Kinase inhibitors and their uses

Abstract

The present disclosure provides compounds that inhibit protein kinases, such as JAK, Axl, or Syk kinases, compositions comprising the compounds and methods of using the compounds to inhibit protein kinase and treat and/or prevent diseases associated with inappropriate kinase activity.

Claims

1. A compound according to structural formula (I): ##STR00193## or a salt, hydrate, solvate or N-oxide thereof, wherein: B is ##STR00194## wherein R.sup.5 and R.sup.6 together form an unsaturated alkylene chain of 4 atoms to form structure (B. 1.a), ##STR00195## wherein the unsaturated alkylene chain formed by R.sup.5 and R.sup.6 is optionally substituted with one or more R.sup.a and/or R.sup.b; R.sup.2 is selected from the group consisting of a (C.sub.6-C.sub.20) aryl optionally substituted with one or more R.sup.8, a 5-20 membered heteroaryl optionally substituted with one or more R.sup.8, a (C.sub.7-C.sub.28) arylalkyl optionally substituted with one or more R.sup.8 and a 6-28 membered heteroarylalkyl optionally substituted with one or more R.sup.8; R.sup.4 is a saturated or non-aromatic unsaturated, bridged or unbridged cycloalkyl containing a total of from 3 to 16 carbon atoms that is substituted with an R.sup.7 group, with the proviso that when R.sup.4 is an unsaturated unbridged cycloalkyl, or a saturated bridged cycloalkyl, the R.sup.7 substituent is optional, wherein R.sup.4 is further optionally substituted with one or more R.sup.f R.sup.7 is —C(O)OR.sup.d, —C(O)NR.sup.dR.sup.d, —C(O)NR.sup.dOR.sup.d, or —C(O)NR.sup.dNR.sup.dR.sup.d; each R.sup.8 group is, independently of the others, selected from the group consisting of a water-solubilizing group, R.sup.a, R.sup.b, C.sub.1-C.sub.8 alkyl optionally substituted with one or more R.sup.a and/or R.sup.b, C.sub.3-C.sub.8 cycloalkyl optionally substituted with one or more R.sup.a and/or R.sup.b, heterocycloalkyl containing 3 to 12 annular atoms, optionally substituted with one or more R.sup.a and/or R.sup.b, C.sub.1-C.sub.8 alkoxy optionally substituted with one or more R.sup.a and/or R.sup.b, and —O—(CH.sub.2).sub.x—R.sup.b, where x is 1-6; each R.sup.a is, independently of the others, selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl, bridged or unbridged C.sub.3-C.sub.10 cycloalkyl, bridged or unbridged heterocycloalkyl containing 3 to 12 annular atoms, heteroaryl, (C.sub.6-C.sub.14) aryl, and (C.sub.7-C.sub.20) arylalkyl, wherein R.sup.a is optionally substituted with one or more R.sup.f; each R.sup.b is, independently of the others, a suitable group selected from the group consisting of ═O, —OR.sup.a, (C.sub.1-C.sub.3) haloalkyloxy, ═S, —SR.sup.a, ═NR.sup.a, ═NOR.sup.a, —NR.sup.cR.sup.c, halogen, —C.sub.1-C.sub.3haloalkyl, —CN, —NC, —OCN, —SCN, —NO, —NO.sub.2, ═N.sub.2, —N.sub.3, —S(O)R.sup.a, —S(O).sub.2R.sup.a, —S(O).sub.2OR.sup.a, —S(O)NR.sup.cR.sup.c, —S(O).sub.2NR.sup.c,R.sup.c,—OS(O)R.sup.a, —OS(O).sub.2R.sup.a, —OS(O).sub.2OR.sup.a, —OS(O).sub.2NR.sup.2R.sup.c, —C(O)R.sup.a, —C(O)OR.sup.a, —C(O)NR.sup.cR.sup.c, —C(O)NR.sup.aOR.sup.a, —C(NH)NR.sup.cR.sup.c, —C(NR.sup.a)NR.sup.cR.sup.c, —C(NOH)R.sup.a, —C(NOH)NR.sup.cR.sup.c, —OC(O)R.sup.a, —OC(O)OR.sup.a,—C(O)NR.sup.cR.sup.c, —OC(NH)NR.sup.cR.sup.c and —OC(NR.sup.a)NR.sup.cR.sup.c; each R.sup.c is, independently of the others, is R.sup.a or two R.sup.c that are bonded to the same nitrogen atom taken together with the nitrogen atom to which they are both attached form a heterocycloalkyl group containing 5 to 8 annular atoms, which optionally includes from 1 to 3 additional heteroatomic groups selected from the group consisting of —O—, —S—, —N(—(CH.sub.2).sub.y—R.sup.a)—, —N(—(CH.sub.2).sub.y—C(O)R.sup.a)—, —N(—(CH.sub.2).sub.y—C(O)OR.sup.a)—, —N(—(CH.sub.2).sub.y—S(O).sub.2R.sup.a)—, —N(—(CH.sub.2).sub.y—S(O).sub.2OR.sup.a)— and —N(—(CH.sub.2).sub.y—C(O)NR.sup.aR.sup.a)—, where y is 0-6, wherein the heterocycloalkyl is optionally substituted with one or more R.sup.f; each R.sup.d is, independently of the others, selected from the group consisting of R.sup.a, R.sup.c and a chiral auxiliary group; and each R.sup.f is independently —C.sub.1-C.sub.8 alkoxy, —C.sub.1-C.sub.8 alkyl, —C.sub.1-C.sub.6 haloalkyl, cyano, nitro, amino, (C.sub.1-C.sub.8 alkyl)amino, di(C.sub.1-C.sub.8 alkyl)amino, phenyl, benzyl, oxo, or halogen, or any two R.sup.f bonded to adjacent atoms, taken together with the atoms to which they are each attached, form a fused saturated or unsaturated cycloalkyl or a fused saturated or unsaturated heterocycloalkyl group containing 5 to 8 annular atoms, wherein the formed cycloalkyl and heterocycloalkyl groups are optionally substituted with one or more groups which are each independently selected from halogen, C.sub.1-C.sub.8 alkyl, and phenyl, the water solubilizing group is of the formula ##STR00196##  where Y is selected from the group consisting of CH and N, Z is selected from the group consisting of —C(H(R.sup.a))—, —CH.sub.2—, —O—, —S—, —N═, ═N, —NH—, —N (—(CH.sub.2).sub.y—R.sup.a)—, —N (—(CH.sub.2).sub.y—C(O)R.sup.a)—, —N ((CH.sub.2).sub.y —C(O)OR.sup.a)—, N (—(CH.sub.2).sub.y —S(O).sub.2R.sup.a)—, —N((CH.sub.2).sub.y —S(O).sub.2OR.sup.a)— and —N(—(CH.sub.2R.sup.a—C(O)NR.sup.cR.sup.c)—, with the proviso that Y and Z are not both simultaneously CH and CH.sub.2, respectively, and the chiral auxiliary is ##STR00197## ##STR00198## where R.sup.9 is hydrogen or C.sub.1-C.sub.8 alkyl.

2. The compound of claim 1 in which B is optionally substituted with 1 or 2 R.sup.g, wherein each R.sup.g is independently ═O, —OH, —C.sub.1-C.sub.6alkoxy, (C.sub.1-C.sub.3) haloalkyloxy, —NR.sup.cR.sup.c, halogen, —C.sub.1-C.sub.3alkyl, —C.sub.1-C.sub.3haloalkyl, —CN, —NO.sub.2, —S(O).sub.2R.sup.a, —S(O).sub.2OR.sup.a, —S(O).sub.2NR.sup.cR.sup.c, —OS(O).sub.2R.sup.a, —OS(O).sub.2OR.sup.a, —OS(O).sub.2NR.sup.cR.sup.c, —C(O)R.sup.a, —C(O)OR.sup.a, —C(O)NR.sup.cR.sup.c, —C(O)NR.sup.aOR.sup.a, —C(NR.sup.a) NR.sup.cR.sup.c, —C(NOH)R.sup.a, —C(NOH)NR.sup.cR.sup.c, —OC(O)R.sup.a, —OC(O)OR.sup.a, —OC(O) NR.sup.cR.sup.c, —OC(NR.sup.a) NR.sup.cR.sup.c; aryl, or (C.sub.7-C.sub.20) arylalkyl.

3. The compound of claim 2 in which R.sup.2 is phenyl substituted with one or more of the same or different R.sup.8.

4. The compound of claim 3 in which R.sup.2 is phenyl substituted with one R.sup.8 group.

5. The compound of claim 4 in which the one R.sup.8 substituent is positioned at the meta or para position.

6. The compound of claim 3 in which R.sup.2 is phenyl substituted with two of the same or different R.sup.8.

7. The compound of claim 6 in which the R.sup.8 substituents are positioned 3,4- or 3,5-.

8. The compound of claim 3 in which R.sup.2 is phenyl substituted with three of the same or different R.sup.8.

9. The compound of claim 8 in which the R.sup.8 substituents are positioned 3,4,5-.

10. The compound of claim 2 in which R.sup.2 is of the formula ##STR00199## wherein one of R.sup.11, R.sup.12 or R.sup.13 is a water-solubilizing group, and the other two of R.sup.11, R.sup.12 and R.sup.13 are each, independently of one another, selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl, halo, hydroxy, (C.sub.1-C.sub.3) hydroxyalkyl, —O(CH.sub.2).sub.x—R.sup.b, —NR.sup.cR.sup.c, —C(O)NR.sup.cR.sup.c, and —C(O)NHR.sup.a.

11. The compound of claim 10, wherein the water solubilizing group is of the formula, ##STR00200## wherein Y is selected from the group consisting of CH and N, and Z is selected from the group consisting of CH.sub.2, CH(R.sup.a), O, S, N, NH, N—(CH.sub.2).sub.y—R.sup.a, N—(CH.sub.2).sub.y—C(O)R.sup.a, N—(CH.sub.2).sub.y—C(O)OR.sup.a, N—(CH.sub.2).sub.y—S(O).sub.2R.sup.a, N—(CH.sub.2).sub.y—S(O).sub.2OR.sup.a and N—(CH.sub.2).sub.y—C(O)NR.sup.cR.sup.c, provided that Y and Z are not simultaneously CH and CH.sub.2, respectively.

12. The compound of claim 11, wherein one of R.sup.11, R.sup.12, and R.sup.13 is halogen, one is hydrogen, and the other is the water-solubilizing group.

13. The compound of claim 12, wherein one of R.sup.11, R.sup.12, and R.sup.13 is fluoro, one is hydrogen, and the other is the water-solubilizing group.

14. The compound of claim 13, wherein one of R.sup.12 is the water solubilizing group, R.sup.11 is hydrogen; and R.sup.13 is fluoro.

15. The compound of claim 11, wherein Y is N and Z is CH(R.sup.a) or N—(CH.sub.2).sub.y—R.sup.a.

16. The compound of claim 15, wherein Z is CH(R.sup.a1), wherein R.sup.a1 is —NR.sup.c.sup.c.

17. The compound of claim 1 in which R.sup.2 is a heteroaryl, optionally substituted with one or more R.sup.h, wherein each R.sup.h is independently ═O, —OH, —C.sub.1-C.sub.6 alkoxy, —C.sub.1-C.sub.3alkyl, (C.sub.1-C.sub.3) haloalkyloxy, —NR.sup.cR.sup.c, Zhalogen, —C.sub.1-C.sub.3haloalkyl, —CN, —NO.sub.2, —S(O).sub.2R.sup.a, —S(O).sub.2OR.sup.a, —S(O).sub.2NR.sup.cR.sup.c, —C(O)R.sup.a, —C(O)OR.sup.a, —C(O)NR.sup.Rc, aryl, or (C.sub.7-C.sub.20) arylalkyl.

18. The compound of claim 1 in which R.sup.4 is selected from the group consisting of ##STR00201## where s is an integer ranging from 1 to 6, and R.sup.7 is selected from the group consisting of —C(O)OR.sup.a and —C(O)NR.sup.cR.sup.c, where R.sup.a and R.sup.c are as previously defined.

19. The compound of claim 18, where R.sup.4 is ##STR00202##

20. The compound of claim 18 in which R.sup.7 is —C(O)O(C.sub.1-C.sub.8 alkyl) or —C(O)NH.sub.2.

21. The compound of claim 20 in which R.sup.7 is —C(O)NH.sub.2.

22. A compound according to claim 1 of structural formula (XII): ##STR00203## or a salt, hydrate, solvate or N-oxide thereof, wherein the bond including the dotted line is a single bond or a double bond.

23. The compound of claim 22 which is enriched in the corresponding diastereomer of structural formula (XIIa): ##STR00204##

Description

5. EXAMPLES

(1) The inventions are further defined by reference to the following examples, which describe the preparation of several exemplary embodiments of the compounds described herein, methods for assaying their biological activity, and methods for their use. It will be apparent to the skilled artisan that many modifications, both to the materials and methods, may be practiced without departing from the scope of the inventions.

Example 1

Synthesis of Racemic 2-Amino-3-dimethylaminocarbonylbicyclo-[2.2.1]hept-5-ene TFA Salt 13

(2) ##STR00045##

(3) To a suspension of N-Boc lactam 10 (1.3 g, 5.52 mmol) in toluene (20 mL) were added 40% methylamine solution in water (3 mL) and p-toluenesulfonic acid monohydrate (70 mg). The reaction mixture was stirred at 100° C. for 17 hours to effect cleavage of the β-lactam ring. The volatiles were evaporated under reduced pressure and the residue was then dissolved in CH.sub.2Cl.sub.2 (10 mL) Trifluoroacetic acid (TFA, 5 mL) was added and the resulting reaction mixture was stirred at room temperature for 3 hours to remove the Boc-protecting group. The volatiles were evaporated under reduced pressure, and the isolated TFA salt 13 was used in the next step without further purification.

Example 2

General Procedure for Synthesis of Purine Mono-SNAr Products

(4) ##STR00046##

(5) A glass tube was charged with the above amount of TFA salt 13, commercially available 2,6-dichloropurine (1.02 g, 5.43 mmol), N, N-diisopropylethylamine (DIPEA, 3.14 mL, 4.96 mmol) and isopropyl alcohol (IPA, 6 mL) The glass tube was sealed and then shaken at 100° C. for 17 hours. The volatiles were evaporated and the resulting residue was purified by flash chromatography eluting with ethyl acetate-methanol (100:5, including 1% triethylamine) to afford 1.25 g of mono-SN.sub.Ar product 14, racemic-(2-exo,3-exo-)-N6-[3-(dimethylamino)carbonylbicyclo-[2.2.1]hept-5-en-2-yl)]-2-chloro-1H-purine-6-amine, in 70% yield. .sup.1H NMR (300 MHz, CD.sub.3OD) δ: 8.05 (s, 1H), 6.35 (m, 2H), 4.68 (m, 1H), 3.00 (s, 1H), 3.04 (s, 1H), 3.00 (s, 3H), 2.95 (s, 1H), 2.83 (s, 1H), 2.68 (s, 3H), 2.39 (d, J=8.7 Hz, 1H), 1.69 (d, J=9.0 Hz, 1H), 1.33 (m, 1H); LC-MS: purity: 90.51%; MS (m/e): 333.43 (M+H).sup.+.

Example 3

General Procedure for Synthesis of Second Purine SNAr Products

(6) ##STR00047##

(7) The mono-SN.sub.Ar product 14 (40 mg, 0.12 mmol) and 3-isopropoxyaniline (44 μl, 0.3 mmol) were added to a microwave vial, followed by the addition of isopropyl alcohol (IPA, 0.8 mL) and 4 drops of TFA. The mixture was irradiated in a microwave oven at 155° C. for 60 minutes to effect the desired reaction. After cooling the reaction vessel to room temperature, the volatiles were evaporated under reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography (RP-HPLC), eluting with a gradient of acetonitrile-water to provide the desired product 129, racemic-(2-exo,3-exo-)-N6-[3-(dimethylamino)carbonylbicyclo[2.2.1]hept-5-en-2-yl)]-N2-(3-isopropoxyphenyl)-1H-purine-2,6-diamine.

