2, 3, 5, 7-tetrasubstituted dihydro-pyrazolo piperidine derivative and preparation method and application thereof
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A technology of dihydropyrazole and hexahydropyridine, which is used in drug combination, organic chemistry, antitumor drugs, etc.
Inactive Publication Date: 2013-12-04
SHANGHAI NORMAL UNIVERSITY
View PDF1 Cites 7 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
However, the number of new anti-cancer drugs on the market in my country and the number of candidate drugs in preclinical research
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
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
preparation example Construction
[0039] 2. The preparation method of the embodiment of the general formula (I) of the present invention
[0040] (1) At room temperature, add 0.16mol methyl acrylate and 7mL methanol to a 100mL three-neck bottle, and slowly add the mixture of 0.04mol substituted aromatic methylamine represented by formula (A) and 4mL methanol into the three-neck bottle while stirring During the process, the temperature of the reaction system should not exceed 50°C. After the dropwise addition, heat and reflux for 8 hours. After the reaction is over, recover methanol and unreacted methyl acrylate, distill under reduced pressure, and obtain light yellow oily liquid N,N-bis(β-methyl acrylate ) Aromatic methylamine.
[0041]Add 15mL of anhydrous toluene and 0.122mol of sodium metal to a 250mL dry three-necked flask, stir and heat to reflux, add 0.2mL of anhydrous methanol, and then slowly add 0.04mol of N,N-bis(β-methyl propionate) aromatic A mixture of methylamine and 20 mL of anhydrous toluene....
Embodiment 1
[0046] Example 1: 2-(4-nitrophenyl)-3-(4-fluorophenyl)-5-(2-furylmethyl)-7-(4-fluorobenzylidene)-2H-pyrazole And [4,3-c] hexahydropyridine (Ⅰ 1 )
[0047] Yield 86%; melting point 245-246°C; 1 H NMR (CDCl 3 ,400MHz)δ2.43-2.49(m,1H),3.16-3.42(m,3H),3.43-3.63(m,2H),4.06(d,J=14.1Hz,1H),4.47(d,J= 12.7Hz,1H),6.11(s,1H),,6.37(s,1H),6.82(t,J=7.2Hz,1H),7.01-7.74(m,13H).IR(KBr,cm -1 )3445,1640,1597,1495,1436,1082,747;;Anal.Calcd for C 30 h 24 f 2 N 4 o 3 :C,68.43;H,4.59;N,10.64.Found:C,68.45;H,4.63;N,10.61.
Embodiment 2
[0048] Example 2: 2-(3-nitrophenyl)-3-(4-fluorophenyl)-5-(2-furylmethyl)-7-(4-fluorobenzylidene)-2H-pyrazole And [4,3-c] hexahydropyridine (Ⅰ 2 )
[0049] Yield 77%; melting point 259-260°C; 1 HNMR(400MHz,)δ2.44-2.51(m,1H),3.15-3.33(m,3H),3.47-3.63(m,2H),4.11(d,J=14.3Hz,1H),4.42(d, J=12.4Hz,1H),6.13(s,1H),,6.37(s,1H),6.87(t,J=7.2Hz,1H),7.03-7.72(m,13H);IR(KBr,cm -1 )3447,1641,1598,1495,1436,1081,748;Anal.Calcd for C 30 h 24 f 2 N 4 o 3 :C,68.43;H,4.59;N,10.64;Found:C,68.41;H,4.61;N,10.61.
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
Login to view more
Abstract
The invention provides 2, 3, 5, 7-tetrasubstituted dihydro-pyrazolo piperidine derivative and a preparation method and application thereof. The derivative is 2, 3-bis(substituted phenyl)-5-subsituted arylmethyl-7-substituted benzylidene dihydro-pyrazolo piperidine derivative, having the following formula (I). The preparation method includes using substituted arylmethyl amine and methyl acrylate as raw materials; subjecting the materials to Michael addition, Dieckmann condensation and hydrolysis-decarboxylation sequentially; allowing for Aldol reaction with substituted benzaldehyde to obtain intermediate N-substituted arylmethyl-3, 5-bis(substituted benzylidene)-4-piperidone; allowing for condensation with substituted phenylhydrazine to obtain a compound according to the formula (I). The derivative is efficient in inhibiting multiplication of various carcinoma cell lines such as leukemia, esophagus cancer, ovarian cancer and breast cancer in human, is well stably metabolic in liver microsomes of human and rat, is free of direct and competitive inhibition on five enzymes of liver microsomes, such as CYP3A4, CYP2D6, CYP2C9, CYP1A2 and CYP2C19, is highly bioavailable, is low in toxicity to normal cells, and is available for the preparation of drugs for the cancers.
Description
technical field [0001] The invention belongs to the field of organic synthesis and medicinal chemistry, and relates to a 2,3,5,7-tetrasubstituted dihydropyrazolohexahydropyridine derivative, specifically a 2,3-disubstituted phenyl-5 -Substituted arylmethyl-7-substituted benzylidene dihydropyrazolohexahydropyridine derivatives and their preparation methods, and related to their preparation and inhibition of human leukemia, human esophageal cancer, human liver cancer, human ovarian cancer and human Breast cancer, and many other human cancer cell lines proliferation drug application. Background technique [0002] According to the estimates of the World Health Organization, there are more than 3 million cancer patients in my country, and 1.6 to 2 million new cancers are diagnosed every year, with an increase of 3% and a younger trend. For example, leukemia, a blood cell cancer, is more likely to occur in adolescents, and its incidence rate ranks first among adolescent tumors, s...
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
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to view more 
Login to view more