1005-37-4

Usage

Uses

Used in Laboratory Research:
NSC36831 is used as a mutagen and carcinogen for [the purpose of inducing genetic mutations and studying the mechanisms of carcinogenesis]. It serves as a valuable tool in understanding how genetic mutations occur and the processes involved in the development of cancer.
Used in Cancer Research:
In the field of cancer research, NSC36831 is used as a chemical carcinogen to [study the effects of chemical carcinogens on human health]. Its application aids in the exploration of the relationship between exposure to certain chemicals and the risk of cancer, providing insights into preventive measures and potential therapeutic targets.
Used in Toxicology Studies:
NSC36831 is also utilized in toxicology studies as a reference compound for [assessing the toxicity of various agents and understanding the dose-response relationships]. This helps in determining the safety profiles of new chemical entities and contributes to the development of guidelines for safe exposure levels.
Used in Risk Assessment and Regulatory Compliance:
Furthermore, NSC36831 is employed in risk assessment and regulatory compliance as a benchmark substance for [evaluating the potential health risks associated with exposure to mutagenic and carcinogenic agents]. This is crucial for setting safety standards and regulations to protect public health.

InChI:InChI=1/C5H7ClN4/c1-8-4-2-3(6)9-5(7)10-4/h2H,1H3,(H3,7,8,9,10)

Upstream product

• 56-05-3 2-Amino-4,6-dichloropyrimidine 
• 74-89-5 methylamine 
• 593-51-1 methylamine hydrochloride 

Downstream Products

• 1159107-85-3 6-(benzyloxy)-N⁴-methylpyrimidine-2,4-diamine 
• 1612180-21-8 6-(4-tert-butylphenyl)-4-N-methylpyrimidine-2,4-diamine 
• 1612179-78-8 4-N-methyl-6-[1-(4-methylbenzenesulfonyl)-1H-indol-3-yl]pyrimidine-2,4-diamine 
• 1612182-07-6 tert-butyl 4-{4-[2-amino-6-(methylamino)pyrimidin-4-yl]-2-(methoxymethyl)phenoxymethyl}piperidine-1-carboxylate 
• 1612182-09-8 3-[2-amino-6-(methylamino)pyrimidin-4-yl]-2-methylbenzonitrile 
• 1612182-10-1 6-(4-methoxy-2,3-dimethylphenyl)-4-N-methylpyrimidine-2,4-diamine 
• 1612182-11-2 6-(4-fluoro-2,3-dimethylphenyl)-4-N-methylpyrimidine-2,4-diamine 
• 1612182-13-4 4-N-methyl-6-[2-methyl-5-(morpholine-4-sulfonyl)phenyl]pyrimidine-2,4-diamine 
• 1612182-70-3 N-({3-[2-amino-6-(methylamino)pyrimidin-4-yl]phenyl}methyl)prop-2-enamide 
• 1612182-79-2 6-[3-(aminomethyl)phenyl]-4-N-methylpyrimidine-2,4-diamine 
• 1612182-69-0 N-({4-[2-amino-6-(methylamino)pyrimidin-4-yl]phenyl}methyl)prop-2-enamide 
• 1612182-80-5 6-[4-(aminomethyl)phenyl]-4-N-methylpyrimidine-2,4-diamine 
• 1609960-30-6 6-(2,3-dichlorophenyl)-4-N-methylpyrimidine-2,4-diamine 
• 1612180-38-7 6-(2,3-dimethylphenyl)-N⁴-methylpyrimidine-2,4-diamine 

Relevant academic research and scientific papers

Inhibitor development of MTH1 via high-throughput screening with fragment based library and MTH1 substrate binding cavity

MutT Homolog 1 (MTH1) has been proven to hydrolyze oxidized nucleotide triphosphates during DNA repair. It can prevent the incorporation of wrong nucleotides during DNA replication and mitigate cell apoptosis. In a cancer cell, abundant reactive oxygen species can lead to substantial DNA damage and DNA mutations by base-pairing mismatch. MTH1 could eliminate oxidized dNTP and prevent cancer cells from entering cell death. Therefore, inhibition of MTH1 activity is considered to be an anti-cancer therapeutic target. In this study, high-throughput screening techniques were combined with a fragment-based library containing 2,313 compounds, which were used to screen for lead compounds with MTH1 inhibitor activity. Four compounds with MTH1 inhibitor ability were selected, and compound MI0639 was found to have the highest effective inhibition. To discover the selectivity and specificity of this action, several derivatives based on the MTH1 and MI0639 complex structure were synthesized. We compared 14 complex structures of MTH1 and the various compounds in combination with enzymatic inhibition and thermodynamic analysis. Nanomolar-range IC50 inhibition abilities by enzyme kinetics and Kd values by thermodynamic analysis were obtained for two compounds, named MI1020 and MI1024. Based on structural information and compound optimization, we aim to provide a strategy for the development of MTH1 inhibitors with high selectivity and specificity.