Example 4

General Procedure for Synthesis of Pyrrolo[2,3-d]pyrimidine Mono-SNAr Products

(8) ##STR00048##

(9) A sealed tube charged with TFA salt 16 (550 mg, 2.06 mmol), 2,4-dichloro-1H-pyrrolo[2,3-d]pyrimidine (350 mg, 1.87 mmol), N, N-diisopropylethylamine (1.02 mL, 6.19 mmol) and isopropyl alcohol (5 mL) was shaken at 60° C. for 48 hours and 100° C. for another 4 hours. The volatiles were evaporated, the resulting residue was then purified by flash chromatography eluting with ethyl acetate to afford 370 mg of mono-SNAr product 17, racemic-(2-exo,3-exo)-N4-(3-aminocarbonylbicyclo[2.2.1]hept-5-en-2-yl)-2-chloro-1H-pyrrolo[2,3-d]pyrimidine-4-amine, in 65% yield. .sup.1H NMR (300 MHz, CD.sub.3OD) δ: 7.01 (d, J=3.6 Hz, 1H), 6.48 (d, J=3.6 Hz, 1H), 6.32 (m, 2H), 4.45 (d, J=7.2 Hz, 1H), 2.95 (s, 1H), 2.83 (s, 1H), 2.66 (dd, J=1.5, 8.1 Hz, 1H), 2.34 (d, J=9.3 Hz, 1H), 1.59 (d, J=9.0 Hz, 1H); LC-MS: purity: 91.82%; MS (m/e): 304.41 (M+H).sup.+

Example 5

General Procedure for Synthesis of Second Pyrrolo[2,3-d]pyrimidine SNAr Products

(10) ##STR00049##

(11) The mono-SNAr product 17 (30 mg, 0.1 mmol) and m-toluidine (22 μl, 0.2 mmol) were added to a microwave vial, followed by the addition of isopropyl alcohol (0.8 mL) and 4 drops of TFA. The mixture was irradiated in a microwave oven at 155° C. for 60 min After cooling to room temperature, the volatiles were evaporated under reduced pressure. The residue was purified by HPLC eluting with acetonitrile-water to provide the desired product 116.

Example 6

General Procedure for Synthesis of Quinazoline Mono-SNAr Products

(12) ##STR00050##

(13) A microwave vial charged with TFA salt 16 (402 mg, 1.5 mmol), commercially available 2,4-dichloroquinazoline (300 mg, 1.5 mmol), N, N-diisopropylethylamine (0.75 mL, 4.5 mmol) and isopropyl alcohol (2 mL) was irradiated in a microwave oven at 160° C. for 40 min After cooling to room temperature, the volatiles were evaporated under reduced pressure. The resulting residue was then purified by flash chromatography eluting with ethyl acetate-hexanes (100:40, including 1% triethylamine) to afford 150 mg of mono-SNAr product 19, racemic-(2-exo,3-exo)-2-chloro-N4-(3-aminocarbonylbicyclo[2.2.1]hept-5-en-2-yl)-4-quinazoline-amine, in 31% yield. .sup.1H NMR (300 MHz, DMSO-d.sub.6) δ: 9.11 (d, J=7.2 Hz, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.81-7.51 (m, 4H), 7.17 (s, 1H), 6.32 (m, 2H), 4.22 (t, J=7.2 Hz, 1H), 2.90 (s, 1H), 2.84 (s, 1H), 2.57 (d, J=8.1 Hz, 1H), 2.24 (d, J=8.7 Hz, 1H), 1.44 (d, J=9.0 Hz, 1H); LC-MS: purity: 100%; MS (m/e): 315.00 (M+H).sup.+.

Example 7

General Procedure for Synthesis of Second Quinazoline SNAr Products

(14) ##STR00051##

(15) The mono-SNAr product 19 (35 mg, 0.11 mmol) and 3-aminophenol (15 mg, 0.13 mmol) were added to a microwave vial, followed by the addition of isopropyl alcohol (0.6 mL) and N, N-diisopropylethylamine (55 μl, 0.33 mmol). The mixture was irradiated in a microwave oven at 160° C. for 1 hour. After cooling to room temperature, the volatiles were evaporated under reduced pressure. The residue was purified by HPLC eluting with acetonitrile-water to provide the desired product 102.

Example 8

Synthesis of Additional Compounds

(16) Additional compounds synthesized using the above-described methods are illustrated in Tables 1 and 2, below.

