WO2022253997A1 - Benzothia(di)azepine compounds and their use as bile acid modulators - Google Patents

Benzothia(di)azepine compounds and their use as bile acid modulators Download PDF

Info

Publication number
WO2022253997A1
WO2022253997A1 PCT/EP2022/065165 EP2022065165W WO2022253997A1 WO 2022253997 A1 WO2022253997 A1 WO 2022253997A1 EP 2022065165 W EP2022065165 W EP 2022065165W WO 2022253997 A1 WO2022253997 A1 WO 2022253997A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
butyl
tetrahydro
dioxido
oxy
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.)
Ceased
Application number
PCT/EP2022/065165
Other languages
English (en)
French (fr)
Inventor
Per-Göran Gillberg
Ingemar Starke
Santosh S. Kulkarni
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.)
Albireo AB
Original Assignee
Albireo AB
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to ES22732489T priority Critical patent/ES3037404T3/es
Priority to EP22732489.4A priority patent/EP4347575B1/en
Priority to MX2023014153A priority patent/MX2023014153A/es
Priority to PL22732489.4T priority patent/PL4347575T3/pl
Priority to KR1020237043618A priority patent/KR20240017844A/ko
Priority to CA3218474A priority patent/CA3218474A1/en
Priority to BR112023024850A priority patent/BR112023024850A2/pt
Priority to AU2022285893A priority patent/AU2022285893A1/en
Priority to IL308582A priority patent/IL308582A/en
Application filed by Albireo AB filed Critical Albireo AB
Priority to JP2023574477A priority patent/JP7842787B2/ja
Priority to CN202280038820.2A priority patent/CN117412955A/zh
Priority to US17/813,152 priority patent/US12365658B2/en
Publication of WO2022253997A1 publication Critical patent/WO2022253997A1/en
Priority to JOJO/P/2023/0302A priority patent/JOP20230302A1/ar
Priority to CONC2023/0016072A priority patent/CO2023016072A2/es
Anticipated expiration legal-status Critical
Priority to ZA2024/00117A priority patent/ZA202400117B/en
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D281/02—Seven-membered rings
    • C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
    • C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/554—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/36—Seven-membered rings

