Ojima I. (ed.) Fluorine in Medicinal Chemistry and Chemical Biology
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Fluorine-containing Drugs for Human Use Approved by FDA in the United States 553
Formula Pharmaceutical action Dosage form CAS No. Approval date/
drug sponsor
C
21
H
25
Cl
3
FN
3
O
Anti - anxiety agent
Gaba modulators
Hypnotic
Sedative
Oral capsule,
elixir, and
tablet
1172 - 18 - 5
Nov. 1985/
Mylan
Sandoz
Par Pharm
Pharm Assoc.
Abraxis
C
15
H
12
FNaO
2
Nonsteroidal anti -
infl ammatory
analgesic
Ophthalmic drops 56767 - 76 - 7
Dec. 1986/
Allergan
Bausch and Lomb
C
15
H
13
FO
2
Nonsteroidal anti -
infl ammatory
analgesic
Oral tablet 5104 - 49 - 4
Oct. 1988/
Pharmacia and
Upjohn
Caraco
Mylan
Pliva
Sandoz
Teva
Theragen
C
11
H
11
F
3
N
2
O
3
Androgen antagonist
Antineoplastic agent
Oral capsule 13311 - 84 - 7
Jan. 1989/
Schering
∆
Barr
Genpharm
IVAX Pharms
Par Pharm
Sandoz
C
27
H
29
F
3
O
6
S Glucocorticoid Inhalation 397864 - 44 - 7
April 2007/
GlaxoSmithKline
C
25
H
31
F
3
O
5
S
Anti - infl ammatory
agent
Bronchodilator agent
Anti - allergic agent
Glucocorticoid
Topical ointment
and cream
Inhalation
80474 - 14 - 2
Dec. 1990/
Altana
GlaxoSmithKline
Roxane
Apotex
Taro Pharms Inds
Perrigo New York
G and W Labs
Tolmar
KV Pharm
Glaxo Grp. Ltd.
554 Fluorine in Medicinal Chemistry and Chemical Biology
Active ingredient/
trade name
Chemical name Structure
Fluvastatin Sodium/
Lescol
sodium ( E ,3 S ,5 R ) - 7 - [3 - (4 -
fl uorophenyl) - 1 - propan - 2 -
yl - indol - 2 - yl] - 3,5 - dihydroxy -
hept - 6 - enoate
N
O
O
F
OH
OH
Na
Fluvoxamine Maleate
but - 2 - enedioic acid;
2 - [[5 - methoxy - 1 - [4 -
(trifl uoromethyl)phenyl]
pentylidene]amino]
oxyethanamine
O
CF
3
N
O
H
2
N
OH
OH
O
O
Fulvestrant/
Faslodex
7 α - [9 - (4,4,5,5,5 -
pentafl uoropentylsulfi nyl)
nonyl]estra - 1,3,5 - (10) -
triene - 3,17 β - diol
HO
OH
(CH
2
)
9
SO(CH
2
)
3
CF
2
CF
3
Gatifl oxacin/
Zymar
1 - cyclopropyl - 6 - fl uoro - 8 -
methoxy - 7 - (3 -
methylpiperazin - 1 - yl) - 4 -
oxo - quinoline - 3 - carboxylic
acid
HN
N
N
F
O
O O
OH
Gefi tinib/
Iressa
N - (3 - chloro - 4 - fl uorophenyl) - 7 -
methoxy - 6 - [3 - 4 - morpholin)
propoxy](4 - quinazolinamine)
O
O
O
N
N
N
HN
F
Cl
Gemcitabine Hydrochloride/
Gemzar
2 ′ - deoxy - 2 ′ ,2 ′ - difl uorocytidine
monohydrochloride
( β - isomer)
N
N
O
OH
HO
F
F
O
NH
2
HCl
Fluorine-containing Drugs for Human Use Approved by FDA in the United States 555
Formula Pharmaceutical action Dosage form CAS No. Approval date/
drug sponsor
C
24
H
25
FNO
4
Na
Antilipemic
Anticholesteremic
agent
Hydroxymethylglutaryl -
CoA reductase
inhibitor
Oral capsule and
tablet
93957 - 55 - 2
Dec. 1993/
Novartis
C
19
H
25
F
3
N
2
O
6
Antidepressant
Anti - anxiety agent
Serotonin uptake
inhibitor
Oral tablet 61718 - 82 - 9
Nov. 2000/
Mylan
Actavis Elizabeth
Barr
Caraco
Genpharm
IVAX Pharms
Sandoz
Synthon Pharms
Maleate Teva
Maleate Torpharm
C
32
H
47
F
5
O
3
S
Estrogen antagonist
Antineoplastic agent
Injectable 129453 - 61 - 8
April 2002/
Astrazeneca
C
19
H
22
FN
3
O
4
Antibacterial agent
Ophthalmic drops
Oral tablet
3
112811 - 59 - 3
March 2003/
Allergan
C
22
H
24
ClFN
4
O
3
Anilinoquinazoline
Antineoplastic Agent
Oral tablet 184475 - 35 - 2
May 2003/
