170959-40-7

Upstream product

• 170959-38-3 C₇H₁₀N₄O₂S 
• 2510-32-9 4-methyl-1,3-oxazole-5-carboxylic acid 
• 6610-29-3 4-methylthiosemicarbazide 
• 62348-24-7 4-Methyl-5-oxazolecarbonyl chloride 
• 170959-38-3 1-(4-methyloxazole-5-carboxyl)-4-methylthiosemicarbazide 

Downstream Products

• 863679-31-6 3-[(3-chloropropyl)sulfanyl]-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole 

Relevant academic research and scientific papers

A mechanistic insight into a simple c-n bond formation via sn2 displacement: A synergistic kinetics and design of experiment approach

A novel series of 1,2,4-triazol-3-yl-azabicyclo[3.1.0]hexanes was recently identified as new highly potent and selective dopamine (DA) D3 receptor antagonists. This class of molecules deserved the Chemical Development special attention to quantify the reliability and robustness of the pivotal SN2 displacement step between the 1,2,4-triazol-3-yl-halide derivative (4) and variously substituted azabicyclo[3.1.0]hexanes (5). To reach this goal we applied the classical Design of Experiment (DoE) approach, simultaneously trying to build up a descriptive kinetic model of the chemistry. The synergistic use of these two techniques allowed us to select new, higher-yielding and more robust reaction conditions and, at the same time, to identify their Design Space.

DOPAMINE D3 RECEPTOR ANTAGONISTS HAVING A MORPHOLINE MOIETY

The disclosure provides compounds of formula (I) or pharmaceutically acceptable salts thereof: The disclosure also provides processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them, and their use

DOPAMINE D3 RECEPTOR ANTAGONISTS HAVING A BICYCLO MOIETY

The disclosure provides compounds having formula (I), wherein the substituents are as defined herein. The compounds are useful for modulating the dopamine D3 receptor and for treating conditions associated therewith, such as addictions, drug dependency, and psychiatric conditions.

DOPAMINE D3 RECEPTOR ANTAGONISTS COMPOUNDS

The disclosure is directed to novel dopamine D3 receptor antagonists, processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, including treating drug dependency and psychosis.

Novel morpholine scaffolds as selective dopamine (DA) D3 receptor antagonists

A new series of morpholine derivatives has been identified as selective DA D3 receptor antagonists; their in vitro profile and pharmacokinetic data are provided.

1,2,4-Triazolyl octahydropyrrolo[2,3-b]pyrroles: A new series of potent and selective dopamine D3 receptor antagonists

A novel series of 1,2,4-triazolyl octahydropyrrolo[2,3-b]pyrroles showing high affinity and selectivity at the DA D3 receptor is reported here. Compounds endowed with high selectivity over the hERG channel were identified and their pharmacokinetic properties thoroughly analyzed. A few derivatives with appropriate developability characteristics were selected for further studies and progression along the screening cascade. In particular, derivative 60a, (DA D3 pKi = 8.4, DA D2 pKi = 6.0 and hERG fpKi = 5.2) showed a balanced profile and further refinements are in progress around this molecule.

1,2,4-Triazolyl 5-Azaspiro[2.4]heptanes: Lead Identification and Early Lead Optimization of a New Series of Potent and Selective Dopamine D3 Receptor Antagonists

A novel series of 1,2,4-triazolyl 5-azaspiro[2.4]heptanes with high affinity and selectivity at the dopamine (DA) D3 receptor (D3R) is described. Some of these compounds also have high selectivity over the hERG channel and were characterized with respect to their pharmacokinetic properties both in vitro and in vivo during lead identification and early lead optimization phases. A few derivatives with overall favorable developability characteristics were selected for further late lead optimization studies.

Exploration of the amine terminus in a novel series of 1,2,4-Triazolo-3-yl- azabicyclo[3.1.0]hexanes as selective dopamine D3 receptor antagonists

A novel series of 1,2,4-triazol-3-yl-azabicyclo[3.1.0]hexanes with high affinity and selectivity for the DA D3 receptor and excellent pharmacokinetic profiles was recently reported. We also recently discussed the role of the linker associated with the triazole moiety. In this manuscript, we are reporting a detailed exploration of the region of the receptor interacting with the amine terminus of the scaffold wherein SAR and developability data associated with these novel templates was undertaken.

1,2,4-Triazolyl azabicyclo[3.1.0]hexanes: A new series of potent and selective dopamine D3 receptor antagonists

The discovery of new highly potent and selective dopamine (DA) D 3 receptor antagonists has recently allowed the characterization of the DA D3 receptor in a range of preclinical animal models of drug addiction. A novel series of 1,2,4-triazol-3-yl-azabicyclo[3.1.0]hexanes, members of which showed a high affinity and selectivity for the DA D3 receptor and excellent pharmacokinetic profiles, is reported here. Members of a group of derivatives from this series showed good oral bioavailability and brain penetration and very high in vitro affinity and selectivity for the DAD3 receptor, as well as high in vitro potency for antagonism at this receptor. Several members of this series also significantly attenuate the expression of conditioned place preference (CPP) to nicotine and cocaine. 2009 American Chemical Society.

PROCESS FOR PREPARING HETEROCYCLIC DERIVATIVES

The present invention relates to a novel process, useful for preparing key intermediates of formula (I) in the synthesis of various compounds, among them compounds which are potent and specific antagonists of D3 receptors, in which X may be Nitrogen or Sulfur;Het means aryl or heteroaryl; each of which may be substituted by 1 to 4 groups J selected from: halogen, C1-C6 alkyl C1-C6 alkoxy, halo C1-C6 alkyl C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, —C(O)R1, nitro, hydroxy, —NR2R3, cyano or a group Z;R1 is a C1-C4 alkyl —OR3 or —NR3R4;R2 is hydrogen or C1-C6 alkyl;R3 is hydrogen or C1-C6 alkyl;R is H, C1-C6 alkyl aryl, benzyl; each of which may be substituted by 1 to 4 groups J;according to the following Scheme 1: in which step a means a reaction in basic conditions of compounds (IIA) with 3-thiosemicarbazide derivatives, followed by a treatment with an inorganic base and n-propane phosphonic cyclic anhydride and final pH adjustment with inorganic acids to give compounds of formula (II).