Ojima I. (ed.) Fluorine in Medicinal Chemistry and Chemical Biology

Fluorine-containing Drugs for Human Use Approved by FDA in the United States 563

Formula Pharmaceutical action Dosage form CAS No. Approval date/

drug sponsor

C

12

H

9

F

3

N

2

O

2

Enzyme inhibitor

Immunosuppressive

agent

Antirheumatic agent

Oral tablet 75706 - 12 - 6

Sept. 1998/

Sanoﬁ Aventis US

Aptoex Inc.

Barr

Kali Labs

Sandoz

∆

Teva Products

C

26

H

30

ClFN

2

O

2

Nonsedating

antihistaminic

Ophthalmic drops 79547 - 78 - 7

Nov. 1993/

Novartis

C

18

H

20

FN

3

O

4

Antibacterial agent

Injectable

Oral solution

Ophthalmic drops

Oral tablet

100986 - 85 - 4

Dec. 1996

Aug. 2000/

Ortho McNeil

Pharm

Santen

C

16

H

20

FN

3

O

4

Anti - infective agent

Protein synthesis

inhibitor

Oral suspension

and tablet

Injectable

165800 - 03 - 3

April 2000/

Pharmacia and

Upjohn

C

17

H

20

ClF

2

N

3

O

3

Anti - infective agent Oral tablet 98079 - 52 - 8

Feb. 1992/

Pharmacia

564 Fluorine in Medicinal Chemistry and Chemical Biology

Active ingredient/

trade name

Chemical name Structure

Lubiprostone/

Amitiza

7 - [(1 R ,4 R ,6 R ,9 S ) - 4 - (1,1 -

diﬂ uoropentyl) - 4 - hydroxy -

8 - oxo - 5 - oxabicyclo[4.3.0]

non - 9 - yl]heptanoic acid

O

H

HO

H

O

F

CO

2

H

Meﬂ oquine Hydrochloride/

Lariam

2,8 - [bis(triﬂ uoromethyl)

quinolin - 4 - yl] - [(2 R ) - 2 -

piperidyl]methanol

hydrochloride

N

OH

N

H

F

3

C

CF

3

• HCl

Melperone

1 - (4 - ﬂ uorophenyl) - 4 - (4 - methyl -

1 - piperidyl)butan - 1 - one

F

N

O

Midazolam Hydrochloride

8 - chloro - 6 - (2 - ﬂ uorophenyl) - 1 -

methyl - 4 H - imidazo[1,5 a ]

[1,4]benzodiazepine

hydrochloride

• HCl

N

Cl

F

Moxiﬂ oxacin

Hydrochloride/

Avelox

Vigamox

7 - [(4a S ,7a S ) - 1,2,3,4,4a,5,7,7a -

octahydropyrrolo[3,4 - b]

pyridin - 6 - yl] - 1 - cyclopropyl -

6 - ﬂ uoro - 8 - methoxy - 4 -

oxoquinoline - 3 - carboxylic

acid hydrochloride

N

CO

2

H

O

F

• HCl

H

Fluorine-containing Drugs for Human Use Approved by FDA in the United States 565

Formula Pharmaceutical action Dosage form CAS No. Approval date/

drug sponsor

C

20

H

32

F

2

O

5

Laxative Oral capsule 136790 - 76 - 6

Jan. 2006/

Sucampo Pharms

C

17

H

17

ClF

6

N

2

O Antimalarial agent Oral tablet 51773 - 92 - 3

May 1989/

Roche

Barr

Roxane

Sandoz

US Army Walter

Reed

C

16

H

22

FNO Antipsychotic agent Oral 3575 - 80 - 2

Not approved/

Ovation

Pharmaceuticals

C

18

H

14

Cl

2

FN

3

Adjuvants, anesthesic

Hypnotic

Sedative

Anti - anxiety agent

GABA modulator

Injectable

Oral syrup

59467 - 96 - 8

June 2000/

Abraxis Pharm

Apotex Inc

Baxter Hlthcare

Bedford

Ben Venue

Hospira

Intl Medicated

Intl Medication

Mayne Pharma

USA

Taylor

Hi Tech Pharma

Paddock

Ranbaxy

Roxane

C

21

H

25

ClFN

3

O

4

Anti - infective agent

Injectable

Opthalmic drops

Oral tablet

186286 - 86 - 8

Dec. 1999/

Bayer Pharms

Alcon

566 Fluorine in Medicinal Chemistry and Chemical Biology

Active ingredient/

trade name

Chemical name Structure

Nilutamide/

Nilandron

5,5 - dimethyl - 3 - [4 - nitro - 3 -

(triﬂ uoromethyl)phenyl]

imidazolidine - 2,4 - dione

N

NH

O

CF

3

O

2

N

Nitisinone/

Orfadin

2 - [2 - nitro - 4 - (triﬂ uoromethyl)

benzoyl]cyclohexane - 1,3 -

dione

O

2

N

CF

3

O

Norﬂ oxacin/

Noroxin

1 - ethyl - 6 - ﬂ uoro - 4 - oxo - 7 -

piperazin - 1 - yl - quinoline -

3 - carboxylic acid

N

O

F

HO

2

C

NH

Oﬂ oxacin/

Ocuﬂ ox

Oﬂ oxacin

Floxin

( - ) - ( S ) - 9 - ﬂ uoro - 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