Heterocyclic compounds as well as preparation method and application thereof

The invention belongs to the field of medicines and particularly relates to heterocyclic compounds with the structural characteristics shown in formula (I) or pharmaceutically acceptable salts, a preparation method and an application of the heterocyclic compounds as a nucleotide oxidative damage repairase MTH1 inhibitor. Pharmacological experiment results indicate that the compounds have significant inhabitation effects on the activity of MTH1 and can be used for preventing and treating clinical diseases related to MTH1.

POLYMER FILM, RETARDATION FILM, POLARIZING PLATE, LIQUID CRYSTAL DISPLAY, AND COMPOUND

Provided is a polymer film containing at least one of a compound represented by formula (1) of hydrates, solvates, or salts thereof. Y is a methine group or nitrogen atom. Qa, Qb, and Qc are a single bond or a divalent linking group. Ra, Rb, and Rc, are hydrogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, cyano group, halogen group, or heterocyclic group. X2 is a single bond or a divalent linking group. X1 is a single bond or a predetermined divalent linking group. R1 and R2 are a hydrogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, or heterocyclic group Formula (1)

Method for synthesizing MTH1 protein inhibitors TH287

The invention discloses a method for synthesizing MTH1 protein inhibitors TH287, and belongs to the technical field of chemical synthesis. The method for synthesizing the MTH1 protein inhibitors TH287 at two steps includes carrying out reflux reaction on

MTH1 INHIBITORS FOR TREATMENT OF INFLAMMATORY AND AUTOIMMUNE CONDITIONS

A compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of autoimmune diseases and inflammatory conditions.

Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors

Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.

CHEMICAL COMPOUNDS

The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Cyclin dependent kinase inhibitors

A range is disclosed of pyrimidine derivatives (I) which can act as inhibitors of cyclin dependent kinases (CDK's) and which thereby can provide useful therapeutic compounds for use in treatment of tumours or other cell proliferation disorders. The compounds of this invention bind to CDK molecules in a manner that appears to differ from that of known CDK inhibitors such as olomoucine and roscovitine. In formula (I), X is O, S or CHRxwhere Rxis H or C1-4alkyl; D is H or NZ1Z2where Z1and Z2are each independently H, C1-4alkyl, C1-4hydroxyalkyl, optionally substituted aryl or optionally substituted aralkyl; A is selected from H, C1-4alkyl, C1-4alkoxy, hydroxy, CH2(CH2)nOH (n=1-4), and NRa1Ra2where Ra1and Ra2are each independently H or C1-4alkyl; Y is or includes an optionally substituted 4- to 8-membered carbocyclic or heterocyclic ring; D′ is H or NZ3Z4where Z3and Z4are each independently H, C1-4alkyl, C1-4hydroxyalkyl, optionally substituted aryl or optionally-substituted aralkyl; E is selected from NO, NO2, N═N—Ar where Ar is an optionally substituted aryl or optionally substituted aralkyl, NRe1Re2or Nre1Nre2Re3(Re1, Re2and Re3each being independently H, C1-4alkyl, C1-4hydroxyalkyl, an optionally substituted aryl or an optionally substituted aralkyl), C(Re)═U (Rebeing hydrogen, C1-4alkyl or substituted alkyl, e.g. hydroxyalkyl, or an unsubstituted or substituted aryl or aralkyl, e.g. benzyl, and U being selected from O, Nre′, NORe′ and N—NRe′Re″ where Re′ and Re″ are each independently H, C1-4alkyl or CONH2), T, CH2T, CHT2and CT3, where T is a halide I, Br, Cl or F.

Composition for slowing down the loss of hair based on pyrimidine N-oxides triaminosubstituted or their sulfoconjugated

Composition for slowing down the loss of hair and for inducing and stimulating its growth, comprising a compound of formula: STR1 in which: R1 and R2 denote H or an alkyl and do not simultaneously denote H; R3 and R4 denote H, an alkyl or a heterocyclic ring with the nitrogen in position 6 and do not simultaneously denote H; X denotes H or a halogen; Y denotes O or OSO3 ; and their addition salts of physiologically acceptable acids.