WO2023237012A1 - Composé deutéré de type acide carboxylique aromatique substitué bicyclique - Google Patents

Composé deutéré de type acide carboxylique aromatique substitué bicyclique Download PDF

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Publication number
WO2023237012A1
WO2023237012A1 PCT/CN2023/098918 CN2023098918W WO2023237012A1 WO 2023237012 A1 WO2023237012 A1 WO 2023237012A1 CN 2023098918 W CN2023098918 W CN 2023098918W WO 2023237012 A1 WO2023237012 A1 WO 2023237012A1
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compound
formula
alkyl
acid
present
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PCT/CN2023/098918
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Chinese (zh)
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丁照中
颜小兵
陈曙辉
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正大天晴药业集团股份有限公司
南京明德新药研发有限公司
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Publication of WO2023237012A1 publication Critical patent/WO2023237012A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the complement system is an important component of the body's innate immunity against infections such as foreign pathogens, bacteria, and parasites.
  • the complement system is also an important component of the connection between innate immunity and adaptive immunity.
  • Complement consists of plasma proteins, including soluble proteins, membrane-bound proteins and complement receptors. It is mainly produced by membrane proteins expressed in the liver or cell surface and plays a role in plasma, tissues or cells.
  • the complement system is mainly activated through three pathways: the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP).
  • Each R is independently selected from D, -F, -Cl, -Br, -I or -OH;
  • T 1 is selected from CH
  • T 2 is selected from N
  • other variables are as defined in the present invention.
  • the R 2 and R 4 together with the atoms to which they are connected form oxetanyl, oxetanyl, oxetanyl, azetidinyl, azetanyl Or azetidinyl, the oxetanyl, oxetanyl, oxetanyl, azetidinyl, azetyl or azetyl are independently optionally substituted by 1, 2 Or substituted by 3 R b , in this case, the R 3 is selected from H or D, and other variables are as defined in the present invention.
  • the R 2 and R 4 together with the atoms to which they are connected form an oxanyl or azacyclohexyl group, which are independently optionally replaced by 1 , 2 or 3 R b substitutions, at this time, the R 3 is selected from H, and other variables are as defined in the present invention.
  • each R b is independently selected from -CH 2 CH 3 , -CH 2 CHF 2 or -CH 2 CF 3 , and other variables are as defined in the invention.
  • the 3-6 membered heterocyclyl group is selected from 4-6 membered saturated heterocyclyl groups containing one N or one O.
  • the 3-6 membered heterocyclyl group is selected from 4-6 membered saturated heterocyclyl groups containing one N.
  • the 3-6 membered heterocyclyl group is selected from 4-6 membered saturated heterocyclyl groups containing one O.
  • the structural unit Selected from Other variables are as defined in the present invention.
  • the structural unit Selected from Other variables are as defined in the present invention.
  • the compound or a pharmaceutically acceptable salt thereof is selected from,
  • R 1 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R b , n, T 1 and T 2 are as defined for the compound of formula (I) of the present invention.
  • the carbon atom with "#" is a chiral carbon atom, existing in the form of (R) or (S) single enantiomer or enriched in one enantiomer;
  • the carbon atoms with "*" are chiral carbon atoms, which exist in the form of (R) or (S) single enantiomer or enriched in one enantiomer.
  • the compound or a pharmaceutically acceptable salt thereof is selected from,
  • R 1 , R 4 , R 5 , R 6 , R 9 and R b are as defined for the compound of formula (I) of the present invention.
  • the carbon atom with "#" is a chiral carbon atom, existing in the form of (R) or (S) single enantiomer or enriched in one enantiomer;
  • the carbon atoms with "*" are chiral carbon atoms, which exist in the form of (R) or (S) single enantiomer or enriched in one enantiomer.
  • the compound or a pharmaceutically acceptable salt thereof is selected from,
  • R 4 is selected from deuterated C 1-3 alkoxy; R 6 and R 9 are each independently selected from H or D.
  • the compound or a pharmaceutically acceptable salt thereof is selected from,
  • R 4 , R 6 and R 9 are as defined for the compound of formula (I) of the present invention.
  • the present invention also provides the following compounds or pharmaceutically acceptable salts thereof,
  • the present invention also provides the following compounds or pharmaceutically acceptable salts thereof,
  • the present invention also provides a pharmaceutical composition, which contains a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt thereof. Furthermore, a pharmaceutically acceptable carrier is also included.
