RU2000115305A

RU2000115305A - AMINOTRIASOL INHIBITORS OF CYCLIN-dependent KINAZ

Info

Publication number: RU2000115305A
Application number: RU2000115305/04A
Authority: RU
Inventors: Киоунг С. КИМ; С. Дэвид КИМБЭЛЛ; Майкл А. ПОСС; Радж Н. МИСРА; Цхен-Вей КАЙ; Дэвид Б. Роулинс; Кевин ВЕБСТЕР; Джон Т. ХАНТ; Уен-Чинг ХЭН
Original assignee: Бристол-Маерс Сквибб Компани
Priority date: 1997-11-12
Filing date: 1998-11-02
Publication date: 2002-09-10

Claims

1. The compounds of the formula:

and their pharmaceutically acceptable salts,
where R ₁ and R ₂ independently of one another denote hydrogen, fluorine or alkyl;
R ₃ is aryl or heteroaryl;
R ₄ denotes hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl; or CO-alkyl, CO-cycloalkyl, CO-aryl, CO-alkyl-cycloalkyl, CO-alkyl-aryl, CO-heteroaryl, CO-alkylheteroaryl, CO-heterocycloalkyl, CO-alkyl-hetero-cycloalkyl; or CONH-alkyl, CONH-cycloalkyl, CONH-aryl, CONH-alkyl-cycloalkyl, CONH-alkyl-aryl, CONH-heteroaryl, CONH-alkyl-heteroaryl, CONH-heterocycloalkyl, CONH-alkyl-heterocycloalkyl; COO-alkyl, COO-cycloalkyl, COO-aryl, COO-alkyl-cycloalkyl, COO-alkyl-aryl, COO-heteroaryl, COO-alkyl-heteroaryl, COO-heterocycloalkyl, COO-alkyl-heterocycloalkyl; or SiO ₂ -alkyl, SiO ₂ -cycloalkyl, SiO ₂ -aryl, SiO ₂ -alkyl-cycloalkyl, SiO ₂ -alkyl-aryl, SiO ₂ -heteroaryl, SiO ₂ -alkyl-heteroaryl, SiO ₂ -heterocycloalkyl, SiO ₂ - alkyl-hetero-cycloalkyl; or C (NCN) NH-alkyl, C (NCN) NH-cycloalkyl, C (NCN) NH-aryl, C (NCN) NH-alkyl-cycloalkyl, C (NCN) NH-alkyl-aryl, C (NCN) NH -heteroaryl, C (NCN) NH-alkyl-heteroaryl, C (NCN) NH-heterocycloalkyl, C (NCN) NH-alkyl-heterocycloalkyl; or C (NNO ₂ ) NH-alkyl, C (NNO ₂ ) NH-cycloalkyl, C (NNO ₂ ) NH-aryl, C (NNO ₂ ) NH-alkyl-cycloalkyl, C (NNO ₂ ) NH-alkyl-aryl, C (NNO ₂ ) NH-heteroaryl, C (NNO ₂ ) NH-alkyl-heteroaryl, C (NNO ₂ ) NH-heterocycloalkyl, C (NNO ₂ ) NH-alkyl-hetero-cycloalkyl; or C (NH) NH-alkyl, C (NH) NH-cycloalkyl, C (NH) NH-aryl, C (NH) NH-alkyl-cycloalkyl, C (NH) NH-alkyl-aryl, C (NH) NH -heteroaryl, C (NH) NH-alkyl-hetero-aryl, C (NH) NH-heterocycloalkyl, C (NH) NH-alkyl-heterocycloalkyl; or C (NH) NHCO-alkyl, C (NH) NHCO-cycloalkyl, C (NH) NHCO-aryl, C (NH) NCHO-alkyl-cycloalkyl, C (NH) NHCO-alkyl-aryl, C (NH) NNCO -heteroaryl, C (NH) NHCO-alkyl-heteroaryl, C (NH) NHCO-heterocycloalkyl, C (NH) NHCO-alkyl-heterocycloalkyl; or C (NOR ₆ ) NH-alkyl, C (NOR ₆ ) NH-cycloalkyl, C (NOR ₆ ) NH-aryl, C (NOR ₆ ) NH-alkyl-cycloalkyl, C (NOR ₆ ) NH-alkyl-aryl, C (NOR ₆ ) NH-heteroaryl, C (NOR ₆ ) NH-alkyl-heteroaryl, C (NOR ₆ ) NH-heterocycloalkyl, C (NOR ₆ ) NH-alkyl-heterocycloalkyl;
R ₅ is hydrogen or alkyl;
R ₆ is hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl;
m represents an integer from 0 to 2; and
n denotes an integer from 1 to 3.

2. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ independently designate hydrogen, fluorine or alkyl; R ₃ means

where Y denotes oxygen, sulfur or NR ₉ ,
R ₄ denotes hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl; or CO-alkyl, CO-cycloalkyl, CO-aryl, CO-alkyl-cycloalkyl, CO-alkyl-aryl, CO-heteroaryl, CO-alkylheteroaryl, CO-heterocycloalkyl, CO-alkyl-hetero-cycloalkyl; or CONH-alkyl, CONH-cycloalkyl, CONH-aryl, CONH-alkyl-cycloalkyl, CONH-alkyl-aryl, CONH-heteroaryl, CONH-alkyl-heteroaryl, CONH-heterocycloalkyl, CONH-alkyl-heterocycloalkyl; COO-alkyl, COO-cycloalkyl, COO-aryl, COO-alkyl-cycloalkyl, COO-alkyl-aryl, COO-heteroaryl, COO-alkyl-heteroaryl, COO-heterocycloalkyl, COO-alkyl-heterocycloalkyl; or SiO ₂ -alkyl, SiO ₂ -cycloalkyl, SiO ₂ -aryl, SiO ₂ -alkyl-cycloalkyl, SiO ₂ -alkyl-aryl, SiO ₂ -heteroaryl, SiO ₂ -alkyl-heteroaryl, SiO ₂ -heterocycloalkyl, SiO ₂ - alkyl-hetero-cycloalkyl; or C (NCN) NH-alkyl, C (NCN) NH-cycloalkyl, C (NCN) NH-aryl, C (NCN) NH-alkyl-cycloalkyl, C (NCN) NH-alkyl-aryl, C (NCN) NH -heteroaryl, C (NCN) NH-alkyl-heteroaryl, C (NCN) NH-heterocycloalkyl, C (NCN) NH-alkyl-heterocycloalkyl; or C (NNO ₂ ) NH-alkyl, C (NNO ₂ ) NH-cycloalkyl, C (NNO ₂ ) NH-aryl, C (NNO ₂ ) NH-alkyl-cycloalkyl, C (NNO ₂ ) NH-alkyl-aryl, C (NNO ₂ ) NH-heteroaryl, C (NNO ₂ ) NH-alkyl-heteroaryl, C (NNO ₂ ) NH-heterocycloalkyl, C (NNO ₂ ) NH-alkyl-heterocycloalkyl; or C (NH) NH-alkyl, C (NH) NH-cycloalkyl, C (NH) NH-aryl, C (NH) NH-alkyl-cycloalkyl, C (NH) NH-alkyl-aryl, C (NH) NH -heteroaryl, C (NH) NH-alkyl-hetero-aryl, C (NH) NH-heterocycloalkyl, C (NH) NH-alkyl-heterocycloalkyl; or C (NH) NHCO-alkyl, C (NH) NHCO-cycloalkyl, C (NH) NHCO-aryl, C (NH) NCHO-alkyl-cycloalkyl, C (NH) NHCO-alkyl-aryl, C (NH) NNCO -heteroaryl, C (NH) NHCO-alkyl-heteroaryl, C (NH) NHCO-heterocycloalkyl, C (NH) NHCO-alkyl-heterocycloalkyl; or C (NOR ₆ ) NH-alkyl, C (NOR ₆ ) NH-cycloalkyl, C (NOR ₆ ) NH-aryl, C (NOR ₆ ) NH-alkyl-cycloalkyl, C (NOR ₆ ) NH-alkyl-aryl, C (NOR ₆ ) NH-heteroaryl, C (NOR ₆ ) NH-alkyl-heteroaryl, C (NOR ₆ ) NH-heterocycloalkyl, C (NOR ₆ ) NH-alkyl-heterocycloalkyl;
R ₅ is hydrogen or alkyl;
R ₆ is hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl;
R ₇ and R _{8 are} independently hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, cycloalkylalkyl, arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl;
R ₉ is hydrogen, alkyl; cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl;
m represents an integer from 0 to 2; and
n denotes an integer from 1 to 3.

3. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ independently represent hydrogen, fluorine or alkyl; R ₃ means

where Y denotes oxygen,
R ₄ denotes hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl; or CO-alkyl, CO-cycloalkyl, CO-aryl, CO-alkyl-cycloalkyl, CO-alkyl-aryl, CO-heteroaryl, CO-alkylheteroaryl, CO-heterocycloalkyl, CO-alkyl-hetero-cycloalkyl; or CONH-alkyl, CONH-cycloalkyl, CONH-aryl, CONH-alkyl-cycloalkyl, CONH-alkyl-aryl, CONH-heteroaryl, CONH-alkyl-heteroaryl, CONH-heterocycloalkyl, CONH-alkyl-heterocycloalkyl; COO-alkyl, COO-cycloalkyl, COO-aryl, COO-alkyl-cycloalkyl, COO-alkyl-aryl, COO-heteroaryl, COO-alkyl-heteroaryl, COO-heterocycloalkyl, COO-alkyl-heterocycloalkyl; or SiO ₂ -alkyl, SiO ₂ -cycloalkyl, SiO ₂ -aryl, SiO ₂ -alkyl-cycloalkyl, SiO ₂ -alkyl-aryl, SiO ₂ -heteroaryl, SiO ₂ -alkyl-heteroaryl, SiO ₂ -heterocycloalkyl, SiO ₂ - alkyl-hetero-cycloalkyl; or C (NCN) NH-alkyl, C (NCN) NH-cycloalkyl, C (NCN) NH-aryl, C (NCN) NH-alkyl-cycloalkyl, C (NCN) NH-alkyl-aryl, C (NCN) NH -heteroaryl, C (NCN) NH-alkyl-heteroaryl, C (NCN) NH-heterocycloalkyl, C (NCN) NH-alkyl-heterocycloalkyl; or C (NNO ₂ ) NH-alkyl, C (NNO ₂ ) NH-cycloalkyl, C (NNO ₂ ) NH-aryl, C (NNO ₂ ) NH-alkyl-cycloalkyl, C (NNO ₂ ) NH-alkyl-aryl, C (NNO ₂ ) NH-heteroaryl, C (NNO ₂ ) NH-alkyl-heteroaryl, C (NNO ₂ ) NH-heterocycloalkyl, C (NNO ₂ ) NH-alkyl-heterocyclo-alkyl; or C (NH) NH-alkyl, C (NH) NH-cycloalkyl, C (NH) NH-aryl, C (NH) NH-alkyl-cycloalkyl, C (NH) NH-alkyl-aryl, C (NH) NH -heteroaryl, C (NH) NH-alkyl-hetero-aryl, C (NH) NH-heterocycloalkyl, C (NH) NH-alkyl-heterocycloalkyl; or C (NH) NHCO-alkyl, C (NH) NHCO-cycloalkyl, C (NH) NHCO-aryl, C (NH) NCHO-alkyl-cycloalkyl, C (NH) NHCO-alkyl-aryl, C (NH) NNCO -heteroaryl, C (NH) NHCO-alkyl-heteroaryl, C (NH) NHCO-heterocycloalkyl, C (NH) NHCO-alkyl-heterocycloalkyl; or C (NOR ₆ ) NH-alkyl, C (NOR ₆ ) NH-cycloalkyl, C (NOR ₆ ) NH-aryl, C (NOR ₆ ) NH-alkyl-cycloalkyl, C (NOR ₆ ) NH-alkyl-aryl, C (NOR ₆ ) NH-heteroaryl, C (NOR ₆ ) NH-alkyl-heteroaryl, C (NOR ₆ ) NH-heterocycloalkyl, C (NOR ₆ ) NH-alkyl-heterocycloalkyl;
R ₅ is hydrogen;
R ₆ is hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl;
R ₇ and R _{8 are} independently hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, cycloalkylalkyl, arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl;
m represents an integer from 0 to 2; and
n denotes an integer from 1 to 3.

4. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ independently designate hydrogen, fluorine or alkyl; R ₃ means

where Y denotes sulfur,
R ₄ denotes hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl; or CO-alkyl, CO-cycloalkyl, CO-aryl, CO-alkyl-cycloalkyl, CO-alkyl-aryl, CO-heteroaryl, CO-alkylheteroaryl, CO-heterocycloalkyl, CO-alkyl-hetero-cycloalkyl; or CONH-alkyl, CONH-cycloalkyl, CONH-aryl, CONH-alkyl-cycloalkyl, CONH-alkyl-aryl, CONH-heteroaryl, CONH-alkyl-heteroaryl, CONH-heterocycloalkyl, CONH-alkyl-heterocycloalkyl; COO-alkyl, COO-cycloalkyl, COO-aryl, COO-alkyl-cycloalkyl, COO-alkyl-aryl, COO-heteroaryl, COO-alkyl-heteroaryl, COO-heterocycloalkyl, COO-alkyl-heterocycloalkyl; or SiO ₂ -alkyl, SiO ₂ -cycloalkyl, SiO ₂ -aryl, SiO ₂ -alkyl-cycloalkyl, SiO ₂ -alkyl-aryl, SiO ₂ -heteroaryl, SiO ₂ -alkyl-heteroaryl, SiO ₂ -heterocycloalkyl, SiO ₂ - alkyl-hetero-cycloalkyl; or C (NCN) NH-alkyl, C (NCN) NH-cycloalkyl, C (NCN) NH-aryl, C (NCN) NH-alkyl-cycloalkyl, C (NCN) NH-alkyl-aryl, C (NCN) NH -heteroaryl, C (NCN) NH-alkyl-heteroaryl, C (NCN) NH-heterocycloalkyl, C (NCN) NH-alkyl-heterocycloalkyl; or C (NNO ₂ ) NH-alkyl, C (NNO ₂ ) NH-cycloalkyl, C (NNO ₂ ) NH-aryl, C (NNO ₂ ) NH-alkyl-cycloalkyl, C (NNO ₂ ) NH-alkyl-aryl, C (NNO ₂ ) NH-heteroaryl, C (NNO ₂ ) NH-alkyl-heteroaryl, C (NNO ₂ ) NH-heterocycloalkyl, C (NNO ₂ ) NH-alkyl-heterocycloalkyl; or C (NH) NH-alkyl, C (NH) NH-cycloalkyl, C (NH) NH-aryl, C (NH) NH-alkyl-cycloalkyl, C (NH) NH-alkyl-aryl, C (NH) NH -heteroaryl, C (NH) NH-alkyl-hetero-aryl, C (NH) NH-heterocycloalkyl, C (NH) NH-alkyl-heterocycloalkyl; or C (NH) NHCO-alkyl, C (NH) NHCO-cycloalkyl, C (NH) NHCO-aryl, C (NH) NCHO-alkyl-cycloalkyl, C (NH) NHCO-alkyl-aryl, C (NH) NHSO -heteroaryl, C (NH) NHCO-alkyl-heteroaryl, C (NH) NHCO-heterocycloalkyl, C (NH) NHCO-alkyl-heterocycloalkyl; or C (NOR ₆ ) NH-alkyl, C (NOR ₆ ) NH-cycloalkyl, C (NOR ₆ ) NH-aryl, C (NOR ₆ ) NH-alkyl-cycloalkyl, C (NOR ₆ ) NH-alkyl-aryl, C (NOR ₆ ) NH-heteroaryl, C (NOR ₆ ) NH-alkyl-heteroaryl, C (NOR ₆ ) NH-heterocycloalkyl, C (NOR ₆ ) NH-alkyl-heterocycloalkyl;
R ₅ is hydrogen;
R ₆ is hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl;
R ₇ and R _{8 are} independently hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, cycloalkylalkyl, arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl;
m represents an integer from 0 to 2; and
n denotes an integer from 1 to 3.

5. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ independently designate hydrogen, fluorine or alkyl; R ₃ means

