IP Library › Granted Patent US 8,227,601
Granted Patent B2
US 8,227,601 · App. 11/919,786 · Granted Jul 24, 2012

Diaryl-purines, azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitor for treatment of HIV

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Quick Facts
Patent No.
US 8,227,601
App. No.
11/919,786
Granted
Jul 24, 2012
Kind
B2
Abstract

This application concerns certain 2-phenylamino-6-aryl amino-, 6-aryloxy-, and 6-arylthio-purines, -azapurines and -deazapurines. These compounds are non-nucleoside reverse transcriptase inhibitors and have potential as anti-HIV treatment.

Claims (1364)

1. A compound of formula

where

the dashed line represents a double bond between either A and B or B and D,

T′ is O or S;

A is ═CZ;

B is ═CH;

D is NW;

Z is H, F, Cl, Br, CH 3 , CH 2 CH 3 , cyclopropyl, or benzyl, the phenyl moiety of said benzyl optionally substituted with one or two groups selected independently from methyl and methoxy;

W is H, Br, methyl, ethyl, cyclopropyl, allyl, CH 2 CF 3 , cyanomethyl, CH 2 CH 2 CN, CH═CHCN, or benzyl, the phenyl moiety of said benzyl optionally substituted with one or two groups selected independently from methyl and methoxy;

V is F, Cl, CN, SO 2 CH 3 , SO 2 NH 2 , SO 2 NHCH 3 , C≡CCH 3 , or CH═CHCN;

Ar is (a), (b), (c), or (d) below

where

the dashed lines in (a) represent optional double bonds;

R P is Cl, Br, I, CN, methyl, ethyl, n-propyl, isopropyl, cyclopropylmethyl, C 3 -C 6 cycloalkyl, CH═CHCN, acetyl, or NH—C 1 -C 6 alkyl, said alkyl and cycloalkyl, groups optionally substituted with methyl, methoxy, halogen, or cyano;

R 4 , R 5 , and R 6 are, independently, H, F, Cl, Br, CH 3 , CH 2 F, CHF 2 , CF 3 , isopropyl, cyclopropyl, OCH 3 , OH, OCF 3 , NH 2 and NHCH 3 ,

or R 6 and R p on adjacent ring atoms, together with the ring atoms to which they are attached, form an additional fused five-membered ring;

Q and Q′ are, independently, N or CH;

R 7 is Cl, Br, I, CH, CF 3 , OCH 3 , isopropyl, cyclopropyl, t-butyl, or cyclobutyl; and

R 8 , R 9 , R 10 and R 11 are, independently, H or CH 3 .

2. The compound of claim 1 , wherein Ar is (a) or (c).

3. The compound of claim 2 , where R 6 either is H or is in the 2-position.

4. The compound of claim 1 , which is a compound of formula IA-1

5. The compound of claim 1 , where

V is CN, and where

W is, H, methyl, Br, or benzyl,

Z is, H, methyl, Cl, Br, or benzyl.

6. The compound of claim 3 which is a compound of formula IA-1a

7. The compound of claim 6 , Where

V is CN or CH═CHCN,

R 6 is methyl, methoxy, or chloro and

R 7 is 6-methyl, or 6-methoxy.

8. The compound of claim 7 , where R P is CN, cyclopropyl, methyl, Br, Cl, CH═CHCN, or acetyl.

9. The compound of claim 8

where

V is CN,

W is H, methyl, ethyl, or benzyl, and

Z is H, chloro, bromo, methyl, or ethyl.

10. A compound of formula IB

where

the dashed line represents a double bond between either A and B or B and D, and where

A is CZ;

B is CH;

D is NW;

Z is H, F, Cl, Br, CH 3 , CH 2 CH 3 , cyclopropyl, or benzyl, the phenyl moiety of said benzyl optionally substituted with methyl or methoxy;

W is H, Br, methyl, ethyl, cyclopropyl, allyl, CH 2 CF 3 , cyanomethyl, CH 2 CH 2 CN, CH═CHCN, or benzyl, the phenyl moiety of said benzyl optionally substituted with methyl or methoxy;

V is F, Cl, CN, SO 2 CH 3 , SO 2 NH, SO 2 NHCH 3 , C≡CCH 3 , or CH═CHCN,

and Ar is (a), (b), or (d) below:

where

R p is Cl, Br, I, CN, methyl, ethyl, n-propyl, isopropyl, cyclopropylmethyl, C 3 -C 6 cycloalkyl, CH═CHCN, acetyl, or NH—C 1 -C 6 alkyl, said alkyl and cycloalkyl groups optionally substituted with methyl, methoxy, halogen, or cyano;

R 4 , R 5 , and R 6 are, independently; H, F, Cl, Br, CH 3 , CH 2 F, CHF 2 , CF 3 , isopropyl, cyclopropyl, OCH 3 , OH, OCF 3 , NH 2 and NHCH 3 ;

Q and Q′ are, independently, N or CH;

R 8 , R 9 , R 10 , R 11 are, independently, H or CH 3 .

