HK1136822B

HK1136822B - Therapeutic compounds and their use in cancer

Info

Publication number: HK1136822B
Application number: HK10100581.3A
Authority: HK
Inventors: Ashok C. Bajji; Se-Ho Kim; Benjamin Markovitz; Richard Trovato; Rajendra Tangallapally; Mark B. Anderson; Daniel Wettstein; Mark Shenderovich; John A. Vanecko
Original assignee: Myriad Genetics, Inc.
Priority date: 2006-05-12
Filing date: 2007-05-14
Publication date: 2013-02-08

Description

Therapeutic compounds and their use in cancer

Cross reference to related applications

Priority of the present application for U.S. provisional application No. 60/799,874 filed on 12/5/2006, U.S. provisional application No. 60/822,159 filed on 11/8/2006, U.S. provisional application No. 60/865,140 filed on 9/11/2006, and U.S. provisional application No. 60/883,707 filed on 5/1/2007, wherein the entire contents of each application are incorporated herein by reference.

Statement regarding federally sponsored research or development

Is free of

Technical Field

The present invention relates to novel compounds and their use in the treatment of disease.

Background

Cancer is highly prevalent: the probability of invasive cancer in women and men in the united states for older people living over 70 years of age is 38% and 46%. About 140 million cancer cases will be newly added in 2006. Although the five-year survival rate of cancer has increased from about 50% in the middle of the 70's 19 th century to 65% of the present, cancer remains fatal. It is expected that 565,000 americans will die from cancer in 2006. (American Cancer Society, Surveillance Research, 2006). While there are multiple therapies for various cancers, the reality remains that most cancers remain incurable, untreatable, and/or become resistant to standard therapies. Therefore, new cancer therapies are needed.

Disclosure of Invention

The present invention relates to compounds of the following formulae I-III. The invention also relates to pharmaceutical compositions containing one or more compounds of formulae I-III and pharmaceutically acceptable excipients. The present inventors have found that the compounds of formula I-III have pharmacological activity. One particular activity of the compounds of formulae I-III was found to be anti-cancer activity.

Formula I

Formula II

Formula III

The present invention provides compounds of formula I wherein:

a is selected from a substituted or unsubstituted aryl, heteroaryl, heterocyclic or carbocyclic group;

b is selected from a substituted or unsubstituted aryl, heteroaryl, heterocyclic or carbocyclic group;

r1 is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, amino, halogen, sulfur, and thioalkyl;

L₁may be saturated, partially saturated or unsaturated, and is selected from- (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH₂)_n-、-(CH₂)_nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-and- (CH)₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8, and wherein each carbon and/or nitrogen may optionally be optionally substituted with one or more groups independently selected from hydroxy, halogen, alkoxy, alkyl, amino, cycloalkyl, -NR₂R₃、-NSO₂R₄、-NC(＝O)NR₂R₃Heteroaryl, aryl, cycloalkyl and heterocyclic substituents; wherein-R₂and-R₃Independently selected from-H, alkyl and-C (═ O) OR₄(ii) a And wherein R₄Is alkyl (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl);

L₂may be saturated, partially saturated or unsaturated, and is selected from- (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH₂)_n-、-(CH₂)_nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-and- (CH)₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8, and wherein each carbon and/or nitrogen may optionally be optionally substituted with one or more groups independently selected from hydroxy, halogen, alkoxy, alkyl, amino, cycloalkyl, -NR ₂R₃、-NSO₂R₄、-NC(＝O)NR₂R₃Heteroaryl, aryl, cycloalkyl and heterocyclic substituents; wherein-R₂and-R₃Independently selected from-H, alkyl and-C (═ O) OR₄(ii) a And wherein R₄Is an alkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl).

Unless otherwise indicated, L₁And L₂Can be in either of two orientations, e.g., - (CH)₂)_nNC(＝S)S(CH₂)_n-means purine- (CH)₂)_nNC(＝S)S(CH₂)_n-phenyl orientation and purine- (CH)₂)_nSC(＝S)N(CH₂)_n-phenyl orientation.

According to one aspect, a is substituted with one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, -C ≡ N, -SO₃And aryl group as a substituent of-COOH. In a more specific aspect of the invention, a is phenyl having one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy and-COOH. In an even more particular aspect, A is a cyclic or acyclic alkyl having one or more groups selected from-F, -Cl, -Br, -I, -OCH₃、-CF₃、-CH₃、-OCF₃、-C(＝O)CH₃-COOH, -C.ident.N and-NO₂Phenyl group as a substituent of (1).

In one aspect of the compounds of the invention, A is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C) _1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂and-NO₂Aryl group of the substituent(s). In a particular aspect, a is phenyl.

In one aspect of the compounds of the invention, A is phenyl having 1-5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroaralkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethylsulfonylamino (trihalomethanesulphonamido), O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one aspect of the compounds of the present invention, B is substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, -SO₃And aryl group as a substituent of-COOH. In a particular aspect, B is phenyl. In a more specific aspect, B is substituted with one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, and-COOH A phenyl group. In an even more particular aspect, B is a cyclic or branched alkyl having one or more groups selected from-F, -Cl, -Br, -I, -CH₃、-OCH₃、-CF₃、-OCF₃、-C(＝O)CH₃-COOH, -C.ident.N and-NO₂Phenyl group as a substituent of (1).

In one aspect of the compounds of the present invention, B is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂、-SO₃and-NO₂Aryl group of the substituent(s).

In one aspect of the compounds of the present invention, B is phenyl having 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethylsulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one embodiment, a is a substituted or unsubstituted benzo [1, 3] dioxole group. In one aspect of this embodiment, A is 6-bromo-benzo [1, 3] dioxol-5-yl. In one aspect of this embodiment, a is an unsubstituted benzo [1, 3] dioxole group. In one aspect of this embodiment, A is 6-iodo-benzo [1, 3] dioxol-5-yl. In one aspect of this embodiment, A is 6-chloro-benzo [1, 3] dioxol-5-yl. In one aspect of this embodiment, A is 6-fluoro-benzo [1, 3] dioxol-5-yl. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one embodiment, A is a substituted or unsubstituted 2, 3-dihydro-1-indanone group. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thioaminothiocarbamoyl, N-thioaminothiocarbamoyl, and C-amido.

According to one embodiment, A is a substituted or unsubstituted 1, 2-indane group. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one embodiment, a is a substituted or unsubstituted benzo [1, 4] dioxanyl group. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one embodiment, a is a substituted or unsubstituted benzoxazinone group. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one embodiment, a is a substituted or unsubstituted benzoxazine group. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one embodiment, a is a substituted or unsubstituted benzodioxine (benzodioxine) group. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one embodiment, a is substituted or unsubstituted naphthyl. In one aspect of this embodiment, A has 1 to 6 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one embodiment, a is a substituted or unsubstituted pyrrole group. In one aspect of this embodiment, A has 1 to 3 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido. According to one aspect, a is unsubstituted.

According to one embodiment, a is a substituted or unsubstituted pyridyl group. In one aspect of this embodiment, A has 1 to 4 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido. According to one aspect of this embodiment, a is unsubstituted.

According to one embodiment, a is substituted or unsubstituted cyclohexyl. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido. According to one aspect of this embodiment, a is unsubstituted.

According to one embodiment, B is a substituted or unsubstituted benzo [1, 3] dioxole group. In one aspect of this embodiment, B is 6-bromo-benzo [1, 3] dioxol-5-yl. In one aspect of this embodiment, B is an unsubstituted benzo [1, 3] dioxole group. In one aspect of this embodiment, B is 6-iodo-benzo [1, 3] dioxol-5-yl. In one aspect of this embodiment, B is 6-chloro-benzo [1, 3] dioxol-5-yl. In one aspect of this embodiment, B is 6-fluoro-benzo [1, 3] dioxol-5-yl. In one aspect of this embodiment, B has 1 to 4 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one embodiment, B is substituted or unsubstituted naphthyl. In one aspect of this embodiment, B has 1 to 6 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido. According to one aspect of this embodiment, B is unsubstituted.

According to one embodiment, B is a substituted or unsubstituted pyrrole group. In one aspect of this embodiment, B has 1-3 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido. According to one aspect of this embodiment, B is unsubstituted.

According to one embodiment, B is a substituted or unsubstituted pyridyl group. In one aspect of this embodiment, B has 1 to 4 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido. According to one aspect of this embodiment, B is unsubstituted.

According to one embodiment, B is substituted or unsubstituted cyclohexyl. In one aspect of this embodiment, B has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido. According to one aspect of this embodiment, B is unsubstituted.

According to one aspect of the present invention there is provided a compound of formula I, wherein:

a is substituted or unsubstituted aryl;

b is substituted or unsubstituted aryl;

L₁may be saturated, partially saturated or unsaturated, and is selected from: - (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH₂)_n-、-(CH₂)_nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-、-(CH₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8, and wherein each carbon and/or nitrogen may optionally be optionally substituted with one or more groups independently selected from hydroxy, halogen, alkoxy, C_1-3Alkyl and C_3-6Cycloalkyl substituents;

L₂may be saturated, partially saturated or unsaturated, and is selected from: - (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH_2)n-、-(CH₂)_nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-、-(CH₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8, and wherein each carbon and/or nitrogen may optionally be optionally substituted with one or more groups independently selected from hydroxy, halogen, alkoxy, C_1-3Alkyl and C_3-6Cycloalkyl substituents; and pharmaceutically acceptable salts thereof.

a is substituted or unsubstituted heteroaryl;

b is substituted or unsubstituted aryl;

L₁May be saturated, partially saturated or unsaturated, and is selected from- (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH₂)_n-、-(CH₂)_nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-、-(CH₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8, and wherein each carbon and/or nitrogen may optionally be optionally substituted with one or more groups independently selected from hydroxy, halogen, alkoxy, C_1-3Alkyl and C_3-6Cycloalkyl substituents;

L₂may be saturated, partially saturated or unsaturated, and is selected from- (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH₂)_n-、-(CH₂)_nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-、-(CH₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from0. 1, 2, 3, 4, 5, 6, 7 and 8, and wherein each carbon and/or nitrogen may optionally be independently selected by one or more from hydroxyl, halogen, alkoxy, C_1-3Alkyl and C_3-6Cycloalkyl substituents; and pharmaceutically acceptable salts thereof.

According to one aspect of the present invention, there is provided a compound of formula I, wherein a is substituted or unsubstituted aryl; b is substituted or unsubstituted heteroaryl; r1 is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, amino, halogen, sulfur, and thioalkyl; and pharmaceutically acceptable salts thereof.

According to one aspect of the present invention, there is provided a compound of formula I, wherein a is substituted or unsubstituted heterocyclyl; b is substituted or unsubstituted aryl; and R1 is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, alkylamino, halogen, sulfur, and thioalkyl.

According to one aspect of the present invention, there is provided a compound of formula I, wherein a is substituted or unsubstituted aryl; b is a substituted or unsubstituted heterocyclic group; r1 is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, amino, halogen, sulfur, and thioalkyl.

According to certain aspects of the invention, in the compounds of formula I, A is substituted or unsubstituted and is selected from indazolyl, 1H-indolyl, benzothiazolyl, 1H-benzotriazolyl, benzoxazolyl, 1H-benzimidazolyl (1H-benzimidadazazolyl), 3H-benzoxazol-2-one, 4H-benzo [1, 4] oxazin-3-one, 1, 3 dihydro-benzimidazol-2-one, 3H-benzothiazol-2-one (3H-benzothiazolo-2-one), 1H-pyrazolo [3, 4-b ] pyridine, 1H-quinoxalin-2-one (1H-quinaxol-2-one), 1H-quinoxalin-2-one, 4H-benzo [1, 4] oxazin-3-one, isoquinoline, indoline, 1, 3 dihydro-indol-2-one, 2, 3-dihydro-benzo [1, 4] dioxin, thienyl (thiophenyl), benzo [ b ] thienyl, naphtho [2, 3-b ] thienyl, thianthrenyl, furyl (furanyl ), isobenzofuryl, chromenyl (chromenyl), xanthenyl (xanthenyl), phenoxathinyl, pyrrolyl, 2H-pyrrolyl, imidazolyl, pyrazolyl, pyridyl (pyridinyl), 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, purinyl (purinyl), 4H-quinolyl (4H-quinolyl), quinolyl (quinolyl), quinoyl, and the like, Isoquinolyl, quinolyl, 2, 3-naphthyridinyl, 1, 5-naphthyridinyl, quinazolinyl, cinnolinyl, pteridinyl, carbazolyl, beta-carbolinyl, phenanthridinyl, acridinyl, peridinyl, phenanthrolinyl, phenazinyl, isothiazolyl, phenothiazinyl, isoxazolyl, furazanyl, phenoxazinyl, 1, 4-dihydroquinoxaline-2, 3-dione, 7aminoisocoumarin (7aminoisocoumarin), pyrido [1, 2-a ] pyrimidin-4-one, pyrazolo [1, 5-a ] pyrimidinyl, pyrazolo [1, 5-a ] pyrimidin-3-yl, 1, 2-benzisoxazolyl, benzimidazolyl, naphtho [1, 2-a ] pyrimidin-3-yl, 1, 2-a ] benzimidazolyl, 1, 5-a ] imidazolyl, 3-a ] benzimidazolyl, phenanthridinyl, phenanthr, 2-oxindolyl, 2-oxobenzimidazolyl, tetrahydrofuranyl, pyranyl, piperidyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, indolinyl, isoindolinyl, quinonyl, quinuclidinyl, morpholinyl, isochroman, chromanyl, pyrazolidinyl, pyrazolinyl, pivaloyl, and tetramoyl.

According to certain aspects of the invention, in the compounds of formula I, B is substituted or unsubstituted and is selected from indazolyl, 1H-indolyl, benzothiazolyl, 1H-benzotriazolyl, benzoxazolyl, 1H-benzimidazolyl, 3H-benzoxazol-2-one, 4H-benzo [1, 4] oxazin-3-one, 1, 3 dihydro-benzimidazol-2-one, 3H-benzothiazol-2-one, 1H-pyrazolo [3, 4-B ] pyridine, 1H-quinoxalin-2-one, 4H-benzo [1, 4] oxazin-3-one, isoquinoline, indoline, 1, 3 dihydro-indol-2-one, 2, 3-dihydro-benzo [1, 4] dioxine, thienyl (thienyl, thiophenyl), benzo [ b ] thienyl, naphtho [2, 3-b ] thienyl, furyl (furyl ), isobenzofuryl, chromenyl, xanthenyl, phenoxathiyl, pyrrolyl, 2H-pyrrolyl, imidazolyl, pyrazolyl, pyridyl (pyridil), 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, purinyl, 4H-quinolizinyl, isoquinolyl, quinolyl, 2, 3-naphthyridinyl, 1, 5-naphthyridinyl, quinazolinyl, cinnolinyl, pteridinyl, carbazolyl, beta-carbolinyl, phenanthridinyl, acridinyl, peridinylphenyl, peridinylphenylyl, Phenanthrolinyl, phenazinyl, isothiazolyl, phenothiazinyl, isoxazolyl, furazanyl, phenoxazinyl, 1, 4-dihydroquinoxaline-2, 3-dione, 7 aminoisocoumarin, pyrido [1, 2-a ] pyrimidin-4-one, pyrazolo [1, 5-a ] pyrimidinyl, pyrazolo [1, 5-a ] pyrimidin-3-yl, 1, 2-benzisoxazol-3-yl, benzimidazolyl, 2-oxindolyl, 2-oxobenzimidazolyl, tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, isochroman, chromanyl, pyrazolidinyl, pyrazolinyl, pivaloyl, and tetramoyl.

In certain aspects of the compounds of the present invention, the A ring is substituted with one or more groups selected from-L₁-C(＝O)OH、-L₁-CH＝CHC(＝O)OH、-L₁-C(＝O)NH₂、-L₁-C(＝O)NH(C_1-3Alkyl), -L₁-C(＝O)N(C_1-3Alkyl radical)₂、-L₁-S(＝O)₂(C_1-3Alkyl), -L₁-S(＝O)₂NH₂、-L₁-S(＝O)₂N(C_1-3Alkyl radical)₂、-L₁-S(＝O)₂NH(C_1-3Alkyl), -L₁-C(＝O)NHOH、-L₁-C(＝O)CH₂NH₂、-L₁-C(＝O)CH₂OH、-L₁-C(＝O)CH₂SH、-L₁-C(＝O)NHCN、-L₁-NHC(＝O)OR_o、-L₁-C(＝O)NHR_o、-L₁-NH(C＝O)NHR_o、-L₁-C(＝O)N(R_o)₂、-L₁-NH(C＝O)N(R_o)₂、-L₁-a substituent of a sulfo group; wherein R is_oIs selected from alkyl and haloalkyl, andL₁independent of any other L in the compound₁And is as defined above.

In certain aspects of the compounds of the present invention, the B ring is substituted with one or more groups selected from-L₁-C(＝O)OH、-L₁-CH＝CHC(＝O)OH、-L₁-C(＝O)NH₂、-L₁-C(＝O)NH(C_1-3Alkyl), -L₁-C(＝O)N(C_1-3Alkyl radical)₂、-L₁-S(＝O)₂(C_1-3Alkyl), -L₁-S(＝O)₂NH₂、-L₁-S(＝O)₂N(C_1-3Alkyl radical)₂、-L₁-S(＝O)₂NH(C_1-3Alkyl), -L₁-C(＝O)NHOH、-L₁-C(＝O)CH₂NH₂、-L₁-C(＝O)CH₂OH、-L₁-C(＝O)CH₂SH、-L₁-C(＝O)NHCN、-L₁-NHC(＝O)OR_o、-L₁-C(＝O)NHR_o、-L₁-NH(C＝O)NHR_o、-L₁-C(＝O)N(R_o)₂、-L₁-NH(C＝O)N(R_o)₂、-L₁-a substituent of a sulfo group; wherein R is_oSelected from alkyl and haloalkyl, and L₁Independent of any other L in the compound₁And is as defined above.

According to one aspect of the compounds of the present invention, L₁Is selected from-CH₂-、-CH₂CH₂-、-CH₂CH₂CH₂、-CH(CH₃)CH₂-、-CH(CH₂CH₃)CH₂-、-CH(CH(CH₃)₂)CH₂-、-C(CH₂CH₂)CH₂-、-C(CH₂CH₂CH₂)CH₂-、-CH(CH(CH₃)CH₂CH₃)CH₂-、-CH(CH(CH₂)₄)CH₂-、-CH(CH(CH₂)₅)CH₂-、-CH(OH)CH₂-and-CH (CH)₂OH)CH₂-. In a more specific aspect, L₁Is selected from-CH₂CH₂-and-CH₂CH₂CH₂. In an even more particular aspect, L₁is-CH₂CH₂-. Unless otherwise indicated, L₁Can be in either of two orientations, e.g., -CH (CH)₂CH₂)CH₂-means purine-CH (CH)₂CH₂)CH₂-phenyl orientation and purine-CH₂CH(CH₂CH₂) -phenyl orientation.

According to one aspect of the invention, there is provided a compound of formula I, wherein L₂Is selected from-CH₂-、-CH₂CH₂-、-CH₂CH₂CH₂、-CH(CH₃)CH₂-、-CH(CH₂CH₃)CH₂-、-CH(CH(CH₃)₂)CH₂-、-C(CH₂CH₂)CH₂-、-C(CH₂CH₂CH₂)CH₂-、-CH(CH(CH₃)CH₂CH₃)CH₂-、-CH(CH(CH₂)₄)CH₂-、-CH(CH(CH₂)₅)CH₂-、-CH(OH)CH₂-and-CH (CH)₂OH)CH₂-. In a more specific aspect, L₂Is selected from-CH₂CH₂-and-CH₂CH₂CH₂-. In an even more particular aspect, L ₂is-CH₂CH₂-. Unless otherwise indicated, L₂Can be in either of two orientations, e.g., -CH (CH)₂CH₂)CH₂-means purine-CH (CH)₂CH₂)CH₂-phenyl orientation and purine-CH₂CH(CH₂CH₂) -phenyl orientation.

According to one aspect of the compounds of the invention, the group A is selected from 2, 5-dimethoxyphenyl, 2, 5-diethoxyphenyl, 2, 4-dimethoxyphenyl, 3, 4, 5-trimethoxyphenyl, 4-chlorophenyl and 4-benzonitrile. In this aspect, the position (numbering) of the substituent is relative to the bond of the phenyl group to the purine core. In a specific embodiment of this aspect, L₁is-S-.

According to one aspect of the compounds of the present invention, the group B is selected from the group consisting of 2-bromophenyl, 2-fluorophenyl, 2-chlorophenyl, 3-fluorophenyl, 3-iodophenyl, 3-bromophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 2, 3-dichlorophenyl, 2, 4-dichlorophenyl, 2, 6-dichlorophenyl, 2, 3-difluorophenyl, 3, 5-difluorophenyl, 4-chloro-2-fluorophenyl, 2-chloro-6-fluorophenyl, pentafluorophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-benzoic acid, 2-trifluoromethylphenyl, 3-methoxyphenyl, 2-nitrophenyl, 3-bromophenyl, and mixtures thereof, 3, 4-dimethoxyphenyl, 3, 5-dimethoxyphenyl, 3, 4, 5-trimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, p-tolyl, o-tolyl, 2, 5-dimethylphenyl, 3, 5-dimethylphenyl, 2, 4, 6-trimethylphenyl, 4-acetophenone, 4-phenol, 4-benzenesulfonic acid, 4-dimethylaminophenyl, tert-butyl-4-carbamate-phenyl, 4-aminophenyl, 3-trifluoromethoxyphenyl, and 3, 5-bistrifluoromethylphenyl. In this aspect, the position (numbering) of the substituent is relative to the bond of the phenyl group to the purine core. In a specific embodiment of this aspect, L ₂Is selected from-CH₂-CH₂-and-CH₂-CH₂-CH₂-。

The present invention also provides compounds of formula II wherein the variables are as in any of the above embodiments and aspects of the compounds of formula I of the present invention.

Formula II

The present invention also provides compounds of formula III wherein the variables are as in any of the above embodiments and aspects of the compounds of formula I of the present invention.

Formula III

a is a substituted or unsubstituted heterocyclic group;

b is substituted or unsubstituted aryl;

L₁may be saturated, partially saturated or unsaturated, and is selected from- (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH₂)_n-、-(CH₂)_nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-and- (CH)₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8 and each carbon and/or nitrogen may optionally be substituted with one or more substituents independently selected from hydroxy, halogen, alkoxy, C_1-3Alkyl and C_3-6Cycloalkyl substituents;

L₂may be saturated, partially saturated or unsaturated, and is selected from- (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH₂)_n-、-(CH₂)_nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-and- (CH)₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8 and each carbon and/or nitrogen may optionally be substituted with one or more substituents independently selected from hydroxy, halogen, alkoxy, C _1-3Alkyl and C_3-6Cycloalkyl substituents; and pharmaceutically acceptable salts thereof.

In one aspect of the invention, a may be substituted or unsubstituted and is selected from aryl or heterocyclyl;

b may be substituted or unsubstituted and is selected from heteroaryl or heterocyclyl having one or more heteroatoms selected from-N-, -O-, -S-and-P-.

R1 is selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, heteroaryl, heterocycle, carbocycle, amino, halogen, sulfur, and thioalkyl;

L₁and L₂As defined above in its broadest aspect; and pharmaceutically acceptable salts thereof.

In another aspect of the invention, a may be substituted or unsubstituted and is selected from benzo [1, 3] dioxole or phenyl.

B may be a substituted or unsubstituted heteroaryl or heterocyclyl group having one or more heteroatoms selected from-N-, -O-, -S-and-P-.

L₁and L₂As above its widest aspectThe definition in the face; and pharmaceutically acceptable salts thereof.

In one aspect of the invention, the group a may be substituted or unsubstituted and is selected from 5-halo-benzo [1, 3] dioxoles (e.g. 5-bromo-benzo [1, 3] dioxole), dimethoxybenzenes (e.g. 1, 4-dimethoxybenzene, 2, 3-dimethoxybenzene and 2, 4-dimethoxybenzene) and diethoxybenzenes (e.g. 1, 4-diethoxybenzene, 2, 3-diethoxybenzene and 2, 4-diethoxybenzene);

In one aspect of the invention, a may be substituted or unsubstituted and is selected from aryl, heteroaryl, heterocyclic and carbocyclic groups;

b may be substituted or unsubstituted and is a heterocyclic group selected from piperidine, pyrrolidine, azetidine (azetidine), piperazine, morpholine and tetrahydropyran.

L₁and L₂As defined above; and pharmaceutically acceptable salts thereof.

the group B is selected from piperidine, piperidine-1-carboxylic acid ethyl ester, piperidine-1-carboxylic acid tert-butyl ester, 2, 6, 6-tetramethyl-piperidine, piperidine-2, 6-dione, piperidine-1-carboxaldehyde, 1-methyl-pyrrolidine, 1-isopropyl-piperazine, tetrahydropyran, adamantane (admantane), piperidine-1-carboxaldehyde, 1-piperidin-1-yl-ethanone, 1-methanesulfonyl-piperidine, 1-propyl-piperidine, 1-trifluoromethanesulfonyl-piperidine, piperidine-1-carboxylic acid tert-butyl ester, pyrrolidine-1-carboxylic acid tert-butyl ester, morpholine-4-carboxylic acid tert-butyl ester, 1-pyrrolidin-1-yl-ethanone, morpholine-1-pyrrolidino-1-yl-ethanone, tert-butyl ester, 2, 6, 6-tetramethyl-piperidine, piperidine, 1-methanesulfonyl-pyrrolidine, pyrrolidine-1-carbaldehyde, azetidine-1-carboxylic acid tert-butyl ester, 1-methyl-azetidine, azetidine-1-carbaldehyde, 1-azetidin-1-yl-ethanone, 1-methanesulfonyl-azetidine, and 1-trifluoromethanesulfonyl-azetidine, cycloheptane, imidazole, undecafluorocyclohexane, cyclohexyl carbamic acid tert-butyl ester, 1-piperazin-1-yl-ethanone, 6-dimethyl-bicyclo [3.1.1] hept-2-ene, 5-methyl-2, 4-dihydro-pyrazol-3-one, piperidine-1-carboxylic acid benzyl ester, morpholine, pyrrolidine-1-carboxylic acid benzyl ester, Piperidine-1, 2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester, benzyl-1, 2, 3, 6-tetrahydropyridine, hexahydro-4 b-aza-cyclopropyl [ cd ] pentalene, 2-isopropyl-piperidine-1-carboxylic acid tert-butyl ester, piperidine-1-carboxylic acid acetamide, piperidine-1-carboxylic acid isopropylamide, piperidine-1-carboxylic acid tert-butylamide, [ { piperidine-1-carbonyl } amino ] -acetic acid ethyl ester, isopropylpiperidine, isobutylpiperidine, 2-dimethyl-1-piperidin-1-yl-propan-1-one, 2-dimethyl-1-piperidin-1-yl-butan-1-one, and mixtures thereof, 2-isopropyl-piperidine, 1-isopropyl-piperazine and 1-cyclopentyl-piperazine.

In one aspect of the invention, a may be substituted or unsubstituted and is selected from benzo [1, 3] dioxole and phenyl;

b may be substituted or unsubstituted and is a heteroaryl or heterocyclyl group selected from piperidine, pyrrolidine, azetidine, piperazine, morpholine and tetrahydropyran.

the group B is selected from piperidine, piperidine-1-carboxylic acid ethyl ester, piperidine-1-carboxylic acid tert-butyl ester, 2, 6, 6-tetramethyl-piperidine, piperidine-2, 6-dione, piperidine-1-carboxaldehyde, 1-methyl-pyrrolidine, 1-isopropyl-piperazine, tetrahydropyran, adamantane, piperidine-1-carboxaldehyde, 1-piperidin-1-yl-ethanone, 1-methanesulfonyl-piperidine, 1-propyl-piperidine, 1-trifluoromethanesulfonyl-piperidine, piperidine-1-carboxylic acid tert-butyl ester, pyrrolidine-1-carboxylic acid tert-butyl ester, morpholine-4-carboxylic acid tert-butyl ester, 1-pyrrolidin-1-yl-ethanone, methyl-ethyl acetate, methyl-1-pyrrolidinone, methyl, 1-methanesulfonyl-pyrrolidine, pyrrolidine-1-carbaldehyde, azetidine-1-carboxylic acid tert-butyl ester, 1-methyl-azetidine, azetidine-1-carbaldehyde, 1-azetidin-1-yl-ethanone, 1-methanesulfonyl-azetidine, and 1-trifluoromethanesulfonyl-azetidine, cycloheptane, imidazole, undecafluorocyclohexane, cyclohexyl carbamic acid tert-butyl ester, 1-piperazin-1-yl-ethanone, 6-dimethyl-bicyclo [3.1.1] hept-2-ene, 5-methyl-2, 4-dihydro-pyrazol-3-one, piperidine-1-carboxylic acid benzyl ester, morpholine, pyrrolidine-1-carboxylic acid benzyl ester, Piperidine-1, 2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester, benzyl-1, 2, 3, 6-tetrahydropyridine, hexahydro-4 b-aza-cyclopropyl [ cd ] pentalene, 2-isopropyl-piperidine-1-carboxylic acid tert-butyl ester, piperidine-1-carboxylic acid acetamide, piperidine-1-carboxylic acid isopropylamide, piperidine-1-carboxylic acid tert-butylamide, [ { piperidine-1-carbonyl } amino ] -acetic acid ethyl ester, isopropylpiperidine, isobutylpiperidine, 2-dimethyl-1-piperidin-1-yl-propan-1-one, 2-dimethyl-1-piperidin-1-yl-butan-1-one, and mixtures thereof, 2-isopropyl-piperidine, 1-isopropylpiperazine and 1-cyclopentyl-piperazine;

In one aspect of the invention, the group a is selected from 5-halo-benzo [1, 3] dioxole, dimethoxybenzene and diethoxybenzene;

the group B is selected from piperidine, piperidine-1-carboxylic acid ethyl ester, piperidine-1-carboxylic acid tert-butyl ester, 2, 6, 6-tetramethyl-piperidine, piperidine-2, 6-dione, piperidine-1-carboxaldehyde, 1-methyl-pyrrolidine, 1-isopropyl-piperazine, tetrahydropyran, adamantane, piperidine-1-carboxaldehyde, 1-piperidin-1-yl-ethanone, 1-methanesulfonyl-piperidine, 1-propyl-piperidine, 1-trifluoromethanesulfonyl-piperidine, piperidine-1-carboxylic acid tert-butyl ester, pyrrolidine-1-carboxylic acid tert-butyl ester, morpholine-4-carboxylic acid tert-butyl ester, 1-pyrrolidin-1-yl-ethanone, methyl-ethyl acetate, methyl-1-pyrrolidinone, methyl, 1-methanesulfonyl-pyrrolidine, pyrrolidine-1-carbaldehyde, azetidine-1-carboxylic acid tert-butyl ester, 1-methyl-azetidine, azetidine-1-carbaldehyde, 1-azetidin-1-yl-ethanone, 1-methanesulfonyl-azetidine and 1-trifluoromethanesulfonyl-azetidine, cycloheptane, imidazole, undecafluorocyclohexane, cyclohexyl carbamic acid tert-butyl ester, 1-piperazin-1-yl-ethanone, 6-dimethyl-bicyclo [3.1.1] hept-2-ene, 5-methyl-2, 4-dihydro-pyrazol-3-one, piperidine-1-carboxylic acid benzyl ester, morpholine, pyrrolidine-1-carboxylic acid benzyl ester, benzyl ester, Piperidine-1, 2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester, benzyl-1, 2, 3, 6-tetrahydropyridine, hexahydro-4 b-aza-cyclopropyl [ cd ] pentalene, 2-isopropyl-piperidine-1-carboxylic acid tert-butyl ester, piperidine-1-carboxylic acid acetamide, piperidine-1-carboxylic acid isopropylamide, piperidine-1-carboxylic acid tert-butylamide, [ { piperidine-1-carbonyl } amino ] -acetic acid ethyl ester, isopropylpiperidine, isobutylpiperidine, 2-dimethyl-1-piperidin-1-yl-propan-1-one, 2-dimethyl-1-piperidin-1-yl-butan-1-one, and mixtures thereof, 2-isopropyl-piperidine, 1-isopropylpiperazine and 1-cyclopentyl-piperazine;

L₁and L₂As set forth above in its broadest aspectDefining; and pharmaceutically acceptable salts thereof.

According to one aspect of the invention, in the compounds of formula I, a is substituted with one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, -C ≡ N, -SO₃And an aryl or heterocyclic group as a substituent of-COOH. In a more specific aspect, a is phenyl having one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, and-COOH. In another specific aspect, A is a cyclic or acyclic alkyl having one or more groups selected from-F, -Cl, -Br, -I, -OCH₃and-OCH₂CH₃Phenyl group as a substituent of (1). In another aspect, a is benzo [1, 3 ] having one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, and-COOH]A dioxole group. In another specific aspect, A is a cyclic or acyclic alkyl having one or more groups selected from-F, -Cl, -Br, -I, -OCH ₃and-OCH₂CH₃Benzo [1, 3] of a substituent of]A dioxole group.

In one aspect, in the compounds of formula I, A is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂and-NO₂Aryl or heterocyclic group of the substituents of (1). In a particular aspect, A is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂and-NO₂Phenyl group as a substituent of (1). In another specific aspect, A is a compound having one or more groups selected from hydroxy, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂and-NO₂Benzo [1, 3] of a substituent of]A dioxole group.

In one aspect, in the compounds of formula I, a is a phenyl or benzo [1, 3] dioxole group having 1-5 substituents independently selected from amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocycle, heteroaralkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethylsulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one aspect, in the compounds of formula I, B is a heterocycle having one or more heteroatoms selected from the group consisting of-N-and-O-, whereinThe heterocyclic group may have one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH₂-an aryl group; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O) -NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO₃(ii) a -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); peptides having 1-5 amino acid residues (selected from natural and non-natural amino acids); -C (═ O) alkyl, where the alkyl is substituted with one or more substituents selected from alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl; and a sulfonyl group. In a particular aspect, B is a piperidine (piperidinyl) group. In a particular aspect, B is a piperidine group substituted with one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH₂-an aryl group; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O) -NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO ₃(ii) a -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); peptides having 1-5 amino acid residues (selected from natural and non-natural amino acids); -C (═ O) alkyl, where the alkyl is substituted with one or more substituents selected from alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl; and a sulfonyl group. In a more specific aspect, B is a cyclic or acyclic alkyl group having one or more groups selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -CH₂-aryl, -C (═ O) alkyl, -C (═ O) -NH-alkyl, cycloalkyl, hydroxy, -SO₃A piperidine group for a substituent of, -COOH (and esters thereof) and sulfonyl. In an even more particular aspect, B is a cyclic compound having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And a piperidine group as a substituent of the cyclopentyl group.

In a particular aspect, B is a homopiperidine (homopiperidinyl) group. In a more specific aspect, B is a homopiperidine group having one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH ₂-an aryl group; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O) -NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO₃(ii) a -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); peptides having 1-5 amino acid residues (selected from natural and non-natural amino acids); -C (═ O) alkyl, where the alkyl is substituted with one or more substituents selected from alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl; and a sulfonyl group. In an even more particular aspect, B is a cyclic compound having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And homopiperidinyl group as a substituent for cyclopentyl.

In a particular aspect, B is a piperazine (piperazinyl) group. In a more specific aspect, B is a piperazine group having one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH₂-an aryl group; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O) -NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO₃(ii) a -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); peptides having 1-5 amino acid residues (selected from natural and non-natural amino acids); -C (═ O) alkyl, where the alkyl is substituted with one or more substituents selected from alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl; and a sulfonyl group. In an even more particular aspect, B is a cyclic compound having one or more substituents selected from-C (═ O), -C (═ O) CH ₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And a piperazine group as a substituent of the cyclopentyl group.

In a particular aspect, B is a pyrrolidine (pyrrolidinyl) group. In a more particular aspect, B is a pyrrolidine group having one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH₂-an aryl group; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O)-NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO₃(ii) a -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); peptides having 1-5 amino acid residues (selected from natural and non-natural amino acids); -C (═ O) alkyl, where the alkyl is substituted with one or more substituents selected from alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl; and a sulfonyl group. In an even more particular aspect, B is a cyclic compound having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And a pyrrolidine group as a substituent of the cyclopentyl group.

In a particular aspect, B is an azetidinyl group. In a more specific aspect, B is an azetidine group having one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH ₂-an aryl group; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O) -NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO₃(ii) a -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); peptides having 1-5 amino acid residues (selected from natural and non-natural amino acids); -C (═ O) alkyl, where the alkyl is substituted with one or more substituents selected from alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl; and sulfonyl groupAnd (4) a base. In an even more particular aspect, B is a cyclic compound having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And an azetidinium group as a substituent of the cyclopentyl group.

In one aspect of the compounds of formula I, B is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂、-SO₃and-NO₂A heterocyclic group of the substituent(s). In a particular aspect, group B is selected from piperidine, piperazine, pyrrolidine, azetidine, tetrahydropyran, and morpholine groups, each having one or more substituents. In a more specific aspect, B is a piperidine group having one or more substituents.

In one aspect, the group B is selected from piperidine, piperazine, pyrrolidine, azetidine, tetrahydropyran, and morpholine, wherein the group B may have 1 to 5 substituents independently selected from the group consisting of acylamino, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halogen, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocycle, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl and C-acylamino. In a more specific aspect, B is a piperidine group having one or more substituents.

According to one embodiment, a is a substituted or unsubstituted benzo [1, 3] dioxole group. In one aspect of this embodiment, a is a 5-bromo-benzo [1, 3] dioxole group. In one aspect of this embodiment, a is an unsubstituted benzo [1, 3] dioxole group. In one aspect of this embodiment, a is a 5-iodo-benzo [1, 3] dioxole group. In one aspect of this embodiment, a is a 5-chloro-benzo [1, 3] dioxole group. In one aspect of this embodiment, a is a 5-fluoro-benzo [1, 3] dioxole group. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

In one aspect of the invention, the group a is substituted with one or more substituents and is selected from phenyl, benzo [1,3]dioxoles, 2, 3-dihydro-1-indanones; group B is substituted with one or more substituents and is selected from piperidine, piperazine, pyrrolidine, azetidine, tetrahydropyran, and morpholine; r₁Is hydrogen; l is₁is-S-; l is₂is-CH₂CH₂-, and pharmaceutically acceptable salts thereof. According to this aspect of the invention, the group a substituents are selected from halo, -CN, alkoxy and the group B substituents are selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And a cyclopentyl group.

In one aspect of the invention, a may be substituted or unsubstituted and is selected from aryl and heterocyclyl;

b may be substituted or unsubstituted and is selected from cycloalkyl and heterocyclyl;

r1 is selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, heteroaryl, heterocycle, carbocycle, amino, halogen, sulfur, and thioalkyl.

In another aspect of the invention, a may be substituted or unsubstituted and is selected from benzo [1, 3] dioxole and phenyl;

B may be substituted or unsubstituted and is selected from heteroaryl, heterocycle and cycloalkyl;

b may be substituted or unsubstituted and is selected from cycloalkyl, heteroaryl and heterocyclyl;

The group B may be substituted or unsubstituted and is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, oxepanyl (oxepane), tetrahydrothienyl (tetrahydrothiophene), thiopyranyl (thiopyranyl), and tetrahydropyranyl;

L₁and L₂As defined above; and itA pharmaceutically acceptable salt.

group-L₂-B is selected from (1-cyclopropyl-propyl) -carbamic acid tert-butyl ester, [1- (tetrahydrothiopyran-4-yl) -propyl ester]-carbamic acid tert-butyl ester, (1-cyclohexyl-propyl) -carbamic acid tert-butyl ester, (1-cyclobutyl-propyl) -carbamic acid tert-butyl ester, N- (1-cyclopropyl-propyl) -methanesulfonamide, 1- (1-cyclopropyl-propyl) -3-isopropyl-urea, (1-cyclopentyl-propyl) -carbamic acid tert-butyl ester, [1- (tetrahydropyran-4-yl) -propyl ] -carbamic acid]-carbamic acid tert-butyl ester, 1-cyclopropyl-propylamine, 1-cyclohexyl-propylamine, 1-cyclobutyl-propylamine, 1-cyclopentyl-propylamine, 1- (tetrahydropyran-4-yl) -propylamine, 1- (tetrahydrothiopyran-4-yl) -propylamine and 1- (1-cyclohexyl-propyl) -1H-pyrrole;

L₁as defined above; and pharmaceutically acceptable salts thereof.

In certain specific aspects of the invention, L₂As defined above, and having one or more groups selected from hydroxy, halogen, alkoxy, amino, C_1-3Alkyl radical, C_3-7Cycloalkyl, -N-C (═ O) OC (CH)₃)₃、-NSO₂CH₃、-NC(＝O)NC(CH₃)₂And a substituent of a pyrrolyl group.

b may be substituted or unsubstituted and is a heteroaryl or heterocyclyl group selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, oxepanyl (oxepane), tetrahydrothienyl (tetrahydrothiophene), thiopyranyl, thiepanyl (thiepane), and tetrahydropyranyl;

The group B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, oxepanyl (oxepane), tetrahydrothienyl (tetrahydrothiophene), thiopyranyl, thiepanyl (thiepane), and tetrahydropyranyl;

According to one aspect of the invention, in the compounds of formula I, a is substituted with one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, -C ≡ N, -SO ₃And the taking of-COOHAryl or heterocyclic radical of a substituent. In another specific aspect, a is phenyl having one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, and-COOH. In another specific aspect, A is a cyclic or acyclic alkyl having one or more groups selected from-F, -Cl, -Br, -I, -OCH₃and-OCH₂CH₃Phenyl group as a substituent of (1). In another aspect, a is benzo [1, 3 ] having one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, and-COOH]A dioxole group. In another specific aspect, A is a cyclic or acyclic alkyl having one or more groups selected from-F, -Cl, -Br, -I, -OCH₃and-OCH₂CH₃Benzo [1, 3 ] of a substituent of]A dioxole group.

In one aspect, in the compounds of formula I, A is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂and-NO₂Aryl or heterocyclic group of the substituent(s). In a particular aspect, A is a compound having one or more groups selected from hydroxy, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C) _1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂and-NO₂Phenyl group as a substituent of (1). In another specific aspect, A is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂and-NO₂Benzo [1, 3 ] of a substituent of]A dioxole group.

In a particular aspect of the compounds of the invention, B is cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclohexyl or cycloheptyl). In another specific aspect, B is a cyclic or acyclic alkyl group having one or more groups selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -CH₂-aryl, -C (═ O) alkyl, -C (═ O) -NH-alkyl, cycloalkyl, hydroxy, -SO₃Cycloalkyl groups as substituents of, -COOH (and esters thereof) and sulfonyl groups. In another specific aspect, B is a cyclic alkyl having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃Cycloalkyl groups as substituents for cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

In a particular aspect of the compounds of the invention, B is thiopyranyl. In another specific aspect, B is a cyclic or acyclic alkyl group having one or more groups selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -CH ₂-aryl, -C (═ O) alkyl, -C (═ O) -NH-alkyl, cycloalkyl, hydroxy, -SO₃Thiopyran groups, -COOH (and esters thereof), and sulfonyl substituents. In another specific aspect, B is a cyclic alkyl having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And thiopyranyl groups which are substituents of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

In a particular aspect of the compounds of the invention, B is tetrahydropyranyl. In another specific aspect, B is a cyclic or acyclic alkyl group having one or more groups selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -CH₂-aryl, -C (═ O) alkyl, -C (═ O) -NH-alkyl, cycloalkyl, hydroxy, -SO₃A tetrahydropyranyl group as a substituent of, -COOH (and esters thereof) and a sulfonyl group. In another specific aspect, B is a cyclic alkyl having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃Tetrahydropyranyl groups as substituents for cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

In one aspect, group B is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuryl, oxepanyl (oxepane), tetrahydrothienyl (tetrahydrothiophene), thiopyranyl, thiepanyl (thiepane), and tetrahydropyranyl, wherein said group B may have from 1 to 5 substituents independently selected from amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocycle, cyano, cyanato, halogen, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocycle, heteroaralkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethylsulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, O-thiopyranyl, thianyl, thiafuranyl, and pyranyl, N-thiocarbamoyl and C-acylamino.

In one aspect of the invention, the group A is substituted with one or more substituents and is selected from phenyl or benzo [1, 3 ]]A dioxole group; the group B is substituted with one or more substituents and is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolyl, thiopyranyl and tetrahydropyranyl; r₁Is hydrogen; l is₁is-S-; l is₂is-CH₂CH₂-, and pharmaceutically acceptable salts thereof. According to this aspect of the invention, the group A is substitutedThe radicals are selected from halogen and alkoxy, and the radical B substituents are selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃Cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

In one aspect, the invention provides compounds of formula I wherein R1 is hydrogen.

In one aspect, the invention provides wherein L₁is-S-a compound of formula I.

In one aspect, the invention provides wherein L₂is-CH₂CH₂-a compound of formula I.

In one aspect, the invention provides compounds of formula I wherein ring B is an optionally substituted adamantane ring.

In one aspect, the invention provides a compound of formula I, wherein L₂Is- (CH)₂)_n-(CH₂)_nAnd each n is independently selected from 0, 1, 2 and 3, and each carbon may optionally be substituted with one or more substituents independently selected from hydroxy, halogen, alkoxy, alkyl, amino, cycloalkyl, -NR ₂R₃、-NSO₂R₄、-NC(＝O)NR₂R₃Heteroaryl, aryl, cycloalkyl and heterocyclic substituents; wherein-R₂and-R₃Independently selected from-H, alkyl and-C (═ O) OR₄(ii) a And wherein R₄Is an alkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl).

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In the event of inconsistencies, the present specification (including definitions) will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.

Detailed Description

1. Definition of

As used herein, "acylamino" (or "acylamido") is any C1-6 acyl (alkanoyl) group defined herein, such as acetylamino, chloroacetylamino, propionylamino, butyrylamino, valerylamino and caproylamino, and aryl-substituted C1-6 acylamino groups, such as benzoylamino and pentafluorobenzoylamino, attached to the amino nitrogen.

As used herein, "acyloxy" is any C1-6 acyl (alkanoyl) group as defined herein linked to an oxy (-O-) group, for example, formyloxy, acetyloxy, propionyloxy, butyryloxy, valeryloxy and hexanoyloxy.