where Y denotes NR ₉ ,
R ₄ denotes hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl; or CO-alkyl, CO-cycloalkyl, CO-aryl, CO-alkyl-cycloalkyl, CO-alkyl-aryl, CO-heteroaryl, CO-alkylheteroaryl, CO-heterocycloalkyl, CO-alkyl-hetero-cyclo-alkyl; or CONH-alkyl, CONH-cycloalkyl, CONH-aryl, CONH-alkyl-cycloalkyl, CONH-alkyl-aryl, CONH-heteroaryl, CONH-alkyl-heteroaryl, CONH-heterocycloalkyl, CONH-alkyl-heterocycloalkyl; COO-alkyl, COO-cycloalkyl, COO-aryl, COO-alkyl-cycloalkyl, COO-alkyl-aryl, COO-heteroaryl, COO-alkyl-heteroaryl, COO-heterocycloalkyl, COO-alkyl-heterocycloalkyl; or SiO ₂ -alkyl, SiO ₂ -cycloalkyl, SiO ₂ -aryl, SiO ₂ -alkyl-cycloalkyl, SiO ₂ -alkyl-aryl, SiO ₂ -heteroaryl, SiO ₂ -alkyl-heteroaryl, SiO ₂ -heterocycloalkyl, SiO ₂ - alkyl-hetero-cycloalkyl; or C (NCN) NH-alkyl, C (NCN) NH-cycloalkyl, C (NCN) NH-aryl, C (NCN) NH-alkyl-cycloalkyl, C (NCN) NH-alkyl-aryl, C (NCN) NH -heteroaryl, C (NCN) NH-alkyl-heteroaryl, C (NCN) NH-heterocycloalkyl, C (NCN) NH-alkyl-heterocycloalkyl; or C (NNO ₂ ) NH-alkyl, C (NNO ₂ ) NH-cycloalkyl, C (NNO ₂ ) NH-aryl, C (NNO ₂ ) NH-alkyl-cycloalkyl, C (NNO ₂ ) NH-alkyl-aryl, C (NNO ₂ ) NH-heteroaryl, C (NNO ₂ ) NH-alkyl-heteroaryl, C (NNO ₂ ) NH-heterocycloalkyl, C (NNO ₂ ) NH-alkyl-heterocycloalkyl; or C (NH) NH-alkyl, C (NH) NH-cycloalkyl, C (NH) NH-aryl, C (NH) NH-alkyl-cycloalkyl, C (NH) NH-alkyl-aryl, C (NH) NH -heteroaryl, C (NH) NH-alkyl-hetero-aryl, C (NH) NH-heterocycloalkyl, C (NH) NH-alkyl-heterocycloalkyl; or C (NH) NHCO-alkyl, C (NH) NHCO-cycloalkyl, C (NH) NHCO-aryl, C (NH) NCHO-alkyl-cycloalkyl, C (NH) NHCO-alkyl-aryl, C (NH) NNCO -heteroaryl, C (NH) NHCO-alkyl-heteroaryl, C (NH) NHCO-heterocycloalkyl, C (NH) NHCO-alkyl-heterocycloalkyl; or C (NOR ₆ ) NH-alkyl, C (NOR ₆ ) NH-cycloalkyl, C (NOR ₆ ) NH-aryl, C (NOR ₆ ) NH-alkyl-cycloalkyl, C (NOR ₆ ) NH-alkyl-aryl, C (NOR ₆ ) NH-heteroaryl, C (NOR ₆ ) NH-alkyl-heteroaryl, C (NOR ₆ ) NH-heterocycloalkyl, C (NOR ₆ ) NH-alkyl-heterocycloalkyl;
R ₅ is hydrogen;
R ₆ is hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl;
R ₇ and R _{8 are} independently hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, cycloalkylalkyl, arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl;
R ₉ is hydrogen, alkyl; cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl;
m represents an integer from 0 to 2; and
n denotes an integer from 1 to 3.

6. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ independently represent hydrogen, fluorine or alkyl;
R ₃ means

where Y denotes oxygen,
R ₄ is CO-alkyl, CO-alkyl-aryl, CO-cycloalkyl, CO-alkyl-heteroaryl, CO-alkyl-heteroalkyl, CO-alkyl-heterocycloalkyl, CONH-alkyl, CONH-alkyl-aryl, CONH-cycloalkyl or CONH -alkyl-heterocycloalkyl;
R ₅ is hydrogen; and
R ₇ and R ₈ are hydrogen;
m is 0; and
n is 1.

7. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ are independently hydrogen, fluorine or alkyl; R ₃ means

where Y denotes oxygen,
R ₄ is CO-alkyl, CO-alkyl-aryl, CO-alkyl-heteroalkyl, CO-cycloalkyl, CO-alkyl-heterocycloalkyl, CO-alkyl-heteroaryl, CONH-alkyl, CONH-alkyl-aryl, CONH-cycloalkyl or CONH -alkyl-heterocycloalkyl;
R ₅ is hydrogen; and
R ₇ and R ₈ are alkyl;
m is 0; and
n is 1.

8. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ are independently hydrogen, fluorine or alkyl;
R ₃ means

where Y denotes oxygen,
R ₄ is CO-alkyl, CO-alkyl-aryl, CO-alkyl-heteroalkyl, CO-cycloalkyl, CO-alkyl-heterocycloalkyl, CO-alkyl-heteroaryl, CONH-alkyl, CONH-alkyl-aryl, CONH-cycloalkyl or CONH -alkyl-heterocycloalkyl;
R ₅ is hydrogen;
R ₇ denotes hydrogen;
R ₈ is alkyl;
m is 0; and
n is 1.

9. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ are independently hydrogen, fluorine or alkyl; R ₃ means

where Y denotes oxygen,
R ₄ is CO-alkyl, CO-alkyl-aryl, CO-alkyl-heteroalkyl, CO-cycloalkyl, CO-alkyl-heterocycloalkyl, CO-alkyl-heteroaryl, CONH-alkyl, CONH-alkyl-aryl, CONH-cycloalkyl or CONH -alkyl-heterocycloalkyl;
R ₅ is hydrogen; and
R ₇ is alkyl;
R ₈ denotes hydrogen
m is 0; and
n is 1.

10. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ independently designate hydrogen, fluorine or alkyl; R ₃ means

where Y denotes sulfur,
R ₄ is CO-alkyl, CO-alkyl-aryl, CO-alkyl-heteroalkyl, CO-cycloalkyl, CO-alkyl-heterocycloalkyl, CO-alkyl-heteroaryl, CONH-alkyl, CONH-alkyl-aryl, CONH-cycloalkyl or CONH -alkyl-heterocycloalkyl;
R ₅ is hydrogen;
R ₇ is hydrogen;
R ₈ is alkyl;
m is 0; and
n is 1.

11. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ independently designate hydrogen, fluorine or alkyl;
R ₃ means

where Y denotes sulfur,
R ₄ is CO-alkyl, CO-alkyl-aryl, CO-alkyl-heteroalkyl, CO-cycloalkyl, CO-alkyl-heterocycloalkyl, CO-alkyl-heteroaryl, CONH-alkyl, CONH-alkyl-aryl, CONH-cycloalkyl or CONH -alkyl-heterocycloalkyl;
R ₅ is hydrogen;
R ₇ is alkyl;
R ₈ is hydrogen;
m is 0; and
n is 1.

12. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ independently designate hydrogen, fluorine or alkyl; R ₃ means

where Y denotes NR ₉ ,
R ₄ is CO-alkyl, CO-alkyl-aryl, CO-alkyl-heteroalkyl, CO-cycloalkyl, CO-alkyl-heterocycloalkyl, CO-alkyl-heteroaryl, CONH-alkyl, CONH-alkyl-aryl, CONH-cycloalkyl or CONH -alkyl-heterocycloalkyl;
R ₅ is hydrogen;
R ₇ is hydrogen;
R ₈ is alkyl;
R ₉ is hydrogen, alkyl, cycloalkyl, aryl, alkyl-cycloalkyl, alkyl-aryl, heteroaryl, alkyl-heteroaryl, heterocycloalkyl, or alkyl-heterocycloalkyl;
m is 0; and
n is 1.

13. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ are independently hydrogen, fluorine or alkyl;
R ₃ means

where Y denotes NR ₉ ,
R ₄ is CO-alkyl, CO-alkyl-aryl, CO-alkyl-heteroalkyl, CO-cycloalkyl, CO-alkyl-heterocycloalkyl, CO-alkyl-heteroaryl, CONH-alkyl, CONH-alkyl-aryl, CONH-cycloalkyl or CONN -alkyl-heterocycloalkyl;
R ₅ is hydrogen;
R ₇ is alkyl;
R ₈ is hydrogen;
R ₉ is alkyl;
m is 0; and
n is 1.

14. Compounds according to Claim. 1, characterized in that R ₁ and R ₂ independently represent hydrogen, fluorine or alkyl;
R ₃ means

where Y denotes NR ₉ ,
R ₄ denotes CO-alkyl, CO-alkyl-aryl, CO-cycloalkyl, CO-alkylheteroaryl, CO-alkyl-heteroalkyl, CO-alkyl-heterocycloalkyl, CONH-alkyl, CONH-alkyl-aryl, CONH-cycloalkyl or CONH-alkyl - heterocycloalkyl;
R ₅ is hydrogen;
R ₇ is alkyl;
R ₈ is hydrogen;
R ₉ is hydrogen;
m is 0; and
n is 1.