Definitions

  • R 2 is independently selected from the group consisting of hydrogen, halogen, hydroxy,
  • R 4C and R 4D are each independently selected from the group consisting of hydrogen and Ci- 4 alkyl
  • R 5 is selected from the group consisting of hydrogen and C1-4 alkyl; or a pharmaceutically acceptable salt thereof.
  • R 5 is hydrogen. In some embodiments, R 5 is methyl.
  • Compounds having a high ASBT inhibiting potency are particularly suitable for the treatment of liver diseases that cause cholestasis, such as progressive familial intrahepatic cholestasis (PFIC), Alagilles syndrome, biliary atresia and non-alcoholic steatohepatitis (NASH).
  • PFIC progressive familial intrahepatic cholestasis
  • Alagilles syndrome biliary atresia
  • NASH non-alcoholic steatohepatitis
  • Biliary atresia is a rare pediatric liver disease that involves a partial or total blockage (or even absence) of large bile ducts. This blockage or absence causes cholestasis that leads to the accumulation of bile acids that damages the liver. In some embodiments, the accumulation of bile acids occurs in the extrahepatic biliary tree.
  • the mutation in ATP8B1 is selected from L127P, G308V, T456M, D554N, F529del, I661T, E665X, R930X, R952X, R1014X, and G1040R.
  • the mutation in ABCB11 is selected from A167T, G238V, V284L, E297G, R4703 ⁇ 4 R470X, D482G, R487H, A570T, N591S, A865V, G982R, R1153C, and R1268Q.
  • PFIC e.g., PFIC-1 and PFIC-2
  • methods of treating PFIC PFIC-1 and PFIC-2 in a subject that includes performing an assay on a sample obtained from the subject to determine whether the subject has a mutation associated with PFIC (e.g., a ATP8B1, ABCB11, ABCB4, TJP2, NR1H4 or Myo5b mutation), and administering (e.g., specifically or selectively administering) a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, to the subject determined to have a mutation associated with PFIC.
  • the mutation is a ATP8B1 or ABCB11 mutation.
  • the mutation in ATP8B1 is selected from L127P, G308V, T456M, D554N, F529del, I661T, E665X, R930X, R952X, R1014X, and G1040R.
  • the mutation in ABCB11 is selected from A167T, G238V, V284L, E297G, R470Q, R470X, D482G, R487H, A570T, N591S, A865V, G982R, R1153C, and R1268Q.
  • PFIC e.g., PFIC-1 and PFIC-2
  • a mutation associated with PFIC e.g., a ATP8B1, ABCB11, ABCB4, TJP2, NR1H4 or Myo5b mutation
  • treatment of NAFLD can be assessed using the NAS.
  • the NAS can be determined as described in Kleiner et al., Hepatology. 2005, 41(6):1313-1321, which is hereby incorporated by reference in its entirety. See, for example, Table 6 for a simplified NAS scheme adapted from Kleiner.
  • NASH in the subject is evidenced by an accumulation of hepatic fat and detection of a biomarker indicative of liver damage.
  • a biomarker indicative of liver damage For example, elevated serum ferritin and low titers of serum autoantibodies can be common features of NASH.
  • treatment of NASH can include a decrease of one or more symptoms associated with NASH; reduction in the amount of hepatic steatosis; a decrease in the NAS; a decrease in hepatic inflammation; a decrease in the level of biomarkers indicative of one or more of liver damage, inflammation, liver fibrosis, and/or liver cirrhosis; and a reduction in fibrosis and/or cirrhosis, a lack of further progression of fibrosis and/or cirrhosis, or a slowing of the progression of fibrosis and/or cirrhosis in the subject following administration of one or more doses of a compound of formula (I), or a pharmaceutically acceptable salt thereof.
  • treatment of NASH can be assessed by measuring hepatic steatosis.
  • treatment of NASH comprises a reduction in hepatic steatosis following administration of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as described herein.
  • hepatic steatosis is determined by one or more methods selected from the group consisting of ultrasonography, computed tomography (CT), magnetic resonance imaging, magnetic resonance spectroscopy (MRS), magnetic resonance elastography (MRE), transient elastography (TE) (e.g., FIBROSCAN ® ), measurement of liver size or weight, or by liver biopsy (see, e.g., Di Lascio et al., Ultrasound Med Biol. 2018, vol. 44(8), p. 1585-1596; Lv et al., J Clin Transl Hepatol. 2018, vol. 6(2), p. 217-221; Reeder et al., J Magn Reson Imaging. 2011, vol.
  • CT computed tomography
  • MRS magnetic resonance spectroscopy
  • MRE magnetic resonance elastography
  • TE transient elastography
  • FIBROSCAN ® transient elastography
  • the presence of hepatic inflammation is determined by one or more methods selected from the group consisting of biomarkers indicative of hepatic inflammation and a liver biopsy sample(s) from the subject.
  • the severity of hepatic inflammation is determined from a liver biopsy sample(s) from the subject. For example, hepatic inflammation in a liver biopsy sample can be assessed as described in Kleiner et al., Hepatology 2005, vol. 41(6), p. 1313-1321 and Brunt et al., Am J Gastroenterol 1999, vol. 94, p. 2467-2474, each of which are hereby incorporated by reference in their entireties.
  • a decrease in the severity of fibrosis, a lack of further progression of fibrosis and/or cirrhosis, or a slowing of the progression of fibrosis and/or cirrhosis indicates treatment of NASH.
  • the severity of fibrosis is determined using a scoring system such as any of the fibrosis scoring systems described herein, for example, the score can indicate the stage of fibrosis, e.g., stage 0 (no fibrosis), stage 1, stage 2, stage 3, and stage 4 (cirrhosis) (see, e.g., Kleiner et al).