  • the present invention also provides the use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the preparation of medicaments for treating diseases related to complement factor B.
  • the present invention also provides a method for treating diseases related to complement factor B, comprising administering a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt thereof to a mammal (preferably a human) in need of such treatment.
  • the present invention also provides the use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the treatment of diseases related to complement factor B.
  • the present invention also provides compounds of the present invention or pharmaceutically acceptable salts thereof for the treatment of diseases associated with complement factor B.
  • the complement factor B-related disease is selected from the group consisting of inflammatory disorders and autoimmune diseases.
  • the pharmaceutically acceptable salt is selected from pharmaceutically acceptable acid addition salts. In some embodiments of the present invention, the pharmaceutically acceptable salt is selected from pharmaceutically acceptable inorganic acid salts, organic acid salts and amino acid salts.
  • examples of pharmaceutically acceptable salts include inorganic acid salts
  • the inorganic acids include, for example, hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, bicarbonate, phosphoric acid, monohydrogen phosphate, phosphoric acid Dihydrogen, sulfuric acid, hydrogen sulfate, hydriodic acid, phosphorous acid, etc.; and organic acid salts, including formic acid, acetic acid, propionic acid, trifluoroacetic acid, isobutyric acid, maleic acid, propylene glycol, etc.
  • Acid benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, tartaric acid and methanesulfonic acid and similar acids; Also included are salts of amino acids (such as arginine, etc.), and salts of organic acids such as glucuronic acid.
  • the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride, hydrobromide, nitrate, carbonate, bicarbonate, phosphate, monohydrogen phosphate, and dihydrogen phosphate.
  • Salt sulfate, bisulfate, hydroiodide, phosphite, formate, acetate, propionate, trifluoroacetate, isobutyrate, maleate, malonic acid Salt, benzoate, succinate, suberate, fumarate, lactate, mandelate, phthalate, benzenesulfonate, p-toluenesulfonate, lemon Acid, tartrate, methanesulfonate, arginine and glucuronate.
  • the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride, formate and trifluoroacetate.
  • the compound of the present invention has obvious inhibitory activity on the activation of human serum alternative pathway, and has a significant inhibitory effect on complement activation stimulated by LPS.
  • the compound of the present invention also has good pharmacokinetic properties and can be developed into a new small molecule inhibitor of complement system Factor B.
  • the term "pharmaceutically acceptable” refers to those compounds, materials, compositions and/or dosage forms which, within the scope of sound medical judgment, are suitable for use in contact with human and animal tissue. , without undue toxicity, irritation, allergic reactions, or other problems or complications, commensurate with a reasonable benefit/risk ratio.
  • the compounds of the present invention may exist in specific geometric or stereoisomeric forms.
  • the present invention contemplates all such compounds, including cis and trans isomers, (-)- and (+)-enantiomers, (R)- and (S)-enantiomers, diastereoisomers isomer, the (D)-isomer, the (L)-isomer, as well as their racemic mixtures and other mixtures, such as enantiomeric or diastereomerically enriched mixtures, all of which belong to the present invention. within the scope of the invention. Additional asymmetric carbon atoms may be present in substituents such as alkyl groups. All such isomers, as well as mixtures thereof, are included within the scope of the present invention.
  • enantiomers or “optical isomers” refer to stereoisomers that are mirror images of each other.
  • diastereomer refers to stereoisomers whose molecules have two or more chiral centers and are in a non-mirror image relationship between the molecules.
  • the following formula (A) represents the compound as a single isomer of formula (A-1) or formula (A-2) It exists in the form or in the form of a mixture of two isomers of formula (A-1) and formula (A-2);
  • the following formula (B) represents that the compound is in the form of formula (B-1) or formula (B-2) It exists as a single isomer or as a mixture of two isomers of formula (B-1) and formula (B-2).
  • the following formula (C) indicates that the compound exists in the form of a single isomer of formula (C-1) or formula (C-2) or in the form of two isomers of formula (C-1) and formula (C-2). Exists in mixture form.
  • the terms “enriched in an isomer,” “enantiomerically enriched,” “enriched in an enantiomer,” or “enantiomerically enriched” refer to one of the isomers or enantiomers.
  • the content of the enantiomer is less than 100%, and the content of the isomer or enantiomer is greater than or equal to 60%, or greater than or equal to 70%, or greater than or equal to 80%, or greater than or equal to 90%, or greater than or equal to 95%, or greater than or equal to 96%, or greater than or equal to 97%, or greater than or equal to 98%, or greater than or equal to 99%, or greater than or equal to 99.5%, or greater than or equal to 99.6%, or greater than or equal to 99.7%, or greater than or equal to 99.8%, or greater than or equal to 99.9%.
