42 results about "Subtype selective" patented technology

The invention discloses E-configuration benzamide compounds, and a pharmaceutical preparation application thereof. The structure of the E-configuration benzamide compounds is disclosed as Formula (I); the chemical name is N-(2-amino-4-fluorophenyl)-4-[N-[(E)-3-(3-pyridyl)acryloyl]aminomethyl]benzamide; and in the structural formula, the configuration of the 3-pyridylacryloyl group is E. The E-configuration benzamide compounds disclosed as Formula (I) have subtype selective histone deacetylase inhibition activity, and are mainly used for inhibiting HDAC1, HDAC2 and HDAC3 in Class I HDAC and HDAC10 in Class IIb HDAC. The E-configuration benzamide compounds disclosed as Formula (I) can be used for treating diseases related to histone deacetylase activity abnormity, such as cancers, including lymphomata, entity tumor, blood system tumors and the like.

This invention relates to a method for modulating α2 subtype GABAA receptors with heterocyclic compounds of formula I, and salts, solvates and prodrugs thereof. The invention further relates to novel heterocyclic compounds and pharmaceutical compositions containing said compounds. In addition the invention relates to the treatment of depression, an anxiety disorder, a psychiatric disorder, a learning or cognitive disorder, a sleep disorder, a convulsive or seizure 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: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, in part, to granulocyte type selective markers that are preferentially expressed in granulocytes and their use in drug screening assays. Additionally, the granulocyte type selective markers are useful in the diagnosis and treatment of granulocyte disorders and in the assessment of the efficacy of therapies of granulocyte disorders.

Opioid receptor compounds and pharmaceutical compositions thereof are presented. Also presented are methods for treating a condition mediated by an opioid receptor by administering an effective amount of the opioid receptor compound to a patient in need thereof.

Disclosed are chemical entities of Formula (I):wherein R1 and Z are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of Formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of Formula (I).

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.

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.

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 chemical entities of formula (I) wherein X, Y, Z, R1, R3, R4, R5 and R6 are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of formula I.

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.

Disclosed are chemical entities of formula I: [INSERT CHEMICAL FORMULA HERE] wherein X, Y, Z, R1, R3, R4, R5 and R6 are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of formula I, and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of formula I.

A method of treating, preventing or ameliorating a disease or condition by inhibiting NR2B subunit containing NMDA receptors using a compound according to formula (I) or a pharmaceutically acceptable salt thereof.

This invention relates to a method for modulating α2 subtype GABAA receptors with heterocyclic compounds of formula I, and salts, solvates and prodrugs thereof. The invention further relates to novel heteocyclic compounds and pharmaceutical compositions containing said compounds. In addition the invention relates to the treatment of depression, an anxiety disorder, a psychiatric disorder, a learning or cognitive disorder, a sleep disorder, a convulsive or seizure disorder or pain

Opioid receptor compounds and pharmaceutical compositions thereof are presented. Also presented are methods for treating a condition mediated by an opioid receptor by administering an effective amount of the opioid receptor compound to a patient in need thereof.

The present invention provides compounds which are subtype selective antagonists of the alpha 2B adrenergic receptor and have no or weak antagonist activity at the other alpha adrenergic receptors. These compounds are useful as tool compounds and, in particular, as tool compounds for developing compounds useful in treating diseases that include but are not limited to chronic pain, visceral pain, corneal pain, neuropathic pain, glaucoma, ischemic neuropathies and other neurodegenerative diseases and conditions. These compounds are also useful as compounds for treating myocardial infarction and preventing acute coronary events. The compounds of this invention are 3-amino-1-thioxo or oxo-1,2,5,6,7,8-hexahydro-2,7-naphthyridine-4-carbonitriles or substituted derivatives thereof.

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.

A method of treating, preventing, or ameliorating a pathological condition associated with a melatonin receptor in a mammal by using a pharmaceutical composition containing a compound of formula (I) as a ligand interacting with the melatonin receptor,R1, R2, R3, R4 and R7 are independently H, halo, alkyloxyl, alkyl or hydroxyl, provided that one of R1, R2, R3 and R7 is X—(CH2)n—R8; R5 is alkyl or arylalkyl; R6 is H or alkyl; X is a bond, O, S, SO, SO2, CO or NH; n=0-10; R8 is alkenyl, substituted or unsubstituted aryl, NR9R10, or OR9; R9 is H, substituted or unsubstituted arylmethyl, or alkenyl; and R10 is H or alkyl.