  • a decrease in the stage of the fibrosis is a decrease in the severity of the fibrosis.
  • a decrease by 1, 2, 3, or 4 stages is a decrease in the severity of the fibrosis.
  • a decrease in the stage e.g., from stage 4 to stage 3, from stage 4 to stage 2, from stage 4 to stage 1, from stage 4 to stage 0, from stage 3 to stage 2, from stage 3 to stage 1, from stage 3 to stage 0, from stage 2 to stage 1, from stage 2 to stage 0, or from stage 1 to stage 0 indicates treatment of NASH.
  • the stage of fibrosis decreases from stage 4 to stage 3, from stage 4 to stage 2, from stage 4 to stage 1, from stage
  • hyaluronic acid pro-inflammatory cytokines
  • a panel of biomarkers consisting of a2- macroglobulin, haptoglobin, apolipoprotein Al, bilirubin, gamma glutamyl transpeptidase (GGT) combined with a subject's age and gender to generate a measure of fibrosis and necroinflammatory activity in the liver (e.g., FIBROTEST ® , FIBROSURE ® ), a panel of biomarkers consisting of bilirubin, gamma-glutamyltransferase, hyaluronic acid, a2-macroglobulin combined with the subject's age and sex (e.g., HEPASCORE ® ; see, e.g., Adams et al., Clin.
  • HEPASCORE ® see, e.g., Adams et al., Clin.
  • the level of aspartate aminotransferase decreases. In some embodiments, the level of alanine aminotransferase (ALT) does not increase. In some embodiments, the level of alanine aminotransferase (ALT) decreases.
  • the "level" of an enzyme refers to the concentration of the enzyme, e.g., within blood. For example, the level of AST or ALT can be expressed as Units/L.
  • the severity of fibrosis is determined by one or more of the FIB-4 score, a panel of biomarkers consisting of a2-macroglobulin, haptoglobin, apolipoprotein Al, bilirubin, gamma glutamyl transpeptidase (GGT) combined with a subject's age and gender to generate a measure of fibrosis and necroinflammatory activity in the liver (e.g., FIBROTEST ® , FIBROSURE ® ), a panel of biomarkers consisting of bilirubin, gamma-glutamyltransferase, hyaluronic acid, a2- macroglobulin combined with the subject's age and sex (e.g., HEPASCORE ® ; see, e.g., Adams et al., Clin.
  • HEPASCORE ® see, e.g., Adams et al., Clin.
  • the decrease in the level of one or more biomarkers indicative of one or more of liver damage, inflammation, liver fibrosis, and/or liver cirrhosis following administration of the compound of formula (I), or a pharmaceutically acceptable salt thereof is by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about
  • AST Aspartate aminotransferase
  • ALT alanine aminotransferase ratio
  • AAR alanine aminotransferase ratio
  • a panel including tissue inhibitor of metalloproteinase-1, hyaluronic acid, and a2- macroglobulin e.g., FIBROSPECT ®
  • a panel including tissue inhibitor of metalloproteinases 1 (TIMP-1), amino- terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA) e.g., the Enhanced Liver Fibrosis (ELF) score 3
  • TIMP-1 tissue inhibitor of metalloproteinases 1
  • PIIINP amino- terminal propeptide of type III procollagen
  • HA hyaluronic acid
  • PAI-1 Collagen isoforms e.g., Collal, Colla2, and Col4al
  • binders include, but are not limited to, starch, pregelatinized starch, gelatin, sugars (such as sucrose, glucose, dextrose, lactose and sorbitol), polyethylene glycol, waxes, natural and synthetic gums (such as acacia gum and tragacanth gum), sodium alginate, cellulose derivatives (such as hydroxypropylmethylcellulose (or hypromellose), hydroxypropylcellulose and ethylcellulose) and synthetic polymers (such as acrylic acid and methacrylic acid copolymers, methacrylic acid copolymers, methyl methacrylate copolymers, aminoalkyl methacrylate copolymers, polyacrylic acid/polymethacrylic acid copolymers and polyvinylpyrrolidone (povidone)).
  • sugars such as sucrose, glucose, dextrose, lactose and sorbitol
  • polyethylene glycol such as acacia gum and tragacanth gum
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an HMG CoA reductase inhibitor, such as fluvastatin, lovastatin, pravastatin, simvastatin, atorvastatin, pitavastatin cerivastatin, mevastatin, rosuvastatin, bervastatin or dalvastatin, or a pharmaceutically acceptable salt thereof.
  • an HMG CoA reductase inhibitor such as fluvastatin, lovastatin, pravastatin, simvastatin, atorvastatin, pitavastatin cerivastatin, mevastatin, rosuvastatin, bervastatin or dalvastatin, or a pharmaceutically acceptable salt thereof.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a dual PPAR alpha/gamma agonist, including glitazars such as saroglitazar, aleglitazar, muraglitazar or tesaglitazar, or a pharmaceutically acceptable salt thereof.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a dual PPAR alpha/delta agonist, such as elafibranor.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a TGR5 receptor modulator, including TGR5 agonists such as 6a- ethyl-23(S)-methylcholic acid (INT-777).
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an FGF19 modulator, such as NGM282.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an FGF21 agonist, such as BMS-986036.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an integrin inhibitor, such as PLN-74809 and PLN-1474.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a stearoyl-CoA desaturase (SCD) Inhibitor, such as aramchol (arachidyl amido cholanoic acid).
  • SCD stearoyl-CoA desaturase
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an apoptosis signal-regulating kinase 1 (ASK1) inhibitor, such as selonsertib.
  • ASK1 apoptosis signal-regulating kinase 1
