130 results about "Indoline" patented technology

The present disclosure provides crystalline forms, solvates and hydrates of (R)-5-fluoro-2-methyl-1-((R)-5-(pyridin-2-yl)-2,3-dihy dro-lH-indene-2-carbonyl)indoline-6- sulfonamide, and methods of making.

The invention provides a fluorescent probe for detecting hydroxyl radicals as well as a preparation method and application thereof, and the preparation method comprises the following steps: (S10) synthesizing a first intermediate compound by taking 2, 3, 3-trimethyl-3H-indoline and methyl iodide as raw materials; (S20) synthesizing a second intermediate compound by taking phosphorus trichloride, cyclohexanone and anhydrous dimethylformamide as raw materials; (S30) mixing and reacting the first intermediate compound and the second intermediate compound to synthesize a compound IR780; and (S40) synthesizing OH-probe on the basis of the IR780. The prepared OH-probe has extremely high sensitivity and excellent selectivity on hydroxyl radicals, can be effectively used for monitoring and mapping the level of the hydroxyl radicals, and can be applied to detection of atherosclerosis, obesity, cancers, neurodegenerative diseases, inflammatory diseases and other free radical related diseases. Wide development prospects and practical application values are realized.

The present invention relates to antibody conjugates which are particularly suitable for targeting cells expressing PTK7, in particular tumor cells. An antibody conjugate according to the present invention has structure (1): AB-[(L6) b-{Z-L-D} x] y (1) wherein AB is an antibody capable of targeting a tumor expressing PTK7; l is a joint connecting Z to D; z is a linking group; l6 is-GlcNAc (Fuc) w-(G) j-S-(L7) w '-wherein G is a monosaccharide, j is an integer in the range of 0 to 10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine, and Fuc is fucose, w is 0 or 1, w' is 0, 1 or 2, and L7 is-N (H) C (O) CH2-,-N (H) C (O) CF2-or-CH2-; d is selected from the group consisting of an anthracycline, a camptothecin, a tubulysin, an endiyne, an amanitine, a duocarmycin, a maytansinoid, an aurestatin, eribulin, a BCL-XL inhibitor, a miscanthus semiaquilaria, a KSP inhibitor, a TLR agonist, an indolo-benzodiazepine dimer or a pyrrolo-benzodiazepine dimer (PBD), and an analog or prodrug thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further relates to a method for preparing said antibody conjugate of structure (1) and to the use of said antibody conjugate of structure (1).

The application discloses a preparation method of an indoline compound based on organic electrosynthesis, and belongs to the technical field of pharmaceutical chemical engineering and related chemistry. The method uses simple arylamine and halogenated olefin as raw materials, and prepares the indoline compound under the electrolysis of an electrode, so that green and efficient synthesis of the indoline compound is realized. The method has the advantages of low cost, high selectivity, mild reaction condition, good functional group compatibility, wide substrate range and environmental friendliness. The indoline compound is an important organic synthesis intermediate, and has a very wide application in the fields of fine chemical engineering and pharmacy. The preparation method has great application value and social and economic benefits.

The present invention belongs to the field of organic synthesis, and particularly relates to indolizino[2,1-a]isoquinoline derivatives, a preparation method and applications thereof. The indolizino[2,1-a]isoquinoline derivative has the structural formula: wherein, R 1 includes an alkyl group, an alkoxy group, hydrogen, fluorine, chlorine, bromine, trifluoromethyl or cyano; R 2 includes an aryl group, an alkoxy group, hydrogen, chlorine or bromine; R 3 includes an aryl group, an alkoxy group, hydrogen, chlorine or bromine; R 4 includes an electron-withdrawing group; R 1 is located at the C8, C9, C10 or C11 position of the indolizino[2,1-a]isoquinoline derivative; R 2 or R 3 is located at the C2 or C3 position of the corresponding indolizino[2,1-a]isoquinoline derivative, and the said R 2 or R 3 can be the same or different. The product of the present invention is a novel product. The preparation method is green and efficient, the preparation conditions are mild, the requirements for equipment are low, the operation is simple, the substrate scope of application is wide, the raw materials are low in price, the production cost is low, the yield is relatively high, and it can be mass-produced industrially, thus having broad application prospects.

The present invention discloses a small molecule compound having a substituted phenylspiro[indoline-3,3'-pyrrolidine] structure, the structure of which is shown in General Formula I, and the definitions of each substituent as described in the specification and claims. The compound of the present invention can inhibit the protein-protein interactions of MDM2-p53 and MDMX-p53 proteins. As a small molecule inhibitor of the protein-protein interactions of MDM2-p53 and MDMX-p53 proteins, it is used in the preparation of a drug for preventing and / or treating diseases related to MDM2 and MDMX, particularly tumors.

