110 results about "LRRK2" patented technology

Compounds of the formula I:

or pharmaceutically acceptable salts thereof,

wherein m, n. X, R¹, R², R³, R⁵, R⁶ and R⁷ are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

Compounds of the formula I:

The present invention is directed to azaindazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

Medical compositions and methods of treating or preventing neurodegeneration in a human suffering from or that is at risk of or susceptible to neurodegeneration or cellular dysfunction associated with expression or impaired cellular function of a neuronal protein encoded by one or more genes that code for alpha-synuclein (SNCA), Parkin RBR E3 ubiquitin protein ligase, (PARK2), Leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase/(PINK1), Daisuke-Junko 1, (DJ-1) and ATPase type 13A2 (ATP13A2), are disclosed. Methods of treatment for these disorders is also provided, comprising administering a vector into a cell, wherein the vector facilitates expression of a molecular component that alters one of the aforementioned genes in the cell or expression of the gene in the cell, the gene being implicated in an etiology of the neurological deficit.

Compounds of the formula I:

or pharmaceutically acceptable salts thereof,

wherein m, n. X, R¹, R², R³, R⁴ and R⁵ are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

A compound of formula Ia or formula Ib, or a pharmaceutically acceptable salt or ester thereof, wherein R¹ is selected from: aryl; heteroaryl; —NHR³; fused aryl-C_4-7-heterocycloalkyl; —CONR⁴R⁵; —NHCOR⁶; —C_3-7-cycloalkyl; -0-C_3-7-cycloalkyl; —NR³R⁶; and optionally substituted —C_1-6 alkyl; wherein said aryl, heteroaryl, fused aryl-C_4-7-heterocycloalkyl and C_4-7-heterocycloalkyl are each optionally substituted; Q is CN, halogen, or is selected from C_1-6-alkyl, C_3-7-cycloalkyl, heterocycloalkyl, aryl and heteroaryl, each of which is optionally substituted with one or more substituents A; R² is selected from hydrogen, aryl, C_1-6-alkyl, C_2-6-alkenyl, C_3-7-cycloalkyl, heteroaryl, C_4-7-heterocycloalkyl and halogen, wherein said C_1-6-alkyl, Cz-B-alkenyl, aryl, heteroaryl and C_4-7-heterocycloalkyl are each optionally substituted; R³ is selected from aryl, heteroaryl, C^4-7-heterocycloalkyl, C_3-7-cycloalkyl, fused aryl-C-heterocycloalkyl and C_1-6-alkyl, each of which is optionally substituted; R⁴ and R⁵ are each independently hydrogen, or optionally substituted C_3-7-cycloalkyl, aryl, heteroaryl, C_1-6-alkyl or C_3-6-heterocycloalkyl; or R⁴ and R⁵ together with the N to which they are attached form a C_3-6-heterocycloalkyl ring; each R⁶ is independently selected from C_1-6-alkyl, C_3-7-cycloalkyl, C-heterocycloalkyl, aryl and heteroaryl, each of which is optionally substituted; each R⁷ is selected from hydrogen, optionally substituted C_1-6-alkyl and C_3-7-cycloalkyl; each of R⁸ and R⁹ is independently hydrogen or optionally substituted C_1-6-alkyl; or R⁸ and R⁹ together with the N to which they are attached form a C_4-6-heterocycloalkyl; each R¹⁰ is selected from C_3-7-cycloalkyl and optionally substituted C_1-6-alkyl; each R¹¹ is independently selected from C_1-6-alkyl, C_3-7-cycloalkyl, C_1-6-alkyl-C_3-7-cycloalkyl, C_4-7-heterocycloalkyl, aryl and heteroaryl, each of which is optionally substituted; A is selected from halogen, —NR⁴S0₂R⁵, —CN, —OR⁶, —NR⁴R⁵, —NR⁷R¹¹, hydroxyl, —CF₃, —CONR⁴R⁵, —NR⁴COR⁵, —NR⁷(CO)NR⁴R⁵, —N0₂, —C0₂H, —C0₂R⁶, —S0₂R⁶, —S0₂NR⁴R⁵, —NR⁴COR⁵, —NR⁴COOR⁵, ₆-alkyl and —COR⁶. Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formulae Ia and Ib.

The present invention provides novel imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives of Formula (I), and the pharmaceutically acceptable salts thereof

wherein R¹, R^1a, R^1b, R², R⁴, R⁵, R⁶, X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula (I) and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.

A method for positron emission tomography (PET) imaging of LRRK2 in tissue of a subject, the method comprising: administering a compound of formula I, formula II or formula III, or a pharmaceutically acceptable salt thereof to the subject, wherein the compound includes at least one C¹¹ or F¹⁸ label thereon; allowing the compound to penetrate into the tissue of the subject; and collecting a PET image of the CNS or brain tissue of the subject

he present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).

The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

The invention discloses a targeted capturing and sequencing kit for parkinsoncs disease gene mutation detection and application of the targeted capturing and sequencing kit. The target capturing and sequencing kit comprises probes, capable of specifically capturing the parkinsoncs disease in a targeted manner, of 19 pathogenic gene coding regions, ie SNCA, PRKN, UCHL1, PINK1, PARK 7, LRRK2, ATP13A2, GIGYF2, HTRA 2, PLA2G6, FBXO7, VPS35, EIF4G1, DNAJC6, SYNJ1, TMEM230, CHCHD2, VPS13C and RIC3. The probes are applied to targeted capture of sequences of 19 gene coding regions related to the parkinsoncs disease, then high-throughput sequencing and analysis are performed on the captured sequences, rapid screening is achieved, and gene mutation related to the parkinsoncs disease can be effectively detected at one time. When being applied to clinical gene diagnosis, the targeted capturing and sequencing kit has the advantages of rapidness and convenience in detection, high sensitivity, good specificity and the like.

The present invention provides compounds having a structure according to Formula I. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

The invention discloses a non-treatment-oriented method for constructing a zebrafish model used for sifting drugs for treating Parkinson's diseases. The method is characterized in that LRRK2 mutationzebrafish is put in 1-5 mM of a hydrogen peroxide solution, and it takes only 3-6 days to construct the zebrafish model. By means of the method, the model for the Parkinson's diseases is constructed in the zebrafish by combining multiple factors such as genes, environments and ageing, and the Parkinson's diseases are simulated in animals with high fidelity; by using the animal model as a medium, relevant micromolecule compounds and genetic engineering recombinant proteins are sifted, and the drugs which are made from the micromolecule compounds and the genetic engineering recombinant proteinsand can obviously avoid deficiency of dopaminergic neurons and lowering of the behavior activeness are obtained. The sifting method is simple, the cost is low, and the stability and reliability are high.