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an LOXL2 inhibitor, such as silane.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an ACC inhibitor, such as GS-0976.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a thyroid hormone receptor-b agonist, such as MGL3196.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a mitochondrial pyruvate carrier inhibitor, such as MS DC-0602 K.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an anti-oxidant agent, such as vitamin E.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a diacylglycerol O-Acyltransferase 2 (DGAT2) inhibitor, such as DGAT2RX and PF-06865571.
  • DGAT2 diacylglycerol O-Acyltransferase 2
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a fatty acid synthase (FASN) Inhibitor, such as TVB-2640.
  • FSN fatty acid synthase
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an AMP-activated protein kinase (AMPK) activator, such as PXL-
  • AMPK AMP-activated protein kinase
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a KIo ⁇ Iiob (KLB) and fibroblast growth factor receptor (FGFR) activator, such as MK-3655 (previously known as NGM-313).
  • KLB KIo ⁇ Iiob
  • FGFR fibroblast growth factor receptor
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an A3 antagonist, such as PBF-1650.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a sulfated oxysterol, such as Dur-928.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a leukotriene D4 (LTD4) receptor antagonist, such as MN-001.
  • LTD4 leukotriene D4
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an anti-lipopolysaccharide (LPS) compound, such as IMM-124E.
  • LPS anti-lipopolysaccharide
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a VAP1 inhibitor, such as BI1467335.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a TLR4 antagonist, such as JKB-121.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a ketohexokinase inhibitor, such as PF-06835919.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an adiponectin receptor agonist, such as ADP-335.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with an autotaxin inhibitor, such as PAT-505 and PF8380.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a chloride channel stimulator, such as cobiprostone and lubiprostone.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a sterol regulatory element-binding protein (SREBP) transcription factor inhibitor, such as CAT-2003 and MDV-4463.
  • SREBP sterol regulatory element-binding protein
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a biguanidine, such as metformin.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with insulin.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a glucosidase inhibitor, such as acarbose or miglitol.
  • compounds of formula (I), or pharmaceutically acceptable salts thereof are administered in combination with a squalene synthase inhibitor, such as TAK-475.
  • Method A Mobile phase: A: 0.1% HCOOH in water: ACN (95:5), B: ACN; flow rate: 1.5 mL/min; column: ZORBAX XDB C-18 (50 x 4.6 mm) 3.5 mM.
  • Method I Mobile phase: A: 0.1% HCOOH in water: ACN (95:5), B: ACN; flow rate: 0.8 mL/min; Column: ZORBAX ECLIPSE PLUS C18 (2.1 x 50) mm, 1.8 pm.
  • Method A Mobile Phase: A: 0.1% HCOOH in water, B: 0.1% HCOOH in ACN; Flow Rate: 0.8 mL/min; Column: Acquity UPLC HSS T3 (2.1 x 50) mm; 1.8 pm. Instrument Name : Shimadzu Nexera X2 LC / 2020 MSD
  • Ratio between CO 2 and co-solvent is ranging between 60:40 and 80:20
  • Method A Mobile phase: 0.5% isopropylamine in IPA; flow rate: 3 mL/min; column: YMC Amylose-SA (250 x 4.6 mm, 5 pm).
  • Method C Mobile Phase: 20 mM ammonia in methanol; flow rate: 3 mL/min; column: YMC Cellulose-SC (250 x 4.6 mm, 5 pm).
  • Method G Mobile Phase: 0.5% isopropylamine in methanol; flow rate: 3 mL/min; column: Lux Al.
  • Method H Mobile Phase: 0.5% isopropylamine in IPA; flow rate: 3 mL/min; column: Lux Al (250 x 4.6 mm, 5 pm).
  • Method I Mobile phase: 0.5% isopropylamine in methanol; flow rate: 3 mL/min; column: Chiral CCS (250 x 4.6 mm, 5 pm).
  • Method P Mobile phase: 0.5% Isopropylamine in methanol, flow rate: 3 mL/min; column: Chiralpak AS-H (250 x 4.6 mm, 5 pm).
  • Method R Mobile phase: 0.1% Isopropylamine in IPA:methanol (1:1), flow rate: 3 mL/min; column: Lux A1 (250 x 4.6 mm, 5 pm).
  • Method B Mobile phase: A: 10 mM NH 4 OAC in water; B: ACN; flow rate: 35 mL/min; column: X select C18 (30 x 150 mm, 5 pm).
  • Method C Mobile phase: A: 10 mM NH 4 HCO 3 in water; B: ACN; flow rate: 1.0 mL/min; column: XBridge C8 (50 x 4.6 mm, 3.5 pm).
  • Method D Mobile phase: A: 0.1% HCOOH in water; B: ACN; flow rate: 1.0 mL/min; column: X-select C18 (30 x 150 mm, 5 pm).
  • Method A Mobile phase: 0.5% isopropylamine in IPA; flow rate: 3 mL/min; column: YMC Amylose-SA (250 x 30 mm, 5 pm).
  • Method B Mobile Phase: 0.5% isopropylamine in IPA; flow rate: 3 mL/min; column: Chiralpak AD-H (250 x 30 mm, 5 pm).
  • DBAD (0.04 g, 0.18 mmol) was then added at 0 °C and the reaction mixture was stirred for 12 hours at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with water (5 mL) and the aqueous layer was extracted with ethyl acetate (2 x 5 mL). The combined organic layer was washed with water (5 mL) and brine (5 mL) and dried over anhydrous Na2S04. The organic part was filtered and concentrated under vacuum. The resulting crude material was purified by Isolera column chromatography (eluent: 30% EtOAc/PE; silica gel: 230-400 mesh) to afford the title compound. Yield: 57% (60 mg, brown solid).