Unless the chain length is otherwise limited, the term "alkenyl" as used herein by itself or as part of another group refers to a straight or branched chain group of 2 to 10 carbon atoms containing at least one double bond between two carbon atoms in the chain. Non-limiting examples of alkenyl groups generally include ethenyl, 1-propenyl, 2-methyl-1-propenyl, 1-butenyl, and 2-butenyl.

The term "alkoxy" as used herein refers to-O-alkyl and-O-cycloalkyl groups as defined herein. Lower alkoxy means-O-lower alkyl. Non-limiting alkoxy groups include oxygen substituted with one of the C1-10 alkyl groups described above, which may be optionally substituted. Non-limiting alkoxy substituents include halogen, morpholino, amino, including alkylamino and dialkylamino, and carboxy including esters thereof.

The term "alkyl" as used herein refers to saturated aliphatic hydrocarbons, including straight and branched chain groups. In one aspect, the alkyl group has 1 to 20 carbon atoms (where appearing herein, a numerical range such as "1 to 20" refers to each integer in the given range; e.g., "1 to 20 carbon atoms" means that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms). In another aspect, it is a medium size alkyl group having 1 to 10 carbon atoms. In yet another aspect, it is a lower alkyl group having 1 to 6 carbon atoms, and even more preferably 1 to 4 carbon atoms. The alkyl group may be substituted or unsubstituted. When it is substituted, the substituent is one or more and is independently selected from the group consisting of cycloalkyl, aryl, heteroaryl, heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-acylamino, N-acylamino, C-carboxy, O-carboxy, cyanato, isocyanato, thiocyanato, isothiocyanato, nitro, silyl and amino. Non-limiting examples of C1-10 alkyl generally include methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, and octyl, which may be optionally substituted.

The term "alkylthio" as used herein refers to both S-alkyl and-S-cycloalkyl groups as defined herein. Non-limiting alkylthio groups include sulfur substituted with one of the C1-10 alkyl groups described above, which alkyl groups may be optionally substituted. Also included are sulfoxides and sulfones of such alkylthio groups.

Unless the chain length is otherwise limited by the context, the term "alkynyl" as used herein refers to a straight or branched chain group of 2 to 10 carbon atoms, wherein there is at least one triple bond between two carbon atoms of the chain. Alkynyl generally includes ethynyl, 1-propynyl, 1-methyl-2-propynyl, 1-butynyl and 2-butynyl.

The term "amino" as used herein refers to-NR₁₇R₁₈Group, R₁₇And R₁₈When it is hydrogen, it is-NH₂A group. R₁₇And R₁₈And may also independently be hydrogen, C1-10 alkyl or cycloalkyl; or R₁₇And R₁₇Binding N to form a ring structure such as piperidine; or R₁₇And R₁₈Binding to N forms a ring such as piperazine. R₁₇And R₁₈One of (a) may be hydrogen and the other alkyl or cycloalkyl. The alkyl or cycloalkyl groups may be optionally substituted.

The term "amino acid" as used herein refers to both natural amino acids and unnatural amino acids. Examples of natural amino acids include, but are not limited to, alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, and protected forms thereof (e.g., boc). Examples of unnatural amino acids include, but are not limited to, O-methyl-L-tyrosine, L-3- (2-naphthyl) alanine, 3-methyl-phenylalanine, O-4-allyl-L-tyrosine, 4-propyl-L-tyrosine, tri-O-ethyl-GlcNAc β -serine, L-dopa, fluorinated phenylalanine, isopropyl-L-phenylalanine, p-azido-L-phenylalanine, p-acyl-L-phenylalanine, p-benzoyl-L-phenylalanine, L-phosphoserine, phosphonoserine, phosphonotyrosine, p-iodo-phenylalanine, p-bromophenylalanine, p-amino-L-phenylalanine, and isopropyl-L-phenylalanine.

The term "aryl" as employed herein by itself or as part of another group refers to a monocyclic, bicyclic or tricyclic aromatic group having 6 to 14 carbons in the ring portion. Non-limiting aryl groups include C6-14 aryl groups, preferably C6-10 aryl groups. C6-14 aryl generally includes phenyl, naphthyl, phenanthryl, anthracyl, indenyl, oxazolyl (azulenyl), biphenyl, biphenylene, and fluorenyl.

The term "aralkyl" as used herein refers to any C1-10 alkyl group substituted with any of the C6-14 aryl groups described above as defined herein. Non-limiting examples of aralkyl groups include benzyl, phenethyl, and naphthylmethyl.

The term "aralkenyl" as used herein means any of the C2-10 alkenyl groups described above substituted with any of the C6-14 aryl groups described above.

The term "arylalkynyl" as used herein refers to C2-10 alkynyl substituted with any of the above C6-14 aryl groups as defined herein.

The term "aralkoxy" as used herein, refers to a C1-10 alkoxy group substituted with any aryl group as defined herein, which may be optionally substituted. Examples of the aralkyloxy group include a benzyloxy group and a phenethyloxy group.

The term "aryloxy" as used herein refers to oxygen substituted with any of the herein defined C6-14 aryl groups, which may be optionally substituted. Examples of the aryloxy group include a phenoxy group and a 4-methylphenoxy group.

The term "arylthio" group as used herein refers to both groups-S-aryl and-S-heteroaryl as defined herein.

The term "carbocycle" or "carbocyclic" as used herein refers to cycloalkyl groups and partially saturated carbocyclic groups. Non-limiting carbocyclic groups are C3-8 cycloalkyl and cycloalkenyl. Cycloalkyl groups typically include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl and cycloheptyl.

The term "cyano" as used herein refers to a-C ≡ N group.

The term "cyanato" as used herein refers to the group-CNO.

The term "halogen" or "halogen group" as used herein refers to fluoro, chloro, bromo and iodo groups.

The term "haloalkyl" as used herein refers to a C1-10 alkyl group substituted with one or more fluoro, chloro, bromo, or iodo groups, such as fluoromethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, 1-difluoroethyl, chloromethyl, chlorofluoromethyl, and trichloromethyl. The halogen groups may be independently selected.

The term "halophenyl" as used herein refers to a phenyl group substituted with one or more fluoro, chloro, bromo, or iodo groups. The halogen groups may be independently selected, for example, bis-halogen substituted phenyl groups may have fluorine and chlorine substituents.

The term "hydrogen" as used herein refers to the-H group.

The term "hydroxy" as used herein refers to an-OH group.

The term "heteroaryl" as used herein refers to groups having 5 to 14 ring atoms; sharing 6, 10 or 14 pi electrons on the ring array; and contains carbon atoms and 1, 2 or 3 heteroatoms of oxygen, nitrogen or sulfur. Non-limiting heteroaryl groups include: thienyl (thiophenyl); benzo [ b ] thienyl; naphtho [2, 3-b ] thienyl; a thianthrenyl group; furyl (furyl ); isobenzofuranyl; a chromenyl group; a xanthyl group; a phenoxathiyl group; pyrrolyl, including but not limited to 2H-pyrrolyl; an imidazolyl group; a pyrazolyl group; pyridyl (pyridyl) groups including, but not limited to, 2-pyridyl, 3-pyridyl, and 4-pyridyl; a pyrazinyl group; a pyrimidinyl group; a pyridazinyl group; a indolizinyl group; an isoindolyl group; 3H-indolyl; an indolyl group; (ii) an indazolyl group; a purine group; 4H-quinolizinyl; an isoquinolinyl group; a quinolyl group; 2, 3-naphthyridinyl; 1, 5-naphthyridinyl; a quinazolinyl group; a cinnolinyl group; pteridinyl; a carbazolyl group; a beta-carboline group; phenanthridinyl; an acridinyl group; peri-naphthodiazenyl; phenanthroline group; a phenazine group; an isothiazolyl group; a phenothiazinyl group; an isoxazolyl group; a furazanyl group; a phenoxazinyl group; 1, 4-dihydroquinoxaline-2, 3-dione; 7 amino isocoumarin; pyrido [1, 2-a ] pyrimidin-4-one; pyrazolo [1, 5-a ] pyrimidinyl, including but not limited to pyrazolo [1, 5-a ] pyrimidin-3-yl; 1, 2-benzisoxazol-3-yl; a benzimidazolyl group; 2-oxindolyl and 2-oxobenzimidazolyl. If the heteroaryl group contains a nitrogen atom in the ring, the nitrogen atom may be in the form of an N-oxide, such as pyridyl N-oxide, pyrazinyl N-oxide and pyrimidinyl N-oxide. Heteroaryl groups can be monocyclic, bicyclic, tricyclic, and/or polycyclic.

The term "heteroaryloxy" as used herein refers to an oxygen substituted with a heteroaryl group, as defined herein, which may be optionally substituted. Non-limiting heteroaryloxy groups include pyridyloxy, pyrazinyloxy, pyrrolyloxy, pyrazolyloxy, imidazolyloxy and thiophenyloxy.

The term "heterocycle" or "heterocyclic" as used herein refers to a saturated or partially saturated 3-7 membered monocyclic, 7-10 membered bicyclic, or 7-14 membered polycyclic ring system, said ring consisting of carbon atoms and 1-5 heteroatoms independently selected from O, N and S, wherein said nitrogen and sulfur heteroatoms may be optionally oxidized, said nitrogen may be optionally quaternized; and includes any bicyclic ring wherein any of the above-defined heterocyclic rings is fused to a benzene ring, and wherein said heterocyclic ring may be substituted on a carbon atom or on a nitrogen atom, provided that the resulting compound is stable (as readily recognized by a person skilled in the art). Non-limiting saturated or partially saturated heterocyclyl groups include tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, isochromanyl, chromanyl, pyrazolidinyl, pyrazolinyl, pivaloyl, and tetramoyl groups.

The term "heteroarylalkoxy" as used herein refers to a C1-10 alkoxy group substituted with a heteroaryl group as defined herein, which heteroaryl group may be optionally substituted.

The term "isocyanato" as used herein refers to the group-NCO.

The term "isothiocyanato" as used herein refers to the-NCS group.

The term "nitro" as used herein means-NO₂A group.

The term "sulfinyl" as used herein refers to the group — S (═ O) R ". R' may be cycloalkyl or alkyl. The alkyl or cycloalkyl groups may be optionally substituted.

The term "sulfonyl" as used herein means-S (═ O)₂R' group. R' may be cycloalkyl or alkyl. The alkyl or cycloalkyl groups may be optionally substituted.

The term "sulfamoyl" as used herein refers to-S (═ O)₂NR₁₇R₁₈。R₁₇And R₁₈May independently be hydrogen, C1-10 alkyl or cycloalkyl; or R₁₇And R₁₈Binding N to form a ring structure such as piperidine; or R₁₇And R₁₈Combine N to form a ring such as piperazine. R₁₇And R₁₈One of which may be hydrogen and the other cycloalkyl or alkyl. The alkyl or cycloalkyl groups may be optionally substituted.

The term "thiocarbonyl" group as used herein refers to a — C (═ S) R "group. R' may be cycloalkyl or alkyl. The alkyl or cycloalkyl groups may be optionally substituted.

The term "thiocyanato" as used herein refers to a-CNS group.

The term "trihalomethylsulfonylamino" as used herein means X₃CS(＝O)₂NR₁₇-a group, wherein X is independently selected from-Br, -Cl, -F and-I groups, and R₁₇As defined herein.

The term "O-carbamoyl" as used herein refers to-OC (═ O) NR₁₇R₁₈A group. R₁₇And R₁₈Can be hydrogen, C1-10 alkyl or cycloalkyl; or R₁₇And R₁₈Binding N to form a ring structure such as piperidine; or R₁₇And R₁₈Combine N to form a ring such as piperazine. R₁₇And R₁₈One of which may be hydrogen and the other alkyl or cycloalkyl. The alkyl or cycloalkyl groups may be optionally substituted.

The term "N-carbamoyl" as used herein means R₁₈OC(＝O)NR₁₇-a group. R₁₈May be hydrogen; r₁₇And R₁₈May be C1-10 alkyl or cycloalkyl; or R₁₇And R₁₈Binding N to form a ring structure such as piperidine; or R₁₇And R₁₈Combine N to form a ring such as piperazine. R₁₇And R₁₈One of which may be hydrogen and the other alkyl or cycloalkyl. The alkyl or cycloalkyl groups may be optionally substituted.

The term "O-thiocarbamoyl" as used herein refers to-OC (═ S) NR₁₇R₁₈A group. R₁₇And R₁₈Can be hydrogen, C1-10 alkyl or cycloalkyl; or R₁₇And R ₁₈Binding N to form a ring structure such as piperidine; or R₁₇And R₁₈Combine N to form a ring such as piperazine. R₁₇And R₁₈One of which may be hydrogen and the other cycloalkyl or alkyl. The alkyl or cycloalkyl groups may be optionally substituted.

The term "N-thiocarbamoyl" as used herein means R₁₇OC(＝S)NR₁₈-a group. R₁₇May be hydrogen; r₁₇And R₁₈May be a C1-10 alkyl or cycloalkyl group. The alkyl or cycloalkyl groups may be optionally substituted.

The term "C-acylamino" as used herein refers to-C (═ O) NR₁₇R₁₈A group. "N-acylamino" means R₁₇C(＝O)NR₁₈-a group (R)₁₈Not hydrogen). R₁₇And R₁₈Can be hydrogen, C1-10 alkyl or cycloalkyl; or R₁₇And R₁₈Binding N to form a ring structure such as piperidine; or R₁₇And R₁₈Combine N to form a ring such as piperazine. R₁₇And R₁₈One of which may be hydrogen and the other alkyl or cycloalkyl. The alkyl or cycloalkyl groups may be optionally substituted.

In certain aspects, unless otherwise indicated, the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, carbocycle and heterocyclyl groups include one or more of halogen, hydroxyl, carboxyl, amino, nitro, cyano, C1-C6 acylamino, C1-C6 acyloxy, C1-C6 alkoxy, aryloxy, alkylthio, C6-C10 aryl, C4-C7 cycloalkyl, C2-C6 alkenyl, C2C 6 alkynyl, C6-C10 aryl (C2-C6) alkenyl, C6-C10 aryl (C2-C6) alkynyl, heterocycle and heteroaryl.

In certain aspects, unless otherwise indicated, the aryl, aralkyl, aralkenyl, aralkynyl, and heteroaryl and heteroarylalkyl groups may be optionally substituted with one or more halogen, C1-C6 haloalkyl, C6-C10 aryl, C4-C7 cycloalkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6C10 aryl (C1-C6) alkyl, C6-C10 aryl (C2-C6) alkenyl, C6-C10 aryl (C2-C6) alkynyl, C1-C6 hydroxyalkyl, nitro, amino, ureido, cyano, C1-C6 amido, hydroxy, thiol, C1-C6 acyloxy, azido, C1-C6 alkoxy, carboxy, or C1-2 alkylenedioxy (e.g., methylenedioxy).

2. Compounds and compositions of the invention

The present invention relates to compounds of formulae I-III. The invention also relates to pharmaceutical compositions comprising one or more compounds of formulae I-III and a pharmaceutically acceptable carrier (excipient). The present inventors have found that the compounds of formula I-III have pharmacological activity. One particular activity that compounds of formulae I-III have been shown to possess is anti-cancer activity. The present invention relates to compounds of the following formulae I-III. The invention also relates to pharmaceutical compositions containing one or more compounds of formulae I-III and pharmaceutically acceptable excipients. The present inventors have found that the compounds of formula I-III have pharmacological activity. One particular activity that compounds of formulae I-III have been shown to possess is anti-cancer activity. The present invention relates to compounds of the following formulae I-III. The invention also relates to pharmaceutical compositions containing one or more compounds of formulae I-III and pharmaceutically acceptable excipients. The present inventors have found that the compounds of formula I-III have pharmacological activity. One particular activity that compounds of formulae I-III have been shown to possess is anti-cancer activity.

Formula I

Formula II

Formula III

The present invention provides compounds of formula I as follows, wherein:

Unless otherwise indicated, L₁And L₂Can be either of two orientations, e.g., - (CH)₂)_nNC(＝S)S(CH₂)_n-means purine- (CH)₂)_nNC(＝S)S(CH₂)_n-phenyl orientation and purine- (CH)₂)_nSC(＝S)N(CH₂)_n-phenyl orientation.

According to one aspect, a is substituted with one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, -C ≡ N, -SO₃And aryl group as a substituent of-COOH. In a more specific aspect of the invention, a is phenyl having one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy and-COOH. In an even more particular aspect of the invention, A is a compound having one or more groups selected from-F, -Cl, -Br, -I, -OCH₃、-CF₃、-CH₃、-OCF₃、-C(＝O)CH₃-COOH, -C.ident.N and-NO₂Phenyl group as a substituent of (1).

In one aspect of the compounds of the invention, A is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C) _1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl) -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂and-NO₂Aryl group of the substituent(s). In a particular aspect, a is phenyl.

In one aspect of the compounds of the invention, A is phenyl having 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethylsulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one aspect of the compounds of the present invention, B is substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, -SO₃And aryl group as a substituent of-COOH. In a particular aspect, B is phenyl. In a more specific aspect, B is phenyl having one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, and-COOH. In an even more particular aspect, B is a cyclic or branched alkyl having one or more groups selected from-F, -Cl, -Br, -I, -CH ₃、-OCH₃、-CF₃、-OCF₃、-C(＝O)CH₃-COOH, -C.ident.N and-NO₂Phenyl group as a substituent of (1).

According to one embodiment, A is a substituted or unsubstituted 2, 3-dihydro-1-indanone group. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

According to one embodiment, a is a substituted or unsubstituted benzodioxine group. In one aspect of this embodiment, A has 1 to 5 substituents independently selected from the group consisting of amido, acyloxy, alkenyl, alkoxy, alkyl, alkylthio, alkynyl, amino, aryl, aralkyl, aralkenyl, aralkynyl, aralkoxy, aryloxy, arylthio, carbocyclic, cyano, cyanato, halo, haloalkyl, halophenyl, hydroxy, heteroaryl, heteroaryloxy, heterocyclic, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfamoyl, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, and C-amido.

a is substituted or unsubstituted aryl;

b is substituted or unsubstituted aryl;

L₁may be saturated, partially saturated or unsaturated, and is selected from: - (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH₂)_n-、-(CH₂)nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-、-(CH₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8, and wherein each carbon and/or nitrogen may optionally be optionally substituted with one or more groups independently selected from hydroxy, halogen, alkoxy, C_1-3Alkyl and C_3-6Cycloalkyl substituents;

L₂may be saturated, partially saturated or unsaturated, and is selected from: - (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH₂)_n-、-(CH₂)_nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-、-(CH₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8, and wherein each carbon and/or nitrogen may optionally be optionally substituted with one or more groups independently selected from hydroxy, halogen, alkoxy, C_1-3Alkyl and C_3-6Cycloalkyl substituents; and pharmaceutically acceptable salts thereof.

a is substituted or unsubstituted heteroaryl;

b is substituted or unsubstituted aryl;

L₂may be saturated, partially saturated or unsaturated, and is selected from- (CH)₂)_n-(CH₂)_n-、-(CH₂)_nC(＝O)(CH₂)_n-、-(CH₂)_nC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝O)O(CH₂)_n-、-(CH₂)_nNC(＝O)N(CH₂)_n-、-(CH₂)_nNC(＝S)S(CH₂)_n-、-(CH₂)_nOC(＝O)S(CH₂)_n-、-(CH₂)_nNH(CH₂)_n-、-(CH₂)_nO(CH₂)_n-、-(CH₂)_nS(CH₂)_n-、-(CH₂)_nNC(＝S)N(CH₂)_n-, wherein each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7 and 8, and wherein each carbon and/or nitrogen may optionally be optionally substituted with one or more groups independently selected from hydroxy, halogen, alkoxy, C_1-3Alkyl and C_3-6Cycloalkyl substituents; and pharmaceutically acceptable salts thereof.

According to one aspect of the present invention, there is provided a compound of formula I, wherein a is substituted or unsubstituted heterocyclyl; b is substituted or unsubstituted aryl; and R1 is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, amino, halogen, sulfur, and thioalkyl.

According to certain aspects of the invention, in the compounds of formula I, A is substituted or unsubstituted and is selected from indazolyl, 1H-indolyl, benzothiazolyl, 1H-benzotriazolyl, benzoxazolyl, 1H-imidazolyl, 3H-benzoxazol-2-one, 4H-benzo [1, 4] oxazin-3-one, 1, 3 dihydro-benzimidazol-2-one, 3H-benzothiazol-2-one, 1H-pyrazolo [3, 4-b ] pyridine, 1H-quinoxalin-2-one, 4H-benzo [1, 4] oxazin-3-one, isoquinoline, indoline, 1, 3 dihydro-indol-2-one, 2, 3-dihydro-benzo [1, 4] dioxine, thienyl (thienyl, thiophenyl), benzo [ b ] thienyl, naphtho [2, 3-b ] thienyl, thianthrenyl, furyl (furyl ), isobenzofuryl, chromenyl, xanthenyl, phenoxathinyl, pyrrolyl, 2H-pyrrolyl, imidazolyl, pyrazolyl, pyridyl (pyridinyl), 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, purinyl, 4H-quinolizinyl, isoquinolyl, quinolyl, 2, 3-naphthyridinyl, 1, 5-naphthyridinyl, quinazolinyl, cinnolinyl, pteridinyl, carbazolyl, beta-carbolinyl, phenanthridinyl, acridinyl, peridinylphenyl, Phenanthrolinyl, phenazinyl, isothiazolyl, phenothiazinyl, isoxazolyl, furazanyl, phenoxazinyl, 1, 4-dihydroquinoxaline-2, 3-dione, 7 aminoisocoumarin, pyrido [1, 2-a ] pyrimidin-4-one, pyrazolo [1, 5-a ] pyrimidinyl, pyrazolo [1, 5-a ] pyrimidin-3-yl, 1, 2-benzisoxazol-3-yl, benzimidazolyl, 2-oxindolyl, 2-oxobenzimidazolyl, tetrahydrofuranyl, pyranyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, isochroman, chromanyl, pyrazolidinyl, pyrazolinyl, pivaloyl, and tetramoyl.

In certain aspects of the compounds of the invention, the A ring is substituted with one or moreIs selected from-L₁-C(＝O)OH、-L₁-CH＝CHC(＝O)OH、-L₁-C(＝O)NH₂、-L₁-C(＝O)NH(C_1-3Alkyl), -L₁-C(＝O)N(C_1-3Alkyl radical)₂、-L₁-S(＝O)₂(C_1-3Alkyl), -L₁-S(＝O)₂NH₂、-L₁-S(＝O)₂N(C_1-3Alkyl radical)₂、-L₁-S(＝O)₂NH(C_1-3Alkyl), -L₁-C(＝O)NHOH、-L₁-C(＝O)CH₂NH₂、-L₁-C(＝O)CH₂OH、-L1-C(＝O)CH₂SH、-L₁-C(＝O)NHCN、-L₁-NHC(＝O)OR_o、-L₁-C(＝O)NHR_o、-L₁-NH(C＝O)NHR_o、-L₁-C(＝O)N(R_o)₂、-L₁-NH(C＝O)N(R_o)₂、-L₁-a substituent of a sulfo group; wherein R is_oSelected from alkyl and haloalkyl, and L₁Independent of any other L in the compound₁And is as defined above.

According to one aspect of the invention, there is provided a compound of formula I, wherein L₂Is selected from-CH₂-、-CH₂CH₂-、-CH₂CH₂CH₂、-CH(CH₃)CH₂-、-CH(CH₂CH₃)CH₂-、-CH(CH(CH₃)₂₎CH₂-、-C(CH₂CH₂)CH₂-、-C(CH₂CH₂CH₂)CH₂-、-CH(CH(CH₃)CH₂CH₃)CH₂-、-CH(CH(CH₂)₄)CH₂-、-CH(CH(CH₂)₅)CH₂-、-CH(OH)CH₂-and-CH (CH)₂OH)CH₂-. In a more specific aspect, L₂Is selected from-CH₂CH₂-and-CH₂CH₂CH₂. In an even more particular aspect, L ₂is-CH₂CH₂-. Unless otherwise indicated, L₂Can be in either of two orientations, e.g., -CH (CH)₂CH₂)CH₂-means purine-CH (CH)₂CH₂)CH₂-phenyl orientation and purine-CH₂CH(CH₂CH₂) -phenyl orientation.

According to one aspect of the compounds of the present invention, the group B is selected from the group consisting of 2-bromophenyl, 2-fluorophenyl, 2-chlorophenyl, 3-fluorophenyl, 3-iodophenyl, 3-bromophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 2, 3-dichlorophenyl, 2, 4-dichlorophenyl, 2, 6-dichlorophenyl, 2, 3-difluorophenyl, 3, 5-difluorophenyl, 4-chloro-2-fluorophenyl, 2-chloro-6-fluorophenyl, pentafluorophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-benzoic acid, 2-trifluoromethylphenyl, 3-methoxyphenyl, 2-nitrophenyl, 3-bromophenyl, and mixtures thereof, 3, 4-dimethoxyphenyl, 3, 5-dimethoxyphenyl, 3, 4, 5-trimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, p-tolyl, o-tolyl, 2, 5-dimethylphenyl, 3, 5-dimethylphenyl, 2, 4, 6-trimethylphenyl, 4-acetophenone, 4-phenol, 4-benzenesulfonic acid, 4-dimethylaminophenyl, tert-butyl-4-carbamate-phenyl, 4-aminophenyl, 3-trifluoromethoxyphenyl, and 3, 5-bistrifluoromethylphenyl. In this aspect, the position (numbering) of the substituent is relative to the bond of the phenyl group to the purine core. In this respect, a specific embodiment In, L₂Is selected from-CH₂-CH₂-and-CH₂-CH₂-CH₂-。

Formula II

Formula III

a is a substituted or unsubstituted heterocyclic group;

b is substituted or unsubstituted aryl;

b may be substituted or unsubstituted and is a heterocyclic group selected from piperidine, pyrrolidine, azetidine, piperazine, morpholine and tetrahydropyran.

L₁and L₂As defined above; and pharmaceutically acceptable salts thereof.

the group B is selected from piperidine, piperidine-1-carboxylic acid ethyl ester, piperidine-1-carboxylic acid tert-butyl ester, 2, 6, 6-tetramethyl-piperidine, piperidine-2, 6-dione, piperidine-1-carboxaldehyde, 1-methyl-pyrrolidine, 1-isopropyl-piperazine, tetrahydropyran, adamantane, piperidine-1-carboxaldehyde, 1-piperidin-1-yl-ethanone, 1-methanesulfonyl-piperidine, 1-propyl-piperidine, 1-trifluoromethanesulfonyl-piperidine, piperidine-1-carboxylic acid tert-butyl ester, pyrrolidine-1-carboxylic acid tert-butyl ester, morpholine-4-carboxylic acid tert-butyl ester, 1-pyrrolidin-1-yl-ethanone, methyl-ethyl acetate, methyl-1-pyrrolidinone, methyl, 1-methanesulfonyl-pyrrolidine, pyrrolidine-1-carbaldehyde, azetidine-1-carboxylic acid tert-butyl ester, 1-methyl-azetidine, azetidine-1-carbaldehyde, 1-azetidin-1-yl-ethanone, 1-methanesulfonyl-azetidine, and 1-trifluoromethanesulfonyl-azetidine, cycloheptane, imidazole, undecafluorocyclohexane, cyclohexyl carbamic acid tert-butyl ester, 1-piperazin-1-yl-ethanone, 6-dimethyl-bicyclo [3.1.1] hept-2-ene, 5-methyl-2, 4-dihydro-pyrazol-3-one, piperidine-1-carboxylic acid benzyl ester, morpholine, pyrrolidine-1-carboxylic acid benzyl ester, Piperidine-1, 2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester, benzyl-1, 2, 3, 6-tetrahydropyridine, hexahydro-4 b-aza-cyclopropyl [ cd ] pentalene, 2-isopropyl-piperidine-1-carboxylic acid tert-butyl ester, piperidine-1-carboxylic acid acetamide, piperidine-1-carboxylic acid isopropylamide, piperidine-1-carboxylic acid tert-butylamide, [ { piperidine-1-carbonyl } amino ] -acetic acid ethyl ester, isopropylpiperidine, isobutylpiperidine, 2-dimethyl-1-piperidin-1-yl-propan-1-one, 2-dimethyl-1-piperidin-1-yl-butan-1-one, and mixtures thereof, 2-isopropyl-piperidine, 1-isopropyl-piperazine and 1-cyclopentyl-piperazine.

In one aspect, in the compounds of formula I, A is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃，-CN、-NH₂and-NO₂Aryl or heterocyclic group of the substituents of (1). In a particular aspect, A is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂and-NO₂Phenyl group as a substituent of (1). In another specific aspect, A is a compound having one or more groups selected from hydroxy, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O) NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂and-NO₂Benzo [1, 3] of a substituent of]Meta-dioxa medicineA cyclopentene group.

According to one aspect, in the compounds of formula I, B is a heterocyclic ring having one or more heteroatoms selected from-N-and-O-, wherein the heterocyclic group may have one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH₂-an aryl group; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O) -NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO₃(ii) a -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); peptides having 1-5 amino acid residues (selected from natural and non-natural amino acids); -C (═ O) alkyl, where the alkyl is substituted with one or more substituents selected from alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl; and a sulfonyl group. In a particular aspect, B is a piperidine (piperidinyl) group. In a particular aspect, B is a piperidine group substituted with one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH₂-an aryl group; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O) -NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO ₃(ii) a -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); having 1-5 amino acid residues (selected from natural and non-natural ammonia)Amino acid); -C (═ O) alkyl, where the alkyl is substituted with one or more substituents selected from alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl; and a sulfonyl group. In a more specific aspect, B is a cyclic or acyclic alkyl group having one or more groups selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -CH₂-aryl, -C (═ O) alkyl, -C (═ O) -NH-alkyl, cycloalkyl, hydroxy, -SO₃A piperidine group for a substituent of, -COOH (and esters thereof) and sulfonyl. In an even more particular aspect, B is a cyclic compound having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And a piperidine group as a substituent of the cyclopentyl group.

In a particular aspect, B is a homopiperidine (homopiperidinyl) group. In a more specific aspect, B is a homopiperidine group having one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH ₂-an aryl group; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O) -NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO₃(ii) a -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); peptides having 1-5 amino acid residues (selected from natural and non-natural amino acids); -C (═ O) alkyl, wherein said alkyl is substituted with one or more substituents (selected from alkyl, amino, alkoxyHaloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl) substituted; and a sulfonyl group. In yet a more particular aspect, B is a cyclic alkyl having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And homopiperidinyl group as a substituent for cyclopentyl.

In a particular aspect, B is a pyrrolidine (pyrrolidinyl) group. In a more particular aspect, B is a pyrrolidine group having one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH₂-an aryl group; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O) -NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO₃(ii) a -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); peptides having 1-5 amino acid residues (selected from natural and non-natural amino acids); -C (═ O) alkyl, where the alkyl is substituted with one or more substituents selected from alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl; and a sulfonyl group. In an even more particular aspect, B is a cyclic compound having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And a pyrrolidine group as a substituent of the cyclopentyl group.

In a particular aspect, B is an azetidinyl group. In a more specific aspect, B is an azetidine group having one or more substituents selected from the group consisting of: hydrogen; halogen; an alkyl group; an alkoxy group; a haloalkyl group; a haloalkoxy group; a nitro group; -CH 2-aryl; -C (═ O) alkyl; -C (═ O) cycloalkyl; -C (═ O) -NH-alkyl; a cycloalkyl group; a hydroxyl group; -SO 3; -COOH (and esters thereof); amino acids (selected from natural and unnatural amino acids); peptides having 1-5 amino acid residues (selected from natural and non-natural amino acids); -C (═ O) alkyl, where the alkyl is substituted with one or more substituents selected from alkyl, amino, alkoxy, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -COOH (and esters thereof), sulfonyl, sulfamoyl; and a sulfonyl group. In yet an even more particular aspect, B is a cyclic compound having one or more substituents selected from-C (═ O), -C (═ O) CH ₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And an azetidinium group as a substituent of the cyclopentyl group.

In one aspect of the compounds of formula I, B is a compound having one or more groups selected from hydroxy, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, -N (C)_1-3Alkyl radical)₂、-NH(C_1-3Alkyl), -C (═ O))NH₂、-C(＝O)NH(C_1-3Alkyl), -C (═ O) N (C)_1-3Alkyl radical)₂、-S(＝O)₂(C_1-3Alkyl), -S (═ O)₂NH₂、-S(＝O)₂N(C_1-3Alkyl radical)₂、-S(＝O)₂NH(C_1-3Alkyl), -CHF₂、-OCF₃、-OCHF₂、-SCF₃、-CF₃、-CN、-NH₂、-SO₃and-NO₂A heterocyclic group of the substituent(s). In a particular aspect, group B is selected from piperidine, piperazine, pyrrolidine, azetidine, tetrahydropyran, and morpholine groups, each having one or more substituents. In a more specific aspect, B is a piperidine group having one or more substituents.

In one aspect of the invention, the group A is substituted with one or more substituents and is selected from phenyl, benzo [1, 3]]Dioxoles, 2, 3-dihydro-1-indanones; group B is substituted with one or more substituents and is selected from piperidine, piperazine, pyrrolidine, azetidine, tetrahydropyran, and morpholine; r₁Is hydrogen; l is₁is-S-; l is₂is-CH₂CH₂-, and pharmaceutically acceptable salts thereof. According to this aspect of the invention, the group a substituents are selected from halo, -CN, alkoxy and the group B substituents are selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃And a cyclopentyl group.

The group B may be substituted or unsubstituted and is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, oxepanyl (oxepane), tetrahydrothienyl (tetrahydrothiophene), thiopyranyl, thiepanyl (thiepane), and tetrahydropyranyl;

L₁and L₂As defined above; and pharmaceutically acceptable salts thereof.

L₁as defined above; and pharmaceutically acceptable salts thereof.

According to one aspect of the invention, in the compounds of formula I, a is substituted with one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, -C ≡ N, -SO ₃And an aryl or heterocyclic group as a substituent of-COOH. In another specific aspect, a is phenyl having one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, and-COOH. In another specific aspect, A is a cyclic or acyclic alkyl having one or more groups selected from-F, -Cl, -Br, -I, -OCH₃and-OCH₂CH₃Phenyl group as a substituent of (1). In another aspect, a is benzo [1, 3 ] having one or more substituents selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -C (═ O) alkyl, hydroxy, and-COOH]A dioxole group. In another specific aspect, A is a cyclic or acyclic alkyl having one or more groups selected from-F, -Cl, -Br, -I, -OCH₃and-OCH₂CH₃Benzo [1, 3 ] of a substituent of]A dioxole group.

In a particular aspect of the compounds of the invention, B is cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclohexyl or cycloheptyl). In another specific aspect, B is a cyclic or acyclic alkyl group having one or more groups selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, -CH₂-aryl radical-C (═ O) alkyl, -C (═ O) -NH-alkyl, cycloalkyl, hydroxy, -SO₃Cycloalkyl groups as substituents of, -COOH (and esters thereof) and sulfonyl groups. In another specific aspect, B is a cyclic alkyl having one or more substituents selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃Cycloalkyl groups as substituents for cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

In one aspect of the invention, the group A is substituted with one or more substituents and is selected from phenyl or benzo [1, 3 ]]A dioxole group; the group B is substituted with one or more substituents and is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolyl, thiopyranyl and tetrahydropyranyl; r₁Is hydrogen; l is₁is-S-; l is₂is-CH₂CH₂-, and pharmaceutically acceptable salts thereof. According to this aspect of the invention, the group a substituents are selected from halo and alkoxy, and the group B substituents are selected from-C (═ O), -C (═ O) CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH(CH₃)₂、-CH₂CH(CH₃)₂、-C(＝O)CH₂C(CH₃)₃Cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

In one aspect, the invention provides wherein L₁A compound of formula I which is-S-.

In one aspect, the invention provides a compound of formula I, wherein L₂Is- (CH)₂)_n-(CH₂)_nAnd each n is independently selected from 0, 1, 2 and 3, and each carbon may optionally be substituted with one or more substituents independently selected from hydroxy, halogen, alkoxy, alkyl, amino, cycloalkyl, -NR₂R₃、-NSO₂R₄、-NC(＝O)NR₂R₃Heteroaryl, aryl, cycloalkyl and heterocyclic substituents; wherein-R ₂and-R₃Independently selected from-H, alkyl and-C (═ O) OR₄(ii) a And wherein R₄Is an alkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl).

Examples of compounds of the invention are given in the examples. In some aspects, compounds of the invention include those of the examples having an IC50 equal to or less than 10 μ Μ. In some aspects, compounds of the invention include those of the examples having an IC50 equal to or less than 5 μ Μ. In some aspects, compounds of the invention include those of the examples having an IC50 equal to or less than 1 μ Μ. In some aspects, compounds of the invention include those of the examples having an IC50 equal to or less than 0.5 μ Μ.

In some aspects, compounds of the invention include those in any aspect of the embodiments of the invention and having an IC50 equal to or less than 10 μ Μ. In some aspects, compounds of the invention include those in any aspect of the embodiments of the invention and having an IC50 equal to or less than 5 μ Μ. In some aspects, compounds of the invention include those in any aspect of the embodiments of the invention and having an IC50 equal to or less than 1 μ Μ. In some aspects, compounds of the invention include those in any aspect of the embodiments of the invention and having an IC50 equal to or less than 0.5 μ Μ.

In some aspects, the invention relates to a compound of the invention attached to a resin. In a particular aspect, the resin is selected from the group consisting of sephadex (sephadex), tentagel and affigel.

As will be understood by those skilled in the art, certain terms in a list of substituents are repeated with (different names for the same substituent) or encompassed by, and/or partially overlap with, the meaning of other terms in the list. It will be appreciated by those skilled in the art that in the compounds of the invention, substituents may be attached to the remainder of the molecule through a variety of positions, preferred positions being exemplified in the examples.

In addition, the compounds of formula I-III may contain asymmetric carbon atoms and thus may exist in racemic and optically active forms. Thus, optical isomers or enantiomers, racemates, tautomers and diastereomers are also encompassed within the compounds of formula I-III. The process of the present invention includes the use of all of these isomers and mixtures thereof. Methods for separating enantiomeric and diastereomeric mixtures are well known to those skilled in the art. The present invention encompasses any isolated racemic or optically active form of the compounds of formula I, or any mixture thereof.

In one embodiment, the present invention provides a compound or pharmaceutical composition comprising the compound, wherein the compound is selected from the group consisting of 8- (2, 5-dimethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-phenyl-propyl) -9H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylsulfanyl) -9-phenethyl-9H-purin-6-ylamine, and combinations thereof, 8- (benzo [1, 3] dioxol-5-ylthio) -3-phenethyl-3H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -9- (3-phenyl-propyl) -9H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -9- [2- (4-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier thereof, and a pharmaceutically acceptable carrier, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (4-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -9- [2- (4-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -3- [2- (4-fluoro-phenyl) -ethyl ] - 3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9-phenethyl-9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3-phenethyl-3H-purin-6-ylamine, 8- (2, 4-dimethoxy-phenylthio) -9-phenethyl-9H-purin-6-ylamine, 8- (2, 4-dimethoxy-phenylthio) -3-phenethyl-3H-purin-6-ylamine, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts thereof, 8- (4-chloro-benzenesulfonyl) -9-phenethyl-9H-purin-6-ylamine, 8- (4-chloro-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine, 4- (6-amino-9-phenethyl-9H-purin-8-ylsulfanyl) -benzonitrile, 4- (6-amino-3-phenethyl-3H-purin-8-ylsulfanyl) -benzonitrile, 9- [2- (3, 4-dimethoxy-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, methods of making and using the compounds, 3- [2- (3, 4-dimethoxy-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-p-tolyl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-p-tolyl-ethyl) -3H-purin-6-ylamine, 9- [2- (2-chloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, optionally substituted phenyl-, benzyl-, or substituted phenyl-, benzyl-, or substituted phenyl-, or, 3- [2- (2-chloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 9- [2- (2, 4-dichloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (2, 4-dichloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenyl-sulfanyl) -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-fluoro-phenyl) -ethyl ] -9H- Purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine, 9- [2- (4-chloro-phenyl) -ethyl ] -8- (3, 4, 5-trimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (4-chloro-phenyl) -ethyl ] -8- (3, 4, 5-trimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 8- (-6-iodo-benzo [1, 3] dioxol-5-ylsulfanyl) -9-phenethyl- 9H-purin-6-ylamine, 8- (6-iodo-benzo [1, 3] dioxol-5-ylsulfanyl) -3-phenethyl-3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-methoxy-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (4-chloro-2-fluorophenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (4-chloro-2-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts thereof, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-pentafluorophenyl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-pentafluorophenyl-ethyl) -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (3-phenyl-propyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (3-phenyl-benzo [1, 3] dioxol-5-ylthio) Yl-propyl) -3H-purin-6-ylamine, 9-phenethyl-8- (3, 4, 5-trimethoxy-phenylthio) -9H-purin-6-ylamine, 3-phenethyl-8- (3, 4, 5-trimethoxy-phenylthio) -3H-purin-6-ylamine, 9- (3-phenyl-propyl) -8- (3, 4, 5-trimethoxy-phenylthio) -9H-purin-6-ylamine, 3- (3-phenyl-propyl) -8- (3, 4, 5-trimethoxy-phenylthio) -3H-purin-6-ylamine, or a pharmaceutically acceptable salt thereof, 8- (benzo [1, 3] dioxol-5-ylthio) -9- (2-pyrrol-1-yl-ethyl) -9H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -3- (2-pyrrol-1-yl-ethyl) -3H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -9- (3-pyrrol-1-yl-propyl) -9H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -3- (3-pyrrol-1-yl- Propyl) -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2-chloro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2-chloro-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, or a pharmaceutically acceptable salt thereof, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-phenyl-butyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-phenyl-butyl) -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [1- (4- Methoxy-phenyl) -cyclopropylmethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- [1- (4-methoxy-phenyl) -cyclopropylmethyl ] -3H-purin-6-ylamine, 9- [1- (4-chloro-phenyl) -cyclobutylmethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [1- (4-chloro-phenyl) -cyclobutylmethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts thereof, 1- (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) -ethanone, 1- (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) -ethanone, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyrrol-1-yl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-pyrrol-1-yl-ethyl) -3H-purin-e (iv) -6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-naphthalen-1-yl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-naphthalen-1-yl-ethyl) -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-o-tolyl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-o-tolyl-ethyl) -3H-purin-6-ylamine, optionally substituted phenyl-thioamine, optionally substituted phenyl-, 9- [2- (4-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (4-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 9- [2- (2, 3-dichloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (2, 3-dichloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenol, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-trifluoromethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-tris-methyl-phenyl) -ethyl ] -9H-purin-6-ylamine Fluoromethyl-phenyl) -ethyl ] -3H-purin-6-ylamine, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylthio) -purin-9-yl ] -ethyl } -benzoic acid, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylthio) -purin-3-yl ] -ethyl } -benzoic acid, 8- (2, 5-dimethoxy-phenylthio) -3- (4-fluoro-benzyl) -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylthio) -9- (4-nitro-benzyl) -9H-purine -6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-methoxy-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-phenyl-butyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-phenyl) -butyl) -3H-purin-6-ylamine, optionally substituted phenyl-N-oxide, optionally substituted phenyl, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ] -3H-purin-6-ylamine, methods of making and using the same, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [1- (4-chloro-phenyl) -cyclobutylmethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [1- (4-chloro-phenyl) -cyclobutylmethyl ] -3H-purin-6-ylamine, 9- [2- (4-chloro-2-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, methods of making and using the same, 3- [2- (4-chloro-2-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- (3-methyl-2-phenyl-pentyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- (3-methyl-2-phenyl-pentyl) -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- (2-cyclopentyl-2-phenyl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- (2-cyclopentyl-2-phenyl-ethyl) -3H-purin-6-ylamine, 9- (2-cyclopentyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- (2-cyclopentyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-methyl-2-phenyl-pentyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (3-methyl-2-phenyl-pentyl) -3H-purin-6-ylamine, 2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -1- (2, 4-dichloro-phenyl) ethanol, 2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -1- (2, 4-dichloro-phenyl) ethanol, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (3-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- [2- (3-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-ethoxy-4-methoxy-phenyl) -purin-6-ylamine ) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-methyl-2-phenyl-butyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (3-methyl-2-phenyl-butyl) -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2, 5-dimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2, 5-dimethyl-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl ] -3H-purin-6-ylamine, 9- [2- (4-chloro-phenyl) -3-methyl-butyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (4-chloro-phenyl) -3-methyl-butyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 9- [2- (2, 4-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (2-chloro-6-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (2-chloro-6-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (2, 5-dimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- [2- (2, 5-dimethyl-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- (3-methyl-2-phenyl-butyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- (3-methyl-2-phenyl-butyl) -3 H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3, 5-dimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3, 5-dimethyl-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyridin-4-yl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyridin-2-yl- Ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-pyridin-2-yl-ethyl) -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-iodo-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-iodo-phenyl) -ethyl ] -3H-purin-6-ylamine, 9- [2- (2-chloro-4-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (2-chloro-4-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 9- [2- (2-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (2-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 9- [2- (3, 5-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (3, 5-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 9- [2- (2, 3-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (2, 3-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 8- (6-bromo-1, 3-benzodioxol-5-ylsulfanyl) -9- [2- (2-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- [2- (2-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (2-bromo-phenyl) -ethyl ] -9H- Purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2-bromo-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-pyridin-3-yl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-pyridin-3-yl-ethyl) -3H-purin-6-ylamine, methods of making and using the same, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3-iodo-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (3-iodo-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-o-tolyl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-o-tolyl-ethyl) -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-naphthalen-1-yl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-naphthalen-1-yl-ethyl) -3H-purin-6-ylamine, 1- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) -ethanone, 1- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) -ethanone, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (2, 3-difluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-1, 3-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2, 3-difluoro-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-p-tolyl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-p-tolyl-ethyl) -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3-tri-tolyl-5-ylthio) -amine Fluoromethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (3-trifluoromethyl-phenyl) -ethyl ] -3H-purin-6-ylamine, 9- (2-benzo [1, 3] dioxol-5-yl-ethyl) -8- (2, 5-dimethoxy-phenylthio) -9H-purin-6-ylamine, 3- (2-benzo [1, 3] dioxol-5-yl-ethyl) -8- (2, 5-dimethoxy-phenylthio) -3H-purin-6-ylamine Amine, 9- (2-cyclohexyl-ethyl) -8- (2, 5-dimethoxyphenyl-thio) -9H-purin-6-ylamine, 3- (2-cyclohexyl-ethyl) -8- (2, 5-dimethoxy-phenylthio) -3H-purin-6-ylamine, 9- (2-biphenyl-4-yl-ethyl) -8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9H-purin-6-ylamine, 3- (2-biphenyl-4-yl-ethyl) -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3H-purin-6-ylamine, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -benzenesulphonic acid, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -benzenesulphonic acid, 2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -1- (2, 4-dichloro-phenyl) -ethanol, and pharmaceutically acceptable salts thereof, 2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -1- (2, 4-dichloro-phenyl) -ethanol, 9- (2-cyclohexyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- (2-cyclohexyl-2-phenyl-ethyl) -8- (25-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 9- (2-biphenyl-4-yl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- (2-biphenyl-4-yl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-trifluoromethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-trifluoromethyl-phenyl) -ethyl ] -3H-purin-6-ylamine, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier thereof, and a pharmaceutically acceptable carrier thereof, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-dimethylamino-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (4-dimethylamino-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (4-dimethylamino-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- [2- (4-dimethylamino-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (2, 5-diethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine, 8- (2, 5-diethoxy-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine, 9- [2- (2-chloro-phenyl) -ethyl ] -8- (2, 5-diethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (2-chloro-phenyl) -ethyl ] -8- (2 5-diethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 9- [2- (3, 5-dimethoxy-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 3- [2- (3, 5-dimethoxy-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (3, 5-dimethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, or a pharmaceutically acceptable salt thereof, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (3, 5-dimethoxy-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylthio) -9- (2-thiophen-3-yl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylthio) -3- (2-thiophen-3-yl-ethyl) -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylthio) -9-2-thiophen-2-yl-ethyl) -9 H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-thiophen-2-yl-ethyl) -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-thiophen-3-yl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-thiophen-3-yl-ethyl) -3H-purin-6-ylamine, optionally substituted phenyl-amino-l-methyl-ethyl-amine, optionally substituted phenyl-3-purin-, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-thiophen-2-yl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-thiophen-2-yl-ethyl) -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine -phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-nitro-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylmethyl) -9-phenethyl-9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylmethyl) -3-phenethyl-3H-purin-6-ylamine, (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) carbamic acid tert-butyl ester, (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) carbamic acid tert-butyl ester, 9- [2- (4-amino-phenyl) -ethyl ] -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine, (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) -carbamic acid tert-butyl ester, (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) -carbamic acid tert-butyl ester, 9- [2- (4-amino-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-trifluoromethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pentafluorophenyl-ethyl) -9H-purin-6-ylamine, 9- [2- (3, 5-bistrifluoromethyl-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (3, 5-bistrifluoromethyl-phenyl) -ethyl ] -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [1- (4-chloro-phenyl) -cyclopropylmethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- [2- (3-nitro-phenyl) -ethyl ] -3H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine -amines, 8- (benzo [1, 3] dioxol-5-ylthio) -9-phenethyl-1, 9-dihydro-purin-6-one and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9-phenethyl-1, 9-dihydro-purin-6-one.

