40 results about "Subtype selectivity" patented technology

Novel peptides which are conformationally constrained backbone cyclized somatostatin analogs, having somatostatin receptor subtype selectivity are disclosed. These patterns or receptor subtype selectivity provide compounds having improved therapeutic utility. Methods for synthesizing the somatostatin analogs and for screening of the somatostatin analogs are also disclosed. Furthermore, pharmaceutical compositions comprising somatostatin analogs, and methods of using such compositions are disclosed.

A compound having selective modulating activity at the alpha 2B and / or alpha 2C adrenergic receptor subtypes is represented by the general Formula 1:whereinn=1-4;X is C or N;R1-R6 can be the same or different and are independently selected from the group consisting of H, C1-6 alkyl, OCH3, OH, F, Cl, Br, CH2OH, CH2N(R7)2, C(O)R8, CH2CN, CF3;wherein R7 is H or C1-6 alkyl; andR8 is C1-6 alkyl or aryl.The compounds of Formula 1 can be incorporated in pharmaceutical compositions and used in methods of treatment of alpha 2 receptor mediated diseases and conditions.

The invention relates to a three-dimensional crystal structure model of alpha1-AR subtype protein and an establishment method thereof. The establishment method comprises the following steps of searching a protein crystal database with an amino acid sequence of the alpha1-AR subtype protein as a probe and obtaining a homologous template beta2-AR with the highest similarity through comparison with the amino acid sequence; utilizing a Prime module of (formula) to carry out homology modeling on the alpha1-AR subtype protein; and adopting an Macromodel module to optimize protein obtained by homology modeling and obtaining the three-dimensional crystal structure model of the alpha1-AR subtype protein through model evaluation. The invention provides model conformations of three alpha1-AR subtype proteins, namely alpha1A-AR, alpha1B-AR and alpha1D-AR and provides the basis for accurately researching structure-function relationship between a target spot and an antagonist; a possible binding packet is modelled, a key residue is found, and the theoretical basis is provided for explaining the selectivity of an alpha1-AR subtype selective antagonist.

The invention particularly discloses a high-flux screening cell model of an alpha1-AR subtype selective antagonist, and a construction method and application thereof. The construction method comprises the following steps: co-transfecting eukaryotic expression plasmids, reporter genes and internal reference plasmids of three alpha1-AR subtypes (alpha1A, alpha1B and alpha1D) to a host cell, thus establishing a transient transfection cell model; successively adding an antagonist to be screened and an agonist into the cell model, and co-culturing for a period of time until cells crack; and performing luciferase activity determination on the cracked products, and determining relative expression quantities of the reporter genes and the internal references, thereby evaluating the inhibition activity of the medicament on the three alpha1-AR subtypes (alpha1A, alpha1B and alpha1D). The method passes model stability / volatility inspection and model verification. The cell model can be used for high-flux screening of an alpha1-AR subtype selective antagonist, and can be further used for screening of potential medicaments for treating benign prostatic hyperplasia.

Methods of use of pharmaceutical compositions and novel peptides which are conformationally constrained backbone cyclized somatostatin analogs, having somatostatin receptor subtype selectivity, are disclosed. These patterns or receptor subtype selectivity provide compounds having improved therapeutic utility. Methods for synthesizing the somatostatin analogs and for screening of the somatostatin analogs are also disclosed. Furthermore, pharmaceutical compositions comprising somatostatin analogs are disclosed.

A compound having selective modulating activity at the alpha 2B and or alpha 2C adrenergic receptor subtypes is represented by the general Formula (1): wherein R1-R6 is independently selected from the group consisting of H, C1-6 alkyl, halogen, CH2OH, CH2N(R7)2) CH2CN, C(O)R8, CF3, and aryl; wherein R7 is H or C1-6 alkyl; and R8 is H, C1-6 alkyl or aryl. The compounds of Formula (1) can be incorporated in pharmaceutical compositions and used in methods of treatment of alpha 2 receptor mediated diseases and conditions.

Disclosed are an E-configuration benzamide compound and pharmaceutical formulation and application thereof. The E-configuration benzamide compound has a structure represented by formula (I), with the chemical name of N-(2-amino-4-fluorophenyl)-4-[N-[(E)-3-(3-pyridine) acryl] aminomethyl] benzamide, and 3-pyridine acryl in the structural formula having E-configuration. The E-configuration benzamide compound represented by formula (I) has subtype selective histone deacetylated enzyme inhibitory activity, mainly inhibiting HDAC1, HDAC2, HDAC3 in type I HADC and HDAC10 in type IIb HDAC. The E-configuration benzamide compound represented by formula (I) can be used to treat diseases related to abnormal activity of the histone deacetylated enzyme, such as cancer, including lymphoma, solid tumor and blood system tumor and the like.

Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are amide, ketone, and ester compounds prepared from certain azabicycloalkane carboxylic acids. The resulting compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the α4β2 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and / or prevent a wide variety of conditions or disorders, such as those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and / or prevented. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g. side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle).