The invention provides powder with reversible photochromic performance as well as a preparation method and application thereof, and the powder with reversible photochromic performance is a photochromic microcapsule and consists of a core material and a wall material, the core material accounts for 30%-50% of the total weight of the microcapsule, and the wall material accounts for 50%-70% of the total weight of the microcapsule; the core material is an indoline spiroheterocyclic compound, and the wall material is a biocompatible polymer. The core material is an indoline spiroheterocyclic compound, and the wall material is a biocompatible polymer; the powder is prepared by taking indoline spiropyran as a photochromic core material through a microcapsule coating process, has reversible response characteristics of developing under ultraviolet irradiation and decolorizing under strong light irradiation, and can be compounded with a tattooing pigment matrix to obtain a tattooing product with active developing and decolorizing regulation and control functions. The problem that the photochromic tattoo pigment is irreversible in color change is solved, and meanwhile the photochromic tattoo pigment has good stability and biocompatibility.

This invention belongs to the field of organic synthetic chemistry technology, specifically relating to a selenium-based indoloquinazoline derivative, its preparation method, and its application, comprising: in an organic solvent, using aromatic amine compounds, malononitrile, and diselenoether as raw materials, in the presence of a palladium catalyst and an organic base, at 90°C... o The reaction was carried out under C conditions with stirring to obtain a selenyl indoline quinazoline derivative. This method features mild reaction conditions, simple operation, high yield, and good functional group compatibility, conforming to the principles of green chemistry. Furthermore, the selenyl indoline quinazoline derivative provided by this invention exhibits good inhibitory activity against Plasmodium, providing a drug lead compound for the development of novel antimalarial drugs and holding significant importance for the prevention and / or treatment of malaria.

The present invention discloses an ultra-thin photosensitive resin coating and a preparation method thereof, relating to the technical field of coating materials. First, the present invention modifies epoxy resin with 3-hydroxy-1-naphthylamine, 5-chloro-1,3,3-trimethyl-2-methylene indoline, 3-aminophthalate and silver chloride to form a photosensitive resin, enabling the coating to change with the change of light; then, ion beam assisted spinning is used to form a copper fiber film on the surface of the spectacle frame, and this is used as the cathode of the electric field. The photosensitive resin is ionized by a high-voltage electric field and deposited on the spectacle frame, and then alumina and silica films are grown layer by layer through electrostatic field assisted spraying, effectively blocking water and oxygen substances. The ultra-thin photosensitive resin coating prepared by the present invention has the effects of photosensitive color change and yellowing resistance.

Embodiments are directed to novel GPR52 activators. In particular, a series of novel 1-(pyrimidin-4-yl)indoline-4-carboxamide analogs that have been identified as potent and selective GPR52 agonists. The optimized GPR52 agonist that, for example, can be used as a valuable pharmacological tool or a drug candidate for investigating the physiological and therapeutic potential of GPR52 activation for various human diseases.

The application provides a preparation method of a near-infrared fluorescent dye using indoline as an electron donor. The method comprises the following steps: under the action of a palladium catalyst, through a Suzuki coupling, using a 1,4-dioxane:water mixed liquid as a solvent, coupling indoline boronic acid and a halogen-containing acceptor, and performing compound purification after high-temperature reaction. The near-infrared fluorescent dye using indoline as an electron donor has strong electron-donating properties, can realize aggregation-induced emission, can emit near-infrared light, and can improve light stability and molar absorption coefficient, so that a large Stokes shift can be realized, the near-infrared fluorescent dye is used for photothermal therapy, and good photothermal therapy efficiency is achieved.

The present invention belongs to the field of pharmaceutical technology and relates to a class of compounds with antibacterial uses, specifically N-allyl-substituted indoline-2-one-3-hydrazine dithiocarboxylate derivatives. The compounds are shown as formula (I): wherein, R1 represents a C1-C4 alkyl group, and R4, R5, R6 and R7 represent a halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group or a trifluoromethoxy group. The compounds involved in the present invention have the activity of inhibiting New Delhi metallo-β-lactamase 1 (NDM-1). When combined with β-lactam antibiotics such as meropenem, they can restore the sensitivity of superbugs to the corresponding antibiotics and can be used as antibacterial drugs.