(17) TABLE-US-00001 TABLE 1 No. Structure Name Spectroscopic Data 101 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-6,7- dimethoxy-N2-(3- hydroxy)phenyl-2,4- qninazoline-diamine .sup.1H NMR (CDCl.sub.3): δ 8.40 (s, 1H), 7.26 (m, 2H), 7.03 (t, J = 8.1 Hz, 1H), 6.87 (m, 2H), 6.46 (dd, J = 2.7, 7.8 Hz, 1H), 6.29 (dd, J = 2.7, 6.0 Hz, 1H), 6.19 (dd, J = 2.7, 6.0 Hz, 1H), 4.15 (d, J = 8.1 Hz, 1H), 4.00 (s, 6H), 3.89 (s, 1H), 3.84 (s, 1H), 3.21 (m, 1H), 2.94 (s, 1H), 2.83 (m, 1H), 2.47 (d, J = 7.8 Hz, 1H), 2.20 (d, J = 9.3 Hz, 1H), 1.47 (d, J = 9.9 Hz, 1H), 1.37 (m, 1H); LC-MS: purity: 100%; MS (m/e): 448.11 (M + H).sup.+ 102 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- hydroxy)phenyl-2,4- quinazoline-diamine .sup.1H NMR (CD.sub.3OD): δ 7.81 (m, 3H), 7.48 (m, 2H), 7.21 (t, J = 8.1 Hz, 1H), 7.13 (s, 1H), 6.99 (m, 1H), 6.69 (dd, J = 1.5, 7.2 Hz, 1H), 6.39 (m, 1H), 4.27 (m, 1H), 3.07 (d, J = 8.1 Hz, 1H), 2.65 (m, 1H), 2.16 (d, J = 9.0 Hz), 1.58 (d, J = 9.3 Hz, 1H); LC- MS: purity: 100%; MS (m/e): 388.39 (M + H).sup.+ 103 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2- (3,4,5-trimethoxy)phenyl- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.10 (s, 1H), 7.77 (s, 1H), 7.10 (m, 2H), 6.31 (m, 2H), 4.67 (m, 1H), 3.31 (s, 3H), 3.30 (s, 6H), 2.98 (s, 1H), 2.84 (s, 1H), 2.67 (d, J = 8.4 Hz, 1H), 2.38 (d, J = 9.3 Hz, 1H), 1.64 (d, J = 8.7 Hz, 1H); LC-MS: purity: 100%; MS (m/e): 452.10 (M + H).sup.+ 104 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-[3- [2-(methylamino)-2- oxoethoxy]phenyl]]-1H- purine-2,6-diamine .sup.1H NMR (DMSO-d.sub.6): δ 8.89 (s, 1H), 8.10 (s, 1H), 7.93 (m, 1H), 7.73 (m, 1H), 7.66- 7.26 (m, 4H), 7.10 (m, 1H), 6.42-6.29 (m, 3H), 2.85 (s, 1H), 2.76 (s, 1H), 2.65 (d, J = 4.5 Hz, 3H), 3.54 (d, J = 8.4 Hz, 1H), 2.19 (d, J = 8.1 Hz, 1H), 1.40 (d, J = 8.4 Hz, 1H); LC-MS: purity: 100%; MS (m/e): 449.07 (M + H).sup.+ 105 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-[3- (2-morpholin-4-yl- ethoxy)phenyl]-1H-purine- 2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.10 (s, 1H), 7.80 (s, 1H), 7.55 (m, 1H), 7.27-7.12 (m, 2H), 6.60- 6.54 (m, 2H), 6.33 (m, 2H), 4.58 (m, 1H), 4.35 (m, 2H), 3.96-3.81 (m, 4H), 3.47 (m, 2H), 3.18 (m, 2H), 3.13 (s, 1H), 2.98 (s, 1H), 2.86 (s, 1H), 2.70 (d, J = 7.8 Hz, 1H), 2.36 (d, J = 8.1 Hz, 1H), 1.64 (d, J = 7.2 Hz, 1H); LC-MS: purity: 100%; MS (m/e): 491.14 (M + H).sup.+ 106 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- aminosulfonyl)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.49 (s, 1H), 8.12 (s, 1H), 7.79-7.75 (m, 2H), 7.45-7.36 (m, 2H), 6.31 (m, 2H), 4.64 (m, 1H), 2.97 (s, 1H), 2.83 (s, 1H), 2.76 (d, J = 7.8 Hz, 1H), 2.39 (d, J = 8.7 Hz, 1H), 1.64 (d, J = 7.5 Hz, 1H); LC-MS: purity: 100%; MS (m/e): 441.00 (M + H).sup.+ 107 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3,4- dihydro-3-oxo-2H-1,4- benzoxazin-7-yl)-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.20 (s, 1H), 7.74 (s, 1H), 7.63 (s, 1H), 7.11 (m, 2H), 6.78 (d, J = 8.4 Hz, 2H), 6.34 (m, 2H), 4.59 (m, 1H), 4.56 (s, 2H), 2.97 (s, 1H), 2.86 (s, 1H), 2.68 (d, J = 8.4 Hz, 1H), 2.36 (d, J = 9.0 Hz, 1H), 1.62 (d, J = 6.9 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 433.03 (M + H).sup.+ 108 (1R,2R,3S,4S)-N6-(3- Aminocarbonyl- bicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- aminosulfonyl)phenyl-1H- purine-2,6-diamine LC-MS: purity: 100%; MS (m/e): 441.49 (M + H).sup.+ 109 0 (1R,2R,3S,4S)-N6-(3- Aminocarbonyl- bicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- fluoro)phenyl-1H-purine- 2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.15 (s, 1H), 7.91 (d, J = 12.6 Hz, 1H), 7.77 (s, 1H), 7.25-7.14 (m, 2H), 6.63-6.56 (m, 1H), 6.37 (m, 2H), 4.53 (m, 1H), 2.98 (s, 1H), 2.87 (s, 1H), 2.70 (d, J = 7.8 Hz, 1H), 2.35 (d, J = 9.0 Hz, 1H), 1.62 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 356.14 (M + H).sup.+ 110 (1R,2R,3S,4S)-N6-(3- Aminocarbonyl- bicyclo[2.2.1] hept-5-en-2-yl)-N2-[3- [2-(methylamino)-2- oxoethoxy]phenyl]]-1H- purine-2,6-diamine LC-MS: purity: 100%; MS (m/e): 449.48 (M + H).sup.+ 111 (1S,2S,3R,4R)-N6-(3- Aminocarbonyl- bicyclo[2.2.1] hept-5-en-2-yl)-N2-[3- [2-(methylamino)-2- oxoethoxy]phenyl]]-1H- purine-2,6-diamine LC-MS: purity: 99.00%; MS (m/e): 449.80 (M + H).sup.+ 112 (1R,2R,3S,4S)-N6-(3- Aminocarbonyl- bicyclo[2.2.1] hept-5-en-2-yl)-N2-[3- (2-morpholin-4-yl- ethoxy)phenyl]-1H-purine- 2,6-diamine LC-MS: purity: 97.49%; MS (m/e): 491.91 (M + H).sup.+ 113 (1S,2S,3R,4R)-N6-(3- Aminocarbonyl- bicyclo[2.2.1] hept-5-en-2-yl)-N2-[3- (2-morpholin-4-yl- ethoxy)phenyl]-lH-purine- 2,6-diamine LC-MS: purity: 99.63%; MS (m/e): 491.72 (M + H).sup.+ 114 (1R,2R,3S,4S)-N6-(3- Aminocarbonyl- bicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- aminosulfonyl-4- methyl)phenyl-1H-purine- 2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.45 (m, 1H), 8.25 (s, 1H), 7.76 (s, 1H), 7.72 (d, J = 2.4, 8.1 Hz, 1H), 7.22 (d, J = 8.1 Hz, 1H), 6.31 (m, 2H), 4.63 (m, 1H), 2.97 (s, 1H), 2.82 (s, 1H), 2.73 (d, J = 8.4 Hz, 1H), 2.60 (s, 3H), 2.37 (d, J = 9.3 Hz, 1H), 1.63 (d, J = 7.8 Hz, 1H); LC-MS: purity: 100%; MS (m/e): 455.51 (M + H).sup.+ 115 Racemic-(2-exo,3-exo)- N6-(3-aminocarbonyl- bicyclo[2.2.1]hept-5- en-2-yl)-N2-(3- methyl)phenyl-1H-purine- 2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (s, 1H), 7.76 (s, 1H), 7.52 (s, 1H), 7.44 (d, J = 7.5 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 6.75 (d, J = 7.5 Hz, 1H), 6.32 (m, 2H), 4.53 (m, 1H), 2.98 (s, 1H), 2.85 (s, 1H), 2.67 (d, J = 8.1 Hz, 1H), 2.35 (d, J = 9.0 Hz, 1H), 2.32 (s, 3H), 1.64 (d, J = 9.3 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 376.14 (M + H).sup.+ 116 Raccmic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- methoxy)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (s, 1H), 7.76 (s, 1H), 7.53 (s, 1H), 7.11 (m, 2H), 6.52 (m, 2H), 6.32 (m, 2H), 4.53 (m, 1H), 3.79 (s, 3H), 2.97 (s, 1H), 2.87 (s, 1H), 2.68 (d, J = 7.8 Hz, 1H), 2.35 (d, J = 9.0 Hz, 1H), 1.64 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 392.13 (M + H).sup.+ 117 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- trifluoromethoxy)phenyl- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.17 (s, 1H), 7.80 (s, 1H), 7.78 (m, 2H), 7.13 (m, 2H), 6.34 (m, 2H), 4.60 (m, 1H), 2.98 (s, 1H), 2.86 (s, 1H), 2.68 (d, J = 8.1 Hz, 1H), 2.36 (d, J = 9.3 Hz, 1H), 1.62 (d, J = 9.0 Hz, 1H); LC- MS: purity: 100.00%; MS (m/e): 446.10 (M + H).sup.+ 118 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-[3- methyl-4-(4- methylpiperazine-1- yl)phenyl]-1H-purine-2,6- diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (s, 1H), 7.77 (s, 1H), 7.55-7.47 (m, 2H), 7.03 (d, J = 8.4 Hz, 1H), 6.34 (m, 2H), 4.60 (m, 1H), 3.44 (m, 4H), 3.13 (m, 4H), 2.97 (s, 3H), 2.95 (s, 1H), 2.85 (s, 1H), 2.67 (d, J = 8.1 Hz, 1H), 2.37 (d, J = 8.7 Hz, 1H), 2.32 (s, 3H), 1.62 (d, J = 8.7 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 474.70 (M + H).sup.+ 119 0 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(4- cyanomethyl)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 7.75 (s, 1H), 7.73 (d, J = 8.7 Hz, 2H), 7.22 (d, J = 8.7 Hz, 2H), 6.33 (m, 2H), 4.61 (m, 1H), 3.82 (s, 2H), 2.98 (s, 1H), 2.86 (s, 1H), 2.69 (d, J = 8.4 Hz, 1H), 2.36 (d, J = 9.0 Hz, 1H), 1.62 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 401.10 (M + H).sup.+ 121 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(1H- indazol-6-yl)-1H-purine- 2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.27 (s, 1H), 8.19 (s, 1H), 7.89 (s, 1H), 7.78 (m, 1H), 7.61 (s, 1H), 7.58 (s, 1H), 7.23 (d, J = 8.4 Hz, 1H), 6.33 (m, 2H), 4.62 (m, 1H), 2.98 (s, 1H), 2.86 (s, 1H), 2.69 (d, J = 8.1 Hz, 1H), 2.38 (d, J = 9.0 Hz, 1H), 1.64 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 402.09 (M + H).sup.+ 122 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- aminocarbonyl)phenyl-1H purine-2,6-diamine .sup.1H NMR (DMSO-d.sub.6): δ 8.97 (s, 1H), 8.13 (s, 1H), 7.97 (m, 1H), 7.74 (m, 1H), 7.28 (m, 3H), 6.29 (m, 2H), 4.39 (m, 1H), 2.92 (s, 1H), 2.88 (s, 1H), 2.22 (d, J = 8.1 Hz, 1H), 1.41 (d, J = 8.4 Hz, 1H); LC-MS: purity: 100%; MS (m/e): 405.12 (M + H).sup.+ 123 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(1H- indol-5-yl)-1H-purine-2,6- diamine .sup.1H NMR (CD.sub.3OD): δ 8.18 (s, 1H), 7.84 (m, 1H), 7.73 (s, 1H), 7.33 (d, J = 8.7 Hz, 1H), 7.21-7.17 (m, 2H), 6.38 (m, 1H), 6.32 (m, 2H), 4.61 (m, 1H), 2.97 (s, 1H), 2.86 (s, 1H), 2.63 (d, J = 8.1 Hz, 1H), 2.38 (d, J = 9.3 Hz, 1H), 1.63 (d, J = 9.0 Hz, 1H); LC- MS: purity: 100.00%; MS (m/e): 402.09 (M + H).sup.+ 124 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- hydroxy)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (s, 1H), 7.76 (s, 1H), 7.31 (m, 1H), 7.05 (m, 2H), 6.41-6.30 (m, 2H), 4.60 (m, 1H), 2.97 (s, 1H), 2.87 (s, 1H), 2.68 (d, J = 8.1 Hz, 1H), 2.36 (d, J = 9.0 Hz, 1H), 1.62 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 378.13 (M + H).sup.+ 125 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(1,3- benzodioxol-5-yl)-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.14 (s, 1H), 7.73 (s, 1H), 7.52 (s, 1H), 6.88 (dd, J = 2.1, 8.1 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H), 6.33 (m, 2H), 5.89 (s, 2H), 4.58 (m, 1H), 2.97 (s, 1H), 2.87 (s, 1H), 2.66 (d, J = 8.4 Hz, 1H), 2.34 (d, J = 9.3 Hz, 1H), 1.62 (d, J = 9.3 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 406.11 (M + H).sup.+ 126 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(4- piperidino)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.15 (s, 1H), 7.75 (s, 1H), 7.65 (d, J = 8.7 Hz, 1H), 7.13 (d, J = 9.0 Hz, 1H), 6.33 (m, 2H), 4.58 (m, 1H), 2.98 (s, 1H), 2.86 (s, 1H), 2.66 (d, J = 7.8 Hz, 1H), 2.34 (d, J = 8.7 Hz, 1H), 1.84 (m, 4H), 1.65 (m, 5H); LC-MS: purity: 100.00%; MS (m/e): 445.64 (M + H).sup.+ 127 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- fluoro)phenyl-1H-purine- 2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.16 (s, 1H), 7.74 (s, 1H), 7.66 (m, 2H), 6.97 (m, 2H), 6.32 (m, 2H), 4.57 (m, 1H), 2.97 (s, 1H), 2.85 (s, 1H), 2.67 (d, J = 8.1 Hz, 1H), 2.35 (d, J = 9.3 Hz, 1H), 1.62 (d, J = 9.3 Hz, 1H); LC- MS: purity: 100.00%; MS (m/e): 380.53 (M + H).sup.+ 128 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3,4- difluoro)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (s, 1H), 7.76 (s, 1H), 7.24-7.01 (m, 3H), 6.34 (m, 2H), 4.60 (m, 1H), 2.98 (s, 1H), 2.87 (s, 1H), 2.67 (d, J = 8.4 Hz, 1H), 2.34 (d, J = 9.0 Hz, 1H), 1.62 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 398.54 (M + H).sup.+ 129 Racemic-(2-exo,3-exo-)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- isopropoxy)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (s, 1H), 7.75 (s, 1H), 7.54 (s, 1H), 7.14-7.05 (m, 2H), 6.49 (d, J = 7.8 Hz, 1H), 6.39-6.31 (m, 2H), 4.62-4.54 (m, 2H), 2.98 (s, 1H), 2.87 (s, 1H), 2.69 (d, J = 6.9 Hz, 1H), 2.36 (d, J = 8.7 Hz, 1H), 1.62 (d, J = 8.7 Hz, 1H), 1.32 (d, J = 5.7 Hz, 6H); LC-MS: purity: 100.00%; MS (m/e): 420.09 (M + H).sup.+ 130 0 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- methylthio)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.19 (s, 1H), 7.83- 7.75 (m, 2H), 7.37-7.33 (m, 1H), 7.18-7.13 (m, 1H), 6.84-6.80 (m, 1H), 6.34 (m, 2H), 4.62 (m, 1H), 2.98 (s, 1H), 2.86 (s, 1H), 2.69 (d, J = 7.5 Hz, 1H), 2.48 (s, 3H), 2.36 (d, J = 9.0 Hz, 1H), 1.62 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 408.03 (M + H).sup.+ 131 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- ethoxy)phenyl-1H-purine- 2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.15 (s, 1H), 7.75 (s, 1H), 7.57 (s, 1H), 7.14-7.04 (m, 2H), 6.50- 6.47 (m, 1H), 6.39-6.31 (m, 2H), 4.62 (m, 1H), 4.01 (q, J = 6.9 Hz, 2H), 2.98 (s, 1H), 2.87 (s, 1H), 2.68 (d, J = 8.1 Hz, 1H), 2.36 (d, J = 8.7 Hz, 1H), 1.62 (d, J = 9.0 Hz, 1H), 1.39 (t, J = 6.9 Hz, 3H); LC-MS: purity: 100.00%; MS (m/e): 406.11 (M + H).sup.+ 132 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-[(4- fluoro-3-methyl)phenyl]- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (s, 1H), 7.75 (s, 1H), 7.55-7.53 (m, 1H), 7.46-7.41 (m, 1H), 6.89 (t, J = 9.0 Hz, 1H), 6.31 (m, 2H), 4.60 (m, 1H), 2.97 (s, 1H), 2.84 (s, 1H), 2.67 (d, J = 8.1 Hz, 1H), 2.36 (d, J = 9.0 Hz, 1H), 2.24 (s, 3H), 1.62 (d, J = 9.0 Hz, 1H); LC- MS: purity: 100.00%; MS (m/e): 394.09 (M + H).sup.+ 133 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-[4-(4- pyridinylmethyl)phenyl]- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.38 (m, 1H), 8.12 (s, 1H), 7.75 (s, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.29 (m, 2H), 7.12 (d, J = 8.7 Hz, 2H), 6.30 (m, 2H), 4.56 (m, 1H), 3.98 (s, 2H), 2.97 (s, 1H), 2.85 (s, 1H), 2.67 (d, J = 8.1 Hz, 1H), 2.35 (d, J = 8.7 Hz, 1H), 1.62 (d, J = 8.7 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 453.08 (M + H).sup.+ 134 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- fluoro-4-methy)phenyl- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): 7.82-7.68 (m, 2H), 7.39-7.01 (m, 2H), 6.35 (m, 2H), 4.60 (m, 1H), 2.97 (s, 1H), 2.87 (s, 1H), 2.67 (d, J = 8.4 Hz, 1H), 2.36 (d, J = 8.7 Hz, 1H), 2.19 (s, 3H), 1.62 (d, J = 8.7 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 394.039 (M + H).sup.+ 135 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(1H- indol-4-yl)-1H-purine-2,6- diamine .sup.1H NMR (CD.sub.3OD): δ 8.30 (s, 1H), 7.82- 7.79 (m, 1H), 7.75 (s, 1H), 7.18 (d, J = 3.3 Hz, 1H), 7.10-7.02 (m, 1H), 6.58 (d, J = 3.3 Hz, 1H), 6.33 (m, 2H), 4.61 (m, 1H), 2.97 (s, 1H), 2.86 (s, 1H), 2.63 (d, J = 8.4 Hz, 1H), 2.38 (d, J = 9.0 Hz, 1H), 1.63 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 401.10 (M + H).sup.+ 136 Racemic-(2-exo,3-exo-)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(2- methoxy)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.54 (s, 1H), 8.50 (m, 1H), 7.80 (s, 1H), 7.71 (m, 1H), 6.91 (m, 3H), 6.34 (m, 2H), 4.58 (m, 1H), 3.92 (s, 3H), 2.99 (s, 1H), 2.89 (s, 1H), 2.69 (d, J = 8.4 Hz, 1H), 2.35 (d, J = 9.0 Hz, 1H), 1.63 (d, J = 7.5 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 392.07 (M + H).sup.+ 137 Racemic-(2-exo,3-exo-)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- methoxy)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.19 (s, 1H), 7.72 (s, 1H), 7.71 (m, 1H), 7.52 (d, J = 9.0 Hz, 2H), 6.84 (d, J = 9.0 Hz, 2H), 6.32 (m, 2H), 4.58 (m, 1H), 3.77 (s, 3H), 2.97 (s, 1H), 2.84 (s, 1H), 2.66 (d, J = 8.4 Hz, 1H), 2.35 (d, J = 9.0 Hz, 1H), 1.62 (d, J = 8.7 Hz, 1H); LC- MS: purity: 100.00%; MS (m/e): 392.07 (M + H).sup.+ 138 Racemic-(2-exo,3-exo-)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3,5- dimethoxy)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.15 (s, 1H), 7.76 (s, 1H), 6.99 (s, 1H), 6.98 (s, 1H), 6.34 (m, 2H), 6.09 (s, 1H), 4.62 (m, 1H), 3.77 (s, 6H), 2.97 (s, 1H), 2.86 (s, 1H), 2.68 (d, J = 9.0 Hz, 1H), 2.37 (d, J = 8.7 Hz, 1H), 1.63 (d, J = 7.2 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 422.06 (M + H).sup.+ 139 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- aminosulfonyl-4- methoxy)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.37 (d, J = 2.7 Hz, 1H), 8.19 (s, 1H), 7.75 (s, 1H), 7.69 (dd, J = 2.7, 9.0 Hz, 1H), 7.09 (d, J = 9.3 Hz, 1H), 6.30 (m, 2H), 4.64 (m, 1H), 3.95 (s, 3H), 2.97 (s, 1H), 2.82 (s, 1H), 2.74 (d, J = 8.1 Hz, 1H), 2.37 (d, J = 9.3 Hz, 1H), 1.64 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100%; MS (m/e): 471.55 (M + H).sup.