The invention relates to a model building method and application of a G protein coupled receptor (GPCR) on a new platform, in particular to model building and application of two subtypes, namely an Atype (ETA receptor) and a B type (ETB receptor), of an endothelin receptor on different cell lines by using an unmarked cell dynamic mass reset technology. The ETA receptor model is constructed on anSH-SY5Y cell line and a PC3 cell line for endogenously expressing ETA receptors respectively, and the ETB receptor model is constructed on a U251 cell line for endogenously expressing ETB receptors. The method has the characteristics of being close to the real environment in vivo, unmarked, real-time in monitoring, high in flux and simple to operate, can screen the ETA receptor and ETB receptor ligands (including agonists and antagonists) with subtype selectivity, and can compare the results of the same compound on the two receptors in the same ratio.

The present invention relates to 1,2,4,5-tetrasubstituted imidazole derivatives as selective cannabinoid CB1 receptor modulators, in particular CB1 receptor antagonists or inverse agonists having a high CB1 / CB2 receptor subtype selectivity, to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said imidazole derivatives. The invention also relates to the use of a compound disclosed herein for the manufacture of a medicament giving a beneficial effect. A beneficial effect is disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art. The invention also relates to the use of a compound of the invention for the manufacture of a medicament for treating or preventing a disease or condition. More particularly, the invention relates to a new use for the treatment of a disease or condition disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art. In embodiments of the invention specific compounds disclosed herein are used for the manufacture of a medicament useful in the treatment of psychiatric and neurological disorders. The compounds have the general formula (I) wherein the symbols have the meanings given in the specification.

The invention discloses an E-configuration benzamide compound and a medicinal preparation thereof and an application thereof. The E-configuration benzamide compound has a structure shown as a formula (I), a chemical name is N-(2-amino-4-fluorophenyl)-4-[N-[(E)-3-(3-pyridine)acryloyl]aminomethyl]benzamide, in the structural formula, the configuration of 3-pyridinyl acryl is E configuration. The E-configuration benzamide compound has subtype selective histone deacetylase inhibition activity, which mainly inhibits HDAC1, HDAC2, and HDAC 3 in an I type of HDAC as well as HDAC10 in a IIb type of HDAC. The E-configuration benzamide compound shown in the formula (I) can be used for treating the disease related to histone deacetylase activity abnormity, such as cancer comprising lymphoma, solid tumor and blood hematological malignancy.

The invention provides well-defined heterocyclic compounds that are useful as subtype selective alpha 2 adrenergic agonists. As such, the compounds described herein are useful in treating a wide variety of disorders associated with selective subtype modulation of alpha 2 adrenergic receptors.

The invention discloses ether aryl piperazine derivatives and salt thereof as well as a preparation method and application of the ether aryl piperazine derivatives and in particular relates to an ether aryl piperazine derivative (I), wherein, the definitions of m, n, o, X, Y, Z, R and R1-R5 are described in the specification. The invention also discloses a preparation method of the ether aryl piperazine derivatives and application of the ether aryl piperazine derivatives in resistance to benign prostatic hyperplasia and tumour. Primary pharmacodynamic study on the ether aryl piperazine derivative compounds is carried out, a dual-luciferase reporter gene and an in-vitro anti-tumour experiment are carried out, and results show that some ether aryl piperazine derivative compounds have good alpha1-AR subtype selectivity and good antitumour activity and can be developed into a novel benign prostatic hyperplasia resistant and anti-tumour medicament.

The invention provides oxazolidine and thiazolidine derivatives that are useful as subtype selective alpha 2 adrenergic agonists. As such, the compounds described herein are useful in treating a wide variety of disorders associated with selective subtype modulation of alpha 2 adrenergic receptors.

The present invention relates to a subtype selective partial agonist of α6 containing nicotinic acetylcholine receptors. Due to its uniquely selective and functional profile, 9-methyl-3-pyridin-3-yl-3,9-diaza-bicyclo[3.3.1]nonane may be useful in the treatment, prevention and / or alleviation of a disease, disorder and / or condition which is responsive to activation of a nicotinic acetylcholine receptor (nAChR) in a subject, wherein the nAChR comprises at least one cholinergic receptor nicotinic alpha 6 subunit (nAChRa6). Preferably, said disease, disorder and / or condition is a Parkinsonian disorder or pain.

A compound having selective modulating activity at the alpha 2B and or alpha 2C adrenergic receptor subtypes is represented by the general Formula (1): wherein R1-R6 is independently selected from the group consisting of H, C1-6 alkyl, halogen, CH2OH, CH2N(R7)2)CH2CN, C(O)R8, CF3, and aryl; wherein R7 is H or C1-6 alkyl; and R8 is H, C1-6 alkyl or aryl. The compounds of Formula (1) can be incorporated in pharmaceutical compositions and used in methods of treatment of alpha 2 receptor mediated diseases and conditions.

Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are amide, ketone, and ester compounds prepared from certain azabicycloalkane carboxylic acids. The resulting compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the α4β2 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and / or prevent a wide variety of conditions or disorders, such as those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and / or prevented. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g. side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle).