,OH 0 0
6-methoxyiropinone (I)
Reference(s):
CH 325 296 (Sandoz; appl 1954)
Stoll, A et a].: Helv Chim Acta (HCACAV) 37,495 (1954); 38, 571 (1955)
methyl
Trade Name(s):
D: Pelerol (Sandoz)-comb.; F: Palerol (Salvoxyl-Wander);
Tropenziline bromide bromide
Trang 3Tropicamide T 2133
Use: parasympatholytic, mydriatic RN: 1508-75-4 MF: C17H20N202 MW: 284.36 EINECS: 216-140-2
LD,,,: 565 m g k g (M, p.0.);
865 m g k g (R, p.0.)
CN: N-ethyl-a-(hydroxymethyl)-N-(4-pyridinylmethyl)benzeneacetamide
HCI + y T N
0-ocetyltropoyl
Tropicarnide
u
Reference(s):
US 2 726 245 (Hoffmann-La Roche; 1955; CH-prior 1952)
Fonnulation(s): eye drops 5 mglml, 5 mg10.5 ml
Trade Name(s):
F: Mydriaticum (Merck Sharp Visumidriatic (Pharmec) USA: Tryptar (Armour); wfm
& Dohme-Chibret)
Tropisetron
(ICS-205930)
ATC: A04AA03 Use: antiemetic, antimigraine, 5-HT,- antagonist
RN: 89565-68-4 MF: C17H20N202 MW: 284.36
CN: JH-Indole-3-carboxylic acid endo-8-methyl-8-azabicyclo[3.2.l]oct-3-yl ester
Trang 42134 T Trospium chloride
indole-3-
carboxylic ocid (I)
indole-3- corbonyl chloride (11)
1.THF
2 BuLi, THF
11 +
0
H
H
Tropisetron 4
1 ,la-corbonyl- 1 - ( 1 H-indol-3-
diirnidozole y1corbonyl)- 1 H-
irnidozole
Reference(s):
a DE 3 322 574 (Novartis; appl 23.6.1983; CH-prior 29.6.1982)
a,b BE 901 274 (Sandoz A G.; appl 14.12.1984; CH-prior 23.12.1983)
use of serotonin-5-HT-antagoni~ts:
DE 3 724 059 (Sandoz-Patent GmbH; appl 21.7.1987; D-prior 7.8.1986)
b DE 3 445 377 (Sandoz-Patent GmbH; appl 13.12.1984; CH-prior 23.12.1983)
Langlois, M et al.: Eur J Med Chem (EJMCA5) 28, 869 (1993)
Formrtlution(s): amp 2 mg/2 rnl, 5 mg/5 rnl; cps 5 rng
Trade Name(s):
D: Navoban (ASTA Medica GB: Navoban (Novartis
AWD; Novartis Pharma) Pharma)
F: Navoban (Novartis I: Navoban (Novartis
Use: anticholinergic, antispasmodic RN: 10405-02-4 MF: C,,H,,CINO, MW: 427.97 EINECS: 233-875-4
LD50: 11.2 mg/kg (M i.v.); 812 mg/kg (M, p.0.);
15.5 mg/kg(R, i.v.); 1510mg/kg(R, p.0.)
CN: (la,3~,5a)-3-[(hydroxydiphcnylacetyl)oxy]spiro[8-azoniabicyclo[3.2.1]octane-8,1'-pyrrolidinium]
chloride
Trang 5Trovafloxacin mesilate T 2 135
nortropine 1,4-dibromo-
butane
a-chlorodiphenyl-
acetyl chloride
Trospium chloride
L
Reference(s):
DE 1 194 422 (Pfleger; appl 5.3.1963)
Formulation(s): amp 1.2 mg/2 rnl, 2 mg/2 ml; drg 15 mg, 20 mg, 30 mg; f c tabl 5 mg; suppos 0.75 mg, 1
rng
Trade Name(s):
D: Spasrnex (Pfleger) Spasmo-Urgenili
Spasrno-Fyt (Madaus) (Madam)-comb
Spasmo-Rhoival (Byk Trospi-forte (medac)
GuldenIByk Tosse) J: Spasmex (Nikken)
Trovafioxacin mesilate
(CP-992 19; CP-992 19-27)
ATC: JOlMA13 Use: antibacterial
RN: 147059-75-4 MF: C,,H,,F3N4O, CH403S MW: 512.47
CN: (1 a,5a,6~)-7-(6-Arnino-3-azabicyclo[3.1 O]hex-3-yl)-l-(2,4-difluorophenyl)-6-fluoro- l,4-dihydro-4-0x0-
1,8-naphthyridine-3-carboxylic acid
monohydrate
RN: 193478-08-9 MF: C2,H,,F3N403 CH401S H 2 0 MW: 530.48
base
RN: 147059-72-1 MF: C,,H,,F3N403 MW: 416.36
hydrochloride
RN: 146961-34-4 MF: C2,H,,F3N4O3 IICI MW: 452.82
1 Et,O
O 2 thermolysis -N,
N-benzyl- ethyl
rnoleimide (I) diazoacetate (11)
ethyl ( l a , 5 a , 6 n ) - 3 - benzyl-2,4-dioxo-3- azabicyclo[3.1 O]hexone-
Trang 621 36 T Trovafloxacin mesilate
1 LiAIH4, THF 1 CI-Cbo , dioxone, NaHC03
2 Hz, Pd-C, CHJOH H 2 Jones reagent acetone
I -b H 0 / ' " ' ' q N b I V
H benzyl chloroformote
(la,Sa,6a)-3-(benzyl-
oxycorbonyl)-3-020-
bicyclo[3.l O]hexone-
6-carboxylic acid (N)
N3
2 Hz, Pd-C CH30H CH3 H H
b B~~'"‘Q diphenylphosphoryl azide
H
ethyl 7-chloro-1-(2.4-
difluorophenyl)-6-fluoro-
4-0x0-1,4-dihydro- l,8-
nophthyridine-3-corboxylote (W)
@ alternative synthesis of N
VII + H 3 C - S 0 3 H +
separation of diastereorners , H3CAOq 0 ?
H N , c b o
dihydro- carbony1)-
pyrral 2.5-dihydro-
F
H
H2N,,,, 2
H3c-s03H
H P N ,N
F
0 Trovofloxocin rnesilate
-
Trang 7Trovafloxacin mesilate T 2 137
NaOH
I + N
@) alternative synthesis of V
H 0 1 BH3 THF
H O2N.,,,qN47 2 H, ~ d - c
0
brornonitro
methane
1 Boc\O/Boc, THF TEA
HJ+,,,+;~ 2 HZ Pd-c cH30H
H"" \
Reference(s):
route for trovajloxacin 6P- diastereomer:
Vilsmaier, E.; Goerz: Synthesis (SYNTBF) 739 (1998)
a US 5 164 402 (Pfizer Inc., 17.1 1.1992; USA-prior 11.7.1990)
Brighty, K.E et al.: Synlett (SYNLES) 1996, 1097
JP 09 012 546 (Chisso Corp.; appl 23.6.1995)
aa Braish, T.E et al.: Synlett (SYNLES) 1996, 1100
Stille, J.K et al.: J Org Chem (JOCEAH) 45 (1 I), 2139-2145 (1980)
ES 2 095 809 (Quimica Synth.; appl 27.7.1995)
ab EP 818 445 (Pfizer Inc.; appl 1.7.1997; USA-pr~or 9.7.1996)
starting material VI:
US 4 571 396 (Warner Lambert Co.; 18.2.1986; USA-prior 16.4.1984)
US 4 775 668 (Pfizer Inc.; 4.10.1988; USA-prior 19.8.1986)
novel crystal forms:
W 0 9 639 406 (Pfizer Inc.; USA-prior 6.6.1995)
W 0 9 707 800 (Pfizer Inc.; appl 29.7.1996; USA-prior 29.8.1995)
polymorphs of the prodrug:
WO 9 708 191 (Pfizer Inc.; appl 5.7.1996; USA-prior 29.8.1995)
suspension for oral administration:
DE 19 706 978 (U Posanski; appl 5.1.1998; D-prior 21.2.1997)
use for treatment of Heliobacter pylori infections:
EP 676 199 (Pfizer Inc.; appl 23.3.1995; USA-prior 7.4.1994)
Formulation(s): tabl 100 mg, 200 mg (as mesylate); vials, 40 ml, 6 0 ml with 5 mglml
Trade Narne(s):
D: Trovan (Pfizer); wfm Turvel (Pfizer); wfm USA: Trovan (Pfizer; 1998); wfm
Trang 82138 T Troxerutin
- - -
Use: vein therapeutic RN: 7085-55-4 MF: C13HJ20L9 MW: 742.68 EINECS: 230-389-4
LDS,,: 27.16 gtkg (R, i.p.)