+ 140 0 Racemic-(2-exo,3-exo-)- N6-[3- (dimethylamino)carbonyl- bicyclo[2.2.1]hept-5-en-2- yl)]-N2-(3- isopropoxy)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.17 (s, 1H), 7.76 (s, 1H), 7.55 (m, 1H), 7.13-7.04 (m, 2H), 6.50- 6.46 (m, 1H), 6.35 (m, 2H), 4.58 (pent, J = 6.0 Hz, 1H), 4.91 (m, 1H), 3.00 (s, 1H), 2.98 (s, 1H), 2.91 (s, 3H), 2.83 (s, 1H), 2.72 (s, 3H), 2.65 (s, 1H), 2.35 (d, J = 9.0 Hz, 1H), 1.68 (d, J = 9.0 Hz, 1H), 1,32 (d, J = 6.0 Hz, 6H); LC-MS: purity: 100.00%; MS (m/e): 448.62 (M + H).sup.+ 141 Racemic-(2-exo,3-exo-)- N6-[3- (dimethylamino)carbonyl- bicyclo[2.2.1]hept-5-en-2- yl)]-N2-(3-methyl)phenyl- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.14 (s, 1H), 7.75 (s, 1H), 7.55 (s, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 2H), 6.75 (d, J = 7.5 Hz, 1H), 6.33 (m, 2H), 4.92 (m, 1H), 3.00 (s, 1H), 2.97 (s, 1H), 2.89 (s, 3H), 2.82 (s, 1H), 2.72 (s, 3H), 2.35 (d, J = 9.3 Hz, 1H), 2.31 (s, 3H), 1.68 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 404.63 (M + H).sup.+ 142 Racemic-(2-exo,3-exo-)- N6-[3- (dimethylamino)carbonyl- bicyclo[2.2.1]hept-5-en-2- yl)]-N2-(3- methoxy)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.08 (s, 1H), 7.78 (s, 1H), 7.54 (s, 1H), 7.10 (m, 2H), 2H), 6.50 (m, 1H), 6.34 (m, 2H), 4.87 (m, 1H), 3.79 (s, 3H), 3.01 (s, 1H), 2.97 (s, 1H), 2.91 (s, 3H), 2.83 (s, 1H), 2.72 (s, 3H), 2.35 (d, J = 9.0 Hz, 1H), 1.68 (d, J = 9.3 Hz, 1H); LC- MS: purity: 100.00%; MS (m/e): 420.58 (M + H).sup.+ 143 Racemic-(2-exo,3-exo-)- N6-[3- (dimethylamino)carbonyl- bicyclo[2.2.1]hept-5-en-2- yl)]-N2-(3- methylthio)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.15 (s, 1H), 7.86 (s, 1H), 7.77 (s, 1H), 7.34-7.30 (m, 1H), 7.14 (t, J = 8.1 Hz, 1H), 6.83-6.80 (m, 1H), 6.34 (m, 2H), 4.87 (m, 1H), 3.02 (s, 1H), 2.98 (m, 1H), 2.90 (s, 3H), 2.82 (s, 1H), 2.71 (s, 3H), 2.48 (s, 3H), 2.35 (d, J = 9.0 Hz, 1H), 1.69 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 436.02 (M + H).sup.+ 144 Racemic-(2-exo,3-exo-)- N6-[3- (dimethylamino)carbonyl- bicyclo[2.2.1]hept-5-en-2- yl)]-N2-(3- aminosulfonyl)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.53 (s, 1H), 8.11 (s, 1H), 7.69-7.64 (m, 2H), 7.44-7.33 (m, 2H), 6.29 (m, 2H), 4.84 (m, 1H), 3.01 (s, 1H), 2.98 (m, 1H), 2.89 (s, 3H), 2.81 (s, 1H), 2.72 (s, 3H), 2.28 (d, J = 9.0 Hz, 1H), 1.68 (d, J = 9.3 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 469.54 (M + H).sup.+ 145 Racemic-(2-exo,3-exo-)- N6-[3- (dimethylamino)carbonyl- bicyclo[2.2.1]hept-5-en-2- yl)]-N2-(4- piperidino)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (m, 2H), 7.79 (s, 1H), 773 (d, d = 9.0 Hz, 2H), 7.20 (d, J = 7.5 Hz, 2H), 6.32 (m, 2H), 4.94 (m, 1H), 2.99 (s, 1H), 2.97 (s, 1H), 2.91 (s, 3H), 2.82 (s, 1H), 2.73 (s, 3H), 2.65 (s, 1H), 2.32 (d, J = 8.7 Hz, 1H), 1.87 (m, 5H), 1.68 (m, 4H); LC-MS: purity: 100.00%; MS (m/e): 473.65 (M + H).sup.+ 146 Racemic-(2-exo,3-exo-)- N6-[3- (dimethylamino)carbonyl- bicyclo[2.2.1]hept-5-en-2- yl)]-N2-[4-(4- pyridinylmethyl)phenyl]- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.40-8.38 (m, 2H), 8.10 (s, 1H), 7.76 (s, 1H), 7.64 (d, J = 8.7 Hz, 2H), 7.30-7.28 (m, 2H), 7.11 (d, J = 8.4 Hz, 2H), 6.32 (m, 2H), 4.90 (m, 1H), 3.98 (s, 2H), 2.95 (m, 2H), 2.90 (s, 3H), 2.81 (s, 1H), 2.73 (s, 3H), 2.65 (s, 1H), 2.32 (d, J = 8.4 Hz, 1H), 1.68 (d, J = 9.3 Hz, 1H); LC- MS: purity: 100.00%; MS (m/e): 481.62 (M + H).sup.+ 147 (1R,2R,3S,4S)-N6-(3- Aminocarbonyl- bicyclo[2.2.1]hept-5- en-2-yl)-N2- (1H-indol-5-yl)-1H- purine-2,6-diamine LC-MS: purity: 100.00%; MS (m/e): 402.50 (M + H).sup.+ 148 (1R,2R,3S,4S)-N6-(3- Aminocarbonyl- bicyclo[2.2.1]hept-5- en-2-yl)-N2-[4-(4- pyridinylmethyl)phenyl]- 1H-purine-2,6-diamine LC-MS: purity: 100.00%; MS (m/e): 453.51 (M + H).sup.+ 149 Racemic-(2-exo,3-exo-)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-[4- (4-morpholinyl)phenyl]- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.20 (s, 1H), 7.72 (s, 1H), 7.54 (d, J = 9.0 Hz, 1H), 6.92 (d, J = 9.0 Hz, 1H), 6.32 (m, 2H), 4.58 (m, 1H), 3.83 (t, J = 4.8 Hz, 4H), 3.07 (t, J = 4.8 Hz, 4H), 2.97 (s, 1H), 2.85 (s, 1H), 2.66 (d, J = 7.8 Hz, 1H), 2.34 (d, J = 9.3 Hz, 1H), 1.62 (d, J = 9.3 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 447.09 (M + H).sup.+ 150 00 Racemic-(2-exo,3-exo-)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(2- methyl-1H-indol-5-yl)-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.27 (s, 1H), 7.68 (m, 1H), 7.16 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H), 6.31 (m, 2H), 6.04 (s, 1H), 4.57 (m, 1H), 2.96 (s, 1H), 2.86 (s, 1H), 2.63 (d, J = 7.8 Hz, 1H), 2.40 (s, 3H), 2.33 (d, J = 8.7 Hz, 1H), 1.62 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 415.75 (M + H).sup.+ 151 01 Racemic-(2-exo)-N6- (bicyclo[2.2.1]hept-2-yl)- N2-(3-methyl)phenyl-1H- purine-2,6-diamine .sup.1H NMR (DMSO-d.sub.6): δ 9.13 (s, 1H), 8.17 (s, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.50 (s, 1H), 7.14 (d, J = 7.5 Hz, 1H), 6.75 (d, J = 7.5 Hz, 1H), 3.96 (s, 1H), 3.40 (brs, 2H), 2.28 (s, 3H), 1.78-1.47 (m, 5H), 1.31-1.14 (m, 3H); LC-MS: purity: 98.80%; MS (m/e): 335.52 (M + H).sup.+ 152 02 Racemic-(2-exo,3-exo-)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- aminocarbonyl-1H-indol- 5-yl)-1H-purine-2,6- diamine .sup.1H NMR (CD.sub.3OD): δ 8.39 (s, 1H), 8.14 (m, 1H), 7.89 (s, 1H), 7.77 (m, 1H), 7.34 (m, 2H), 6.29-6.21 (m, 2H), 4.62 (m, 1H), 2.94 (s, 1H), 2.81 (s, 1H), 2.68 (d, J = 8.7 Hz, 1H), 2.65 (s, 1H), 2.36 (d, J = 9.0 Hz, 1H), 1.61 (d, J = 8.7 Hz, 1H ); LC-MS: purity: 100.00%; MS (m/e): 444.04 (M + H).sup.+ 153 03 Racemic-(2-exo)-N6- (bicyclo[2.2.1]hept-2-yl)- N2-(3-isopropoxy)phenyl- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.17 (s, 1H), 7.33 (s, 1H), 7.18 (m, 2H), 6.50 (m, 1H), 4.52 (pent, J = 6.0 Hz, 1H), 2.38 (m, 1H), 2.31 (s, 1H), 1.92-1.84 (m, 1H), 1.58-1.36 (m, 5H), 1.30 (d, J = 6.0 Hz, 6H), 1.23-1.17 (m, 2H); LC-MS: purity: 100.00%; MS (m/e): 379.06 (M + H).sup.+ 154 04 Racemic-(2-exo)-N6- (bicyclo[2.2.1]hept-2-yl)- N2-(3-methoxy)phenyl- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.10 (s, 1H), 7.33 (s, 1H), 7.68 (m, 1H), 7.41 (m, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H), 6.50 (dd, J = 2.4, 7.8 Hz, 1H), 4.06 (m, 1H), 3.79 (s, 3H), 2.41 (m, 1H), 2.34 (s, 1H), 1.94-1.87 (m, 1H), 1.60-1.36 (m, 5H), 1.27-1.21 (m, 2H); LC-MS: purity: 100.00%; MS (m/e): 351.02 (M + H).sup.+ 155 05 Racemic-(2-exo)-N6- (bicyclo[2.2.1]hept-2-yl)- N2-(3- aminosulfonyl)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.26 (m, 1H), 8.09 (s, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.42 (m, 2H), 7.35 (t, J = 7.8 Hz, 1H), 3.99 (m, 1H), 2.37 (m, 1H), 2.32 (s, 1H), 1.94-1.86 (m, 1H), 1.58-1.32 (m, 5H), 1.25-1.22 (m, 2H); LC- MS: purity: 100.00%; MS (m/e): 399.97 (M + H).sup.+ 156 06 Racemic-(2-exo)-N6- (bicyclo[2.2.1]hept-2-yl)- N2-(4-piperidino)phenyl- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.07 (s, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 3.99 (m, 1H), 3.39 (m, 4H), 2.44 (m, 1H), 2.37 (s, 1H), 1.89 (m, 4H), 1.71-1.24 (m, 10H); LC-MS: purity: 100.00%; MS (m/e): 404.07 (M + H).sup.+ 157 07 Racemic-(2-exo)-N6- (bicyclo[2.2.1]hept-2-yl)- N2-[4-(4- pyridinylmethyl)phenyl]- 1H-purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.35 (m, 1H), 8.11 (s, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.13 (d, J = 6.0 Hz, 1H), 7.05 (d, J = 7.8 Hz, 1H), 3.99 (m, 1H), 3.92 (s, 2H), 2.41 (m, 1H), 2.32 (s, 1H), 1.86-1.80 (m, 1H), 1.60-1.13 (m, 5H); LC-MS: purity: 100.00%; MS (m/e): 412.05 (M + H).sup.+ 158 08 Racemic-(2-exo)-N6- (bicyclo[2.2.1]hept-2-yl)- N2-(1H-indol-5-yl)-1H- purine-2,6-diamine .sup.1H NMR (DMSO-d.sub.6): δ 8.46 (brs, 1H), 8.06 (s, 1H), 7.75 (m, 1H), 7.32 (m, 1H), 7.22 (m, 2H), 7.06 (brs, 1H), 6.27 (m, 1H), 4.02 (m, 1H), 3.30 (s, 1H), 2.30 (s, 1H), 2.24 (s, 1H), 1.74-1.09 (m, 7H); LC-MS: purity: 100.00%; MS (m/e): 360.06 (M + H).sup.+ 159 09 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- methyl)phenyl-1H- pyrrolo[2,3-d]pyrimidine- 2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.22 (s, 1H), 7.49 (s, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 6.78 (s, 1H), 6.76 (d, J = 7.5 Hz, 1H), 6.33 (m, 2H), 4.52 (m, 1H), 2.96 (s, 1H), 2.89 (s, 1H), 2.66 (d, J = 8.1 Hz, 1H), 2.32 (s, 3H), 1.59 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 375.04 (M + H).sup.+ 160 0 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(1H- indol-5-yl)-1H- pyrrolo[2,3-d]pyrimidine- 2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.33 (s, 1H), 7.79 (m, 1H), 7.37 (d, J = 8.7 Hz, 1H), 7.25 (d, J = 3.0 Hz, 1H), 7.16 (dd, J = 2.4, 8.7 Hz, 1H), 6.77 (d, J = 3.6 Hz, 1H), 6.41 (d, J = 3.3 Hz, 1H), 6.31 (m, 2H), 4.45 (d, J = 7.8 Hz, 1H), 2.96 (s, 1H), 2.91 (s, 1H), 2.61 (d, J = 8.1 Hz, 1H), 2.31 (d, J = 8.7 Hz, 1H), 1.59 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 400.04 (M + H).sup.+ 161 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- aminosulfonyl)phenyl-1H- pyrrolo[2,3-d]pyrimidine- 2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.42 (m, 1H), 8.17 (s, 1H), 7.83 (m, 1H), 7.40 (m, 2H), 6.80 d, J = 3.6 Hz, 1H), 6.37 (d, J = 3.6 Hz, 1H), 6.33 (m, 2H), 4.55 (m, 1H), 2.96 (s, 1H), 2.86 (s, 1H), 2.74 (d, J = 8.1 Hz, 1H), 2.33 (d, J = 8.7 Hz, 1H), 1.58 (d, J = 9.3 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 440.01 (M + H).sup.+ 162 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(4- piperidino)phenyl-1H- pyrrolo[2,3-d]pyrimidine- 2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.19 (m, 2H), 7.61 (d, J = 9.0 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H), 6.79 (m, 1H), 6.35 (m, 2H), 4.43 (m, 1H), 3.23 (m, 4H), 2.97 (s, 1H), 2.90 (s, 1H), 2.65 (d, J = 8.1 Hz, 1H), 2.29 (d, J = 9.0 Hz, 1H), 1.84-1.57 (m, 7H); LC-MS: purity: 100.00%; MS (m/e): 444.54 (M + H).sup.+ 163 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-[4- (4-morpholinyl)phenyl]- 1H-pyrrolo[2,3- d]pyrimidine-2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.19 (m, 2H), 7.50 (d, J = 9.0 Hz, 2H), 6.96 (d, J = 9.0 Hz, 2H), 6.80 (d, J = 3.6 Hz, 1H), 6.38 (d, J = 3.6 Hz, 1H), 6.32 (m, 2H), 4.41 (d, J = 7.8 Hz, 1H), 3.84 (t, J = 4.8 Hz, 4H), 3.10 (t, J = 4.8 Hz, 4H), 2.97 (s, 1H), 2.90 (s, 1H), 2.63 (d, J = 9.3 Hz, 1H), 2.29 (d, J = 8.7 Hz, 1H), 1.59 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 446.49 (M + H).sup.+ 164 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonyIbicyclo[2.2.1] hept-5-en-2-yl)-N2-[4- (4- pyridinylmethyl)phenyl]- 1H-pyrrolo[2,3- d]pyrimidine-2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.40 (m, 1H), 8.13 (m, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.30 (m, 1H), 7.15 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 3.3 Hz, 1H), 6.36 (d, J = 3.3 Hz, 1H), 6.28 (m, 2H), 4.41 (d, J = 7.5 Hz, 1H), 4.00 (s, 2H), 2.97 (s, 1H), 2.90 (s, 1H), 2.62 (d, J = 9.3 Hz, 1H), 2.29 (d, J = 8.7 Hz, 1H), 1.58 (d, J = 9.3 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 452.53 (M + H).sup.+ 165 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-2-yl)-N2-(3- methyl)phenyl-1H-purine- 2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.22 (s, 1H), 7.66 (s, 1H), 7.47 (m, 1H), 7.13 (t, J = 7.8 Hz, 1H), 6.76 (d, J = 3.3 Hz, 1H), 6.30 (d, J = 3.3 Hz, 1H), 4.47 (d, J = 8.4 Hz, 1H), 2.68 (d, J = 8.4 Hz, 1H), 2.44 (m, 1H), 2.39 (s, 1H), 2.33 (s, 3H), 2.12 (d, J = 10.2 Hz, 1H), 1.70-1.28 (m, 5H); LC-MS: purity: 99.70%; MS (m/e): 377.84 (M + H).sup.+ 166 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-2-yl)-N2-(1H- indol-5-yl)-1H-purine-2,6- diamine .sup.1H NMR (CD.sub.3OD): δ 8.31 (s, 1H), 7.80 (m, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.25 (d, J = 3.3 Hz, 1H), 7.16 (dd, J = 2.1, 8.4 Hz, 1H), 6.77 (d, J = 3.3 Hz, 1H), 6.41 (dd, J = 3.3, 5.7 Hz, 1H), 4.48 (d, J = 7.8 Hz, 1H), 2.70 (d, J = 8.4 Hz, 1H), 2.42 (s, 1H), 2.36 (m, 1H), 2.19 (d, J = 10.2 Hz, 1H), 1.69-1.30 (m, 5H); LC-MS: purity: 99.92%; MS (m/e): 402.90 (M + H).sup.+ 167 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-2-yl)-N2-[4-(4- morpholinyl)phenyl]-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.21 (s, 1H), 7.52 (d, J = 9.0 Hz, 2H), 6.95 (d, J = 9.0 Hz, 2H), 6.78 (d, J = 3.6 Hz, 1H), 6.34 (d, J = 3.6 Hz, 1H), 4.45 (d, J = 7.8 Hz, 1H), 3.84 (t, J = 4.8 Hz, 4H), 3.09 (t, J = 4.8 Hz, 4H), 2.71 (d, J = 8.4 Hz, 1H), 2.43 (s, 1H), 2.35 (m, 1H), 2.15 (d, J = 10.2 Hz, 1H), 1.67- 1.29 (m, 5H); LC-MS: purity: 100.00%; MS (m/e): 448.13 (M + H).sup.+ 168 Racemic-(2-exo,3-exo)- N6-(3-amino- carbonylbicyclo[2.2.1] hept-2-yl)-N2-(4- piperidino)phenyl-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.24 (s, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.08 (d, J = 8.7 Hz, 2H), 6.79 (d, J = 9.0 Hz, 1H), 6.75 (d, J = 3.3 Hz, 1H), 6.38 (d, J = 3.3 Hz, 1H), 4.57 (d, J = 7.8 Hz, 1H), 3.19 (m, 2H), 3.02 (t, J = 4.8 Hz, 2H), 2.85 (d, J = 7.8 Hz, 1H), 2.52 (s, 1H), 2.38 (m, 1H), 2.26 (d, J = 9.9 Hz, 1H), 1.80-1.36 (m, 1H); LC-MS: purity: 100.00%; MS (m/e): 446.18 (M + H).sup.+ 169 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-[4- (1,1- dimethylethyl)phenyl]-1H- pyrrolo[2,3-d]pyrimidine- 2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.20 (s, 1H), 7.60 (m, 1H), 7.52 (m, 1H), 7.19 (t, J = 7.8 Hz, 1H), 7.03-7.00 (m, 1H), 7.78 (d, J = 3.6 Hz, 1H), 6.36 (d, J = 3.6 Hz, 1H), 6.31 (m, 2H), 4.52 (d, J = 6.6 Hz, 1H), 2.96 (s, 1H), 2.88 (s, 1H), 2.67 (d, J = 9.3 Hz, 1H), 2.31 (d, J = 9.0 Hz, 1H), 1.59 (d, J = 9.0 Hz, 1H), 1.34 (s, 9H); LC-MS: purity: 100.00%; MS (m/e): 417.57 (M + H).sup.+ 170 0 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-[3- [2-(methylamino)-2- oxoethoxy]phenyl]]-1H- pyrrolo[2,3-d]pyrimidine- 2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (s, 1H), 7.60 (m, 1H), 7.18 (d, J = 4.8 Hz, 1H), 6.80 (d, J = 3.3 Hz, 1H), 6.57 (m, 1H), 6.36 (d, J = 3.3 Hz, 1H), 6.32 (m, 2H), 4.50 (m, 3H), 2.96 (s, 1H), 2.89 (s, 1H), 2.82 (s, 3H), 2.67 (d, J = 9.3 Hz, 1H), 2.31 (d, J = 9.0 Hz, 1H), 1.59 (d, J = 9.3 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 448.51 (M + H).sup.+ 171 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(4- phenylmethyl)phenyl-1H- pyrrolo[2,3-d]pyrimidine- 2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.15 (s, 1H), 7.68 (s, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.25-7.09 (m, 5H), 6.76 (d, J = 3.6 Hz, 1H), 6.34 (d, J = 3.6 Hz, 1H), 6.27 (m, 2H), 4.36 (d, J = 6.9 Hz, 1H), 3.93 (s, 2H), 2.97 (s, 1H), 2.89 (s, 1H), 2.59 (d, J = 7.5 Hz, 1H), 2.23 (d, J = 9.3 Hz, 1H), 1.57 (d, J = 9.6 Hz, 1H); LC- MS: purity: 100.00%; MS (m/e): 451.56 (M + H).sup.+ 172 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(3- isopropoxy)phenyl-1H- pyrrolo[2,3-d]pyrimidine- 2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.17 (s, 1H), 7.51 (m, 1H), 7.13 (t, J = 8.1 Hz, 1H), 7.06-7.03 (m, 1H), 6.80 (d, J = 3.6 Hz, 1H), 6.51 (dd, J = 2.4, 8.1 Hz, 1H), 6.42 (dd, J = 3.0, 5.4 Hz, 1H), 6.32 (m, 2H), 4.61 (pent, J = 6.0 Hz, 1H), 4.48 (d, J = 7.8 Hz, 1H), 2.97 (s, 1H), 2.91 (s, 1H), 2.68 (d, J = 7.8 Hz, 1H), 2.31 (d, J = 8.7 Hz, 1H), 1.59 (d, J = 9.0 Hz, 1H), 1.32 (d, J = 6.0 Hz, 6H); LC-MS: purity: 100.00%; MS (m/e): 419.56 (M + H).sup.+ 173 Racemic-(2-exo,3-exo)- N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)-N2-(2,3- dihydro-1-methylsulfonyl- 1H-indol-5-yl)-1H- pyrrolo[2,3-d]pyrimidine- 2,4-diamine .sup.1H NMR (CD.sub.3OD): δ 8.19 (s, 1H), 7.65 (m, 1H), 7.42 (dd, J = 2.1, 8.7 Hz, 1H), 7.23 (d, J = 8.7 Hz, 1H), 6.79 d, J = 3.3 Hz, 1H), 6.36 (d, J = 3.3 Hz, 1H), 6.32 (m, 2H), 4.44 (d, J = 8.7 Hz, 1H), 3.96 (t, J = 8.4 Hz, 2H), 2.97 (s, 1H), 2.88 (s, 1H), 2.65 (d, J = 8.7 Hz, 1H), 2.31 (d, J = 9.3 Hz, 1H), 1.58 (d, J = 9.3 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 480.98 (M + H).sup.+