In one embodiment, the present invention provides a compound and a pharmaceutical composition comprising the compound, wherein the compound is selected from the group consisting of 8- (2, 5-dimethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-phenyl-propyl) -9H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -9-phenethyl-9H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -9- (3-phenyl-propyl) -9H-purin-6-ylamine, and pharmaceutically acceptable salts thereof, 8- (benzo [1, 3] dioxol-5-ylthio) -9- [2- (4-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -9- [2- (4-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9-phenethyl-9H-purin-6-ylamine, 8- (2, 4-dimethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine, 8- (4-chloro-benzenesulfonyl) -9-phenethyl-9H-purin-6-ylamine, 4- (6-amino-9-phenethyl-9H-purin-8-ylsulfanyl) -benzonitrile 9- [2- (3, 4-dimethoxy-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-p-tolyl-ethyl) -9H-purin-6-ylamino 9- [2- (2-chloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (2, 4-dichloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 9- [2- (4-chloro-phenyl) -ethyl ] -8- (3, 4, 5-trimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (-6-iodo-benzo [1, 3] dioxol-5-ylsulfanyl) -9-phenethyl-9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts thereof, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamino 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (4-chloro-2-fluorophenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-pentafluorophenyl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- (3-phenyl-propyl) -9H-purin-6-ylamine, 9-phenethyl-8- (3, 4, 5-trimethoxy-thiophenyl) -9H-purin-6-ylamine, 9- (3-phenyl-propyl) -8- (3, 4, 5-trimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylsulfanyl) -9- (2-pyrrol-1-yl-ethyl) -9H-purin-6-ylamine, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier thereof, and a pharmaceutically acceptable carrier thereof, 8- (benzo [1, 3] dioxol-5-ylsulfanyl) -9- (3-pyrrol-1-yl-propyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (2-chloro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- (2-phenyl-butyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [1- (4-methoxy-phenyl) -cyclopropylmethyl ] -9H-purin-6-ylamine, 9- [1- (4-chloro-phenyl) -cyclobutylmethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 1- (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) -ethanone, 1- (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) -ethanone, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyrrol-1-yl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-naphthalen-1-yl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-o-tolyl-ethyl) -9H-purin-6-ylamine, 9- [2- (4-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (2, 3-dichloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenol, or mixtures thereof, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenol, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-trifluoromethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -benzoic acid, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -benzoic acid, 1-methyl-ethyl-phenyl-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (4-nitro-benzyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-phenyl-butyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, optionally substituted phenyl-9-purin-6-ylamine, optionally substituted phenyl-2-ethyl-amine, optionally substituted phenyl-2-, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [1- (4-chloro-phenyl) -cyclobutylmethyl ] -9H-purin-6-ylamine, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts thereof, 9- [2- (4-chloro-2-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylthio) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (3-methyl-2-phenyl-pentyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-cyclopentyl-2-phenyl-ethyl) -9H-purin-6-ylamine, 9- (2-cyclopentyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-methyl-2-phenyl-pentyl) -9H-purin-6-ylamine, 2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -1- (2, 4-dichloro-phenyl) ethanol, 2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -1- (2, 4-dichloro-phenyl) ethanol, optionally substituted phenyl ether, benzyl ether, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (3-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-methyl-2-phenyl-butyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2, 5-dimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 9- [2- (4-chloro-phenyl) -3-methyl-butyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (2, 4-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (2-chloro-6-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2, 5-dimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (3-methyl-2-phenyl-butyl) -9H-purin- 6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3, 5-dimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyridin-4-yl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyridin-2-yl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-iodo-phenyl) -ethyl ] -9H-purine -6-ylamine, 9- [2- (2-chloro-4-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (2-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (3, 5-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (2, 3-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (6-bromo-1, 3-benzodioxol-5-ylsulfanyl) -9- [2- (2-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (2-bromo-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- (2-pyridin-3-yl-ethyl) -9H-purine -6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3-iodo-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-o-tolyl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-naphthalen-1-yl-ethyl) -9H-purin-6-ylamine, or a pharmaceutically acceptable salt thereof, 1- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) -ethanone, 1- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) -ethanone, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (2, 3-difluoro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-p-tolyl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3-trifluoromethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 9- (2-benzo [1, 3] dioxol-5-yl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- (2-cyclohexyl-ethyl) -8- (2, 5-dimethoxyphenyl-sulfanyl) -9H-purin-6-ylamine, 9- (2-biphenyl-4-yl-ethyl) -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -benzenesulfonic acid, 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -benzenesulfonic acid, N-tert-butyl-phenyl-ethyl-benzyl-amide, N-butyl-ethyl-benzyl-amide, N-, 2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -1- (2, 4-dichloro-phenyl) -ethanol, 2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -1- (2, 4-dichloro-phenyl) -ethanol, 9- (2-cyclohexyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- (2-Biphenyl-4-yl-Ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-trifluoromethyl-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-dimethylamino-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (4-dimethylamino-benzene -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-diethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine, 9- [2- (2-chloro-phenyl) -ethyl ] -8- (2, 5-diethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (3, 5-dimethoxy-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [2- (3, 5-dimethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-thiophen-3-yl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9-2-thiophen-2-yl-ethyl) -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- (2-thiophen-3-yl-ethyl) -9H-purin-6-ylamine, or a pharmaceutically acceptable salt thereof, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-thiophen-2-yl-ethyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (2, 5-methoxy-phenylsulfanyl) -9- [2- (2-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (6-bromo-benzo [1, 3] dioxol-5-ylmethyl) -9-phenethyl-9H- Purin-6-ylamine, (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) carbamic acid tert-butyl ester, (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) carbamic acid tert-butyl ester, 9- [2- (4-amino-phenyl) -ethyl ] -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine, (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) -carbamic acid tert-butyl ester, (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) -carbamic acid tert-butyl ester, 9- [2- (4-amino-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-trifluoromethoxy-phenyl) -ethyl ] -ethyl } -phenyl) -carbamic acid tert-butyl ester Yl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pentafluorophenyl-ethyl) -9H-purin-6-ylamine, 9- [2- (3, 5-bistrifluoromethyl-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine, 9- [2- (3, 5-bistrifluoromethyl-phenyl) -ethyl ] -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier thereof, and a pharmaceutically acceptable carrier, 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [1- (4-chloro-phenyl) -cyclopropylmethyl ] -9H-purin-6-ylamine, 8- (2, 5-dimethoxy-phenylthio) -9- [2- (3-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine, 8- (benzo [1, 3] dioxol-5-ylthio) -9-phenethyl-1, 9-dihydro-purin-6-one and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9-phenethyl-1, 9-dihydro-purin-6-one.

In one aspect, the present invention also provides a compound of formulae I and II below, wherein the compound is selected from the group consisting of 2- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -piperidine-1-carboxylic acid ethyl ester; 2- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -piperidine-1-carboxylic acid ethyl ester; 2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylic acid ethyl ester; 2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidine-1-carboxylic acid ethyl ester; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; 4- (2- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; 4- (2- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -3H-purin-3-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; 3- (2- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; 8- [ (2, 5-dimethoxyphenyl) thio ] -9- [2- (tetrahydro-2H-pyran-4-yl) ethyl ] -9H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -3- [2- (tetrahydro-2H-pyran-4-yl) ethyl ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [2- (tetrahydro-2H-pyran-4-yl) ethyl ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [2- (2, 2, 6, 6-tetramethylpiperidin-4-yl) ethyl ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [2- (1-methylpyrrolidin-2-yl) ethyl ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (tetrahydro-2H-pyran-4-yl) ethyl ] -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (2, 2, 6, 6-tetramethylpiperidin-4-yl) ethyl ] -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (1-methylpyrrolidin-2-yl) ethyl ] -9H-purin-6-amine; 9- [2- (1-adamantane) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine; 3- [2- (1-adamantane) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-6-amine; 4- (2- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carbaldehyde; 4- (2- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -3H-purin-3-yl } ethyl) piperidine-1-carbaldehyde; 8- [ (2, 5-dimethoxyphenyl) thio ] -3- [2- (2, 2, 6, 6-tetramethylpiperidin-4-yl) ethyl ] -3H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -9- [2- (2, 2, 6, 6-tetramethylpiperidin-4-yl) ethyl ] -9H-purin-6-amine; 4- (2- { 6-amino-8- [ (2, 5-diethoxyphenyl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carbaldehyde; 9- [2- (1-acetylpiperidin-4-yl) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine; 3- [2- (1-acetylpiperidin-4-yl) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- {2- [1- (methylsulfonyl) piperidin-4-yl ] ethyl } -3H-purin-6-amine; 2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) morpholine-4-carboxylic acid tert-butyl ester; 2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) morpholine-4-carboxylic acid tert-butyl ester; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [1- (methylsulfonyl) piperidin-3-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- {2- [1- (methylsulfonyl) piperidin-3-yl ] ethyl } -3H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -9- {2- [1- (methylsulfonyl) piperidin-2-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [1- (methylsulfonyl) piperidin-2-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- {2- [1- (methylsulfonyl) piperidin-2-yl ] ethyl } -3H-purin-6-amine; 9- (2-cycloheptylethyl) -8- [ (2, 5-dimethoxyphenyl) thio ] -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (undecyl-cyclohexyl) ethyl ] -9H-purin-6-amine; 3- (2-cycloheptylethyl) -8- [ (2, 5-dimethoxyphenyl) thio ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [2- (undecyl-cyclohexyl) ethyl ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [1- (methylsulfonyl) piperidin-4-yl ] ethyl } -9H-purin-6-amine; 8- (1, 3-benzodioxol-5-ylthio) -9- {2- [1- (methylsulfonyl) piperidin-4-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [2- (1H-imidazol-1-yl) ethyl ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (1H-imidazol-1-yl) ethyl ] -9H-purin-6-amine; 9- [2- (4-acetylpiperazin-1-yl) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine; 3- [2- (4-acetylpiperazin-1-yl) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -9- [2- (undecyl-cyclohexyl) ethyl ] -9H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -3- [2- (undecyl-cyclohexyl) ethyl ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (1-propylpiperidin-2-yl) ethyl ] -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2- {1- [ (trifluoromethyl) sulfonyl ] piperidin-4-yl } ethyl) -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- (2- {1- [ (trifluoromethyl) sulfonyl ] piperidin-4-yl } ethyl) -3H-purin-6-amine; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethylidene) piperidine-1-carboxylic acid tert-butyl ester; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethylidene) piperidine-1-carboxylic acid tert-butyl ester; (3S) -3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; (3R) -3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; (3R) -3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; (2R) -tert-butyl 2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylate; (2R) -tert-butyl 2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidine-1-carboxylate; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2- {1- [ (trifluoromethyl) sulfonyl ] piperidin-2-yl } ethyl) -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- (2- {1- [ (trifluoromethyl) sulfonyl ] piperidin-2-yl } ethyl) -3H-purin-6-amine; tert-butyl [ cis-4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) cyclohexyl ] carbamate; tert-butyl [ cis-4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) cyclohexyl ] carbamate; 9- [2- (1-acetylpiperidin-3-yl) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine; 3- [2- (1-acetylpiperidin-3-yl) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2- {1- [ (trifluoromethyl) sulfonyl ] piperidin-3-yl } ethyl) -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- (2- {1- [ (trifluoromethyl) sulfonyl ] piperidin-3-yl } ethyl) -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [2- (6, 6-dimethylbicyclo [3.1.1] hept-2-en-3-yl) ethyl ] -3H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -9- [2- (6, 6-dimethylbicyclo [3.1.1] hept-2-en-3-yl) ethyl ] -9H-purin-6-amine; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) -5-methyl-2, 4-dihydro-3H-pyrazol-3-one; 4- (2- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -9H-purin-9-yl } ethyl) -5-methyl-2, 4-dihydro-3H-pyrazol-3-one; 4- (2- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -3H-purin-3-yl } ethyl) -5-methyl-2, 4-dihydro-3H-pyrazol-3-one; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylic acid phenylmethyl ester; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidine-1-carboxylic acid benzyl ester; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2-morpholin-4-ylethyl) -9H-purin-6-amine; 2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) pyrrolidine-1-carboxylic acid tert-butyl ester; 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) pyrrolidine-1-carboxylic acid tert-butyl ester; 2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) pyrrolidine-1-carboxylic acid tert-butyl ester; 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) pyrrolidine-1-carboxylic acid tert-butyl ester; (2S) -2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; (2S) -2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidine-1-carboxylic acid tert-butyl ester; (3R) -3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) pyrrolidine-1-carboxylic acid tert-butyl ester; 2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) pyrrolidine-1-carboxylic acid benzyl ester; (3S) -3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) pyrrolidine-1-carboxylic acid tert-butyl ester; 2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) pyrrolidine-1-carboxylic acid benzyl ester; 1-tert-butyl 2-ethyl (2S, 4S) -4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1, 2-dicarboxylate; 1-tert-butyl 2-ethyl (2S, 4R) -4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidine-1, 2-dicarboxylate; 9- [2- (1-benzyl-1, 2, 3, 6-tetrahydropyridin-4-yl) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine; 3- [2- (1-benzyl-1, 2, 3, 6-tetrahydropyridin-4-yl) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [ (3-endo) -8-methyl-8-azabicyclo [3.2.1] oct-3-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- {2- [ (3-endo) -8-methyl-8-azabicyclo [3.2.1] oct-3-yl ] ethyl } -3H-purin-6-amine; (2R, 4S) -4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) -2-isopropylpiperidine-1-carboxylic acid tert-butyl ester; (2S, 4S) -4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) -2-isopropylpiperidine-1-carboxylic acid tert-butyl ester; (2S, 4R) -4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) -2-isopropylpiperidine-1-carboxylic acid tert-butyl ester; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) -N-ethylpiperidine-1-carboxamide; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) -N-isopropylpiperidine-1-carboxamide; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) -N- (tert-butyl) piperidine-1-carboxamide; ethyl N- { [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] carbonyl } aminoacetate; 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) -N-ethylpiperidine-1-carboxamide; 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) -N-isopropylpiperidine-1-carboxamide; 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) -N- (tert-butyl) piperidine-1-carboxamide; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) -N-ethylpiperidine-1-carboxamide; 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) -N-isopropylpiperidine-1-carboxamide; 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) -N-ethylpiperidine-1-carboxamide; 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) -N-isopropylpiperidine-1-carboxamide; 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) -N- (tert-butyl) piperidine-1-carboxamide; ethyl N- { [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidin-1-yl ] carbonyl } aminoacetate; 8- [ (2, 5-dimethoxyphenyl) thio ] -9- {2- [4- (2, 2-dimethylpropanoyl) piperazin-1-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (1-isopropylpiperidin-2-yl) ethyl ] -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [2- (1-isopropylpiperidin-2-yl) ethyl ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (1-isobutylpiperidin-2-yl) ethyl ] -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [2- (1-isobutylpiperidin-2-yl) ethyl ] -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [1- (2, 2-dimethylpropionyl) piperidin-3-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- {2- [1- (2, 2-dimethylpropionyl) piperidin-3-yl ] ethyl } -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [1- (2, 2-dimethylpropionyl) piperidin-4-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- {2- [1- (2, 2-dimethylpropionyl) piperidin-4-yl ] ethyl } -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (1-isobutylpiperidin-4-yl) ethyl ] -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [1- (3, 3-dimethylbutyryl) piperidin-3-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2-piperidin-4-ylethyl) -9H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -3- (2-piperidin-4-ylethyl) -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- (2-piperidin-4-ylethyl) -3H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -9- (2-piperidin-4-ylethyl) -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2-piperidin-3-ylethyl) -9H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -9- (2-piperidin-3-ylethyl) -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2-piperidin-4-ylideneethyl) -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [ (3R) -piperidin-3-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [ (3S) -piperidin-3-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [ (2R) -piperidin-2-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2-pyrrolidin-3-ylethyl) -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [ (2S) -piperidin-2-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [ (3R) -pyrrolidin-3-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [ (2R, 4S) -2-isopropylpiperidin-4-yl ] ethyl } -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [ (2S) -2-isopropylpiperidin-4-yl ] ethyl } -9H-purin-6-amine; 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-piperidin-1-yl-ethyl) -9H-purin-6-ylamine; 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-piperidin-1-yl-ethyl) -3H-purin-6-ylamine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (4-isopropylpiperazin-1-yl) ethyl ] -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [2- (4-isopropylpiperazin-1-yl) ethyl ] -3H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -9- (2-piperidin-1-ylethyl) -9H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -3- (2-piperidin-1-ylethyl) -3H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2-piperidin-1-ylethyl) -9H-purin-6-amine; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- (2-piperidin-1-ylethyl) -3H-purin-6-amine; 8- [ (2, 5-dimethoxyphenyl) thio ] -9- [2- (4-isopropylpiperazin-1-yl) ethyl ] -9H-purin-6-amine; 9- [2- (4-cyclopentylpiperazin-1-yl) ethyl ] -8- [ (2, 5-dimethoxyphenyl) thio ] -9H-purin-6-amine; 3- [2- (4-cyclopentylpiperazin-1-yl) ethyl ] -8- [ (2, 5-dimethoxyphenyl) thio ] -3H-purin-6-amine; 1- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-2, 6-dione; 1- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidine-2, 6-dione; and pharmaceutically acceptable salts thereof.

In one aspect, the present invention also provides a compound of formulae I and II below, wherein the compound is selected from the group consisting of tert-butyl (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } -1-cyclopropylpropyl) carbamate; (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } -1-cyclopropylpropyl) carbamic acid tert-butyl ester; (3- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -9H-purin-9-yl } -1-cyclopropylpropyl) carbamic acid tert-butyl ester; (3- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -3H-purin-3-yl } -1-cyclopropylpropyl) carbamic acid tert-butyl ester; [3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } -1- (tetrahydro-2H-thiopyran-4-yl) propyl ] carbamic acid tert-butyl ester; [3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } -1- (tetrahydro-2H-thiopyran-4-yl) propyl ] carbamic acid tert-butyl ester; tert-butyl [3- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -9H-purin-9-yl } -1- (tetrahydro-2H-thiopyran-4-yl) propyl ] carbamate; tert-butyl [3- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -3H-purin-3-yl } -1- (tetrahydro-2H-thiopyran-4-yl) propyl ] carbamate; (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } -1-cyclohexylpropyl) carbamic acid tert-butyl ester; (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } -1-cyclohexylpropyl) carbamic acid tert-butyl ester; (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } -1-cyclobutylpropyl) carbamic acid tert-butyl ester; (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } -1-cyclobutylpropyl) carbamic acid tert-butyl ester; n- (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } -1-cyclopropylpropyl) methanesulfonamide; n- (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } -1-cyclopropylpropyl) methanesulfonamide; n- (3- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -9H-purin-9-yl } -1-cyclopropylpropyl) methanesulfonamide; n- (3- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -3H-purin-3-yl } -1-cyclopropylpropyl) methanesulfonamide; n- (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } -1-cyclopropylpropyl) -N' -isopropylurea; n- (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } -1-cyclopropylpropyl) -N' -isopropylurea; {3- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -1-cyclopentyl-propyl } -carbamic acid tert-butyl ester; {3- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -1-cyclopentyl-propyl } -carbamic acid tert-butyl ester; [3- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -1- (tetrahydropyran-4-yl) -propyl ] -carbamic acid tert-butyl ester; [3- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-3-yl ] -1- (tetrahydropyran-4-yl) -propyl ] -carbamic acid tert-butyl ester; [3- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-3-yl ] -1- (tetrahydropyran-4-yl) -propyl ] -carbamic acid tert-butyl ester; 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [ 3-cyclohexyl-3- (1H-pyrrol-1-yl) propyl ] -3H-purin-6-amine; 9- (3-amino-3-cyclobutylpropyl) -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine; 9- (3-amino-3-cyclopropylpropyl) -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine; 3- (3-amino-3-cyclopropylpropyl) -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-6-amine; 9- [ 3-amino-3- (tetrahydro-2H-thiopyran-4-yl) propyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine; 9- (3-amino-3-cyclohexylpropyl) -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine; 9- (3-amino-3-cyclopentyl-propyl) -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine; 9- [ 3-amino-3- (tetrahydropyran-4-yl) -propyl ] -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine; and pharmaceutically acceptable salts thereof.

In another aspect, the present invention relates to a pharmaceutical composition for the treatment or prevention of HSP90 dependent diseases, which composition comprises a compound of the invention, in particular one or more compounds of formulae I-III, and one or more pharmaceutical excipients.

In another aspect, the invention features a method of treating an individual having an HSP 90-mediated disorder by: administering to the subject a pharmaceutical composition comprising a pharmaceutically effective amount of one or more compounds of formulas I-III and/or pharmaceutically acceptable salts thereof.

In one aspect, the invention provides a method for treating an individual having a disorder selected from the group consisting of: inflammatory diseases, infections, autoimmune diseases, stroke, ischemia, cardiac disorders, neurological disorders, fibrogenic disorders, proliferative disorders, tumors, leukocytosis, neoplasms (neoplasms), cancers, carcinomas (carcinosmas), metabolic diseases and malignant diseases. In a particular aspect, the method involves identifying and administering to a patient in need of treatment.

In yet another aspect, the invention provides a method for treating an individual suffering from a fibrogenic disorder such as scleroderma, polymyositis, systemic lupus erythematosus, rheumatoid arthritis, cirrhosis, keloid formation, interstitial nephritis, and pulmonary fibrosis.

The invention also includes a method of treatment comprising administering to an animal (e.g., a patient in need thereof) a therapeutically effective amount of one or more compounds of formulas I-III and/or pharmaceutically acceptable salts thereof. The therapeutic methods are useful for treating cancer, a class of diseases characterized by uncontrolled growth and spread of abnormal cells. Such diseases include, but are not limited to, Hodgkin's disease, non-Hodgkin's lymphoma, acute lymphocytic leukemia, chronic lymphocytic leukemia, multiple myeloma, neuroblastoma, breast cancer, ovarian cancer, lung cancer, Wilms 'tumor, cervical cancer, testicular cancer, soft tissue sarcoma, primary macroglobulinemia, bladder cancer, chronic myelogenous leukemia, primary brain cancer, malignant melanoma, small cell lung cancer, gastric cancer, colon cancer, malignant insulinoma, malignant carcinoid cancer, choriocarcinoma, mycosis fungoides, head and neck cancer, osteogenic sarcoma, pancreatic cancer, acute myelogenous leukemia, hairy cell leukemia, neuroblastoma, rhabdomyosarcoma, Kaposi's sarcoma, genitourinary cancer, thyroid cancer, esophageal cancer, malignant hypercalcemia, cervical hyperplasia, renal cell cancer, endometrial cancer, Polycythemia vera, essential thrombocythemia, adrenocortical carcinoma, skin cancer and prostate cancer.

In general, administration of a compound of formulae I-III in an amount of from about 0.01 μ g/kg to about 100mg/kg per day on a total body weight basis may be effective. The active ingredient may be administered at one time, or may be divided into smaller doses to be administered at predetermined time intervals. A suitable dosage unit for each administration may be, for example, from about 1. mu.g to about 2000mg, preferably from about 5. mu.g to about 1000 mg.

It should be understood that the dosage ranges given above are exemplary only and are not intended to limit the scope of the invention. The therapeutically effective amount of each active compound will vary depending upon a variety of factors; such factors include, but are not limited to, the activity of the compound used, the stability of the active compound in the patient, the severity of the symptoms to be alleviated, the total weight of the patient treated, the route of administration, the ease with which the active compound is absorbed, distributed and excreted by the body, the age and sensitivity of the patient to be treated, etc.; as will be apparent to those skilled in the art. The amount administered can be adjusted over time depending on various factors.

In the pharmaceutical composition, the active agent may be in the form of any pharmaceutically acceptable salt. The term "pharmaceutically acceptable salt" as used herein refers to a relatively non-toxic organic or inorganic salt of the active compound, including inorganic or organic acid addition salts of the compound. Examples of basic active ingredient compound salts include, but are not limited to, hydrochloride, hydrobromide, sulfate, bisulfate, nitrate, acetate, phosphate, oxalate, valerate, oleate, borate, benzoate, laurate, stearate, palmitate, lactate, tosylate, citrate, maleate, succinate, tartrate, naphthylate salt, fumarate, methanesulfonate, laurylsulfonate, glucoheptonate, and the like. See, e.g., Berge, et al.j.pharm.sci., 66: 1-19(1997). Examples of the acidic active ingredient compound salt include, for example, alkali metal salts, alkaline earth metal salts, and ammonium salts. Thus, suitable salts may be aluminium, calcium, lithium, magnesium, potassium, sodium and zinc salts. In addition, organic salts may also be used, including, for example, salts of lysine, N' -dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methyl reduced glucamine), procaine, and tris.

For oral administration, the active compounds may be incorporated into formulations including pharmaceutically acceptable carriers such as binders (e.g., gelatin, cellulose, tragacanth (gum tragacanth)), excipients (e.g., starch, lactose), lubricants (e.g., magnesium stearate, silicon dioxide), disintegrants (e.g., alginates, protamine (Primogel) and corn starch), and sweetening or flavoring agents (e.g., glucose, sucrose, saccharin, methyl salicylate and peppermint). The formulations may be administered orally in the form of encapsulated gelatin capsules or compressed tablets. Capsules and tablets may be prepared by any conventional method. The capsules and tablets may also be coated with various coatings known in the art to improve the odor, taste, color and shape of the capsules and tablets. In addition, liquid carriers such as fatty oils may also be included in the capsules.

Suitable oral agents may also be in the form of suspensions, syrups, chewing gums, wafers, elixirs and the like. Conventional agents for modifying the odor, taste, color and shape of a particular dosage form may also be included, if desired. In addition, to facilitate administration to patients who cannot swallow through enteral feeding tubes (enteral feeding tubes), the active compounds can be dissolved in an acceptable lipophilic vegetable oil carrier such as olive oil, corn oil and safflower oil.

The active compounds may also be administered parenterally in the form of solutions or suspensions or in lyophilized form which can be converted into a solution or suspension prior to use. In such formulations, a diluent or a pharmaceutically acceptable carrier such as sterile water and physiological saline buffer may be used. Other conventional solvents, pH buffers, stabilizers, antibacterial agents, surfactants, and antioxidants may be included in the formulation. For example, useful ingredients include sodium chloride, acetate, citrate or phosphate buffers, glycerol, glucose, nonvolatile oils, methylparaben, polyethylene glycol, propylene glycol, sodium bisulfate, benzyl alcohol, ascorbic acid, and the like. The parenteral formulations may be stored in any conventional container such as vials and ampoules.

The topical route of administration includes nasal, buccal, mucosal, rectal or vaginal administration. For topical administration, the active compounds may be formulated as lotions, creams, ointments, gels, powders, pastes, sprays, suspensions, drops and aerosols. Thus, one or more thickening agents, humectants, and stabilizers may be included in the formulation. Examples of such agents include, but are not limited to, polyethylene glycol, sorbitol, xanthan gum, petrolatum, beeswax or mineral oil, lanolin, squalene, and the like. One particular form of topical administration is delivery via a transdermal patch. Methods for making transdermal patches are disclosed in, for example, Brown, et al, Annual reviews of Medicine, 39: 221-229(1988), the contents of which are incorporated herein by reference.

Subcutaneous implantation for sustained release of the active compound may also be a suitable route of administration. The implantation of an active compound in any suitable dosage form into the subcutaneous space, for example under the anterior abdominal wall, requires surgical procedures. See, e.g., Wilson et al, j.clin.psych.45: 242-247(1984). Hydrogels can be used as carriers for sustained release of the active compound. Hydrogels are well known in the art. They are typically prepared by cross-linking high molecular weight biocompatible polymers into a network that swells in water to form a gel-like substance. Preferably the hydrogel is biodegradable or bioabsorbable. Hydrogels made from polyethylene glycol, collagen, or poly (glycolic acid-co-L-lactic acid) may be useful for the present invention. See, e.g., Phillips et al, j.pharmaceut.sci., 73: 1718-1720(1984).

The active compound may also be conjugated to a water-soluble, non-immunogenic, non-peptide, high molecular weight polymer to form a polymer conjugate. For example, the active compound is covalently attached to polyethylene glycol to form a conjugate. Typically, such conjugates Exhibit improved solubility, stability and reduced toxicity and immunogenicity. Thus, the active compounds in the conjugates may have a longer half-life in vivo and exhibit better therapeutic efficacy when administered to a patient. See generally Burnham, am.j.hosp.pharm., 15: 210-218(1994). Pegylated proteins are currently used in protein replacement therapy and as other therapeutic uses. For example, pegylated interferon (PEG-INTRON)) Can be used for treating hepatitis B in clinic. Pegylated adenosine deaminase (A)) Can be used for treating Severe Combined Immunodeficiency Disease (SCIDS). Pegylated L-asparaginase () Can be used for treating Acute Lymphocytic Leukemia (ALL). Preferably, the covalent bond between the polymer and the active compound and/or the polymer itself is hydrolytically degradable under physiological conditions. The above conjugates, known as "prodrugs", readily release the active compound in vivo. Controlled release of the active compound can also be achieved by incorporating the active ingredient in microcapsules, nanocapsules or hydrogels as is well known in the art. Other pharmaceutically acceptable prodrugs of the compounds of the present invention include, but are not limited to, esters, carbonates, thiocarbonates, N-acyl derivatives, N-acyloxyalkyl derivatives, quaternary ammonium derivatives of tertiary amines, N-Mannich bases, Schiff bases, amino acid conjugates, phosphates, metal salts, and sulfonates.

Liposomes can also be used as carriers for the active compounds of the invention. Liposomes are microparticles composed of various lipids, such as cholesterol, phospholipids, fatty acids, and derivatives thereof. Various modified lipids can also be used. Liposomes can reduce the toxicity of the active compounds and increase their stability. Methods for preparing liposomal suspensions including active ingredients therein are generally known in the art. See, for example, U.S. Pat. Nos. 4,522,811; prescott, ed., Methodsin Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976).

The active compounds may also be administered in combination with another active agent that synergistically treats or prevents the same condition or is effective against another disease or condition in the patient being treated, provided that the other active agent does not interfere with or adversely affect the efficacy of the active compounds of the present invention. Such other active agents include, but are not limited to, anti-inflammatory agents, antiviral agents, antibiotics, antifungal agents, anticoagulant agents, cardiovascular agents, cholesterol lowering agents, anticancer agents, hypertension agents, and the like.

Suitable examples of antineoplastic agents which may be used in conjunction with the compounds and methods of the present invention generally include alkylating agents, antimetabolites, epiphyllotoxins, antineoplastic enzymes, topoisomerase inhibitors, procarbazine, mitoxantrone (mitoxantrone), platinum coordination complexes, biological response modifiers and growth inhibitors, hormone/anti-hormone therapeutics, and hematopoietic growth factors. Examples of antineoplastic classes include anthracyclines, vincas (vinca drugs), mitomycins, bleomycin, cytotoxic nucleosides, epothilones (epothilones), discodermolides, pteridines, enediynes (diynenes), podophyllotoxins (podophylotoxin). Particularly useful members of these classes include, for example, carminomycin, daunorubicin (daunorubicin), aminopterin, methotrexate (methotrexate), methotrexate (methopterin), methotrexate dichloride, mitomycin C, podofycin, 5-fluorouracil, 6-mercaptopurine, gemcitabine (gemcitabine), cytarabine (cytarabine), podophyllotoxin or podophyllotoxin derivatives (e.g., etoposide phosphate or podophyllotoxin (teniposide)), melphalan (melphalan), vinblastine (vinblastine), vincristine (vinchristine), isocvinblastine, vindesine (vindesine), vinblastine (leurosisine), paclitaxel (paclitaxel), and the like. Other useful antineoplastic agents include estramustine (estramustine), carboplatin (carboplatin), cyclophosphamide, bleomycin, gemcitabine (gemcitibine), ifosfamide (ifosamide), melphalan, hexamethylmelamine, thiotepa (thiotepa), cytarabine (cytarabine), idatrexate, trimetrexate (trimetrexate), dacarbazine, L-asparaginase, camptothecin, CPT-11, topotecan, ara-C, bicalutamide, flutamide (flutamide), leuprolide (leuprolide), pyridobenzindole (pyridobenzindole) derivatives, interferons, and interleukins.

Examples

Unless otherwise indicated, the chemical reagents are standard commercially available reagents and their original products are used. Or their preparation is readily and known to those of ordinary skill in the art, or is cited or described herein.

The abbreviations are in agreement with those in the ACS Style Guide. By "dry" glassware is meant oven/dryer dried. Unless otherwise indicated, the solvents were ACS grade. Analytical TLC plates (TLC plates) (Silica Gel 60F 254, EM Science, Gibbstown, NJ, or Merck #5715) were used to follow the course of the reaction and were purified by the MPLC system from Isco (Foxy Jr flow collector, UA-6 detector) using an Isco Silica Gel flash column (10 or 40 g). Recording on a Varian Mercury 400MHz device¹H NMR spectrum and chemical shifts are expressed in parts per million (ppm, δ) relative to the internal standard TMS. In Thermo Finnigan LCQ-Deca (injection volume 5uL, XTerra MS-C)₁₈3.5 μm 2.1X 50mm column, XTerra MS-C₁₈5 μm 2.1 × 20mm guard bar), electrospray ionization source (ESI source) to obtain mass spectrum; analytical HPLC on HP1050 (injection volume 5. mu.l, XTerra RP-C₁₈5 μm 4.6X 250mm column with XTerra MS-C₁₈5 μm 2.1 × 20mm guard bar); and preparative HPLC was performed on Agilent 1100Prep-LC, where different columns and conditions were chosen depending on the compound. GCMS was performed on an Agilent Technology 6890N or Shimadzu QP5000/17A device.

All reactions were performed in a oven-dried or oven-dried glass vessel under positive pressure of dry nitrogen or dry argon, and stirred with magnetic force, unless otherwise indicated. Unless otherwise indicated, the chemical reagents are standard commercially available reagents and their original products are used. Or their preparation is readily and known to those of ordinary skill in the art, or is cited or described herein. The yield is not optimal. Chemical names were generated by ISIS AutoNom and ACD laboratory software.

Abbreviations

If the following abbreviations appear herein, they have the following meanings:

general procedure

General procedure for the preparation of intermediates

Substituted alcohols are commercially available or prepared according to known literature procedures. These substituted alcohols are converted into the corresponding leaving groups (Cl, Br, OM or OT) according to synthetic methods known to the person skilled in the art. General methods for preparing the compounds are given below, and the preparation of representative compounds is specified in the experimental section.

FIG. 1 shows a schematic view of a

LG＝Cl、Br、OM、OT

Reagent: i) SOCl₂，CHCl₃Or CBr₄，PPh₃/PPh₃Polymers, DCM or CH₃SO₂Cl，NEt₃DCM or pTsCl, NEt₃，DMAP，DCM

FIG. 2

Reagent: i) CHCl₃，Br₂Rt; ii) NaH, substituted benzenethiol, DMF, 60 ℃; iii) Ar-X, CuI, a reagent of copper neoxide, t-BuONa, DMF, 60-110 ℃; or Pd ₂dba₃，Xanthpos，K₂CO₃Or Cs₂CO₃Dioxane, 100 ℃; iv) R5-LG, Barton base, DMF, 60-110 ℃.

8-bromoadenine 2 was prepared by known methods (US 2005/0049263). Nucleophilic attack of bromoadenine by aryl thiolate (arylthiolate) anions (US2005/0049263), or copper-catalyzed coupling of aryl iodide to mercaptoadenine 3, can give compound 4; the coupling reaction was achieved at 60-110 ℃ using CuI/neocupron reagent as catalyst and t-BuONa/DMF as base/solvent combination (j.med.chem, 2005, 48, 2892). Alternatively, 4 can be prepared by palladium-catalyzed coupling of an aryl halide to mercaptoadenine 3. Derivatives of 8-arylsulfanyladenine (8-arylsulfanyladenonine) 4 are alkylated in DMF for 1-18 hours using various alkylating agents in the presence of a base at 30-110 ℃. The formation of a mixture of regioisomers (regiooisomers) 5 and 6 was observed by HPLC and LC-MS analysis. The solvent was evaporated at the end of this period; or after the aqueous and organic phases are worked up, the organic layer is collected and passed over Na₂SO₄And (5) drying. After removal of organic solvent and preparative HPLC [ X-Terra prep-RP 1810 um, 19 × 250mm (water), mobile phase: solvent A: HPLC grade water containing 0.01% TFA, and solvent B: b with 0.01% TFA Nitrile, general elution gradient-solvent B from 15% to 80% over 15-25 min elution time]After purification, the N-3 and N-9 alkylated products were isolated as trifluoroacetate salts.

General procedure for the preparation of intermediates

Intermediate 1

8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine

A250 mL flask was charged with 8-mercaptoadenine (2.00g, 11.98mmol) and 5, 6-dibromo-benzo- [1, 3]]Dioxole (6.07g, 24.0mmol), Pd₂dba₃(0.548g，0.599mmol)、Xantphos(0.693g，1.20mmol)、K₂CO₃(3.31g, 23.95mmol) and anhydrous dioxane (25 mL). The resulting mixture was heated at 100 ℃ for 16h under a nitrogen atmosphere. The reaction mixture was cooled, filtered and washed with 2/2/0.5 CH₂Cl₂EtOAc and MeOH. The combined filtrates were concentrated in vacuo. In SiO₂Purification by Chromatography (CH)₂Cl₂EtOAc/MeOH, 2/2/0/5) dark brown residue, which was then recrystallized from MeOH gave the title compound (1.4g, 32%).¹H NMR(DMSO-d₆)δ8.08(s，1H)，7.38(s，1H)，7.23(s，1H)，6.12(s，2H)。

Intermediates 2-36 were prepared following the procedure described for intermediate 1.

TABLE 1

Intermediate 37

8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine

8- (2, 5-dimethoxy-phenylsulfonyl) -9H-purin-6-ylamine was prepared according to known methods (j.med.chem., 2006, 49, 817).

Intermediates 38-42 were prepared according to known methods (j.org.chem., 2004, 69, 3230).

TABLE 2

General alkylation procedure:

examples 1 and 2

8- (2, 5-dimethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine

A mixture of 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine (0.050g, 0.165mmol), (2-bromo-ethyl) -benzene (0.032g, 0.165mmol) and Barton base (3.00mmol) in DMF (1.3mL) was heated at 90-100 deg.C for 6-15H. The temperature of the reaction mixture was then allowed to drop to ambient temperature. After removal of the solvent under reduced pressure, the residue was purified by preparative HPLC and separated by lyophilization to give the N-9 isomer and the N-3 isomer. 8- (2, 5-dimethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine: the yield of the product is 9.0 percent,¹H NMR(DMSO-d₆)δ8.18(s，1H)，7.43(bs，2H)，7.26-7.16(m，3H)，7.04-7.00(m，3H)，6.85(dd，J＝8.8，4.0Hz，1H)，6.45(d，J＝2.8Hz，1H)，4.37(t，J＝7.2Hz，2H)，3.74(s，3H)，3.60(s，3H)，2.97(t，J＝7.2Hz，2H)；LC-MS(MH⁺)408.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine: the yield of the product is 8.0 percent,¹H NMR(DMSO-d₆)δ7.71(s，1H)，7.29-7.12(m，5H)，6.90(d，J＝8.8Hz，1H)，6.88(d，J＝6.4Hz，1H)，6.68(dd，J＝8.8，2.8Hz，1H)，4.33(t，J＝7.2Hz，2H)，3.77(s，3H)，3.58(s，3H)，3.15(t，J＝7.2Hz，2H)；LC-MS(MH⁺)408.1。

the following examples 3-233 were prepared in analogy to the procedures described in examples 1 and 2 and isolated as trifluoroacetate after preparative HPLC purification.

Example 3

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (3-bromo-propyl) -benzene.