  • isomeric excess or “enantiomeric excess” refers to the difference between the relative percentages of two isomers or two enantiomers. For example, if the content of one isomer or enantiomer is 90% and the content of the other isomer or enantiomer is 10%, then the isomer or enantiomeric excess (ee value) is 80% .
  • the compounds of the present invention may contain unnatural proportions of atomic isotopes on one or more of the atoms that make up the compound.
  • compounds can be labeled with radioactive isotopes, such as tritium ( 3 H), iodine-125 ( 125 I), or C-14 ( 14 C).
  • deuterated drugs can be replaced by heavy hydrogen to form deuterated drugs. The bond between deuterium and carbon is stronger than the bond between ordinary hydrogen and carbon. Compared with non-deuterated drugs, deuterated drugs can reduce side effects and increase drug stability. , enhance efficacy, extend drug biological half-life and other advantages. All variations in the isotopic composition of the compounds of the invention, whether radioactive or not, are included within the scope of the invention.
  • substituted means that any one or more hydrogen atoms on a specific atom are replaced by a substituent, which may include deuterium and hydrogen variants, as long as the valence state of the specific atom is normal and the substituted compound is stable.
  • it means two hydrogen atoms are replaced.
  • Oxygen substitution does not occur on aromatic groups.
  • optionally substituted means that it may or may not be substituted. Unless otherwise specified, the type and number of substituents may be arbitrary on the basis of chemical achievability.
  • any variable e.g., R
  • its definition in each instance is independent.
  • said group may optionally be substituted by up to two R's, with independent options for R in each case.
  • substituents and/or variants thereof are permitted only if such combinations result in stable compounds.
  • linking group When the number of a linking group is 0, such as -(CRR) 0 -, it means that the linking group is a single bond.
  • the substituent can be bonded through any atom thereof.
  • a pyridyl group as a substituent can be bonded through any one of the pyridine rings.
  • the carbon atom is attached to the substituted group.
  • the direction of connection is arbitrary, for example, The middle linking group L is -MW-.
  • -MW- can be connected to ring A and ring B in the same direction as the reading order from left to right. You can also connect ring A and ring B in the opposite direction to the reading order from left to right.
  • any one or more sites of the group can be connected to other groups through chemical bonds.
  • connection mode of the chemical bond is non-positioned and there are H atoms at the connectable site, when the chemical bond is connected, the number of H atoms at the site will be reduced correspondingly with the number of connected chemical bonds and become the corresponding valence. group.
  • the chemical bond connecting the site to other groups can be a straight solid line bond straight dashed key or wavy lines express.
  • the straight solid line bond in -OCH 3 means that it is connected to other groups through the oxygen atom in the group;
  • the straight dotted bond in means that it is connected to other groups through both ends of the nitrogen atoms in the group;
  • the wavy lines in indicate that the phenyl group is connected to other groups through the 1 and 2 carbon atoms in the phenyl group;
  • variable such as R
  • the variable is designated as being substituted on that ring and cannot be substituted on other rings of the polycyclic system, For example Indicates that ring A and ring B are combined rings, and the substituent R 1 is a substituent of ring A, and the substituent R 2 is a substituent of ring B, Indicates that the five-membered ring in the spiro ring system is replaced by n R's.
  • halogen or halogen by itself or as part of another substituent means a fluorine, chlorine, bromine or iodine atom.
  • C 1-3 alkyl is used to mean a straight or branched chain saturated hydrocarbon group consisting of 1 to 3 carbon atoms.
  • the C 1-3 alkyl group includes C 1-2 and C 2-3 alkyl groups, etc.; it can be monovalent (such as methyl), divalent (such as methylene) or multivalent (such as methine) .
  • Examples of C 1-3 alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (including n - propyl and isopropyl), and the like.
  • C 1-3 alkoxy means those alkyl groups containing 1 to 3 carbon atoms that are attached to the remainder of the molecule through an oxygen atom.
  • the C 1-3 alkoxy group includes C 1-2 , C 2-3 , C 3 and C 2 alkoxy groups, etc.
  • Examples of C 1-3 alkoxy include, but are not limited to, methoxy, ethoxy, propoxy (including n-propoxy and isopropoxy), and the like.