The present invention discloses a method for synthesizing indoline, which is characterized in that: under the co-catalysis of yttrium bis(trimethylsilylamide) and tris(pentafluorophenyl)borane, an additive, a hydrogen source, and an indole compound are used as raw materials to react in a solvent to obtain an indoline compound; the structural formula of the indole compound is the structural formula of the indoline compound. The raw materials of the method of the present invention are widely sourced or easy to prepare, with simple operation, controllable selectivity, high yield, mild conditions, and wide generality.

The present application relates to methods of activating intracellular serotonin receptors using indoline derivatives of general formula (I) or pharmaceutically acceptable salts, solvates and / or prodrugs thereof, and to the treatment of diseases, disorders or conditions by activating intracellular serotonin receptors. The diseases, disorders, or conditions include, for example, psychosis, mental disorders, and CNS disorders. The invention also relates to a novel indoline derivative as well as a composition and application thereof. Wherein Q is selected from (Q1), (Q2), (Q3), (Q4), (Q5) and (Q6). # imgabs0 #

Cell parameters of the crystal compound are as follows: diffraction data are collected in an omega-theta scanning mode by using MoK alpha rays monochromatized by a graphite monochromator on an Oxford X-ray single crystal diffractometer at the temperature of 273 k, and the crystal compound is characterized in that the crystal belongs to a triclinic system, P-1; the cell parameters are as follows: alpha is equal to 79.857 (3) degrees; beta is equal to 87.082 (3) degrees; gamma is equal to 87.829 (3) degrees; the synthesis method of the crystal chlorine compound (I) comprises the following steps: weighing 0.02 35 g of benzophenone hydrazone and 0.6720 g of 1.0 g of 7-chloroisatin and acetic acid ketone monohydrate complex, putting into a 150mL flask, adding 100.0 mL of chlorobenzene as a solvent, stirring at room temperature for 48 hours, carrying out column chromatography separation, eluting with petroleum ether / dichloromethane (1 / 1), and carrying out vacuum drying to obtain the crystal chlorine compound (I). And naturally volatilizing the collected front component points to obtain the target crystal compound I, namely the 6-bromo-3-diphenylmethylene indoline-2-ketone crystal. The application of the crystal chlorine compound (I) is that the crystal chlorine compound (I) has a relatively strong inhibition effect on epidermophyton flocculent, and the IC50 value of the crystal chlorine compound (I) is 0.063 + / -0.008.

The invention discloses simple synthesis and antibacterial application of amino alcohol spiro indoline. The invention provides a skeleton structure of amino alcohol spiro indoline. The invention provides a synthesis method of the amino alcohol spiro-indoline compound, which comprises the following steps: uniformly mixing indole and o-aminobenzoic acid ester in a solvent, reacting at 80 DEG C under an acidic condition, and preparing the amino alcohol spiro-indoline compound without separation and borane reduction after an intermediate is obtained. The invention also provides an application of the amino alcohol spiroindoline skeleton in the aspect of bacteriostasis, and the amino alcohol spiroindoline skeleton is used for preparing a bactericide. The invention provides a method for efficiently synthesizing amino alcohol spiro indoline through two-step continuous reaction.

Provided are a crystal form and an amorphous substance of an indoline spiro compound represented by formula (1), and a preparation method therefor and the use thereof. The X-ray powder diffraction pattern of the crystal form comprises characteristic peaks at 5.43±0.20°, 12.28±0.20° and 17.91±0.20° 2θ, as determined by using Cu-Kα radiation; and the XRPD spectrum of the amorphous substance has no obvious diffraction peak. The provided crystal form and the amorphous substance have high purity and good stability, and are beneficial to drug formation.

The invention discloses an indoline compound containing a pyrazole structure as well as a preparation method and application thereof, belongs to the technical field of medicines, and relates to the indoline compound containing the pyrazole structure as shown in a general formula I, a stereoisomer of the indoline compound and pharmaceutically acceptable salt of the indoline compound. The invention also relates to a preparation method of the compounds and application of the compounds in preparation of drugs for treating diseases related to PD-1 / PD-L1 protein / protein interaction. The compound provided by the invention has high-level inhibition activity on PD-1 / PD-L1 protein / protein interaction, so that the compound has a good inhibition effect on PD-1 / PD-L1 protein / protein interaction. The indoline compound containing the pyrazole structure, the stereoisomer of the indoline compound and the pharmaceutically acceptable salt of the indoline compound can be used for preparing drugs for diseases related to PD-1 / PD-L1 signal channel abnormity, such as cancers, infectious diseases and autoimmune diseases.

