233755-70-9

Upstream product

• 220462-02-2 2-chloro-4-(3-methylpyrazol-1-yl)benzoic acid methyl ester 
• 85953-29-3 methyl 2-chloro-4-fluorobenzoate 
• 220461-68-7 2-chloro-4-(3-methyl-1H-pyrazol-1-yl)-benzoic acid 

Downstream Products

• 955402-85-4 C₂₂H₁₉ClN₄O 
• 955402-83-2 C₁₉H₁₆ClN₃O₃ 
• 1143023-20-4 2-chloro-N-[(6-{[3-(4-methylpiperazin-1-yl)propyl]sulfonyl}-1,3-benzothiazol-2-yl)carbamoyl]-4-(3-methyl-1H-pyrazol-1-yl)benzamide 
• 220461-67-6 2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzamide 
• 530089-00-0 (2Z)-{1-[2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzoyl]-4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene}acetic acid 
• 955402-87-6 C₂₄H₂₁ClN₄O₃ 
• 220461-57-4 [2-Chloro-4-(3-methyl-pyrazol-1-yl)-phenyl]-(4H,10H-pyrazolo[5,1-c][1,4]-benzodiazepin-5-yl)-methanone 
• 220461-58-5 [2-chloro-4-(3-methyl-pyrazol-1-yl)-phenyl]-(5,10-dihydro-4H-tetrazolo[5,1-c][1,4]benzodiazepin-5-yl)-methanone 
• 220460-92-4 VNA-932 
• 1209963-38-1 5-[2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzoyl]-1-methyl-1,4,5,10-tetrahydro pyrazolo[3,4-b][1,5]benzodiazepine 

Relevant academic research and scientific papers

Identification, optimization, and pharmacology of acylurea GHS-R1a inverse agonists

Ghrelin plays a major physiological role in the control of food intake, and inverse agonists of the ghrelin receptor (GHS-R1a) are widely considered to offer utility as antiobesity agents by lowering the set-point for hunger between meals. We identified an acylurea series of ghrelin modulators from high throughput screening and optimized binding affinity through structure-activity relationship studies. Furthermore, we identified specific substructural changes, which switched partial agonist activity to inverse agonist activity, and optimized physicochemical and DMPK properties to afford the non-CNS penetrant inverse agonist 22 (AZ-GHS-22) and the CNS penetrant inverse agonist 38 (AZ-GHS-38). Free feeding efficacy experiments showed that CNS exposure was necessary to obtain reduced food intake in mice, and it was demonstrated using GHS-R1a null and wild-type mice that this effect operates through a mechanism involving GHS-R1a.

Subtlety of the Structure-Affinity and Structure-Efficacy Relationships around a Nonpeptide Oxytocin Receptor Agonist

Very few nonpeptide oxytocin agonists have currently been reported, and none of them seem suitable for the in vivo investigation of the oxytocin mediated functions. In an attempt to rationalize the design of better tools, we have systematically studied the structural determinants of the affinity and efficacy of representative ligands of the V1a, V2, and OT receptor subtypes. Despite apparently obvious similarity between the ligand structures on one hand, and between the receptor subtypes on the other hand, the binding affinity and the functional activity profiles of truncated and hybrid ligands highlight the subtlety of ligand-receptor interactions for obtaining nonpeptide OT receptor agonists.

Synthesis and structure-activity relationships of amide derivatives of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetic acid as selective arginine vasopressin V2 receptor agonists

A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives was synthesized, and their structure-activity relationships were examined in order to identify potent and selective arginine vasopressin V2 receptor agonists. Attempts to substitute other chemical groups in place of the 2-pyridilmethyl moiety of 1a led to the discovery that potent V2 binding affinity could be obtained with a wide range of functional groups. This structural tolerance allowed for the manipulation of other attributes, such as selectivity against V1a receptor affinity or avoidance of the undesirable inhibition of cytochrome P450 (CYP), without losing potent affinity for the V2 receptor. Some representative compounds obtained in this study were also found to decrease urine volume in awake rats.

Optimization of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives as arginine vasopressin V2 receptor agonists and discussion of their binding modes

A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives were optimized to achieve potent agonistic activity, both in vitro and in vivo, for the arginine vasopressin V2 receptor, resulting in the eventual di

Identification and synthesis of major metabolites of Vasopressin V2-receptor agonist WAY-151932, and antagonist, Lixivaptan

Small molecule agonists and antagonists of the V2-vasopressin receptor have been discovered and have undergone clinical trials. In conjunction with these discovery programs, the synthesis and biological testing of various metabolites associated with these clinical targets were actively pursued. We now report the results of our synthetic efforts and the corresponding biological data generated for several of the metabolites of WAY-151932 and CL-347985 (Lixivaptan).

4,4-DIFLUORO-1,2,3,4-TETRAHYDRO-5H-1-BENZAZEPINE DERIVATIVES OR SALTS THEREOF

4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine derivatives, which have excellent arginine vasopressin V2 activity and are useful for a drug for the treatment of central diabetes insipidus and/or nocturia.

Vasopressin agonist formulation and process

This invention provides novel formulations for vasopressin agonist compounds, or a pharmaceutically acceptable salt thereof, having the general structure: and processes for making them, the formulations comprising from about 1% to about 20% of active ingredient, from about 1% to about 18% of a surfactant component, from about 50% to about 80% of a component of one or more polyethylene glycols, from about 1% to about 20% of a component of one or more sucrose fatty acid esters and/or polyvinylpyrrolidone and, optionally, one or more preservatives or antioxidants.

Tricyclic vasopressin agonists

This invention relates to new compounds selected from those of the general formula (I), or a pharmaceutically acceptable salt, ester or prodrug form thereof: wherein D, E and G are N or CH, which serve as vasopressin agonists and are useful in treating disorders such as diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleeding and coagulation disorders, and the inability to temporarily delay urination and pharmaceutical compositions and methods for same.

Novel design of nonpeptide AVP V2 receptor agonists: Structural requirements for an agonist having 1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine as a template

The discovery of a series of nonpeptide arginine vasopressin V2 receptor agonists is described. After identifying the aniline derivative 8 as our lead compound from the metabolites of compound 7 that showed antidiuretic activity by po administr