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-phenyl-propyl) -9H-purin-6-ylamine: the yield is 21 percent,¹H NMR(DMSO-d₆)δ8.17(s，1H)，7.45(bs，2H)，7.25-7.00(m，6H)，6.85(dd，J＝8.8，2.6，1H)，6.74(d，J＝2.8Hz，1H)，4.19(t，J＝7.6Hz，2H)，3.75(s，3H)，3.59(s，3H)，2.60(t，J＝7.6Hz，2H)，1.94(m，2H)；LC-MS[M+H]⁺422.1。

examples 4 and 5

8- (benzo [1, 3] dioxol-5-ylthio) -9-phenethyl-9H-purin-6-ylamine and 8- (benzo [1, 3] dioxol-5-ylthio) -3-phenethyl-3H-purin-6-ylamine

From 8- (benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and (2-bromo-ethyl) -benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (benzo [1, 3]]Dioxol-5-ylsulfanyl) -9-phenethyl-9H-purin-6-ylamine: the yield is 31 percent,¹H NMR(DMSO-d₆)δ8.32(s，1H)，7.28-7.19(m，3H)，7.08-7.05(m，2H)，6.95(m，3H)，6.06(s，2H)，4.43(t，J＝6.8Hz，2H)，3.02(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺392.1. 8- (benzo [1, 3]]Dioxol-5-ylsulfanyl) -3-phenethyl-3H-purin-6-ylamine: the yield is 13 percent,¹H NMR(DMSO-d₆)δ8.35(s，1H)，8.17(bs，2H)，7.34-7.10(m，8H)，6.16(s，2H)，4.53(t，J＝6.8Hz，2H)，3.16(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺392.1。

example 6

8- (benzo [1, 3] dioxol-5-ylsulfanyl) -9- (3-phenyl-propyl) -9H-purin-6-ylamine

From 8- (benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and (3-bromo-propyl) -benzene the title compound was prepared. 8- (benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (3-phenyl-propyl) -9H-purin-6-ylamine: ¹H NMR(DMSO-D₆)δ8.37(s，1H)，7-29-7.11(m，5H)，7.05(s，1H)，6.96(s，2H)，7.07(s，2H)，4.21(t，J＝7.4Hz，2H)，2.59(t，J＝7.4Hz，2H)，1.97(q，J＝8.4Hz，2H)；LC-MS[M+H]⁺406.13。

Example 7

8- (benzo [1, 3] dioxol-5-ylthio) -9- [2- (4-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine

From 8- (benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -4-nitro-benzene the title compound was prepared. 8- (benzo [1, 3]]Dioxol-5-ylthio) -9- [2 (4-nitro-phenyl) -ethyl]-9H-purin-6-ylamine: the yield of the product is 43 percent,¹H NMR(DMSO-d₆)δ8.14(s，1H)，8.09(d，J＝8.8Hz，2H)，7.38(bs，2H)，7.31(d，J＝8.8Hz，2H)，6.88-6.82(m，3H)，6.02(s，2H)，4.47(t，J＝6.8Hz，2H)，3.20(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺437.1。

example 8

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -4-nitro-benzene. The compound was purified by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-nitro-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 35 percent,¹HNMR(DMSO-d₆)δ8.18(s，1H)，8.0(d，J＝8.8Hz，2H)，7.46(bs，2H)，7.26(d，J＝8.8Hz，2H)，6.96(d，J＝9.2，1H)，6.77(dd，J＝8.8，3.2Hz，1H)，6.27(d，J＝3.2Hz，1H)，4.50(t，J＝6.8Hz，2H)，3.75(s，3H)，3.56(s，3H)，3.22(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺453.5。

examples 9 and 10

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (4-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -4-fluoro-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-fluoro-phenyl) -ethyl ]-9H-purin-6-ylamine: the yield is 20 percent,¹H NMR(DMSO-d₆)δ8.30(s，1H)，7.05-7.01(m，5H)，6.88(dd，J＝8.8，2.8Hz，1H)，6.56(d，J＝2.8Hz，1H)，4.43(t，J＝6.8Hz，2H)，3.73(s，3H)，3.62(s，3H)，3.02(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺426.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (4-fluoro-phenyl) -ethyl]-3H-purin-6-ylamine: yield 17%, LC-MS [ M + H ]]⁺426.1。

Examples 11 and 12

8- (benzo [1, 3] dioxol-5-ylthio) -9- [2- (4-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (benzo [1, 3] dioxol-5-ylthio) -3- [2- (4-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -4-fluoro-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- [2- (4-fluoro-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 33 percent,¹H NMR(DMSO-d₆)δ8.27(s，1H)，8.10(bs，2H)，7.07-7.04(m，4H)，6.95-6.93(m，3H)，6.02(s，2H)，4.41(t，J＝6.8Hz，2H)，3.02(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺410.1. 8- (benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- [2- (4-fluoro-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 11 percent,¹H NMR(DMSO-d₆)δ8.35(s，1H)，8.23(bs，2H)，7.33-7.09(m，7H)，6.15(s，2H)，4.51(t，J＝7.2Hz，2H)，3.15(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺410.1。

examples 13 and 14

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9-phenethyl-9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3-phenethyl-3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2 ]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and (2-bromo-ethyl) -benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -9-phenethyl-9H-purin-6-ylamine: the yield is 38 percent,¹H NMR(DMSO-d₆)δ8.31(s，1H)，7.37(s，1H)，7.26-7.18(m，3H)，7.09-7.06(m，2H)，6.75(s，1H)，6.09(s，2H)，4.42(t，J＝7.2Hz，2H)，3.05(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺472.0. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -3-phenethyl-3H-purin-6-ylamine: the yield is 25 percent,¹H NMR(DMSO-d₆)δ8.33(s，1H)，7.52(s，1H)，7.41(s，1H)，7.30-7.12(m，5H)，6.18(s，2H)，4.52(t，J＝6.8Hz，2H)，3.17(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺472.0。

examples 15 and 16

8- (2, 4-dimethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine and 8- (2, 4-dimethoxy-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 4-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (2-bromo-ethyl) -benzene. The isomers were separated by preparative HPLC. 8- (2, 4-dimethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine: the yield is 29 percent,¹H NMR(DMSO-d₆)δ8.23(s，1H)，7.82(bs，2H)，7.29-7.18(m，4H)，7.09(dd，J＝8.4，1.6Hz，2H)，6.65(d，J＝2.4Hz，1H)，6.55(dd，J＝8.8，2.8，1H)，4.42(t，J＝7.2Hz，2H)，3.77(s，3H)，3.74(s，3H)，3.01(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺408.1. 8- (2, 4-dimethoxy-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine: the yield is 15 percent,¹H NMR(DMSO-d₆)δ7.62(bs，1H)，7.31-7.23(m，4H)，7.16-7.12(m，2H)，6.83(bs，1H)，6.73(bs，1H)，4.52(t，J＝7.2Hz，2H)，3.86(s，3H)，3.81(s，3H)，3.16(t，J＝7.2Hz，2H)，LC-MS[M+H]⁺408.1。

examples 17 and 18

8- (4-chloro-benzenesulfonyl) -9-phenethyl-9H-purin-6-ylamine and 8- (4-chloro-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine

The title compound was prepared by an analogous procedure to examples 1 and 2 from 8- (4-chloro-phenylsulfanyl) -9H-purin-6-ylamine and (2-bromo-ethyl) -benzene. The isomers were separated by preparative HPLC. 8- (4-chloro-benzenesulfonyl) -9-phenethyl-9H-purin-6-ylamine: the yield is 45 percent, ¹H NMR(DMSO-d₆)δ8.22(s，1H)，7.64(bs，2H)，7.44-7.40(m，2H)，7.32-7.17(m，5H)，7.03(dd，J＝8.0，1.6Hz，2H)，4.38(t，J＝7.2Hz，2H)，3.01(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺382.0. 8- (4-chloro-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine: the yield is 28 percent,¹H NMR(DMSO-d₆)δ8.17(s，1H)，8.10(bs，2H)，7.60(d，J＝8.4Hz，2H)，7.49(d，J＝8.8Hz，2H)，7.28-7.22(m，3H)，7.12(dd，J＝8.4，1.6Hz，2H)，4.49(t，J＝6.8Hz，2H)，3.16(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺382.0。

examples 19 and 20

4- (6-amino-9-phenethyl-9H-purin-8-ylthio) -benzonitrile and 4- (6-amino-3-phenethyl-3H-purin-8-ylthio) -benzonitrile

The title compound was prepared by an analogous procedure to examples 1 and 2 from 4- (6-amino-9H-ylsulfanyl) -benzonitrile and (2-bromo-ethyl) -benzene. The isomers were separated by preparative HPLC. 4- (6-amino-9-phenethyl-9H-purin-8-ylsulfanyl) -benzonitrile: the yield is 22 percent,¹H NMR(DMSO-d₆)δ8.32(8，1H)，7.77(dd，J＝6.8，2.0Hz，2H)，7.33(dd，J＝6.4，2.0Hz，2H)，7.24-7.16(m 3H)，7.01(dd，J＝8.0，2.0Hz，2H)，4.42(t，J＝7.2Hz，2H)，3.04(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺373.0. 4- (6-amino-3-phenethyl-3H-purin-8-ylsulfanyl) -benzonitrile: the yield is 16 percent,¹H NMR(DMSO-d₆)δ8.47(bs，1H)，8.31(bs，1H)，8.25(s，1H)，7.85(dd，J＝8.4，1.6Hz，2H)，7.68(d，J＝8.4Hz，2H)，7.30-7.20(m，3H)，7.13(dd，J＝8.4，1.6Hz，2H)，4.52(t，J＝7.2Hz，2H)，3.18(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺373.0。

examples 21 and 22

9- [2- (3, 4-dimethoxy-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (3, 4-dimethoxy-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 4- (2-bromo-ethyl) -1, 2-dimethoxy-benzene. The isomers were separated by preparative HPLC. 9- [2- (3, 4-dimethoxy-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 52 percent, ¹H NMR(DMSO-d₆)δ8.29(s，1H)，7.02(d，J＝8.8Hz，1H)，6.87(dd，J＝9.2，2.8Hz，1H)，6.77(d，J＝8.4Hz，1H)，6.58(d，J＝1.6Hz，1H)，6.54(d，J＝3.2Hz，1H)，6.49(dd，J＝8.0，2.4Hz，1H)，4.41(t，J＝7.2Hz，2H)，3.73(s，3H)，3.68(s，3H)，3.64(s，3H)，3.61(s，3H)，2.94(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺468.2. 3- [2- (3, 4-dimethoxy-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 26 percent,¹HNMR(DMSO-d₆)δ8.25(s，1H)，8.15(bs，2H)，6.82(d，J＝8.4Hz，2H)，6.73(bs，2H)，6.58(d，J＝6.4Hz，2H)，4.52(t，J＝6.4Hz，2H)，3.77(s，3H)，3.71(s，3H)，3.70(s，3H)，3.68(s，3H)，3.09(t，J＝6.4Hz，2H)；LC-MS[M+H]⁺468.1。

examples 23 and 24

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-p-tolyl-ethyl) -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-p-tolyl-ethyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -4-methyl-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethyl)Oxy-phenylsulfanyl) -9- (2-p-tolyl-ethyl) -9H-purin-6-ylamine: the yield is 37 percent,¹H NMR(DMSO-d₆)δ8.24(s，1H)，7.77(bs，2H)，7.03(m，3H)，6.92(d，J＝8.0Hz，2H)，6.86(dd，J＝8.8，3.2Hz，1H)，6.50(d，J＝2.8Hz，1H)，4.36(t，J＝7.2Hz，2H)，3.74(s，3H)，3.60(s，3H)，2.94(t，J＝7.2Hz，2H)，2.23(s，3H)；LC-MS[M+H]⁺422.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-p-tolyl-ethyl) -3H-purin-6-ylamine: the yield is 28 percent,¹H NMR(DMSO-d₆)δ8.84(s，1H)，8.34(s，1H)，8.20(bs，2H)，7.25-6.99(m，7H)，4.50(t，J＝7.2Hz，2H)，3.76(s，3H)，3.73(s，3H)，3.12(t，J＝7.2Hz，2H)2.25(s，3H)；LC-MS[M+H]⁺422.1。

examples 25 and 26

9- [2- (2-chloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (2-chloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-chloro-benzene. The isomers were separated by preparative HPLC. 9- [2- (2-chloro-phenyl) -ethyl ]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 18 percent,¹HNMR(DMSO-d₆)δ8.23(s，1H)，7.82(bs，2H)，7.36(dd，J＝8.0，1.2Hz，1H)，7.24-7.15(m，2H)，7.03-6.99(m，2H)，6.85(dd，J＝9.2，3.2Hz，1H)，6.47(d，J＝2.8Hz，1H)，4.46(t，J＝7.2Hz，2H)，3.73(s，3H)，3.61(s，3H)，3.16(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺442.1. 3- [2- (2-chloro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 11 percent,¹H NMR(DMSO-d₆)δ8.34(s，1H)，8.16(bs，1H)，7.41(m，1H)，7.29-7.11(m，6H)，4.56(t，J＝6.8Hz，2H)，3.76(s，3H)，3.72(s，3H)，3.30(t，J＝6.8Hz，2H)，LC-MS[M+H]⁺442.1。

examples 27 and 28

9- [2- (2, 4-dichloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (2, 4-dichloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenyl-sulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2, 4-dichloro-benzene. The isomers were separated by preparative HPLC. 9- [2- (2, 4-dichloro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 41 percent,¹HNMR(DMSO-d₆)δ8.28(s，1H)，7.50(d，J＝2.8Hz，1H)，7.25(dd，J＝8.4，2.0Hz，1H)，7.05(d，J＝8.4Hz，1H)，7.01(d，J＝9.2Hz，1H)，6.86(dd，J＝9.2，2.8Hz，1H)，6.52(d，J＝2.8Hz，1H)，4.48(t，J＝6.8Hz，2H)，3.73(s，3H)，3.62(s，3H)，3.17(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺476.1. 3- [2- (2, 4-dichloro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenyl-thio) -3H-purin-6-ylamine: the yield is 13 percent,¹H NMR(DMSO-d₆)δ8.37(s，1H)，8.15(bs，2H)，7.58(d，J＝2.0Hz，1H)，7.36(dd，J＝8.4，2.0Hz，1H)，7.26(d，J＝8.0Hz，1H)，7.22-7.09(m，3H)，4.54(t，J＝6.8Hz，2H)，3.76(s，3H)，3.73(s，3H)，3.29(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺476.1。

examples 29 and 30

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-fluoro-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-fluoro-phenyl) -ethyl ]-9H-purin-6-ylamine: the yield is 37 percent,¹H NMR(DMSO-d₆)δ8.27(s，1H)，7.28-7.22(m，1H)，7.12-7.00(m，4H)，6.87(dd，J＝8.8，3.2Hz，1H)，6.55(d，J＝3.2Hz，1H)，4.45(t，J＝6.8，Hz，2H)，3.72(s，3H)，3.62(s，3H)，3.08(t，J＝6.8，2H)；LC-MS[M+H]⁺426.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-fluoro-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 18 percent,¹H NMR(DMSO-d₆)δ8.37(s，1H)，8.19(bs，2H)，7.33-7.08(m，7H)，4.55(t，J＝7.2Hz，2H)，3.76(s，3H)，3.73(s，3H)，3.23(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺426.1。

examples 31 and 32

9- [2- (4-chloro-phenyl) -ethyl ] -8- (3, 4, 5-trimethoxy-phenylthio) -9H-purin-6-ylamine and 3- [2- (4-chloro-phenyl) -ethyl ] -8- (3, 4, 5-trimethoxy-phenylthio) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (3, 4, 5-trimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -4-chloro-benzene. The isomers were separated by preparative HPLC. 9- [2- (4-chloro-phenyl) -ethyl]-8- (3, 4, 5-trimethyl)Oxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 7 percent,¹HNMR(DMSO-d₆)δ8.21(s，1H)，7.29(br d，J＝8.8Hz，2H)，7.05(br d，J＝8.8Hz，2H)，6.71(s，2H)，4.41(t，J＝7.6Hz，2H)，3.71(s，6H)，3.63(s，3H)，2.99(t，J＝7.6Hz，2H)；LC-MS[M+H]⁺472.0. 3- [2- (4-chloro-phenyl) -ethyl]-8- (3, 4, 5-trimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 7 percent,¹H NMR(DMSO-d₆)δ8.19(s，1H)，7.29-7.26(m，2H)，7.13-7.10(m，4H)，4.60(t，J＝6.8Hz，2H)，3.88(s，6H)，3.86(s，3H)3.23(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺472.1。

examples 33 and 34

8- (-6-iodo-benzo [1, 3] dioxol-5-ylthio) -9-phenethyl-9H-purin-6-ylamine and 8- (6-iodo-benzo [1, 3] dioxol-5-ylthio) -3-phenethyl-3H-purin-6-ylamine

From 8- (6-iodo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and (2-bromo-ethyl) -benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (-6-iodo-benzo [1, 3] ]Dioxol-5-ylsulfanyl) -9-phenethyl-9H-purin-6-ylamine: the yield is 11 percent,¹H NMR(DMSO-d₆)δ8.31(s，1H)，7.49(s，1H)，7.27-7.19(m，3H)，7.10-7.09(m，2H)，6.74(s，1H)，6.07(s，2H)，4.41(t，J＝7.2Hz，2H)，3.04(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺518.0. 8- (6-iodo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -3-phenethyl-3H-purin-6-ylamine: the yield is 6 percent,¹H NMR(CD₃OD)δ8.06(s，1H)，7.56(s，1H)，7.38(s，1H)，7.29-7.18(m，3H)，7.11-7.08(m，2H)，6.13(s，2H)，4.59(t，J＝7.2Hz，2H)，3.22(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺518.0。

examples 35 and 36

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-methoxy-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-methoxy-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-methoxy-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 27 percent,¹HNMR(DMSO-d₆)δ8.24(s，1H)，7.13(t，J＝8.0Hz，1H)，7.01(d，J＝6.8Hz，1H)，6.86(dd，J＝8.8，3.2Hz，1H)，6.75(m，1H)，6.60-6.51(m，2H)，6.50(d，J＝3.2Hz，1H)，4.40(t，J＝7.2Hz，2H)，3.74(s，3H)，3.67(s，3H)，3.60(s，3H)，2.96(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺438.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-methoxy-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 15 percent,¹H NMR(DMSO-d₆)δ8.32(bs，1H)，7.24-7.09(m，4H)，6.79(d，J＝8.0Hz，1H)，6.72(bs，1H)，6.67(d，J＝7.6Hz，1H)，4.53(t，J＝7.2Hz，2H)，3.77(s，3H)，3.71(s，3H)，3.70(s，3H)，3.15(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺438.1。

examples 37 and 38

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-fluoro-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-fluoro-phenyl) -ethyl ]-9H-purin-6-ylamine: the yield is 19 percent,¹H NMR(DMSO-d₆)δ8.23(s，1H)，7.82(bs，2H)，7.24(dd，J＝6.0，2.0Hz 1H)，7.03-6.97(m，2H)，6.90-6.85(m，2H)，6.82(d，J＝7.2Hz，1H)，6.51(d，J＝2.8Hz，1H)，4.43(t，J＝7.2Hz，2H)，3.74(s，3H)，3.61(s，3H)，3.03(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺426.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-fluoro-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 9 percent,¹H NMR(DMSO-d₆)δ8.35(s，1H)，8.11(bs，2H)，7.31(q，J＝8.0Hz，1H)，7.23-7.01(m，5H)，6.94(d，J＝7.2Hz，1H)，4.55(t，J＝7.2Hz，2H)，3.77(s，3H)，3.72(s，3H)，3.20(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺426.1。

examples 39 and 40

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (4-chloro-2-fluorophenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (4-chloro-2-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -4-chloro-2-fluoro-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -9- [2- (4-chloro-2-fluorophenyl) -ethylBase of]-9H-purin-6-ylamine: the yield is 20 percent,¹H NMR(DMSO-d₆)δ8.24(s，1H)，7.36(s，1H)，7.31-7.27(m，1H)，7.16-7.04(m，2H)，6.72(s，1H)，6.10(s，2H)，4.44(t，J＝7.1Hz，2H)，3.12(t，J＝7.1，Hz，2H)；LC-MS[M+H]⁺523.9. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- [2- (4 chloro-2-fluoro-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 9 percent,¹H NMR(DMSO-d₆)δ8.37(s，1H)，7.49(s，1H)，7.39-7.30(m，2H)，7.22-7.19(m，2H)，6.18(s，2H)，4.58(t，J＝7.6Hz，2H)，3.22(t，J＝7.6Hz，2H)；LC-MS[M+H]⁺523.9。

examples 41 and 42

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-pentafluorophenyl-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-pentafluorophenyl-ethyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2, 3, 4, 5, 6-pentafluoro-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (2-pentafluorophenyl-ethyl) -9H-purin-6-ylamine: the yield is 41 percent,¹H NMR(DMSO-d₆)δ8.19(s，1H)，7.38(s，1H)，6.79(s，1H)6.13(s，2H)，4.44(t，J＝7.4Hz，2H)，3.22(t，J＝7.4Hz，2H)；LC-MS[M+H]⁺561.9. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (2-pentafluorophenyl-ethyl) -3H-purin-6-ylamine: yield 13%, LC-MS [ M + H ]]⁺561.9。

Examples 43 and 44

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (3-phenyl-propyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (3-phenyl-propyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and (3-bromo-propyl) -benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (3-phenyl-propyl) -9H-purin-6-ylamine: the yield is 20 percent, ¹H NMR(DMSO-d₆)δ8.32(s，1H)，7.40(s，1H)，7.28-7.23(m，2H)，7.19-7.13(m，3H)，6.92(s，1H)，6.92(s，1H)6.10(s，2H).4.23(t，J＝7.2Hz，2H)，2.59(t，J＝7.2Hz，2H)，2.03-1.95(m，2H)；LC-MS[M+H]⁺486.0. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -3- (3-phenyl-propyl) -3H-purin-6-ylamine: the yield is 4 percent,¹H NMR(DMSO-d₆)δ8.59(s，1H)，8.20(s，1H)，7.49(s，1H)，7.38(s，1H)，7.27-7.23(m，2H)，7.18-7.15(m，3H)，6.17(s，2H).4.33(t，J＝6.8Hz，2H)，2.63(t，J＝7.6Hz，2H)，2.23-2.15(m，2H)；LC-MS[M+H]⁺486.0。

examples 45 and 46

9-phenethyl-8- (3, 4, 5-trimethoxy-phenylthio) -9H-purin-6-ylamine and 3-phenethyl-8- (3, 4, 5-trimethoxy-phenylthio) -3H-purin-6-ylamine

From 8- (3, 4, 5-trimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (C) by a procedure analogous to examples 1 and 22-bromo-ethyl) -benzene the title compound was prepared. The isomers were separated by preparative HPLC. 9-phenethyl-8- (3, 4, 5-trimethoxy-thiophenyl) -9H-purin-6-ylamine: the yield is 38 percent,¹H NMR(DMSO-d₆)δ8.29(s，1H)，7.27-7.18(m，3H)，7.06-7.04(m，2H)，6.74(s，2H)，4.17(t，J＝6.8Hz，2H)，3.71(s，6H)，3.64(s，3H)，2.97(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺438.1. 3-phenethyl-8- (3, 4, 5-trimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 14 percent,¹H NMR(DMSO-d₆)δ8.37(s，1H)，7.31-7.21(m，3H)，7.15-7.13(m，2H)，7.10(s，2H)，4.54(t，J＝6.8Hz，2H)，3.80(s，6H)，3.73(s，3H)3.17(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺438.1。

examples 47 and 48

9- (3-phenyl-propyl) -8- (3, 4, 5-trimethoxy-phenylthio) -9H-purin-6-ylamine and 3- (3-phenyl-propyl) -8- (3, 4, 5-trimethoxy-phenylthio) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (3, 4, 5-trimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (3-bromo-propyl) -benzene. The isomers were separated by preparative HPLC. 9- (3-phenyl-propyl) -8- (3, 4, 5-trimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 34 percent, ¹H NMR(DMSO-d₆)δ8.30(s，1H)，7.26-7.22(m，2H)，7.16(tt，J＝7.6，1.2Hz，1H)，7.12-7.10(m，2H)，6.78(s，2H)，4.24(t，J＝7.2Hz，2H)，3.72(s，6H)，3.63(s，3H)，2.56(t，J＝7.6Hz，2H)，1.94(tt，J＝7.6，7.2Hz，2H)；LC-MS[M+H]⁺452.0. 3- (3-phenyl-propyl) -8- (3, 4, 5-trimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 13 percent,¹H NMR(DMSO-d₆)δ8.61(s，1H)，7.27-7.23(m，2H)，7.18-7.15(m，3H)，7.06(s, 2H), 4.35(t, J ═ 7.2Hz, 2H), 3.77(s, 6H), 3.71(s, 3H)2.64(t, J ═ 7.2Hz, 2H), 2.20 (quintuple, J ═ 7.2Hz, 2H); LC-MS [ M + H ]]⁺452.0。

Examples 49 and 50

8- (benzo [1, 3] dioxol-5-ylthio) -9- (2-pyrrol-1-yl-ethyl) -9H-purin-6-ylamine and 8- (benzo [1, 3] dioxol-5-ylthio) -3- (2-pyrrol-1-yl-ethyl) -3H-purin-6-ylamine

From 8- (benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -1H-pyrrole the title compound was prepared. The isomers were separated by preparative HPLC. 8- (benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (2-pyrrol-1-yl-ethyl) -9H-purin-6-ylamine: the yield is 27 percent,¹H NMR(CD₃OD)δ8.24(s，1H)，7.09(dd，J＝8.0，1.6Hz，1H)，7.00(d，J＝1.6Hz，1H)，6.90(d，J＝8.0Hz，1H)，6.42(t，J＝2.0Hz，2H)，6.03(s，2H)，5.98(t，J＝2.0Hz，2H)，4.58-4.55(m，2H)，4.41-4.38(m，2H)；LC-MS[M+H]⁺381.2. 8- (benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (2-pyrrol-1-yl-ethyl) -3H-purin-6-ylamine: the yield is 16 percent,¹H NMR(CD₃OD)δ7.60(s，1H)，7.32(dd，J＝8.0，1.6Hz，1H)，7.25(d，J＝1.6Hz，1H)，7.05(d，J＝8.0Hz，1H)，6.49(t，J＝2.4Hz，2H)，6.13(s，2H)，6.02(t，J＝2.0Hz，2H)，4.67(br t，J＝6.0Hz，2H)，4.40(br t，J＝6.0Hz，2H)；LC-MS[M+H]⁺381.1。

examples 51 and 52

8- (benzo [1, 3] dioxol-5-ylthio) -9- (3-pyrrol-1-yl-propyl) -9H-purin-6-ylamine and 8- (benzo [1, 3] dioxol-5-ylthio) -3- (3-pyrrol-1-yl-propyl) -3H-purin-6-ylamine

From 8- (benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (3-bromo-propyl) -1H-pyrrole the title compound was prepared. The isomers were separated by preparative HPLC. 8- (benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (3-pyrrol-1-yl-propyl) -9H-purin-6-ylamine: the yield is 23 percent,¹H NMR(CD₃OD) δ 8.18(s, 1H), 7.06(dd, J ═ 8.0, 1.6Hz, 1H), 7.00(d, J ═ 1.6Hz, 1H), 6.88(d, J ═ 8.0Hz, 1H), 6.69(t, J ═ 2.4Hz, 2H), 6.04(t, J ═ 2.4Hz, 2H), 6.02(s, 2H), 4.20(br t, J ═ 7.6Hz, 2H), 4.01(t, J ═ 6.8Hz, 2H), 2.21 (quintuple, J ═ 6.8Hz, 2H); LC-MS [ M + H ]]⁺395.1. 8- (benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (3-pyrrol-1-yl-propyl) -3H-purin-6-ylamine: the yield is 11 percent,¹H NMR(CD₃OD) δ 8.31(s, 1H), 7.29(dd, J ═ 8.0, 2.0Hz, 1H), 7.21(d, J ═ 2.0Hz, 1H), 7.02(d, J ═ 8.0Hz, 1H), 6.60(t, J ═ 2.4Hz, 2H), 6.11(s, 2H), 5.96(t, J ═ 2.4Hz, 2H), 4.35(t, J ═ 6.8Hz, 2H), 4.03(t, J ═ 6.8Hz, 2H), 2.45 (quintuple, J ═ 6.8Hz, 2H); LC-MS [ M + H ]]⁺395.1。

Examples 53 and 54

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2-chloro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2-chloro-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3 ] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-chloro-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylthio) -9- [2- (2-chloro-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 32 percent,¹H NMR(CD₃OD)δ8.18(s，1H)，7.34(brd，J＝7.2Hz，1H)，7.22(br t，J＝7.2Hz，1H)，7.20(s，1H)，7.14(br t，J＝7.2Hz，1H)，7.02(br d，J＝7.2Hz，1H)，6.89(s，1H)，6.05(s，2H)，4.57(t，J＝6.4Hz，2H)，3.35(t，J＝6.4Hz，2H)；LC-MS[M+H]⁺506.0. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylthio) -3- [2- (2-chloro-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 16 percent,¹H NMR(CD₃OD)δ8.12(s，1H)，7.37-7.34(m，3H)，7.26-7.18(m，2H)，7.14(m，1H)，6.16(s，2H)，4.64(t，J＝6.8Hz，2H)，3.38(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺506.0。

examples 55 and 56

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 2- (2-bromo-ethyl) -1, 3, 5-trimethyl-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2, 4, 6-trimethyl-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 18 percent,¹H NMR(DMSO-d₆)δ8.39(s，1H)，7.04(d，J＝9.0Hz，1H)，6.90-6.81(m，3H)，6.51(s，1H)，4.21(t，J＝8.8Hz，2H)，3.77(s，3H)，3.61(s，3H)，3.00-2.91(m，2H)，2.27(s，6H)，2.19(s，3H)；LC-MS[M+H]⁺450.20. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ]-3H-purin-6-ylamine: the yield is 6 percent,¹H NMR(DMSO-d₆)δ8.52(s，1H)，7.28-7.09(m，3H)，6.82(s，2H)，4.30(t，J＝13.3Hz，2H)，3.78(s，3H)，3.76(s，3H)，3.10(t，J＝15.1Hz，2H)，2.19(s，9H)；LC-MS[M+H]⁺450.20。

examples 57 and 58

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-phenyl-butyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-phenyl-butyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and (1-bromomethyl-propyl) -benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (2-phenyl-butyl) -9H-purin-6-ylamine: the yield is 25 percent,¹H NMR(DMSO-d₆)δ8.29(s，1H)，7.36(s，1H)，7.27-7.09(m，5H)，6.69(s，1H)，6.10(s，2H)，4.49-4.30(m，2H)，3.21-3.11(m，1H)，1.72-1.63(m，2H)，0.70(t，J＝7.6Hz，3H)；LC-MS[M+H]⁺499.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (2-phenyl-butyl) -3H-purin-6-ylamine: the yield is 8 percent,¹H NMR(DMSO-d₆)δ8.17(s，1H)，7.51(s，1H)，7.38(s，1H)，7.28-7.09(m，5H)，6.19(s，2H)，4.61-4.52(m，1H)，4.47-4.42(m，1H)，3.31-3.22(m，1H)，1.72-1.61(m，2H)，0.72(t，J＝7.1Hz，3H)；LC-MS[M+H]⁺499.1。

examples 59 and 60

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [1- (4-methoxy-phenyl) -cyclopropylmethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [1- (4-methoxy-phenyl) -cyclopropylmethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (1-bromomethyl-cyclopropyl) -4-methoxy-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3] ]Dioxol-5-ylsulfanyl) -9- [1- (4-methoxy-phenyl) -cyclopropylmethyl]-9H-purin-6-ylamine: the yield is 30 percent,¹H NMR(CD₃OD)δ7.45(s，1H)，7.26(s，1H)，7.19(s，1H)，7.02(d，J＝8.8Hz，2H)，6.78(d，J＝8.9Hz，2H)，6.10(s，2H)4.49(s，2H)，3.72(s，3H)，1.20-1.18(m，2H)，0.91-0.88(m，2H)；LC-MS[M+H]⁺527.0. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -3- [1- (4-methoxy-phenyl) -cyclopropylmethyl]-3H-purin-6-ylamine: the yield is 9 percent,¹H NMR(CD₃OD)δ8.16(br s，1H)，7.16(s，1H)，7.02(d，J＝8.8Hz，2H)，6.81(s，1H)，6.76(d，J＝8.8Hz，2H)，6.04(s，2H)，4.40(s，2H)，3.72(s，3H)，1.31-1.26(m，2H)，0.89-0.82(m，2H)；LC-MS[M+H]⁺527.0。

examples 61 and 62

9- [1- (4-chloro-phenyl) -cyclobutylmethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [1- (4-chloro-phenyl) -cyclobutylmethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (1-bromomethyl-cyclobutyl) -4-chloro-benzene. The isomers were separated by preparative HPLC. 9- [1- (4-chloro-phenyl) -cyclobutylmethyl group]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 10 percent,¹H NMR(DMSO-d₆)δ8.28(s，1H)，7.32-7.28(m，2H)，6.97-6.91(m，3H)，6.85-6.81(m，1H)，6.52(d，J＝3.0Hz，1H)，4.59(s，2H)3.62(s，3H)，3.61(s，3H)，2.68-2.60(m，2H)，2.31-2.21(m，2H)，2.17-2.08(m，1H)，1.83-1.75(m，1H)；LC-MS[M+H]⁺482.10. 3- [1- (4-chloro-phenyl) -cyclobutylmethyl group]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 4 percent,¹H NMR(DMSO-d₆)δ8.19(s，1H)，7.35-7.29(m，2H)，7.22-7.05(m，3H)，6.98-6.95(m，2H)，4.66(s，2H)3.78(s，3H)，3.76(s，3H)，2.52-2.41(m，2H)，2.32-2.21(m，2H)，2.07-1.99(m，1H)，1.81-1.70(m，1H)；LC-MS[M+H]⁺482.10。

examples 63 and 64

1- (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) -ethanone and 1- (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) -ethanone

Prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- [4- (2-chloro-ethyl) -phenyl]-ethanone the title compound was prepared. The isomers were separated by preparative HPLC. 1- (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl]-ethyl } -phenyl) -ethanone: the yield is 26 percent,¹H NMR(DMSO-d₆)δ8.29(s，1H)，7.78(d，J＝8.4Hz，2H)，7.17(d，J＝8.0，2H)，7.01(d，J＝8.8Hz，1H)，6.86(dd，J＝9.2，2.8Hz，1H)，6.49(d，J＝3.2Hz，1H)，4.50(t，J＝7.2Hz，2H)，3.74(s，3H)，3.60(s，3H)，3.12(t，J＝7.2Hz，2H)，2.52(s，3H)；TOF LC-MS[M+H]⁺450.16. 1- (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl]-ethyl } -phenyl) -ethanone: the yield is 11 percent,¹H NMR(DMSO-d₆)δ8.37(b s，1H)，8.14(bs，2H)，7.88(d，J＝8.4Hz，2H)，7.30(d，J＝8.4Hz，2H)，7.26-7.06(m，3H)，4.57(t，J＝6.8Hz，2H)，3.77(s，3H)，3.72(s，3H)，3.27(t，J＝7.2Hz，2H)，2.56(s，3H)；TOF LC-MS[M+H]⁺450.16。

examples 65 and 66

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyrrol-1-yl-ethyl) -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-pyrrol-1-yl-ethyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -1H-pyrrole. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyrrol-1-yl-ethyl) -9H-purin-6-ylamine: the yield is 26 percent,¹H NMR(DMSO-d₆)δ8.29(s，1H)，7.01(d，J＝9.2Hz，1H)，6.88(dd，J＝9.2，3.2Hz，1H)，6.55(d，J＝2.8Hz，1H)，6.43(t，J＝2.0Hz，2H)，5.90(t，J＝2.0Hz，2H)，4.52(t，J＝6.4Hz，2H)，4.29(t，J＝6.4Hz，2H)，3.71(s，3H)，3.62(s，3H)；TOF LC-MS[M+H]⁺397.14. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-pyrrol-1-yl-ethyl) -3H-purin-6-ylamine: the yield is 16 percent,¹H NMR(DMSO-d₆)δ8.16(bs，1H)，7.81(bs，1H)，7.24-7.02(m，3H)，6.56(m，2H)，5.95(m，2H)，4.62(m，2H)，4.46-4.34(m，2H)，3.77(s，3H)，3.73(s，3H)；TOFLC-MS[M+H]⁺397.14。

examples 67 and 68

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-naphthalen-1-yl-ethyl) -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-naphthalen-1-yl-ethyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -naphthalene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-naphthalen-1-yl-ethyl) -9H-purin-6-ylamine: the yield is 28 percent,¹H NMR(DMSO-d₆)δ8.33(s，1H)，8.13-8.10(m，1H)，7.94-7.92(m，1H)，7.81(d，J＝8.4Hz，1H)，7.56-7.52(m，2H)，7.37(t，J＝7.2Hz，1H)，7.14(d，J＝6.0Hz，1H)，7.02(d，J＝8.8Hz，1H)，6.86(dd，J＝9.2，2.8Hz，1H)，6.50(d，J＝3.2Hz，1H)，4.50(t，J＝6.4Hz，2H)，3.72(s，3H)，3.60(s，3H)，3.45(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺458.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-naphthalen-1-yl-ethyl) -3H-purin-6-ylamine: the yield is 14 percent,¹H NMR(DMSO-d₆)δ8.19(d，J＝8.4Hz，1H)，8.11(bs，1H)，7.95(d，J＝8.0Hz，1H)，7.85(d，J＝8.0Hz，1H)，7.58-7.40(m，3H)，7.32-7.26(m，2H)，7.17(bs，1H)，7.09(bs，1H)，4.60(t，J＝7.2Hz，2H)，3.78(s，3H)，3.72(s，3H)，3.64(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺458.1。

examples 69 and 70

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-o-tolyl-ethyl) -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-o-tolyl-ethyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-methyl-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-o-tolyl-ethyl) -9H-purin-6-ylamine: the yield is 23 percent, ¹H NMR(DMSO-d₆)δ8.31(bs，1H)，7.18-7.00(m，4H)，6.90-6.84(m，2H)，6.56(bs，1H)，4.36(t，J＝7.2Hz，2H)，3.74(s，3H)，3.61(s，3H)，2.98(t，J＝7.2Hz，2H)，2.26(s，3H)；TOF LC-MS[M+H]⁺422.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-o-tolyl-ethyl) -3H-purin-6-ylamine: the yield is 15 percent,¹H NMR(DMSO-d₆)δ8.15(bs，1H)，7.24(bs，1H)，7.20-7.06(m，5H)，6.99(d，J＝7.6Hz，1H)，4.46(t，J＝7.2Hz，2H)，3.76(s，3H)，3.72(s，3H)，3.16(t，J＝7.2Hz，2H)，2.32(s，3H)；TOF LC-MS[M+H]⁺422.1。

examples 71 and 72

9- [2- (4-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (4-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -4-bromo-benzene. The isomers were separated by preparative HPLC. 9- [2- (4-bromo-phenyl) -ethyl]-8- (2, 5-dimethyl)Oxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 27 percent,¹HNMR(DMSO-d₆)δ8.24(b s，1H)，7.40(dd，J＝6.8，2.0Hz，2H)，7.02(d，J＝8.8Hz，1H)，6.98(dd，J＝6.4，2.0Hz，2H)，6.87(dd，J＝8.8，2.8Hz，1H)，6.50(d，J＝2.8Hz，1H)，4.41(t，J＝7.2Hz，2H)，3.74(s，3H)，3.61(s，3H)，2.98(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺488.05. 3- [2- (4-bromo-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 13 percent,¹HNMR(DMSO-d₆)δ8.15(bs，1H)，7.51-7.44(m，2H)，7.24(bs，1H)，7.18(d，J＝8.4Hz，1H)，7.14-7.09(m，3H)，4.53(t，J＝6.8Hz，2H)，3.76(s，3H)，3.73(s，3H)，3.16(t，J＝6.8Hz，2H)；TOF LC-MS[M+H]⁺488.05。

examples 73 and 74

9- [2- (2, 3-dichloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (2, 3-dichloro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2, 3-dichloro-benzene. The isomers were separated by preparative HPLC. 9- [2- (2, 3-dichloro-phenyl) -ethyl ]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 14 percent,¹HNMR(DMSO-d₆)δ8.23(s，1H)，7.46(dd，J＝8.0，1.6Hz，1H)，7.16(t，J＝8.0Hz，1H)，7.0(d，J＝9.4Hz，1H)，6.95(dd，J＝7.6，1.6Hz，1H)，6.85(dd，J＝8.8，3.2Hz，1H)，6.45(d，J＝2.8Hz，1H)，4.48(t，J＝7.2Hz，2H)，3.74(s，3H)，3.60(s，3H)，3.22(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺476.0. 3- [2- (2, 3-dichloro-phenyl) -ethyl]-8- (2, 5-dimethyl)Oxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 10 percent,¹H NMR(DMSO-d₆)δ8.09(bs，2H)，7.50(d，J＝7.2Hz，1H)，7.31-7.24(m，1H)，7.22-7.10(m，3H)，4.60-4.52(m，2H)，3.76(s，3H)，3.71(s，3H)，3.40-3.30(m，2H)；TOF LC-MS[M+H]⁺476.0。

examples 75 and 76

4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenol and 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenol

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 4- (2-bromo-ethyl) -phenol. 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl]-ethyl } -phenol: the yield is 15 percent,¹H NMR(DMSO-d₆)δ9.24(s，1H)，8.19(s，1H)，7.53(bs，2H)，7.02(d，J＝9.2Hz，1H)，6.85(dd，J＝8.0，2.8Hz，2H)，6.81(d，J＝8.4Hz，2H)，6.62(d，J＝8.4Hz，1H)，6.46(d，J＝2.8Hz，1H)，4.30(t，J＝7.6Hz，2H)，3.74(s，3H)，3.60(s，3H)，2.85(t，J＝7.6Hz，2H)；LC-MS[M+H]⁺424.1. 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl]-ethyl } -phenol: the yield is 7 percent,¹H NMR(DMSO-d₆)δ9.31(bs，1H)，8.28(bs，1H)，7.3-7.0(m，3H)，6.90(d，J＝8.8Hz，2H)，6.66-6.59(m，2H)，4.46(t，J＝7.2Hz，2H)，3.76(s，3H)，3.72(s，3H)，3.04(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺424.1。

examples 77 and 78

9- [2- (3-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (3-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-bromo-benzene. The isomers were separated by preparative HPLC. 9- [2- (3-bromo-phenyl) -ethyl ]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 24 percent,¹HNMR(DMSO-d₆)δ8.24(s，1H)，7.89(bs，2H)，7.37(dd，J＝8.0，0.8Hz，1H)，7.24(bs，1H)，7.17(t，J＝8.0Hz，1H)，7.04-6.98(m，2H)，6.88(dd，J＝8.8，3.2Hz，1H)，6.53(d，J＝3.2Hz，1H)，4.41(t，J＝7.2Hz，2H)，3.75(s，3H)，3.62(s，3H)，3.00(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺486.1. 3- [2- (3-bromo-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 13 percent,¹H NMR(DMSO-d₆)δ8.39(bs，1H)，8.15(bs，2H)，7.45-7.43(m，2H)，7.29-7.12(m，2H)，7.19-7.09(m，3H)，4.54(t，J＝7.2Hz，2H)，3.77(s，3H)，3.72(s，3H)，3.18(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺486.1。

examples 79 and 80

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-trifluoromethyl-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-trifluoromethyl-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-chloro-ethyl) -3-trifluoromethyl-benzene by similar procedures as examples 1 and 2A compound (I) is provided. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-trifluoromethyl-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 10 percent,¹H NMR(DMSO-d₆)δ8.16(s，1H)，7.59(bs，2H)，7.52(d，J＝8.0Hz，1H)，7.43(t，J＝8.0Hz，1H)，7.34(s，1H)，7.28(d，J＝8.0Hz，1H)，7.01(d，J＝9.2Hz，1H)，6.85(d，J＝6.0Hz，1H)，6.46(bs，1H)，4.44(t，J＝6.8Hz，2H)，3.74(s，3H)，3.60(s，3H)，3.12(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺476.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-trifluoromethyl-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 5 percent,¹H NMR(DMSO-d₆)δ8.38(bs，1H)，8.12(bs，1H)，7.64-7.42(m，3H)，7.26-7.02(m，3H)，4.58(m，2H)，3.76(s，3H)，3.71(s，3H)，3.29(m，2H)；LC-MS[M+H]⁺476.1。

examples 81 and 82

4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -benzoic acid and 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -benzoic acid

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 4- (2-chloro-ethyl) -benzoic acid. The isomers were separated by preparative HPLC. ¹H NMR (acetone-d)₆)δ8.27(s，1H)，7.91(d，J＝8.0Hz，2H)，7.24(d，J＝8.0Hz，2H)，7.00(d，J＝8.8Hz，1H)，6.86(dd，J＝8.8，3.2Hz，1H)，6.69(d，J＝3.2Hz，1H)，4.55(t，J＝7.6Hz，2H)，3.81(s，3H)，3.67(s，3H)，3.21(t，J＝7.6Hz，2H)；TOF LC-MS[M+H]⁺452.14。

