Derivatives benzothiadiazole, benzoxadiazole and benzodiazines, the method of production thereof and pharmaceutical composition


C07D271/04 - 1,2,3-Oxadiazoles; Hydrogenated 1,2,3-oxadiazoles

 

The invention relates to new derivatives of benzothiadiazole, benzoxazoles and benzodiazines formula I in free base form or in the form of a pharmaceutically acceptable acid salt additive that can be used as an anxiolytic drug in the treatment of any condition, which is associated with increased endogenous levels of CRF or in which violated the regulation of the hPa system (hypothalamic - pituitary), or various diseases that are caused by CRF1or the manifestation of which contributes CRF1such as arthritis, asthma, allergies, anxiety, depression, etc., In the compounds of the formula I X represents O, S or CH=CH, R1and R2independently from each other hydrogen atom, halogen or C1-C4alkyl; Het is a radical having one of the formulas (a), (C), (e), (m), where R3and R8independently from each other - From1-C4alkyl; R4is a hydrogen atom, halogen, C1-With4alkyl or cyano; R5and R6independently of each other a hydrogen atom, a C1-C7alkyl, C3-C7alkenyl,3-C7cycloalkyl,3-C7cycloalkyl-C1-C4alkyl, C1-C4alkoxy-C2-C5alkyl or benzyl; R7- is the effect of the compounds of formula II, where X, R1and R2have the meanings indicated above, a Y is a radical having one of the formulas (a'), ('), (e'), (m'), where R3-R8and W have the meanings indicated above; Hal is halogen, with a compound of formula III HN(R5)(R6), where R5and R6have the meanings indicated above, and the allocation thus obtained the compounds of formula I in free base form or in the form of an acid additive salt. The pharmaceutical composition includes the compound of formula I in free base form or in the form of an acid additive salt in combination with a pharmaceutical carrier or diluent. 3 S. and 3 C.p. f-crystals.

Description text in facsimile form (see graphic part) TC


Claims

1. Derivatives benzothiadiazole, benzoxadiazole and benzodiazines formula I

where X Is O, S or CH=CH;

R1 is within one of the following formulas:

where R3and R8independently from each other - C1-C4alkyl;

R4is a hydrogen atom, halogen, C1-C4alkyl or cyano;

R5and R6independently of each other a hydrogen atom, a C1-C7alkyl,

With3-C7alkenyl,3-C7cycloalkyl,3-C7cycloalkyl-C1-C4alkyl, C1-C4alkoxy-C2-C5alkyl or benzyl;

R7- C1-C4alkyl;

W - N,

in free form or in the form of an acid additive salt.

2. Connection on p. 1, representing 5,7-dimethyl-4-[2,5-dimethyl-6-(di-n-propyl)aminopyrimidine-4-yl]amino-2,1,3-benzothiadiazole in free base form or in the form of an acid additive salt.

3. The method of obtaining the compounds of formula I on p. 1 or its salt, including interaction of the compounds of formula II

where X, R1and R2have the values listed in paragraph 1;

Y is a radical having one of the following formulas:

Hal is halogen,

with the compound of the formula III

where R5and R6have the values listed in paragraph 1,

and the allocation thus obtained the compounds of formula I in free base form or in the form of an acid additive salt.

4. Connection under item 1 or 2, in free base form or in the form of a pharmaceutically acceptable acid salt additive, intended for the preparation of a pharmaceutical preparation.

5. Connection under item 1 or 2, in free base form or in the form of a pharmaceutically acceptable acid salt additive intended for use as an anxiolytic drug in the treatment of any condition, which is associated with increased endogenous levels of CRF or in which violated the regulation of the hPa system (hypothalamic-pituitary), or various diseases that are caused by CRF or manifestation which contributes CRF.

6. The pharmaceutical composition intended for use as an anxiolytic drug in the treatment of any condition, which is associated with increased endogenous levels of CRF or in which violated the regulation of the hPa system (hypothalamic-pituitary), or various diseases that are caused by CRF or pharmazevtichesky acceptable acid salt additive in combination with a pharmaceutical carrier or diluent.

 

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