The application provides a chiral 2-position disubstituted indoline compound and a synthesis method and application thereof. The application uses a simple structure palladium catalyst and a chiral ligand as a catalyst system, and uses a newly designed allyl benzoxazinone as a raw material to perform a palladium catalyzed intramolecular asymmetric cyclization reaction, so that efficient asymmetric synthesis of the chiral 2-position disubstituted indoline compound is realized. The synthesis method is simple, the reaction condition is mild, the cost is low, and the efficiency is high; the raw material is cheap and easy to obtain, atom economy is good, and the substrate is widely applicable; the target product has high yield and high enantioselectivity; the chiral 2-position disubstituted indoline compound obtained by the application has excellent inhibition effect on bladder cancer cells, provides a scientific basis for developing a new candidate drug for treating bladder cancer, and has important significance for the treatment of bladder cancer.

The invention discloses a photochromic spiropyrane derivative containing an adamantyl group and a preparation method and application thereof, the photochromic spiropyrane derivative containing the adamantyl group takes 4-dimethylaminopyridine and dicyclohexylcarbodiimide as catalysts, and 2-(3 ', 3'-dimethyl-6-nitro spiro [chromene-2, 2 '-diketone)-1, 2, 4-triazole-2-yl]-1, 3, 4-triazole-2-yl]-1, 3, 4-triazole-2-yl]-1, 3, 4-triazole-2-yl]-1, 3, 4 According to the invention, 2, 2 '-indoline]-1'-yl) ethanol and an adamantane carboxylic acid compound are subjected to an esterification reaction, adamantanoate series large steric hindrance groups are introduced to spiropyrane molecules, a relatively loose accumulation mode of the compound is caused, and pi-pi accumulation of the spiropyrane molecules is effectively prevented, so that a photochromic reaction of spiropyrane in a solid state is realized; the preparation method is simple, post-treatment is convenient, and the prepared photochromic spiropyrane derivative containing the adamantyl group is high in yield and good in fat solubility.

This invention discloses a method for preparing spirocyclic indolineone compounds, belonging to the field of organic synthesis. The method, under the action of a palladium catalyst, utilizes the combined action of ligands and additives to react in an organic solvent at a temperature of 60-130°C to generate the corresponding spirocyclic indoline compounds, which are then oxidized to spirocyclic indolineone compounds under the action of an oxidant. This invention uses readily available C3-alkynyl-branched indole derivatives as raw materials, achieving rapid construction of spirocyclic indolineone compounds through a two-step process involving the formation of one ring and three chemical bonds. The reaction conditions are mild, the operation is simple, and it has advantages such as readily available reactants, broad substrate applicability, and easy separation of the target product.

The invention belongs to the field of organic synthesis, and provides a thietane indoline heterocyclic compound as well as a preparation method and application thereof. R1 and R2 are respectively and independently selected from one of hydrogen, methyl, methoxyl and halogen, R3 is selected from one of t-butyloxycarboryl and 4-chlorobenzoyl, R4 is selected from one of hydrogen, methyl and phenyl, and R5 is selected from methyl or n-propyl; x represents an oxygen atom or an amino group with a protecting group. The preparation method comprises the following steps: putting an indole derivative compound into an organic solvent containing a photocatalyst, and reacting under the irradiation of visible light to obtain the thietane indoline heterocyclic compound. The preparation method provided by the invention can be used for synthesizing the functionalized thietane indoline heterocyclic compound with high stereoselectivity and high yield, and is low in reaction cost, mild in reaction condition and simple and convenient to operate.

The invention relates to a method for preparing a compound shown in a formula (A). The method for stereospecifically synthesizing (2S, 3aS, 7aS)-octahydro-1H-indole-2-carboxylic acid as shown in a formula (A) comprises the step of hydrogenating a compound as shown in a formula (I) in an aqueous medium in the presence of a metal catalyst and alkali to form the compound as shown in the formula (A). In addition, the invention also comprises a method for synthesizing the compound as shown in the formula (I) by resolving the indoline-2-carboxylic acid as shown in the formula (II). The method of the present invention provides a compound represented by formula (A) with higher chiral purity and higher yield, and does not produce large amounts of undesired by-products. The catalyst and the resolving agent (R)-(+)-alpha-methylbenzylamine can be recycled and reused, and the efficiency is higher, so that the method disclosed by the invention has cost benefit.