F

HO

2

C

N

O

Paliperidone/

Invega

3 - [2 - [4 - (6 -

ﬂ uorobenzo[d]isoxazol - 3 - yl) -

1 - piperidyl]ethyl] - 7 -

hydroxy - 4 - methyl - 1,5 -

diazabicyclo[4.4.0]deca -

3,5 - dien - 2 - one

N

HO

N

O

CH

3

N

O

F

Fluorine-containing Drugs for Human Use Approved by FDA in the United States 567

Formula Pharmaceutical action Dosage form CAS No. Approval date/

drug sponsor

C

12

H

10

F

3

N

3

O

4

Androgen antagonist

Antineoplastic agent

Oral tablet 63612 - 50 - 0

April 1999/

Sanoﬁ Aventis US

C

14

H

10

F

3

NO

5

Enzyme inhibitor Oral capsule 104206 - 65 - 7

Jan. 2002/

Swedish Orphan

C

16

H

18

FN

3

O

3

Anti - infective agent

Enzyme inhibitor

Oral tablet 70458 - 96 - 7

Oct. 1986/

Merck

C

18

H

20

FN

3

O

4

Anti - infective agent

Antibacterial agent

Injectable

Opthalmic drops

Oral tablet

82419 - 36 - 1

July 1993/

Bedford

Allergan

Bausch and Lomb

Hi Tech Pharma

Novex

Pharmaforce

Daiichi

Ortho McNeil

Pharm

Dr Reddys Labs

Par Pharm

Ranbaxy

Teva

C

23

H

27

FN

4

O

3

Antipsychotic agent Oral tablet 144598 - 75 - 4

Dec. 2006/

Janssen

568 Fluorine in Medicinal Chemistry and Chemical Biology

Active ingredient/

trade name

Chemical name Structure

Pantoprazole Sodium/

Protonix

sodium 5 - (diﬂ uoromethoxy) - 2 -

[[(3,4 - dimethoxy - 2 -

pyridinyl)methyl]

sulﬁ nyl] - 1 H - benzimidazole

sesquihydrate

• 1.5 H

2

O

N

S

O

N

OCF

2

H

3

CO

H

3

CO

Na

+

Paramethasone Acetate/

Haldrone

∆

[2 - [(6 S ,8 S ,9 S ,10 R ,11 S ,13 S ,14 S ,

16 R ,17 R ) - 6 - ﬂ uoro - 11,17 -

dihydroxy - 10,13,16 -

trimethyl - 3 - oxo - 7,8,9,11,12,

14,15,16 - octahydro - 6 H -

cyclopenta[a]phenanthren -

17 - yl] - 2 - oxoethyl] acetate

O

HO

H F

H

HO

H

Paroxetine Hydrochloride/

Paxil

(3 S ,4 R ) - 3 - (1,3 - benzodioxol - 5 -

yloxymethyl) - 4 - (4 -

ﬂ uorophenyl)piperidine

hydrochloride

O

H

N

F

• HCl

Paroxetine Mesylate/

Pexeva

(3 S ,4 R ) - 3 - (1,3 - benzodioxol - 5 -

yloxymethyl) - 4 - (4 -

ﬂ uorophenyl)piperidine

methanesulfonic acid

O

H

N

F

SO

OH

Fluorine-containing Drugs for Human Use Approved by FDA in the United States 569

Formula Pharmaceutical action Dosage form CAS No. Approval date/

drug sponsor

C

16

H

14

F

2

N

3

NaO

4

S

⋅ 1.5 H

2

O

Anti - ulcer agent

Injectable

Oral tablet

138786 - 67 - 1

March 2001/

Wyeth Pharms

Inc.

C

24

H

31

FO

6

Anti - inﬂ ammatory

agent

Glucocorticoid

Oral tablet 1597 - 82 - 6

Prior to 1982/

Lilly

∆

C

19

H

21

ClFNO

3

Serotonin uptake

inhibitor

Antidepressive agent

Antiobessional agent

Oral tablet and

suspension

78246 - 49 - 8

Dec. 1992/

GlaxoSmithKline

Torpharm

Apotex Inc.

