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CN-121971447-A - Application of amide compound in preparation of pancreatic tumor treatment drugs

CN121971447ACN 121971447 ACN121971447 ACN 121971447ACN-121971447-A

Abstract

The invention discloses an application of an amide compound in preparing a medicine for treating pancreatic tumors, and belongs to the technical field of medicines. The invention discloses an application of N- [ 2-amino-5- (1, 3-benzodioxol-5-ylmethyl) pyridin-3-yl ] benzamide or a pharmaceutically acceptable salt, solvate, metabolite or prodrug thereof in preparing a product for preventing or treating tumor diseases. The compound can remarkably inhibit proliferation of various typical pancreatic cancer cell lines, simultaneously has strong inhibition activity on various subtypes of PI3K, can effectively promote apoptosis of pancreatic cancer cells through inhibition on PI3K, realizes high-efficiency pancreatic cancer resisting effect, and has good application prospect and clinical value in the aspect of developing novel pancreatic cancer targeted therapeutic drugs.

Inventors

  • YU LI
  • ZHU JINGYU
  • DENG YUYING
  • WU LING
  • WU MENGJIA
  • SONG ZHIQIAN

Assignees

  • 常州工程职业技术学院

Dates

Publication Date
20260505
Application Date
20260313

Claims (10)

  1. Use of n- [ 2-amino-5- (1, 3-benzodioxol-5-ylmethyl) pyridin-3-yl ] benzamide or a pharmaceutically acceptable salt, solvate, metabolite or prodrug thereof for the preparation of a product for the prevention or treatment of a neoplastic disease; The structural formula of the N- [ 2-amino-5- (1, 3-benzodioxol-5-ylmethyl) pyridin-3-yl ] benzamide is as follows: 。
  2. 2. the use according to claim 1, wherein the neoplastic disease comprises a neoplastic disease mediated by PI3K activation.
  3. 3. The use according to claim 1, wherein the neoplastic disease comprises pancreatic cancer.
  4. 4. The use according to claim 1, wherein the product comprises a tumor angiogenesis inhibitor.
  5. 5. The use according to claim 1, wherein the product comprises a PI3K inhibitor.
  6. 6. The use according to claim 1, wherein the prevention or treatment of a neoplastic disease comprises at least one of: (1) Inhibiting proliferation of pancreatic cancer cell lines including PANC-1, capan-2, CFPAC-1, MIA PaCa-2, SU.86.86, and BxPC-3; (2) Promoting apoptosis of pancreatic cancer cells; (3) Inhibiting PI3K signaling pathway.
  7. 7. A PI3K inhibitor, comprising N- [ 2-amino-5- (1, 3-benzodioxol-5-ylmethyl) pyridin-3-yl ] benzamide or a pharmaceutically acceptable salt, solvate, metabolite, or prodrug thereof.
  8. 8. A medicament, wherein the active component of the medicament comprises N- [ 2-amino-5- (1, 3-benzodioxol-5-ylmethyl) pyridin-3-yl ] benzamide or a pharmaceutically acceptable salt, solvate, metabolite or prodrug thereof.
  9. 9. The drug of claim 8, wherein the drug comprises an adjuvant comprising at least one of solvents, propellants, solubilizing agents, co-solvents, emulsifiers, binders, disintegrants, fillers, lubricants, wetting agents, tonicity modifiers, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adherents, integrating agents, permeation enhancers, pH modifiers, buffers, plasticizers, surfactants, foaming agents, antifoaming agents, thickening agents, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, release retarders, and pharmaceutically acceptable adjuvants; The dosage form of the medicament comprises solid, semi-solid or liquid.
  10. 10. Use of a medicament according to claim 8 or 9 for the preparation of a product for the prophylaxis or treatment of pancreatic cancer.

