Derivatives of benzo(5,6)cyclohepta(1,2-b)pyridine, pharmaceutical composition and methods of inhibiting abnormal cell growth and farnesyl-protein transferase

 

The invention relates to new compounds derived from benzo(5,6)-cyclohepta-(1,2)-pyridine of the formula I, where R1means of groups a), b), C), d), e), f), i) k) l) m) n) o) p), r), s); R2and R3together form a bond when the value of R1- group a) or group m) or mean hydrogen for the other R1; R4the hydrogen for the other R1or bromine when the value of R1group o) or group f); R5the hydrogen for the other R1or bromine for R1group r or group s), and their pharmaceutically acceptable salts or solvate. This invention also relates to a method for inhibiting the abnormal growth of cells, comprising introducing an effective amount of compounds of formula I, the method of inhibiting farnesyl-protein transferase responsible for pancreatic cancer, lung cancer, myeloid leukemia, follicular thyroid cancer, myelodysplasia syndrome, epidermal carcinoma, carcinoma of the bladder, colon cancer, breast cancer or prostate cancer in a patient, ordaudio such inhibition, comprising introducing an effective amount of the compounds of formula I. the Invention also relates to a pharmaceutical composition having activity pharmaceutically acceptable carrier. 4 C. and 6 C.p. f-crystals, 1 PL.







Description text in facsimile form (see graphic part).


Claims

1. Derivatives of benzo(5,6)cyclohepta(1,2-b)pyridine of the formula l

where R1means a group of

R2and R3together form a bond;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2who appoints the group

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3together form a bond;

R4means hydrogen;

R5means hydrogen;

or R1means € bromine;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means bromine;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means bromine;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means bromine;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means bromine;

and their pharmaceutically acceptable salts or solvate.

2. Derivatives of benzo(5,6)cyclohepta(1,2-b)pyridine formula I on p. 1, where R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

>5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3together form a bond;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means bromine;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means bromine;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means bromine;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means bromine.

3. Derivatives of benzo(5,6)cyclohepta(1,2-b)pyridine formula I on p. 1, where

R1means a group of

R2and R

R2and R3mean hydrogen;

R4means hydrogen;

R5means hydrogen;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means bromine;

or R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means bromine.

4. Derived benzo(5,6)cyclohepta(1,2-b)pyridine formula I on p. 1, where R1means a group of

R2and R3mean hydrogen;

R4means hydrogen;

R5means bromine.

5. Method of inhibiting abnormal cell growth, including the introduction of an effective amount of the compounds under item 1.

6. The method according to p. 5, in which inhibiting the cells are tumor cells expressing an activated ras oncogene.

7. The method according to p. 5, in which the inhibition of abnormal cell growth inhibition is farnesyl-protein transferase.

8. The method according to p. 5, which inhibit tumor cells in which the Ras protein is activated in uncage the military for pancreatic cancer, lung cancer, myeloid leukemia, follicular thyroid cancer, myelodysplasia syndrome, epidermal carcinoma, carcinoma of the bladder, colon cancer, breast cancer or prostate cancer in a patient in need of such inhibition, comprising introducing an effective amount of the compounds under item 1 or 3.

10. Pharmaceutical composition having activity of inhibiting abnormal cell growth comprising an effective amount of the compounds under item 1 or 3 in combination with a pharmaceutically acceptable carrier.

 

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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
< / BR>
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< / BR>
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< / BR>
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