(18) TABLE-US-00002 TABLE 2 No. Structure Name Spectroscopic Data 174 3-(2-(4-(4- cyclohexylpiperazine- 1-carbonyl) phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 572.06 (M + H), 570.02 (M − H). 175 3-(2-(3-fluoro-4-(4-(4- methylpiperazin-1- yl)piperidin-1- yl)phenylamino) thieno[3,2-d]pyrimidin- 4-ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 577.10 (M + H), 575.06 (M − H). 176 3-(2-(4-(1,4′- bipiperidin-1′-yl)-3- fluorophenylamino) thieno[3,2-d]pyrimidin- 4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 562.27 (M + H), 560.35 (M − H). 177 3-(2-(3-fluoro-4-(4- methyl-1,4′- bipiperidin-1′- yl)phenylamino) thieno[3,2-d] pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 576.13 (M + H), 574.08 (M − H). 178 3-(2-(4-(4- (bicyclo[3.3.1]nonan- 9-yl)piperazin-1- yl)phenylamino) thieno[3,2-d] pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 584.16 (M + H), 582.12 (M − H). 179 3-(2-(3-fluoro-4-(4- morpholinopiperidin- 1-yl)phenyl- amino)thieno[3,2-d] pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 564.05 (M + H), 562.02 (M − H). 180 0 3-(2-(4-((R)-3- (dimethylamino) pyrrolidine-1-carbonyl) phenylamino)thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 518.20 (M + H), 516.29 (M − H). 181 3-(2-(4-(4-(8-methyl- 8-aza- bicyclo[3.2.1]octan-3- yl)piperazin-1- yl)phenylamino) thieno[3,2-d] pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 585.26 (M + H), 583.38 (M − H). 182 3-(2-(3,4-dihydro-2H- benzo[b][1,4]dioxepin-7- ylamino)thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 449.97 (M + H), 447.91 (M − H). 183 3-(2-(4-(2- (cyclooctyl(methyl) amino)ethoxy)phenyl- amino)thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 561.09 (M + H), 559.06 (M − H). 184 3-(2-(4-(1- (bicyclo[2.2.1]heptan- 2-yl)piperidin-4- yl)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide MS (ES) 555.35 (M + H), 553.23 (M − H). 185 3-(2-(4-(2-(pyrrolidin-1- yl)ethoxy)phenylamino)- 6,7-dihydro-5H- cyclopenta[d]pyrimidin- 4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3, 300 MHz) 11.20 (s, 1H), 8.25 (d, 1H), 7.58 (d, 2H), 6.78 (m, 3H), 6.29 (m, 1H), 6.20 (m, 1H), 5.87 (s, 1H), 4.29 (m, 2H), 4.09 (t, 1H), 3.46 (m, 6H), 3.02 (s, 1H), 2.89 (m, 3H), 2.54 (m, 4H), 2.17 (m, 6H), 1.53 (d, 1H) ppm; MS (ES) 475.17 (M + H) 186 3-(6-benzyl-4-(4-(2- (pyrrolidin-1- yl)ethoxy)phenylamino)- 5,6,7,8- tetrahydropyrido[4,3- d]pyrimidin-2- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (MeOD.sub.4, 300 MHz) 7.55 (d, 2H), 7.30-7.42 (m, 5H), 7.02 (d, 2H), 6.35 (m, 1H), 6.23 (m, 1H), 4.33 (t, 2H), 4.09 (d, 1H), 3.87 (s, 2H), 3.65 (t, 2H), 3.44 (m, 4H), 3.31 (m, 2H), 2.98 (s, 1H), 2.86 (m, 2H), 2.74 (m, 2H), 2.55 (d, 1H), 2.13 (m, 3H), 2.06 (d, 1H), 1.51 (d, 1H) ppm; MS (ES) 580.26 (M + H). 187 (2S,3R)-3-(2-(4-(2- (pyrrolidin-1- yl)ethoxy)phenylamino) thieno[3,2- d]pyrimidin-4-ylamino) bicyclo[2.2.1]hept- 5-ene-2-carboxamide .sup.1H NMR (CDCl.sub.3, 300 MHz) 8.04 (s, 1H), 7.72 (d, 1H), 7.49 (d, 2H), 7.20 (d, 1H), 6.78 (d, 2H), 6.23 (m, 1H), 6.11 (m, 1H), 4.21 (t, 2H), 4.08 (d, 1H), 3.47 (t, 2H), 3.55 (m, 4H), 2.94 (s, 1H), 2.88 (s, 1H), 2.46 (d, 1H), 2.03 (m, 5H), 1.47 (d, 1H) ppm; MS (ES) 491 (M + H). 188 (2S,3R)-3-(2-(4-(2- (pyrrolidin-1- yl)ethoxy)phenylamino) thieno[2,3- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3/MeOD.sub.4, 300 MHz) 8.20 (s, 1H), 7.49 (d, 2H), 7.24 (br s, 1H), 6.97 (d, 1H), 6.83 (d, 1H), 6.75 (d, 2H), 6.24 (m, 1H), 6.18 (m, 1H), 4.19 (m, 3H), 3.44 (m, 2H), 3.35 (m, 4H), 2.95 (s, 1H), 2.85 (s, 1H), 2.04 (m, 5H), 1.49 (d, 1H) ppm; MS (ES) 491 (M + H). 189 (2S,3R)-3-(1-benzyl- 6-(4-(2-(pyrrolidin-1- yl)ethoxy)phenylamino)- 1H-pyrazolo[3,4- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3, 300 MHz) 7.61 (s, 1H), 7.58 (d, 2H), 7.24 (s, 5H), 6.93 (d, 1H), 6.81 (d, 2H), 6.20 (m, 2H), 5.60 (br s, 1H), 5.25 (s, 2H), 4.36 (m, 1H), 4.07 (m, 2H), 2.96 (s, 1H), 2.88 (m, 2H), 2.66 (m, 4H), 2.46 (d, 1H), 2.17 (d, 1H), 1.80 (m, 5H), 1.54 (d, 1H) ppm; .sup.13C NMR (CDCl.sub.3, 75 MHz) 176.53, 161.64, 158.85, 157.31, 154.20, 138.92, 137.45, 135.69, 134.29, 128.93, 128.42, 128.26, 122.62, 121.33, 115.13, 99.69, 67.81, 57.40, 55.44, 54.88, 53.08, 48.45, 47.35, 46.43, 44.92, 32.21, 30.99, 23.97; MS (ES) 565 (M + H). 190 0 3-(2-(4-((R)-1- methylpiperidin-3- yloxy)phenylamino) thieno[3,2-d]pyrimidin- 4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3/MeOD.sub.4, 300 MHz) 8.34 (s, 2H), 7.64 (d, 1H), 7.49 (d, 2H), 7.10 (d, 1H), 6.83 (d, 2H), 6.21 (m, 1H), 6.17 (m, 1H), 4.42 (m, 1H), 4.18 (d, 1H), 3.10 (m, 1H), 2.88 (m, 3H), 2.40-2.60 (m, 3H), 2.50 (s, 3H), 2.05 (d, 1H), 1.89 (m, 2H), 1.40-1.80 (m, 3H) ppm; MS (ES) 491 (M + H). 191 3-(2-(3-fluoro-4-(((S)- 1-methylpyrrolidin-2- yl)methoxy)phenyl- amino)thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3/MeOD.sub.4, 300 MHz) 8.39 (s, 1H), 7.77 (m, 1H), 7.66 (d, 1H), 7.14 (m, 2H), 6.92 (m, 1H), 6.35 (m, 1H), 6.29 (m, 1H), 4.30 (m, 2H), 4.18 (m, 1H), 3.50 (m, 1H), 3.35 (m, 1H), 2.99 (m, 2H), 2.75 (m, 4H), 2.51 (d, 1H), 1.95-2.25 (m, 5H), 1.56 (d, 1H) ppm; MS (ES) 509 (M + H). 192 3-(2-(4-(4- cyclohexylpiperazin- 1-yl)-3- fluorophenylamino) thieno[3,2-d]pyrimidin- 4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (DMSO-d.sub.6, 300 MHz) 10.00 (br s, 1H), 9.49 (br s, 1H), 8.95 (br s, 1H), 8.12 (d, 1H), 7.75-7.85 (m, 2H), 7.29 (m, 2H), 7.21 (d, 1H). 7.08 (t, H), 6.34 (m, 1H), 6.29 (m, 1H), 4.18 (t, 1H), 3.48 (m, 4H), 3.23 (m, 2H), 3.04 (m, 2H), 2.93 (s, 1H), 2.48 (m, 2H), 2.11 (m, 2H), 1.84 (m, 2H), 1.25-1.45 (m, 5H), 1.13 (m, 1H) ppm; MS (ES) 562.08 (M + H). 193 3-(2-(3-fluoro-4-(4- methyl-1,4-diazepan- 1-yl)phenylamino) thieno[3,2-d]pyrimidin- 4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3/MeOD.sub.4, 300 MHz) 8.12 (s, 1H), 7.70 (d, 1H), 7.60 (m, 1H), 7.15 (d, 1H), 7.05 (m, 1H), 6.73 (t, 1H), 6.23 (m, 2H), 4.08 (d, 1H), 3.36 (m, 6H), 3.21 (m, 2H), 2.93 (m, 2H), 2.81 (s, 3H), 2.49 (d, 1H), 2.25 (m, 2H), 1.96 (d, 1H), 1.46 (d, 1H) ppm; MS (ES) 508.16 (M + H). 194 3-(2-(3-fluoro-4-(2- (pyrrolidin-1- yl)ethoxy)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3, 300 MHz) 8.21 (s, 2H), 7.68 (m, 2H), 7.08 (m, 2H), 6.84 (t, 1H), 6.21 (s, 2H), 4.24 (m, 2H), 4.10 (d, 1H), 3.42 (m, 2H), 3.31 (m, 4H), 2.91 (m, 2H), 2.46 (d, 1H), 1.97 (m, 5H), 1.46 (d, 1H) ppm; MS (ES) 509.19 (M + H). 195 3-(2-(3-fluoro-4-(4- (pyrrolidin-1- yl)piperidin-1- yl)phenylamino) thieno[3,2-d]pyrimidin- 4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (DMSO-d.sub.6, 300 MHz) 10.50 (br s, 1H), 10.10 (br s, 1H), 9.15 (br s, 1H), 8.14 (d, 1H), 7.74 (m, 2H), 7.25 (m, 2H), 7.04 (t, 1H), 6.36 (m, 1H), 6.28 (m, 1H), 4.17 (t, 1H), 3.52 (m, 2H), 3.39 (m, 2H), 3.20 (m, 1H), 3.07 (m, 2H), 2.93 (s, 2H), 2.63 (m, 2H), 2.51 (m, 4H), 2.11 (m, 2H), 1.78-2.00 (m, 5H), 1.44 (d, 2H) ppm; MS (ES) 548.35 (M + H). 196 3-(2-(3-fluoro-4-(4- methylpiperazin-1- yl)phenylamino) thieno[3,2-d]pyrimidin- 4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3/MeOD.sub.4, 300 MHz) 7.71 (d, 1H), 7.55 (d, 1H), 7.17 (m, 2H), 6.85 (t, 1H), 6.19 (m, 2H), 4.09 (d, 1H), 3.15-3.30 (m, 8H), 2.90 (s, 2H), 2.73 (s, 3H), 2.43 (d, 1H), 1.97 (d, 1H), 1.45 (d, 1H); MS(ES) 494.21 (M + H). 197 (1S,2R,3S,5R)- N,2,6,6-tetramethyl-2- (2-(4-(2-(pyrrolidin-1- yl)ethoxy)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[3.1.1] heptane-3- carboxamide .sup.1H NMR (CDCl.sub.3, 300 MHz) 9.08 (br s, 1H), 8.63 (s, 1H), 7.62 (d, 1H), 7.39 (d, 2H), 7.18 (d, 1H), 6.82 (d, 2H), 6.70 (br s, 1H), 4.23 (m, 2H), 3.27 (m, 2H), 3.12 (m, 4H), 3.01 (m, 2H), 2.87 (m, 4H), 2.14 (m, 3H), 2.00 (m, 5H), 1.59 (s, 3H), 1.24 (s, 3H), 1.06 (s, 3H) ppm; .sup.13C NMR (CDCl.sub.3, 75 MHz) 176.18, 169.83, 156.06, 154.68, 154.62, 132.76, 132.59, 124.16, 120.04, 114.72, 109.73, 65.44, 61.20, 54.64, 54.56, 50.36, 47.15, 40.40, 38.73, 32.86, 30.21, 29.48, 27.22, 26.19, 23.80, 23.67; MS(ES) 549.29 (M + H). 198 (1S,2R,3S,5R)-2-(2- (4-(4- cyclohexylpiperazin-1- yl)phenylamino) thieno[3,2-d]pyrimidin- 4-ylamino)-N,2,6,6- tetramethylbicyclo[3.1.1] heptane-3- carboxamide .sup.1H NMR (CDCl.sub.3, 300 MHz) 11.24 (s, 1H), 9.73 (s, 1H), 7.68 (d, 1H), 7.37 (d, 2H), 7.25 (d, 1H), 6.86 (d, 2H), 6.50 (br s, 1H), 3.20-3.50 (m, 8H), 3.15 (m, 1H), 2.85 (m, 5H), 2.16 (m, 4H), 1.94 (m, 4H), 1.74 (m, 1H), 1.52 (s, 3H), 1.20-1.50 (m, 3H), 1.30 (m, 5H), 1.04 (s, 1H) ppm; MS (ES) 602 (M + H). 199 (2S,3R)-3-(2-(4-(4- methylpiperazine-1- carbonyl)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3/MeOD.sub.4, 300 MHz) 7.75 (m, 3H), 7.32 (d, 2H), 7.26 (d, 1H), 6.27 (m, 1H), 6.18 (m, 1H), 4.15 (d, 1H), 3.22 (s, 3H), 3.11 (m, 6H), 2.95 (m, 2H), 2.73 (m, 2H), 2.48 (d, 1H), 2.01 (d, 1H), 1.50 (d, 1H) ppm; MS (ES) 504.20 (M + H). 200 0 (2S,3R)-3-(2-(4-((S)- 3-(dimethyl- amino)pyrrolidin-1- yl)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3/MeOD.sub.4, 300 MHz) 8.15 (s, 2H), 7.65 (d, 1H), 7.32 (d, 2H), 7.09 (d, 1H), 6.43 (d, 2H), 6.16 (m, 1H), 6.08 (m, 1H); 3.53 (m, 1H), 3.99 (m, 3H), 3.19 (m, 2H), 2.87 (d, 2H), 2.60 (s, 6H), 2.38 (d, 1H), 2.28 (m, 1H), 2.14 (m, 1H), 1.96 (d, 1H), 1.43 (d, 1H) ppm; MS(ES) 490.12 (M + H). 201 (2S,3S)-3-(2-(4-((R)- 3-(dimethyl- amino)pyrrolidin-1- yl)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3/MeOD.sub.4, 300 MHz) 8.22 (s, 2H), 7.72 (d, 1H), 7.44 (d, 2H), 7.20 (d, 1H), 6.54 (d, 2H), 6.28 (m, 1H), 6.19 (m, 1H), 4.20 (m, 1H), 2.40- 2.80 (m, 4H), 3.31 (m, 1H), 2.96 (m, 2H), 2.67 (s, 6H), 2.50 (m, 1H), 2.36 (m, 1H), 2.22 (m, 1H), 2.09 (m, 1H), 1.56 (m, 1H) ppm; MS (ES) 490.31 (M + H). 202 (2S,3R)-3-(2-(3- fluoro-4-(5-methyl- 2,5-diaza- bicyclo[2.2.1]heptan- 2-yl)phenyl- amino)thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H NMR (CDCl.sub.3/MeOD.sub.4, 300 MHz) 8.34 (s, 2H), 7.73 (m, 2H), 7.14 (m, 2H), 6.63 (t, 1H), 6.31 (m, 2H), 4.46 (m, 1H), 4.29 (m, 1H), 4.14 (m, 1H), 3.63 (m, 2H), 3.30-3.40 (m, 2H), 3.00 (m, 2H), 2.78 (s, 3H), 2.57 (d, 1H), 2.16 (m, 3H), 1.57 (d, 1H) ppm; MS (ES) 506.12 (M + H). 