646071-31-0

Upstream product

• 120-92-3 cyclopentanone 
• 870-46-2 t-butoxycarbonylhydrazine 
• 79201-39-1 tert-butyl 2-cyclopentylidenehydrazine carboxylate 

Downstream Products

• 24214-72-0 cyclopentylhydrazine hydrochloride 
• 693287-72-8 (1-cyclopentyl-5-(4-methylthiophenyl)pyrazol-3-yl)methanol 
• 693287-71-7 methyl 1-cyclopentyl-5-(4-methylthiophenyl)pyrazol-3-carboxylate 
• 693287-73-9 [1-cyclopentyl-5-(4-methanesulfonyl-phenyl)-1H-pyrazol-3-yl]-methanol 
• 30241-37-3 1-cyclopentyl-3-methyl-1H-pyrazol-5-amine 
• 1055924-99-6 N'-(2-cyano-9-methyl-9H-purin-6-yl)-N'-cyclopentyl-4-({4-[(4-methyl-1-piperazinyl)carbonyl]-1-piperidinyl}methyl)benzohydrazide trifluoroacetate 
• 1055925-94-4 N'-{2-cyano-9-[2-(dimethylamino)ethyl]-9H-purin-6-yl}-N'-cyclopentyl-6-{4-[(4-methyl-1-piperazinyl)methyl]phenyl}-2-pyridinecarbohydrazide trifluoroacetate 
• 1055924-97-4 N'-(2-cyano-9-methyl-9H-purin-6-yI)-N'-cyclopentyl-4-({4-[(1-methyl-4-piperidinyl)methyl]-1-piperazinyl}methyl)benzohydrazide trifluoroacetate 
• 1055924-93-0 N'-(2-cyano-9-methyl-9H-purin-6-yI)-N'-cyclopentyl-4-{[4-(4-methyl-1-piperazinyl)-1-piperidinyl]methyl}benzohydrazide trifluoroacetate 
• 1055925-51-3 N'-(2-cyano-9-methyl-9H-purin-6-yI)-N'-cyclopentyl-5-{4-[(4-methyl-1-piperazinyl)methyl]phenyl}-3-pyridinecarbohydrazide trifluoroacetate 
• 1055925-53-5 N'-(2-cyano-9-methyl-9H-purin-6-yI)-N'-cyclopentyl-6-{4-[(4-methyl-1-piperazinyl)methyl]phenyl}-2-pyridinecarbohydrazide trifluoroacetate 
• 1055925-87-5 N'-{2-cyano-9-[2-(dimethylamino)ethyl]-9H-purin-6-yl}-N'-cyclopentyl-4-[(4-methyl-1-piperazinyl)methyl]benzohydrazide trifluoroacetate 
• 1055925-04-6 N'-(2-cyano-9-methyl-9H-purin-6-yI)-N'-cyclopentyl-4-{[3-(1-pyrrolidinyl)-1-azetidinyl]methyl}benzohydrazide trifluoroacetate 
• 1055926-08-3 N'-(2-cyano-9-methyl-9H-purin-6-yl)-N'-cyclopentyl-4-[(4-methyl-1-piperazinyl)methyl]benzohydrazide trifluoroacetate 

Relevant academic research and scientific papers

Pyrazole Agonist of the Apelin Receptor Improves Symptoms of Metabolic Syndrome in Mice

Apelin receptor agonism improves symptoms of metabolic syndrome. However, endogenous apelin peptides have short half-lives, making their utility as potential drugs limited. Previously, we had identified a novel pyrazole-based agonist scaffold. Systematic modification of this scaffold was performed to produce compounds with improved ADME properties. Compound 13 with favorable agonist potency (cAMPi EC50 = 162 nM), human liver microsome stability (T1/2 = 62 min), and pharmacokinetic profile in rodents was identified. The compound was tested in a mouse model of diet-induced obesity (DIO) and metabolic syndrome for efficacy. Treatment with 13 led to significant weight loss, hypophagia, improved glucose utilization, reduced liver steatosis, and improvement of disease-associated biomarkers. In conclusion, a small-molecule agonist of the apelin receptor has been identified that is suitable for in vivo investigation of the apelinergic system in DIO and perhaps other diseases where this receptor has been implicated to play a role.

