EP4196220A1 - Triazole-pyridinyl substituted azacyclohexyl acetic acid compounds as lpa receptor antagonists - Google Patents

Triazole-pyridinyl substituted azacyclohexyl acetic acid compounds as lpa receptor antagonists

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Publication number
EP4196220A1
EP4196220A1 EP21791479.5A EP21791479A EP4196220A1 EP 4196220 A1 EP4196220 A1 EP 4196220A1 EP 21791479 A EP21791479 A EP 21791479A EP 4196220 A1 EP4196220 A1 EP 4196220A1
Authority
EP
European Patent Office
Prior art keywords
compound
methyl
ealkyl
substituted
ring
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP21791479.5A
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German (de)
English (en)
French (fr)
Inventor
Ping Chen
Zhenwei CAI
Fei Jiang
Peihua Sun
Hongjian Zhang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Viva Star Biosciences Ltd
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Viva Star Biosciences Ltd
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Publication date
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Publication of EP4196220A1 publication Critical patent/EP4196220A1/en
Pending legal-status Critical Current

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    • 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
    • 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
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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

  • Lysophosphatidic acid is a small glycerolphospholipid (1- or 2-acyl-sn-glycerol 3- phosphate) with a molecular weight of 430 - 480 Dalton, consisting of a glycerol backbone which is esterified with a phosphate group and a fatty acid with variable chain length and degree of saturation (Yang and Chen, World J Gastroenterol 24:4132-4151, 2018).
  • agent refers to a biological, pharmaceutical, or chemical compound or another moiety.
  • Non-limiting examples include simple or complex organic or inorganic molecules, a peptide, a protein, an oligonucleotide, an antibody, an antibody derivative, an antibody fragment, a vitamin, a vitamin derivative, a carbohydrate, a toxin, or a chemotherapeutic compound, and metabolites thereof.
  • Various compounds can be synthesized, for example, small molecules and oligomers (e.g., oligopeptides and oligonucleotides), and synthetic organic compounds based on various core structures.
  • various natural sources can provide active compounds, such as plant or animal extracts, and the like. A skilled artisan can readily recognize that there is no limit as to the structural nature of the agents of this disclosure.
  • Prodrugs can increase the bioavailability of the compound when administered to a subject (e.g., by permitting enhanced absorption into the blood following oral administration) or which enhance delivery to a biological compartment of interest (e.g., the brain or lymphatic system) relative to the parent compound.
  • exemplary prodrugs include derivatives of a disclosed compound with enhanced aqueous solubility or active transport through the gut membrane, relative to the parent compound.
  • saturated straight chain alkyls include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl groups; while saturated branched alkyls include, but are not limited to, isopropyl, sec-butyl, isobutyl, tert-butyl, isopentyl, 2-methylbutyl, 3 -methylbutyl, 2-methylpentyl, 3 -methylpentyl, 4-methylpentyl, 2- methylhexyl, 3 -methylhexyl, 4-methylhexyl, 5-methylhexyl, 2,3-dimethylbutyl, and the like.
  • fluoroalkyl and fluoroalkoxy include haloalkyl and haloalkoxy groups, respectively, in which the halo is fluorine, such as, but not limited to, trifluoromethyl, difluoromethyl, 2,2,2- trifluoroethyl, l-fluoromethyl-2-fluoroethyl, -O-CHF2, and the like.
  • halo is fluorine, such as, but not limited to, trifluoromethyl, difluoromethyl, 2,2,2- trifluoroethyl, l-fluoromethyl-2-fluoroethyl, -O-CHF2, and the like.
  • alkyl, alkenyl, alkynyl and alkoxy groups are as defined herein and can be optionally further substituted as defined herein.
  • Examples of a ketone-contianing heterocycle include, without limitation, pyridin-2(lH)-one, pyrazin-2(lH)-one, pyrimidin-2(lH)-one, pyrimidin-4(3H)-one, pyridazin-3(2H)-one, pyridin- 4(lH)-one, imidazolidin-2-one, l,3-dihydro-2H-imidazol-2-one, 2,4-dihydro-3H-l,2,4-triazol-3- one, oxazol-2(3H)-one, and oxazolidin-2-one.