203 (2S,3R)-3-(2-(4-(2- methyl-2-(pyrrolidin- 1-yl) propoxy)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 8.92 (s, 1H), 8.12 (s, 1H), 7.94 (d, J = 5.1 Hz, 1H), 7.73 (d, J = 9.0 Hz, 2H), 7.66 (s, 2H), 7.22 (s, 1H), 7.10 (d, J = 5.4 Hz, 1H), 6.93 (d, J = 8.7 Hz, 2H), 6.33 (s, 2H), 4.26 (t, J = 6.6 Hz, 1H), 3.99 (s, 2H), 3.19 (s, 4H), 2.87 (d, J = 9.6 Hz, 2H), 2.55 ( d, J = 6.6 Hz, 1H), 2.17 (d, J = 8.7 Hz, 1H), 1.86 (s, 4H), 1.43 (d, J = 8.1 Hz, 1H), 1.34 (s, 6H) ppm; MS (ES) 519.12 (M + H), 517.26 (M − H). 204 (2S,3R)-3-(2-(4-(2- (cyclopentyl(methyl) amino)ethoxy)phenyl- amino)thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 8.98 (s, 1H), 8.11 (s, 1H), 7.95 (d, J = 5.4 Hz, 1H), 7.73 (d, J = 9.0 Hz, 2H), 7.66 (s, 2H), 7.23 (s, 1H), 7.11 (d, J = 5.4 Hz, 1H), 6.93 (d, J = 9.0 Hz, 2H), 6.32 (s, 2H), 4.26-412 (m , 4H), 3.69 (t, 1H), 3.55 (s, 2H), 2.89 (s, 2H), 2.85 (s, 3H), 2.53 (d, J = 8.4 Hz, 1H), 2.16 (d, J = 8.7 Hz, 1H), 1.71 (s, 4H), 1.55 (s, 2H), 1.43 (d, J = 8.7 Hz, 1H) ppm; MS (ES) 519.03 (M + H), 516.91 (M − H). 205 (2S,3R)-3-(2-(4-(4- (diethylamino)piperidin- 1-yl)-3- fluorophenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 9.10 (s, 1H), 8.13 (s, 1H), 7.95 (d, J = 5.4 Hz, 1H), 7.89 (d, J = 15.6 Hz, 1H), 7.54 (d, J = 6.9 Hz, 1H), 7.68 (s, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.24 (s, 1H), 7.13 (d, J = 5.1 Hz, 1H), 6.93 (t, J = 8.7 Hz, 1H), 6.34 (s, 2H), 4.25 (t, J = 7.5 Hz, 1H), 2.89 (s, 4H), 2.80 (m, 4H), 2.64 (t, J = 11.4 Hz, 3H), 2.55 (d, J = 7.8 Hz, 1H), 2.16 (d, J = 8.4 Hz, 1H), 1.87 (d, J = 11.1 Hz, 2H), 1.72-1.61 (m, 2H), 1.42 (d, J = 8.4 Hz, 1H), 1.09 (t, J = 7.2 Hz, 6H) ppm; MS (ES) 550.19 (M + H), 548.32 (M − H). 206 (2S,3R)-3-(2-(3- fluoro-4-(4-(methyl- sulfonyl)piperazin-1- yl)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 9.23 (s, 1H), 8.11 (s Hz, 1H), 7.97 (d, J = 5.1 Hz, 1H), 7.90 (d, J = 15.3 Hz, 1H), 7.69 (s, 1H), 7.34 (d, J = 8.7 Hz, 1H), 7.25 (s, 1H), 7.15 (d, J = 5.1 Hz, 1H), 6.99 (t, J = 9.3 Hz, 1H), 6.34 (s, 2H), 4.25 (t, J = 7.5 Hz, 1H), 3.26 (s, 4H), 3.03 (s, 4H), 2.93 (s, 3H), 2,89 (s, 2H), 2.56 (d, J = 8.1 Hz, 1H), 2.16 (d, J = 8.4 Hz, 1H), 1.43 (d, J = 8.4 Hz, 1H) ppm; MS (ES) 558.12 (M + H), 556.25 (M −H). 207 (2S,3R)-3-(2-(4-(4-(2- amino-2- oxoethyl)piperazin-1- yl)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 8.80 (s, 1H), 8.11 (s, 1H), 7.92 (d, J = 5.4 Hz, 1H), 7.68-7.60 (m, 4H), 7.21 (s, 2H), 7.09 (d, J = 4.5 Hz, 1H), 6.33 (s, 2H), 4.26 (t, J = 8.1 Hz, 1H), 3.24 (s, 2H), 3.13 (s, 4H), 2.87 (d, J = 9.0 Hz, 2H), 2,74 (s, 4H), 2.55 (d, J = 7.8 Hz, 1H), 2.17 (d, J = 8.7 Hz, 1H), 1.42 (d, J = 8.4 Hz, 1H) ppm; MS (ES) 519.17 (M + H), 517.30 (M − H). 208 ethyl 4-(4-(4- ((2R,3S)-3- carbamoylbicyclo[2.2.1] hept-5-en-2- ylamino)thieno[3,2- d]pyrimidin-2- ylamino)-2- fluorophenyl)piperazine- 1-carboxylate .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 9.39 (s, 1H), 8.03 (m, 1H), 7.85 (d, J = 15.0 Hz, 1H), 7.71 (s, 1H), 7.31-7.25 (m, 2H), 7.20-7.16 (m, 1H), 7.10-6.95 (m, 1H), 6.34 (s, 2H), 4.23 (t, J = 1.5 Hz, 1H), 4.10-4.02 (m, 2H), 3.51 (s, 4H), 2.90 (s, 6H), 2.56 (d, J = 8.1 Hz, 1H), 2.15 (d, J = 7.5 Hz, 1H), 1.43 (d, J = 6.9 Hz, 1H), 1.23-1.16 (m, 3H) ppm; MS (ES) 552.18 (M + H), 550.26 (M − H). 209 (2S,3R)-3-(2-(3- fluoro-4-(4-methyl- 1,4-bipiperidin-1′- yl)phenylamino)-6- (trifluoromethyl) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 9.27 (s, 1H), 8.11 (s, 1H), 7.86 (d, J = 15.3 Hz, 1H), 7.79 (s, 1H), 7.52 (s, 1H), 7.32 (d, J = 9.0 Hz, 1H), 7.14 (s, 1H), 6.95 (t, J = 9.0 Hz, 1H), 6.33 (s, 2H), 4.27 (t, J = 7.2 Hz, 1H), 3.23 (d, J = 11.4 Hz, 4H), 2.95 (m, 1H), 2.88 (d, J = 4.5, Hz 2H), 2.72-2.58 (m, 4H), 2.54 (d, J = 8.1 Hz, 1H), 2.21 (d, J = 8.1 Hz, 1H), 1.98 (d, J = 10.2 Hz, 2H), 1.77- 170 (m, 4H), 1.52 (m, 1H), 1.43 (d, J = 8.4 Hz, 1H), 1.33-1.23 (m, 2H), 0.91 (d, J = 6.0 Hz, 3H) ppm; MS (ES) 644.15 (M + H), 642.32 (M − H). 210 0 (2S,3R)-3-(2-(4-(2- (pyrrolidin-1- yl)ethoxy)phenyl- amino)-6- (trifluoromethyl) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 9.05 (s, 1H), 8.02 (d, J = 6.3 Hz, 1H), 7.72 (d, J = 10.5 Hz, 2H), 7.68 (s, 1H), 7.49 (s, 1H), 7.12 (s, 1H), 6.90 (d, J = 9.0 Hz, 2H), 6.30 (s, 2H), 4.27 (t, J = 7.5 Hz, 1H), 4.15 (m, 2H), 3.30 (s, 2H), 3.08 (s, 4H), 2.87 (d, J = 10.2 Hz, 2H), 2.54 (d, J = 7.8 Hz, 1H), 2.20 (d, J = 8.4 Hz, 1H), 1.86 (s, 4H), 1.43 (d, J = 8.4 Hz, 1H) ppm; MS (ES) 559.07 (M + H), 557.28 (M − H). 211 (2S,3R)-3-(2-(4-(4- cyclohexylpiperazine- 1-carbonyl)phenyl- amino)-6- (trifluoromethyl) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 9.45 (s, 1H), 8.14 (d, J = 6.9 Hz, 1H), 8.11 (s, 1H), 7.85 (d, J = 8.4 Hz, 2H), 7.82 (s, 1H), 7.48 (s, 1H), 7.30 (d, J = 8.7 Hz, 2H), 7.09 (s, 1H), 6.32 (s, 2H), 4.32 (t, J = 8.1 Hz, 1H), 3.49 (s, 2H), 3.31 (m, 4H), 2.88 (d, J = 8.4 Hz, 2H), 2.56 (d, J = 6.6 Hz, 2H), 2.25 (d, J = 9.0 Hz, 2H), 1.75 (s, 4H), 1.56 (d, J = 11.7 Hz, 1H), 1.44 (d, J = 8.1 Hz, 1H), 1.00-1.30 (m, 6H) ppm; MS (ES) 640.22 (M + H), 638.34 (M − H). 212 (2S,3R)-3-(6-chloro- 2-(4-(2-(pyrrolidin-1- yl)ethoxy)phenyl- amino)thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 9.16 (s, 1H), 8.03 (s, 1H), 7.94 (d, J = 6.3 Hz, 1H), 7.78 (d, J = 9.3 Hz, 2H), 7.61 (s, 1H), 7.20 (s, 1H), 6.90 (d, J = 9.0 Hz, 2H), 6.32 (s, 2H), 4.20 (m, 3H), 3.42 (s, 2H), 3.21 (s, 4H), 2.87 (d, J = 9.3 Hz, 2H), 2.54 (d, J = 8.4 Hz, 1H), 2.17 (d, J = 8.1 Hz, 1H), 1.90 (s, 4H), 1.43 (d, J = 7.8 Hz, 1H) ppm; MS (ES) 525.10 (M + H), 523.22 (M − H). 213 (2S,3R)-3-(6-chloro- 2-(4-(4-cyclohexyl- piperazine-1- carbonyl)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 9.52 (s, 1H), 8.11 (s, 1H), 8.07 (d, J = 6.9 Hz, 1H), 7.92 (d, J = 8.4 Hz, 2H), 7.60 (s, 1H), 7.28 (d, J = 8.4 Hz, 2H), 7.17 (s, 1H), 6.33 (s, 2H), 4.28 (t, J = 7.2 Hz, 1H), 3.47 (s, 4H), 3.31 (s, 2H), 2.89 (s, 2H), 2.56 (d, J = 8.1 Hz, 2H), 2.60-2.17 (m, 2H), 1.73 (s, 4H), 1.56 (d, J = 11.4 Hz, 1H), 1.44 (d, J = 8.4 Hz, 1H), 1.00-1.30 (m, 6H) ppm; MS (ES) 606.15 (M + H), 604.31 (M − H). 214 (2S,3R)-3-(6-chloro- 2-(3-fluoro-4-(4- methyl-1,4′- bipiperidin-1′- yl)phenylamino) thieno[3,2- d]pyrimidin-4- ylamino)bicyclo[2.2.1] hept-5-ene-2- carboxamide .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 9.27 (s, 1H), 8.05 (s, 1H), 7.96 (d, J = 15.9 Hz, 1H), 7.62 (s, 1H), 7.38 (d, J = 8.7 Hz, 1H), 7.20 (s, 1H), 6.94 (t, J = 9.0 Hz, 1H), 6.33 (s, 2H), 4.25 (t, J = 7.2 Hz, 1H), 3.23 (d, J = 11.4 Hz, 4H), 2.89 (s, 2H), 2.72-2.58 (m, 4H), 2.54 (d, J = 8.1 Hz, 1H), 2.16 (d, J = 9.0 Hz, 1H), 1.97 (d, J = 9.9 Hz, 2H), 1.77-170 (m, 4H), 1.52 (m, 1H), 1.43 (d, J = 8.7 Hz, 1H), 1.33-1.23 (m, 2H), 0.91 (d, J = 6.3 Hz, 3H) ppm; MS (ES) 610.18 (M + H), 608.28 (M − H). 215 Racemic-(2-exo,3-exo)- N4-(3-aminocarbonyl- bicyclo[2.2.1]hept-5- en-2-yl)-N2-(3-methyl- 4-(2-(1-pyrrolidinyl) ethoxy)phenyl)-2,4- quinazoline-diamine .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 8.78 (s, 1H), 8.42-8.34 (m, 1H), 7.62-7.51 (m, 3H), 7.32 (d, J = 8.7 Hz, 1H), 7.17 (s, 1H), 7.12 (t, J = 7.4 Hz, 1H), 6.82 (d, J = 8.4 Hz, 1H), 6.32-6.29 (m, 2H), 4.35-4.25 (m, 1H), 4.03 (t, J = 6.0 Hz, 2H), 2.88 (t, J = 6.0 Hz, 2H), 2.86 (s, 2H), 2.68-2.58 (m, 4H), 2.57-2.55 (m, 3H), 2.22 (d, J = 8.7 Hz, 1H), 2.14 (s, 3H), 1.74-1.64 (m, 4H), 1.43 (d, J = 8.1 Hz, 1H) ppm; MS (ES) 499.47 (M + H), 497.30 (M − H). 216 Racemic-(2-exo,3- exo)-N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-(3-Chloro-4-(2-(1- pyrrolidinyl)ethoxy) phenyl)-2,4- quinazoline-diamine .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 9.06 (s, 1H), 8.52-8.42 (m, 1H), 8.07 (s, 1H), 7.67-7.61 (m, 2H), 7.55 (t, J = 7.8 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 7.19 (s, 1H), 7.15 (t, J = 7.2 Hz, 1H), 7.04 (d, J = 9.0 Hz, 1H), 6.33 (s, 2H), 4.30- 4.22 (m, 1H), 4.10 (t, J = 5.7 Hz, 2H), 2.89-2.85 (m, 3H), 2.70-2.60 (m, 4H), 2.55 (d, J = 8.4 Hz, 1H), 2.42-2.38 (m, 1H), 2.20 (d, J = 7.5 Hz, 1H), 1.74-1.64 (m, 4H), 1.42 (d, J = 9.0 Hz, 1H) ppm; MS (ES) 519.18 (M + H), 517.25 (M − H). 217 Racemic-(5-exo,6- exo)-N4-(4,7- methano-1,2- benzisoxazol- 3a,4,5,6,7,7a- hexahydro-3-phenyl- 5-aminocarbonyl-6- yl)-N2-(3- methyl)phenyl-1H- pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.23 (s, 1H), 7.72 (m, 1H), 7.58-7.55 (m, 1H), 7.47-7.43 (m, 3H), 7.37-7.20 (m, 4H), 7.00-6.98 (m, 1H), 4.79 (m, 1H), 3.76 (d, J = 7.8 Hz, 1H), 2.84 (d, J = 8.7 Hz, 1H), 2.78 (s, 1H), 2.51 (s, 1H), 2.40 (s, 3H), 2.13 (d, J = 10.8 Hz, 1H), 1.54 (d, J = 8.7 Hz, 1H); LC-MS: purity: 94.96%; MS (m/e): 495.10 (M + H).sup.+ 218 Racemic-(5-exo,6- exo)-N4-(4,7- methano-1,2- benzisoxazol- 3a,4,5,6,7,7a- hexahydro-3-phenyl- 6-aminocarbonyl-5- yl)-N2-(3- methyl)phenyl-1H- pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.17 (s, 1H), 7.75 (m, 2H), 7.44 (m, 4H), 7.38 (s, 1H), 7.30 (m, 1H), 7.01 (m, 1H), 4.65 (d, J = 7.5 Hz, 1H), 3.87 (d, J = 8.1 Hz, 1H), 2.98 (d, J = 7.8 Hz, 1H), 2.67 (d, J = 4.8 Hz, 1H), 2.40 (s, 3H), 2.23 (d, J = 11.4 Hz, 1H), 1.58 (d, J = 8.7 Hz, 1H); LC-MS: purily: 100.00%; MS (m/e): 495.11 (M + H).sup.+ 219 Racemic-(5-exo,6- exo)-N4-(4,7- methano-1,2- benzisoxazol- 3a,4,5,6,7,7a- hexahydro-3-phenyl- 5-aminocarbonyl-6- yl)-N2-[4-(4- morpholinyl)phenyl]- 1H-pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.21 (s, 1H), 7.64-7.07 (m, 10H), 4.79 (m, 1H), 3.84 (m, 2H), 3.78 (m, 4H), 3.11 (m, 4H), 2.84 (d, J = 8.4 Hz, 1H), 2.78 (s, 1H), 2.50 (s, 1H), 2.13 (d, J = 11.1 Hz, 1H), 1.53 (d, J = 11.4 Hz, 1H); LC-MS: purity: 89.26% 220 0 Racemic-(2-exo,3- exo)-N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[(4′-cyano[1,1′- biphenyl]-4-yl)]-1H- pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.20-8.18 (m, 1H), 7.82-7.61 (m, 6H), 8.35 (t, J = 8.1 Hz, 1H), 8.16 (t, J = 8.1 Hz, 1H), 6.98-6.92 (m, 2H), 6.80 (d, J = 3.6 Hz, 1H), 6.35 (d, J = 3.6 Hz, 1H), 6.21 (m, 1H), 6.06 (m, 1H), 4.47 (d, J = 7.5 Hz, 1H), 2.93 (s, 1H), 2.83 (s, 1H), 2.60 (d, J = 8.1 Hz, 1H), 2.29 (d, J = 8.7 Hz, 1H), 1.55 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 462.04 (M + H).sup.+ 221 Racemic-(2-exo,3- exo)-N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-(3-morpholin-4- yl-methylphenyl)-1H- pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.23 (s, 1H), 7.78 (m, 1H), 7.31-6.80 (m, 3H), 6.38 (m, 2H), 4.51 (d, J = 9.3 Hz, 1H), 3.85-3.63 (m, 4H), 2.97 (s, 1H), 2.93 (s, 1H), 2.88-2.76 (m, 6H), 2.64 (d, J = 8.7 Hz, 1H), 2.42 (d, J = 9.3 Hz, 1H), 1.59 (d, J = 9.6 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 460.09 (M + H).sup.