11. A compound of formula IB-1

where

the dashed line represents a double bond between either A,and B or B and D;

A is CZ;

B is CH

D is NW;

Z is H, F, Cl, Br, CH 3 , CH 2 CH 3 , cyclopropyl, or benzyl, the phenyl moiety of said benzyl optionally substituted with methyl or methoxy;

W is H, Br, methyl, ethyl, cyclopropyl, allyl, CH 2 CF 3 , CH 2 CN, CH 2 CH 2 CN, CH═CHCN, or benzyl, the phenyl moiety of said benzyl optionally substituted with methyl or methoxy;

V is F, Cl, CN, SO 2 CH 3 , SO 2 NH 2 , SO 2 NHCH 3 , C≡CCH 3 , or CH═CHCN;

R p is Cl, Br, I, CN, CH═CHCN, methyl, ethyl, n-propyl, isopropyl, cyclopropylmethyl, C 3 -C 6 cycloalkyl, acetyl, and NH—C 3 -C 6 alkyl;

R 6 is H, F, Cl, Br, CH 3 , CH 2 F, CHF 2 , CF 3 , isopropyl, cyclopropyl, OCH 3 , OH, OCF 3 , NH 2 and NHCH 3 ;

R 7 is Cl, Br, I, CH 3 , CF 3 , OCH 3 , isopropyl, cyclopropyl, t-butyl, or cyclobutyl.

12. The compound of claim 11 , where

V is CN or CH═CHCN,

R 6 is 2-methyl, 2-methoxy, or 2-chloro and

R 7 is 6-methyl, or 6-methoxy.

