42 results about "P2X3 Receptor" patented technology

The invention discloses a dihydropyrimidine compound as well as a preparation method and an application thereof, and belongs to the technical field of medicinal chemistry. The structure of the dihydropyrimidine compound provided by the invention is as shown in a formula I in the specification. The preparation method provided by the invention comprises the following steps: carrying out substitution reaction on a compound a and a compound k under the catalysis of alkali to generate a compound b; performing substitution reaction on the compound c and the compound d under an alkaline condition to obtain a compound e; carrying out Mitsunobu reaction on the compound e and f to obtain an intermediate g, and carrying out coupling reaction on the compound g and b to generate a compound h. The invention provides the application of the compound shown in the formula I or salt, solvate, allomer, metabolite, nitric oxide and prodrug thereof in preparation of drugs for treating or preventing P2X3 and / or / P2X2 / 3 receptor related diseases. The dihydropyrimidine compound disclosed by the invention has a good P2X3 receptor antagonism effect and better safety.

The invention discloses a dihydropyrimidine compound as well as a preparation method and application thereof, belongs to the technical field of medicinal chemistry, and solves the problems of poor effect and large adverse reaction of a P2X3 receptor inhibitor in the prior art. The structure of the dihydropyrimidine compound is as shown in a formula I in the specification. The invention further provides a preparation method of the compound shown in the formula I and application of the compound in preparation of drugs for treating or preventing P2X3 and / or P2X2 / 3 receptor related diseases. The dihydropyrimidine compound provided by the invention has good affinity with P2X3, has a relatively strong antagonistic effect on a P2X3 receptor, and is safe and effective.

The subject invention relates to novel P2X3 receptor antagonists that play a critical role in treating disease states associated with pain, in particular peripheral pain, inflammatory pain, or tissue injury pain that can be treated using a P2X3 receptor subunit modulator.

The invention relates to a heterocyclic derivative inhibitor as well as a preparation method and an application thereof. In particular, the present invention relates to a compound represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and a use thereof as a P2X3 inhibitor in the treatment of P2X3 receptor dysfunction diseases, especially in the treatment of neurogenic diseases.

The invention discloses applications of a P2X3 acceptor conditioning agent benzimidazole compound in preparation of medicines used for treating respiratory diseases. The general formula of the P2X3 acceptor conditioning agent benzimidazole compound is disclosed in the invention. The P2X3 acceptor conditioning agent benzimidazole compound can be used for preparation of medicines used for treating and / or preventing and / or delaying and / or adjuvant therapy of respiratory diseases, is capable of improving COPD damaged pulmonary function obviously, reducing pulmonary artery high pressure obviously,improving lung tissue fibrosis deposition, possesses excellent treatment effect, is high in clinical application value, and is promising in prospect.

The subject invention relates to novel P2X3 receptor antagonists that play a critical role in treating disease states associated with pain, in particular peripheral pain, inflammatory pain, or tissue injury pain that can be treated using a P2X3 receptor subunit modulator.

The subject invention relates to novel P2X3 receptor antagonists that play a critical role in treating disease states associated with pain, in particular peripheral pain, inflammatory pain, or tissue injury pain that can be treated using a P2X3 receptor subunit modulator.

The subject invention relates to novel P2X3 receptor antagonists that play a critical role in treating disease states associated with pain, in particular peripheral pain, inflammatory pain, or tissue injury pain that can be treated using a P2X3 receptor subunit modulator.

The subject invention relates to novel P2X3 receptor antagonists that play a critical role in treating disease states associated with pain, in particular peripheral pain, inflammatory pain, or tissue injury pain that can be treated using a P2X3 receptor subunit modulator.

The present invention relates to novel P2X3 receptor antagonists, which play an important role in the treatment of pain-related disease states, especially peripheral pain, inflammatory pain or tissue injury pain that can be treated with P2X3 receptor subunit modulators.

The subject invention relates to novel P2X3 receptor antagonists that play a critical role in treating disease states associated with pain, in particular peripheral pain, inflammatory pain, or tissue injury pain that can be treated using a P2X3 receptor subunit modulator.

The invention relates to novel application of emodin in the field of pharmacy, i.e. the application of emodin in preparing medicaments for treating P2X3 mediated neuropathic pains / nervous system diseases. In experiments, the emodin is observed to have an effect on inhibiting algesia behavioral reaction and is further observed to have an effect on inhibiting the mRNA and protein expression of nerve cell P2X3 receptors of rat dorsal root ganglia in a neuropathic pain model and rat trigeminal ganglion in a trigeminal neuralgia model by applying the technologies of immunohistochemistry, in-situ hybridization, RT-PCR (Reverse Transcription-Polymerase Chain Reaction), protein blotting and the like. The experiments prove that the mechanism of the effect of the emodin on inhibiting chronic pains (neuropathic pains) and pains transmitted by trigeminal ganglion nerve cells is to block algesia information transmission mediated by a primary sensory nerve cell P2X3 receptor. The invention provides a novel method for preventing and treating the pains mediated by the neuropathic pains and / or the trigeminal ganglion nerve cells; meanwhile, the invention shows that the emodin has the effect on influencing the P2X3 receptor, which is beneficial to medicinal application on preventing and treating nerve system diseases related to the P2X3 receptor.