The invention discloses a preparation method of (S)-indoline-2-carboxylic acid. Specifically, (S)-2-chlorophenylalanine is adopted as a raw material, (S)-2-chlorophenylalanine is efficiently catalyzed by a catalyst composed of copper / ligand to be subjected to intramolecular C-N bond coupling reaction to prepare (S)-indoline-2-carboxylic acid, the method is easy to operate, the raw materials are easy to obtain, the catalytic efficiency is high, the reaction time is short, the reaction yield is high, the product purity is high, and the method is suitable for industrial production. The industrial production is easy. # imgabs0 #

Small molecule ERα biomodulators that kill therapy-resistant ERα positive breast, ovarian, and endometrial cancer cells are disclosed. In one embodiment, the small molecule biomodulator has increased therapeutic utility because of an increased ability to kill therapy-resistant cancer cells compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen, and fulvestrant / ICI). The small molecule biomodulators not only inhibit proliferation of the cancer cells but kills them, which prevents reactivation of tumors years later. Compounds of the invention, such as ErSO-TFPy, are effective for treating ERα positive cancers such as breast cancer, ovarian cancer, uterine cancer, cervical carcinoma, endometrial cancer, and the like.

The invention discloses a synthesis method of indoline and benzotriaza compounds, and belongs to the field of organic synthesis. According to the invention, alpha-halogenated hydrazone and 2-aminochalcone are used as reactants, a ring closing alkali is added, and a reaction is carried out in an organic solvent at 0-60 DEG C for 2-24 hours to respectively obtain indoline as shown in a formula (I) or a benzotriaza compound as shown in a formula (II). According to the present invention, the alpha-halogenated hydrazone is adopted as the one-carbon synthon to participate in the cyclization reaction, such that the indoline derivative is constructed, and the benzotriaza compound is synthesized; the method is simple to operate and high in yield, and has excellent diastereoselectivity (gt; 19: 1). In addition, the invention also expands the range of the alpha-halogenated hydrazone participating in the [3 + 4] cyclization reaction as a triatomic synthon. # imgabs0 #

The present application relates to the technical field of pharmaceutical intermediates, and in particular to a synthesis method of chiral indanamine, which comprises the following steps: taking indanone as a raw material, using a chiral biphosphine catalyst of ruthenium to synthesize chiral indanamine in a cis form with high yield and high stereoselectivity, and then obtaining chiral indanamine in a trans form through a transposition process.The reaction process is as follows: the chiral indanamine in the trans form has a content of greater than 99%, 98% ee and a total yield of greater than 90%, the catalyst is convenient and easy to obtain, the operation is simple, the raw material is easy to obtain, the three-waste pollution is small, the energy consumption is low, and the method is suitable for industrial production.

The invention provides a silodosin intermediate and a preparation method thereof, and relates to the technical field of medicine preparation. Comprising the following steps: S1, 3-(indoline-1-yl) propyl benzoate is used as a raw material and is subjected to a substitution reaction with a bromination reagent, and 3-(5.7-dibromo-indoline-1-yl) propyl benzoate is obtained; s2, carrying out a substitution reaction on the 3-(5.7-dibromo-indoline-1-yl) propyl benzoate to obtain 3-(7-cyano-5-bromo-indoline-1-yl) propyl benzoate, and carrying out a substitution reaction on the 3-(5.7-dibromo-indoline-1-yl) propyl benzoate to obtain 3-(7-cyano-5-bromo-indoline-1-yl) propyl benzoate; s3, carrying out nucleophilic addition on the 3-(7-cyano-5-bromo-indoline-1-yl) propyl benzoate and epoxypropane, and carrying out ring opening on the 3-(7-cyano-5-(2-hydroxy-propyl) indoline-1-yl) propyl benzoate, so as to obtain 3-(7-cyano-5-(2-hydroxy-propyl) indoline-1-yl) propyl benzoate; s4, the 3-(7-cyano-5-(2-hydroxy-propyl) indoline-1-yl) propyl benzoate is subjected to oxidation, and the 3-(7-cyano-5-(2-oxopropyl) indoline-1-yl) propyl benzoate is generated. According to the synthesis method disclosed by the invention, all raw materials are easy to obtain, high-risk and high-pollution reagents are not used, the synthesis method is safe and environment-friendly, and the prepared silodosin intermediate is good in purity and high in yield.

The application belongs to the field of pharmaceutical chemistry, and provides a carboxyl chalcone derivative and a preparation method thereof, a structural general formula of the carboxyl chalcone derivative is shown in formula (I) or formula (II); in formula (I), R1 is methyl, ethyl, n-propyl, ethynyl, methylamino, dimethylamino, methylthio or methylsulfonyl; in formula (II), R2 is 3-thiophene, 2-thiazole, dihydrobenzofuran, benzodioxolane, benzodioxane, indole, dihydroindole, quinoline or naphthalene. The carboxyl chalcone derivative has excellent inhibitory effect on xanthine oxidase, and can be applied to the preparation of drugs with xanthine oxidase as a target. The application provides more candidate compounds for the development of xanthine oxidase inhibitors.