  • a ketone-containing heterocyclyl is obtainable by removing a hydrogen atom from its corepsonding ketone-contianing heterocycle at any available N-H or C-H position.
  • a heterocyclyl group may be optionally substituted by one or more of substituents disclosed herein.
  • R 5 at each occurrence is independently hydrogen, halogen, Ci-ealkyl, haloCi -ealkyl, OH, Ci- ealkyl-OH, Ci-ealkoxy, Ci-ealkyl-Ci-ealkoxy, haloCi-ealkoxy, CN, C3-7cycloalkyl, NR a R b , or Ci- 6 alkyl-NR a R b ; each occurrence of R 6a and R 6 is independently hydrogen, halogen, CN, methyl, ethyl, propyl, or cyclopropyl;
  • X 1 is N, or CR 6a ;
  • R 6a is hydrogen, or methyl
  • R 4 is independently hydrogen, halogen, Ci-ealkyl, haloCi-ealkyl, C2-ealkenyl, C2-ealkynyl, Ci- ealkoxy, (CH2)p-Ci-ealkoxy, phenyl, (CH2) P -phenyl, O(CH2) P -phenyl, CN, C3-7cycloalkyl, (CH2) P - C3-7cycloalkyl, C2-ealkenyl-C3-7cycloalkyl, C2-ealkynyl-C3-7cycloalkyl, O(CH2) P -C3-7cycloalkyl, (CH2)q-5-6-membered heteroaryl ring substituted with 1-4 R 11 , (CH2)q-5-7-membered heterocyclyl ring substituted with 1-4 R 11 , in which each phenyl is independently optionally substituted with 1- 3 of halogen, Ci-ealkyl, or Ci-ealkoxy
  • R 5 at each occurrence is independently hydrogen, halogen, Ci-ealkyl, haloCi-ealkyl, OH, Ci-ealkyl- OH, Ci-ealkoxy, Ci-ealkyl-Ci-ealkoxy, haloCi-ealkoxy, CN, C3-7cycloalkyl, NR a R b , or Ci-ealkyl- NR a R b ;
  • R 13 at each occurrence is independently hydrogen, Ci-4alkyl, or C3-5cycloalkyl; each occurrence of Ra and Rb is independently hydrogen or Ci-ealkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain additional one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of Cwalkyl, phenyl and benzyl; n is 0, 1 or 2; p at each occurrence is independently 1, 2, 3 or 4; and t is 0, 1, 2 or 3.
  • L 2 is a covalent bond or (CR 7 R 7 ) P ;
  • L 3 is a covalent bond, O or NR 7 , provided that at least one of L 2 and L 3 is not a covalent bond;
  • R 6 is hydrogen, halogen, CN, methyl, ethyl, propyl, or cyclopropyl;
  • the compound of Formula I includes a compound of Formula (III):
  • R 7 at each occurrence is independently hydrogen, Ci-4alkyl, C3-5cycloalkyl, or two R 7 groups together with the carbon atom to which they are attached, form a 3-5-membered cycloalkyl ring; each occurrence of R 9 and R 10 is independently hydrogen, Ci-ealkyl substituted with 1-4 R 11 , (CR 12 R 12 )q-C2-ealkenyl substituted with 1-4 R 11 , (CR 12 R 12 )q-C2-ealkynyl substituted with 1-4 R 11 , (CR 12 R 12 )q-C3-7cycloalkyl substituted with 1-4 R 11 , (CR 12 R 12 )q-phenyl substituted with 1-4 R 11 , (CR 12 R 12 )q-5-6-membered heteroaryl ring substituted with 1-4 R 11 , (CR 12 R 12 )q-5-7-membered heterocyclyl ring substituted with 1-4 R 11 ; or R 9 and R 10 , together with the nitrogen
  • R 11 at each occurrence independently hydrogen, Ci-ealkyl, haloCi-ealkyl, C2-ealkenyl, C2-ealkynyl, Ci-ealkoxy, (CH2)p-Ci-ealkoxy, phenyl, (CH2) P -phenyl, O(CH2) P -phenyl, CN, C3-7cycloalkyl, (CH2) P -C3-7cycloalkyl, C2-6alkenyl-C3-7cycloalkyl, C2-6alkynyl-C3-7cycloalkyl, O(CH2) P -C3- 7cycloalkyl, in which each phenyl is independently optionally substituted with 1-3 of halogen, Ci- ealkyl, or Ci-ealkoxy;
  • the compound of Formula I includes a compound of Formula (Illb) or (Ilbb) :
  • L 2 is a covalent bond or (CR 7 R 7 ) P ;
  • X 1 is N, or CR 6a ;
  • R 6a is hydrogen, or methyl
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising a compound disclosed herein, and a pharmaceutically acceptable carrier.
  • Scheme 12 describes the synthesis of l-azinemethyl-piperidine-3 -carboxylic acids 48, 49 and 50.
  • Carbonyl insertion of azine halide 1 in the presence of CO gas and appropriate catalyst in methanol gives azine carboxylate 42, which is then reduced with appropriate reductant to give azine methyl alcohol 43.
  • Treatment of azine methyl alcohol 43 with MsCl in the presence of appropriate base gives the corresponding mesylate 44.
  • Alkylation piperidine carboxylate 45 with mesylate 44 in the presence appropriate base affords azine methyl-piperidine-3 -carboxylate 46.
  • Deprotection of azine methyl-piperidine-3 -carboxylate 46 gives hydroxylmethyl azole 47, which is then converted to corresponding acids 48, 49 and 50 using similar methods as described herein over several steps.