+ 222 Racemic-(2-exo,3- exo)-N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-(3-N,N-diethyl- aminocarbonyl- phenyl)-1H- pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (s, 1H), 8.01 (s, 1H), 7.64 (dd, J = 2.1, 7.8 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 7.5 Hz, 1H), 6.80 (d, J = 3.6 Hz, 1H), 3.35 (d, J = 3.6 Hz, 1H), 6.32 (m, 2H), 4.48 (d, J = 7.5 Hz, 1H), 3.56 (m, 4H), 2.96 (s, 1H), 2.88 (s, 1H), 2.66 (d, J = 6.3 Hz, 1H), 2.32 (d, J = 8.7 Hz, 1H), 1.58 (d, J = 9.6 Hz, 1H), 1.27 (t, J = 6.6 Hz, 3H), 1.16 (t, J = 6.6 Hz, 3H); LC-MS: purity: 100.00%; MS (m/e): 460.09 (M + H).sup.+ 223 Racemic-(2-exo,3- exo)-N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[3-(4- pyridinylmethoxy)] phenyl-1H-pyirolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.52 (m, 2H), 8.10 (m, 2H), 7.68-6.63 (m, 4H), 6.39 (d, J = 3.3 Hz, 1H), 6.35-6.26 (m, 2H), 5.18 (s, 2H), 4.46 (d, J = 8.1 Hz, 1H), 2.94 (s, 1H), 2.91 (s, 1H), 2.65 (d, J = 8.1 Hz, 1H), 2.30 (d, J = 9.0 Hz, 1H), 1.58 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 468.11 (M + H).sup.+ 224 Racemic-(2-exo,3- exo-)-N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[3-(4-pyridinyl- methoxy)]phenyl- 1H-purine-2,6- diamine .sup.1H NMR (CD.sub.3OD): δ 8.52 (dd, J = 1.8, 4.5 Hz, 2H), 8.23 (s, 1H), 7.76 (s, 1H), 7.73 (m, 1H), 7.53 d, J = 6.0 Hz, 2H), 6.59 (m, 1H), 6.34-6.26 (m, 2H), 5.18 (s, 2H), 4.48 (d, J = 7.8 Hz, 1H), 2.96 (s, 1H), 2.86 (s, 1H), 2.67 (d, J = 8.7 Hz, 1H), 2.35 (d, J = 8.7 Hz, 1H), 1.62 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 469.35 (M + H).sup.+ 225 Racemic-(2-exo,3- exo)-N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[3-(3- pyridinylmethoxy)] phenyl-1H-pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.65 (d, J = 1.5 Hz, 1H), 8.50 (dd, J = 1.5, 4.8 Hz, 1H), 8.11 (bs, 2H), 7.96-7.34 (m, 1H), 7.72 (t, J = 2.1 Hz, 1H), 7.49-7.44 (m, 1H), 7.19 (t, J = 8.1 Hz, 1H), 7.07-7.04 (m, 1H), 6.82 (d, J = 3.6 Hz, 1H), 6.68-6.64 (m, 1H), 6.38 (d, J = 3.6 Hz, 1H), 6.29 (m, 1H), 6.20 (m, 1H), 5.15 (s, 2H), 4.44 (d, J = 7.8 Hz, 1H), 2.94 (s, 1H), 2.90 (s, 1H), 2.65 (d, J = 8.1 Hz, 1H), 2.29 (d, J = 9.3 Hz, 1H), 1.56 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 468.09 (M + H).sup.+ 226 Racemic-(2-exo,3- exo-)-N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[3-(3-pyridinyl- methoxy)phenyl]- 1H-purine-2,6- diamine .sup.1H NMR (CD.sub.3OD): δ 8.65 (m, 1H), 8.49 (dd, J = 1.8, 5.1 Hz, 1H), 8.11 (bs, 2H), 7.97-7.94 (m, 1H), 7.79 (t, J = 1.8 Hz, 1H), 7.76 (s, 1H), 7.49-7.44 (m, 1H), 7.16 (t, J = 8.1 Hz, 1H), 7.09-7.05 (m, 1H), 6.62-6.58 (m, 1H), 6.28 (m, 1H), 6.21 (m, 1H), 5.15 (s, 2H), 4.62 (d, J = 7.8 Hz, 1H), 2.95 (s, 1H), 2.85 (s, 1H), 2.67 (d, J = 7.2 Hz, 1H), 2.34 (d, J = 9.3 Hz, 1H), 1.61 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 469.06 (M + H).sup.+ 227 Racemic-(2-exo,3- exo)-N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[4-(N-methoxy)- aminocarbonyl- methylphenyl]-1H- pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.15 (m, 1H), 7.63 (d, J = 8.7 Hz, 1H), 7.20 (d, J = 8.4 Hz, 2H), 6.34 (m, 4H), 4.45 (d, J = 7.5 Hz, 1H), 3.68 (s, 3H), 3.35 (s, 2H), 2.97 (s, 1H), 2.91 (s, 1H), 2.65 (d, J = 8.1 Hz, 1H), 2.30 (d, J = 8.4 Hz, 1H), 1.59 (d, J = 9.6 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 448.06 (M + H).sup.+ 228 Racemic-(2-exo,3- exo-)-N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[4-(N-methoxy)- aminocarbonyl- methylphenyl]-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.23 (m, 1H), 8.14 (s, 1H), 7.76 (d, J = 1.8 Hz, 1H), 7.64 (m, 2H), 7.50 (m, 2H), 7.24-7.13 (m, 4H), 6.33 (m, 2H), 4.45 (m, 1H), 3.68 (s, 3H), 3.57 (s, 2H), 2.98 (s, 1H), 2.87 (s, 1H), 2.66 (d, J = 7.2 Hz, 1H), 2.36 (d, J = 9.3 Hz, 1H), 1.62 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 449.05 (M + H).sup.+ 229 Racemic-(2-exo,3- exo)-N4-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[3-(N-methoxy)- aminocarbonyl- methylphenyl]-1H- pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.16 (m, 1H), 7.62 (m, 2H), 7.22 (m, 1H), 6.87 (m, 1H), 6.80 (m, 1H), 6.38 (m, 1H), 6.33 (m, 2H), 4.50 (d, J = 7.2 Hz, 1H), 3.68 (s, 3H), 3.38 (s, 2H), 2.97 (s, 1H), 2.89 (s, 1H), 2.69 (d, J = 8.1 Hz, 1H), 2.32 (d, J = 9.3 Hz, 1H), 1.59 (d, J = 8.7 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 448.07 (M + H).sup.+ 230 0 Racemic-(2-exo,3- exo-)-N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[3-(N-methoxy)- aminocarbonyl- methylphenyl]-1H- purine-2,6-diamine .sup.1H NMR (CD.sub.3OD): δ 8.32 (s, 1H), 7.76 (d, J = 2.4 Hz, 1H), 7.69 (s, 1H) < 7.60- 7.42 (m, 2H), 7.19 (m, 2H), 7.02 (m, 1H), 6.84 (m, 1H), 6.61 (m, 2H), 6.33 (m, 2H), 4.61 (m, 1H), 3.69 (s, 3H), 3.37 (s, 2H), 2.98 (s, 1H), 2.85 (s, 1H), 2.71 (d, J = 7.8 Hz, 1H), 2.38 (d, J = 8.7 Hz, 1H), 1.63 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 449.65 (M + H).sup.+ 231 Racemic-(2-exo,3- exo)-N4-(3- hydrazidebicyclo[2.2.1] hept-2-yl)-N2-(3- methoxyphenyl)-1H- pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.18 (m, 2H), 7.96 (m, 1H), 7.43 (m, 1H), 7.16 (m, 2H), 6.80 (m, 1H), 6.54 (m, 1H), 6.39 (m, 2H), 4.49 (m, 1H), 3.81 (s, 3H), 2.77- 2.20 (m, 5H), 1.65-1.31 (m, 6H); LC- MS: purity: 100.00%; MS (m/e): 408.08 (M + H).sup.+ 232 Racemic-(2-exo,3- exo)-N4-(3-ethoxy- carbonylbicyclo[2.2.1] hept-5-en-2- yl)-N2-(3- methoxyphenyl)-1H- pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 7.24 (m, 2H), 7.08 (m, 1H), 6.92 (s, 1H), 6.78 (m, 2H), 6.36 (m, 2H), 4.12 (q, J = 4.2 Hz, 2H), 3.81 (s, 3H), 3.05 (s, 1H), 2.95 (s, 1H), 2.69 (d, J = 8.1 Hz, 1H), 2.40 (d, J = 9.0 Hz, 1H), 1.59 (d, J = 8.7 Hz, 1H), 0.89 (t, J = 4.2 Hz, 3H); LC-MS: purity: 95.69%; MS (m/e): 420.66 (M + H).sup.+ 233 Racemic-(2-exo,3- exo)-N4-(N-methoxy- 3-aminocarbonyl- bicyclo[2.2.1]hept- 5-en-2-yl)-N2-(3- methoxyphenyl)-1H- pyrrolo[2,3- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.24 (s, 1H), 7.92 (s, 1H), 7.11 (m, 2H), 6.79 (m, 1H), 6.50 (m, 1H), 6.38 (m, 2H), 6.27 (m, 1H), 4.53 (d, J = 7.5 Hz, 1H), 3.78 (s, 3H), 2.93 (s, 1H), 2.90 (s, 1H), 2.46 (d, J = 8.4 Hz, 1H), 2.41 (d, J = 8.4 Hz, 1H), 1.63 (d, J = 8.7 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 421.01 (M + H).sup.+ 234 Racemic-(2-exo,3- exo-)-N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[4-[2-(1- pyrrolidinyl)ethoxy] phenyl]-1H-purine- 2,6-diamine LC-MS: purity: 100.00%; MS (m/e): 475.18 (M + H).sup.+ 235 Racemic-(2-exo,3- exo-)-N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[3-chloro-4-[2-(1- pyrrolidinyl)ethoxy] phenyl]-1H-purine- 2,6-diamine LC-MS: purity: 93.00%; MS (m/e): 509.17 (M + H).sup.+ 236 Racemic-(2-exo,3- exo-)-N6-(3-amino- carbonylbicyclo[2.2.1] hept-5-en-2-yl)- N2-[3-fluoro-4-[2-(1- pyrrolidinyl)ethoxy] phenyl]-1H-purine- 2,6-diamine LC-MS: purity: 74.34%; MS (m/e): 493.18 (M + H).sup.+ 237 Racemic-(2-exo,3- exo-)-7-methyl-N4-(3- aminocarbonyl- bicyclo[2.2.1]hept-5- en-2-yl)-N2-[4- methoxyphenyl]- thieno[3,2- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 7.65 (s, 1H), 7.50 (m, 2H), 6.94 (m, 2H), 6.36 (m, 1H), 6.23 (m, 1H), 4.25 (d, J = 7.2 Hz, 1H), 3.81 (s, 3H), 2.98 (s, 1H), 2.94 (s, 1H), 2.59 (d, J = 7.8 Hz, 1H), 2.37 (s, 3H), 2.18 (d, J = 9.6 Hz, 1H), 1.57 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 422.13 (M + H).sup.+ 238 Racemic-(2-exo,3- exo-)-7-methyl-N4-(3- aminocarbonyl- bicyclo[2.2.1]hept-5- en-2-yl)-N2-[(3,4,5- trimethoxyphenyl]- thieno[3,2- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.09 (s, 1H), 7.52 (s, 1H), 7.14 (s, 1H), 6.32 (m, 1H), 6.27 (m, 1H), 4.47 (d, J = 7.2 Hz, 1H), 3.855 (s, 3H), 3.851 (s, 3H), 3.75 (s, 1H), 2.97 (s, 1H), 2.90 (s, 1H), 2.65 (d, J = 6.9 Hz, 1H), 2.36 (s, 3H), 2.30 (d, J = 9.6 Hz, 1H), 1.58 (d, J = 9.6 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 482.13 (M + H).sup.+ 239 Racemic-(2-exo,3- exo-)-7-methyl-N4-(3- aminocarbonyl- bicyclo[2.2.1]hept-5- en-2-yl)- N2-[1H-indol-5-yl]- thieno[3,2- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.21 (s, 1H), 7.87 (s, 1H), 7.59 (s, 1H), 7.39 (m, 1H), 7.25 (m, 2H), 6.42 (m, 1H), 6.29 (m, 1H), 6.18 (m, 1H), 4.30 (d, J = 8.7 Hz, 1H), 2.95 (m, 2H), 2.56 (d, J = 9.0 Hz, 1H), 2.36 (s, 3H), 2.19 (d, J = 9.6 Hz, 1H), 1.55 (d, J = 9.3 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 431.10 (M + H).sup.+ 240 0 Racemic-(2-exo,3- exo-)-7-methyl-N4-(3- aminocarbonyl- bicyclo[2.2.1]hept-5- en-2-yl)-N2-[4-[2-(1- pyrrolidinyl)ethoxy] phenyl]-thieno[3,2- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 7.72 (s, 1H), 7.61 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 6.36 (m, 1H), 6.24 (m, 1H), 4.36 (m, 2H), 4.24 (d, J = 7.5 Hz, 1H), 3.68 (m, 4H), 3.25 (m, 2H), 3.01 (s, 1H), 2.98 (s, 1H), 2.59 (d, J = 7.8 Hz, 1H), 2.39 (s, 3H), 2.20 (d, J = 9.3 Hz, 1H), 2.09 (m, 4H), 1.57 (d, J = 9.0 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 505.20 (M + H).sup.+ 241 Racemic-(2-exo,3- exo-)-7-methyl-N4-(3- aminocarbonyl- bicyclo[2.2.1]hept-5- en-2-yl)- N2-[3-fluoro-4-[2- (1-pyrrolidinyl) ethoxy]phenyl]- thieno[3,2- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.05 (s, 1H), 7.92 (d, J = 12.3 Hz, 2H), 7.29-7.16 (m, 2H), 6.36 (m, 1H), 6.34 (m, 1H), 4.38 (m, 2H), 4.32 (d, J = 7.8 Hz, 1H), 3.69 (m, 4H), 3.28 (m, 2H), 3.01 (s, 2H), 2.63 (d, J = 7.5 Hz, 1H), 2.38 (s, 3H), 2.21 (d, J = 9.6 Hz, 1H), 2.15 (m, 4H), 1.59 (d, J = 8.7 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 523.22 (M + H).sup.+ 242 Racemic-(2-exo,3- exo-)-7-methyl-N4-(3- aminocarbonyl- bicyclo[2.2.1]hept-5- en-2-yl)-N2-(4- aminosulfonyl)phenyl- thieno[3,2- d]pyrimidine-2,4- diamine .sup.1H NMR (CD.sub.3OD): δ 8.13 (s, 1H), 7.98 (m, 2H), 7.78 (m, 2H), 7.43 (m, 1H), 6.36 (m, 2H), 4.46 (d, J = 6.6 Hz, 1H), 2.98 (s, 1H), 2.95 (s, 1H), 2.68 (d, J = 8.4 Hz, 1H), 2.35 (s, 3H), 2.27 (d, J = 8.7 Hz, 1H), 1.58 (d, J = 9.3 Hz, 1H); LC-MS: purity: 100.00%; MS (m/e): 471.08 (M + H).sup.+

