Unlock instant, AI-driven research and patent intelligence for your innovation.

Benzo-cycloheptyl-pyridine derivatives containing cyanoguanidine structure, preparation method, and pharmaceutical compositions and medicinal application thereof

A technology of compound and alkyl, applied in drug combination, antipyretic, organic chemistry, etc., can solve the problem of short action time and achieve strong H1 antagonistic effect

Inactive Publication Date: 2012-10-17
ANHUI HONGYE PHARMA
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Classic H 1 Receptor antagonists easily pass through the blood-brain barrier and have affinity with related receptors, causing major side effects such as drowsiness and sedation
In addition, this type of drug has a short action time, and if the dose is increased, it will produce greater toxic and side effects.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Benzo-cycloheptyl-pyridine derivatives containing cyanoguanidine structure, preparation method, and pharmaceutical compositions and medicinal application thereof
  • Benzo-cycloheptyl-pyridine derivatives containing cyanoguanidine structure, preparation method, and pharmaceutical compositions and medicinal application thereof
  • Benzo-cycloheptyl-pyridine derivatives containing cyanoguanidine structure, preparation method, and pharmaceutical compositions and medicinal application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048]4-(8-Chloro-5H-benzo[5,6]cycloheptane[1,2-b]pyridin-11(6H)-ylidene)-N'-cyano-N-(methylthio) Piperidine-1-amidine (4)

[0049] Deslortadine 6g (0.0193mol), dimethyl dicarboxylate 3g, absolute ethanol 60ml, stirred at room temperature, the solid gradually completely dissolved into a clear liquid, and methyl mercaptan gas was released. After 1 hour, a large amount of white solids were precipitated during the reaction. Continue to react for 1h, filter with suction, and dry to obtain 6.4g of white crystals, mp162-163.5°C, yield 81.2%.

[0050] 1 H NMR (300MHz, CDCl 3 )δ: 2.36-2.44 (m, 2H, CH 2 ), 2.47-2.72 (m, 2H, CH 2 ), 2.75(s, 3H, SMe), 2.78-2.90(m, 2H, CH 2 ), 3.28-3.39 (m, 2H, CH 2 ), 3.50-3.60 (m, 2H, CH 2 ), 4.03-4.15 (m, 2H, CH 2 ), 7.09-7.14(m, 3H, Ar), 7.18(t, 1H, Ar), 7.47(dd, 1H, Ar), 8.40(dd, 1H, Ar)

[0051] IR (cm -1 ): 2929, 2180, 1548, 1540, 1434, 991.

[0052] 4-(8-Chloro-5H-benzo[5,6]cycloheptane[1,2-b]pyridin-11(6H)-ylidene)-N'-cyano-N-butylpipe...

Embodiment 2

[0058] 4-(8-Chloro-5H-benzo[5,6]cycloheptane[1,2-b]pyridin-11(6H)-ylidene)-N'-cyano-N-pentylpiperidine- 1-amidine (I 2 )

[0059] Taking 4-n-pentylamine as raw material, the preparation method is the same as I 1 . A yellow solid was obtained, mp: 155~156°C, yield 37.2%. Anal.calcd for C 26 h 30 ClN 5 : C, 69.70; H, 6.75; N, 15.63. Found C, 69.69; H, 6.81; N, 15.71.

[0060] MS (ESI, 70ev, m / z): 448.2 [M+H] + , 470.1[M+Na] +

[0061] 1 H NMR (300MHz, CDCl 3 )δ: 0.89(t,3H,CH 3 ); 1.25~1.33(m, 4H, 2CH 2 ); 1.52~1.61 (m, 2H, CH 2 ); 2.36~2.39(m, 2H, =C(CH 2 ) 2 ); 2.41~2.81(m, 2H, =C(CH 2 ) 2 ); 2.83~2.84(m, 2H, N(CH 2 ) 2 ); 3.27~3.39 (m, 6H, PhCH 2 , NCH 2 , N(CH 2 ) 2 ); 3.67~3.73 (m, 2H, CH 2 ); 4.82(br, 1H, NH); 7.09~7.17(m, 4H, Ar-H, pyridine-H); 7.48(dd, 1H, J=7.5Hz, pyridine-H); 8.40(dd, 1H, J=3.9Hz, pyridine-H).

[0062] IR (cm -1 ): 3290, 2953, 2928, 2868, 2158, 1573, 1553, 1503, 1435, 1322, 1295, 999, 993, 827, 810

Embodiment 3

[0064] 4-(8-Chloro-5H-benzo[5,6]cycloheptane[1,2-b]pyridin-11(6H)-ylidene)-N'-cyano-N-octylpiperidine- 1-amidine (I 3 )

[0065] Taking 4-n-octylamine as raw material, the preparation method is the same as I 1 . A white solid was obtained, mp: 136~137°C, yield 41.4%. Anal.calcd for C 29 h 36 ClN 5 : C, 71.07; H, 7.40; N, 14.29. Found C, 71.01; H, 7.38; N, 1432.

[0066] MS (ESI, 70ev, m / z): 490.2 [M+H] + , 512.3[M+Na] +

[0067] 1 H NMR (300MHz, CDCl 3 )δ: 0.86(t, 3H, CH 3 ); 1.25~1.26(m, 10H, 5CH 2 ); 1.53~1.57 (m, 2H, CH 2 ); 2.35~2.40(m, 2H, =C(CH 2 ) 2 ); 2.50~2.78(m, 2H, =C(CH 2 ) 2 ); 2.80~2.84(m, 2H, N(CH 2 ) 2 ); 3.24~3.39 (m, 6H, PhCH 2 , NCH 2 , N(CH 2 ) 2 ); 3.65 ~ 3.72 (m, 2H, CH 2 ); 4.88(br, 1H, NH); 7.08~7.16(m, 4H, Ar-H, pyridine-H); 7.46(dd, 1H, J=7.6Hz, pyridine-H); 8.38(dd, 1H, J=3.5Hz, pyridine-H).

[0068] IR (cm -1 ): 3285, 2952, 2920, 2852, 2161, 1571, 1538, 1436, 1329, 1297, 1254, 1174, 1085, 993, 829, 783

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to compounds as represented by general formula (I) and pharmaceutically acceptable salts thereof. The compounds have good anti-allergic / anti-inflammatory effects. The invention also relates to a preparation method for the compounds and medicinal preparations containing the compounds. According to the invention, a series of the compounds as represented by general formula (I) and the pharmaceutically acceptable salts thereof are synthesized.

Description

technical field [0001] The invention belongs to the technical field of chemical industry, and relates to a benzo[5,6]cycloheptyl[1,2-b]pyridine derivative containing a cyanoguanidine structure, a preparation method, a pharmaceutical composition and a medical application thereof. Background technique [0002] Allergic disease is a common disease, which is related to the body's own active substances (Autacoids). Histamine is one of the main chemical mediators of allergic reactions, and its physiological effects are the direct cause of disease. Histamine receptors have H 1 、H 2 、H 3 Three: excited H 1 receptors, can cause smooth muscle contraction of intestinal tract, uterus, bronchi and other organs, and in severe cases, cause bronchial smooth muscle spasm and dyspnea. In addition, it can also cause capillary dilation, increased wall permeability, increased gland secretion, edema and itching, and participate in the occurrence of immune response and allergic reaction. [...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D401/04A61K31/4545A61P29/00A61P37/08
Inventor 金荣富陈静周金培陈学锋刘武昆
Owner ANHUI HONGYE PHARMA