Description

Application of amide compound in preparation of pancreatic tumor treatment drugs Technical Field The invention relates to the technical field of medicines, in particular to application of an amide compound in preparation of a medicine for treating pancreatic tumors. Background Pancreatic cancer is a digestive system tumor with extremely high malignancy, the pathological characteristics of the pancreatic cancer are expressed as rapid invasive growth, and the global morbidity of the pancreatic cancer continuously rises in recent years. Current tumor treatment strategies have shifted from traditional cytotoxic modes to molecular level intervention, with most of the research focused on the field of targeted therapies. However, currently available targeted drugs for the treatment of pancreatic cancer, such as erlotinib, an epidermal growth factor receptor inhibitor, everolimus, a rapamycin target protein inhibitor, and sunitinib, a tyrosine kinase inhibitor, have improved therapeutic effects to some extent, but have corresponding toxic and side effects and have developed obvious drug resistance phenomena. Therefore, a novel and efficient drug for targeted treatment of pancreatic tumors needs to be developed, and nonspecific killing is reduced while the treatment effect is enhanced, so that toxic and side effects of the drug are reduced, and the accuracy of targeted treatment is improved. In the molecular pathogenesis of tumors, phosphatidylinositol 3-kinase (PI 3K) signaling pathway is of great interest for its critical regulation of proliferation, metabolism, survival, anti-apoptosis of cells. The PI3K kinase family is classified into class I, II, and III according to structure and substrate selectivity, wherein class I PI3K is most closely related to tumorigenesis and development, and is classified into class IA (pi3kα, pi3kβ, pi3kδ) and class IB (pi3kγ). Studies have demonstrated that deregulation of molecules in PI3K cell signaling pathways and their molecular cross-talk play an important role in the molecular pathogenesis of pancreatic cancer, about 50% of which exhibit excessive activation of PI3K signaling. Overactivation of PI3K/Akt signaling may be achieved by a variety of mechanisms that may differ at each stage of cancer occurrence, including overexpression of the Akt gene, mutation of activation of the KRAS gene, increased transcription of the pik3cg gene encoding p110γ, inactivation of oncostatin function associated with activation of nuclear factor κb, upregulation of the growth factor pathway, and activation of G protein-coupled receptor signaling. At present, a significant part of pancreatic cancers (46-70%) have high expression of phosphorylated Akt, which further highlights the great potential of PI3K pathway as a pancreatic cancer treatment target. Drug development aiming at PI3K signaling pathway has become a research hotspot in the field of anti-tumor, and currently developed PI3K inhibitors are mainly divided into pan-PI3K inhibitors, PI3K subtype selective inhibitors and PI3K/mTOR double-target inhibitors. Of these, the pan-PI3K inhibitor-representative drug was Copanlisib developed by Bayer, inc. for the treatment of recurrent follicular lymphoma. PI3K subtype selective inhibitors include Idelalisib, duvelisib, aleplisib and the like. The PI3K/mTOR dual-target inhibitor can more effectively block proliferation and survival of tumor cells by simultaneously inhibiting PI3K and mTOR signaling pathways, but may increase the risk of adverse reactions due to stronger inhibition. Meanwhile, the downstream signal path of PI3K is extremely complex, and only one specific subtype (such as PI3K alpha or PI3K delta) is inhibited, so that tumor cells can possibly activate other subtypes to form compensatory paths, thereby inducing drug resistance. In contrast, pan-PI3K inhibitors are able to more fully block the entire PI3K signaling pathway. In addition, studies have found that there are significant differences in the gene expression levels of the PI3K isoforms (α, β, δ, γ) in different pancreatic cancer cell lines, which present challenges for the development of subtype selective inhibitors, making it difficult to identify a universally dominant targeting subtype. Therefore, the development of a novel pan-PI3K inhibitor capable of inhibiting the activity of class I PI3K in a broad spectrum has important scientific significance and clinical value for improving the applicability and the effectiveness of pancreatic cancer treatment and overcoming drug resistance. Disclosure of Invention Aiming at the problems existing in the prior art, the invention provides application of an amide compound in preparing a medicine for treating pancreatic tumors. The amide compound N- [ 2-amino-5- (1, 3-benzodioxol-5-ylmethyl) pyridine-3-yl ] benzamide has an inhibiting effect on PI3K, can promote apoptosis of tumor cells by inhibiting PI3K, and has better applicability to pancreatic cancer treatment. The technical schem