4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl]-ethyl } -benzoic acid methyl esterAcid: the yield is 11 percent,¹H NMR(CD₃OD)δ8.19(s，1H)，7.93(d，J＝7.2Hz，2H)，7.29(s，1H)，7.24(d，J＝7.6Hz，2H)，7.19(s，2H)，4.64(t，J＝8.0Hz，2H)，3.81(s，6H)，3.36-3.28(m，2H)；LC-MS[M+H]⁺452.1。

example 83

8- (2, 5-dimethoxy-phenylsulfanyl) -3- (4-fluoro-benzyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1-bromomethyl-4-fluoro-benzene. The compound was purified by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (4-fluoro-benzyl) -3H-purin-6-ylamine: the yield is 34 percent,¹H NMR(DMSO-d₆)δ8.55(s，1H)，8.1(bs，2H)，7.51(m，2H)，7.15(m，2H)，6.97(m，2H)，6.76(dd，J＝8.8，2.8Hz，1H)，5.44(s，2H)，3.74(s，3H)，3.50(s，3H)；LC-MS[M+H]⁺412.1。

example 84

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (4-nitro-benzyl) -9H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1-bromomethyl-4-nitro-benzene. The compound was purified by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (4-nitro-benzyl) -9H-purin-6-ylamine: the yield is 10 percent,¹H NMR(DMSO-d₆)δ8.20(s，1H)，8.04(d，J＝6.8Hz，2H)，7.57(bs，2H)，7.30(d，6.8Hz，2H)，6.88(d，J＝8.4Hz，1H)，6.70(dd，J＝9.2，3.2Hz，1H)，6.25(d，J＝2.8Hz，1H)，5.52(s，2H)，3.71(s，3H)，3.52(s，3H)；LC-MS[M+H]⁺439.1。

examples 85 and 86

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-methoxy-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-methoxy-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-methoxy-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 27 percent,¹HNMR(DMSO-d₆)δ8.26(s，1H)，7.19-7.15(m，1H)，7.00(d，J＝8.8Hz，1H)，6.89-6.73(m，4H)，6.47(d，J＝2.4Hz，1H)，4.42(t，J＝7.2Hz，2H)，3.73(s，3H)，3.67(s，3H)，3.61(s，3H)，3.01(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺438.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-methoxy-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 11 percent,¹H NMR(DMSO-d₆)δ8.20(bs，1H)，7.26-7.16(m，3H)，7.15-7.08(m，1H)，6.98(dd，J＝7.2，1.6Hz，1H)，6.91(d，J＝7.2Hz，1H)，6.83(t，J＝7.2Hz，1H)，4.51(t，J＝6.8Hz，2H)，3.76(s，3H)，3.70(s，3H)，3.58(s，3H)，3.13(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺438.1。

examples 87 and 88

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-phenyl-butyl) -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-phenyl) -butyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (1-bromomethyl-propyl) -benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-phenyl-butyl) -9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.28(s，1H)，7.26-7.18(m，3H)，7.08-7.01(m，3H)，6.88(dd，J＝3.2，9.0Hz，1H)，6.50(d，J，＝2.9Hz，1H)，4.45-4.29(m，2H)，3.74(s，3H)，3.60(s，3H)，3.15-3.05(m，1H)，1.71-1.59(m，2H)，0.65(t，J＝7.3Hz，3H)；LC-MS[M+H]⁺)436.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-phenyl) -butyl) -3H-purin-6-ylamine: the yield is 31 percent,¹H NMR(DMSO-d₆)δ8.20(s，1H)，7.31-7.08(m，8H)，4.63-4.51(m，1H)，4.48-4.39(m，1H)，3.79(s，3H)，3.77(s，3H)，3.29-3.20(m，1H)，1.75-1.61(m，2H)，0.73(t，J＝7.0Hz，3H)；LC-MS[M+H]⁺436.1。

examples 89 and 90

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 5- (2-bromo-ethyl) -1, 2, 3-trimethoxy-benzene. By preparative HPLCThe isomers are isolated. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 22 percent,¹H NMR(DMSO-d₆)δ8.30(s，1H)，7.04(d，J＝9.0Hz，1H)，6.88(dd，J＝9.0，3.0Hz，1H)，6.58(d，J＝2.9Hz，1H)，6.26(s，2H)，4.42(t，J＝6.9Hz，2H)，3.77(s，3H)，3.66(s，6H)，3.62(s，3H)，3.59(s，3H)，2.96(t，J＝6.9Hz，2H)；LC-MS[M+H]⁺498.2. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 5 percent,¹H NMR(DMSO-d₆)δ8.36(s，1H)，7.26-7.04(m，3H)，6.41(s，2H)，4.56(t，J＝6.8Hz，2H)，3.77(s，3H)，3.74(s，3H)，3.69(s，6H)，3.61(s，3H)，3.09(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺498.2。

examples 91 and 92

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 5- (2-bromo-ethyl) -1, 2, 3-trimethoxy-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -9- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl ]-9H-purin-6-ylamine: the yield is 23 percent,¹H NMR(DMSO-d₆)δ8.28(s，1H)，7.38(s，1H)，6.74(s，1H)，6.27(s，2H)，6.19(s，2H)，4.40(t，J＝7.4Hz，2H)，3.67(s，6H)，3.59(s，3H)，2.96(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺561.10. 8- (6-bromo)-benzo [1, 3]]Dioxol-5-ylthio) -3- [2- (3, 4, 5-trimethoxy-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 8 percent,¹H NMR(DMSO-d₆)δ8.28(s，2H)，7.47(s，1H)，7.38(s，1H)，6.39(s，2H)，6.17(s，2H)，4.53(t，J＝6.8Hz，2H)，3.69(s，6H)，3.60(s，3H)，3.11(t，J＝6.9Hz，2H)；LC-MS[M+H]⁺561.1。

examples 93 and 94

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2, 4, 6-trimethyl-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 2- (2-bromo-ethyl) -1, 3, 5-trimethyl-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -9- [2- (2, 4, 6-trimethyl-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 23 percent,¹H NMR(DMSO-d₆)δ8.38(s，1H)，7.38(s，1H)，6.84(s，2H)，6.76(s，1H)，6.09(s，2H)，4.25(t，J＝7.8Hz，2H)，3.01(t，J＝7.8Hz，2H)，2.27(s，6H)，2.19(s，3H)；LC-MS[MH]⁺513.1. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -3- [2- (2, 4, 6-trimethyl-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 10 percent,¹H NMR(DMSO-d₆)δ8.52(s，1H)，7.50(s，1H)，7.42(s，1H)，6.82(s，2H)，6.20(s，2H)，4.28(t，J＝8.4Hz，2H)，3.19(t，J＝8.3Hz，2H)，2.19(s，9H)；LC-MS[M+H]⁺513.1。

examples 95 and 96

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [1- (4-chloro-phenyl) -cyclobutylmethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [1- (4-chloro-phenyl) -cyclobutylmethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3 ] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (1-bromomethyl-cyclobutyl) -4-chloro-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylthio) -9- [1- (4-chloro-phenyl) -cyclobutylmethyl]-9H-purin-6-ylamine: the yield is 16 percent,¹H NMR(CD₃OD)δ8.16(br s，1H)，7.26(d，J＝8.8Hz，2H)，7.14(s，1H)，6.95(d，J＝8.9Hz，2H)，6.82(s，1H)6.04(s，2H)，4.59(s，2H)，2.77-2.69(m，2H)，2.42-2.36(m，2H)，2.35-2.26(m，1H)，1.95-1.85(m，1H)；LC-MS[M+H]⁺545.0. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylthio) -3- [1- (4-chloro-phenyl) -cyclobutylmethyl]-3H-purin-6-ylamine: the yield is 7 percent,¹H NMR(CD₃OD)δ7.39(br s，1H)，7.29-7.24(m，3H)，7.19(brs，1H)，6.97-6.92(m，2H)，6.09(s，2H)4.69(s，2H)，2.58-2.50(m，2H)，2.44-2.34(m，2H)，2.24-2.17(m，1H)，1.91-1.82(m，1H)；LC-MS[M+H]⁺545.0。

examples 97 and 98

9- [2- (4-chloro-2-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (4-chloro-2-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -4-chloro-2-fluoro-benzene. The isomers were separated by preparative HPLC. 9- [2- (4-chloro-2-fluoro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 34 percent,¹HNMR(DMSO-d₆)δ8.29(s，1H)，7.30(dd，J＝10.0，2.1，Hz，1H)，7.16-7.00(m，3H)，6.88(dd，J＝8.8，3.0，Hz，1H)，6.57(d，J＝2.9Hz，1H)，4.46(t，J＝6.8Hz，2H)，3.74(s，3H)，3.62(s，3H)，3.10(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺460.1. 3- [2- (4-chloro-2-fluoro-phenyl) -ethyl ]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 12 percent,¹H NMR(DMSO-d₆)δ8.39(s，1H)，7.40-7.38(m，1H)，7.25-7.02(m，5H)，4.53(t，J＝6.4Hz，2H)，3.77(s，3H)，3.71(s，3H)，3.21(t，J＝6.4Hz，2H)；LC-MS[M+H]⁺460.1。

examples 99 and 100

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (3-methyl-2-phenyl-pentyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (3-methyl-2-phenyl-pentyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and (1-bromomethyl-2-methyl-butyl) -benzene the title compound was prepared. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (3-methyl-2-phenyl-pentyl) -9H-purin-6-ylamine, a mixture of diastereomers: the yield is 19 percent,¹H NMR(DMSO-d₆)δ8.23(s，1H)，8.21(s，1H)，7.36(s，2H)，7.15-7.10(m，6H)，7.04-6.99(m，4H)，6.59(s，2H)，6.08(s，4H)，4.59(m，2H)，4.50(m，2H)，3.30(m，2H)，3.20(m，2H)，2.45(m，4H)，1.05(d，J＝6.4Hz，3H)，0.90(t，J＝7.2Hz，3H)，0.76-0.70(m，6H)；LC-MS[M+H]⁺528.1. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (3-methyl-2-phenyl-pentyl) -3H-purin-6-ylamine, a mixture of diastereomers: the yield is 3 percent,¹H NMR(DMSO-d₆)δ8.01(s，1H)，7.99(s，1H)7.48(s，2H)，7.39(s，2H)，7.24-7.10(m，6H)，7.05-7.03(m，4H)，6.19(s，2H)，6.17(s，2H)，4.70(m，1H)，4.47(m，1H)，3.39(m，2H)，2.45(m，2H)，1.78(m，2H)，1.24(m，2H)，1.01(d，J＝6.4Hz，3H)，0.85(t，J＝7.6Hz，3H)，0.76(t，J＝7.6Hz，3H)，0.68(d，J＝6.4Hz，3H)；LC-MS[M+H]⁺528.1。

examples 101 and 102

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-cyclopentyl-2-phenyl-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-cyclopentyl-2-phenyl-ethyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3 ] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and (2-bromo-1-cyclopentyl-ethyl) -benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -9- (2-cyclopentyl-2-phenyl-ethyl) -9H-purin-6-ylamine: the yield is 20 percent,¹H NMR(DMSO-d₆)δ8.21(s，1H)，7.34(s，1H)，7.14-7.06(m，3H)，6.99(d，J＝8.0Hz，2H)，6.57(s，1H)，6.08(bs，2H)，4.47(d，J＝8.0Hz，2H)，3.20(m，1H)，2.55(m，1H)，2.01-1.80(m，4H)，1.49-1.30(m，4H)；LC-MS[M+H]⁺540.1。8-(6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -3- (2-cyclopentyl-2-phenyl-ethyl) -3H-purin-6-ylamine: the yield is 11 percent,¹H NMR(DMSO-d₆)δ7.91(bs，1H)，7.48(bs，1H)，7.40(bs，1H)，7.21-7.12(m，3H)，7.02(d，J＝7.2Hz，2H)，6.16(s，1H)，4.65(dd，J＝9.2，4.4Hz，1H)，4.41(t，J＝12Hz，1H)，3.21(m，2H)，2.43-2.23(m，1H)，1.99-1.80(m，1H)，1.70-1.20(m，6H)，0.96-0.91(m，1H)；LC-MS[M+H]⁺540.1。

examples 103 and 104

9- (2-cyclopentyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- (2-cyclopentyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (2-bromo-1-cyclopentyl-ethyl) -benzene. The isomers were separated by preparative HPLC. 9- (2-cyclopentyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: the yield is 15 percent,¹HNMR(DMSO-d₆)δ8.20(s，1H)，7.12-7.06(m，3H)，7.01(d，J＝8.8Hz，1H)，6.96-6.93(m，2H)，6.86(dd，J＝8.8，2.8Hz，1H)，6.45(d，J＝2.4Hz，1H)，4.49-4.45(m，2H)，3.74(s，3H)，3.60(s，3H)，3.18-3.01(m，1H)，2.23-2.22(m，1H)，2.00-1.25(m，6H)，0.80-0.61(m，2H)；LC-MS[M+H]⁺476.2. 3- (2-cyclopentyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: the yield is 15 percent, ¹H NMR(DMSO-d₆)δ7.99(bs，1H)，7.24-7.10(m，6H)，7.03(d，J＝6.8Hz，2H)，4.65(m，2H)，3.77(s，3H)，3.72(s，3H)，2.60-2.40(m，2H)，2.00-1.25(m，8H)；LC-MS[M+H]⁺476.2。

Examples 105 and 106

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-methyl-2-phenyl-pentyl) -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (3-methyl-2-phenyl-pentyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (1-bromomethyl-2-methyl-butyl) -benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-methyl-2-phenyl-pentyl) -9H-purin-6-ylamine, mixture of diastereomers: the yield is 25 percent,¹H NMR(DMSO-d₆)δ8.18(s，1H)，8.16(s，1H)，7.24-7.06(m，6H)，7.03-6.94(m，6H)，6.86-6.84(m，2H)，6.39(m，2H)，4.60-4.45(m，2H)，3.75(s，6H)，3.59(s，6H)，3.50(m，4H)，2.43(m，4H)，0.98(d，J＝6.4Hz，6H)，0.90-0.88(m，2H)，0.72-0.67(m，6H)；LC-MS[M+H]⁺464.2. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (3-methyl-2-phenyl-pentyl) -3H-purin-6-ylamine, mixture of diastereomers: the yield is 9 percent,¹H NMR(DMSO-d₆)δ7.99(s，2H)，7.24-7.10(m，10H)，7.06-7.04(m，6H)，4.70(m，1H)，4.50(m，1H)，3.77(s，6H)，3.74(m，2H)，3.73(s，6H)，2.45(m，4H)，1.02(d，J＝6.4Hz，3H)，0.88-0.88(m，3H)，0.79-0.72(m，3H)，0.69(d，J＝6.4Hz，3H)；LC-MS[M+H]⁺464.2。

examples 107 and 108

2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -1- (2, 4-dichloro-phenyl) ethanol and 2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -1- (2, 4-dichloro-phenyl) ethanol

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 2-chloro-1- (2, 4-dichloro-phenyl) -ethanol. The isomers were separated by preparative HPLC. 2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ]-1- (2, 4-dichloro-phenyl) ethanol: the yield is 17 percent,¹H NMR(DMSO-d₆)δ10.10(s，1H)，7.98(s，1H)，7.61(d，J＝8.8Hz，1H)，7.53(d，J＝2.0Hz，1H)，6.95(d，J＝3.2Hz，1H)，6.87(d，J＝8.8Hz，1H)，6.76(dd，J＝8.8，3.2Hz，1H)，6.54(bs，2H)，6.42(bs，1H)，5.54(t，J＝8.8Hz，1H)，4.21(t，J＝8.8Hz，2H)3.68(s，3H)，3.67(s，3H)；TOF LC-MS[M+H]⁺492.0. 2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl]-1- (2, 4-dichloro-phenyl) ethanol: the yield of the product is 1.0 percent,¹H NMR(DMSO-d₆)δ8.10(bs，1H)，7.63-7.58(m，2H)，7.49(dd，J＝8.0，2.4Hz，1H)，6.58(bs，1H)，6.17(bs，2H)，5.63(m，1H)，4.50(m，2H)，3.76(s，3H)，3.68(s，3H)；LC-MS[M+H]⁺492.1。

examples 109 and 110

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (3-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-fluoro-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo)-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- [2- (3-fluoro-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 22 percent,¹H NMR(DMSO-d₆)δ8.18(s，1H)，7.34(s，1H)，7.27-7.21(m，1H)，7.02-6.97(m，1H)，6.93-6.89(m，1H)，6.83(d，J＝7.6Hz，1H)，6.65(s，1H)，6.08(s，2H)，4.41(t，J＝7.2Hz，2H)，3.07(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺490.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- [2- (3-fluoro-phenyl) -ethyl]-3H-purin-6-ylamine: the yield is 17 percent,¹H NMR(DMSO-d₆)δ8.10(bs，1H)，7.50-7.26(m，3H)，7.10-7.00(m，2H)，6.93(d，J＝7.6Hz，1H)，6.16(bs，2H)，4.53(t，J＝6.4Hz，2H)，3.201(t，J＝6.4Hz，2H)；LC-MS[M+H]⁺490.0。

examples 111 and 112

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 4- (2-chloro-ethyl) -2-ethoxy-1-methoxy-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.32(s，1H)，7.03(d，J＝9.2Hz，1H)，6.88(dd，J＝8.8，2.8Hz，1H)，6.76(d，J＝8.41H)，6.59-6.56(m，2H)，6.48-6.46(m，1H)，4.42(t，J＝6.8Hz，2H)3.95-3.89(m，2H)，3.73(s，3H)，3.65(s，3H)，3.62(s，3H)，2.94(t，J＝6.8Hz，2H)，1.28(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺482.2. 8- (2, 5-dimethoxy-phenylsulfanyl) -3-[2- (3-ethoxy-4-methoxy-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.32(s，1H)，7.24(d，J＝2.8Hz，1H)，7.19-7.18(m，1H)，7.13-7.12(m，1H)，6.82(d，J＝8.40Hz，1H)6.72(d，J＝2.0Hz，1H)，6.56(dd，J＝8.0，2.0Hz，1H)，4.52(t，J＝6.8Hz，2H)3.97-3.92(m，2H)，3.77(s，3H)，3.73(s，3H)，3.69(s，3H)，3.08(t，J＝6.8Hz，2H)，1.29(t，J＝6.8Hz，3H)；LC-MS[M+H]⁺482.2。

examples 113 and 114

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-methyl-2-phenyl-butyl) -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (3-methyl-2-phenyl-butyl) -3H-purin-6-ylamine

The title compound was prepared by an analogous procedure to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (1-chloromethyl-2-methyl-propyl) -benzene. The isomers were separated by preparative HPLC.

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (3-methyl-2-phenyl-butyl) -9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.23(s，1H)，7.15-7.07(m，3H)，7.03(d，J＝9.2Hz，1H)，6.98-6.96(m，2H)，6.87(dd，J＝6.0，3.2Hz，1H)，6.46(d，J＝2.4Hz，1H)4.60-4.47(m，1H)，3.74(s，3H)，3.60(s，3H)，3.17-3.04(m，2H)，1.99-1.94(m，1H)，1.0(d，J＝6.8Hz，3H)，0.92(d，J＝6.4Hz，3H)；LC-MS[M+H]⁺450.2. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (3-methyl-2-phenyl-butyl) -3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.06(s，1H)，7.23-7.14(m，5H)，7.09-7.04(m，2H)，4.79-4.75(m，1H)，4.54-4.48(m，2H)，3.8(s，3H)，3.74(s，3H)，3.17-3.13(m，1H)，2.0-1.96(m，1H)，1.03(d，J＝6.8Hz，3H)，0.718(d，J＝6.4Hz，3H)；LC-MS[M+H]⁺450.2。

examples 115 and 116

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2, 5-dimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2, 5-dimethyl-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 2- (2-chloro-ethyl) -1, 4-dimethyl-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2, 5-dimethyl-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.36(s，1H)，7.06-7.01(m，2H)，6.93-6.88(m，2H)，6.71(s，1H)，6.59(d，J＝2.8Hz，1H)，4.33(t，J＝7.6Hz，2H)，3.75(s，3H)，3.63(s，3H)，2.92(t，J＝7.6Hz，2H)，2.21(s，3H)，2.17(s，3H)；LC-MS[M+H]⁺436.2. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2, 5-dimethyl-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.43(s，1H)，7.25(s，1H)，7.16(s，1H)，7.04(d，J＝8.0Hz，2H)，6.96-6.94(m，1H)，6.84(s，1H)，4.44(t，J＝7.6Hz，2H)，3.76(s，3H)，3.73(s，3H)，3.10(t，J＝7.6Hz，2H)，2.19(s，3H)，2.17(s，3H)；LC-MS[M+H]⁺436.2。

examples 117 and 118

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 4- (2-chloro-ethyl) -2-ethoxy-1-methoxy-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3] ]Dioxol-5-ylsulfanyl) -9- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl]-9H-purin-6-ylamine: LC-MS [ M + H ]]⁺546.0. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -3- [2- (3-ethoxy-4-methoxy-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.25(s，1H)，7.50(s，1H)，7.38(8，1H)，6.80(d，J＝8.4Hz，1H)，6.69(d，J＝1.6Hz，1H)，6.55(dd，J＝8.4，1.6Hz，1H)，6.17(s，2H)，4.51(t，J＝7.2Hz，2H)，3.96-3.91(m，2H)，3.68(s，3H)，3.09(t，J＝7.2Hz，2H)，1.31-1.27(m，3H)；LC-MS[M+H]⁺546.05。

examples 119 and 120

9- [2- (4-chloro-phenyl) -3-methyl-butyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (4-chloro-phenyl) -3-methyl-butyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by an analogous procedure to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1-chloro-4- (1-chloromethyl-2-methyl-propyl) -benzene. The isomers were separated by preparative HPLC.

9- [2- (4-chloro-phenyl) -3-methyl-butyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.25(s，1H)，7.16-7.15(m，2H)，7.04-6.99(m，2H)，6.88(s，2H)，6.44(s，1H)，4.52(d，J＝6.2Hz，2H)，3.75(s，3H)，3.61(s，3H)，3.06(m，1H)，1.98(s，1H)，1.01(d，J＝5.6Hz，3H)，0.67(d，J＝6.0Hz，3H)；LC-MS[M+H]⁺484.1. 3- [2- (4-chloro-phenyl) -3-methyl-butyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine: LC-MS [ M + H ]]⁺484.1。

Example 121

9- [2- (2, 4-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-chloro-ethyl) -2, 4-difluoro-benzene. The compound was purified by preparative HPLC. LC-MS [ M + H ] ]⁺444.1。

Examples 122 and 123

9- [2- (2-chloro-6-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (2-chloro-6-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1-chloro-2- (2-chloro-ethyl) -3-fluoro-benzene. The isomers were separated by preparative HPLC. 9- [2- (2-chloro-6-fluoro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.23(s，1H)，7.30-7.21(m，2H)，7.13-7.08(m，1H)，7.08(d，J＝3.2Hz，1H)，6.86(dd，J＝9.2，3.2Hz，1H)，6.53(d，J＝3.2Hz，1H)，4.48(t，J＝6.6Hz，2H)，3.73(s，3H)，3.62(s，3H)，3.30(t，J＝6.0Hz，2H)；LC-MS[M+H]⁺460.1. 3- [2- (2-chloro-6-fluoro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.37(s，1H)，7.36-7.26(m，2H)，7.19-7.15(m，3H)，7.11-7.09(m，1H)，7.57(t，J＝6.4Hz，2H)，3.75(s，3H)，3.73(s，3H)，3.34(t，J＝6.0Hz，2H)；LC-MS[M+H]⁺486.1。

examples 124 and 125

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2, 5-dimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2, 5-dimethyl-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 2- (2-chloro-ethyl) -1, 4-dimethyl-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3] ]Dioxol-5-ylsulfanyl) -9- [2- (2, 5-dimethyl-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.30(s，1H)，7.37(s，1H)，7.01(d，J＝7.6Hz，1H)，6.84(d，J＝7.6Hz，1H)，6.74(s，1H)，6.70(s，1H)，6.09(s，2H)，4.33(t，J＝7.6Hz，2H)，3.20(t，J＝7.6Hz，2H)，2.21(s，3H)，2.17(s，3H)；LC-MS[M+H]⁺500.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- [2- (2, 5-dimethyl-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.43(s，1H)，7.50(s，1H)，7.41(s，1H)，7.04(d，J＝7.6Hz，1H)，6.95-6.93(m，1H)，6.85(s，1H)，6.18(s，2H)，4.41(t，J＝7.6Hz，2H)，3.12(t，J＝8.0Hz，2H)，2.19(s，3H)，2.16(s，3H)；LC-MS[M+H]⁺500.0。

examples 126 and 127

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (3-methyl-2-phenyl-butyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (3-methyl-2-phenyl-butyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1-chloro-4- (1-chloromethyl-2-methyl-propyl) -benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (3-methyl-2-phenyl-butyl) -9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.14(s，1H)，7.13-7.07(m，3H)，7.00-6.98(m，2H)，6.56-6.52(m，2H)，6.08(s，2H)，4.53-4.44(m，2H)，3.17-3.13(m，1H)，1.99-1.97(m，1H)，1.04(d，J＝6.8Hz，3H)，0.70(d，J＝6.8Hz，3H)；LC-MS[M+H]⁺514.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (3-methyl-2-phenyl-butyl) -3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.0(s，1H)，7.39(s，1H)，7.24-7.19(m，3H)，7.18-7.11(m，1H)，7.09-7.02(m，2H)，6.12(s，2H)，4.75-4.71(m，1H)，4.50-4.43(m，1H)，3.25-3.19(m，1H)，1.98-1.90(m，1H)，1.02(d，J＝6.8Hz，3H)，0.710(d，J＝6.8Hz，3H)；LC-MS[M+H]⁺514.0。

examples 128 and 129

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2, 6-dichloro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2, 6-dichloro-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1, 3-dichloro-2- (2-chloro-ethyl) -benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -9- [2- (2, 6-dichloro-phenyl) -ethyl]-9H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.23(s，1H)，7.36-7.34(m，2H)，7.28-7.24(m，1H)，7.18(s，1H)，6.81(s，1H)，6.09(s，2H)，4.64(t，J＝6.4Hz，2H)，3.52(t，J＝6.4Hz，2H)；LC-MS[M+H]⁺539.9. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -3- [2- (2, 6-dichloro-phenyl) -ethyl]-3H-purin-6-ylamine, LC-MS [ M + H]⁺539.9。

Examples 130 and 131

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2-chloro-6-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2-chloro-6-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1-chloro-2- (2-chloro-ethyl) -3-fluoro-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio-9- [2- (2-chloro-6-fluoro-phenyl) -ethyl ]-9H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.24(s，1H)，7.32-7.27(m，1H)，7.22-7.20(m，2H)，7.07-7.03(m，1H)，6.82(s，1H)，6.10(s，2H)，4.60(t，J＝8.0Hz，2H)，3.41(t，J＝6.4Hz，2H)；LC-MS[M+H]⁺523.9. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -3- [2- (2-chloro-6-fluoro-phenyl) -ethyl]-3H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.34(s，1H)，7.36-7.29(m，2H)，7.26-7.23(m，2H)，7.09-7.05(m，1H)，6.17(s，2H)，4.68(t，J＝6.8Hz，2H)，3.46(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺523.9。

Examples 132 and 133

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3, 5-dimethyl-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3, 5-dimethyl-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-chloro-ethyl) -3, 5-dimethyl-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3, 5-dimethyl-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.33(s，1H)，7.05(d，J＝8.8Hz，1H)，6.90(dd，J＝6.0，3.2Hz，1H)，6.60(d，J＝3.2Hz，1H)，6.82(s，1H)，6.65(s，2H)，4.37(t，J＝7.2Hz，2H)，3.75(s，3H)，3.63(s，3H)，2.87(t，J＝7.2Hz，2H)，2.18(s，6H)；LC-MS[M+H]⁺436.2. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3, 5-dimethyl-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.42(s，1H)，7.25(d，J＝2.8Hz，1H)，7.19-7.17(m，1H)，7.11-7.09(m，1H)，6.87(s，1H)，6.87(s，2H)，4.49(t，J＝6.4Hz，2H)，3.77(s，3H)，3.73(s，3H)，3.07(t，J＝6.4Hz，2H)，2.21(s，6H)；LC-MS[M+H]⁺436.2。

example 134

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyridin-4-yl-ethyl) -9H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 4- (2-chloro-ethyl) -pyridine. The compound was purified by preparative HPLC. ¹H NMR(CD₃OD)δ8.68(d，J＝6.4Hz，2H)，8.27(s，1H)，7.84(d，J＝6.4Hz，2H)，7.06-6.98(m，3H)，4.75(t，J＝6.8Hz，2H)，3.75(s，3H)，3.74(s，3H)，3.53(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺409.1。

Examples 135 and 136

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyridin-2-yl-ethyl) -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-pyridin-2-yl-ethyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 2- (2-bromo-ethyl) -pyridine. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pyridin-2-yl-ethyl) -9H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.63-8.60(m，2H)，8.22(s，1H)，8.18(dt，J＝8.0，2.0Hz，1H)，7.77(dd，J＝8.0，2.0Hz，1H)，7.07-6.99(m，3H)，4.69(t，J＝6.8Hz，2H)，3.75(s，3H)，3.74(s，3H)，3.41(t，J＝6.8Hz，2H)；TOF LC-MS[M+H]⁺409.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-pyridin-2-yl-ethyl) -3H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.70-8.50(m，2H)，8.40(s，1H)，8.11(d，J＝7.6Hz，1H)，7.72(m，1H)，7.29(dd，J＝6.8，1.2Hz，1H)，7.23-7.17(m，2H)，4.69(t，J＝7.2Hz，2H)，3.81(s，3H)，3.80(s，3H)，3.41(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺409.1。

examples 137 and 138

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-iodo-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-iodo-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-iodo-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-iodo-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.23(s，1H)，7.56-7.52(m，1H)，7.41(s，1H)，7.04-7.01(m，3H)，6.88(d，J＝8.8Hz，1H)，6.53(s，1H)，4.39(t，J＝6.8Hz，2H)，3.76(s，3H)，3.62(s，3H)，2.97(t，J＝6.8Hz，2H)；LC-MS[M+H]+534.0. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (3-iodo-phenyl) -ethyl ]-3H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.21(s，1H)，7.60(d，J＝8.4Hz，1H)，7.49(s，1H)，7.30(s，1H)，7.20-7.14(m，3H)，7.06(t，J＝7.6Hz，1H)，4.58(t，J＝7.2Hz，2H)，3.82(s，3H)，3.81(s，3H)，3.18(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺534.0。

examples 139 and 140

9- [2- (2-chloro-4-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (2-chloro-4-fluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-chloro-4-fluoro-benzene. The isomers were separated by preparative HPLC. 9- [2- (2-chloro-4-fluoro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.21(s，1H)，7.17(dd，J＝8.8，2.8Hz，1H)，7.08-6.92(m，5H)，4.59(t，J＝6.8Hz，2H)，3.73(s，6H)，3.31(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺460.1. 3- [2- (2-chloro-4-fluoro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.19(s，1H)，7.28(s，1H)，7.21-7.18(m，4H)，7.03-6.97(m，1H)，4.63(t，J＝6.8Hz，2H)，3.81(s，3H)，3.80(s，3H)，3.36(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺460.1。

examples 141 and 142

9- [2- (2-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (2-bromo-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

Prepared by analogous procedure as examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1-bromo-2- (2-bromo-ethyl) -benzeneThe title compound. The isomers were separated by preparative HPLC. 9- [2- (2-bromo-phenyl) -ethyl ]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine:¹H NMR(DMSO-d6)δ8.27(s，1H)，7.54(dd，J＝8.0，1.2Hz，1H)，7.22(t，J＝7.2Hz，1H)，7.14(t，J＝7.6Hz，1H)，7.00(t，J＝7.8Hz，1H)，6.99(d，J＝8.8Hz，1H)，6.86(dd，J＝8.8，2.8Hz，1H)，6.51(s，1H)，4.48(t，J＝6.8Hz，2H)，3.72(s，3H)，3.61(s，3H)，3.18(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺486.1. 3- [2- (2-bromo-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.27(s，1H)，7.54(d，J＝7.6Hz，1H)，7.30-7.25(m，2H)，7.19-7.14(m，4H)，4.65(t，J＝6.8Hz，2H)，3.81(s，3H)，3.80(s，3H)，3.39(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺486.1。

examples 143 and 144

9- [2- (3, 5-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (3, 5-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3, 5-difluoro-benzene. The isomers were separated by preparative HPLC. 9- [2- (3, 5-difluoro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.28(s，1H)，7.07-7.03(m，3H)，6.81-6.72(m，3H)，4.58(t，J＝6.8Hz，2H)，3.75(s，3H)，3.74(s，3H)，3.20(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺444.1. 3- [2- (3, 5-difluoro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.28(s，1H)，7.31(s，1H)，7.20-7.19(m，2H)，6.90-6.80(m，3H)，4.61(t，J＝7.2Hz，2H)，3.81(s，3H)，3.80(s，3H)，3.26(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺444.1。

examples 145 and 146

9- [2- (2, 3-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (2, 3-difluoro-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2, 3-difluoro-benzene. The isomers were separated by preparative HPLC. 9- [2- (2, 3-difluoro-phenyl) -ethyl ]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.26(s，1H)，7.14-7.10(m，1H)，7.03-6.98(m，4H)，6.85-6.81(m，1H)，4.61(t，J＝6.8Hz，2H)，3.75(s，3H)，3.74(s，3H)，3.30(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺444.1. 3- [2- (2, 3-difluoro-phenyl) -ethyl]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.24(s，1H)，7.29(dd，J＝2.8，0.8Hz，1H)，7.19-7.13(m，3H)，7.10-7.05(m，1H)，6.94(dt，J＝7.6，1.2Hz，1H)，4.64(t，J＝6.8Hz，2H)，3.81(s，3H)，3.80(s，3H)，3.34(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺444.1。

examples 147 and 148

8- (6-bromo-1, 3-benzodioxol-5-ylsulfanyl) -9- [2- (2-fluoro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- [2- (2-fluoro-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-fluoro-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- [2- (2-fluoro-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.17(s，1H)，7.33(s，1H)，7.25-7.22(m，1H)，7.11-7.02(m，3H)，6.65(s，1H)，6.08(s，2H)，4.41(t，J＝7.2Hz，2H)，3.10(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺489.9. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- [2- (2-fluoro-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.19(s，1H)，7.37(s，1H)，7.36(s，1H)，7.30-7.22(m，1H)，7.14-7.00(m，3H)，6.16(s，2H)，4.62(t，J＝6.8Hz，2H)，3.29(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺489.9。

examples 149 and 150

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2-bromo-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2-bromo-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1-bromo-2- (2-bromo-ethyl) -benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- [2- (2-bromo-phenyl) -ethyl]-9H-purin-6-ylamine：¹H NMR(CD₃OD)δ8.22(s，1H)，7.52(dd，J＝8.0，1.2Hz，1H)，7.21-7.11(m，3H)，7.04(dd，J＝7.8，1.6Hz，1H)，6.95(s，1H)，6.06(s，2H)，4.60(t，J＝6.8Hz，2H)，3.31(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺550.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- [2- (2-bromo-phenyl) -ethyl]-3H-purin-6-ylamine:¹HNMR(CD₃OD)δ8.16(s，1H)，7.52(dd，J＝8.0，1.6Hz，1H)，7.37(s，1H)，7.36(s，1H)，7.30-7.23(m，1H)，7.17-7.14(m，2H)，6.16(s，2H)，4.64(t，J＝6.8Hz，2H)，3.38(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺550.0。

examples 151 and 152

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-pyridin-3-yl-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-pyridin-3-yl-ethyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 3- (2-chloro-ethyl) -pyridine. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (2-pyridin-3-yl-ethyl) -9H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.75-7.74(m，2H)，8.38(d，J＝8.0Hz，1H)，8.27(s，1H)，7.93(t，J＝8.0Hz，1H)，7.26(s，1H)，7.15(s，1H)，6.09(s，2H)，4.70(t，J＝6.8Hz，2H)，3.49(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺473.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (2-pyridin-3-yl-ethyl) -3H-purin-6-ylamine: ¹H NMR(CD₃OD)δ8.65-7.84(m，1H)，8.43(s，1H)，8.17(d，J＝8.0Hz，1H)，7.90(s，1H)，7.76(m，1H)，7.38(s，1H)，7.36(s，1H)，6.16(s，2H)，4.70(t，J＝7.2Hz，2H)，3.43(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺473.0。

Examples 153 and 154

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3-iodo-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (3-iodo-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-iodo-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -9- [2- (3-iodo-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.18(s，1H)，7.58(dd，J＝7.6，1.2Hz，1H)，7.52(s，1H)，7.15(s，1H)，7.07(d，J＝8.0Hz，1H)，7.01(t，J＝7.6，1.2Hz，1H)，7.00(s，1H)，6.07(s，2H)，4.46(t，J＝7.6Hz，2H)，3.08(t，J＝7.6Hz，2H)；TOF LC-MS[M+H]⁺597.9. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -3- [2- (3-iodo-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(CDCl₃)δ7.64-7.58(m，2H)，7.46(s，1H)，7.19(s，1H)，7.18(s，1H)，7.04-6.98(m，1H)，6.94-6.89(m，1H)，6.08(s，2H)，4.48(t，J＝9.2Hz，2H)，3.18(t，J＝9.2Hz，2H)；TOF LC-MS[M+H]⁺597.9。

examples 155 and 156

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-o-tolyl-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-o-tolyl-ethyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-methyl-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3] ]Dioxol-5-ylsulfanyl) -9- (2-o-tolyl-ethyl) -9H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.27(s，1H)，7.24(s，1H)，7.15(d，J＝7.2Hz，1H)，7.11(dt，J＝7.2，1.2Hz，1H)，7.03(s，1H)，7.01(dt，J＝7.2，1.6Hz，1H)，6.87(d，J＝7.6Hz，1H)，6.07(s，2H)，4.51(t，J＝7.2Hz，2H)，3.20(t，J＝7.2Hz，2H)，2.37(s，3H)；TOF LC-MS[M+H]⁺486.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (2-o-tolyl-ethyl) -3H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.18(s，1H)，7.37(s，1H)，7.36(s，1H)，7.17-7.09(m，2H)，7.04(dt，J＝7.2，1.6Hz，1H)，6.93(d，J＝7.2Hz，1H)，6.16(s，2H)，4.54(t，J＝7.2Hz，2H)，3.23(t，J＝7.2Hz，2H)，2.26(s，3H)；TOF LC-MS[M+H]⁺486.0。

examples 157 and 158

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-naphthalen-1-yl-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-naphthalen-1-yl-ethyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamineAnd 1- (2-bromo-ethyl) -naphthalene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (2-naphthalen-1-yl-ethyl) -9H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.14(s，1H)，8.09(d，J＝7.6Hz，1H)，7.88(d，J＝8.0Hz，1H)，7.79(d，J＝8.0Hz，1H)，7.58(dt，J＝8.4，1.6Hz，1H)，7.52(dt，J＝8.4，1.6Hz，1H)，7.36(t，J＝8.0Hz，1H)，7.22(d，J＝7.6Hz，1H)，7.13(s，1H)，6.95(s，1H)，6.06(s，2H)，4.62(t，J＝7.2Hz，2H)，3.60(t，J＝7.2Hz，2H)；TOFLC-MS[M+H]⁺522.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (2-naphthalen-1-yl-ethyl) -3H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.33(s，1H)，8.18(d，J＝8.0Hz，1H)，8.28-7.83(m，2H)，7.57-7.39(m，4H)，7.35-7.32(m，2H)，6.13(s，2H)，4.73(t，J＝8.0Hz，2H)，3.77(t，J＝8.0Hz，2H)；TOF LC-MS[M+H]⁺522.0。

Examples 159 and 160

1- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) -ethanone and 1- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) -ethanone

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- [4- (2-chloro-ethyl) -phenyl]-ethanone the title compound was prepared. The isomers were separated by preparative HPLC. 1- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -purin-9-yl]-ethyl } -phenyl) -ethanone:¹H NMR(CDCl₃)δ8.18(s，1H)，7.98(d，J＝8.4Hz，2H)，7.24(d，J＝8.4Hz，2H)，7.13(s，1H)，6.96(s，1H)，6.06(s，2H)，4.53(t，J＝7.6Hz，2H)，3.24(t，J＝7.6Hz，2H)，2.59(s，3H)；TOF LC-MS[M+H]⁺514.05. 1- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -purin-3-yl]-ethyl } -phenyl) -ethanone:¹H NMR(CDCl₃)δ7.89(d，J＝8.0Hz，2H)，7.61(s，1H)，7.25(s，1H)，7.19(s，1H)，7.11(d，J＝8.0Hz，2H)，6.11(s，2H)，4.54(t，J＝7.2Hz，2H)，3.30(t，J＝7.2Hz，2H)，2.59(s，3H)；TOF LC-MS[M+H]⁺514.05。

examples 161 and 162

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2, 3-difluoro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-1, 3-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2, 3-difluoro-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2, 3-difluoro-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- [2- (2, 3-difluoro-phenyl) -ethyl ]-9H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.30(s，1H)，7.07(s，1H)，7.03(dt，J＝7.6，1.6Hz，1H)，6.93-6.90(m，1H)，6.80(s，1H)，6.70(dt，J＝7.6，1.6Hz，1H)，6.00(s，2H)，4.50(t，J＝6.8Hz，2H)，3.21(t，J＝6.8Hz，2H)；TOF LC-MS[M+H]⁺508.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- [2- (2, 3-difluoro-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(CDCl₃)δ7.70(s，1H)，7.24(s，1H)，7.19(s，1H)，7.15-7.07(m，1H)，7.01-6.95(m，1H)，6.63(dt，J＝8.0，1.6Hz，1H)，6.10(s，2H)，4.54(t，J＝6.8Hz，2H)，3.30(t，J＝6.8Hz，2H)；TOF LC-MS[M+H]⁺508.0。

examples 163 and 164

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-p-tolyl-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-p-tolyl-ethyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -4-methyl-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (2-p-tolyl-ethyl) -9H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.16(s，1H)，7.14(s，1H)，7.09(d，J＝7.6Hz，2H)，7.00(d，J＝7.6Hz，2H)，6.99(s，1H)，6.07(s，2H)，4.47(t，J＝7.6Hz，2H)，3.11(t，J＝7.6Hz，2H)，2.31(s，3H)；TOF LC-MS[M+H]⁺486.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (2-p-tolyl-ethyl) -3H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.26(s，1H)，7.40(s，1H)，7.33(s，1H)，7.09(d，J＝7.6Hz，2H)，7.02(d，J＝7.6Hz，2H)，6.19(s，2H)，4.61(t，J＝7.2Hz，2H)，3.21(t，J＝7.2Hz，2H)，2.27(s，3H)；TOFLC-MS[M+H]⁺486.0。

examples 165 and 166

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3-trifluoromethyl-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (3-trifluoromethyl-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-trifluoromethyl-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- [2- (3-trifluoromethyl-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.16(s，1H)，7.54(d，J＝8.0Hz，1H)，7.41(t，J＝7.2Hz，2H)，7.32(d，J＝7.6Hz，1H)，7.15(s，1H)，7.04(s，1H)，6.08(s，2H)，4.53(t，J＝7.6Hz，2H)，3.23(t，J＝7.6Hz，2H)；TOF LC-MS[M+H]⁺540.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- [2- (3-trifluoromethyl-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(CDCl₃)δ7.71(s，1H)，7.56(d，J＝8.0Hz，1H)，7.43(t，J＝7.6Hz，1H)，7.38(s，1H)，7.25(s，1H)，7.20(s，1H)，7.18(d，J＝7.6Hz，1H)，6.10(s，2H)，4.53(t，J＝7.2Hz，2H)，3.31(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺540.0。

examples 167 and 168

9- (2-benzo [1, 3] dioxol-5-yl-ethyl) -8- (2, 5-dimethoxy-phenylthio) -9H-purin-6-ylamine and 3- (2-benzo [1, 3] dioxol-5-yl-ethyl) -8- (2, 5-dimethoxy-phenylthio) -3H-purin-6-ylamine

Prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 5- (2-bromo-ethyl) -benzo [1, 3]]-dioxoles to prepare the title compound. By preparative HPLCThe isomers are isolated. 9- (2-benzo [1, 3]]Dioxol-5-yl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: ¹H NMR (acetone-d)₆)δ8.39(s，1H)，7.04(d，J＝8.8Hz，1H)，6.94(dd，J＝8.8，3.2Hz，1H)，6.83(d，J＝3.3Hz，1H)，6.90(d，J＝8.0Hz，1H)，6.68(s，1H)，6.54(dd，J＝8.0，1.6Hz，1H)，5.94(s，2H)，4.54(t，J＝7.2Hz，2H)，3.79(s，3H)，3.71(s，3H)，3.08(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺452.1. 3- (2-benzo [1, 3]]Dioxol-5-yl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.26(s，1H)，7.34(d，J＝2.8Hz，1H)，7.22-7.05(m，2H)，6.74-6.70(m，2H)，6.53(dd，J＝8.0，2.0Hz，1H)，5.97(s，2H)，4.58(t，J＝7.2Hz，2H)，3.81(s，3H)，3.79(s，3H)，3.16(t，J＝7.2Hz，2H)；TOFLC-MS[M+H]⁺452.1。

Examples 169 and 170

9- (2-cyclohexyl-ethyl) -8- (2, 5-dimethoxyphenyl-thio) -9H-purin-6-ylamine and 3- (2-cyclohexyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (2-bromo-ethyl) -cyclohexane. The isomers were separated by preparative HPLC. 9- (2-cyclohexyl-ethyl) -8- (2, 5-dimethoxyphenyl-sulfanyl) -9H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.24(s，1H)，6.96(d，J＝9.2Hz，1H)，6.84(dd，J＝9.2，2.8Hz，1H)，6.80(d，J＝2.8Hz，1H)，4.26(t，J＝7.6Hz，2H)，3.81(s，3H)，3.67(s，3H)，2.09-2.07(m，2H)，1.79-1.70(m，1H)，1.68-1.60(m，4H)，0.99-0.82(m，6H)；TOF LC-MS[M+H]⁺414.2。3-(2-cyclohexyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.04(s，1H)，7.20(d，J＝2.8Hz，1H)，7.02(dd，J＝9.2，2.8Hz，1H)，6.93(d，J＝9.2Hz，1H)，4.31(t，J＝7.6Hz，2H)，3.794(s，3H)，3.79(s，3H)，1.9-1.6(m，3H)，1.38-1.20(m，4H)，0.99-0.82(m，6H)；TOF LC-MS[M+H]⁺414.2。

examples 171 and 172

9- (2-Biphenyl-4-yl-ethyl) -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 3- (2-Biphenyl-4-yl-ethyl) -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 4- (2-bromo-ethyl) -biphenyl the title compound was prepared. The isomers were separated by preparative HPLC. 9- (2-Biphenyl-4-yl-Ethyl) -8- (6-bromo-benzo [1, 3] ]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.19(s，1H)，7.58-7.51(m，4H)，7.46-7.42(m，1H)，7.30-7.28(m，3H)，7.14(s，1H)，6.99(d，J＝2.8Hz，2H)，6.04(s，2H)，4.54(t，J＝7.6Hz，2H)，3.20(t，J＝7.6Hz，2H)；TOF LC-MS[M+H]⁺548.0. 3- (2-Biphenyl-4-yl-Ethyl) -8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3H-purin-6-ylamine:¹H NMR(CDCl₃)δ7.63(s，1H)，7.58-7.51(m，4H)，7.46-7.42(m，2H)，7.39-7.36(m，1H)，7.25(s，1H)，7.20(s，1H)，7.06(d，J＝8.4Hz，2H)，6.09(s，2H)，4.55(t，J＝6.8Hz，2H)，3.26(t，J＝6.8Hz，2H)；TOF LC-MS[M+H]⁺548.0。

examples 173 and 174

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-cyclohexyl-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-cyclohexyl-ethyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and (2-bromo-ethyl) -cyclohexane the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (2-cyclohexyl-ethyl) -9H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.19(s，1H)，7.14(s，1H)，7.10(s，1H)，6.06(s，2H)，4.28(t，J＝7.6Hz，2H)，1.84-1.60(m，7H)，1.30-1.18(m，4H)，0.99-0.80(m，2H)；TOF LC-MS[M+H]⁺487.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (2-cyclohexyl-ethyl) -3H-purin-6-ylamine:¹H NMR(CDCl₃)δ8.03(s，1H)，7.22(s，1H)，7.17(s，1H)，6.08(s，2H)，4.33(t，J＝7.2Hz，2H)，1.84-1.80(m，2H)，1.79-1.70(m，5H)，1.30-1.18(m，4H)，0.99-0.80(m，2H)；TOFLC-MS[M+H]⁺487.0。

examples 175 and 176

4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -benzenesulfonic acid and 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -benzenesulfonic acid

From 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-yl by a procedure analogous to examples 1 and 2 Amine and 4- (2-bromo-ethyl) -benzenesulfonic acid the title compound was prepared. The isomers were separated by preparative HPLC. 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl]-ethyl } -benzenesulfonic acid:¹H NMR(DMSO-d6)δ8.40(s，1H)，7.47(d，J＝8.0Hz，2H)，7.06(d，J＝9.2Hz，1H)，7.01(d，J＝8.0Hz，2H)，6.93(dd，J＝9.2，3.2Hz，1H)，6.75(d，J＝3.2Hz，1H)，4.45(t，J＝7.2Hz，2H)，3.73(s，3H)，3.65(s，3H)，3.01(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺488.1. 4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl]-ethyl } -benzenesulfonic acid:¹H NMR(DMSO-d6)δ8.24(s，1H)，7.56(d，J＝8.4Hz，2H)，7.30(s，1H)，7.23-7.16(m，2H)，7.10(d，J＝8.4Hz，2H)，4.59(t，J＝7.2Hz，2H)，3.79(s，3H)，3.77(s，3H)，3.21(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺488.1。

examples 177 and 178

2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -1- (2, 4-dichloro-phenyl) -ethanol and 2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -1- (2, 4-dichloro-phenyl) -ethanol

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 2-chloro-1- (2, 4-dichloro-phenyl) -ethanol the title compound was prepared. The isomers were separated by preparative HPLC. 2- [ 6-amino-8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -purin-9-yl]-1- (2, 4-dichloro-phenyl) -ethanol:¹h NMR (acetone-d)₆)δ8.13(s，1H)，7.66(d，J＝8.2Hz，1H)，7.43(d，J＝2.0Hz，1H)，7.39(dd，J＝8.2，2.0Hz，1H)，7.23(s，1H)，7.11(s，1H)，6.10(s，2H)，5.51(t，J＝8.0Hz，1H)，4.39(d，J＝8.0Hz，2H)；TOF LC-MS[M+H]⁺555.9. 2- [ 6-amino-8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -purin-3-yl]-1- (2, 4-dichloro-phenyl) -ethanol:¹h NMR (acetone-d) ₆)δ8.53(s，1H)，7.62(d，J＝8.2Hz，1H)，7.48(d，J＝2.0Hz，1H)，7.39(dd，J＝8.2，2.0Hz，1H)，7.33(s，1H)，7.30(s，1H)，6.22(s，2H)，5.51(dd，8.4，3.2Hz，1H)，4.74(dd，J＝13.2，3.2Hz，1H)，4.37(dd，J＝13.2，3.2Hz，1H)；TOF LC-MS[M+H]⁺555.9。