13. The compound of claim 12 , where R p is CN, cyclopropyl, methyl, Br, Cl, CH═CHCN, or acetyl.

14. The compound of claim 4 which is selected from compounds in Table 1:

Ar

V

W

Z

o,o′-diCH 3 O-p-(CH═CECN)phenyl

CN

H

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

benzyl

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

benzyl

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

3-Me-benzyl

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

4-Me-benzyl

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

3-MeO-benzyl

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

4-MeO-benzyl

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

H

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

H

Br

o,o′,diCH 3 O-p-(CH═CHCN)phenyl

CN

cyclopropyl

CH 2 CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

CH 2 CF 3

CH 2 CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

H

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

benzyl

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

benzyl

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

3-Me-benzyl

cyclopropyl

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

3-MeO-benzyl

benzyl

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

H

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

C≡CCH 3

CH 2 CH 3

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

Cl

CH 2 CH═CH 2

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 CH 3

CH 2 CH═CH 2

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

Cl

CH 2 CH 3

CH 2 CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

Cl

H

H

4-cyclopropylnaphth-1-yl

CN

H

CH 3

4-cyclopropylnaphth-1-yl

CN

benzyl

CH 3

4-cyclopropylnaphth-1-yl

CN

benzyl

H

4-cyclopropylnaphth-1-yl

CN

H

H

4-cyclopropylnaphth-1-yl

CH═CHCN

H

CH 3

4-cyclopropylnaphth-1-yl

CH═CHCN

benzyl

CH 3

4-cyclopropylnaphth-1-yl

CH═CHCN

benzyl

H

4-cyclopropylnaphth-1-yl

CH═CHCN

H

H

4-cyclopropylnaphth-1-yl

SO 2 NHCH 3

CH 2 CN

F

4-cyclopropylnaphth-1-yl

SO 2 NHCH 3

cyclopropyl

Cl

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

CH 2 CH 2 CN

Br

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

CH 2 CN

benzyl

o,o′-di-CH 3 O-p-CN-phenyl

C≡CCH 3

3-MeO-benzyl

F

o,o′-di-CH 3 O-p-CN-phenyl

F

3-Me-benzyl

Cl

o,o′-di-CH 3 O-p-CN-phenyl

CN

H

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

CN

benzyl

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

CN

benzyl

H

o,o′-di-CH 3 O-p-CN-phenyl

CN

H

H

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

H

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

benzyl

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

benzyl

H

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

H

H

o,o′-di-CH 3 -p-CN-phenyl

CN

H

CH 3

o,o′-di-CH 3 -p-CN-phenyl

CN

benzyl

CH 3

o,o′-di-CH 3 -p-CN-phenyl

CN

3,5-di MeO-benzyl

CH 3

o,o′-dt-CH 3 -p-CN-phenyl

CN

benzyl

o,o′-di-CH 3 -p-CN-phenyl

CN

H

H

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

H

CH 3

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

benzyl

CH 3

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

benzyl

H

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

H

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

H

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

benzyl

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

benzyl

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

H

F

4-cyclopropylnaphth-1-yl

CN

H

F

4-cyclopropylnaphth-1-yl

CN

benzyl

F

4-cyclopropylnaphth-1-yl

CH═CHCN

H

F

4-cyclopropylnaphth-1-yl

CH═CHCN

benzyl

F

o,o′-di-CH 3 O-p-CN-phenyl

CN

H

F

o,o′-di-CH 3 O-p-CN-phenyl

CN

benzyl

F

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

H

F

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

benzyl

F

o,o′-di-CH 3 -p-CN-phenyl

CN

H

F

o,o′-di-CH 3 -p-CN-phenyl

CN

benzyl

F

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

H

F

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

benzyl

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

H

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

benzyl

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

benzyl

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

H

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

H

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

F

benzyl

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

F

benzyl

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