  • deuterated means that 1, 2, 3 or more H atoms in a substituent are replaced by its isotope deuterium atoms.
  • deuterated C 1-3 alkyl means that 1, 2, 3 or more H atoms in a C 1-3 alkyl group are replaced by its isotope deuterium atoms, deuterated C 1-3 Examples of alkyl groups include, but are not limited to -CD 3 , -CD 2 CD 3 and the like.
  • deuterated C 1-3 alkoxy means that 1, 2, 3 or more H atoms in a C 1-3 alkoxy group are replaced by their isotopic deuterium atoms, deuterated C 1
  • deuterated C 1 Examples of -3 alkoxy include but are not limited to -OCD 3 , -OCD 2 CD 3 and the like.
  • the term "3-6 membered heterocyclyl" by itself or in combination with other terms respectively represents a saturated or partially unsaturated monocyclic cyclic group consisting of 3 to 6 ring atoms, of which 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from O, S and N, and the remainder are carbon atoms, wherein the nitrogen atoms are optionally quaternized, and the nitrogen and sulfur heteroatoms may be optionally oxidized (i.e., NO and S (O) p , p is 1 or 2). Furthermore, in the case of the "3-6 membered heterocyclyl", the heteroatom may occupy the attachment position of the heterocyclyl to the rest of the molecule.
  • the 3-6-membered heterocyclic groups include 4-6-membered, 5-6-membered, 4-membered, 5-membered and 6-membered heterocyclic groups, etc.
  • Examples of 3-6 membered heterocyclyl groups include, but are not limited to, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, tetrahydrothiophenyl (including Tetrahydrothiophen-2-yl and tetrahydrothiophen-3-yl, etc.), tetrahydrofuranyl (including tetrahydrofuran-2-yl, etc.), tetrahydropyranyl, piperidinyl (including 1-piperidinyl, 2-piperidinyl) Aldinyl and 3-piperidinyl, etc.), piperazinyl (including 1-piperazinyl and 2-piperazinyl, etc
  • C n-n+m or C n -C n+m includes any specific case of n to n+m carbons, for example, C 1-12 includes C 1 , C 2 , C 3 , C 4 , C 5 , C 6 , C 7 , C 8 , C 9 , C 10 , C 11 , and C 12 , also include any range from n to n+m, for example, C 1-12 includes C 1- 3. C 1-6 , C 1-9 , C 3-6 , C 3-9 , C 3-12 , C 6-9 , C 6-12 , and C 9-12 ; similarly, n yuan to n+m means that the number of atoms in the ring is n to n+m.
  • a 3-12-membered ring includes a 3-membered ring, a 4-membered ring, a 5-membered ring, a 6-membered ring, a 7-membered ring, an 8-membered ring, and a 9-membered ring.
  • Ring, 10-membered ring, 11-membered ring, and 12-membered ring also include any range from n to n+m, for example, 3-12-membered ring includes 3-6-membered ring, 3-9-membered ring, 5-6 ring, 5-7-membered ring, 6-7-membered ring, 6-8-membered ring, and 6-10-membered ring, etc.
  • the compounds of the present invention can be prepared by a variety of synthetic methods well known to those skilled in the art, including the specific embodiments listed below, embodiments formed by combining them with other chemical synthesis methods, and methods well known to those skilled in the art. Equivalent alternatives and preferred embodiments include, but are not limited to, embodiments of the present invention.
  • the solvent used in the present invention is commercially available.
  • Compounds are named according to conventional naming principles in the field or use For software naming, commercially available compounds adopt supplier catalog names.
  • Figure 1 is a diagram of the PD model in mice induced by LPS activation of complement.
  • the complement system alternative pathway kit is used to determine the inhibitory activity of the test compound against the complement alternative pathway in human serum.
  • the compound of the present invention has obvious inhibitory activity on the activation of human serum bypass pathway.
  • the compound of the present invention was prepared into a clear solution of 3 mg/mL using 20% PEG400/10% solution/70% water. Rats were fasted overnight before administration, dose: 30 mg/kg, administration method: oral gavage. Collect blood before and 0.25, 0.5, 1, 2, 4, 7, and 24 hours after administration, place it in a heparinized anticoagulant test tube, centrifuge at 7000 rpm (5204g), 4°C, separate plasma, and store at -80°C save. Eat 4 hours after dosing. The LC/MS/MS method was used to determine the content of the test compound in rat plasma after oral administration. Plasma samples were analyzed after pretreatment with precipitated proteins. Experimental results:
  • C max peak concentration
  • T maax peak time
  • T 1/2 drug elimination half-life
  • AUC 0-last 0-area under the drug-time curve within the last sampling time.