Identification of potent pyrazole based APELIN receptor (APJ) agonists

The apelinergic system comprises the apelin receptor and its cognate apelin and elabela peptide ligands of various lengths. This system has become an increasingly attractive target for pulmonary and cardiometabolic diseases. Small molecule regulators of this receptor with good drug-like properties are needed. Recently, we discovered a novel pyrazole based small molecule agonist 8 of the apelin receptor (EC50 = 21.5 μM, Ki = 5.2 μM) through focused screening which was further optimized to initial lead 9 (EC50 = 0.800 μM, Ki = 1.3 μM). In our efforts to synthesize more potent agonists and to explore the structural features important for apelin receptor agonism, we carried out structural modifications at N1 of the pyrazole core as well as the amino acid side-chain of 9. Systematic modifications at these two positions provided potent small molecule agonists exhibiting EC50 values of 100 nM. Recruitment of β-arrestin as a measure of desensitization potential of select compounds was also investigated. Functional selectivity was a feature of several compounds with a bias towards calcium mobilization over β-arrestin recruitment. These compounds may be suitable as tools for in vivo studies of apelin receptor function.

Discovery, synthesis and characterization of a series of (1-alkyl-3-methyl-1H-pyrazol-5-yl)-2-(5-aryl-2H-tetrazol-2-yl)acetamides as novel GIRK1/2 potassium channel activators

The present study describes the discovery and characterization of a series of 5-aryl-2H-tetrazol-3-ylacetamides as G protein-gated inwardly-rectifying potassium (GIRK) channels activators. Working from an initial hit discovered during a high-throughput screening campaign, we identified a tetrazole scaffold that shifts away from the previously reported urea-based scaffolds while remaining effective GIRK1/2 channel activators. In addition, we evaluated the compounds in Tier 1 DMPK assays and have identified a (3-methyl-1H-pyrazol-1-yl)tetrahydrothiophene-1,1-dioxide head group that imparts interesting and unexpected microsomal stability compared to previously-reported pyrazole head groups.

Drug Discovery against Psoriasis: Identification of a New Potent FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor, 1-(4-((1H-Pyrazolo[3,4-d]pyrimidin-4-yl)oxy)-3-fluorophenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea, That Showed Potent Activity in a Psoriatic Animal Model

Psoriasis is a chronic T-cell-mediated autoimmune disease, and FMS-like tyrosine kinase 3 (FLT3) has been considered as a potential molecular target for the treatment of psoriasis. In this investigation, structural optimization was performed on a lead compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (1), which showed a moderate inhibitory activity againt FLT3. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis led to the discovery of a number of potent FLT3 inhibitors. One of the most active compounds, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-fluorophenyl)-3-(5-tert-butylisoxazol-3-yl)urea (18b), was then chosen for in-depth antipsoriasis studies because this compound displayed the highest potency in a preliminary antipsoriasis test. Compound 18b exhibited significant antipsoriatic effects in the K14-VEGF transgenic mouse model of psoriasis, and no recurrence was found 15 days later after the last administration. Detailed mechanisms of action of compound 18b were also investigated. Collectively, compound 18b could be a potential drug candidate for psoriasis treatment.

PROTEIN KINASE INHIBITORS

The present invention relates to a novel family of inhibitors of protein kinases. In particular, the present invention relates to inhibitors of the members of the Tec and Src protein kinase families.

Discovery of ectoparasiticidal hydrazonotrifluoromethanesulfonanilides

A series of hydrazonotrifluorosulfonanilide derivatives were synthesized and evaluated for in vitro activity against the ectoparasites Ctenocephalides felis and Rhipicephalus sanguineus. Some compounds with excellent activity against tick were identified.

Hydrazinopyrimidines as cysteine protease inhibitors

Substituted heteroaryl nitrile derivatives of Formula I, processes for their preparation, pharmaceutical compositions comprising such compounds and use of the compounds as cysteine protease inhibitors are provided.

PURINES AS CYSTEINE PROTEASE INHIBITORS

Substituted heteroaryl nitrile derivatives of Formula I, processes for their preparation, pharmaceutical compositions comprising such compounds and use of the compounds as cysteine protease inhibitors are provided.

N-PHENYL-1,1,1-TRIFLUOROMETHANESULFONAMIDE HYDRAZONE DERIVATIVE COMPOUNDS AND THEIR USAGE IN CONTROLLING PARASITES

Novel N-phenyl-1,1,1-trifluoromethanesulfonamide compounds useful for controlling endo and/or ectoparasites in the environment are provided, together with methods of making the same, and methods of using the inventive compounds to treat parasite infestations in vivo and ex vivo.

FUSED PYRIMIDINE DERIVATIVE

The present invention provides a fused pyrimidine derivative having an insulin secretion stimulating activity represented by Formula (I): {wherein R1 represents a hydrogen atom, lower alkyl, or the like; n represents an integer of 0 to 3; and X1 and X2 may be the same or different and each represents a hydrogen atom, lower alkyl, or the like; and formula (II): represents formula (III): [wherein X--Y--Z represents R2C=CR3-NR4 (wherein R2, R3 and R4 may be the same or different and each represents a hydrogen atom, lower alkyl, or the like)]}, or a pharmaceutically acceptable salt thereof.