Alphapharm

Sandoz

∆

Teva

Caraco

Mylan

Roxane

Zydus Pharms

USA

Aurobindo

Pharma

C

20

H

24

FNO

6

S

Antidepressive agent

Antiobessional agent

Oral tablet 64006 - 44 - 6

July 2003/

JDS Pharms

570 Fluorine in Medicinal Chemistry and Chemical Biology

Active ingredient/

trade name

Chemical name Structure

Pegaptanib Sodium/

Macugen

((2 ′ - deoxy - 2 ′ - ﬂ uoro)C - Gm - Gm -

A - A - (2 ′ - deoxy - 2 ′ - ﬂ uoro)U -

(2 ′ - deoxy - 2 ′ - ﬂ uoro)C - Am -

Gm - (2 ′ - deoxy - 2 - ﬂ uoro)U - Gm -

Am - Am - (2 ′ - deoxy - 2 ′ -

ﬂ uoro)U - Gm - (2 ′ - deoxy - 2 ′ -

ﬂ uoro)C - (2 ′ - deoxy - 2 ′ - ﬂ uoro)U -

(2 ′ - deoxy - 2 ′ - ﬂ uoro)U - Am -

(2 ′ - deoxy - 2 ′ - ﬂ uoro)U - Am - (2 ′ -

deoxy - 2 ′ - ﬂ uoro)C - Am - (2 ′ -

deoxy - 2 ′ - ﬂ uoro)U - (2 ′ - deoxy -

2 ′ - ﬂ uoro)C - (2 ′ - deoxy - 2 ′ -

ﬂ uoro)C - Gm - (3 ′ 3 ′ ) - dT),

5 ′ - ester with a, a ′ - [4,12 -

dioxo - 6 - [[[5 - (phosphoonoxy)

pentyl]amino]carbonyl] -

3,13 - dioxa - 5,11 - diaza - 1,

15 - pentadecanediyl]bis[ ω -

methoxypoly(oxy - 1,2 -

ethanediyl)], sodium salt.

Perﬂ exane

∆

1,1,1,2,2,3,3,4,4,5,5,6,6,6 -

tetradecaﬂ uorohexane

F

Perﬂ ubron/

Imagent

∆

1 - bromo - 1,1,2,2,3,3,4,4,5,5,6,

6,7,7,8,8,8 -

heptadecaﬂ uorooctane

F

Br

F

Perﬂ uoropolymethylisopropyl

Ether;

Polytetraﬂ uoroethylene

∆

Perﬂ utren/

Deﬁ nity

1,1,1,2,2,3,3,3 - octaﬂ uoropropane

CF

3

F

3

C

F

Pimozide/

Orap

3 - [1 - [4,4 - bis(4 -

ﬂ uorophenyl)butyl]piperidin -

4 - yl] - 1H - benzimidazol - 2 - one

N

H

N

O

N

F

Fluorine-containing Drugs for Human Use Approved by FDA in the United States 571

Formula Pharmaceutical action Dosage form CAS No. Approval date/

drug sponsor

C

294

H

342

F

13

N

107

Na

28

O

188

P

28

[C

2

H

4

O]

n

(where

n is

approximately

900)

Neovascular age -

related macular

degeneration (wet)

agent

Injectable 222716 - 86 - 1

Dec. 2004/

OSI Eye Tech

C

6

F

14

Preparation of lipid

microspheres

Imaging agent

Injectable 355 - 42 - 0

May 2002/

Imcor PH

C

8

BrF

17

Contrast media

Radiation - sensitizing

agent

Anti - obesity agent

Oral liquid 423 - 55 - 2

Aug. 1993/

Alliance Pharm

Chemical warfare

protectant

Topical

Feb. 2000/

US Army

C

3

F

8

Contrast media Injectable 76 - 19 - 7

July 2001/

Bristol Myers

Squibb

C

28

H

29

F

2

N

3

O

Antipsychotic agent

Dopamine antagonist

Anti - dyskinesia agent

Oral tablet 2062 - 78 - 4

July 1984/

Teva

572 Fluorine in Medicinal Chemistry and Chemical Biology

Active ingredient/

trade name

Chemical name Structure

Polythiazide/

Renese

Minizide

6 - chloro - 2 - methyl - 1,

1 - dioxo - 3 - (2,2,2 -

triﬂ uoroethylsulfanylmethyl) -

3,4 - dihydrobenzo[ e ][1,2,4]

thiadiazine - 7 - sulfonamide

N

O

2

S

NH

Cl

SO

2

H

2

N

S

CF

3

Posaconazole/

Noxaﬁ l

4 - [4 - [4 - [4 - [[(5 R ) - 5 - (2,4 -

diﬂ uorophenyl) - 5 - (1,2,4 -

triazol - 1 - ylmethyl)oxolan -

3 - yl]methoxy]phenyl]piperazin -

1 - yl]phenyl] - 2 - [(2 S ,3 S ) - 2 -

hydroxypentan - 3 - yl] - 1,2,4 -

triazol - 3 - one

O

F

N

O

OH

N

Quazepam/

Doral

7 - chloro - 5 - (2 - ﬂ uorophenyl) - 1 -

(2,2,2 - triﬂ uoroethyl) - 3 H - 1,4 -

benzodiazepine - 2 - thione

N

S

F

3

C

F

Cl

Riluzole/

Rilutek

6 - (triﬂ uoromethoxy) - 1,3 -

benzothiazol - 2 - amine

NS

O

NH

2

CF

3

Ojima I. (ed.) Fluorine in Medicinal Chemistry and Chemical Biology

Подождите немного. Документ загружается.