28 results about "Isoindoline" patented technology

The application discloses a 3-(5-(aminomethyl)-1-oxoisoindoline-2-yl)piperidine-2,6-dione derivative and a synthesis method and application thereof, and relates to a 3-(5-(aminomethyl)-1-oxoisoindoline-2-yl)piperidine-2,6-dione derivative which is a compound with the following general formula (I): wherein R1 is selected from,,,,,,,,, and R2 is selected from,,, and. The compound can significantly inhibit the proliferation of leukemia, multiple myeloma, lymphoma, breast cancer, liver cancer and the like at a low dose (nanomole), can effectively degrade IKZF1, IKZF3, BRD4, GSPT1 and CK1 alpha, and has the prospect of being developed into an anti-tumor drug. The application solves the problem that the existing malignant hematological disease treatment drugs have a high safety risk.

The present disclosure provides a compound of Formula (I'): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein Rx, X1, X2, and Ri are as defined herein, and methods of making and using same.

The present application relates to compounds of Formula (I) or pharmaceutically acceptable salts, solvates and / or prodrugs thereof, to compositions comprising these compounds or pharmaceutically acceptable salts, solvates and / or prodrugs thereof, and various uses in the treatment of diseases, disorders or conditions that are treatable by inhibiting or blocking NUAK kinase, such as cancers and fibrosis.

Provided are compounds of the structural Formula (I): and pharmaceutically acceptable salts and compositions thereof, which are useful for treating a variety of conditions associated with ALK.

The application discloses a reaction type thermoplastic resin with a large free volume, a preparation method and a bismaleimide resin composition, and belongs to the technical field of polymer material toughening. N 2 a nucleophilic polycondensation reaction to obtain a polyaryletherketone / sulfone copolymer containing a reaction type group, wherein the bisphenol compound is selected from one or more of phenolphthalein, thymolphthalein, bisphenol fluorene and isoindolinone-based bisphenol. The application introduces a bisphenol compound with a large side group into the molecular chain of the thermoplastic resin to construct a large free volume structure, and simultaneously utilizes TGSH to provide an active propenyl group, so that the resin can participate in the curing and cross-linking reaction of bismaleimide. The bismaleimide resin composition using the resin as a toughening agent has a significantly improved toughness after curing.

The application belongs to the technical field of organic synthesis, and particularly relates to a kind of bromine-containing isoindoline-1-ketone compound and preparation method thereof.The preparation method of the bromine-containing isoindoline-1-ketone compound uses commercially available aldehyde-derived imine as raw material, is reacted with aryl bromide oxazoline compound under butyl lithium condition, and then is subjected to acid-mediated cascade cyclization process, to efficiently construct isoindoline-1-ketone skeleton.The isoindoline-1-ketone compound can be directly used as an organic catalyst, the N-H functional group remaining in the structure of the isoindoline-1-ketone compound has reactivity, can be coupled with other bioactive molecules as a key connection site, to construct functional derivatives, the amide carbonyl group thereof can be further reduced, to be converted into pyrrolidine structural unit, and the structure itself can be used as a catalytically active center, to expand its application in the field of catalysis.

Disclosed are compounds of Formula (I): or stereoisomers, tautomers, or salts thereof, wherein X, Y, W, Z, L, R3, R4, R5, R6, R7, m, n, and p are defined herein. Also disclosed are methods of using such compounds to decrease the level Cyclin E1; and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of proliferative disorders, such as cancer.