  • pharmaceutically acceptable carrier or adjuvant refers to a carrier or adjuvant that may be administered to a subject, together with a compound of this invention, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the compound.
  • Step 1 2-ethyl-3-iodo-6-(l-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-lH-l,2,3- triazol-4-yl)pyridine
  • Step 2 benzyl (S)-3,3-difluoro-5-(2-methoxy-2-oxoethyl)piperidine-l-carboxylate (3A) and benzyl (R)-3,3-difluoro-5-(2-methoxy-2-oxoethyl)piperidine-l-carboxylate (3B)
  • Step 2 (2-methyl-6-(l-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-lH-l,2,3-triazol- 4-yl)pyridin-3-yl)methanol
  • Step 1 N'-[(lE)-cyclopropylmethylidene]-4-methylbenzene-l-sulfonohydrazide
  • Step 1 l-(6-methoxypyridin-3-yl)cyclobutan-l-ol [0203] To a stirred solution of 5-bromo-2-methoxypyridine (1.38 mL, 10.6 mmol) in dry THF (25 mL) was added n-BuLi (5.5 mL, 13.8 mmol) drop-wisely at -78 °C. After stirring at this temperature for 30 mins, cyclobutanone (1.2 mL, 15.9 mmol) was added and the resulting mixture was stirred at -78 °C for 30 mins and r.t. for 30 mins. The mixture was quenched with ice-water and extracted with EtOAc (2 x 10 mL).
  • Step 1 (R)-2-((tert-butoxycarbonyl)amino)-3-cyclopropylpropanoic acid
  • Step 1 2-[4-(5-bromo-6-methylpyridin-2-yl)-l-methyl-lH-l,2,3-triazol-5-yl]acetonitrile
  • Step 4 2-[4-(5-bromo-6-methylpyridin-2-yl)-l-methyl-lH-l,2,3-triazol-5-yl]ethyl methanesulfonate
  • Step 7 2-[5,5-difluoro-l-(2-methyl-6- ⁇ l-methyl-5-[2-(6-oxo-5-propyl-l,6-dihydropyridazin-
  • Step 8 ethyl 2-(l-(4-fluoro-2-methyl-6-(l-methyl-5-(((methylsulfonyl)oxy)methyl)-lH-l,2,3- triazol-4-yl)pyridin-3-yl)piperidin-3-yl)acetate
  • Step 6 ethyl 2-(l-(6-bromo-2-ethyl-4-fluoropyridin-3-yl)piperidin-3-yl)acetate
  • Step 8 methyl (S)-2-(l-(2-cyano-6-(l-methyl-5-(((methylsulfonyl)oxy)methyl)-lH-l,2,3- triazol-4-yl)pyridin-3-yl)-5,5-difluoropiperidin-3-yl)acetate
  • Example 52 and 53 (R) or (S)-2-(l-(2-ethyl-6-(l-methyl-5-((2-oxo-5-propylpyridin-l(2H)- yl)methyl)-lH-l,2,3-triazol-4-yl)pyridin-3-yl)-2-oxopiperidin-3-yl)acetic aci and (S) or (R)-2- (l-(2-ethyl-6-(l-methyl-5-((2-oxo-5-propylpyridin-l(2H)-yl)methyl)-lH-l,2,3-triazol-4- yl)pyridin-3-yl)-2-oxopiperidin-3-yl)acetic acid Step 1: (4-(6-ethyl-5-iodopyridin-2-yl)-l-methyl-lH-l,2,3-triazol-5-yl)methyl methanesulfonate
  • Example 53 (S) or (R)-2-(l-(2-ethyl-6-(l-methyl-5-((2-oxo-5-propylpyridin-l(2H)- yl)methyl)-lH-l,2,3-triazol-4-yl)pyridin-3-yl)-2-oxopiperidin-3-yl)acetic acid
  • Step 8 2-[(3R)-l-(6- ⁇ l-methyl-5-[(2-oxo-5-propyl-l,2-dihydropyridin-l-yl)methyl]-lH- l,2,3-triazol-4-yl ⁇ -2-(trifluoromethyl)pyridin-3-yl)piperidin-3-yl]acetic acid
  • Step 3 3-bromo-2-(difluoromethyl)-6-[3-(oxan-2 yloxy)prop-l-yn-l-yl]pyridine
  • Step 4 3-bromo-2-(difluoromethyl)-6- ⁇ l-methyl-5-[(oxan-2-yloxy)methyl]-lH-l,2,3-triazol- 4-yl ⁇ pyridine
  • Step 5 ethyl 2-[(3R)-l-[2-(difluoromethyl)-6- ⁇ l-methyl-5-[(oxan-2-yloxy)methyl]-lH-l,2,3- triazol-4-yl ⁇ pyridin-3-yl] piperidin-3-yl] acetate
  • Step 6 ethyl (S)-2-(l-(2-cyano-6-(l-methyl-5-(((methylsulfonyl)oxy)methyl)-lH-l,2,3- triazol-4-yl)pyridin-3-yl)piperidin-3-yl)acetate
  • Step 7 ethyl (S)-2-(l-(2-cyano-6-(l-methyl-5-(((methylsulfonyl)oxy)methyl)-lH-l,2,3- triazol-4-yl)pyridin-3-yl)piperidin-3-yl)acetate
  • Step 8 [(3R)-l-[2-(difluoromethyl)-6- ⁇ l-methyl-5-[(2-oxo-5-propyl-l,2-dihydropyridin-l- yl)methyl]-lH-l,2,3-triazol-4-yl ⁇ pyridin-3-yl]piperidin-3-yl]acetate [0359] To a mixture of 2- ⁇ 4-[6-(difluoromethyl)-5-[(3R)-3-(2-ethoxy-2-oxoethyl)piperidin-l- yl]pyridin-2-yl]-l-methyl-lH-l,2,3-triazol-5-yl ⁇ ethane-l-sulfonic acid (60 mg, 0.1 mmol) and 5- propylpyridin-2-ol (17 mg, 0.1 mmol) in toluene (5 mL) and water (1 mL) was added K2CO3 (51 mg, 0.3
  • Step 9 2-[(3R)-l-[2-(difluoromethyl)-6- ⁇ l-methyl-5-[(2-oxo-5-propyl-l,2-dihydropyridin-l- yl)methyl]-lH-l,2,3-triazol-4-yl ⁇ pyridin-3-yl]piperidin-3-yl]acetic acid
  • Example 61 2-((S)-l-(6-(5-(((S)-4-(cyclopropylmethyl)-3-methyl-2-oxoimidazolidin-l- yl)methyl)-l-methyl-lH-l,2,3-triazol-4-yl)-2-ethylpyridin-3-yl)-5,5-difluoropiperidin-3- yl)acetic acid
  • Step 2 methyl 2-[(3S)-l-[6-(5- ⁇ [(4S)-4-(cyclopropylmethyl)-3-methyl-2-oxoimidazolidin-l- yl]methyl ⁇ -l-methyl-lH-l,2,3-triazol-4-yl)-2-ethylpyridin-3-yl]-5,5-difluoropiperidin-3- yl] acetate