  • DBAD (0.04 g, 0.18 mmol) was then added at 0 °C and the reaction mixture was stirred for 1 hour at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with water (5 mL) and the aqueous layer was extracted with ethyl acetate (2 x 5 mL). The combined organic layer was washed with water (5 mL) and brine (5 mL) and dried over anhydrous Na2S04. The organic part was filtered and concentrated under vacuum. The resulting crude material was purified by Isolera column chromatography (eluent: 20-22% EtOAc/PE; silica gel: 230-400 mesh) to afford the title compound. Yield: 51% (0.1 g, white solid).
  • the two diastereoisomers of Intermediate 50 were separated by chiral SFC Instrument (method N). The material was concentrated under vacuum at 40 °C. The first eluting fraction corresponded to diastereomer 1 and the second eluting fraction corresponded to diastereomer 2. Each of the two fractions was then individually treated for further purification. The obtained residue was diluted with ethyl acetate (30 ml) and washed with dilute HCI (1.5 N, 10 mL) and water (10 mL). The organic part was then dried over anhydrous Na2S04, filtered and concentrated under vacuum to afford a purified diastereomer of the title compound. The absolute configuration of the two diastereomers is not known.
  • Diastereoisomer 1 Yield: 43% (0.13 g, off-white gum).
  • Diastereoisomers 1 and 2 of the title compound were prepared from diastereoisomer 1 (0.13 g) and diastereoisomer 2 (0.13 g) of Intermediate 51, respectively, following the same procedure as described for Intermediate 52. After work-up of the reaction mixtures, the crude materials were purified by Isolera column chromatography (eluent: 22% EtOAc/PE; silica gel: 230-400 mesh) to afford the title compounds. The absolute configuration of the two diastereomers is not known.
  • Diastereoisomer 1 Yield: 69% (95 mg, pale yellow solid).
  • Stereoisomers 1 and 2 of the title compound were prepared from enantiomer 1 (0.3 g) and enantiomer 2 (0.3 g) of Intermediate 9, respectively, following the same procedure as described for Intermediate 55. The absolute configuration of the two stereoisomers is not known.
  • Stereoisomer 1 Yield: 47.1% (0.18 g, brown solid).
  • Stereoisomer 1 Yield: 54.9% (0.15 g, white solid).
  • 1 H-NMR 400 MHz, CDCI 3 ): d 7.39 (s, 1H), 7.22-7.20 (m, 2H), 6.98 (s, 1H), 6.83-6.78 (m, 1H), 6.67-6.65 (m, 2H), 4.44-4.38 (m, 2H), 427-4.25 (m,lH), 4.09- 4.04 (m, 2H), 3.87-3.80 (m, 5H), 3.61 (s, 3H), 3.23 (s, 1H), 2.57 (s, 3H), 2.33 (s, 3H), 1.75-1.70 (m, 1H), 1.58 (s, 3H), 1.50-1.28 (m, 3H).
  • Enantiomer 2 of the title compound was obtained following the same procedure, starting from 0.4 g of enantiomer 2 of Intermediate 11. The resulting crude was purified by prep-HPLC purification (Method B) to afford of the title compound.
  • the absolute configuration of the two enantiomers is not known.
  • Enantiomer 1 Yield: 75% (15 mg, white solid).
  • Enantiomer 2 Yield: 13% (50 mg, off-white solid).
  • Enantiomer 2 of the title compound was obtained following the same procedure, starting from 0.13 g of enantiomer 2 of Intermediate 13. The absolute configuration of the two enantiomers is not known.
  • Enantiomer 1 Yield: 26% (30 mg, white solid).
  • Enantiomer 2 Yield: 20% (25 mg, white solid).
  • Enantiomer 1 Yield: 37% (20 mg, off-white solid).
  • Enantiomer 1 Yield: 24% (15 mg, off-white solid).
  • Enantiomer 2 Yield: 23% (15 mg, off-white solid).
  • Enantiomer 2 Yield: 13% (5 mg, off-white solid).
  • Diastereoisomer 1 Yield: 57% (55 mg, white solid).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
PCT/EP2022/065165 2021-06-03 2022-06-03 Benzothia(di)azepine compounds and their use as bile acid modulators Ceased WO2022253997A1 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
IL308582A IL308582A (en) 2021-06-03 2022-06-03 Benzothia(di)azepine compounds and their uses as gastric acid modulators
MX2023014153A MX2023014153A (es) 2021-06-03 2022-06-03 Compuestos de benzotia(di)azepina y su uso como moduladores del acido biliar.
JP2023574477A JP7842787B2 (ja) 2021-06-03 2022-06-03 ベンゾチア（ジ）アゼピン化合物及び胆汁酸モジュレータとしてのそれらの使用
KR1020237043618A KR20240017844A (ko) 2021-06-03 2022-06-03 벤조티아(디)아제핀 화합물 및 담즙산 조절제로서의 이의 용도
CA3218474A CA3218474A1 (en) 2021-06-03 2022-06-03 Benzothia(di)azepine compounds and their use as bile acid modulators
BR112023024850A BR112023024850A2 (pt) 2021-06-03 2022-06-03 Compostos de benzotia(di)azepina e seus usos como moduladores de ácido biliar
AU2022285893A AU2022285893A1 (en) 2021-06-03 2022-06-03 Benzothia(di)azepine compounds and their use as bile acid modulators
ES22732489T ES3037404T3 (en) 2021-06-03 2022-06-03 Benzothia(di)azepine compounds and their use as bile acid modulators
PL22732489.4T PL4347575T3 (pl) 2021-06-03 2022-06-03 Związki benzotio(di)azepinowe i ich zastosowanie jako modulatorów kwasów żółciowych
EP22732489.4A EP4347575B1 (en) 2021-06-03 2022-06-03 Benzothia(di)azepine compounds and their use as bile acid modulators
CN202280038820.2A CN117412955A (zh) 2021-06-03 2022-06-03 苯并硫杂(二)氮杂环庚三烯化合物及其作为胆汁酸调节剂的用途
US17/813,152 US12365658B2 (en) 2021-06-03 2022-07-18 Benzothia(di)azepine compounds and their use as bile acid modulators
JOJO/P/2023/0302A JOP20230302A1 (ar) 2021-06-03 2023-11-23 مركبات بنزوثيا(داي) أزيبين واستخدامها كمعدلات لحمض الصفراء
CONC2023/0016072A CO2023016072A2 (es) 2021-06-03 2023-11-23 Compuestos de benzotia(di)azepina y su uso como moduladores del ácido biliar
ZA2024/00117A ZA202400117B (en) 2021-06-03 2024-01-02 Benzothia(di)azepine compounds and their use as bile acid modulators