The subject invention relates to novel P2X3 receptor antagonists that play a critical role in treating disease states associated with pain, in particular peripheral pain, inflammatory pain, or tissue injury pain that can be treated using a P2X3 receptor subunit modulator.

The invention provides a dinucleoside polyphosphate analogue, or a pharmaceutically acceptable salt thereof, for use in the inhibition (or down-regulation) of a pain, via a transducing ATP-gated P2X3 receptor, often by means of high-affinity desensitisation (HAD) mechanism.

The invention relates to a nitrogen-containing ring derivative inhibitor as well as a preparation method and an application thereof. In particular, the present invention relates to a compound represented by general formula (I), a preparation method thereof, a pharmaceutical composition containing the compound, and uses of the compound as a P2X3 inhibitor in treatment of P2X3 receptor dysfunction diseases, especially in treatment of neurogenic diseases.

The invention refers to medicine and pharmacology, namely, to biologically active peptides, which modulate purinergic signaling. For that, the peptide with the following amino acid sequence is proposed:Gly1-Tyr2-Cys3-Ala4-Thr5-Lys6-Gly7-Ile8-Lys9-Cys10-Asn11-Asp12-Ile13-His14-Cys15-Cys16-Ser17-Gly18-Leu19-Lys20-Cys21-Asp22-Ser23-Lys24-Arg25-Lys26-Val27-Cys28-Val29-Lys30-Gly31,or a sequence with at least 90% homology hereto.Peptides in the invention can be used for prevention and treatment of diseases mediated by purinergic receptors. The peptides can be used for development of new drugs on their basis, for example, analgesics, as well for investigation of mechanisms of pain occurrence, for identification and testing of new modulators of P2X3 receptors. The peptides in the invention can be produced using chemical synthesis or biotechnologically using the nucleotide sequence of the corresponding gene.

The invention discloses a crystal form of a heterocyclic compound as well as a preparation method and application of the crystal form. The crystal form of the compound is as shown in a formula A. The crystal form is a crystal form I, a crystal form II, a crystal form III, a crystal form IV, a crystal form V, a crystal form VI, a crystal form VII, a crystal form VIII or a crystal form IX. The invention discloses a preparation method of the crystal form, a composition and application of the crystal form in preparation of a P2X3 receptor antagonist. The invention also relates to the application of the compound in preparation of medicines for preventing and / or treating pains, urinary tract diseases or respiratory system diseases. The P2X3 receptor antagonist has the advantages of high P2X3 antagonistic activity, good selectivity, low toxicity, good metabolic stability and small taste influence.

The invention discloses an N-formamido pyrazoline derivative, a compound represented by a general formula (I) or an enantiomer, a diastereoisomer, an epimer, a racemate or pharmaceutically acceptablesalt thereof. The compound is an antagonist of a ligand gated non-selective cationic channel receptor subtype P2X3, and can be used for treating or preventing various diseases mediated by a P2X3 receptor.

The invention provides application of long non-coding RNA (Ribonucleic Acid) uc.48+ small interfering RNA to preparation of medicine for treating DM (Diabetes Mellitus) complicating neuropathic pain. Experiments prove that NONRATT021972 small interfering RNA can reduce the expression of a dorsal root ganglion neuron P2X3 receptor, can reduce the generation of a DM rat dorsal root ganglion cell inflammatory factor-TNF-alpha (Tumor Necrosis Factor-alpha), can inhibit the nociceptive information transmission of the dorsal root ganglion, can reduce the nociception stimulation of the nerve injury and inflammatory substances, can reduce the pain behavior of a rat with the type 2 DM neuropathic pain, and can be applied to the preparation of medicine for treating DM complicating neuropathic pain, DM complicating nerve injury relevant diseases and DM complicating nerve injury sensory nerve inflammatory diseases.

The present invention relates to use 1,3-thiazol-2-yl substituted benzamide compounds of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds for the treatment or prophylaxis of diseases which are associated with nerve fiber sensitization, and / or other pathological conditions associated with autonomic imbalance caused by increased chemoreceptor sensitivity, in particular for the treatment of breathing disorders, Cheyne Stokes respiration, central and obstructive sleep apnea, cardiovascular disease, hypertension, resistant hypertension, and heart failure, which are related to increased activity of P2X3 receptors.

