387867-13-2

Usage

Uses

Used in Oncology:
Tandutinib is used as an anticancer agent for the treatment of AML and other cancer indications. It acts as an oral, small-molecule inhibitor of FLT3, blocking the growth of cells expressing an internal tandem duplication within the juxtamembrane domain of the FLT3 receptor, which is found in some AML cells. Tandutinib also impairs the growth of colon cancer cells through its actions on the c-Kit receptor and reverses multidrug resistance in vitro by impairing the efflux activity of the multidrug resistance protein 7.
Used in Antipsoratic Applications:
Tandutinib is used as an antipsoratic agent, helping to manage and treat psoriasis, a chronic skin condition characterized by the rapid growth and shedding of skin cells.
Used in Combination Therapy for AML:
In a phase I/II clinical trial, Tandutinib displayed promising antileukemic activity (90% complete remissions) when administered in combination with cytarabine and daunorubicin for the treatment of newly diagnosed AML patients. This combination therapy enhances the efficacy of Tandutinib and improves treatment outcomes for patients with AML.

references

[1] kelly lm1, yu jc, boulton cl, apatira m, li j, sullivan cm, williams i, amaral sm, curley dp, duclos n, neuberg d, scarborough rm, pandey a, hollenbach s, abe k, lokker na, gilliland dg, giese na. ct53518, a novel selective flt3 antagonist for the treatment of acute myelogenous leukemia (aml). cancer cell. 2002 jun;1(5):421-32.

InChI:InChI=1/C31H42N6O4/c1-23(2)41-25-10-8-24(9-11-25)34-31(38)37-17-15-36(16-18-37)30-26-20-28(39-3)29(21-27(26)32-22-33-30)40-19-7-14-35-12-5-4-6-13-35/h8-11,20-23H,4-7,12-19H2,1-3H3,(H,34,38)

Upstream product

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• 461429-53-8 6-methoxy-4-(piperazin-1-yl)-7-(3-(piperidin-1-yl)propoxy)quinazoline 
• 792899-38-8 N-(4-isopropoxyphenyl)piperazine-1-carboxamide 
• 288383-71-1 4-chloro-6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazoline 
• 399037-37-7 N-(4-isopropoxyphenyl)piperazine-1-carboxamide hydrochloride 
• 741702-11-4 4-[6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinazolin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester 
• 205259-42-3 4-(7-benzyloxy-6-methoxy-4-quinazolinyl)-1-piperazinecarboxylic acid tert-butyl ester 
• 461429-76-5 4-[7-(3-chloropropoxy)-6-methoxy-quinazolin-4-yl]piperazine-1-carboxylic acid tert-butyl ester 
• 401819-62-3 4-(7-hydroxy-6-methoxy-4-quinazolinyl)-1-piperazinecarboxylic acid tert-butyl ester 
• 205259-40-1 4-benzyloxy-5-methoxy-2-nitrobenzoic acid benzyl ester 
• 205259-41-2 2-amino-4-benzyloxy-5-methoxybenzoic acid benzyl ester 
• 179688-01-8 7-(benzyloxy)-6-methoxyquinazolin-4(3H)-one 
• 162364-72-9 7-benzyloxy-4-chloro-6-methoxyquinazoline 

Relevant academic research and scientific papers

LACTATE SALT OF 4-[6-METHOXY-7-(3-PIPERIDIN-1-YL-PROPOXY)QUINAZOLIN-4-YL]PIPERAZINE-1-CARBOXYLIC ACID(4-ISOPROPOXYPHENYL)-AMIDE AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF CANCER AND OTHER DISEASES OR DISORDERS

This invention provides a compound of formula (I): or a crystalline form thereof, or a pharmaceutical composition thereof, or an oral pharmaceutical dosage form thereof; processes for the synthesis or manufacture of the compound of formula (I), or a cryst

LACTATE SALT OF 4-(6-METHOXY-7-(3-PIPERIDIN-1-YL-PROPOXY)QUINAZOLIN-4-YL]PIPERAZINE-1-CARBOXYLIC ACID(4-ISOPROPOXYPHENYL)-AMIDE AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF CANCER AND OTHER DISEASES OR DISORDERS

This invention provides a compound of formula (I): or a crystalline form thereof, or a pharmaceutical composition thereof, or an oral pharmaceutical dosage form thereof; processes for the synthesis or manufacture of the compound of formula (I), or a crystalline form thereof, or a pharmaceutical composition thereof, or an oral pharmaceutical dosage form thereof; and the use of said compound, or a crystalline form thereof, or a pharmaceutical composition thereof, or an oral pharmaceutical dosage form thererof, for the treatment of patients suffering from or subject to diseases, disorders or conditions involving cell survival, proliferation, and migration, including cardiovascular disease (e.g., arteriosclerosis and vascular reobstruction), cancer, (e.g., AML and malignant glioma) glomerulosclerosis, fibrotic disease and inflammation.

Improved synthesis of substituted 6,7-dihydroxy-4-quinazolineamines: Tandutinib, erlotinib and gefitinib

The synthesis of three substituted 6,7-dihydroxy-4-quinazolineamines: tandutinib (1), erlotinib (2) and gefitinib (3) in improved yields is reported. The intermediates were characterized by NMR and the purities determined by HPLC.

Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family

We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed against members of PDGFR receptor have been developed through modifications of the novel quinazoline template I. Systematic modifications in the A-bicyclic ring and D-rings of protype I were carried out to afford potent analogues, which display IC50 values of 50 values of 50-200 nM, whereas 15-20-fold less potent activity against CSF1R was observed. This analogue also inhibits autophosphorylation of Flt-3 ligand-stimulated wild-type Flt-3 and a constitutively activated Flt-3/internal tandem duplication (ITD) with IC50 values of 30-100 nM. Through this optimization process, 75 was found to be metabolically stable and has desirable pharmacokinetic properties in all animal species studied (F% > 50%, T1/2 > 8 h). Oral administration of 75 promotes mice survival and significantly delayed disease progression in a Flt-3/ITD-mediated leukemia mouse model and shows efficacy in a nude mouse model of chronic myelomonocytic leukemia.