F

H

H

4-cyclopropylnaphth-1-yl

SO 2 NH 2

H

CH 3

4-cyclopropylnaphth-1-yl

SO 2 NH 2

benzyl

CH 3

4-cyclopropylnaphth-1-yl

SO 2 NH 2

benzyl

H

4-cyclopropylnaphth-1-yl

SO 2 NH 2

H

H

4-cyclopropylnaphth-1-yl

F

H

CH 3

4-cyclopropylnaphth-1-yl

F

benzyl

CH 3

4-cyclopropylnaphth-1-yl

F

benzyl

H

4-cyclopropylnaphth-1-yl

F

H

H

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

H

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

benzyl

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

benzyl

H

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

H

H

o,o′-di-CH 3 O-p-CN-phenyl

F

H

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

F

benzyl

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

F

benzyl

H

o,o′-di-CH 3 O-p-CN-phenyl

F

H

H

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

H

CH 3

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

benzyl

CH 3

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

3-Me-benzyl

CH 3

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NHCH 3

benzyl

H

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

benzyl

H

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

H

H

o,o′-di-CH 3 -p-CN-phenyl

F

H

CH 3

o,o′-di-CH 3 -p-CN-phenyl

F

benzyl

CH 3

o,o′-di-CH 3 -p-CN-phenyl

F

benzyl

H

o,o′-di-CH 3 -p-CN-phenyl

F

H

H

o,o′-di-CH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

H

F

o,o′-di-CH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

benzyl

F

o,o′-di-CH 3 O-p-(CH═CHCN)phenyl

F

benzyl

F

o,o′-di-CH 3 O-p-(CH═CHCN)phenyl

F

H

F

4-cyclopropylnaphth-1-yl

SO 2 NH 2

H

F

4-cyclopropylnaphth-1-yl

SO 2 NH 2

benzyl

F

4-cyclopropylnaphth-1-yl

F

H

F

4-cyclopropylnaphth-1-yl

F

benzyl

F

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

H

F

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

benzyl

F

o,o′-di-CH 3 O-p-CN-phenyl

F

H

F

o,o′-di-CH 3 O-p-CN-phenyl

F

benzyl

F

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

H

F

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

benzyl

F

o,o′-di-CH 3 -p-CN-phenyl

F

H

F

o,o′-di-CH 3 -p-CN-phenyl

F

benzyl

F

2,4,6-trimethyl phenyl

CN

H

CH 3

2,4,6-trimethyl phenyl

CN

benzyl

CH 3

2,4,6-trimethyl phenyl

CN

benzyl

H

2,4,6-trimethyl phenyl

CN

H

H

2,4,6-trimethyl phenyl

CH═CHCN

H

CH 3

2,4,6-trimethyl phenyl

CH═CHCN

benzyl

CH 3

2,4,6-trimethyl phenyl

CH═CHCN

benzyl

H

2,4,6-trimethyl phenyl

CH═CHCN

H

H

2,4,6-trimethyl phenyl

CN

H

F

2,4,6-trimethyl phenyl

CN

benzyl

F

2,4,6-trimethyl phenyl

CH═CHCN

H

F

2,4,6-trimethyl phenyl

CHCHCN

benzyl

F

2,4,6-trimethyl phenyl

SO 2 NH 2

H

CH 3

2,4,6-trimethyl phenyl

SO 2 NH 2

benzyl

CH 3

2,4,6-trimethyl phenyl

SO 2 NH 2

benzyl

H

2,4,6-trimethyl phenyl

SO 2 NH 2

H

H

2,4,6-trimethyl phenyl

F

H

CH 3

2,4,6-trimethyl phenyl

F

benzyl

CH 3

2,4,6-trimethyl phenyl

F

benzyl

H

4-cyclopropyl phenyl

F

H

H

4-cyclopropyl phenyl

SO 2 NH 2

H

F

4-cyclopropyl phenyl

SO 2 NH 2

benzyl

F

4-cyclopropyl phenyl

F

H

F

4-cyclopropyl phenyl

F

benzyl

F

o,o′-dimethyl-p-cyclopropyl phenyl

CN

H

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

CN

benzyl

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

CN

benzyl

H

o,o′-dimethyl-p-cyclopropyl phenyl

CN

H

H

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

H

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

benzyl

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

benzyl

H

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

H

H

o,o′-dimethyl-p-cyclopropyl phenyl

CN

H

F

o,o′-dimethyl-p-cyclopropyl phenyl

CN

benzyl

F

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

H

F

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

benzyl

F

o,o′-dimethyl-p-cyclopropyl phenyl

SO 2 NH 2

H

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

SO 2 NH 2

benzyl

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

SO 2 NH 2

benzyl

H

o,o′-dimethyl-p-cyclopropyl phenyl

SO 2 NH 2

H

H

o,o′-dimethyl-p-cyclopropyl phenyl

F

H

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

F

benzyl

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

F

benzyl

H

o,o′-dimethyl-p-cyclopropyl phenyl

F

H

H

o,o′-dimethyl-p-cyclopropyl phenyl

SO 2 NH 2

H

F

o,o′-dimethyl-p-cyclopropyl phenyl

SO 2 NH 2

benzyl

F

o,o′-dimethyl-p-cyclopropyl phenyl

F

H

F

o,o′-dimethyl-p-cyclopropyl phenyl

F

benzyl