The invention relates to application of small interfering RNA of long non-coding ribonucleic acid MRAK009713 to preparation of drugs for treating neuropathic pain. The small interfering RNA of the long non-coding ribonucleic acid MRAK009713 can alleviate pain behavior responses of rats with neuropathic pain, reduce P2X3 receptor expression on the dorsal root ganglion, and has the effects of preventing and treating pain. The small interfering RNA of the long non-coding ribonucleic acid MRAK009713 can further be applied to preparation of drugs for preventing and treating involved P2X3 receptor-mediated nervous system diseases. The small interfering RNA of the long non-coding ribonucleic acid MRAK009713 can be prepared into oral liquids, injections, lozenges or other preparations in local or whole body dosage forms, which are suitable for treating neuropathic pain, and preventing and treating involved P2X3 receptor-mediated nervous system diseases.

The invention relates to a new purpose of resveratrol in the pharmaceutical field, that is, an application of resveratrol in the preparation of medicines for treating P2X3-mediated chronic pain diseases. Experimental observation results show that resveratrol can inhibit pain related behaviors, and observation results of experiments applied with technologies of immunohistochemistry, in situ hybridization, RT-PCR, protein blotting and the like show that resveratrol can inhibit the mRNA expression and the protein expression of a P2X3 acceptor of the dorsal root ganglia from a neuropathic pain model rat. Experiments confirm that the mechanism of the inhibition effect of resveratrol to chronic pains is the antagonism of the primary sensory ganglion P2X3 acceptor-mediated pain information transmission. According to the invention, a new chronic pain (neuropathic pain) control method is ascertained, and simultaneously a case that resveratrol has effects of P2X3 acceptor antagonists is disclosed, so above observations of the invention are in favor of the application of resveratrol in the preparation of purine X3 acceptor (P2X3 acceptor) specificity antagonists.

The invention discloses the novel use of a VEGF antibody and a VEGF receptor antagonist in the fields of pain-killing vaccines and pharmacy, namely the use of the VEGF antibody or the VEGF receptor antagonist in the preparation of an acute / chronic pain killing vaccine and a medicament for treating P2X3 and P2X2 / 3 purine receptor-mediated nerve system diseases. Through experiments it is observed that the VEGF antibody can inhibit the algetic behavior response; and by using immunohistochemistry, in-situ hybridization, RT-PCR, protein blotting and other techniques, it is observed that the VEGF antibody can inhibit the expression of mRNAs and proteins of the P2X2 and P2X3 receptors, VEGF and F1k-1 / VEGFR2 of rat dorsal root ganglia of a model of neuropathic pain. Experiments prove that the pain killing mechanism of the VEGF antibody is that the pain is killed by neutralizing the VEGF or antagonist VEGF receptor to reduce pathologic pains and by blocking the pain information transmission of dorsal root neurons. The invention provides a new method for preventing and treating acute and chronic pains. Meanwhile, it is shown that the VEGF antibody can inhibit the expression of the P2X2 and P2X3 receptors, which is favorable for the use of the VEGF antibody and the VEGF receptor antagonist in the prevention and treatment of nerve system diseases related to the P2X2 and P2X3 receptors.

The present invention relates to compounds of formula I that inhibit P2X purine receptor 3; in particular, the present invention relates to compounds that are aminoquinazoline derivatives, processes for preparing such compounds, pharmaceutical compositions comprising them and therapeutic uses thereof. The compounds of the invention are useful in the treatment of many disorders associated with the P2X3 receptor mechanism, such as respiratory diseases, including cough, asthma, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD).

The subject invention relates to the rhesus monkey P2X3 receptor, nucleic acids encoding this receptor, methods of modulating the activity of a target purinergic receptor using the P2X3 receptor and to uses of these methods. In particular, such methods may be used, for example, to accelerate the rate of resensitization of a desensitized receptor.

The invention provides a novel compound capable of effectively antagonizing a P2X3 receptor, which is a compound as shown in a formula I, a tautomer, a stereoisomer, a hydrate, a solvate, a pharmaceutically acceptable salt or a prodrug thereof, a preparation method of the novel compound, and application of the novel compound in preparation of medicines.

The invention relates to the technical field of biological medicines. The bladder overactivity is presented clinically with frequent micturition and urgent urination, and also appears in neurogenic bladder, overactive bladder, bladder outlet obstruction, interstitial cystitis and other diseases. A polypeptide micromolecule capable of inhibiting the activity of a P2X3 acceptor is provided and has an amino acid sequence as shown in SEQ ID NO.: 1. The invention also provides application of the polypeptide micromolecule in preparation of a medicine for preventing and treating bladder overactivity.