Examples 179 and 180

9- (2-cyclohexyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- (2-cyclohexyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (2-bromo-1-cyclohexyl-ethyl) -benzene. The isomers were separated by preparative HPLC. 9- (2-cyclohexyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.33(s，1H)，7.16-7.03(m，6H)，6.94(dd，J＝8.8，2.8Hz，1H)，6.79(d，J＝2.8Hz，1H)，4.75(dd，J＝9.2，6.0Hz，1H)，4.65(dd，J＝9.2，6.0Hz，1H)，3.79(s，3H)，3.70(s，3H)，3.30-3.20(m，1H)，2.07-2.04(m，2H)，1.82-1.78(m，1H)，1.64-1.54(m，2H)，1.36-1.27(m，2H)，1.20-1.13(m，2H)，0.9-0.84(m，2H)；LC-MS[M+H]⁺490.2. 3- (2-cyclohexyl-2-phenyl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ7.81(s，1H)，7.37(d，J＝2.8Hz，1H)，7.26-7.10(m，7H)，4.92(dd，J＝9.2，4.4Hz，1H)，4.42(dd，J＝9.2，2.8Hz，1H)，3.87(s，3H)，3.83(s，3H)，3.79(m，1H)，2.0-1.0(m，11H)；LC-MS[M+H]⁺490.2。

Examples 181 and 182

9- (2-Biphenyl-4-yl-Ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- (2-Biphenyl-4-yl-Ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 4- (2-bromo-ethyl) -biphenyl. The isomers were separated by preparative HPLC. 9- (2-biphenyl-4-yl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine: ¹H NMR (acetone-d)₆)δ8.28(s，1H)，7.63(d，J＝8.4Hz，2H)，7.56(d，J＝8.4Hz，2H)，7.46(t，J＝8.0Hz，2H)，7.35(t，J＝8.0Hz，1H)，7.23(d，J＝8.8Hz，2H)，6.88(dd，J＝8.8，2.8Hz，1H)，6.70(d，J＝2.8Hz，1H)，4.54(t，J＝7.2Hz，2H)，3.82(s，3H)，3.64(s，3H)，3.15(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺484.1. 3- (2-biphenyl-4-yl-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.27(s，1H)，7.63(d，J＝8.0Hz，2H)，7.59(d，J＝8.4Hz，2H)，7.46(d，J＝8.4Hz，2H)，7.37(d，J＝7.2Hz，1H)，7.35(t，J＝8.0Hz，1H)，7.24(d，J＝8.4Hz，2H)，7.10(d，J＝9.2Hz，1H)，7.06(dd，J＝9.2，2.8Hz，1H)，4.66(t，J＝7.6Hz，2H)，3.82(s，3H)，3.79(s，3H)，3.12(t，J＝7.6Hz，2H)；TOF LC-MS[M+H]⁺484.1。

Examples 183 and 184

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-trifluoromethyl-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-trifluoromethyl-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-trifluoromethyl-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-trifluoromethyl-phenyl) -ethyl]-9H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.36(s，1H)，7.72(d，J＝8.0Hz，1H)，7.52(t，J＝7.6Hz，1H)，7.45(t，J＝7.6Hz，1H)，7.20(d，J＝7.6Hz，1H)，7.02(d，J＝9.2Hz，1H)，6.92(dd，J＝9.2，2.8Hz，1H)，6.81(d，J＝2.8Hz，1H)，4.63(t，J＝7.2Hz，2H)，3.78(s，3H)，3.70(s，3H)，3.37(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺476.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-trifluoromethyl-phenyl) -ethyl]-3H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.38(s，1H)，7.72(d，J＝8.0Hz，1H)，7.56(t，J＝7.6Hz，1H)，7.48(t，J＝7.6Hz，1H)，7.32(d，J＝2.4Hz，1H)，7.27(d，J＝7.6Hz，1H)，7.13-7.07(m，2H)，4.64(t，J＝7.2Hz，2H)，3.80(s，3H)，3.79(s，3H)，3.44(t，J＝7.2Hz，2H)；TOF LC-MS[M+H]⁺476.1。

Examples 185 and 186

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-dimethylamino-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (4-dimethylamino-phenyl) -ethyl ] -3H-purin-6-ylamine

By means of analogy to the implementationThe procedures of examples 1 and 2 were carried out from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and [4- (2-bromo-ethyl) -phenyl ]-dimethyl-amine to prepare the title compound. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (4-dimethylamino-phenyl) -ethyl]-9H-purin-6-ylamine:¹HNMR (acetone-d)₆)δ8.43(s，1H)，7.13(d，J＝8.8Hz，2H)，7.07(d，J＝8.8Hz，2H)，7.05(d，J＝8.8Hz，1H)，6.97(dd，J＝8.8，2.8Hz，1H)，6.90(d，J＝2.8Hz，1H)，4.57(t，J＝7.2Hz，2H)，3.78(s，3H)，3.72(s，3H)，3.13(t，J＝7.2Hz，2H)，3.04(s，6H)；TOF LC-MS[M+H]⁺451.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (4-dimethylamino-phenyl) -ethyl]-3H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.27(s，1H)，7.13(dd，J＝2.4，0.8Hz，1H)，7.20-7.04(m，6H)，4.60(t，J＝7.2Hz，2H)，3.81(s，3H)，3.80(s，3H)，3.20(t，J＝7.2Hz，2H)，3.03(s，6H)；TOF LC-MS[M+H]⁺451.1。

Examples 187 and 188

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (4-dimethylamino-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (4-dimethylamino-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and [4- (2-bromo-ethyl) -phenyl]-dimethyl-amine to prepare the title compound. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -9- [2- (4-dimethylamino-phenyl) -ethyl]-9H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.45(s，1H)，7.25(s，1H)，7.13(d，J＝8.8Hz，2H)，7.05(d，J＝8.8Hz，2H)，6.93(s，1H)，6.13(s，2H)，4.58(t，J＝7.2Hz，2H)，3.16(t，J＝7.2Hz，2H)，3.02(s，6H)；TOF LC-MS[M+H]⁺515.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -3- [2- (4-dimethylamino-phenyl) -ethyl ]-3H-purin-6-ylamine:¹h NMR (acetone-d)₆)δ8.24(s，1H)，7.40(s，1H)，7.34(s，1H)，6.96(d，J＝8.4Hz，2H)，6.71(d，J＝8.4Hz，2H)，6.19(s，2H)，4.57(t，J＝7.2Hz，2H)，3.13(t，J＝7.2Hz，2H)，2.91(s，6H)；TOF LC-MS[M+H]⁺515.0。

Examples 189 and 190

8- (2, 5-diethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine and 8- (2, 5-diethoxy-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-diethoxy-phenylsulfanyl) -9H-purin-6-ylamine and (2-bromo-ethyl) -benzene. The isomers were separated by preparative HPLC. 8- (2, 5-diethoxy-phenylsulfanyl) -9-phenethyl-9H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.25(s，1H)，7.26-7.20(m，3H)，7.11-7.07(m，2H)，7.00-6.96(m，3H)，4.55(t，J＝7.2Hz，2H)，4.00-3.91(m，4H)，3.13(t，J＝7.2Hz，2H)，1.35(t，J＝7.2Hz，3H)，1.56(t，J＝6.8Hz，3H)；LC-MS[M+H]⁺436.5. 8- (2, 5-diethoxy-phenylsulfanyl) -3-phenethyl-3H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.12(s，1H)，7.30-7.25(m，4H)，7.16-7.15(m，2H)，7.11-7.08(m，2H)，4.61(t，J＝7.2Hz，2H)，4.08-4.01(m，4H)，3.23(t，J＝7.2Hz，2H)，1.38(t，J＝7.2Hz，3H)，1.21(t，J＝6.8Hz，3H)；LC-MS[M+H]⁺436.5。

examples 191 and 192

9- [2- (2-chloro-phenyl) -ethyl ] -8- (2, 5-diethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (2-chloro-phenyl) -ethyl ] -8- (2, 5-diethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-diethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-chloro-benzene. The isomers were separated by preparative HPLC. 9- [2- (2-chloro-phenyl) -ethyl]-8- (2, 5-diethoxy-phenylsulfanyl) -9H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.25(s，1H)，7.35(dd，J＝8.0，1.2Hz，1H)，7.23(dt，J＝7.6，2.0Hz，1H)，7.15(dt，J＝7.6，1.2Hz，1H)，7.05(dd，J＝7.6，2.0Hz，1H)，6.96-6.94(m，3H)，4.63(t，J＝6.8Hz，2H)，3.99-3.91(m，4H)，3.33(t，J＝6.8Hz，2H)，1.35(t，J＝6.4Hz，3H)，1.17(t，J＝6.4Hz，3H)；LC-MS[M+H]⁺470.5. 3- [2- (2-chloro-phenyl) -ethyl ]-8- (2, 5-diethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹HNMR(CD₃OD)δ8.11(s，1H)，7.36(dd，J＝7.6，2.0Hz，1H)，7.28-7.27(bs，1H)，7.25-7.20(m，2H)，7.18-7.14(m，3H)，4.66(t，J＝7.2Hz，2H)，4.07-4.02(m，4H)，3.41(t，J＝7.2Hz，2H)，1.38(t，J＝6.0Hz，3H)，1.21(t，J＝6.0Hz，3H)；LC-MS[M+H]⁺470.5。

examples 193 and 194

9- [2- (3, 5-dimethoxy-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- [2- (3, 5-dimethoxy-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3, 5-dimethoxy-benzene. The isomers were separated by preparative HPLC. 9- [2- (3, 5-dimethoxy-phenyl-ethyl)]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine:¹HNMR(DMSO-d₆)δ8.33(s，1H)，7.03(d，J＝9.0Hz，1H)，6.91-6.86(m，1H)，6.58(d，J＝2.9Hz，1H)，6.30(t，J＝1.9Hz，1H)，6.17(d，J＝2.2Hz，2H)，4.42(t，J＝7.0Hz，2H)，3.75(s，3H)，3.66(s，6H)，3.20(s，3H)，2.95(t，J＝7.0Hz，2H)；LC-MS[M+H]⁺468.1. 3- [2- (3, 5-dimethoxy-phenyl-ethyl)]-8- (2, 5-dimethoxy-phenylsulfanyl) -3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.37(s，1H)，7.25-7.03(m，3H)，6.37(t，J＝2.1Hz，1H)，6.29(d，J＝2.3Hz，2H)，4.55(t，J＝7.1Hz，2H)，3.78(s，3H)，3.73(s，3H)，3.69(s，6H)，3.10(t，J＝7.1Hz，2H)；LC-MS[M+H]⁺468.1。

examples 195 and 196

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (3, 5-dimethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (3, 5-dimethoxy-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3, 5-dimethoxy-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3] ]Dioxol-5-ylthio) -9- [2- (3, 5-dimethoxy-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.21(s，1H)，7.35(s，1H)，6.20(s，1H)，6.29(t，J＝2.2Hz，1H)，6.18(d，J＝2.2Hz，2H)，6.07(s，2H)，4.39(t，J＝7.2Hz，2H)，3.64(s，6H)，2.97(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺531.0. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylthio) -3- [2- (3, 5-dimethoxy-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.31(s，1H)，7.49(s，1H)，7.39(s，1H)，6.36(t，J＝2.3Hz，1H)，6.27(d，J＝2.2Hz，2H)，6.17(s，2H)，4.52(t，J＝7.2Hz，2H)，3.67(s，6H)，3.10(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺531.0。

examples 197 and 198

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-thiophen-3-yl-ethyl) -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-thiophen-3-yl-ethyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 3- (2-bromo-ethyl) -thiophene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-thiophen-3-yl-ethyl) -9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.26(s，1H)，7.34(dd，J＝1.2，5.1Hz，1H)，7.01(d，J＝9.0Hz，1H)，6.92-6.85(m，2H)，6.73(dd，J＝3.3，1.0Hz，1H)，6.57(d，J＝3.1Hz，1H)，4.41(t，J＝6.8Hz，2H)，3.74(s，3H)，3.61(s，3H)，3.25(t，J＝7.4Hz，2H)；LC-MS[M+H]⁺414.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-thiophen-3-yl-ethyl) -3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.41(s，1H)，7.38(dd，J＝5.1，1.2Hz，1H)，7.26-7.05(m，3H)，6.96-6.93(m，1H)，6.82-6.80(m，1H)，4.57(t，J＝7.1Hz，2H)，3.78(s，3H)，3.73(s，3H)，3.42(t，J＝6.9Hz，2H)；LC-MS[M+H]⁺414.1。

examples 199 and 200

8- (2, 5-dimethoxy-phenylsulfanyl) -9-2-thiophen-2-yl-ethyl) -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-thiophen-2-yl-ethyl) -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 2- (2-bromo-ethyl) -thiophene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9-2-thiophen-2-yl-ethyl) -9H-purin-6-ylamine: ¹H NMR(DMSO-d₆)δ8.35(s，1H)，7.44(dd，J＝4.9，2.9Hz，1H)，7.11-7.02(m，2H)，6.93-6.83(m，2H)，6.62(d，J＝3.0Hz，1H)，4.43(t，J＝6.8Hz，2H)，3.72(s，3H)，3.63(s，3H)，3.02(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺414.1. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- (2-thiophen-2-yl-ethyl) -3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.37(s，1H)，7.51(dd，J＝4.9，2.7Hz，1H)，7.28-7.02(m，4H)，6.98(dd，J＝4.9，1.2Hz，1H)，4.57(t，J＝6.8Hz，2H)，3.78(s，3H)，3.73(s，3H)，3.21(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺414.1。

examples 201 and 202

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-thiophen-3-yl-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-thiophen-3-yl-ethyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 3- (2-bromo-ethyl) -thiophene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (2-thiophen-3-yl-ethyl) -9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.26(s，1H)，7.38-7.31(m，2H)，6.90(dd，J＝5.1，3.5Hz，1H)，6.79-6.76(m，2H)，6.10(s，2H)，4.41(t，J＝6.8Hz，2H)，3.29(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺477.9. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (2-thiophen-3-yl-ethyl) -3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.39(s，1H)，7.50(s，1H)，7.38-7.35(m，2H)，6.95(dd，J＝5.1，3.3Hz，1H)，6.81(dd，J＝3.5，1.2Hz，1H)，6.19(s，2H)，4.55(t，J＝6.8Hz，2H)，3.42(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺477.9。

examples 203 and 204

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- (2-thiophen-2-yl-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- (2-thiophen-2-yl-ethyl) -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2 ]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 2- (2-bromo-ethyl) -thiophene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- (2-thiophen-2-yl-ethyl) -9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.29(s，1H)，7.45(dd，J＝4.9，2.9Hz，1H)，7.39(s，1H)，7.12(dd，J＝3.0，1.2Hz，1H)，6.89(dd，J＝4.9，1.4Hz，1H)，6.80(s，1H)，6.10(s，2H)，4.40(t，J＝7.2Hz，2H)，3.18(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺477.9. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -3- (2-thiophen-2-yl-ethyl) -3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.36(s，1H)，7.52-7.48(m，2H)，7.39(s，1H)，7.18(dd，J＝3.0，1.2Hz，1H)，6.98-6.95(m，1H)，6.19(s，2H)，4.54(t，J＝7.2Hz，2H)，3.20(t，J＝7.2Hz，2H)；LC-MS[M+H⁺477.9。

examples 205 and 206

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-nitro-phenyl) -ethyl ] -3H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-nitro-benzene. The isomers were separated by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (2-nitro-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.25(s，1H)，8.02-7.97(m，1H)，7.92-7.89(m，1H)，7.48-7.41(m，2H)，7.00(d，J＝9.0Hz，1H)，6.85(dd，J＝9.0，3.1Hz，1H)，6.42(d，J＝3.0Hz，1H)，4.53(t，J＝6.9Hz，2H)，3.75(s，3H)，3.60(s，3H)，3.21(t，J＝6.9Hz，2H)；LC-MS[M+H⁺453.13. 8- (2, 5-dimethoxy-phenylsulfanyl) -3- [2- (2-nitro-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.43(s，1H)，8.14-8.10(m，2H)，7.60-7.57(m，2H)，7.26-7.05(m，3H)，4.60(t，J＝6.9Hz，2H)，3.78(s，3H)，3.74(s，3H)，3.35(t，J＝6.9Hz，2H)；LC-MS [M+H]⁺453.13。

examples 207 and 208

8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -9- [2- (2-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylthio) -3- [2- (2-nitro-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2-nitro-benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -9- [2- (2-nitro-phenyl) -ethyl]-9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.19(s，1H)，8.02-7.90(m，1H)，7.93-7.91(m，1H)，7.50-7.40(m，2H)，7.29(s，1H)，6.53(s，1H)，6.18(s，2H)，4.49(t，J＝6.9Hz，2H)，3.26(t，J＝7.0Hz，2H)；LC-MS[M+H]⁺516.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) -3- [2- (2-nitro-phenyl) -ethyl]-3H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.41(s，1H)，8.12-8.09(m，2H)，7.59-7.54(m，2H)，7.50(s，1H)，7.39(s，1H)，6.19(s，2H)，4.59(t，J＝6.9Hz，2H)，3.36(t，J＝7.0Hz，2H)；LC-MS[M+H]⁺516.0。

examples 209 and 210

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylthio) -9H-purin-6-ylamine (J.Comb.chem, 2001, 3, 518) and (2-bromo-ethyl) -Benzene the title compound was prepared. The isomers were separated by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylmethyl) -9-phenethyl-9H-purin-6-ylamine: the yield is 11 percent,¹H NMR(DMSO-d6)δ8.24(s，1H)，7.30-7.20(m，4H)，7.11-7.09(m，2H)，6.69(s，1H)，6.05(s，2H)，4.40-4.34(m，2H)，3.97(s，2H)，3.04-2.98(m，2H)；LC-MS[M+H]⁺452.0. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylmethyl) -3-phenethyl-3H-purin-6-ylamine: yield 8%, (CD)₃OD)δ8.19(s，1H)，7.26-7.20(m，3H)，7.17(s，1H)，7.11-7.07(m，2H)，7.06(s，1H)，6.05(s，2H)，4.67(t，J＝6.8Hz，2H)，4.45(s，2H)，3.26(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺452.1。

Examples 211 and 212

(4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) carbamic acid tert-butyl ester and (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) carbamic acid tert-butyl ester

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and [4- (2-bromo-ethyl) -phenyl]-carbamic acid tert-butyl ester the title compound is prepared. The isomers were separated by preparative HPLC. (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -purin-9-yl]-ethyl } -phenyl) carbamic acid tert-butyl ester:¹H NMR(DMSO-d₆)δ9.30(s，1H)，8.35(s，1H)，7.36(s，1H)，7.30(d，J＝8.2Hz，2H)，6.99(d，J＝8.4Hz，2H)，6.71(s，1H)，6.09(s，2H)，4.39(t，J＝6.6Hz，2H)，2.99(t，J＝6.8Hz，2H)，1.48(s，9H)；LC-MS[M+H]⁺586.0. (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3]]DioxolesEn-5-ylsulfanyl) -purin-3-yl]-ethyl } -phenyl) carbamic acid tert-butyl ester:¹H NMR(DMSO-d₆)δ9.30(s，1H)，8.29(s，1H)，7.68-7.31(m，4H)，6.99(d，J＝8.4Hz，2H)，6.19(s，2H)，4.99(t，J＝6.6Hz，2H)，3.09(t，J＝6.8Hz，2H)，1.48(s，9H)；LC-MS[M+H]⁺586.0。

example 213

9- [2- (4-amino-phenyl) -ethyl ] -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine

To (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3]]Dioxol-5-ylthio) purin-9-yl]-Ethyl } -phenyl) -carbamic acid tert-butyl ester (0.03g, 0.04mmol) in dichloromethane (4.3mL) TFA (0.02mL, 0.22mmol) was added and the reaction mixture was stirred at room temperature overnight. At the end of this period the reaction was diluted with 100mL of toluene and then concentrated under reduced pressure. This procedure was repeated 3 more times to give the title product as a TFA salt (0.03g, 95%). ¹H NMR(DMSO-d₆)δ8.19(s，1H)，7.24(s，1H)，7.19-7.02(m，4H)，7.00(s，1H)，6.13(s，2H)，4.45(t，J＝6.8Hz，2H)，3.18(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺486.3。

Examples 214 and 215

(4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -phenyl) -carbamic acid tert-butyl ester and (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -phenyl) -carbamic acid tert-butyl ester

Prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and [4- (2-bromo-ethyl) -phenyl]-carbamic acid tert-butyl ester the title compound is prepared. The isomers were separated by preparative HPLC. (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl]-ethyl } -phenyl) -carbamic acid tert-butyl ester:¹H NMR(DMSO-d₆)δ9.28(s，1H)，8.28(s，1H)，7.31(d，J＝8.4Hz，2H)，7.03(d，J＝8.4Hz，1H)，6.92-6.84(m，3H)，6.58(d，J＝3.0Hz，1H)，4.39(t，J＝6.8Hz，2H)，3.74(s，3H)，3.61(s，3H)，2.91(t，J＝6.8Hz，2H)，1.49(s，9H)；LC-MS[M+H]⁺523.22. (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl]-ethyl } -phenyl) -carbamic acid tert-butyl ester:¹H NMR(DMSO-d₆)δ9.32(s，1H)，8.31(s，1H)，7.38(d，J＝8.4Hz，2H)，7.29-7.10(m，3H)，7.01(d，J＝8.6Hz，2H)，4.50(t，J＝6.8Hz，2H)，3.79(s，3H)，3.65(s，3H)，3.09(t，J＝6.8Hz，2H)，1.49(s，9H)；LC-MS[M+H]⁺523.2。

example 216

9- [2- (4-amino-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine

Prepared by a procedure analogous to example 213 from (4- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl]-ethyl } -phenyl) -carbamic acid tert-butyl ester the title compound is prepared.¹H NMR(DMSO-d₆)δ8.19(s，1H)，7.19-6.92(m，7H)，4.45(t，J＝6.8Hz，2H)，3.78(s，6H)，3.17(t，J＝6.8Hz，2H)；LC-MS[M+H]⁺423.1。

Example 217

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-trifluoromethoxy-phenyl) -ethyl ] -9H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-trifluoromethoxy-benzene. The compound was purified by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-trifluoromethoxy-phenyl) -ethyl]-9H-purin-6-ylamine: the yield is 17 percent,¹H NMR(CD₃OD)δ8.18(s，1H)，7.33(t，J＝8.0Hz，1H)，7.12-7.10(m，2H)，7.04-7.01(m，3H)，6.95(bs，1H)，4.57(t，J＝7.2Hz，2H)，3.75(s，3H)，3.74(s，3H)，3.24(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺492.1。

example 218

8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pentafluorophenyl-ethyl) -9H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -2, 3, 4, 5, 6-pentafluoro-benzene. The compound was purified by preparative HPLC. 8- (2, 5-dimethoxy-phenylsulfanyl) -9- (2-pentafluorophenyl-ethyl) -9H-purin-6-ylamine. Yield 23%, LC-MS [ M + H ]]⁺498.1。

Example 219

9- [2- (3, 5-bis-trifluoromethyl-phenyl) -ethyl ] -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3, 5-bis-trifluoromethyl-benzene. The compound was purified by preparative HPLC. 9- [2- (3, 5-bis-trifluoromethyl-phenyl) -ethyl ]-8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine:¹H NMR(DMSO-d₆)δ8.10(s，1H)，7.86(s，1H)，7.54(s，2H)，7.01(d，J＝9.0Hz，1H)，6.83(dd，J＝11.0，3.0Hz，1H)，6.40(d，J＝2.9Hz，1H)，4.50(t，J＝7.2Hz，2H)，3.75(s，3H)，3.59(s，3H)，3.24(t，J＝7.2Hz，2H)；LC-MS[M+H]⁺544.1。

example 220

9- [2- (3, 5-bis-trifluoromethyl-phenyl) -ethyl ] -8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3, 5-bis-trifluoromethyl-benzene the title compound was prepared. The compound was purified by preparative HPLC.¹HNMR(DMSO-d₆)δ8.13(s，1H)，7.79(s，1H)，7.66(s，2H)，7.23(s，1H)，7.01(s，1H)，6.09(s，2H)，4.59(t，J＝7.4Hz，2H)，3.35(t，J＝7.4Hz，2H)；LC-MS[M+H]⁺607.0。

Example 221

8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9- [1- (4-chloro-phenyl) -cyclopropylmethyl ] -9H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (-bromomethyl-cyclopropyl) -4-chloro-benzene the title compound was prepared. The compound was purified by preparative HPLC. 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfanyl) -9- [1- (4-chloro-phenyl) -cyclopropylmethyl]-9H-purin-6-ylamine:¹H NMR(CD₃OD)δ8.24(s，1H)，7.24(d，J＝9.3Hz，2H)，7.19(s，1H)，714(d，J＝8.6Hz，2H)，6.93(s，1H)，6.08(s，2H)4.49(s，2H)，1.41-1.35(m，2H)，0.95-0.91(m，2H)；LC-MS[M+H]⁺531.8。

example 222

8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -3- [2- (3-nitro-phenyl) -ethyl ] -3H-purin-6-ylamine

From 8- (6-bromo-benzo [1, 3] by a procedure analogous to examples 1 and 2 ]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-nitro-benzene the title compound was prepared. The compound was purified by preparative HPLC.¹H NMR(DMSO-d₆)δ8.29(s，1H)，7.99-7.95(m，1H)，7.56-7.42(m，2H)，7.33(s，1H)，7.10-7.05(m，1H)，6.72(s，1H)，6.10(s，2H)，4.60(t，J＝6.9Hz，2H)，3.36(t，J＝7.0Hz，2H)；LC-MS[M+H]⁺516.0。

Example 223

8- (2, 5-dimethoxy-phenylsulfanyl) -9- [2- (3-nitro-phenyl) -ethyl ] -9H-purin-6-ylamine

The title compound was prepared by a procedure analogous to examples 1 and 2 from 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine and 1- (2-bromo-ethyl) -3-nitro-benzene. The compound was purified by preparative HPLC.¹H NMR(DMSO-d₆)δ8.28(s，1H)，7.96(dd，J＝8.0，1.3Hz，1H)，7.53-7.42(m，2H)，7.07-7.03(m，1H)，7.00(d，J＝9.0Hz，1H)，6.87(dd，J＝3.1，9.0Hz，1H)，6.53(d，J＝2.8Hz，1H)，4.60(t，J＝6.9Hz，2H)，3.71(s，3H)，3.62(s，3H)，3.33(t，J＝6.9Hz，2H)；LC-MS[M+H]⁺453.13。

FIG. 2

Example 224

8- (benzo [1, 3] dioxol-5-ylsulfanyl) -9-phenethyl-1, 9-dihydro-purin-6-one

Step 1: 6-chloro-N⁴-phenethyl-pyrimidine-4, 5-diamine

To a flask containing dichloropyrimidine (2.8g, 17.0mmol) in n-butanol (0.1M) was added amine (2.3mL, 18.6mmol) and TEA (4.7mL, 33.9 mmol). The resulting reaction mixture was then heated to 120 ℃ until disappearance of starting material as judged by TLC (about 4 h). The reaction was then cooled to room temperature and poured into hexane, at which time a solid formed. The solid was filtered off using a glass funnel and the solid cake was washed with hexane. The solid (3.8g, 90% yield) was not further purified It is used after being dissolved.¹H NMR(CDCl₃)δ8.07(s，1H)，7.38-7.21(m，5H)，5.29(bs，1H)，3.81(t，J＝7.1Hz，2H)，3.60(bs，2H)，2.97(t，J＝7.3Hz，2H)。

Step 2: 9-phenethyl-1, 9-dihydro-purin-6-ones

To a flask containing a solution of the above chloropyrimidine product (1.0g, 4.0mmol) in formamide (0.25M) was added 2mL of formic acid. The resulting reaction mixture was then heated to 175 ℃ for 4h, at which point HPLC indicated the starting material had been consumed. The reaction was allowed to cool and water (0.80M) was added. The solid formed was filtered off using a glass funnel and the solid filter cake was washed with toluene. The solid (0.6g, 64%) was then used in the next reaction without further purification.¹H NMR(DMSO-d₆)δ12.29(s，1H)，8.04(s，1H)，7.90(s，1H)，7.31-7.7.10(m，5H)，4.39(t，J＝7.0Hz，2H)，3.13(t，J＝7.3Hz，2H)。

And step 3: 8-bromo-9-phenethyl-1, 9-dihydro-purin-6-one

To the solution of purinone (0.29g, 1.21mmol) in dioxane (0.1M) from step 2 of the above reaction was added NBS (0.32g, 1.81 mmol). The resulting reaction mixture was heated to 105 ℃ until HPLC showed the starting material had been consumed (about 2 h). The reaction was cooled to room temperature and passed through MPLC with 0-20% MeOH/CH₂Cl₂Is purified by a solvent gradient. Fractions containing the product were collected and concentrated to give the desired product (0.22g, 57% yield).¹H NMR(DMSO-d₆)δ12.49(s，1H)，8.08(s，1H)，7.30-7.21(m，3H)，7.10-7.04(m，2H)，4.36(t，J＝7.0Hz，2H)，3.17(t，J＝7.3Hz，2H)。

And 4, step 4: 8- (benzo [1, 3] dioxol-5-ylsulfanyl) -9-phenethyl-1, 9-dihydro-purin-6-one

To a solution of sodium hydride (0.035g, 0.882mmol, 60% in mineral oil) in DMF (0.1M) at 0 deg.C was added the desired thiophenol (0.140g, 0.882 mmol). The reaction mixture was allowed to warm to room temperature and mixed for 15min at which time it was added Bromo-purinone from step 3 of the above reaction (0.113g, 0.353 mmol). The resulting reaction mixture was then heated at 90 ℃ overnight. The reaction was then cooled to room temperature, concentrated, and then passed through MPLC with 0-20% MeOH/CH₂Cl₂And (5) purifying. Fractions containing the product were collected and concentrated to give the desired product (0.098g, 71% yield).¹H NMR(CDCl₃)δ12.95(s，1H)，8.02(s，1H)，7.29-6.80(m，8H)，5.95(s，2H)，4.47(t，J＝7.4Hz，2H)，3.09(t，J＝7.4Hz，2H)；LC-MS[M+H]⁺393.0。

Example 225

8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -9-phenethyl-1, 9-dihydro-purin-6-one

To a solution of purine from step 4 of the above reaction (0.088g, 0.266mmol) in AcOH (0.2M) was added bromine (0.02mL, 0.319 mmol). The resulting reaction mixture was covered with aluminum foil and mixed at room temperature until HPLC indicated the starting material had been consumed. The resulting solution was diluted with 150mL of toluene and concentrated. This step was repeated 2 more times and the solid formed was purified by preparative HPLC to give the desired product as a white solid (0.059g, 46% yield).¹H NMR(DMSO-d₆)δ12.42(s，1H)，8.09(m，1H)，7.39(s，1H)，7.25-7.17(m，3H)，7.10-7.04(m，2H)，6.81(s，1H)，6.05(s，2H)，4.39(t，J＝7.1Hz，2H)，3.03(t，J＝7.1Hz，2H)；LC-MS[M+H]⁺472.3。

Example 226-

Example 226-. All compounds were isolated as trifluoroacetate salts. As will be readily understood by those skilled in the art, the side on the purine ring system N is amino (-NH)₂) And side-O on the indane ring is a hydroxyl group.

TABLE 3

Intermediate 43

Synthesis of 2- (2-chloro-ethyl) -1-propyl-piperidine

To a solution of 2- (1-propyl-piperidin-2-yl) -ethanol (0.150g, 0.875mmol) in dichloromethane (5mL) was added thionyl chloride (1.0mL, 13.70mmol) at room temperature and the reaction mixture was refluxed for 3 h. The solvent and excess thionyl chloride were removed under reduced pressure. The product was dissolved in dichloromethane and evaporated to dryness. The product was used in the next step without further purification. GC-MS m/z 189.00.

Intermediate 44

Synthesis of 1- [4- (2-bromo-ethyl) -piperidin-1-yl ] -ethanone

To 1- [4- (2-hydroxy-ethyl) -piperidin-1-yl at 0 deg.C]To a solution of ethanone (0.500g, 2.92mmol) in dichloromethane (15mL) were added carbon tetrabromide (1.45g, 4.38mmol), triphenylphosphine (0.728g, 2.77mmol) and imidazole (0.398g, 5.84 mmol). The temperature of the reaction mixture was slowly raised to room temperature and stirring was continued at room temperature for 18 h. The reaction was diluted with dichloromethane and washed with water. The organic layer was dried (Na)₂SO₄) Filtered, and the solvent evaporated. The product was purified chromatographically on silica gel using a gradient of 0-10% methanol in dichloromethane. GC-MS m/z 235.

Intermediate 45

Synthesis of (S) -2- (2-methanesulfonyloxy-ethyl) -piperidine-1-carboxylic acid tert-butyl ester.

To a solution of (S) -2- (2-hydroxy-ethyl) -piperidine-1-carboxylic acid tert-butyl ester (0.300g, 1.30mmol) in dichloromethane (5mL) was added methanesulfonyl chloride (0.304mL, 3.9mmol) and triethylamine (0.547mL, 3.9mmol) over 1-16h at room temperature. The reaction mixture was diluted with dichloromethane and NaHCO₃(10%, W/V) and then water. The dichloromethane layer was dried (Na)₂SO₄) Filtered, and the solvent evaporated to dryness. The product was sufficiently pure for the next step to be used without any further purification. LC-MS [ M + Na ]]329.9。

Intermediate 46

Synthesis of toluene-4-sulfonic acid 2- (1-benzyl-1, 2, 3, 6-tetrahydro-pyridin-4-yl) -ethyl ester

To a solution of 2- (1-benzyl-1, 2, 3, 6-tetrahydro-pyridin-4-yl) ethanol (0.822g, 4.09mmol) (j.med.chem.1990, 33, 3133) in dichloromethane was added p-toluenesulfonyl chloride (1.71g, 9.00mmol), triethylamine (2.3mL, 16.4mmol) and DMAP (0.050g, 0.41mmol) at room temperature and stirring continued for 3h at room temperature. The reaction mixture was diluted with dichloromethane and NaHCO₃(10%, W/V) aqueous solution, and then saturated NaCl solution. The organic layer was dried (Na) ₂SO₄) Filtered, and the solvent evaporated to dryness. The product was purified by flash chromatography on silica gel using a gradient of 0-10% methanol in dichloromethane.¹H NMR(CDCl₃)δ7.77(d，8.4Hz，2H)，7.34-7.30(m，5H)，7.26(m，1H)，5.36(m，1H)，4.09(t，J＝6.8Hz，2H)，3.54(s，2H)，2.92-2.88(m，2H)，2.50(t，J＝5.6Hz，2H)，2.44(s，3H)，2.31(brt，J＝6.8Hz，2H)，2.20-1.84(m，2H)。

Intermediates 47-86, listed in table 4, were prepared in a similar procedure to intermediates 43-46 using the appropriate starting materials.

TABLE 4

Intermediates 87 and 88

Synthesis of trans-2-isopropyl-4- [2- (toluene-4-sulfonyloxy) -ethyl ] -piperidine-1-carboxylic acid tert-butyl ester and cis-2-isopropyl-4- [2- (toluene-4-sulfonyloxy) -ethyl ] -piperidine-1-carboxylic acid tert-butyl ester.

A mixture of cis and trans isomers of tert-butyl 2-isopropyl-4-methoxycarbonylmethyl-piperidine-1-carboxylate was prepared according to known literature procedures (org. lett.2000, 2, 3679). Followed by NaBH₄Treatment of the ester with/LiCl followed by the presence of NEt₃And catalytic amount of DMAP, adding TsCl to obtain cis-2-isopropyl-4- [2- (toluene-4-sulfonyloxy) -ethyl]-piperidine-1-carboxylic acid tert-butyl ester and cis-2-isopropyl-4- [2- (toluene-4-sulfonyloxy) -ethyl]-piperidine-1-carboxylic acid tert-butyl ester and separating them by ISCO flash chromatography. Cis-2-isopropyl-4- [2- (toluene-4-sulfonyloxy) -ethyl]-piperidine-1-carboxylic acid tert-butyl ester,¹HNMR(CDCl₃)δ7.79(dt，J＝8.4，2.0Hz，2H)，7.35(d，J＝8.4Hz，2H)，4.04(m，2H)，3.78(ddd，J＝14.0，8.0，2.0Hz，1H)，3.52(q，8.4Hz，1H)，2.83(ddd，J＝14.5，10.8，6.8Hz，1H)，2.46(s，3H)，1.86-1.76(m，2H)，1.69-1.59(m，3H)，1.52(m，1H)，1.45(m，9H)，1.06(m，1H)，1.00(m，1H)，0.85(d，J＝6.4Hz，6H)。

cis-2-isopropyl-4- [2- (toluene-4-sulfonyloxy) -ethyl ]-piperidine-1-carboxylic acid tert-butyl ester，¹H NMR(CDCl₃)δ7.79(dt，J＝8.8，2.2Hz，2H)，7.35(d，J＝8.8Hz，2H)，4.10-4.02(m，2H)，3.89(m，1H)，3.67(m，1H)，2.68 and 2.59(two t，J＝14.4 and 13.6Hz，1H)，2.46(s，3H)，1.93(m，1H)，1.75(brd，J＝14.0Hz，1H)，1.68(m，1H)，1.55-1.47(m，3H)，1.43(s，9H)，1.07(dt，J＝12.8，5.2Hz，1H)，0.97(m，1H)。

Intermediate 89

Synthesis of toluene-4-sulfonic acid 2- (8-methyl-8-aza-bicyclo [3.2.1] oct-3-yl) -ethyl ester

2- (8-methyl-8-aza-bicyclo [3.2.1] oct-3-yl) ethanol was prepared from commercially available 3-tropinone according to known literature procedures (j.med.chem.2001, 44, 3937). Intermediate 46 was converted to the corresponding tosylate following the procedure described for preparation of intermediate 46 and used in the next step without further purification.

Intermediate 90

Synthesis of 4[2- (toluene-4-sulfonyloxy) -ethylene ] -piperidine-1-carboxylic acid tert-butyl ester.

The title product was prepared in three steps in sequence: starting from N-Boc-4-piperidone, a standard Wittig reaction was performed followed by DIBAL reduction to give 4- (2-hydroxy-ethylene) -piperidine-1-carboxylic acid tert-butyl ester. The alcohol was treated according to the procedure described for the preparation of intermediate 46 to give the corresponding tosylate.¹H NMR(CDCl₃)δ7.77(dt，J＝8.4，2.0Hz，2H)，7.35(d，J＝2H)，5.37(m，1H)，4.09(t，J＝6.4Hz，2H)，3.97-3.78(m，2H)，3.42(t，J＝6.4Hz，2H)，2.46(s，3H)，2.34(brt，J＝7.2Hz，2H)，1.98-1.92(m，2H)，1.47(s，9H)。

Intermediate 91

Synthesis of toluene-4-sulfonic acid 2- (8-oxa-bicyclo [3.2.1] oct-3-yl) ethyl ester

Known [4+3 ] of furan and oxyallyl (oxyally) derived from 1, 1, 3-trichloroacetone by commercial availability]Cycloaddition reaction followed by reduction with zinc (J.org.chem.1999, 64, 3398 and J.am.chem.Soc.2001, 123, 5590) to synthesize 8-oxa-bicyclo [3.2.1 ]Oct-6-en-3-one. Reduction of the internal double bond of the cycloaddition product using Pd/C in MeOH to give 8-oxa-bicyclo [3.2.1]Octane-3-one. The resulting ketone is subjected to the conditions of Eadsworth-Horner-Emmons to obtain the α, β -unsaturated ester. Catalytic hydrogenation of the conjugated ester produces an inseparable mixture (. about.1: 1) of diastereomers which are not diastereoselective. The mixture of diastereomers is then subjected to the following two steps. Said step comprising the use of NaBH₄Reduction of esters by LiCl followed by the presence of NEt₃By treatment with TsCl to obtain oxabicyclo [3.2.1]Octaneethylmethylbenzenesulfonate (oxabicyclo [3.2.1]]octaneethylmethylbenzensolfonate)。¹H NMR(CDCl₃)：δ7.81-7.78(m，2H)，7.37-7.34(m，2H)，4.35-4.28(m，2H)，4.07-4.02(m，2H)，2.46(s，3H)，2.07(m，1H)，1.95-1.87(m，2H)，1.82-1.76(m，1H)，1.68-1.63(m，2H)，1.55-1.50(m，2H)，1.43-1.28(m，2H)，1.10(m，1H)。

Intermediate 92

Synthesis of toluene-4-sulfonic acid 2- (1-methyl-8-oxa-bicyclo [3.2.1] oct-3-yl) -ethyl ester.

The title compound was synthesized starting from 2-methylfuran following the procedure for intermediate 91.¹H NMR(CDCl₃)：δ7.81-7.78(m，2H)，7.37-7.35(m，2H)，4.37-4.29(m，1H)，4.07-4.02(m，2H)，2.46(s，3H)，2.10-1.96(m，2H)，1.89-1.50(m，6H)，1.39(m，1H)，1.27(s，1.5H)，1.26(s，1.5H)，1.25(m，1H)，1.10(m，1H)。

Intermediate 93

2- {1- (1-Ethyl-1H-tetrazol-5-yl) piperidin-4-yl) ethyl-4-ethylbenzenesulfonate

Preparation of intermediate 93 by 3 consecutive steps

Step 1: n-ethyl-4- (2-hydroxyethyl) piperidine-1-carbothioic acid amide.

To 2- (piperidin-4-yl) ethanol (509mg, 3.94mmol) in CH₂Cl₂(13mL) was added isothiocyanatoethane (343. mu.L, 3.94 mmol). After stirring at room temperature for 10h, the mixture was concentrated in vacuo to give the title compound (716mg, 84%): ¹H NMR(CDCl₃)δ5.38(brs，1H)，4.59(d，J＝13.6Hz，1H)，3.74-3.67(m，3H)，3.15(d，J＝12.8Hz，1H)，3.00(t，J＝13.2Hz，2H)，2.65(t，J＝12.4Hz，1H)，1.81-1.72(m，3H)，1.55-1.52(m，3H)，1.28-1.22(m，4H)。

Step 2: 2- {1- (1-Ethyl-1H-tetrazol-5-yl) piperidin-4-yl } ethanol.

To N-ethyl-4- (2-hydroxyethyl) piperidine-1-carbothioamide (200mg, 0.93mmol), HgCl at room temperature₂(277mg, 1.02mmol) and NaN₃(181mg, 2.78mmol) in DMF (2.5mL) was added NEt₃(388μL，2.78mmol). After stirring for 10 hours, the reaction mixture was filtered and the filter cake was washed with CH₂Cl₂And (6) washing. The combined filtrate and washings were washed with brine and dried (Na)₂SO₄) Filtered and concentrated in vacuo to give a residue which was SiO-₂Chromatography (60% EtOAc/hexanes) to give the title compound (85mg, 41%):¹H NMR(CDCl₃)δ4.18(q，J＝7.2Hz，2H)，3.75(td，J＝6.8，5.2Hz，2H)，3.51(brd，J＝12.4，2H)，3.03(td，J＝12.4，2.8Hz，2H)，1.84(brd，J＝14.4Hz，2H)，1.71(m，1H)，1.59(q，J＝6.8Hz，2H)，1.56(t，J＝7.2Hz，3H)，1.48-1.38(m，2H)。

and step 3: 2- {1- (1-Ethyl-1H-tetrazol-5-yl) piperidin-4-yl) ethyl-4-ethylbenzene sulfonate.

The title compound (79mg, 55%) was obtained from 2- {1- (1-ethyl-1H-tetrazol-5-yl) piperidin-4-yl } ethanol (85mg, 0.38mmol) following the procedure for intermediate 46.¹H NMR(CDCl₃)δ7.80(brd，J＝8.0Hz，2H)，7.37(brd，J＝8.0Hz，2H)，4.15(q，J＝7.6Hz，2H)，4.10(t，J＝6.0Hz，2H)，3.46(brd，J＝12.4，2H)，2.97(td，J＝12.4，2.0Hz，2H)，2.46(s，3H)，1.71(brd，J＝12.8Hz，2H)，1.67-1.63(m，3H)，1.54(t，J＝7.6Hz，3H)，1.41-1.31(m，2H)。

The compounds summarized below in table 5 were prepared following the procedure for intermediate 46 using the appropriate starting materials.

TABLE 5

Intermediate 97

2- {1- (tert-Butoxycarbonyl) -3, 3-dimethylpiperidin-4-yl } ethyl-4-ethylbenzene sulfonate.

The title compound was prepared in 4 sequential steps

Step 1: (E) -tert-butyl-4- { (ethoxycarbonyl) methylene } -3, 3-dimethylpiperidine-1-carboxylate.

To a suspension of NaH (0.212g, 5.29mmol) in THF (2mL) at 0 deg.C was added a solution of triethyl 2-phosphonopropionate (1.05mL, 5.29mmol) in THF (2 mL). The mixture was stirred at room temperature for 1h, then a solution of tert-butyl-3, 3-dimethyl-4-oxopiperidine-1-carboxylate (J.Org.chem.,. 2001, 66, 2487) (0.600g, 2.64mmol) in THF was added and stirred for 10 h. The resulting mixture was quenched with water and the product portion was Et₂And (4) extracting. The combined extracts were washed with brine and dried (Na)₂SO₄) Filtered and concentrated in vacuo. The remainder is treated with SiO₂Chromatographic purification (gradient: 5% EtOAc/hexanes-40% EtOAc/hexanes) to give the title compound (784mg, 100%);¹H NMR(CDCl₃)δ5.73(s，1H)，4.15(q，J＝6.8Hz，2H)，3.52-3.42(m，2H)，3.25-3.18(m，2H)，3.05(t，J＝5.6Hz，2H)，1.47(s，9H)，1.29(t，J＝6.8Hz，3H)，1.12(s，6H)。

step 2: tert-butyl 4- { (ethoxycarbonyl) methyl } -3, 3-dimethylpiperidine-1-carboxylate.