Example 9

The Compounds Inhibit Protein Kinases

(19) JAK inhibition was tested in human Ramos B-cells activated with IL-4. Twenty to 24 hours post stimulation, the cells are stained for upregulation of CD23 and analyzed by FACS. Stimulation of the B-cells with IL-4 leads to the activation of the JAK/STAT pathway through phosphorylation of the JAK kinase JAK1 and JAK3, which in turn phosphorylate and activate transcription of factor STAT-5. The low-affinity IgE receptor (CD23) is upregulated by activated STAT-5.

(20) For the assay, human Ramos B-cells (ATCC, Catalog No. CRL-1596) are cultured in RPMI 1640 medium (Cellgro, Catalog No. 10-040-CM) containing 10% fetal bovine serum (JRH, Catalog No. 12106-500M) according to the propagation protocol supplied with the cells, and maintained at a density of approximately 3.5×10.sup.5 cells/ml. The day before the assay, the cells are diluted to 3.5×10.sup.5 cells/ml to insure they are in the logarithmic growth phase. The cells are spun down, and suspended in RPMI 1640 medium containing 5% fetal bovine serum to a density of 3.5×10.sup.4 cells/ml and aliquots dispensed into a 96-well tissue culture plate. Cells are incubated with test compound (dissolved in DMSO) or DMSO (control) for 1 hr at 37° C. and then stimulated with IL-4 (Pepotech, Catalog No. 200-04) for 20-24 hours (final concentration is 50 Units/ml). Cells are then spun down, stained with anti-CD23-PE antibody (BD Pharmigen, Catalog No. 555711) and analyzed by FACS.

(21) All of the compounds in Table 1 were tested for their ability to inhibit JAK kinases in this cellular assay. All of the compounds tested exhibited IC.sub.50s of less than 1 μM, with the exception of compounds 101, 102, 110, 122, 125, 135, 140-146, 150, 152, 153, and 168. Compounds 125, 135, 142, 150, 152 and 168 exhibited IC.sub.50s of greater than 10 μM. Compound 110 exhibited an IC.sub.50 of less than 10 μM. Compounds 101, 102, 122, 140, 141, 143-147, and 153 exhibited IC.sub.50s of less than 5 μM.

(22) Compounds 217-231 and 233-242 in Table 2 were tested for their ability to inhibit JAK kinases in this cellular assay. All of the compounds tested exhibited IC.sub.50s of less than 1 μM, with the exception of compounds 217, 218, 219, 223-226, 231, 233, and 237-242. Compounds 223-226 exhibited IC.sub.50s of greater than 10 μM. Compounds 217 and 219 exhibited an IC.sub.50 of less than 10 μM. Compounds 218, 231, 233, and 237-242 exhibited IC.sub.50s of less than 5 μM.

(23) The compounds of the invention were tested in the following assay for their ability to inhibit Axl activity.

Phospho-Akt in-Cell Western Assay

(24) Reagents and Buffers:

(25) Cell culture plate: 96 well assay plate (Corning 3610), white, clear bottom, tissue-culture treated.

(26) Cells: Hela cells.

(27) Starvation medium: For Axl stimulation: 0.5% FCS (fetal calf serum) in DMEM, plus Axl/Fc (extracellular domain of AXL fused to immunoglobulin Fc region) (R&D, 154-AL) 500 ng/mL.

(28) For EGF (epidermal growth factor) stimulation: 0.5% FCS in DMEM (Dulbecco's modified Eagles medium).

(29) Poly-L-Lysine 0.01% solution (the working solution): 10 μg/ml, dilute In PBS (phosphate buffered saline).

(30) Axl antibody cross-linking: 1.sup.st: Mouse anti-Axl (R&D, MAB154). 2.sup.nd: Biotin-SP-conjugated AffiniPure goat anti-mouse IgG (H+L) (Jackson ImmunoResearch #115-065-003).

(31) Fixing buffer: 4% formaldehyde in PBS.

(32) Wash buffer: 0.1% TritonX-100 in PBS.

(33) Quenching buffer: 3% H.sub.2O.sub.2, 0.1% Azide in wash buffer, Azide and hydrogen peroxide (H.sub.2O.sub.2) are added fresh.

(34) Blocking buffer: 5% BSA in TBST (tris buffered saline plus 0.1% Tween 20).

(35) Primary antibody: Rabbit anti-human Phospho-Akt antibody (Cell Signaling 9271): 1×250 diluted in blocking buffer.

(36) Secondary antibody: HRP (horse radish peroxidase)-conjugated Goat anti-Rabbit secondary, stock solution: Jackson ImmunoResearch (Goat anti-Rabbit HRP, #111-035-144) 1:1 diluted in glycerol, store at −20° C. The working solution: 1×2000 dilution of stock in blocking buffer.

(37) Chemiluminescent working solution (Pierce, 37030): SuperSignal ELISA (enzyme linked immunosorbant assay) Pico Chemiluminescent substrate.

(38) Crystal Violet solution: Stock: 2.5% Crystal violet in methanol, filtered and kept at ambient temperature. The working solution: dilute the stock 1:20 with PBS immediately before use.

(39) 10% SDS: working solution: 5% SDS (sodium dodecylsulfate), diluted in PBS

(40) Methods:

(41) Day 1:

(42) A 96 well TC (tissue culture treated) plate was coated with 10 μg/mL poly-L-Lysine at 37° C. for 30 min, washed twice with PBS, and air-dried for 5 minutes before cells were added. Hela cells were seeded at 10,000 cells/well and the cells were starved in 100 μL starvation medium containing Axl/Fc for 24 hrs.

(43) Day 2:

(44) The cells were pre-treated with test compounds by adding 100 μL of 2× test compound to the starvation medium on the cells. The cells were incubated at 37° C. for 1 hr before stimulation.

(45) The cells were stimulated by Axl-antibody cross-linking as follows: A 5×1.sup.st/2.sup.nd Axl antibody mixture was made (37.5 μg/mL 1.sup.st/100 μg/mL 2.sup.nd) in starvation medium and nutated at 4° C. with thorough mixing for 1-2 hours for clustering. The resulting mix was warmed to 37° C. 50 μL of 5× Axl 1.sup.st/2.sup.nd of antibody cluster was added to the cells and the cells were incubated at 37° C. for 5 min.

(46) After 5 minutes stimulation, the plate was flicked to remove medium and the plate was tapped onto paper towels. Formaldehyde (4.0% in PBS, 100 μL) was added to fix the cells and the cells were incubated at ambient temperature for 20 min without shaking.

(47) The cells were washed with a plate washer buffer to remove the formaldehyde solution. The plate was flicked to remove excess wash buffer and tapped onto paper towels. Quenching buffer (100 μL) was added to each well and the cells were incubated at ambient temperature for 20 minutes without shaking.

(48) The cells were washed with a plate washer buffer to remove the quenching buffer. Blocking buffer (100 μL) was added and the cells were incubated at ambient temperature for at least an hour with gentle shaking.

(49) The cells were washed with a plate washer buffer and diluted primary antibody (50 μL) was added to each well (blocking buffer was added to the negative control wells instead). The plates were incubated overnight at 4° C. with gentle shaking.

(50) Day 3:

(51) The wash buffer was removed, diluted secondary antibody (100 μL) was added, and the cells were incubated at ambient temperature for 1 hour with gentle shaking. During the incubation, the chemiluminescent reagent was brought to ambient temperature.

(52) The secondary antibody was removed by washing the cells 1× with wash buffer, 1× with PBS by plate washer. The PBS was removed from the plate and the chemiluminescent reagent (80 μL: 40 μL A and 40 μL B) was added to each well at ambient temperature.

(53) The resulting chemiluminescence was read with a Luminomitor within 10 minutes to minimize changes in signal intensity. After reading the chemiluminescence, the cells were washed 1× with wash buffer and 1× with PBS by plate washer. The plate was tapped onto paper towels to remove excess liquid from wells and air-dried at ambient temperature for 5 minutes.

(54) Crystal Violet working solution (60 μL) was added to each well and the cells were incubated at ambient temperature for 30 min. The crystal violet solution was removed, and the wells were rinsed with PBS, then washed 3× with PBS (200 μL) for 5 minutes each.

(55) 5% SDS solution (70 μL) was added to each well and the cells were incubated on a shaker for 30 min at ambient temperature.

(56) The absorbance was read at 590 nM on a Wallac photospec. The 590 nM readings indicated the relative cell number in each well. This relative cell number was then used to normalize each luminescence reading.

(57) All the compounds in Table 2 were tested for their ability to inhibit Axl kinase. All of the compounds tested exhibited IC.sub.50s of less than 1 μM, with the exception of compounds 182, 185, 186, 188, 189, 197, 198, 208-211, 215-234, and 237-242. Compounds 189, 208, 210, 217-220, 227, 228, 230, 237-239, and 242 exhibited an IC.sub.50 of greater than 10 μM. Compounds 211, 223, 224, 229, 231, 232, and 240 exhibited IC.sub.50s of less than 10 μM. Compounds 182, 185, 186, 197, 198, 209, 215, 216, 221, 222, 225, 226, 233, 234, and 241 exhibited IC.sub.50s of less than 5 μM.

(58) All of the compounds in Table 1 were tested for their ability to inhibit Lck kinase, with the exception of compounds 138, 139, 147, 148, 149, and 168-173. With the exception of compounds 135, 136, 151, 152, 153, and 165, all of these compounds exhibited IC.sub.50s of less than 1 μM. Compound 136 exhibited an IC.sub.50 of less than 10 μM. Compounds 135, 151, 152, 153, and 165 exhibited IC.sub.50s of less than 5 μM.

(59) Compounds 104, 107, 109, 112, 113, 131, 134, 136, 148, and 154 were tested for their ability to inhibit kinase Lyn b. With the exception of compound 136, which exhibited an IC.sub.50 of greater than 10 μM, all of the compounds tested exhibited IC.sub.50s of less than 1 μM.

(60) All of the compounds on Table 1 were tested in a cell-based Syk assay for their ability to inhibit Syk kinase, with the exception of compounds 138, 139, 147-149, and 168-173. Compound 140 exhibited an IC.sub.50 of greater than 10 μM. Compounds 110, 136, 141-146, 151 and 153 exhibited IC.sub.50s of less than 10 μM. All others exhibited IC.sub.50s of less than 1 μM. Compounds 190-192, 217-231, and 235-239 in Table 2 were tested in a cell-based Syk assay for their ability to inhibit Syk kinase. All of the compounds tested exhibited IC.sub.50s of less than 1 μM, with the exception of compounds 217-219, 221, 227, 228, 230, 231, and 235-239. Compounds 217, 219, 228, 237, and 238 exhibited an IC.sub.50 of greater than 10 μM. Compounds 218, 227, and 236 exhibited IC.sub.50s of less than 10 μM. Compounds 221, 230, 231, 235, and 239 exhibited IC.sub.50s of less than 5 μM.

(61) Compounds 218, 220, and 221 in Table 2 were tested for their ability to inhibit PRK1 kinase. All of the compounds tested exhibited IC.sub.50s of less than 5 μM.

(62) Although the foregoing inventions have been described in some detail to facilitate understanding, it will be apparent that certain changes and modifications may be practiced within the scope of the appended claims. Accordingly, the described embodiments are to be considered as illustrative and not restrictive, and the invention is not to be limited to the details given herein, but may be modified within the scope and equivalents of the appended claims.

(63) All literature and patent references cited throughout the application are incorporated into the application by reference for all purposes.