The invention specifically discloses a 1 ‑High-throughput screening cell model of AR subtype-selective antagonists and its construction method and application. The construction method is to use α 1 ‑AR three subtypes (α 1A ,α 1B ,α 1D ) eukaryotic expression plasmid, reporter gene and internal reference plasmid were co-transfected into host cells, and a transient cell model was established. Antagonists and agonists to be screened were added to the cell model successively. After a period of co-culture, the cells were lysed and the lysates were processed. Assay of luciferase activity, determine the relative expression of reporter gene and internal control, so as to evaluate the effect of the drug on α 1 ‑AR three subtypes: α 1A 、α 1B and alpha 1D inhibitory activity. This method passes model stability, volatility inspection and model verification. available for alpha 1 ‑High-throughput screening of AR subtype-selective antagonists can be further used to screen potential drugs for the treatment of benign prostatic hyperplasia.

This invention relates to a method for modulating α2 subtype GABAA receptors with heterocyclic compounds of formula I, and salts, solvates and prodrugs thereof. The invention further relates to novel heteocyclic compounds and pharmaceutical compositions containing said compounds. In addition the invention relates to the treatment of depression, an anxiety disorder, a psychiatric disorder, a learning or cognitive disorder, a sleep disorder, a convulsive or seizure disorder or pain

The invention discloses the application of Buxusemine H and Buxusemine L, a boxwood alkaloid, in pharmaceutical preparation, and belongs to the field of pharmaceutical technology. Specifically, the invention provides the application of Buxusemine H and Buxusemine L, a boxwood alkaloid, in preparing drugs for treating inflammatory pain, visceral pain and neuropathic pain, and in preparing Ca v 3.2 Application in selective inhibitors of low voltage-gated calcium channel subtypes. Buxusemine H and Buxusemine L inhibit Ca v 3.2 The activity of low voltage-gated calcium channels is prominent, and the response to Ca v 3.2 and Ca v 3.1 The selectivity of low voltage-gated calcium channels is 9 and 30 respectively, which is significantly better than the candidate molecule Z944 in clinical trials (in Ca v 3.1 and Ca v 3.2) and the boxwood alkaloid analog cyclovibrobuxin D (in Ca v 3.1 and Ca v Buxusemine L has no selectivity in Na v 1.7 Na v Buxusemine L has outstanding specificity in ion channels involved in pain conduction, such as TRPV1, TPRA1, TRPM8, ASIC3, P2X2 and P2X4. At the same time, Buxusemine L can significantly relieve L-cysteine-induced inflammatory pain, acetic acid-induced visceral pain and sciatic nerve ligation-induced neuropathic pain in mice, and its effect is comparable to that of the positive controls Mibefradil and Z944.

The invention provides methods for treating disorders associated with selective subtype modulation of alpha 2 adrenergic receptors. In particular, the invention provides methods employing well-defined N-[1-(2 and / or 3-substituted-phenyl)-alkyl]-(4,5-dihydro-1H-imidazol-2-yl)-amines and pharmaceutical compositions thereof to treat disorders associated with selective subtype alpha 2 adrenergic receptor modulation, such as ocular disorders, pain and central nervous system (CNS) motor disorders.

The invention discloses a single base editing system for regulating and controlling selective expression of a CaMKII-delta subtype. The system is composed of a Cas9 protein mutant fused with base deaminase and sgRNA for recognizing a CaMKII-delta gene sequence. Wherein the sgRNA guides the fusion protein to realize single base substitution of a splicing donor of a target site intron 15 or a splicing ligand of intron 16 in the CaMKII-delta, the RNA splicing process of the target gene CaMKII-delta is effectively regulated and controlled, the CaMKII-delta 3 subtype is selectively expressed by the CaMKII-delta gene subjected to directional splicing regulation, and meanwhile, the CaMKII-delta 9 is eliminated. The invention further provides application of the base editing system in treating ischemic cardiomyopathy, cardiac CaMKII-delta subtype selective expression is regulated through single base mutation, myocardial damage caused by blood reperfusion is efficiently reversed, and the base editing system is expected to be applied to treatment of ischemic cardiomyopathy.

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.

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.