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN202111024711 2021-06-03
IN202111024711 2021-06-03

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US17/813,152 Continuation US12365658B2 (en) 2021-06-03 2022-07-18 Benzothia(di)azepine compounds and their use as bile acid modulators

Publications (1)

Publication Number Publication Date
WO2022253997A1 true WO2022253997A1 (en) 2022-12-08

Family

ID=82156361

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2022/065165 Ceased WO2022253997A1 (en) 2021-06-03 2022-06-03 Benzothia(di)azepine compounds and their use as bile acid modulators

Country Status (20)

Country Link
US (1) US12365658B2 (https=)
EP (1) EP4347575B1 (https=)
JP (1) JP7842787B2 (https=)
KR (1) KR20240017844A (https=)
CN (1) CN117412955A (https=)
AR (1) AR126076A1 (https=)
AU (1) AU2022285893A1 (https=)
BR (1) BR112023024850A2 (https=)
CA (1) CA3218474A1 (https=)
CL (1) CL2023003568A1 (https=)
CO (1) CO2023016072A2 (https=)
ES (1) ES3037404T3 (https=)
HU (1) HUE072404T2 (https=)
IL (1) IL308582A (https=)
JO (1) JOP20230302A1 (https=)
MX (1) MX2023014153A (https=)
PL (1) PL4347575T3 (https=)
TW (1) TW202313579A (https=)
WO (1) WO2022253997A1 (https=)
ZA (1) ZA202400117B (https=)

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023203248A1 (en) 2022-04-22 2023-10-26 Albireo Ab Subcutaneous administration of an asbt inhibitor
WO2023237728A1 (en) 2022-06-09 2023-12-14 Albireo Ab Treating hepatitis
US12024495B2 (en) 2019-12-04 2024-07-02 Albireo Ab Benzothiazepine compounds and their use as bile acid modulators
US12060338B2 (en) 2019-12-04 2024-08-13 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2024177984A1 (en) * 2023-02-20 2024-08-29 Assembly Biosciences, Inc. Benzothia(dia)zepine compounds for treatment of hbv and hdv
US12091394B2 (en) 2018-06-20 2024-09-17 Albireo Ab Crystal modifications of odevixibat
US12134606B2 (en) 2020-12-04 2024-11-05 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2024240249A1 (zh) * 2023-05-25 2024-11-28 正大天晴药业集团股份有限公司 一种苯并噻二氮卓化合物及其用途
US12187690B2 (en) 2019-02-06 2025-01-07 Albireo Ab Benzothiadiazepine compounds and their use as bile acid modulators
US12187812B2 (en) 2010-11-04 2025-01-07 Albireo Ab IBAT inhibitors for the treatment of liver diseases
US12202809B2 (en) 2019-12-04 2025-01-21 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2025043094A1 (en) 2023-08-23 2025-02-27 Assembly Biosciences, Inc. Benzothia(dia)zepine compounds for treatment of hbv and hdv
US12264159B2 (en) 2018-11-21 2025-04-01 Enanta Pharmaceuticals, Inc. Functionalized heterocycles as antiviral agents
WO2025146507A1 (en) 2024-01-05 2025-07-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2025146508A1 (en) 2024-01-05 2025-07-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
US12365658B2 (en) 2021-06-03 2025-07-22 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
US12447156B2 (en) 2020-11-12 2025-10-21 Albireo Ab Treating progressive familial intrahepatic cholestasis (PFIC) with IBAT inhibitors
US12496282B2 (en) 2017-08-28 2025-12-16 Enanta Pharmaceuticals, Inc. Hepatitis B antiviral agents
US12508234B2 (en) 2018-06-20 2025-12-30 Albireo Ab Pharmaceutical formulation of odevixibat
WO2026038156A1 (en) 2024-08-15 2026-02-19 Assembly Biosciences, Inc. Novel crystalline forms
US12617774B2 (en) 2025-05-30 2026-05-05 Novartis Ag Substituted indole compounds and methods of use thereof

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106659726A (zh) 2014-06-25 2017-05-10 Ea制药株式会社 固体制剂及其着色防止或着色减少方法
TWI835997B (zh) 2019-02-06 2024-03-21 瑞典商艾爾比瑞歐公司 苯并噻氮呯化合物及其用作膽酸調節劑之用途
ES2973355T3 (es) 2019-12-04 2024-06-19 Albireo Ab Compuestos de benzotia(di)azepina y su uso como moduladores del ácido biliar