Disclosed herein are compound or pharmaceutically acceptable salts or stereoisomers thereof of formula I:X1 is linear or branched C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-8 membered heterocycloalkyl, wherein X1 is unsubstituted or substituted with one or more of halogen, linear or branched C1-6 alkyl, linear or branched C1-6 heteroalkyl, CF3, CHF2, CMeF2, —O—CHF2, —O—(CH2)2—OMe, OCF3, C1-6 alkylamino, —CN, —N(H)C(O)—C1-6alkyl, —OC(O)—C1-6alkyl, —OC(O)—C1-4alkylamino, —C(O)O—C1-6alkyl, —COOH, —C1-6alkylC(O)OH, —C1-6alkylC(O)O—C1-6alkyl, NH2, C1-4 alkoxy, C1-4 alkylhydroxy, —CH2F, —N(H)C(O)—O—C1-6 alkyl, and C(OH)(CF3); or X1 together with the N atom of the carbamate forms a 4-8 membered heterocycloalkyl, which is unsubstituted or substituted with one or more of halogen, linear or branched —C1-6 alkyl, CF3, CHF2, CMeF2, —O—(CH2)2—OMe, OCF3, OCHF2, C1-6 alkylamino, —CN, —N(H)C(O)—C1-6alkyl, —OC(O)—C1-6alkyl, —C(O)O—C1-6alkyl, —COOH, —C1-6alkylC(O)OH, —C1-6alkylC(O)O—C1-6alkyl, NH2, C1-4 alkylhydroxy, and C1-4 alkoxy; X2 is H, C3-6 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-8 membered heterocycloalkyl, wherein X2 is unsubstituted or substituted with one or more of linear or branched C1-6 alkyl, —C1-4 alkoxy, NH2, NMe2, halogen, CF3, CHF2, CMeF2, —O—(CH2)2—OMe, OCF3, OCHF2, and C1-4 alkylhydroxy; L1 is a covalent bond, linear or branched C1-6 alkyl; L2 is a covalent bond, linear or branched C1-6 alkyl; and L3 is a covalent bond, linear or branched C1-6 alkyl, —O—, or —C1-4 alkoxy, wherein linear or branched C1-6 alkyl is unsubstituted or substituted with one or more of halogen. Disclosed herein is also their use as modulators of cereblon, methods of preparation of these compounds, compositions comprising these compounds, and methods of using them in the treatment of abnormal cell growth in mammals, especially humans.

N-Biarylmethylene substituted pyrrolopyridinone, pyrrolopyrazinone, pyrrolopyrimidinone, and isoindolin-1-one compounds having a tertiary alcohol-containing group substituted on the biarylmethylene are positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChRM1). The compounds and pharmaceutical compositions may be used in treating neurological disorders, psychiatric disorders, or a combination thereof.

The present invention relates to a pharmaceutical compound and a formulation comprising the compound, wherein the compound is of formula I or II: The present invention relates to a pharmaceutical compound and a formulation having the structure shown in JPEG2026522984000107.jpg75161. The compound and the formulation are suitable for pharmaceutical use in the prevention or treatment of diseases or disorders characterized by pericyte dysfunction, detachment and / or loss; in therapeutic treatments for vascular stabilization; in treatments for promoting, restoring or maintaining pericyte adhesion to blood vessels; and / or in the treatment of vascular-related diseases in patients.

The application belongs to the technical field of medicine and chemical industry, and particularly relates to a method for preparing 3-(2-hydroxyethyl) isoindoline-1-ketone compounds through continuous flow reaction. The application provides a method for preparing 3-(2-hydroxyethyl) isoindoline-1-ketone compounds through continuous flow reaction. The extremely high specific surface area of a micro-reactor realizes instantaneous uniform mixing of reagents and efficient heat transfer, completely avoids decomposition of organic lithium reagents, side reactions and safety hazards caused by local overheating, and enables originally dangerous low-temperature organic lithium reactions to be safely carried out at a higher and more energy-saving temperature. Efficient mass transfer in the micro-channel greatly accelerates the reaction rate, and the reaction time of each step is shortened from several hours in the kettle process to several minutes to tens of minutes. The three-step reaction is seamlessly connected, and the intermediate does not need to be separated, so that the continuous synthesis from raw materials to products is realized, and the total production efficiency is greatly improved.

Provided is a pigment composition comprising an isoindoline-based pigment (1) and a quinophthalone sulfonate derivative (2), said pigment composition having, in a powder X-ray diffraction pattern using CuKα radiation as an X-ray source, a diffraction peak at a position where a Bragg angle θ is (27.1°±0.5°) / 2, and having a crystallite diameter of not more than 15.5 nm, as calculated by the Scherrer equation using the Bragg angle θ and the full width at half maximum B of the diffraction peak.

A 4-carboxyamino isoindoline-1,3-dione compound represented by formula (I), or an optical isomer thereof, or a pharmaceutically acceptable salt thereof, or a solvate (e.g. hydrate) thereof, or a clathrate thereof, or a racemate thereof, or an isotopically-labeled material thereof, or a nitroxide thereof; and pharmaceutical compositions and uses thereof. The compound has good anti-multiple myeloma activity, and can effectively treat and / or prevent the growth of multiple myeloma.

The present invention relates to: an isoindolinone derivative compound having a glutarimide mother nucleus in which quinoline is substituted; and application thereof, and, more specifically, to an isoindolinone derivative compound having a glutarimide mother nucleus, in which quinoline is substituted, with a thalidomide analog structure. A compound of chemical formula 1, according to the present invention, specifically binds to a CRBN protein and is involved in functions thereof. Therefore, the compound of the present invention can be effectively used in the prevention or treatment of leprosy, chronic graft versus host disease, inflammatory diseases or cancer, which are caused by activity of the CRBN protein.