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

CH 3

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

cyclopropyl

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

cyclopropyl

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

CH 3

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

CH 3

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

cyclopropyl

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

cyclopropyl

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

CH 3

H

4-cyclopropylnaphth-1-yl

CN

CH 3

CH 3

4-cyclopropylnaphth-1-yl

CN

cyclopropyl

CH 3

4-cyclopropylnaphth-1-yl

CN

cyclopropyl

H

4-cyclopropylnaphth-1-yl

CN

CH 3

H

4-cyclopropylnaphth-1-yl

CH═CHCN

CH 3

CH 3

4-cyclopropylnaphth-1-yl

CH═CHCN

cyclopropyl

CH 3

4-cyclopropylnaphth-1-yl

CH═CHCN

cyclopropyl

H

4-cyclopropylnaphth-1-yl

CH═CHCN

CH 3

H

o,o′-di-CH 3 O-p-CN-phenyl

CN

CH 3

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

CN

cyclopropyl

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

CN

cyclopropyl

H

o,o′-di-CH 3 O-p-CN-phenyl

CN

CH 3

H

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

CH 3

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

cyclopropyl

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

cyclopropyl

H

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

CH 3

H

o,o′-di-CH 3 -p-CN-phenyl

CN

CH 3

CH 3

o,o′-di-CH 3 -p-CN-phenyl

CN

cyclopropyl

CH 3

o,o′-di-CH 3 -p-CN-phenyl

CN

cyclopropyl

H

o,o′-di-CH 3 -p-CN-phenyl

CN

CH 3

H

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

CH 3

CH 3

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

cyclopropyl

CH 3

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

cyclopropyl

H

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

CH 3

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

CH 3

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CN

cyclopropyl

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

cyclopropyl

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

CH═CHCN

CH 3

F

4-cyclopropylnaphth-1-yl

CN

CH 3

F

4-cyclopropylnaphth-1-yl

CN

cyclopropyl

F

4-cyclopropylnaphth-1-yl

CH═CHCN

CH 3

F

4-cyclopropylnaphth-1-yl

CH═CHCN

cyclopropyl

F

o,o′-di-CH 3 O-p-CN-phenyl

CN

CH 3

F

o,o′-di-CH 3 O-p-CN-phenyl

CN

cyclopropyl

F

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

CH 3

F

o,o′-di-CH 3 O-p-CN-phenyl

CH═CHCN

cyclopropyl

F

o,o′-di-CH 3 -p-CN-phenyl

CN

CH 3

F

o,o′-di-CH 3 -p-CN-phenyl

CN

cyclopropyl

F

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

CH 3

F

o,o′-di-CH 3 -p-CN-phenyl

CH═CHCN

cyclopropyl

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

CH 3

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

cyclopropyl

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

cyclopropyl

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

CH 3

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NHCH 3

CH 3

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

F

cyclopropyl

CH 3

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

F

cyclopropyl

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

F

CH 3

H

4-cyclopropylnaphth-1-yl

SO 2 NH 2

CH 3

CH 3

4-cyclopropylnaphth-1-yl

SO 2 NH 2

cyclopropyl

CH 3

4-cyclopropylnaphth-1-yl

SO 2 NH 2

cyclopropyl

H

4-cyclopropylnaphth-1-yl

SO 2 NH 2

CH 3

H

4-cyclopropylnaphth-1-yl

F

CH 3

CH 3

4-cyclopropylnaphth-1-yl

F

cyclopropyl

CH 3

4-cyclopropylnaphth-1-yl

F

cyclopropyl

H

4-cyclopropylnaphth-1-yl

F

CH 3

H

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

CH 3

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NHCH 3

CH 3

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

cyclopropyl

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

cyclopropyl

H

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

CH 3

H

o,o′-di-CH 3 O-p-CN-phenyl

F

CH 3

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

F

cyclopropyl

CH 3

o,o′-di-CH 3 O-p-CN-phenyl

F

cyclopropyl

H

o,o′-di-CH 3 O-p-CN-phenyl

F

CH 3

H

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

CH 3

CH 3

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

cyclopropyl

CH 3

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

cyclopropyl

H

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

CH 3

H

o,o′-di-CH 3 -p-CN-phenyl

F

CH 3

CH 3

o,o′-di-CH 3 -p-CN-phenyl

F

cyclopropyl

CH 3

o,o′-di-CH 3 -p-CN-phepyl

F

cyclopropyl

H

o,o′-di-CH 3 -p-CN-phenyl