Astrazeneca
C
9
H
11
F
2
N
3
O
4
⋅ HCl
Antineoplastic agent
Enzyme inhibitor
Antiviral agent
Injectable 122111 - 03 - 9
May 1996/
Lilly
556 Fluorine in Medicinal Chemistry and Chemical Biology
Active ingredient/
trade name
Chemical name Structure
Gemifl oxacin Mesylate/
Factive
( R , S ) - 7 - [(4Z) - 3 - (aminomethyl) -
4 - (methoxyimino) - 1 -
pyrrolidinyl] - 1 - cyclopropyl -
6 - fl uoro - 1,4 - dihydro
- 4 - oxo - 1,8 - naphthyridine - 3 -
carboxylic acid
N N N
O
N
H
2
N
H
3
CO
F
CO
2
H
CH
3
SO
3
H
Grepafl oxacin
Hydrochloride
∆
/
Raxaar
1 - cyclopropyl - 6 - fl uoro - 5 -
methyl - 7 - (3 - methylpiperazin -
1 - yl) - 4 - oxo - 2,3 -
dihydroquinoline - 3 -
carboxylic acid
hydrochloride
N
HO
N
F
NH
O O
HCl
Halazepam
∆
/
Paxipam
7 - chloro - 5 - phenyl - 1 - (2,2,2 -
trifl uoroethyl) - 3 H - 1,4 -
benzodiazepin - 2 - one
N
N
Cl
F
F
F
O
Halcinonide/
Halog
(11 β ,16 α ) - 21 - chloro - 9 - fl uoro -
11 - hydroxy - 16,17 - [(1 -
methylethylidene)bis(oxy)] -
pregn - 4 - ene - 3,20 - dione
O
O
O
HO
H
F
H
O
Cl
Halobetasol Propionate/
Ultravate
(11 β ,16 α ) - 21 - chloro - 9 - fl uoro -
11 - hydroxy - 16 - methyl - 17 -
(1 - oxopropoxy)pregn -
1,4 - diene - 3,20 - dione
O
O
O
HO
H
F
H
O
Cl
F
Fluorine-containing Drugs for Human Use Approved by FDA in the United States 557
Formula Pharmaceutical action Dosage form CAS No. Approval date/
drug sponsor
C
18
H
20
FN
5
O
4
⋅
CH
4
O
3
S
Antibacterial agent Oral tablet 204519 - 65 - 3
April 2003/
Oscient
C
19
H
22
FN
3
O
3
⋅ HCl
Antibacterial agent Oral tablet 161967 - 81 - 3
Nov. 1997/
Otsuka
C
17
H
12
ClF
3
N
2
O
Anti - anxiety agent
Sedative
Oral tablet 23092 - 17 - 3
Sept. 1981/
Schering
C
24
H
32
ClFO
5
Anti - infl ammatory
agent
Glucocorticoid
Topical cream,
ointment, and
solution
3093 - 35 - 4
Nov. 1974/
Ranbaxy
C
25
H
31
ClF
2
O
5
Glucocorticoid
Vasoconstrictor agent
Topical cream
and ointment
66852 - 54 - 8
Dec. 1990/
Ranbaxy
Altana
Perrigo Israel
Taro
G and W Labs
558 Fluorine in Medicinal Chemistry and Chemical Biology
Active ingredient/
trade name
Chemical name Structure
Halofantrine Hydrochloride/
Halfan
∆
1,3 - dichloro - α - [2 -
(dibutylamino) ethyl] - 6 -
(trifl uoromethyl) - 9 -
phenanthrene - methanol
hydrochloride
F
3
C
Cl
Cl
HO
N
HCl
Haloperidol
4 - [4 - (4 - chlorophenyl) - 4 -
hydroxy - 1 - piperidyl] - 1 - (4 -
fl uorophenyl)butan - 1 - one
F
N
O
HO
Cl
Haloperidol Decanoate/
Haldol
[4 - (4 - chlorophenyl) - 1 - [4 - (4 -
fl uorophenyl) - 4 - oxo - butyl] -
4 - piperidyl] decanoate
F
N
O
O
Cl
O
7
Haloperidol Lactate/
Haldol
4 - [4 - (4 - chlorophenyl) - 4 -
hydroxy - 1 - piperidyl] - 1 - (4 -
fl uorophenyl)butan - 1 -
one;2 - hydroxypropanoic
acid
F
N
O
O
Cl
O
HO
Fluorine-containing Drugs for Human Use Approved by FDA in the United States 559
Formula Pharmaceutical action Dosage form CAS No. Approval date/
drug sponsor
C
26
H
30
Cl
2
F
3
NO ⋅
HCl
Antimalarial Oral tablet 36167 - 63 - 2
July 1992/
GlaxoSmithKline
C
21
H
23
ClFNO
2
Antiemetics
Antipsychotic agent
Dopamine antagonist
Anti - dyskinesia agent
Oral tablet 52 - 86 - 8
April 1967/
Mylan
Par Pharm
Sandox
Watson Labs
C
31
H
41
ClFNO
3
Antipsychotic agent Injectable 74050 - 97 - 8
Jan. 1986/
Ortho McNeil
Abraxis Pharm
Apotex Inc.