(E) -tert-butyl 4- { (ethoxycarbonyl) methylene } -3, 3-dimethylpiperidine-1-carboxylate (784mg, 2.64mmol) was hydrogenated in MeOH (10mL) containing Pd/C (131mg) under one atmosphere of pressure. After 10h, the mixture was filtered and the filter cake was washed with MeOH. The combined filtrates were concentrated to give the title compound (540mg, 68%):¹H NMR(CDCl₃)δ4.13(q，J＝6.8Hz，2H)，4.05(m，1H)，3.57(m，1H)，2.57(m，1H)，2.46(dd，J＝15.2，3.2Hz，1H)，1.93(dd，J＝15.2，10.4Hz，1H)，1.76(m，1H)，1.59-1.50(m，2H)，1.45(s，9H)1.34(m，1H)，1.26(t，J＝6.8Hz，3H)，0.91(s，3H)，0.79(s，3H)。

and step 3: tert-butyl 4- (2-hydroxyethyl) -3, 3-dimethylpiperidine-1-carboxylate.

At 0 ℃ to NaBH₄(204mg, 5.40mmol) and LiCl (229mg, 5.40mmol) in EtOH (8mL) was added a solution of tert-butyl 4- { (ethoxycarbonyl) methyl } -3, 3-dimethylpiperidine-1-carboxylate (538mg, 1.80mmol) in THF (10 mL). After stirring at room temperature for 10h, the mixture was quenched with water and the product portion was treated with Et₂And (4) extracting. The combined extracts were dried (Na)₂SO₄) Filtered and concentrated in vacuo. The remainder is treated with SiO₂Chromatographic purification (gradient: 40% EtOAc/hexanes-90% EtOAc/hexanes) to give the title compound (275mg, 59%).

And 4, step 4: 2- {1- (tert-Butoxycarbonyl) -3, 3-dimethylpiperidin-4-yl } ethyl-4-ethylbenzene sulfonate.

The title compound (350mg, 55%) was obtained from tert-butyl 4- (2-hydroxyethyl) -3, 3-dimethylpiperidine-1-carboxylate (275mg, 1.07mmol) according to the procedure for the intermediate 46.¹H NMR(CDCl₃)δ7.79(brd，J＝8.0Hz，2H)，7.36(brd，J＝8.0Hz，2H)，4.15-3.96(m，4H)，3.60(m，1H)，2.46(s，3H)，2.61-2.23(m，2H)，1.89(m，1H)，1.44(s，9H)，1.26(m，3H)，0.84(s，3H)，0.74(s，3H)。

Intermediate 98

2- (1- { (Z) - [ (tert-Butoxycarbonyl) amino ] [ (tert-butyloxycarbonyl) imino ] methyl } piperidin-4-yl) ethyl 4-methylbenzenesulfonate

Step 1: di-tert-butyl { (Z) - [4- (2-hydroxyethyl) piperidin-1-yl ] methylene } biscarbamate.

To 2- (piperidin-4-yl) ethanol (400mg, 3.10mmol) and NEt₃(864 μ L, 6.20mmol) of CH₂Cl₂(8mL) to the solution were added 1, 3-bis (tert-butyloxycarbonyl) -2-methyl-2-thioisourea (899mg, 3.10mmol) and HgCl ₂(842mg, 3.10 mmol). After stirring at room temperature for 10h, with CH₂Cl₂The reaction mixture is extracted. The combined extracts were dried (Na)₂SO₄) Filtered and concentrated in vacuo. The remainder is treated with SiO₂Chromatographic purification (gradient: 50% EtOAc/hexanes-90% EtOAc/hexanes) to give the title compound (969mg, 84%):¹H NMR(CDCl₃)δ10.16(brs，1H)，4.25-4.20(m，2H)，3.75-3.65(m，2H)，2.94(t，J＝12.8Hz，2H)，1.78-1.72(m，3H)，1.54(q，J＝6.4Hz，2H)，1.49(s，18H)，1.38-1.29(m，2H)。

step 2: 2- (1- { (Z) - [ (tert-Butoxycarbonyl) amino ] [ (tert-butyloxycarbonyl) imino ] methyl } piperidin-4-yl) ethyl 4-methylbenzenesulfonate.

From di-tert-butyl { (Z) - [4- (2-hydroxyethyl) piperidin-1-yl following the procedure for intermediate 46]Methylene } biscarbamate (484mg, 1.307mmol) gave the title compound (446mg, 65%).¹H NMR(CDCl₃)δ10.16(brs，1H)，7.79(d，J＝8.4Hz，2H)，7.36(d，J＝8.4Hz，2H)，4.07(t，J＝6.0Hz，2H)，4.20-3.91(m，2H)，2.85(t，J＝12.8Hz，2H)，2.46(s，3H)，1.61-1.59(m，5H)，1.48(s，9H)，1.28-1.18(m，2H)。

Intermediate 99

2- (1- { (E) - [ (tert-Butoxycarbonyl) imino ] [ (tert-butyloxycarbonyl) (propyl) amino ] methyl } piperidin-4-yl) ethyl-4-methylbenzenesulfonate

The title compound was prepared by 2 sequential steps

Step 1: 2- (1- { (E) - [ (tert-Butoxycarbonyl) imino ] [ (tert-butyloxycarbonyl) (propyl) amino ] methyl } piperidin-4-yl) ethanol

To di-tert-butyl { (Z) - [4- (2-hydroxyethyl) piperidin-1-yl group]Methylene Binocarbamate (200mg, 0.538mmol), Bu₄NI (40mg, 0.11mmol) and KOH (70mg, 1.3mmol) in CH₂Cl₂(2.5mL) and H₂To the mixture in O (2.5mL) was added iodopropane (63. mu.L, 0.65mmol) and refluxed for 3 h. After cooling to room temperature, the product fraction was passed over CH ₂Cl₂Extraction, brine washing and drying (Na)₂SO₄) Filtered and concentrated in vacuo. The remainder is treated with SiO₂Chromatographic purification (gradient: 40% EtOAc/hexanes-100% EtOAc/hexanes) to give the title compound (192mg, 86%); LC-MS [ M + H ]]⁺442.5。

Step 2: 2- (1- { (E) - [ (tert-Butoxycarbonyl) imino ] [ (tert-butyloxycarbonyl) (propyl) amino ] methyl } piperidin-4-yl) ethyl-4-methylbenzenesulfonate

Following a procedure analogous to that described for intermediate 46 from 2- (1- { (E) - [ (tert-butoxycarbonyl) imino)][ (tert-Butoxycarbonyl) (propyl) amino]Methyl } piperidin-4-yl) ethanol (190mg, 0.460mmol) gave the title compound (189mg, 72%).¹H NMR(CDCl₃)δ7.79(d，J＝7.2Hz，2H)，7.36(d，J＝7.2Hz，2H)，4.49(brs，1H)，4.12-4.02(m，2H)，2.46(s，3H)，1.74-1.52(m，7H)，1.31-1.05(m，2H)，0.87(t，J＝7.2Hz，3H)。

Intermediate 100

5- (2- { [ 4-methylphenyl) sulfonyl ]

Oxy } ethyl) -3, 4-dihydropyridine-1- (2H) -carboxylic acid tert-butyl ester.

The title compound is prepared following a procedure analogous to that described for intermediate 46 using the appropriate starting materials.¹H NMR(CDCl₃) δ 7.79(d, J ═ 8.4Hz, 2H), 7.34(d, J ═ 8.4Hz, 2H), 6.66 and 6.56(s, 1H), 4.06(q, J ═ 6.8Hz, 2H), 3.46-3.41(m, 2H), 2.45(s, 3H), 2.31(t, J ═ 7.2Hz, 2H), 1.91(m, 1H), 1.85(m, 1H), 1.78-1.70(m, 2H), 1.48(s, 9H).

Intermediate body 101

1- (1-prop-2-yn-1-yl) piperidin-4-yl) ethyl 4-methylbenzenesulfonate

The title compound was prepared following the procedure for intermediate 46 using the appropriate starting materials. LC-MS [ M + H ]]⁺322.1。

Intermediates 102-104 summarized in Table 6 were prepared following a procedure analogous to that described for intermediate 46 using the appropriate starting materials.

TABLE 6

Examples 337 and 338

2- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl ] -ethyl } -piperidine-1-carboxylic acid ethyl ester and 2- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl ] -ethyl } -piperidine-1-carboxylic acid ethyl ester.

Example 1 example 2

A mixture of 8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine (0.29g, 0.66mmol), (2-chloro-ethyl) -piperidine-1-carboxylic acid ethyl ester (0.174g, 0.79mmol) and Barton base (0.163mL, 0.79mmol) in DMF (3mL) was heated at 90-100 deg.C for 15H. The reaction mixture was then brought to ambient temperature. After removal of the solvent under reduced pressure, the solid phase was purified by preparative HPLC [ X-Terra prep-RP 1810 um, 19 × 250mm (water), mobile phase: solvent A: HPLC grade water with 0.01% TFA, and B: acetonitrile with 0.01% TFA, general elution gradient-solvent B from 15% to 80% over an experimental period of 15 to 25 minutes ]The residue was purified. After lyophilization of the HPLC fractions, the N-9 and N-3 isomers were separated as trifluoroacetate salts. 2- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-9-yl]-ethyl } -piperidine-1-carboxylic acid ethyl ester.¹H NMRδ(CD₃OD)8.29(s，1H)，7.05-6.97(m，3H)，4.39-4.30(m，2H)，4.21-4.15(m，1H)，4.09-3.9(m，3H)，3.70(d，5.2Hz，2H)，3.75(s，3H)，3.73(s，3H)，2.98-2.88(m，1H)，2.34-2.28(m，1H)，2.02-1.98(m，1H)，1.78-1.70(m，1H)，1.66-1.58(m，2H)，1.34-1.24(m，4H)；LC-MS TOF[M+H]⁺487.2. 2- {2- [ 6-amino-8- (2, 5-dimethoxy-phenylsulfanyl) -purin-3-yl]-ethyl } -piperidine-1-carboxylic acid ethyl ester.¹H NMRδ(CD₃OD)8.41(s，1H)，7.2(s，1H)，7.12(m，2H)，4.32-4.30(m，2H)，4.08(m，1H)，3.79(s，3H)，3.78(s，3H)，3.48-4.41(m，1H)，3.36-3.35(m，3H)，3.2-3.17(m，1H)，3.13-3.12(m，2H)，1.7-1.6(m，5H)，1.28-1.22(m，3H)；LC-MS TOF[M+H]⁺487.2。

Example 339-464 summarized in Table 7 was prepared according to procedures analogous to those described in examples 337 and 338. All compounds were isolated as trifluoroacetate salts.

Example 465

Synthesis of 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2-piperidin-4-ylethyl) -9H-purin-6-amine

To 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio at room temperature]To a solution of tert-butyl-9H-purin-9-yl } ethyl) piperidine-1-carboxylate (0.030g) in DCM (10mL) was added trifluoroacetic acid (5mL) and stirring was continued at room temperature for 1-16H. The solvent and excess trifluoroacetic acid were evaporated to dryness. The oily residue was co-evaporated with toluene (3X 5mL) to give the title product as the trifluoroacetate salt.¹H NMR(DMSO-d₆)δ8.21(s，1H)，7.40(s，1H)，6.85(s，1H)，6.10(s，2H)，4.19(t，J＝7.6Hz，2H)，3.25-3.20(m，2H)，2.80-2.75(m，2H)，1.88-1.85(m，2H)，1.68-1.62(m，2H)，1.50-1.42(M，1H)，1.30-1.24(m，2H)；LC-MS[M+H]⁺477.1。

Example 466

Synthesis of 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (2-piperidin-3-ylethyl) -9H-purin-6-amine.

To 3- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio at room temperature]To a suspension of tert-butyl-9H-purin-9-yl } ethyl) piperidine-1-carboxylate (0.03g) in ethyl acetate (10mL) was added 6N HCl (5mL) and stirring was continued at room temperature for 1-16H. The solvent and excess hydrochloric acid were evaporated to dryness. The oily residue was coevaporated with toluene (3X 5mL) to give the title product as the hydrochloride salt.¹H NMR(CD₃OD)δ8.38(s，1H)，7.29(s，1H)，7.26(s，1H)，6.10(s，2H)，4.43-4.41(m，2H)，3.49-3.46(m，1H)，2.95-2.92(m，1H)，2.80-2.65(m，2H)，1.92-1.76(m，4H)，1.39-1.23(m，4H)；TOFLC-MS[M+H]⁺]477.1。

Example 467-Ashi 472 and examples 479 and 480 were synthesized in analogy to the procedure described for example 465 using the appropriate starting materials in Table 7 and isolated as the trifluoroacetate salt, and the analytical data for these examples are summarized in Table 8. Examples 473-478 and 481-484 were synthesized in a similar manner to example 466 and were isolated as the HCl salt, and the analytical data of the examples are summarized in Table 8.

TABLE 8

Examples 485 and 486

1- (2- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio ] -9H-purin-9-yl } ethyl) piperidine-2, 6-dione and 8- (2, 5-dimethoxy-benzenesulfonyl) -9-vinyl-9H-purin-6-ylamine.

The title compound was prepared in 2 consecutive reaction steps as follows:

step 1: synthesis of 9- (bromo-ethyl) -8- (2, 5-dimethoxy-phenylsulfanyl) -9H-purin-6-ylamine:

8- (2, 5-Dimethoxyphenylthio) -9H-purin-6-amine (1.00g, 3.30mmol), 1, 3-dibromoethane (1.42mL, 16.48mmol) and Cs were mixed at room temperature₂CO₃A mixture of (1.29g, 3.96mmol) in DMF (11mL) was stirred for 1-2 days. Then the reaction mixture is passed over CH₂Cl₂Diluted, washed with brine and dried (Na)₂SO₄) Filtered and concentrated in vacuo. After standing for 10h, the mixture was passed through CH₂Cl₂And (6) processing. The resulting solid was filtered, washed with EtOAc and air dried to give the product (274mg, 20%). The combined filtrates were concentrated and purified by column Chromatography (CH)₂Cl₂EtOAc/MeOH 1/1/0.1 to 1/1/0.5) gave additional product (200mg, 15%):¹H NMR(DMSO)δ8.18(s，1H)，7.95(brs，2H)，7.02(d，J＝8.8Hz，1H)，6.87(dd，J＝8.8，3.2Hz，1H)，6.57(d，J＝3.2Hz，1H)，4.61(t，J＝6.0Hz，2H)，3.86(t，J＝6.0Hz，2H)，3.76(s，3H)，3.62(s，3H)；TOF LC-MS[M+H]⁺410.0. if the reaction is carried out under otherwise identical reaction conditions except for an elevated temperature of from 85 to 90 deg.C, a 1: 1 mixture of the N9 and N3 isomers is obtained.

Step 2: coupling the product of step 1 with glutarimide (gultamide)

A solution of glutarimide (10mg, 0.091mmol) in DMF (0.5mL) was treated with NaH (4.3mg, 0.11mmol) at room temperature. After stirring for 15min, a solution of intermediate (N-9) from step 1 (34mg, 0.083mmol) in DMF (1mL) was added dropwise to the glutarimide anion solution. The resulting mixture was heated at 60 ℃ for 10h, cooled to room temperature and quenched with AcOH (10 μ L). The reaction mixture was extracted with EtOAc, washed with brine, dried (Na) ₂SO₄) Filtered and concentrated in vacuo. The crude material was purified by preparative HPLC to give the desired compound (8mg) with the elimination of 8- (2, 5-dimethoxy-benzenesulfonyl) -9-vinyl-9H-purin-6-ylamine (10 mg). 1- (2- { 6-amino-8- [ (2, 5-dimethoxyphenyl) thio]-9H-purin-9-yl } ethyl) piperidine-2, 6-dione.¹H NMR(CD₃OD)δ8.30(s，1H)，7.10(d，J＝2.8Hz，1H)，7.06(d，J＝8.8Hz，1H)，7.02(dd，J＝8.8，2.8Hz，12H)，4.54-4.50(m，2H)，4.24-4.22(m，2H)，3.78(s，3H)，3.75(s，3H)，2.57(t，J＝6.8Hz，4H)，1.89(quintet，J＝6.8Hz，2H)；TOF-MS[M+H]⁺443.1. 8- (2, 5-dimethoxy-benzenesulfonyl) -9-vinyl-9H-purin-6-ylamine.¹H NMR(DMSO-d₆)δ8.24(s，1H)，7.57(dd，J＝15.6，8.8Hz，1H)，7.03(d，J＝9.2Hz，1H)，6.87(dd，J＝9.2，3.2Hz，1H)，6.43(d，J＝3.2Hz，1H)，6.39(d，J＝15.6Hz，1H)，5.24(d，J＝8.8Hz，1H)，3.76(s，3H)，3.61(s，3H)。

Examples 487 and 488

8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- [2- (4-isopropylpiperazin-1-yl) ethyl ] -9H-purin-6-amine and 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- [2- (4-isopropylpiperazin-1-yl) ethyl ] -3H-purin-6-amine.

The title compound was prepared in the following 2-step reaction sequence:

step 1: synthesis of 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfonyl) -9- (2-bromo-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfonyl) -3- (2-bromo-ethyl) -3H-purin-6-ylamine

The procedure followed for steps 1 of 485 and 486 of the examples used 8- (6-bromo-benzo [1, 3]]Dioxol-5-ylsulfonyl) -9H-purin-6-ylamine (200mg, 0.546mmol) to give the title compound 8- (6-bromo-benzo [1, 3] benzo ]Dioxol-5-ylsulfonyl) -9- (2-bromo-ethyl) -9H-purin-6-ylamine and 8- (6-bromo-benzo [1, 3 ]]An inseparable mixture of dioxol-5-ylsulfonyl) -3- (2-bromo-ethyl) -3H-purin-6-ylamine (112mg, 43%) with a 2: 1 ratio of N9 and N3 isomers.¹H NMR(DMSO)δ8.17(s，1H)，7.48(brs，2H)，7.36(s，1H)，6.87(s，1H)，6.09(s，2H)，4.61(t，J＝6.0Hz，2H)，3.89(t，J＝6.0Hz，2H；TOF LC-MS[M+H]⁺473.9。

Step 2: coupling the product of step 1 with 1-isopropylpiperazine

A mixture of the product of step 1 above (50mg, 0.11mmol) and 1-isopropylpiperazine (378mg, 2.64mmol) was heated at 55 ℃ for 10h and purified by preparative HPLC to give N9-isomer (8mg) and N3-isomer (17 mg). 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-9- [2- (4-isopropylpiperazin-1-yl) ethyl]-9H-purin-6-amine.¹H NMR(CD₃OD)δ8.32(s，1H)，7.27(s，1H)，7.22(s，1H)，6.09(s，2H)，4.48(t，J＝5.6Hz，2H)，3.51-3.40(m，3H)，3.24-3.18(m，2H)，3.41-2.98(br t，J＝10.8Hz，2H)，2.91(t，J＝5.6Hz，2H)，2.58-2.49(m，2H)，1.32(d，J＝6.4Hz，6H)；TOF-MS[M+H]⁺520.1. 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-3- [2- (4-isopropylpiperazin-1-yl) ethyl]-3H-purin-6-amine.¹HNMR(CD₃OD) δ 8.51(s, 1H), 7.39(s, 1H), 7.36(s, 1H), 6.16(s, 2H), 4.51(t, J ═ 5.6Hz, 2H), 3.48 (heptad, J ═ 6.4Hz, 1H), 3.45-3.40(m, 2H), 3.19-3.14(m, 2H), 3.00(br d, J ═ 10.0Hz, 2H), 2.95(t, J ═ 5.6Hz, 2H), 2.49(br t, J ═ 11.2Hz, 2H), 1.35(d, J ═ 6.4Hz, 6H); TOF LC-MS [ M + H ]]⁺520.1。

Example 489-495 was synthesized in analogy to the procedures described in examples 487 and 488 using the appropriate starting materials and was isolated as the trifluoroacetate salt after preparative HPLC purification. The analytical data for the examples are summarized in table 9.

TABLE 9

Examples 496 and 497

Synthesis of 1- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-2, 6-dione and 1- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidine-2, 6-dione.

The title example was prepared from the product of step 1, examples 487 and 488 using glutarimide according to the procedure for said examples 485 and 486. 1- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-9H-purin-9-yl } ethyl) piperidine-2, 6-dione¹H NMR(CD₃OD) δ 8.30(s, 1H), 7.26(s, 1H), 7.23(s, 1H), 6.08(s, 2H), 4.53-4.49(m, 2H), 4.26-4.23(m, 2H), 2.55(t, J ═ 6.8Hz, 4H), 1.86 (quintuple, J ═ 6.8Hz, 2H); TOF LC-MS [ M + H ]]⁺505.0. 1- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-3H-purin-3-yl } ethyl) piperidine-2, 6-dione. TOF LC-MS [ M + H ]]⁺505.0。

The corresponding elimination product which accompanies the desired product is also isolated. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -9-vinyl-9H-6-ylamine (example 498)¹H NMR(CD₃OD)δ8.26(s，1H)，7.27(s，1H)，7.21(dd，J＝15.6，9.6Hz，1H)，7.16(s，1H)，6.27(dd，J＝15.6，1.2Hz，1H)，6.09(s，2H)，5.47(dd，J＝9.6，1.2Hz，1H)；LC-MS[M+H]⁺392.0. 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -3-vinyl-3H-6-ylamine (example 499). ¹H NMR(CD₃OD)δ8.68(s，1H)，7.363(s，1H)，7.362(dd，J＝15.6，9.2Hz，1H)，7.35(s，1H)，6.27(dd，J＝15.6，2.0Hz，1H)，6.15(s，2H)，5.51(dd，J＝9.2，2.0Hz，1H)；LC-MS[M+H]⁺392.1。

Example 500-645, summarized in Table 10, was prepared according to the procedures of examples 337 and 338 and isolated as the trifluoroacetate salt after preparative HPLC purification.

Watch 10

Example 646

8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (3-piperidin-2-ylpropyl) -9H-purin-6-amine

The title compound was prepared according to the procedure for the example 465 using the product from example 638. LC-MS [ M + H ]]⁺491.4。

Example 647

8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (3-piperidin-3-ylpropyl) -9H-purin-6-amine

The title compound was prepared according to the procedure for the example 465 using the product obtained from example 637. LC-MS [ M + H ]]⁺491.4。

Example 648

8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (piperidin-4-ylmethyl) -9H-purin-6-amine

The procedure according to said embodiment 465 uses a slaveThe title compound was prepared from the product obtained in example 639. LC-MS [ M + H ]]⁺463.3。

Example 649

8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- (piperidin-3-ylmethyl) -9H-purin-6-amine

The title compound was prepared according to the procedure for the example 465 using the product from example 641. LC-MS [ M + H ] ]⁺463.3。

Example 650

[2- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] acetic acid

The title product was prepared according to the procedure for the example 465 using the product obtained from example 645. LC-MS [ M + H ]]⁺535.4。

Example 651

Reagent: a) barton base, THF, 100 deg.C, MW, 15 min; b) t-BuOK, DMF, 90-100 deg.C, 6h

Step 1: 9- [2- (1-acetylpiperidin-4-yl) -ethyl ] -8-bromo-9H-purin-6-amine and 3- [2- (1-acetylpiperidin-4-yl) -ethyl ] -8-bromo-3H-purin-6-amine.

At room temperatureTo a suspension of 8-bromoadenine (0.042g, 0.197mmol) and toluene-4-sulfonic acid 2- (1-acetyl-piperidin-4-yl) -ethyl ester (0.077g, 0.237mmol) in THF was added Barton base (50. mu.l, 0.237 mmol). The reaction mixture was heated in a microwave reactor at 100 ℃ for 15min, at the end of which period the reaction was cooled to room temperature and the crude product was purified by Isco silica gel flash column using a gradient of 0-5% methanol in dichloromethane to give 0.030g (42%) of 9- [2- (1-acetylpiperidin-4-yl) -ethyl ] -ethyl]-8-bromo-9H-purin-6-amine, LC-MS [ M + H]⁺366.2, and 0.015g (21%) of 3- [2- (1-acetylpiperidin-4-yl) -ethyl]-8-bromo-3H-purin-6-amine, LC-MS [ M + H ]⁺366.2。

Step 2: 9- [2- (1-acetylpiperidin-4-yl) ethyl ] -8- [ (6-nitro-1, 3-benzothiazol-2-yl) thio ] -9H-purin-6-amine.

Reagent: a) t-BuOK, 5-nitro-2-mercaptobenzothiazole, DMF, 90-100 ℃, 6h

To a suspension of 5-nitro-2-mercaptobenzothiazole (0.040g, 0.246mmol) in DMF (1.0mL) at room temperature was added (CH)₃)₃COK (0.028g, 0.246mmol) and stirring was continued for 30 min. To the above reaction mixture was added 9- [2- (1-acetylpiperidin-4-yl) -ethyl ] in DMF (1mL) at room temperature]-8-bromo-9H-purin-6-amine (0.030g, 0.082 mmol). The reaction mixture was heated at 130 ℃ for 6h and at the end of this period the solvent was evaporated and purified by preparative HPLC [ X-Terra prep-RP 1810 um, 19X 250mm (water), mobile phase: solvent A: HPLC grade water with 0.01% TFA, and B: acetonitrile with 0.01% TFA, general elution gradient-solvent B from 15% to 80% over an experimental period of 15 to 25 minutes]The crude product was purified. The HPLC fractions were freeze-dried to give the title product. 9- [2- (1-acetylpiperidin-4-yl) ethyl]-8- [ (6-nitro-1, 3-benzothiazol-2-yl) thio]-9H-purin-6-amine.¹H NMR(CD₃OD)δ8.80(s，1H)，8.30(d，J＝2.4Hz，1H)，8.00(d，J＝9.2Hz，1H)，7.84(s，1H)，4.80(t，J＝7.6Hz，2H)，3.90-3.80(m，2H)，3.20-3.10(m，3H)，3.10-2.60(m，3H)，2.00(s，3H)，1.94-1.80(m，3H).LC-MS[M+H]⁺499.13。

Example 652-661 was prepared according to the procedure of example 651 using the appropriate starting materials, and the analytical data for the example is summarized in table 11. All these compounds were isolated as trifluoroacetate salts after purification by preparative HPLC.

TABLE 11

Intermediate 115

Methanesulfonic acid 3-tert-butyloxycarbonylamino-3- (tetrahydropyran-4-yl) -propyl ester

To [ 3-hydroxy-1- (tetrahydropyran-4-yl) -propyl at 0 DEG C]-carbamic acid tert-butyl ester (0.200g, 0.770mmol) and NEt₃(192. mu.L, 0.920mmol) of CH₂Cl₂To the solution (8mL) was added MsCl (72. mu.L, 0.92mmol) and the mixture was stirred at room temperature for 10 h. The solvent was evaporated to dryness and EtOAC was added. The ethyl acetate layer is subjected to NaHCO₃Washing with an aqueous solution and drying (Na)₂SO₄) Filtration and evaporation of the solvent under reduced pressure gave methanesulfonic acid 3-tert-butoxycarbonylamino-3- (tetrahydropyran-4-yl) -propyl ester (0.162 g). LC-MS [ M + Na ]]360.2. The product was sufficiently pure for the next step to be used without further purification.

Intermediate body 116

Methanesulfonic acid 3-cyclopropyl-3-methanesulfonylamino-propyl ester

The title compound (0.120g) was prepared from N- (1-cyclopropyl-3-hydroxy-propyl) -methanesulfonamide following the procedure for intermediate 115. The product was used in the next step without further purification.

Intermediate 117

Methanesulfonic acid 3-tert-butoxycarbonylamino-3-cyclobutyl-propyl ester

To a solution of 3-tert-butoxycarbonylamino-3-cyclobutyl-propionic acid (0.300g, 1.23mmol) in THF (12mL) at 0 deg.C was added BH ₃-SMe₂(1.70mL, 3.33 mmol; 2.0M solution in THF). After stirring at room temperature for 10h, the reaction mixture was taken up in saturated NaHCO₃Quench, EtOAc extraction, brine wash, dry (Na)₂SO₄) And concentrated in vacuo to give (1-cyclobutyl-3-hydroxy-propyl) -carbamic acid tert-butyl ester (0.100 g); LC-MS [ M + H ]]⁺230.0. The product was sufficiently pure for the next step without further work-upOne step purification was used in the next step.

The title product (0.082g) was prepared by a procedure analogous to intermediate 115 using the above alcohol. LC-MS [ M + H ]]⁺308.3。

Intermediate 118

1- (3-bromo-1-cyclopropyl-propyl) -3-isopropyl-urea

To 3-amino-3-cyclopropan-1-ol hydrochloride (0.25g, 1.65mmol) and NEt at 0 deg.C₃(690. mu.L, 4.95mmol) of CH₃CN (5mL) solution was added 2-isocyanatopropane (180. mu.L, 1.80 mmol). After stirring at room temperature for 10H, the reaction mixture was taken over H₂O quench, EtOAC extraction, brine wash, drying (Na)₂SO₄) Filtered and concentrated in vacuo to give 1- (1-cyclopropyl-3-hydroxy-propyl) -3-isopropyl-urea (0.189 g).

1- (1-cyclopropyl-3-hydroxy-propyl) -3-isopropyl-urea (0.189g, 0.950mmol) was then dissolved in CH₂Cl₂(10mL) and adding CBr₄(0.477g, 1.40mmol), the mixture was cooled to 0 ℃. Adding the bound PPh to the mixture in portions ₃Resin of polymer (0.889g, 1.40 mmol; 1.6 mmol/g). After stirring at room temperature for 3h, the mixture was passed over CH₂Cl₂Diluted (50mL), filtered and passed through CH₂Cl₂The MeOH/acetone washes. The combined filtrates were concentrated in vacuo to give 1- (3-bromo-1-cyclopropyl-propyl) -3-isopropyl-urea (0.212 g). GC-MS m/z 262.

Examples 662 and 663

(3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } -1-cyclopropylpropyl) carbamic acid tert-butyl ester and (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } -1-cyclopropylpropyl) carbamic acid tert-butyl ester

Reacting 8- (6-bromo-benzo [1, 3 ]]A mixture of dioxol-5-ylsulfanyl) -9H-purin-6-ylamine (0.145g, 0.396mmol), (3-bromo-1-cyclopropyl-propyl) -carbamic acid tert-butyl ester (0.228g, 0.82mmol) and Barton base (0.140g, 0.82mmol) in DMF (4mL) was heated at 80-100 ℃ for 6-15H. After cooling, the reaction mixture was concentrated under reduced pressure. By preparative HPLC [ X-Terra prep-RP 1810 um, 19 × 250mm (water), mobile phase: solvent A: HPLC grade water with 0.01% TFA, and B: acetonitrile with 0.01% TFA, general elution gradient-solvent B from 15% to 80% over an experimental period of 15 to 25 minutes ]Purifying the residue. The HPLC fractions were freeze-dried and the N-9 and N-3 isomers were isolated as trifluoroacetate salts. (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-9H-purin-9-yl } -1-cyclopropylpropyl) carbamic acid tert-butyl ester.¹H NMR(DMSO-d₆)δ8.17(s，1H)，7.37(s，1H)，6.79(s，1H)，6.10(s，2H)，4.20-4.19(m，2H)，2.90-2.85(m，2H)，2.00-1.80(m，2H)，1.38(s，9H)，0.40-0.20(m，4H)；LC-MS[M+H]⁺563.10. (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-3H-purin-3-yl } -1-cyclopropylpropyl) carbamic acid tert-butyl ester.¹H NMR(DMSO-d₆)δ8.49(s，1H)，7.51(s，1H)，7.40(s，1H)，6.18(s，2H)，4.35-4.30(m，2H)，2.92-2.85(m，2H)，2.20-1.50(m，6H)，1.38(s，9H)；LC-MS[M+H]⁺563.10。

Example 664-685 was synthesized in a similar procedure to the examples 662 and 663 using the appropriate starting material, which was isolated as the trifluoroacetate salt after preparative HPLC purification.

TABLE 12

Example 686

9- (3-amino-3-cyclobutylpropyl) -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine.

To (3- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-9H-purin-9-yl } -1-cyclobutylpropyl) carbamic acid tert-butyl ester (0.015g, 0.026mmol) in EtOAc (2mL) concentrated HCl (1mL) was added dropwise and the resulting mixture was stirred at room temperature overnight. After concentration under reduced pressure, the remaining HCl was removed by co-evaporation with toluene to give the title product as a hydrochloride salt (0.005 g). ¹H MNR(CD₃OD)δ8.33(s，1H)，7.29(s，1H)，7.19(s，1H)，6.09(s，2H)，4.40-4.28(m，2H)，3.49-3.40(m，4H)，2.50-1.70(m，6H)；LC-MS[M+23]⁺477.9。

Example 687-692 was synthesized in the same manner as described in example 686 using the appropriate starting materials and was isolated as the hydrochloride salt.

Watch 13

Intermediate 119

Toluene-4-sulfonic acid 2- [1- ((S) -2-tert-Butoxycarbonylamino-propionyl) -piperidin-4-yl ] -ethyl ester

Reagent: (a) N-boc-L-Ala-OSu, Et₃N，DMF，120℃，(b)p-TsCl，Et₃N, catalyst DMAP, THF.

At room temperature, to4-Piperidinol (0.25g, 1.93mmol) and NEt₃(403. mu.L, 2.89mmol) in DMF (3mL) was added N-boc-L-Ala-Osu (0.553g, 193mmol) and the mixture was stirred at 120 ℃ for 10 h. The reaction mixture was diluted with EtOAc (60 mL). Ethyl acetate layer via H₂O (60mL) and brine (60mL) over Na₂SO₄Drying, filtering and evaporating the solvent under reduced pressure to give { (S) -2- [4- (2-hydroxy-ethyl) -piperidin-1-yl]-1-methyl-2-oxo-ethyl } -carbamic acid tert-butyl ester (0.581 g). LC-MS [ M + H ]]⁺301.0. The product was sufficiently pure for the next step to be used without further purification. To a mixture of ethanol (0.581g, 1.93mmol), triethylamine (808. mu.L, 5.8mmol) and N, N-lutidine (10mg) in THF (10mL) was added p-toluenesulfonyl chloride (p-TsCl) (0.479g, 2.51mmol) at room temperature and the reaction mixture was stirred for 12 h. The reaction mixture was concentrated in vacuo and diluted with EtOAc (90mL), saturated NaHCO ₃Aqueous solution (75mL), H₂O (75mL) and brine (75 mL). The EtOAc layer was washed with Na₂SO₄Dried, filtered and the solvent evaporated under reduced pressure to give the crude product. The crude product was purified by Isco silica gel flash column using hexane-EtOAc (1: 3) to give pure toluene-4-sulfonic acid 2- [1- ((S) -2-tert-butoxycarbonylamino-propionyl) -piperidin-4-yl]-ethyl ester (0.805 g).¹H NMR(CDCl₃)δ7.79(d，J＝8.2Hz，2H)，7.36(d，J＝8.2Hz，2H)，5.55(d，J＝7.8Hz，1H)，4.62-4.50(m，2H)，4.06(q，J＝6.2Hz，2H)，3.88-3.75(m，1H)，2.97(q，J＝12.1Hz，1H)，2.53(dt，J＝2.7，12.8Hz，1H)，2.46(s，3H)，1.75-1.55(m，4H)，1.49-1.40(m，10H)，1.27(d，J＝7.0Hz，3H)，1.12-0.98(m，2H)；LC-MS[M+H]⁺455.2。

Intermediate body 120

Toluene-4-sulfonic acid 2- [1- (2-dimethylamino-acetyl) -piperidin-4-yl ] -ethyl ester

Reagent: (a) me₂NCH₂COOH, EDCI, DMAP, DMF. (b) P-toluenesulfonyl chloride, Et₃N, catalyst DMAP, THF

To a mixture of N, N-dimethylaminopyridine (1.18g, 9.66mmol), EDCI (1.48g, 7.73mmol) in DMF (5mL) was added carboxylic acid (0.398g, 3.86mmol) followed by 4-piperidineethanol (0.5g, 3.86 mmol). The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with EtOAc (75mL) and washed with brine (60 mL). The EtOAc layer was over Na₂SO₄Dried, filtered and the solvent evaporated under reduced pressure to give the crude amide. The crude product was used in the next tosylation reaction without further purification. To a mixture of the above crude product (0.827g, 3.86mmol) and triethylamine (3.22mL, 23.18mmol) in THF (20mL) was added p-toluenesulfonyl chloride (2.21g, 11.59mmol) at room temperature and stirred for 12 h. The reaction mixture was concentrated in vacuo and the crude product was dissolved in EtOAc (100mL) and saturated NaHCO ₃The aqueous solution (90mL) was washed with brine (90 mL). The EtOAc layer was washed with Na₂SO₄Drying, filtration and evaporation of the solvent under reduced pressure gave the crude product which was purified by Isco silica flash column using hexane-EtOAc (1: 9) to give 0.45g of toluene-4-sulfonic acid 2- [1- (2-dimethylamino-acetyl) -piperidin-4-yl]-ethyl ester. LC-MS [ M + H ]]⁺369.2。

Intermediate 121

Acetic acid (S) -1-methyl-2-oxo-2- {4- [2- (toluene-4-sulfonyloxy) -ethyl ] -piperidin-1-yl } -ethyl ester

Reagent: a) (S) -CH₃CH(OCOCH₃)COCl，NEt₃THF; b) p-toluenesulfonyl chloride, Et₃N, catalyst DMAP, THF

In the roomTo a mixture of piperidineethanol (2g, 15.5mmol) and triethylamine (4.3mL, 31.0mmol) in tetrahydrofuran (15mL) was added dropwise acetic acid (S) -1-chlorocarbonyl-ethyl ester (2.1mL, 17.0mmol) at room temperature. The reaction mixture was stirred at room temperature for 8 h. The reaction mixture was dissolved in ethyl acetate (100mL) and saturated NaHCO was used₃The aqueous solution (90mL) and the saline solution (90mL) were washed sequentially. The ethyl acetate layer was washed with Na₂SO₄The solvent was dried, filtered and evaporated under reduced pressure to give a crude product (1.6g), which was used in the next tosylation reaction without further purification. The crude product obtained in the above step was dissolved in tetrahydrofuran (20mL) and triethylamine (2.28mL, 16.4mmol) and N, N-lutidine (20mg) were added at room temperature followed by p-toluenesulfonyl chloride (1.5g, 7.9mmol) and the reaction mixture was stirred for 12 h. The reaction mixture was concentrated in vacuo and diluted with EtOAc (90mL) and saturated NaHCO ₃Aqueous solution (75mL), H₂O (75mL) and brine (75 mL). The EtOAc layer was washed with Na₂SO₄Dried, filtered and the solvent evaporated under reduced pressure to give the crude product. The crude product was purified by Isco silica flash column using hexane-EtOAc (1: 3) solvent system to give pure (S) -acetic acid 1-methyl-2-oxo-2- {4- [2- (toluene-4-sulfonyloxy) -ethyl]Piperidin-1-yl } -ethyl ester (2.3 g).¹H NMR(CDCl₃)δ7.79(d，J＝8.2Hz，2H)，7.36(d，J＝8.2Hz，2H)，5.37(d，J＝6.6Hz，1H)，4.53(t，J＝14.0Hz，1H)，4.14-4.00(m，2H)，3.78(t，J＝13.0Hz，1H)，3.10-2.92(m，1H)，2.60-2.40(m，4H)，2.12(s，3H)，1.80-1.50(m，5H)，1.41(d，J＝6.6Hz，3H)，1.20-1.00(m，2H)；LC-MS[M+H]⁺398.3。

Intermediate 122-151 summarized in Table 14 was prepared using one of the methods described for intermediate 119-121.

TABLE 14

Examples 693 and 694

[ (S) -2- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-9-yl ] -ethyl } -piperidin-1-yl) -1-methyl-2-oxo-ethyl ] -carbamic acid tert-butyl ester and [ (S) -2- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3] dioxol-5-ylsulfanyl) -purin-3-yl ] -ethyl } -piperidin-1-yl) -1-methyl-2-oxo-ethyl ] -carbamic acid tert-butyl ester.

Reagent: (a) barton base, DMF, 90-100 deg.C

Toluene-4-sulfonic acid 2- [1- ((S) -2-tert-butoxycarbonylamino-propionyl) -piperidin-4-yl]-ethyl ester (0.223g, 0.49mmol), 8- (6-bromo-benzo [1, 3]]A mixture of dioxol-5-ylsulfanyl) -9H-purin-6-ylamine (0.075g, 0.20mmol) and Barton base (101 μ L, 0.49mmol) in DMF (2.5mL) was heated at 90-100 deg.C for 15H. After cooling, the reaction mixture was concentrated under reduced pressure. Passing system Preparative HPLC [ X-Terra prep-RP 1810 um, 19 × 250mm (water), mobile phase: solvent A: HPLC grade water with 0.01% TFA, and solvent B: acetonitrile with 0.01% TFA, general elution gradient-solvent B from 15% to 80% over an experimental period of 15 to 25 minutes]Purifying the residue. The HPLC fractions were freeze-dried and the N-9 and N-3 isomers were isolated as trifluoroacetate salts. [ (S) -2- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -purin-9-yl]-ethyl } -piperidin-1-yl) -1-methyl-2-oxo-ethyl]-tert-butyl carbamate:¹H NMR(CDCl₃)δ8.20(s，1H)，7.15(s，1H)，7.06(s，1H)，6.07(s，2H)，5.57(d，J＝7.8Hz，1H)，4.68-4.55(m，2H)，4.29(t，J＝7.4Hz，2H)，3.96-3.85(m，1H)，1.98-1.75(m，4H)，1.66-1.5(m，1H)，1.44(s，9H)，1.36-1.22(m，5H)；TOF-MS[M+H]⁺648.16. { (S) -2- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -purin-3-yl]-ethyl } -piperidin-1-yl) -1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester, TOF-MS [ M + H]⁺648.16。

Example 695-one 741 was synthesized in the same manner as described in examples 693 and 694 using appropriate starting materials and was isolated as the trifluoroacetate salt after preparative HPLC purification.

Watch 15

Example 742

9- (2- {1- [ (2S) -2-aminopropionyl ] piperidin-4-yl } ethyl) -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine

Reagent: (a) TFA, DCM.

To [ (S) -2- (4- {2- [ 6-amino-8- (6-bromo-benzo [1, 3 ] at room temperature ]Dioxol-5-ylsulfanyl) -purin-9-yl]-ethyl } -piperidin-1-yl) -1-methyl-2-oxo-ethyl]Tert-butyl carbamate (0.014g, 0.021mmol) in DCM (3mL) was added TFA (100 μ L) dropwise and the resulting mixture was stirred at room temperature overnight. After concentration under reduced pressure, the remaining TFA was removed to give the title compound (0.015g) as a TFA salt.¹H NMR(CD₃OD)δ8.34(s，1H)，7.28(s，1H)，7.23(s，1H)，6.09(s，2H)，4.54-4.44(m，2H)，4.39(t，J＝7.42Hz，2H)，3.85(broad d，J＝13.2Hz，1H)，3.19-3.08(m，1H)，2.75-2.63(m，1H)，2.00-1.80(m，4H)，1.70-1.58(m，1H)，1.44(dd，J＝14.8，7.0Hz，3H)，1.35-1.13(m，2H)；LC-MS [M+H]⁺548.2。

Example 743-755, summarized in Table 16, was synthesized in the same manner as described for example 742 using the appropriate starting materials and isolated as the trifluoroacetate salt.

TABLE 16

Examples 756 and 757

(2S) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidin-1-yl ] -1-oxopropan-2-ol and (2S) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -1-oxopropan-2-ol

Reagent: (a) barton base, DMF, 90-100 deg.C; (b) h, LiOH₂O，MeOH-THF-H₂O(1∶1∶1)。

Step 1: in accordance with saidThe procedures of examples 1 and 2 used 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine (0.200g, 0.54mmol) and acetic acid (S) -1-methyl-2-oxo-2- {4- [2- (toluene-4-sulfonyloxy) -ethyl ]-piperidin-1-yl } -ethyl ester (0.325g, 0.81mmol) was subjected to the alkylation reaction to give a mixture of N-3 and N-9 isomers. Acetic acid (1S) -2- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] salt]-3H-purin-3-yl } ethyl) piperidin-1-yl]-1-methyl-2-oxoethyl ester, LC-MS [ M + H]⁺591.1, respectively; and (1S) -2- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio acetate]-9H-purin-9-yl } ethyl) piperidin-1-yl]-1-methyl-2-oxoethyl ester, LC-MS [ M + H]⁺591.1. The crude mixture was used for the next hydrolysis reaction without further purification.

Step 2: to the above product in MeOH-THF-H₂LiOH. H was added to a solution of O mixture (1: 1, 10mL)₂O (0.1g), and the resulting mixture was stirred at room temperature overnight. After concentration of the reaction mixture under reduced pressure, the reaction mixture was purified by preparative HPLC [ X-Terraprep-RP 1810 um, 19 × 250mm (water), mobile phase: solvent A: HPLC grade water with 0.01% TFA, and solvent B: acetonitrile with 0.01% TFA, general elution gradient-solvent B from 15% to 80% over an experimental period of 15 to 25 minutes]Purifying the residue. The title compound was isolated as the trifluoroacetate salt after lyophilization of the HPLC fractions. (2S) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] thio ]-3H-purin-3-yl } ethyl) piperidin-1-yl]-1-oxoprop-2-ol, TOF-MS [ M + H]⁺549.1, respectively; and (2S) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-9H-purin-9-yl } ethyl) piperidin-1-yl]-1-oxopropan-2-ol,¹HNMR(CD₃OD)δ8.31(s，1H)，7.28(s，1H)，7.20(s，1H)，6.09(s，2H)，4.60-4.45(m，2H)，4.37(t，J＝7.8Hz，2H)，4.00(d，J＝12.0Hz，1H)，3.10-2.98(m，1H)，2.70-2.56(m，1H)，1.96-1.79(m，4H)，1.70-1.55(m，1H)，1.30(dd，J＝7.0，10.1Hz，3H)，1.26-1.10(m，2H)；LC-MS[M+H]⁺549.1。

example 758-

Examples 758 and 765 were prepared according to the procedures described for examples 756 and 757 using the appropriate starting materials. All compounds summarized in table 17 were isolated as trifluoroacetate salts after HPLC purification.