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EP21791479.5A 2020-08-11 2021-10-09 Triazole-pyridinyl substituted azacyclohexyl acetic acid compounds as lpa receptor antagonists Pending EP4196220A1 (en)

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EP4058144A1 (en) 2019-11-15 2022-09-21 Gilead Sciences, Inc. Triazole carbamate pyridyl sulfonamides as lpa receptor antagonists and uses thereof
TWI843503B (zh) 2020-06-03 2024-05-21 美商基利科學股份有限公司 Lpa受體拮抗劑及其用途
EP4161936A1 (en) 2020-06-03 2023-04-12 Gilead Sciences, Inc. Lpa receptor antagonists and uses thereof
CN117751106A (zh) * 2021-04-30 2024-03-22 唯久生物技术(苏州)有限公司 作为lpa拮抗剂的新型三唑-吡啶取代的吡咯烷基和四氢-2h-吡喃基乙酸化合物
WO2022240879A1 (en) 2021-05-11 2022-11-17 Gilead Sciences, Inc. Lpa receptor antagonists and uses thereof
KR20240007233A (ko) 2021-05-13 2024-01-16 길리애드 사이언시즈, 인코포레이티드 Lpa 수용체 길항제 및 이의 용도
WO2023107938A1 (en) 2021-12-08 2023-06-15 Gilead Sciences, Inc. Lpa receptor antagonists and uses thereof
TW202342017A (zh) 2022-02-25 2023-11-01 美商洛子峰生物有限公司 用於治療與ｌｐａ受體活性相關的病狀的化合物及組合物
TW202417426A (zh) * 2022-07-25 2024-05-01 大陸商武漢人福創新藥物研發中心有限公司 三氮唑類化合物及其作為lpar1拮抗劑的用途
WO2025051266A1 (zh) * 2023-09-08 2025-03-13 西藏海思科制药有限公司 杂芳环衍生物的lpar1拮抗剂及其用途
WO2025162421A1 (zh) * 2024-02-04 2025-08-07 西藏海思科制药有限公司 Lpar1拮抗剂及其用途

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CN116669727B (zh) 2025-07-08
CA3191452A1 (en) 2022-02-17
JP2023544476A (ja) 2023-10-24
IL300525A (en) 2023-04-01
KR20240068583A (ko) 2024-05-17

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