  • mice Female C57BL/6J mice, 7-9 weeks old, weighing 17-23 grams; supplier: Shanghai Sipur-Bika Experimental Animal Co., Ltd.
  • LPS lipopolysaccharide
  • Salmonella typhimurium Salmonella typhimurium
  • sterile PBS phosphate buffer pH 7.2-7.4
  • Normal mouse group negative control: animals received i.p. Inject 100 ⁇ L of sterile PBS and administer vehicle alone by gavage (IO).
  • Model group positive control: animals received intraperitoneal LPS and PO administration of vehicle (20% PEG400/10% solutol/70% water).
  • Drug group Samples were collected 4 hours after compound administration (vehicle: 20% PEG400/10% solution/70% water, administration volume: 5 mL/kg, dose: 10 mg/kg).
  • Sample collection 0.3 mL of blood sample was collected from the orbital venous plexus. All blood samples were added into commercial EDTA-K2 anticoagulant tubes with a specification of 1.5 mL (supplier is Jiangsu Kangjian Medical Products Co., Ltd.). After blood samples are collected, within half an hour, centrifuge at 4°C and 3000g for 10 minutes to aspirate the supernatant plasma, quickly transfer it to dry ice, and store it in a -80°C refrigerator for Western blot analysis of downstream C3d protein levels after complement activation.
  • Mouse plasma (5 ⁇ L) + Lysis buffer (lysis buffer, 27.5 ⁇ L) + Loading buffer (loading buffer, 12.5 ⁇ L) + Reducing buffer (reducing buffer, 5 ⁇ L), mix well, incubate at 100°C for 15 minutes, and load the sample
  • the volume is 5 ⁇ L/well, that is, the plasma loading volume per well is 0.5 ⁇ L.
  • the C3d protein level in the serum of mice in the model group increased by 40% to 50% compared with the normal group.
  • the C3d protein level in the serum of mice in each drug group increased by 40% to 50%.

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Abstract

L'invention concerne un composé tel que représenté par la formule (I) et un sel pharmaceutiquement acceptable de celui-ci.
PCT/CN2023/098918 2022-06-07 2023-06-07 Composé deutéré de type acide carboxylique aromatique substitué bicyclique WO2023237012A1 (fr)

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CN114057692A (zh) * 2020-08-07 2022-02-18 上海美悦生物科技发展有限公司 一种杂环类化合物、其制备方法及用途
WO2022218429A1 (fr) * 2021-04-16 2022-10-20 正大天晴药业集团股份有限公司 Composés d'acide carboxylique aromatique substitués bicycliques
WO2022256586A2 (fr) * 2021-06-03 2022-12-08 Chinook Therapeutics, Inc. Composés d'indole substitués et leurs procédés d'utilisation
WO2023020566A1 (fr) * 2021-08-18 2023-02-23 四川海思科制药有限公司 Dérivé de cycle hétéroaromatique contenant de l'azote benzo et son utilisation en médecine
WO2023072197A1 (fr) * 2021-10-27 2023-05-04 Hansoh Bio Llc Dérivés de pipéridinyl indole, leurs procédés de préparation et leurs utilisations médicales

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114057758A (zh) * 2020-08-07 2022-02-18 上海美悦生物科技发展有限公司 补体因子b抑制剂及其药物组合物、制备方法和用途
CN114057692A (zh) * 2020-08-07 2022-02-18 上海美悦生物科技发展有限公司 一种杂环类化合物、其制备方法及用途
WO2022218429A1 (fr) * 2021-04-16 2022-10-20 正大天晴药业集团股份有限公司 Composés d'acide carboxylique aromatique substitués bicycliques
WO2022256586A2 (fr) * 2021-06-03 2022-12-08 Chinook Therapeutics, Inc. Composés d'indole substitués et leurs procédés d'utilisation
WO2023020566A1 (fr) * 2021-08-18 2023-02-23 四川海思科制药有限公司 Dérivé de cycle hétéroaromatique contenant de l'azote benzo et son utilisation en médecine
WO2023072197A1 (fr) * 2021-10-27 2023-05-04 Hansoh Bio Llc Dérivés de pipéridinyl indole, leurs procédés de préparation et leurs utilisations médicales

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