Bedford
Sandoz
Sicor Pharms
C
24
H
27
ClFNO
4
Oral concentrate
and solution
Injectable
75478 - 79 - 4
July 1959/
Ortho McNeil
Teva Pharms
Watsons Labs
Pharm Assoc.
Silarx
560 Fluorine in Medicinal Chemistry and Chemical Biology
Active ingredient/
trade name
Chemical name Structure
Halothane
∆
/
Fluothane
2 - bromo - 2 - chloro - 1,1,
1 - trifl uoroethane
Br
ClF
F
F
Hydrofl umethiazide/
Salutensin
∆
Saluron
Diucardin
∆
1,1 - dioxo - 6 - (trifl uoromethyl) -
3,4 - dihydro - 2 H - benzo[ e ]
[1,2,4]thiadiazine - 7 -
sulfonamide
S
NH
H
N
S
F
3
C
NH
2
O
O
O O
Isofl urane
V
/
Forane
2 - chloro - 2 - (difl uoromethoxy) -
1,1,1 - trifl uoroethane
O
F
F
F
Cl
F
F
Isofl urophate/
Floropryl
∆
2 - (fl uoro - propan - 2 -
yloxyphosphoryl)oxypropane
O
P
O
F
O
Lansoprazole/
Prevacid
2 - [[3 - methyl - 4 - (2,2,2 -
trifl uoroethoxy)pyridin - 2 - yl]
methylsulfi nyl] - 1 H -
benzoimidazole
NH
N
S
N
O
F
3
C
O
Lapatinib Ditosylate/
Tykerb
N - [3 - chloro - 4 - [(3 - fl uorophenyl)
methoxy]phenyl] - 6 - [5 - [(2 -
methylsulfonylethylamino)
methyl]furan - 2 - yl]quinazolin -
4 - amine; 4 -
methylbenzenesulfonic acid;
hydrate
N
N
HN
O
O
HN
S
O
O
Cl
S
O
O
OH
S
OO
OH
H
2
O
F
Fluorine-containing Drugs for Human Use Approved by FDA in the United States 561
Formula Pharmaceutical action Dosage form CAS No. Approval date/
drug sponsor
C
2
HBrClF
3
Anesthetic Inhalation 151 - 67 - 7
March 1958/
Wyeth Ayerst
∆
Hospira
∆
C
8
H
8
F
3
N
3
O
4
S
2
Antihypertensive agent
Diuretic
Sodium chloride
symporter inhibitor
Oral tablet 135 - 09 - 1
July 1959/
Shire
Wyeth
∆
Watson Labs
∆
Par Pharm
C
3
H
2
ClF
5
O Anesthetic Inhalation 26675 - 46 - 7
Dec. 1979/
Baxter Hlthcare
Corp.
Halocarbon Prods
Hospira
Marsam Pharms
LLCC
Minrad
Rhodia
C
6
H
14
FO
3
P
Cholinesterase
inhibitor
Miotic
protease inhibitor
Ophthalmic
ointment
55 - 91 - 4
April 1957/
Merck
C
16
H
14
F
3
N
3
O
2
S
Anti - infective agent
Anti - ulcer agent
Enzyme inhibitor
Oral capsule and
tablet
Injectable
103577 - 45 - 3
May 1995/
Tap Pharm
C
43
H
44
ClFN
4
O
11
S
3
Antineoplastic agent
Protein kinase inhibitor
Oral tablet 388082 - 78 - 8
March 2007/
GlaxoSmithKline
562 Fluorine in Medicinal Chemistry and Chemical Biology
Active ingredient/
trade name
Chemical name Structure
Lefl unomide/
Arava
5 - methyl - N - [4 -
(trifl uoromethyl)phenyl] -
1,2 - oxazole - 4 - carboxamide
HN
O
O
N
F
3
C
Levocabastine
Hydrochloride/
Livostin
∆
(3 S ,4 R ) - 1 - [4 - cyano - 4 - (4 -
fl uorophenyl)cyclohexyl] - 3 -
methyl - 4 - phenylpiperidine -
4 - carboxylic acid
hydrochloride
N
N
O
HO
F
• HCl
Levofl oxacin/
Levaquin
Quixin
Iquix
( - ) - ( S ) - 9 - fluoro - 2,3 - dihydro - 3 - methyl -
10 - (4 - methyl - 1 - piperazinyl) -
7 - oxo - 7 H - pyrido(1,2,3 - de ) -
1,4 - benzoxazine - 6 - carboxylic
acid
N
O
OHO
O
N
F
N
Linezolid/
Zyvox
N - [[3 - (3 - fl uoro - 4 -
morpholinylphenyl) - 2 -
oxooxazolidin - 5 - yl]
methyl]acetamide
O
N
F
N
O
O
NH
O
Lomefl oxacin
Hydrochloride/
Maxaquin
1 - ethyl - 6,8 - difl uoro - 7 - (3 -
methyl - 1 - piperazinyl) - 4 - oxo -
3 - quinolinecarboxylic acid
hydrochloride
N
CO
2
H
N
F
HN
F
O
• HCl