The present disclosure relates to compounds according to Formula I or a pharmaceutically acceptable salt and / or solvate thereof, wherein X 1 is H, F, or CI; R 1 is H, a substituted aryl, a substituted non-aromatic heterocyclyl, or a heteroaryl; and R 2 is H or C(0)NH2. Furthermore, the present disclosure demonstrates that the compounds of the present disclosure penetrate the central nervous system, thereby allowing for the treatment of central nervous system cancers.

A 4-carbonylamino isoindolin-1-one compound represented by formula (I), or an optical isomer thereof, or a pharmaceutically acceptable salt thereof, or a solvate (e.g. hydrate) thereof, or a clathrate thereof, or a racemate thereof, or an isotopically-labeled material thereof, or a nitroxide thereof; and pharmaceutical compositions and uses thereof. The compound has good anti-multiple myeloma activity, and can effectively treat and / or prevent the growth and reproduction of multiple myeloma.

Provided herein are isoindolinones, e.g., a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a zinc-figure protein, casein kinase 1α, GSPT1, or PDE6D.

To provide a method of identifying a subject having cancer who is likely to be responsive to a treatment compound.SOLUTION: A method includes: administering the treatment compound to the subject having the cancer; obtaining a sample from the subject; determining the level of a biomarker in the sample from the subject; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject changes as compared to a reference level of the biomarker; wherein the treatment compound is Compound 1, Compound 2, or Compound 3.SELECTED DRAWING: Figure 1

This disclosure relates, in one aspect, to substituted N-(2-(2,6-dioxopiperidinyl-3-yl)-1,3-dioxoisoindoline-5-yl)arylsulfonamide analogs used as modulators of cereblon (CRBN) activity, methods for their preparation, pharmaceutical compositions comprising the same, and methods of using the same to treat various clinical conditions and diseases, such as uncontrolled cell proliferation diseases that may be associated with cereblon protein dysfunction and / or GSPT1 dysfunction, such as cancer. In various further aspects, the disclosed compounds can selectively modulate the degradation of the GSPT1 protein, i.e., the disclosed compounds can act as GSPT1 degrading agents. This abstract is intended as a scanning tool for searching in a particular field and is not intended to limit the scope of this disclosure.

Provided herein are certain isoindolinone compounds and imaging agents useful for detecting a disease or condition associated with protein aggregation, compositions thereof, and methods of their use.

The present invention relates to an isoindolinone derivative compound having a glutarimide mother nucleus, and an application thereof, and more specifically, to an isoindolinone derivative compound in which a glutarimide mother nucleus is substituted with phenylcyclopropane having a thalidomide analog structure. The compound of chemical formula 1 according to the present invention specifically binds to the CRBN protein and is involved in functions thereof. Thus, the compound of the present invention may be beneficially used in the prevention or treatment of leprosy, chronic graft versus host disease, inflammatory diseases, or cancer caused by actions of the CRBN protein.

Isoindolinone compounds represented by the structural formula (I) or pharmaceutically-acceptable salts thereof can be used for the treatment of a proliferative disorder. Pharmaceutical compositions contain the isoindolinone compound or a salt thereof, and a pharmaceutically acceptable carrier.

The present disclosure describes crystalline forms of 2-(tert-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol fumarate salts and pharmaceutical compositions of same. Also described are methods of using the crystalline forms treating Alzheimer's Disease, Dementia with Lewy Bodies and Dry age-related macular degeneration in a subject in need thereof, comprising administering the crystalline form to the subject. Methods of making the solid forms are also described.

Provided herein a compound for use in a method of treating multiple myeloma, wherein the compound is Compound 2 of the formula: or a tautomer, isotopolog, or pharmaceutically acceptable salt thereof, and wherein the method comprises administering a therapeutically effective amount of the compound to a patient in need thereof.

Provided herein are pharmaceutical compositions (e.g., oral administration formulations) comprising (S)-4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile or an enantiomer, mixture of enantiomers, tautomer, isotopologue, or pharmaceutically acceptable salt thereof, and a carrier or diluent. Also provided herein are methods of preparing and using the pharmaceutical compositions. JPEG2023533314000040.jpg155133 JPEG2023533314000041.jpg146134

The present application provides a pigment composition containing isoindoline compounds, which is excellent in dispersibility, weather resistance, and heat resistance, has good storage stability, and can form an image or the like having high chroma, the pigment composition containing an isoindoline compound represented by the following formula (1) and an isoindoline compound represented by the following formula (2). In addition, a colored composition, a paint, an ink, an ink set, a printed matter, and a packaging material using the pigment composition are provided.