TABLE 17

Examples 766 and 767

(2R) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidin-1-yl ] -1-oxopropan-2-ol and (2R) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -1-oxopropan-2-ol

Reagent: (a) TBDPS-Cl, Et₃N，THF，(b)LiOH.H₂O，MeOH，THF，H₂O，(c)(COCl)₂DCM, catalyst DMF, (d) 4-piperidineethanol, Et₃N, THF, (e) p-toluenesulfonyl chloride, Et₃N, catalyst DMAP, THF, (f) intermediate 34, Barton base, DMF, 90-100 ℃, (g) TBAF, THF.

Step 1: (2R) -2- { [ tert-butyl (diphenyl) silyl ] oxy } propanoic acid

To a mixture of (R) -methyl 2-hydroxy-propionate (1.0g, 9.6mmol) and triethylamine (4.0mL, 28.81mmol) in tetrahydrofuran (12mL) was added tert-butyldiphenylsilyl chloride (3.68mL, 14.4mmol) at room temperature and the reaction mixture was stirred for 12 h. After the reaction was complete, the reaction mixture was diluted with EtOAc (80mL) and washed with water (70mL) and brine (70 mL). The EtOAc layer was washed with Na ₂SO₄Drying and evaporation of the solvent in vacuo to give (2R) -2- { [ tert-butyl (diphenyl) silyl]Oxy } propanoic acid methyl ester (3.28 g). The crude material was sufficiently pure for the next step and was used without further purification. The crude material was taken up in THF-MeOH-H₂O (1: 1, 20mL) and LiOH₂O (1.17g, 28.0 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was neutralized with concentrated HCl and concentrated in vacuo. The residue was diluted with 75mL of water and extracted with EtOAc (3X 50mL), and the combined EtOAc layers were Na₂SO₄Dried and evaporated in vacuo. The crude carboxylic acid was purified by Isco silica flash column using EtOAc to give the carboxylic acid (0.6 g).¹H NMR(CDCl₃)δ7.70-7.60(m，4H)，7.50-7.38(m，6H)，4.32(q，J＝6.6Hz，1H)，1.30(d，J＝7.0Hz，9H)；LC-MS[M-H]⁺327.2。

Step 2: 2- [1- ((2R) -2- { [ tert-butyl- (diphenyl) silyl ] -oxy } propanoyl) -piperidin-4-yl ] -ethanol

To a mixture of the above carboxylic acid (0.6g, 1.82mmol) in dichloromethane (15mL) was added oxalyl chloride (464. mu.L, 3.65mmol) at ice-cold temperature, followed by two drops of N, N-dimethylformamide. The reaction mixture was left at room temperature and stirred for 6 h. At the end of this period, the excess oxalyl chloride was evaporated under reduced pressure to give the corresponding acid chloride. The acid chloride was diluted with 2mL of THF and added to a mixture of 4-piperidineethanol (0.235g, 1.8mmol) and triethylamine (763. mu.L, 5.48mmol) in THF (7mL) at room temperature. The reaction mixture was stirred overnight and after completion of the reaction mixture was used EtOAc (60mL) is diluted and saturated NaHCO₃Aqueous solution (60mL) and brine (60 mL). The EtOAc layer was washed with Na₂SO₄Dried, filtered and the solvent evaporated under reduced pressure to give the crude product. The crude product was purified by Isco silica gel flash column using hexane-EtOAc (1: 3) to give 0.748g of 2- [1- ((2R) -2- { [ tert-butyl- (diphenyl) silyl]-oxy } propanoyl) -piperidin-4-yl]-ethanol.¹H NMR(CDCl₃) δ 7.70-7.60(m, 4H), 7.46-7.33(m, 6H), 4.55(t, J ═ 5.4Hz, 1H), 4.43(d, J ═ 12.8Hz, 1H), 4.26 and 4.06(2d, J ═ 12.5Hz, 1H), 3.66(q, J ═ 5.8Hz, 2H), 2.86 and 2.69(2t, J ═ 12.8Hz, 1H), 2.5-2.34(m, 1H), 1.70-1.54(m, 4H), 1.43(q, J ═ 6.6Hz, 2H), 1.34(t, J ═ 7.0Hz, 3H), 1.20-1.28(m, 1H), 1.08(s, 9H); LC-MS [ M + H ]]440.3。

And step 3: 2- [1- ((2R) -2- { [ tert-butyl- (diphenyl) -silyl ] -oxy } -propionyl) -piperidin-4-yl ] -ethyl 4-methylbenzenesulfonate

To 2- [1- ((2R) -2- { [ tert-butyl- (diphenyl) silyl group at room temperature]-oxy } propanoyl) -piperidin-4-yl]To a solution of ethanol (0.748g, 1.7mmol) in tetrahydrofuran (10mL) was added triethylamine (711. mu.L, 5.11mmol) and N, N-lutidine (10mg), followed by p-toluenesulfonyl chloride (0.487g, 2.55mmol), and the reaction mixture was stirred for 12 h. The reaction mixture was concentrated in vacuo and diluted with EtOAc (60mL) and saturated NaHCO ₃Aqueous solution (50mL) and brine (50 mL). The EtOAc layer was washed with Na₂SO₄Dried, filtered and the solvent evaporated under reduced pressure to give the crude product. The crude product was purified by Isco silica gel flash column using hexane-EtOAc (1: 3) to give 0.69g of 2- [1- ((2R) -2- { [ tert-butyl- (diphenyl) -silyl]-oxy } -propionyl) -piperidin-4-yl]-ethyl 4-methylbenzenesulfonate.¹H NMR(CDCl₃)δ7.79(d，J＝7.8Hz，2H)，7.68-7.58(m，4H)，7.40-7.32(m，8H)，4.60-4.50(m，1H)，4.44-4.35(m，1H)，4.30-3.96(m，4H)，2.85-2.58(m，1H)，2.45(s，3H)，2.40-2.25(m，1H)，1.58-1.42(m，5H)，1.40-1.30(m，5H)，1.07(s，9H)，1.00-0.80(m，1H)；LC-MS[M+23]⁺616.2。

And 4, step 4: 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [1- ((2R) -2- { [ tert-butyl (diphenyl) silyl ] oxy } propanoyl) piperidin-4-yl ] ethyl } -9H-purin-6-amine and 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- {2- [1- ((2R) -2- { [ tert-butyl (diphenyl) silyl ] oxy } propanoyl) piperidin-4-yl ] ethyl } -3H-purin-6-amine

The procedure according to said examples 1 and 2 was followed using 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine (0.172g, 0.47mmol) and 2- [1- ((2R) -2- { [ tert-butyl- (diphenyl) -silyl ] obtained from step 3]-oxy } -propionyl) -piperidin-4-yl]-Ethyl 4-methylbenzenesulfonate (0.280g, 0.47mmol) to give 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ]-9- {2- [1- ((2R) -2- { [ tert-butyl (diphenyl) silyl]Oxy } propionyl) piperidin-4-yl]Ethyl } -9H-purin-6-amino, LC-MS [ M +1 ]]⁺787.1, respectively; and 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-3- {2- [1- ((2R) -2- { [ tert-butyl (diphenyl) silyl]Oxy } propionyl) piperidin-4-yl]Ethyl } -3H-purin-6-amino, LC-MS [ M + H ]]⁺787.1。

And 5: (2R) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -1-oxopropan-2-ol and (2R) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidin-1-yl ] -1-oxopropan-2-ol

To a mixture of 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9- {2- [1- ((2R) -2- { [ tert-butyl (diphenyl) silyl ] oxy } propanoyl) piperidin-4-yl ] ethyl } -9H-purin-6-amine and 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3- {2- [1- ((2R) -2- { [ tert-butyl (diphenyl) silyl ] oxy } propanoyl) piperidin-4-yl ] ethyl } -3H-purin-6-amine (0.314g, 0.398mmol) in THF (5mL), a solution of tetra-n-butylammonium fluoride (0.47mL, 0.47mmol) in 1.0M THF was added and the reaction mixture was stirred at room temperature overnight. After completion of the reaction, the reaction mixture was concentrated and purified by preparative HPLC [ X-Terraprep-RP 1810 um, 19 × 250mm (water), mobile phase: solvent A: HPLC grade water with 0.01% TFA, and solvent B: acetonitrile with 0.01% TFA, general elution gradient-solvent B from 15% to 80% over an experimental time of 15 to 25 minutes ]. The HPLC fractions were freeze-dried and the N-9 and N-3 isomers were isolated as trifluoroacetate salts.

(2R) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] methyl ester]-3H-purin-3-yl } ethyl) piperidin-1-yl]-1-oxoprop-2-ol, LC-MS [ M + H]⁺549.1, respectively; and (2R) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-9H-purin-9-yl } ethyl) piperidin-1-yl]-1-oxoprop-2-ol, LC-MS [ M + H]⁺549.1。

Examples 768 and 769

(2S) -1- (4- {2- [ 6-amino-8- (2, 3-dihydro-1-benzofuran-5-ylthio) -9H-purin-9-yl ] ethyl } piperidin-1-yl) -1-oxopropan-2-ol and (2S) -1- (4- {2- [ 6-amino-8- (2, 3-dihydro-1-benzofuran-5-ylthio) -3H-purin-3-yl ] ethyl } piperidin-1-yl) -1-oxopropan-2-ol

The title compound was synthesized in analogy to the procedures of examples 756 and 757 using 8- (2, 3-dihydro-benzofuran-5-ylsulfanyl) -9H-purin-6-ylamine (0.100g, 0.350mmol) and acetic acid (S) -1-methyl-2-oxo-2- {4- [2- (toluene-4-sulfonyloxy) -ethyl]-piperidin-1-yl } -ethyl ester (0.278g, 0.700mmol) was prepared to give acetic acid (1S) -2- (4- {2- [ 6-amino-8- (2, 3-dihydro-1-benzofuran-5-ylthio) -9H-purin-9-yl]Ethyl } piperidin-1-yl) -1-methyl-2-oxoethyl ester, LC-MS [ M + H]⁺511.2 and acetic acid (1S) -2- (4- {2- [ 6-amino-8- (2, 3-dihydro-1-benzofuran-5-ylthio) -3H-purin-3-yl ]Ethyl } piperidin-1-yl) -1-methyl-2-oxoethyl ester, LC-MS [ M + H]⁺511.2 by mixingA compound (I) is provided.

The above mixture was treated with lioh.h as described in examples 62 and 63₂O-treatment and separation of the isomers by preparative HPLC. (2S) -1- (4- {2- [ 6-amino-8- (2, 3-dihydro-1-benzofuran-5-ylthio) -9H-purin-9-yl]Ethyl } piperidin-1-yl) -1-oxopropan-2-ol.¹H NMR(CD₃OD)δ8.28(s，1H)，7.49(s，1H)，7.40(dd，J＝1.9，8.2Hz，1H)，6.84(d，J＝8.2Hz，1H)，4.62(t，J＝8.5Hz，，2H)，4.59-4.42(m，2H)，4.34(t，J＝7.4Hz，，2H)，4.06-3.97(m，1H)，3.25(t，J＝8.5Hz，，2H)，3.10-2.98(m，1H)，2.70-2.39(m，1H)，1.96-1.74(m，4H)，1.70-1.55(m，1H)，1.35-1.10(m，5H)；TOF-MS[M+H]⁺469.2. (2S) -1- (4- {2- [ 6-amino-8- (2, 3-dihydro-1-benzofuran-5-ylthio) -3H-purin-3-yl]Ethyl } piperidin-1-yl) -1-oxopropan-2-ol. TOF-MS [ M + H]⁺469.2。

Examples 770 and 771

(2S) -3- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } ethyl) piperidin-1-yl ] -3-oxopropan-1, 2-diol and (2S) -3- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -3-oxopropan-1, 2-diol

Reagent: barton alkali, DMF, 90-100 deg.C, 16 h; b) AcOH aqueous solution, rt, 12h

Step 1: the procedure according to said examples 1 and 2 was followed using 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine (0.100g, 0.27mmol) and toluene-4-sulfonic acid 2- [1- ((S) -2, 2-dimethyl- [1, 3]Dioxacyclopentadienone-4-carbonyl) -piperidin-4-yl ]-Ethyl ester (0.224g, 0.54mmol) to give 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-3- [2- (1- { [ (4S) -2, 2-bisMethyl-1, 3-dioxolan-4-yl radical]Carbonyl } piperidin-4-yl) ethyl]-3H-purin-6-amine, LC-MS [ M + H]⁺605.2 and 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-9- [2- (1- { [ (4S) -2, 2-dimethyl-1, 3-dioxolan-4-yl]Carbonyl } piperidin-4-yl) ethyl]-9H-purin-6-amine, LC-MS [ M + H]⁺605.2 of the mixture. The crude mixture was used in the next reaction without further purification.

Step 2: the 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio from step 1]-3- [2- (1- { [ (4S) -2, 2-dimethyl-1, 3-dioxolan-4-yl]Carbonyl } piperidin-4-yl) ethyl]-3H-purin-6-amine and 8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-9- [2- (1- { [ (4S) -2, 2-dimethyl-1, 3-dioxolan-4-yl]Carbonyl } piperidin-4-yl) ethyl]The crude mixture of-9H-purin-6-amine (0.31g, 0.51mmol) was dissolved in 60% aqueous AcOH (5mL) and the reaction mixture was stirred for 12H. By K₂CO₃The reaction mixture was neutralized and the contents evaporated. The residue was diluted with MeOH-DCM (1: 2) (10mL) and filtered. The filtrate was evaporated under reduced pressure. By preparative HPLC [ X-Terra prep-RP 1810 um, 19 × 250mm (water), mobile phase: solvent A: HPLC grade water with 0.01% TFA, and solvent B: acetonitrile with 0.01% TFA, general elution gradient-solvent B from 15% to 80% over an experimental period of 15 to 25 minutes ]Purifying the mixture. The HPLC fractions were freeze-dried and the N-9 and N-3 isomers were isolated as trifluoroacetate salts. (2S) -3- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] methyl ester]-3H-purin-3-yl } ethyl) piperidin-1-yl]-3-oxopropan-1, 2-diol. TOF-MS [ M + H]⁺565.09 and (2S) -3- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-9H-purin-9-yl } ethyl) piperidin-1-yl]-3-oxopropan-1, 2-diol.¹H NMR(CD₃OD)δ8.34(s，1H)，7.28(s，1H)，7.22(s，1H)，6.09(s，2H)，4.55-4.45(m，2H)，4.38(t，J＝7.0Hz，2H)，4.12-4.02(m，1H)，3.73-3.58(m，2H)，3.12-3.00(m，1H)，2.70-2.60(m，1H)，1.95-1.55(m，5H)，1.30-1.10(m，2H)；TOF-MS[M+H]⁺565.09。

Example 772

((1S) -2- {4- [2- (6-amino-8-bromo-9H-purin-9-yl) ethyl ] piperidin-1-yl } -1-methyl-2-oxoethyl) carbamic acid tert-butyl ester

Reagent: a) barton base, THF, 100 deg.C, MW, 15 min;

to a suspension of 8-bromoadenine (0.08g, 0.367mmol) and toluene-4-sulfonic acid 2- [1- ((S) -2-tert-butoxycarbonylamino-propionyl) -piperidin-4-yl ] -ethyl ester (0.200g, 0.440mmol) in THF at room temperature was added Barton base (91. mu.1, 0.40 mmol). The reaction mixture was heated in a microwave reactor at 100 ℃ for 15min, at the end of this period the reaction was cooled to room temperature and the crude product was purified by an Isco silica gel flash column using a 0-30% gradient of EtOAc-hexane to give tert-butyl { (1S) -2- [4- (2- { 6-amino-8- [ (7-chloro-1, 3-benzothiazol-2-yl) thio ] -3H-purin-3-yl } ethyl) piperidin-1-yl ] -1-methyl-2-oxoethyl } carbamate and { (1S) -2- [4- (2- { 6-amino-8- [ (7-chloro-1, 3-benzothiazol-2-yl) thio ] -9H-purin-9-yl } ethyl Yl) piperidin-1-yl ] -1-methyl-2-oxoethyl } carbamic acid tert-butyl ester (0.090g, 49%).

Example 773

{ (1S) -2- [4- (2- { 6-amino-8- [ (7-chloro-1, 3-benzothiazol-2-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -1-methyl-2-oxoethyl } carbamic acid tert-butyl ester

Reagent: a) 7-chloro-2-mercaptobenzothiazole, (CH)₃)₃COK，DMF，130℃，6h；

At room temperatureTo a suspension of 7-chloro-2-mercaptobenzothiazole (0.020g, 0.097mmol) in DMF (2.0mL) was added (CH)₃)₃COK (0.011g, 0.97mmol) and stirring continued for 30 min. To the above reaction mixture was added ((1S) -2- {4- [2- (6-amino-8-bromo-9H-purin-9-yl) ethyl) at room temperature]A mixture of piperidin-1-yl } -1-methyl-2-oxoethyl) carbamic acid tert-butyl ester (0.040g, 0.081mmol) in DMF (1 mL). The reaction mixture was heated at 130 ℃ for 6h, at the end of this period the solvent was evaporated and the residue was purified by preparative HPLC [ X-terrra prep-RP 1810 um, 19X 250mm (water), mobile phase: solvent A: HPLC grade water with 0.01% TFA, and solvent B: acetonitrile with 0.01% TFA, general elution gradient-solvent B from 15% to 80% over an experimental period of 15 to 25 minutes]Purifying the crude product. The HPLC fractions were freeze-dried to give the title product.¹H NMRδ(CD₃OD)，8.35(s，1H)，7.85-7.82(m，1H)，7.50-7.40(m，2H)，4.40(t，J＝7.2Hz，2H)，4.00-3.90(m，2H)，1.80-1.70(m，4H)，1.21-1.15(m，6H)，1.15(s，9H)，1.10(s，3H)；LC-MS[M+H]⁺617.1。

Example 774

9- (2- {1- [ (2S) -2-aminopropionyl ] piperidin-4-yl } ethyl) -8- [ (7-chloro-1, 3-benzothiazol-2-yl) thio ] -9H-purin-6-amine

To a solution of the Boc-protected product of example 773 in DCM was added TFA and stirred at rt for 3 h. The solvent and excess TFA were evaporated under reduced pressure and the remaining TFA was removed by co-evaporation with toluene to give the title product as the trifluoroacetate salt.¹H NMRδ(CD₃OD)，8.35(s，1H)，7.84-7.82(m，1H)，7.50-7.40(m，2H)，4.40(t，J＝7.2Hz，2H)，4.00-3.90(m，1H)，1.80-1.70(m，4H)，1.41-1.37(m，4H)，1.32-1.30(m，3H)，1.20(s，3H)；LC-MS[M+H]⁺517.1。

Example 775

(2S) -1- [4- (2- { 6-amino-8- [ (7-chloro-1, 3-benzothiazol-2-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -1-oxopropan-2-ol

Step 1: acetic acid (1S) -2- {4- [2- (6-amino-8-bromo-9H-purin-9-yl) ethyl ] piperidin-1-yl } -1-methyl-2-oxoethyl ester

The title compound was synthesized according to the procedure for the preparation of examples 756 and 757 (step 1) using acetic acid (S) -1-methyl-2-oxo-2- {4- [2- (toluene-4-sulfonyloxy) -ethyl]-piperidin-1-yl } -ethyl ester and 8-bromoadenine to give (1S) -2- {4- [2- (6-amino-8-bromo-9H-purin-9-yl) ethyl acetate]Piperidin-1-yl } -1-methyl-2-oxoethyl ester and (1S) -2- {4- [2- (6-amino-8-bromo-3H-purin-3-yl) ethyl acetate]Piperidin-1-yl } -1-methyl-2-oxoethyl ester. The mixture was purified by Isco silica flash column using EtOAc to give (1S) -2- {4- [2- (6-amino-8-bromo-9H-purin-9-yl) ethyl acetate]Piperidin-1-yl } -1-methyl-2-oxoethyl ester. LC-MS [ M + H ]]⁺439.1。

Step 2: acetic acid (1S) -2- [4- (2- { 6-amino-8- [ (7-chloro-1, 3-benzothiazol-2-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -1-methyl-2-oxoethyl ester

The procedure of example 81 was followed using acetic acid (1S) -2- {4- [2- (6-amino-8-bromo-9H-purin-9-yl) ethyl]Piperidin-1-yl } -1-methyl-2-oxoethyl ester and 7-chloro-2-mercaptobenzothiazolePreparation of the title Compound, LC-MS [ M + H]⁺562.1, along with the hydrolysate, the mixture was used in the next step without any further purification.

And step 3: (2S) -1- [4- (2- { 6-amino-8- [ (7-chloro-1, 3-benzothiazol-2-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -1-oxopropan-2-ol

Suspending the crude product of step 2 in methanol and adding K₂CO₃And stirring was continued for 2 h. The title product was isolated as the trifluoroacetate salt after purification by preparative HPLC. LC-MS [ M + H ]]⁺518.1。

Examples 776 and 777

9- {2- [1- (1-acetyl-L-prolyl) piperidin-4-yl ] ethyl } -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine and 3- {2- [1- (1-acetyl-L-prolyl) piperidin-4-yl ] ethyl } -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-6-amine

The procedure according to said examples 1 and 2 was followed using 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and toluene-4-sulfonic acid 2- [1- [ (S) -1-acetyl-pyrrolidine-2-carbonyl) -piperidin-4-yl ]-ethyl ester to prepare the title compound. The product was isolated as the trifluoroacetate salt after preparative HPLC purification and freeze drying of the HPLC fractions. 9- {2- [1- (1-acetyl-L-prolyl) piperidin-4-yl]Ethyl } -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] sulfide]-9H-purin-6-amine¹H NMR(CD₃OD)δ8.28(s，1H)，7.28(s，1H)，7.19 and 7.17(s，1H)，6.09(s，2H)，4.47(m，1H)，4.37(t，J＝7.2Hz，2H)，4.04(m 1H)，3.67-3.56(m，2H)，3.15(m，1H)，2.64(m，1H)，2.23(m，1H)，2.08and 2.076(s，3H)，2.06-1.96(m，2H)，1.91-1.78(m，6H)，1.62(m，1H)，1.23(m，1H)，1.11(m，1H)；LC-MS[M+H]⁺616.1. 3- {2- [1- (1-acetyl-L-prolyl) piperidin-4-yl]Ethyl } -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] sulfide]-3H-purin-6-amine. LC-MS [ M + H ]]⁺616.1。

Examples 778 and 779

Tert-butyl { (1S) -2- [3- ({ 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } methyl) piperidin-1-yl ] -1-methyl-2-oxoethyl } carbamate and tert-butyl { (1S) -2- [3- ({ 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } methyl) piperidin-1-yl ] -1-methyl-2-oxoethyl } carbamate.

The procedure according to said examples 1 and 2 was followed using 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and toluene-4-sulfonic acid 1- ((S) -2-tert-butoxycarbonylamino-propionyl) -piperidin-3-ylmethyl ester the title compound was prepared. The product was isolated as the trifluoroacetate salt. { (1S) -2- [3- ({ 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio) ]-9H-purin-9-yl } methyl) piperidin-1-yl]-1-methyl-2-oxoethyl } carbamic acid tert-butyl ester, LC-MS [ M + H]⁺634.5, respectively; and { (1S) -2- [3- ({ 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-3H-purin-3-yl } methyl) piperidin-1-yl]-1-methyl-2-oxoethyl } carbamic acid tert-butyl ester, LC-MS [ M + H]⁺634.5。

Example 780

9- ({1- [ (2S) -2-aminopropionyl ] piperidin-3-yl } methyl) -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine

The title compound was synthesized according to the procedure for the preparation of example 50 using { (1S) -2- [3- ({ 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-9H-purin-9-yl } methyl) piperidin-1-yl]-1-methyl-2-oxoethyl } aminomethane tert-butanoate, and isolating as trifluoroacetate. LC-MS [ M + H ]]⁺534.4。

Examples 781 and 782

Tert-butyl { (1R) -2- [4- ({ 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } methyl) piperidin-1-yl ] -1-methyl-2-oxoethyl } carbamate and tert-butyl { (1R) -2- [4- ({ 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -3H-purin-3-yl } methyl) piperidin-1-yl ] -1-methyl-2-oxoethyl } carbamate.

The procedure according to said examples 1 and 2 was followed using 8- (6-bromo-benzo [1, 3 ]]Dioxol-5-ylsulfanyl) -9H-purin-6-ylamine and toluene-4-sulfonic acid 1- ((R) -2-tert-butoxycarbonylamino-propionyl) -piperidin-4-ylmethyl ester the title compound was prepared. The title compound was isolated as the trifluoroacetate salt after purification by preparative HPLC. { (1R) -2- [4- ({ 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio)]-9H-purin-9-yl } methyl) piperidin-1-yl]-1-methyl-2-oxoethyl } carbamic acid tert-butyl ester, LC-MS [ M + H]⁺634.5, respectively; and { (1R) -2- [4- ({ 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio]-3H-purin-3-yl } methyl) piperidin-1-yl]-1-methyl-2-oxoethyl } carbamic acid tert-butyl ester, LC-MS [ M + H]⁺634.5。

Active examples

Binding assays

By improvement by Kim et alThe binding of the compound to purified Hsp90 was monitored using BODIPY-labeled geldanamycin (BODIPY-GM) in a fluorescence polarization assay (Journal of biomolecular Screening 2004, 9 (5): 375-381). Dilutions of compounds (in 100% DMSO) were added to black-bottom 96-well plates (Greiner; final 2% DMSO) and equal volumes of assay buffer (20mM HEPES-KOH pH 7.3, 50mM KCl, 5mM MgCl) were added sequentially ₂，20mM Na₂MoO₄0.01% NP-40, 0.1mg/mL bovine serum gamma globulin [ Invitrogen, P2045]2mM DTT) and purified human Hsp90(Stressgen, SPP-770; final concentration 30nM) to give a final volume of 50 μ l. The plates were incubated overnight at room temperature. Parallel and perpendicular fluorescence measurements were taken at an excitation/emission wavelength of 485/530nm (LJL BioSystems analysis AD plate reader). Background fluorescence (buffer only) was subtracted and Fluorescence Polarization (FP) values in mP units were calculated from parallel and perpendicular fluorescence readings as follows:

FP (parallel-perpendicular)/(parallel + perpendicular) 1000

Percent inhibition was calculated by: the FP values were normalized to the values obtained from the DMSO-containing parallel reactions and these normalized values were subtracted from 100%. Fluorescence of the intrinsic compounds was monitored independently and FP data points mixed with compound fluorescence were removed from the assay.

Her 2-luciferase assay

HCT116 cells stably transfected with Her2 (kinase domain) -luciferase fusion were seeded in black 96-well plates at 10,000 cells in 100 μ l per well (DMEM supplemented with 10% serum) and cultured overnight. Compound dilutions (in 100% DMSO) were added to each well (final concentration 0.4% DMSO) and the plates were incubated for 4 hours. The plates were equilibrated to room temperature (5min), 100. mu.l of Steady-Glo reagent (Promega # E2520) was added to each well, and the plates were incubated for 5min at room temperature. Luminescence was then measured (TopCount, Perkin-Elmer).

Cytotoxicity assays

HCT116 cells were seeded into black 96-well plates at 5,000 cells in 100 μ l per well (DMEM supplemented with 10% serum) and cultured overnight. Compound dilutions (in 100% DMSO) were added to each well (final concentration 0.4% DMSO) and the plates were incubated for 72 hours. The plate was equilibrated to room temperature (5 min). Add 50. mu.l lysis buffer to each well, then 50. mu.l matrix solution (ATPLite [2step ], Perkin-Elmer, #601941) and incubate the plates for 5 minutes at room temperature. Luminescence was then measured (TopCount, Perkin-Elmer).

Watch 18

Examples of the invention	Percent inhibition of Compound at 5. mu.M concentration	IC50(μM)
			1		0.34
2		3.47
			3	36
4	75	0.65
			5	8
6	66	1.06
			7	22
8		18.0
			9		1.0
10		＞50
			11		0.6
12		＞10
			13		0.045
14		5.0
			15		6.5
16	6
			17		＞10
18	0

19		＞10
			20	0	＞10
21		＞10
			22		＞10
23		＞10
			24		＞10
25		0.041
			26		＞10
27		＞10
			28	0
29		0.15
			30	16	＞10
31		＞10
			32		＞10
33		0.017
			34		＞10
35		0.80
			36		＞5
37		0.8
			38		＞10
39		0.23
			40		＞10
41		0.50
			42		＞5
43		0.70
			44		27
45		8.1
			46		＞10
47		＞10
			48		＞10
49	55	1.2
			50	3
51	52	1.5
			52	0
53		0.045
			46		＞10

47		＞10
			48		＞10
49	55	1.2
			50	3
51	52	1.5
			52	0
53		0.045
			46		＞10
47		＞10
			48		＞10
49	55	1.2
			50	3
51	52	1.5
			52	0
53		0.045
			46		＞10
47		＞10
			48		＞10
49	55	1.2
			50	3
51	52	1.5
			52	0
53		0.045
			54	13
55		1.7
			56	3
57		0.4
			58	8
59		＞25
			60	30
61		＞10
			62		＞10
63		＞5
			64		＞5
65	61	0.50
			66	5

67	56	1.5
			68	0
69	69	0.25
			70	7
71	41	＞25
			72	0
73	2	＞3
			74	0
75		2.9
			76	6
77		1.9
			78	17
79		0.30
			80	10
81	23
			82	5
83	0
			84	0	＞5
85		0.36
			86		＞5
87	12
			88		1.3
89		＞10
			90	6
91		0.2
			92	0
93		0.19
			94	0
95		＞3
			96	2
97		0.45
			98	0
99		0.3
			100	39
101		＞3
			102	39

103		＞1
			104	38
105		＞1
			106	41
107	0
			108	30
109		0.3
			110	16
111		10.00
			112	0
113		0.55
			114	14
115		0.110
			116	0
117	54	0.30
			118	0
119	15
			120	0
121	54	0.52
			122		0.085
123	0
			124		0.22
125	12
			126		0.30
127	51
			128		0.066
129	54
			130		0.04
131	18
			132	54	0.50
133	0
			134		＞3
135		1.3
			136	16
137		0.210
			138	0

139		0.09
			140	0
141		0.04
			142	0
143		＞3
			144	0
145		＞3
			146	0
147		0.044
			148	35
149		0.07
			150	0
151		0.05
			152	20
153		0.60
			154	＞10
155		0.095
			156	16
157	58	0.50
			158	0
159	63	0.80
			160	0
161	17	0.32
			162	0
163	＞10
			164	0
165	60	0.30
			166	0
167	44	＞25
			168	0
169	37	0.470
			170	3
171		＞25
			172	＞10
173	44	＞25
			174	37	＞25

175	46	14.00
			135		1.3
136	16
			137		0.210
138	0
			139		0.09
140	0
			141		0.04
142	0
			143		＞3
144	0
			145		＞3
146	0
			147		0.044
148	35
			149		0.07
150	0
			151		0.05
152	20
			153		0.60
154	＞10
			155		0.095
156	16
			157	58	0.50
158	0
			159	63	0.80
160	0
			161	17	0.32
162	0
			163	＞10
164	0
			165	60	0.30
166	0
			167	44	＞25
168	0
			169	37	0.470

170	3
			171		＞25
172	＞10
			173	44	＞25
174	37	＞25
			175	46	14.00
176	6
			177	0
178	9
			179	8
180	＞10
			181		＞25
182	＞10
			183	100	1.100
184	0
			185		＞2.5
186	0
			187		＞2.5
188	21
			189		＞8
190	8
			191		＞8
192	0
			193	39	0.31
194	0
			195	80	0.079
196	10
			197		0.170
198	18
			199		0.110
200	18
			201		0.072
202	9
			203		0.09
204	11
			205	80	0.240

206	0
			207		0.038
208	46	＞25
			209		0.45
210	8
			211		＞25
212	4
			213	52	0.310
214		0.950
			215	0
216	78	＞8
			217		＞10
218		＞3
			219		＞8
220		2
			221		＞9
222	71	0.062
			223		0.50
224		＞5
			225		＞25
226		＞25
			227	0
228		＞8
			229	24
230		0.210
			231		＞25
232		＞25
			233		0.500
234	0
			235		＞8
236	0
			237		＞25
238		＞25
			239		＞25
240		＞8
			241	0

242		ND
			243		＞1
244		ND
			245	1
246		ND
			247		3.0
248		＞5
			249		0.100
250		0.900
			251		0.075
252		＞25
			253		＞8
254		＞8
			255		0.250
256		0.470
			257		＞25
258		＞25
			259		12.0
260		1.50
			261		＞25
262		＞25
			263		＞25
264		ND
			265	20
266		12.0
			267		＞25
268	7.0
			269		5.50
270	7.0
			271		＞25
272	16
			273		1.30
274	0.0
			275		＞3.0
276	0.0
			277		＞8.0

278	1.0
			279		＞25.0
280	0.0
			281		0.120
282		0.055
			283		12.0
284	3.0
			285		1.30
286		3.0
			287		0.06
288		4.00
			289		1.60
290		0.07
			291	0.0
292		＞25.0
			293	0.0
294		＞25.0
			295	0.0
296		0.350
			297	8.0
298		＞25.0
			299	0.0
300		0.400
			301	5.0
302		＞25.0
			303	21.0
304		＞25.0
			305	29.0
306		＞25.0
			307	40.0
308		0.180
			309	25.0
310		＞25.0
			311	0.0
312		＞25
			313	3.0

314		6.80
			315	21.0
316		18.0
			317	0.0
318		7.0
			319	27.0
320		0.240
			321	49.0
322		0.100
			323	0.0
324		2.80
			325	0.0
326		0.035
			327	33.0
328		＞8.0
			329	25.0
330		0.070
			331	25.0
332		1.00
			333	43.0
334		2.30
			335		3.00
336	13.0
			337		＞8
338	0
			339		0.115
340	23
			341		0.200
342		19
			343	0
344	22
			345	3
346		0.325
			347		2.5
348		0.800
			349	12

350	25
			351	8
352	35
			353		0.057
354		0.250
			355		＞25
356		＞25
			357	0
358		0.450
			359	3
360	5
			361		2.90
362		＞25
			363		0.300
364		0.102
			365	31
366	20
			367		＞25
368	Has fluorescence
			369		0.035
370		0.600
			371		0.700
372		0.100
			373	15
374		＞25
			375		＞1
376	0
			377	Has fluorescence
378		0.240
			379		9.80
380	4
			381		0.390
382		0.140
			383		21
384		＞1
			385	ND	ND

386		0.110
			387		＞8
388	13
			389	38
390		0.310
			391		1.2
392		2.9
			393	0
394		0.700
			395	0
396		0.810
			397	1
398		0.140
			399		0.950
400		6.0
			401	2
402		0.590
			403	14
404	ND	ND
			405		＞8
406		＞25
			407		＞25
408	ND	ND
			409		0.130
410	11
			411		0.200
412	0
			413	28
414		0.54
			415		0.46
416		0.200
			417	0
418		0.300
			419		2.90
420	7
			421	28

422		＞3
			423	0
424		0.152
			425	6
426		0.150
			427	32
428		＞8
			429		3.8
430	15
			431		0.130
432		0.065
			433		0.125
434		0.037
			435		0.195
436		0.390
			437		0.390
438	ND	ND
			439	24
440	60
			441	45
442	4
			443	36
444		1.10
			445		0.305
446	4
			447		0.210
448	45
			449		0.200
450	57
			451		0.195
452	21
			453		0.700
454		0.305
			455		0.060
456		ND
			457		＞2.00

458		0.380
			459	18
460		2.80
			461	15
462		7.90
			463	14％
464		0.40
			465		0.470
466		0.060
			467	0
468	9
			469		8.8
470		0.280
			471		0.600
472		0.070
			473		0.035
474		0.140
			475		0.172
476		0.090
			477		0.467
478		0.140
			479		0.199
480		0.160
			481		0.050
482	0.0
			483		0.184
484		0.600
			485		1
486		7
			487		0.900
488	29
			489		1.40
490		25
			491		0.039
492		0.900
			493		8.9

494	5.5
		495	6
496	0.081
		497		25
498	0.525
		499	21
500	0.060
		501		ND
502	0.140
		503		0.190
504	ND
		505		0.085
506	ND
		507		0.405
508	ND
		509		ND
510	0.250
		511		ND
512	0.110
		513		ND
514	0.110
		515		ND
516	0.600
		517		ND
518	0.140
		519		ND
520	＞2.00
		521		ND
522	0.053
		523		ND
524	0.100
		525	13.00
526	0.300
		527	19.00
528	＞5.00
		529		ND

530		2.50
			531		ND
532		5.00
			533	0.00
534		5.00
			535	1.00
536		＞5.00
			537		＞5.00
538		1.60
			539		＞5.00
540		＞5.00
			541	4.00
542		＞5.00
			543	0.00
544		1.40
			545		0.050
546		＞5.00
			547	12.00
548		＞5.00
			549	11.00
550		＞5.00
			551	0.00
552		ND
			553		＞5.00
554	0.00
			555		0.700
556		2.00
			557		1.50
558		＞5.00
			559		＞5.00
560		＞5.00
			561		＞5.00
562		ND
			563		＞5.00
564		＞2.00
			565		＞5.00

566	1.00
			567		＞5.00
568	0.00
			569		＞5.00
570	0.00
			571		＞5.00
572	0.00
			573		1.40
574		1.80
			575		0.80
576	31
			577		0.140
578		0.550
			579		0.310
580		0.400
			581		0.240
582		0.900
			583	55.00
584		1.40
			585		0.600
586		0.450
			587		ND
588		＞2.00
			589		ND
590		0.500
			591		ND
592		＞5.00
			593		ND
594		0.270
			595	43.00
596		ND
			597		0.310
598		ND
			599		0.260
600		ND
			601		＞8.00

602	31.00
			603	4.00
604		0.190
			605		0.056
606	49.00
			607		0.062
608	5.00
			609		0.045
610		0.088
			611	22.00
612		0.230
			613	15.00
614		1.80
			615	13.00
616		0.090
			617	83.00
618		0.041
			619	76.00
620		0.170
			621		＞5.00
622		＞5.00
			623		＞4.00
624		0.580
			625		0.110
626		ND
			627		＞8.00
628	23.00
			629		＞25.00
630		9.00
			631		2.00
632		＞3.00
			633		1.50
634		8.10
			635		2.10
636	25.00
			637		＞25.00

638		＞25.00
			639		0.900
640	19.00
			641		1.10
642	15.00
			643		5.00
644		0.200
			645		0.450
646		0.060
			647		ND
648		0.684
			649		ND
650		＞2.00
			651		＞5.00
652	0.00
			653		＞2.00
654		2.00
			655		＞5.00
656		＞5.00
			657		0.190
658		＞5.00
			659		4.00
660		＞5.00
			661		0.060
649		ND
			650		＞2.00
651		＞5.00
			652	0.00
653		＞2.00
			654		2.00
655		＞5.00
			656		＞5.00
657		0.190
			658		＞5.00
659		4.00
			660		＞5.00

661		0.060
			662		0.300
663	15
			664	Has fluorescence
665	0
			666		0.800
667	0
			668		4.8
669	10
			670		1.6
671		1.0
			672		0.9
673	0
			674		0.08
675	49
			676		0.95
677	ND
			678	Has fluorescence
679	ND
			680	14
681		1.0
			682		0.19
683	5
			684
685
			686		ND
687		0.080
			688	30
689		0.120
			690		0.29
691		0.125
			692		2.00
693		0.059
			695		0.410
697		0.600

698	55
			699		0.600
701		0.200
			703		0.190
705		0.080
			707		0.070
709		0.230
			711		0.600
713		0.495
			715		＞2
717		0.200
			719		0.800
720	ND
			722		0.130
723	ND
			724		0.105
725		0.100
			726	26
727		32
			728		0.200
730		＞5
			731	1.0
732		＞5
			734		＞2
736	ND
			738	ND
740		＞5
			741	ND	ND
742		0.140
			743		0.040
744		0.068
			745		0.123
746		0.240
			747		0.110
748		0.210
			749		0.330

750		0.180
			751		0.195
752		0.130
			753		0.059
754		0.050
			755		0.140
756	ND
			757		0.205
760		0.325
			761	ND	ND
764	ND
			765	ND
766	ND
			767	ND
768		＞5
			769	ND
771		0.120
			772		＞5
773		0.390
			774		0.200
775		1.80
			776		0.310
778		2.00
			779	43.00
780		ND
			781		ND
782		ND

Compounds active in luciferase refolding assays

ND-undetermined

Claims

1. A compound of formula I

Formula I

Wherein:

a is

Having 1-5 substituents independently selected from halogen, cyano, nitro, C_1-6Phenyl substituted with amido, alkoxy and aralkoxy, wherein the alkoxy is C_1-10An alkyl-substituted oxygen linkage (-O-), said aralkyloxy being phenyl-substituted C_1-10An alkoxy group;

a substituted or unsubstituted benzo [1, 3] dioxole group, wherein said substituted benzo [1, 3] dioxole group has 1-5 substituents independently selected from halogen;

an unsubstituted 2, 3-dihydro-1-indanone group;

a substituted 1, 2-indanyl group having 1-5 substituents independently selected from alkoxy or alkyl, wherein said alkoxy is C_1-10An alkyl-substituted oxygen linkage (-O-), said alkyl being an alkyl group having 1 to 10 carbon atoms;

a substituted pyridyl group having 1-4 substituents independently selected from halogen or alkoxy, wherein the alkoxy is C_1-10An alkyl-substituted oxygen linkage (-O-); or

An unsubstituted benzothiazolyl group;

b is an unsubstituted piperidine group, or a piperidine group substituted with one or more substituents selected from the group consisting of: hydrogen, alkyl, haloalkyl, -CH ₂-phenyl, -C (═ O) alkyl, -C (═ O) cycloalkyl, -C (═ O) NHCH where cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl₂C(＝O)OCH₂CH₃-C (═ O) -NH-alkyl, -COOH, -C (═ O) OCH₂CH₃、-C(＝O)OC(CH₃)₃or-C (═ O) OCH₂-phenyl, an amino acid, -C (═ O) alkyl wherein the alkyl group is substituted with one or more substituents selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and sulfonyl, wherein said alkyl is an alkyl having 1 to 10 carbon atoms, and said haloalkyl is C substituted with one or more fluoro, chloro, bromo or iodo groups_1-10Alkyl, said alkoxy is C_1-10An alkyl-substituted oxygen linkage (-O-), said amino acid being selected from glycine, alanine, leucine or valine, or a tert-butyloxycarbonyl-protected form thereof, and said sulfonyl group being-S (═ O)₂R 'radical, in which R')Is an alkyl group having 1 to 6 carbon atoms optionally substituted with halogen;

r1 is selected from hydrogen;

L₁is-S-;

L₂is- (CH)₂)_n-(CH₂)_n-, wherein each n is independently selected from 1, 2 and 3;

and pharmaceutically acceptable salts thereof;

with the proviso that the compound of formula I excludes 8- (2-iodo-5-methoxy-phenylsulfanyl) -9- (3-piperidin-1-yl-propyl) -9H-purin-6-ylamine, and 8- (2-iodo-5-methoxy-phenylsulfanyl) -9- (2-piperidin-1-yl-ethyl) -9H-purin-6-ylamine.

2. The compound of claim 1, wherein a is selected from 2, 5-dimethoxyphenyl, 2, 5-diethoxyphenyl, 3, 4, 5-trimethoxyphenyl or 6-bromo-benzo [1, 3] dioxol-5-yl.

3. The compound of claim 1 or 2, wherein B is substituted with one or more groups selected from hydrogen, alkyl, haloalkyl, -CH₂-phenyl, -C (═ O) alkyl, -C (═ O) -NH-alkyl, -COOH, -C (═ O) OCH₂CH₃，-C(＝O)OC(CH₃)₃or-C (═ O) OCH₂-phenyl, -C (═ O) alkyl wherein the alkyl group is substituted with one or more substituents selected from the group consisting of hydroxy, amino, alkyl and alkoxy, and a piperidine group for the substituents of sulfonyl.

4. A compound according to claim 1 or 2, wherein B is substituted with one or more substituents selected from-C (═ O) CH₃、-CH₃、-CH₂CH₂CH₃、-C(＝O)OCH₂CH₃、-S(＝O)₂CH₃、-S(＝O)₂CF₃、-C(＝O)OC(CH₃)₃、-C(＝O)OCH₂-phenyl, -CH₂-phenyl, -CH (CH)₃)₂、-C(＝O)NHCH₂CH₃、-C(＝O)NHCH(CH₃)₂、-C(＝O)NHC(CH₃)₃、-C(＝O)NHCH₂C(＝O)OCH₂CH₃、-C(＝O)C(CH₃)₃、-CH₂CH(CH₃)₂and-C (═ O) CH₂C(CH₃)₃A piperidine group of the substituent(s).

5. A compound selected from the group consisting of 9- [2- (1-acetylpiperidin-4-yl) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine, 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carbaldehyde, 4- (2- { 6-amino-8- [ (7-bromo-2, 3-dihydro-1, 4-benzodioxol-6-yl) thio ] -9H-purin-9-yl } ethyl) Piperidine-1-carbaldehyde, (2S) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -1-oxopropan-2-ol, 4- (2- { 6-amino-8- [ (1-oxo-2, 3-dihydro-1H-inden-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carbaldehyde, 2- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -2-oxoethanol and 6- ({9- [2- (1-acetylpiperidin-4-yl) ethyl ] -6-amino-9H-purin-8-yl } thio) -1, 3-benzodioxole-5-carbonitrile.

6. The compound of claim 5 wherein said compound is 9- [2- (1-acetylpiperidin-4-yl) ethyl ] -8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-6-amine.

7. The compound of claim 5 wherein said compound is 4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidine-1-carbaldehyde.

8. The compound of claim 5 wherein said compound is (2S) -1- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -1-oxopropan-2-ol.

9. The compound of claim 5 wherein said compound is 2- [4- (2- { 6-amino-8- [ (6-bromo-1, 3-benzodioxol-5-yl) thio ] -9H-purin-9-yl } ethyl) piperidin-1-yl ] -2-oxoethanol.

10. The compound of claim 5, wherein the compound is 6- ({9- [2- (1-acetylpiperidin-4-yl) ethyl ] -6-amino-9H-purin-8-yl } thio) -1, 3-benzodioxole-5-carbonitrile.