15. The compound according to claim 1, characterized in that it represents
N- [5 - [[(5-ethyl-2-oxazolyl) methyl] thio] -2-thiazolyl] acetamide;
N- [5 - [[(5-ethyl-2-oxazolyl) methyl] thio] -2-thiazolyl] benzamide;
N- [5 - [[(5-ethyl-2-oxazolyl) methyl] thio] -2-thiazolyl] benzenesulfonamide;
N- [5 - [[(4,5-dimethyl-2-oxazolyl) methyl] thio] -2-thiazolyl] acetamide;
N- [5 - [[(5-tert. Butyl-2-oxazolyl) methyl] thio] -2-thiazolyl] acetamide;
N- [5 - [[(5-tert. Butyl-2-oxazolyl) methyl] thio] -2-thiazolyl] trimethylacetamide;
N- [5 - [[(4-ethyl-2-oxazolyl) methyl] thio] -2-thiazolyl] acetamide; or a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

17. A pharmaceutical composition comprising a compound according to claim 1 in combination with a pharmaceutically acceptable carrier and an anti-cancer agent in the form of a fixed dosage form.

18. The pharmaceutical composition of claim 16, comprising the compound of claim 1 in combination with a pharmaceutically acceptable carrier, characterized in that it is used in combination with an anticancer treatment or in combination with an anticancer agent administered sequentially.

19. The pharmaceutical composition according to claim 18, characterized in that said combination, comprising said compound according to claim 1 and said pharmaceutically acceptable carrier, is administered prior to the use of an anti-cancer treatment or an anti-cancer agent.

20. The pharmaceutical composition according to claim 18, characterized in that said combination, including said compound according to claim 1 and said pharmaceutically acceptable carrier, is administered after anti-cancer treatment or after administration of the anti-cancer agent.

21. A method of inhibiting protein kinases, comprising administering to a mammal in need thereof an effective amount of the compound according to claim 1.

22. A method of inhibiting cyclin-dependent kinases, comprising administering to a mammal in need thereof an effective amount of a compound according to claim 1.

23. A method of inhibiting cdc2 (cdkl), comprising administering to a mammal in need thereof an effective amount of a compound according to claim 1.

24. A method of inhibiting cdk2, comprising administering to a mammal in need thereof an effective amount of the compound according to claim 1.

25. A method of inhibiting cdk3, comprising administering to a mammal in need thereof an effective amount of the compound according to claim 1.

26. A method of inhibiting cdk4, comprising administering to a mammal in need thereof an effective amount of the compound according to claim 1.

27. A method of inhibiting cdk5, comprising administering to a mammal in need thereof an effective amount of the compound according to claim 1.

28. A method of inhibiting cdk6, comprising administering to a mammal in need thereof an effective amount of the compound according to claim 1.

29. A method of inhibiting cdk7, comprising administering to a mammal in need thereof an effective amount of the compound according to claim 1.

30. A method of inhibiting cdk8, comprising administering to a mammal in need thereof an effective amount of the compound according to claim 1.

31. A method of treating proliferative diseases, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 16.

32. A method of treating cancer, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 16.

33. A method for the treatment of inflammatory diseases, inflammation of the intestines or transplant rejection, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 16.

34. A method of treating arthritis, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 16.

35. A method of treating an infection caused by HIV, or treating and preventing the development of AIDS, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 16.

36. A method of treating viral infections, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 16.

37. A method of treating fungal infections, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 16.

38. A method for preventing the development of cancer or the recurrence of the appearance of tumors, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 16.

39. A method of treating neurodegenerative diseases, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 16.

40. A method of treating proliferative diseases, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 17.

41. A method of treating cancer, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 17.

42. A method for preventing the development of cancer or the recurrence of the appearance of tumors, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 17.

43. A method of treating proliferative diseases, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 18.

44. A method of treating cancer, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 18.

45. A method for preventing the development of cancer or the recurrence of the appearance of tumors, comprising administering to a mammal in need thereof a therapeutically effective amount of a composition according to claim 18.