CN: 2-[3,4-bis(2-hydroxyethoxy)phenyl]-3-[[6-0-(6-deoxy-a-~-rnannopyranosy1)-~-~-glucopyranosyl]oxy]- 5-hydroxy-7-(2-hydroxyethoxy)-4H-l-benzopyran-4-one
DAS 1 06 1 327 (Zyma; appl 30.12.1957; CH-prior 4.7.1957)
GB 833 174 (Zyma S.A.; appl 27.6.1958; CH-prior 4.7.1957)
synthesis with cthylcne oxide:
DAS 1 543 974 (Zyma; appl 8.10.1966; F-prior 25.10.1965; CH-prior 9.3.1966)
DAS 1 793 746 (Zyrna; appl 8.10.1966; F-prior 25.10.1965)
Formulation(s): cps 300 rng; eye drops 50 mgtml; f c drg 300 rng; f c tabl 250 rng, 300 rng; s r tabl 300
rng
Trade Name(s):
D: Drisi-Ven (Sertiirner)
Pherarutin (Kanoldt)
Posorutin (Ursapharm) F:
Troxerutin-ratiopharrn
(ratiopharm)
Troxeven (Kreussler)
Vastribil (Farmasan)
Veno SL 300 (Ursapharrn)
GB :
numerous combination preparations
Ginkor (Beaufour)-comb
RhCobral (Niverpham) RhCoflux (Niverpharrn) Veinarnitol (Negma) VivCne (Labs de L' ACrocid) Paroven (Zyma); wfm
I: Derrnoangiopan (Abiogen Pharrna)-comb
Ernorril (Po1i)-comb
Flebil (Molteni) Premium (Synthelab0)- comb
Venolen (Farrnacologico Milanese)
Troxipide
RN: 99777-81-8 MF: C,,H2,N204 MW: 294.35
CN: (k)-3,4,5-trirnethoxy-N-3-piperidinylbenzarnide
ATC: A02BXI I
Usc: ulcer therapeutic
base
RN: 30751-05-4 MF: C15H2,N204 MW: 294.35
LDsu: 100 rng/kg (M, i.v.); 2 g/kg (M, p.0.);
21 00 rnglkg (R, p.0.)
Trang 9monohydrochloride
RN: 3075 1-03-2 MF: C,SH,,N,04 HCI MW: 330.8 1
LDso: 300 mglkg (M, i.p.); 2000 mglkg (M, p.0.); 1550 mglkg (M, s.c.);
340 m d k g (R, i.p.); 21 00 m g k g (R, p.0.)
3-amino- 3.4.5-trimethoxy- 3-(3.4.5-trimethoxy-
pyridine benzoyl chloride benzamid0)pyridine
Reference(s):
DOS 1 938 512 (Kyorin; J-prior 30.6.1969)
DOS 1 967 324 (Kyorin; J-prior 30.6.1969)
US 3 647 805 (Kyorin; 7.3.1972; appl 1 1.7.1969)
Irikura, T et al.: J Med Chem (JMCMAR), 14, 357 (1971)
medical use for treatment ofgastritis:
EP 254 068 (Kyorin; appl 25.6.1987; J-prior 26.6.1986)
Form~dation(s): tabl 50 rng, 100 rng
Trade Name(s):
J: Aplace (Kyorin; 1986)
ATC: N06AX02 Use: antidepressant, essential amino acid RN: 73-22-3 MF: CI,Hl2N2O, MW: 204.23 EINECS: 200-795-6
LD,,: >16 g k g (R, p.0.)
CN: L-tryptophan
acrolein diethyl ocetomido-
molonoie
H
Trang 10racemization of N-ocetyl-D-tryptophan
3-cyano-
propian-
aldehyde
3-(5-hydantoiny1)-
propionaldehyde ( N )
5-(3-indoly1rnethyl)- hydantoin
aminaocylase
0 0 COOH
DL-tryptophan (V)
Reference(s1:
a Warner, O.T.; Moe, O.A.: J Am Chem Soc (JACSAT) 70,2765 (1948)
b Komachiya, Y et al.: Nippon Kagaku Kaishi (NKAKB8) 86, 856 (1965)
erlzyrnatic rueenlate resolution:
Chibata, I et al.: Bull Agric Chem Soc Jpn (BACOAV) 21,58, 304 (1957)
purification:
U S 5 057 615 (Mitsui Toatsu; 15.10.1991; J-prior 27.6.1989)
combination with beta blocking agents:
IJS 4 161 530 (Ciba-Gcigy; 17.7.1979; CH-prior 6.1.1975)
GR 1 53 1 091 (Ciba-Gcigy; appl 5.1.1976; CH-prior 6.1.1975)
Volk, W et a].: Arzneim.-Forsch (ANCEAD) 28 (II), 1798 (1978)
newer syntheses for DL-tryptophan:
Hengartner, M et al.: J Org Chem (JOCEAH) 44, 3748 (1979)
Fbrtnulation(s): f c tabl 500 mg; tabl 500 mg
Trade Narne(s):
D: Ardey tropin (Ardeypharm) Actitonic (Reygagne)- Tryptacin (Arther); wfm
Lypharm (esparma) GB: Optimax (Merck)-comb Control Products); wfm numerous combination J : Eltrip (Ono) Tryptophane (Nature's
F: Actitonic (Amido; as DL- USA: Trofan (Upsher-Smith); Tryptophane (Solgar); wfm