F

CH 3

H

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

CH 3

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

SO 2 NH 2

cyclopropyl

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

F

cyclopropyl

F

o,o′-diCH 3 O-p-(CH═CHCN)phenyl

F

CH 3

F

4-cyclopropylnaphth-1-yl

SO 2 NH 2

CH 3

F

4-cyclopropylnaphth-1-yl

SO 2 NH 2

cyclopropyl

F

4-cyclopropylnaphth-1-yl

F

CH 3

F

4-cyclopropylnaphth-1-yl

F

cyclopropyl

F

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

CH 3

F

o,o′-di-CH 3 O-p-CN-phenyl

SO 2 NH 2

cyclopropyl

F

o,o′-di-CH 3 O-p-CN-phenyl

F

CH 3

F

o,o′-di-CH 3 O-p-CN-phenyl

F

cyclopropyl

F

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

CH 3

F

o,o′-di-CH 3 -p-CN-phenyl

SO 2 NH 2

cyclopropyl

F

o,o′-di-CH 3 -p-CN-phenyl

F

CH 3

F

o,o′-di-CH 3 -p-CN-phenyl

F

cyclopropyl

F

4-cyclopropyl phenyl

CN

CH 3

CH 3

2,4,6-trimethyl phenyl

CN

cyclopropyl

CH 3

2,4,6-trimethyl phenyl

CN

cyclopropyl

H

2,4,6-trimethyl phenyl

CN

CH 3

H

2,4,6-trimethyl phenyl

CH═CHCN

CH 3

CH 3

2,4,6-trimethyl phenyl

CH═CHCN

cyclopropyl

CH 3

2,4,6-trimethyl phenyl

CH═CHCN

cyclopropyl

H

2,4,6-trimethyl phenyl

CH═CHCN

CH 3

H

2,4,6-trimethyl phenyl

CN

CH 3

F

2,4,6-trimethyl phenyl

CN

cyclopropyl

F

2,4,6-trimethyl phenyl

CH═CHCN

CH 3

F

2,4,6-trimethyl phenyl

CH═CHCN

cyclopropyl

F

2,4,6-trimethyl phenyl

SO 2 NH 2

CH 3

CH 3

2,4,6-trimethyl phenyl

SO 2 NH 2

cyclopropyl

CH 3

2,4,6-trimethyl phenyl

SO 2 NH 2

cyclopropyl

H

2,4,6-trimethyl phenyl

SO 2 NH 2

CH 3

H

2,4,6-trimethyl phenyl

F

CH 3

CH 3

2,4,6-trimethyl phenyl

F

cyclopropyl

CH 3

2,4,6-trimethyl phenyl

F

cyclopropyl

H

4-cyclopropyl phenyl

F

CH 3

H

4-cyclopropyl phenyl

SO 2 NH 2

CH 3

F

4-cyclopropyl phenyl

SO 2 NH 2

cyclopropyl

F

4-cyclopropyl phenyl

F

CH 3

F

4-cyclopropyl phenyl

F

cyclopropyl

F

2,4,6-trimethyl phenyl

CN

CH 3

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

CN

cyclopropyl

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

CN

cyclopropyl

H

o,o′-dimethyl-p-cyclopropyl phenyl

CN

CH 3

H

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

CH 3

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

cyclopropyl

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

cyclopropyl

H

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

CH 3

H

o,o′-dimethyl-p-cyclopropyl phenyl

CN

CH 3

F

o,o′-dimethyl-p-cyctopropyl phenyl

CN

cyclopropyl

F

o,o′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

CH 3

F

o,0′-dimethyl-p-cyclopropyl phenyl

CH═CHCN

cyclopropyl

F

o,o′-dimethyl-p-cyclopropyl phenyl

SO 2 NH 2

CH 3

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

SO 2 NH 2

cyclopropyl

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

SO 2 NH 2

cyclopropyl

H

o,o′-dimethyl-p-cyclopropyl phenyl

SO 2 NH 2

CH 3

H

o,o′-dimethyl-p-cyclopropyl phenyl

F

CH 3

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

F

cyclopropyl

CH 3

o,o′-dimethyl-p-cyclopropyl phenyl

F

cyclopropyl

H

2,4,6-trimethyl phenyl

F

CH 3

H

2,4,6-trimethyl phenyl

SO 2 NH 2

CH 3

F

2,4,6-trimethyl phenyl

SO 2 NH 2

cyclopropyl

F

2,4,6-trimethyl phenyl

F

CH 3

F

2,4,6-trimethyl phenyl

F

cyclopropyl

F

o,o′-di-CH 3 -p-acetyl-phenyl

CN

CH 3

H

o,o′-di-CH 3 -p-acetyl-phenyl

CN

H

H

o,o′-di-CH 3 -p-acetyl-phenyl

CN

CH 3

Cl

o,o′-di-CH 3 -p-acetyl-phenyl

CN

H

Cl.

15. A compound of claim 1 , that is 4-(7-chloro-2-(4-cyanophenylamino)-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile:

16. The compound of claim 3 , wherein Ar is (c)

where

R P is Br or C 3 -cycloalkyl;

R 6 is H; and

R 7 is Cl or CH 3 ;

or

R P is CN, methyl, C 3 -cycloallcyl, CH═CHCN or acetyl;

R 6 is CH 3 ; and

R 7 is CH 3 ;

or

R P is CN or CH═CHCN;

R 6 is OCH 3 ; and

R 7 is OCH 3 ;

or

R P is C 3 -cycloalkyl;

R 6 is CF 3 ; and

R 7 is CF 3 .

17. The compound of claim 4 , wherein Ar is (c)

where

R P is Br, CN, methyl, C 3 -cycloalkyl or acetyl; and

R 6 is not H.

18. The compound of claim 3 , wherein Ar is (a)

where

the dashed lines represent double bonds;

R P is Br or C 3 -cycloalkyl; and

R 4 , R 5 and R 6 are H.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 2, 2010
From: HONG, ZHI
To: ARDEA BIOSCIENCES, INC.
Reel/Frame 023887/0943 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 3, 2009
From: GIRARDET, JEAN-LUC; KOH, YUNG-HYO; SHAW, STEPHANIE; KIM, HONG WOO
To: ARDEA BIOSCIENCES, INC.
Reel/Frame 022193/0954 →