101 results about "Indoline" patented technology

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.

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 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 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 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.

The present invention relates to a method for preparing the compound of formula (A). The stereospecific synthesis method for (2S,3aS,7aS)-octahydro-1H-indole-2-carboxylic acid of formula (A) includes hydrogenating the compound of formula (I) in an aqueous solvent in the presence of a metal catalyst and an alkali to form the compound of formula (A). Furthermore, the present invention also includes a method for synthesizing the compound of formula (I) by decomposing the indoline-2-carboxylic acid of formula (II). The method of the present invention provides the compound of formula (A) with higher chiral purity and higher yield without substantially large amounts of undesirable byproducts. The method of the present invention is cost-effective for the recyclability and reuse of the catalyst and decomposition agent (R)-(+)-α-methylbenzylamine with higher efficiency.

The present disclosure provides crystalline forms, solvates, and hydrates of (R)-5-fluoro-2-methyl-1-((R)-5-(pyridin-2-yl)-2,3-dihydro-1H-inden-2-carbonyl)indoline-6-sulfonamide and methods of preparation.

The present application relates to a kind of small molecule probes and its preparation method and application, the chemical structure of the probe is as shown in the following formula: Wherein, R1 is 1-propyl sulfonic acid or 1-butyl sulfonic acid;R2 independently selected from trifluoromethyl or sulfur pentafluoride group, the substitution position of R2 is the ortho, para or meta of hydroxyl on benzene ring;Preparation method is by the condensation reaction of salicylaldehyde containing fluorine substituent group and indoline, directly introduce containing fluorine substituent group into the spiro-pyran molecule structure with pH response, prepared with 19 F MRI and fluorescence imaging pH-responsive bimodal imaging small molecule probe.Compared with the prior art, the small molecule probe of the present application exhibits significantly different 19 F NMR chemical shift and fluorescence intensity, high-resolution 19 F MRI imaging and fluorescence imaging, greatly improve the sensitivity and accuracy of imaging, has important application prospect in the field of biosensing, cell imaging, medical diagnosis etc.

The invention relates to the technical field of medicinal chemistry, and discloses a spiro [indene-indoline] compound, a preparation method thereof and an application of the spiro [indene-indoline] compound as a bactericide, in the air atmosphere, benzaldehyde compounds derived from the third position of indole and amine compounds are mixed, a solvent is added, under the action of a catalyst, stirring reaction is performed at the temperature of 25-60 DEG C, and the spiro [indene-indoline] compound is obtained. The structural formula of the spiro [indene-indoline] compound is shown as a formula I in the specification. The spiro [indene-indoline] compound prepared by the invention has excellent inhibitory activity on four common pathogenic fungi: strawberry botrytis cinerea, valsa mali, cucumber fusarium wilt and peanut root rot, and a new solution is provided for overcoming the drug resistance of fungi, so that the spiro [indene-indoline] compound has important application value in the field of agricultural germ control.

The invention discloses an application of 2-methyl indoline in prevention and control of nematodes. The invention relates to an application of 2-methylindoline in prevention and control of nematodes. The 2-methylindoline is diluted to 12.5-50 [mu] g / ml for use. The nematodes are root-knot nematodes. The nematodes are meloidogyne incognita. The preparation method of the 2-methylindoline comprises the following steps: after cigar fermented tobacco leaves are extracted with methanol, extracting with ethyl acetate to obtain an extract containing the 2-methylindoline. A nematode pesticide comprises the 2-methyl indoline in any one of the applications mentioned above. The nematode insecticide is a botanical insecticide. The small molecule compound 2-methylindoline is applied to prevention and control of nematodes, can significantly kill root-knot nematodes, has a good prevention and control effect, and has high application potential.

A class of competitive and reversible GlyT2 inhibitors is provided that demonstrate a differentiated pharmacological profile from earlier inhibitors, such as ORG25543. ORG25543 and genetic GlyT2 knockout paradigms can elicit neuromotor or excitatory adverse effects. To overcome these challenges, SAR- and SKR-driven hit-to-lead campaigns were used to design improved, competitive and reversible GlyT2 inhibitors with improved drug-like characteristics and demonstrates a differentiated pharmacological profile. These improved GlyT2 inhibitors include indole, indoline, or indazole cores substituted with a variety of groups to modify the reversible binding activity thereof. The compounds described herein are shown to possess properties useful for safe, efficacious, and orally bioavailable non-opioid analgesics for the treatment of neuropathic pain.