Citations (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0489423A1 (de) 1990-12-06 1992-06-10 Hoechst Aktiengesellschaft Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindung als Arzneimittel
EP0549967A1 (de) 1991-12-20 1993-07-07 Hoechst Aktiengesellschaft Polymere und Oligomere von Gallensäurederivaten, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
WO1993016055A1 (en) 1992-02-17 1993-08-19 The Wellcome Foundation Limited Hypolipidaemic benzothiazepine compounds
EP0573848A2 (de) 1992-06-12 1993-12-15 Hoechst Aktiengesellschaft Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel
WO1994018183A1 (en) 1993-02-15 1994-08-18 The Wellcome Foundation Limited Hypolipidaemic condensed 1,4-thiazepines
WO1994018184A1 (en) 1993-02-15 1994-08-18 The Wellcome Foundation Limited Hypolipidaemic compounds
EP0624593A2 (de) 1993-05-08 1994-11-17 Hoechst Aktiengesellschaft Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel
EP0624596A2 (de) 1993-05-08 1994-11-17 Hoechst Aktiengesellschaft Tetrazolderivate von Gallebnsäuren, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel
EP0624594A2 (de) 1993-05-08 1994-11-17 Hoechst Aktiengesellschaft Monomere Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel
EP0624595A2 (de) 1993-05-08 1994-11-17 Hoechst Aktiengesellschaft nor-Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel
WO1996005188A1 (en) 1994-08-10 1996-02-22 The Wellcome Foundation Limited Hypolipidemic 1,4-benzothiazepine-1,1-dioxides
WO1996008484A1 (en) 1994-09-13 1996-03-21 Monsanto Company Novel benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
WO1996016051A1 (en) 1994-11-17 1996-05-30 The Wellcome Foundation Limited Hypolipidemic benzothiazepines
EP0864582A2 (en) 1997-03-14 1998-09-16 Hoechst Aktiengesellschaft Hypolipidemic 1,4-benzothiazepine-1,-dioxides
DE19825804A1 (de) 1998-06-10 1999-12-16 Hoechst Marion Roussel De Gmbh 1,4-Benzothiazepin-1,1-dioxidderivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung
EP1173205A1 (en) 1999-04-19 2002-01-23 AstraZeneca AB An oral formulation for ileum administering comprising an inhibitor compound of the ileal bile acid transport
WO2003020710A1 (en) 2001-09-04 2003-03-13 Astrazeneca Ab Benzothiazepine derivatives
WO2003022286A1 (en) 2001-09-08 2003-03-20 Astrazeneca Ab Benzothiazepine and benzothiadiazepine derivatives with ileal bile acid transport (ibat) inhibitory activity for the treatment hyperlipidaemia
WO2003022830A1 (en) 2001-09-07 2003-03-20 Astrazeneca Ab Benzothiepine ileal bile acid transport inhibitors
WO2003022825A1 (en) 2001-09-07 2003-03-20 Astrazeneca Ab Benzothiazepine derivatives for the treatment of hyperlipidemia
WO2003061663A1 (en) 2002-01-26 2003-07-31 Astrazeneca Ab Use of benzothiazepines having activity as inhibitors of ileal bile acid transport for reducing cholesterololemia
WO2003091232A2 (en) 2002-04-25 2003-11-06 Astrazeneca Ab Benzothiadiazepine derivatives, processes for their preparation and pharmaceutical compositions containing them
WO2003106482A1 (en) 2002-06-14 2003-12-24 Astrazeneca Ab Peptides derivatives comprising thiazepine group for the treatment of hyperlipidemic conditions
WO2004006899A1 (en) 2002-07-13 2004-01-22 Astrazeneca Ab Combination of an ibat inhibitor and a metal salt for the treatment of diarrhoea
WO2004076430A1 (en) 2003-02-25 2004-09-10 Astrazeneca Ab Benzothiazepine and benzothiepine derivatives
EP1535913A1 (en) 2002-08-28 2005-06-01 Asahi Kasei Pharma Corporation Novel quaternary ammonium compounds
US20050215882A1 (en) 2004-03-23 2005-09-29 The Regents Of The University Of Michigan Noninvasive method to determine fat content of tissues using MRI
WO2007009656A2 (de) 2005-07-15 2007-01-25 Sanofi-Aventis Deutschland Gmbh Neues 1,4-benzothiazepin-1,1-dioxidderivat mit verbesserten eigenschaften, verfahren zu dessen herstellung, diese verbindung enthaltende arzneimittel und dessen verwendung
WO2007009655A1 (de) 2005-07-15 2007-01-25 Sanofi-Aventis Deutschland Gmbh 1,4-BENZOTHIAZEPIN-l, 1-DIOXIDDERIVAT, VERFAHREN ZU DESSEN HERSTELLUNG, DIESE VERBINDUNG ENTHALTENDE ARZNEIMITTEL UND DESSEN VERWENDUNG ALS HYPOLIPIDÄMIKUM
WO2011137135A1 (en) 2010-04-27 2011-11-03 Glaxosmithkline Llc Chemical compounds
WO2013063526A1 (en) * 2011-10-28 2013-05-02 Lumena Pharmaceuticals, Inc. Bile acid recycling inhibitors for treatment of hypercholemia and cholestatic liver disease
US9295677B2 (en) 2008-02-26 2016-03-29 Qing Bile Therapeutics Inc. Polyhydroxylated bile acids for treatment of biliary disorders
US20160146715A1 (en) 2014-11-21 2016-05-26 Samsung Display Co., Ltd. Dust sensor and electronic product using the same
WO2017138877A1 (en) 2016-02-09 2017-08-17 Albireo Ab Oral cholestyramine formulation and use thereof
WO2017138878A1 (en) 2016-02-09 2017-08-17 Albireo Ab Oral cholestyramine formulation and use thereof
EP3210977A2 (en) 2014-10-20 2017-08-30 CJ Healthcare Corporation Novel aminoalkyl benzothiazepine derivative and use thereof
US9872844B2 (en) 2014-02-27 2018-01-23 Nusirt Sciences, Inc. Compositions and methods for the reduction or prevention of hepatic steatosis
US20180140219A1 (en) 2016-11-23 2018-05-24 Mayo Foundation For Medical Education And Research System and method for generating nonalcoholic fatty liver disease activity score (nas) using magnetic resonance elastography
WO2019032027A1 (en) 2017-08-09 2019-02-14 Albireo Ab CHOLESTYRAMINE TABLETS, ORAL FORMULATIONS OF CHOLESTYRAMINE AND THEIR USE
WO2019032026A1 (en) 2017-08-09 2019-02-14 Albireo Ab CHOLESTYRAMINE GRANULES, ORAL FORMULATIONS OF CHOLESTYRAMINE AND THEIR USE
US20200247769A1 (en) * 2019-02-06 2020-08-06 Albireo Ab Benzothiadiazepine compounds and their use as bile acid modulators
US20200247768A1 (en) * 2019-02-06 2020-08-06 Albireo Ab Benzothiazepine compounds and their use as bile acid modulators
WO2021110886A1 (en) 2019-12-04 2021-06-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2021110887A1 (en) 2019-12-04 2021-06-10 Albireo Ab Benzothiazepine compounds and their use as bile acid modulators
WO2021110883A1 (en) 2019-12-04 2021-06-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2021110885A1 (en) 2019-12-04 2021-06-10 Albireo Ab Benzothiadiazepine compounds and their use as bile acid modulators
WO2022029101A1 (en) 2020-08-03 2022-02-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators

Family Cites Families (128)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3539380A (en) 1968-01-08 1970-11-10 Upjohn Co Methylcellulose and polyalkylene glycol coating of solid medicinal dosage forms
GB1573487A (en) 1977-05-23 1980-08-28 Bristol Myers Co Bile acid binding composition
EP0019115B1 (de) 1979-04-30 1983-01-12 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Pankreozymin-Cholezystokinin aktive Peptide, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel
CA1313135C (en) 1987-02-09 1993-01-26 The Dow Chemical Company Cholestyramine composition and process for its preparation
US5167965A (en) 1987-02-09 1992-12-01 The Dow Chemical Company Palatable cholestyramine granules, tablets and methods for preparation thereof
US4900757A (en) 1988-12-08 1990-02-13 Merrell Dow Pharmaceuticals Inc. Hypocholesterolemic and antiatherosclerotic uses of bix(3,5-di-tertiary-butyl-4-hydroxyphenylthio)methane
JP2800242B2 (ja) 1989-03-30 1998-09-21 大正製薬株式会社 粒剤の製造方法
IL95574A (en) 1989-09-09 1994-11-11 Knoll Ag Colestyramine preparation
DE3930168A1 (de) 1989-09-09 1991-03-14 Knoll Ag Verbesserte verabreichungsform fuer colestyramin
JP2542122B2 (ja) 1990-04-18 1996-10-09 旭化成工業株式会社 球状核、球形顆粒およびその製造方法
JPH05186357A (ja) 1991-12-31 1993-07-27 Shigeo Ochi 飲食物消化分解産物吸収抑制手段
US5350584A (en) 1992-06-26 1994-09-27 Merck & Co., Inc. Spheronization process using charged resins
US5994391A (en) 1994-09-13 1999-11-30 G.D. Searle And Company Benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
US6262277B1 (en) 1994-09-13 2001-07-17 G.D. Searle And Company Intermediates and processes for the preparation of benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
US6642268B2 (en) 1994-09-13 2003-11-04 G.D. Searle & Co. Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors
US5811388A (en) 1995-06-07 1998-09-22 Cibus Pharmaceutical, Inc. Delivery of drugs to the lower GI tract
AU724620B2 (en) 1996-01-16 2000-09-28 Sokol, Ronald J Dr. Use of antioxidant agents to treat cholestatic liver disease
DE19608592A1 (de) 1996-03-06 1997-09-11 Hoechst Ag Antikörper zur selektiven immunologischen Bestimmung von Gallensäuren in biologischen Matrices
HUP9903047A3 (en) 1996-03-11 2002-12-28 G D Searle & Co Chicago Novel benzothiazepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
CA2253593C (en) 1996-05-23 2008-07-08 Novartis Ag Prevention and treatment of colorectal cancer by 6-fluoroursodeoxycholic acid (6-fudca)
AU3940897A (en) 1996-07-24 1998-02-10 Zumtobel Staff Gmbh Adapter for a retaining means used to secure a built-in lamp in a mounting hole,or retaining means or built-in lamp provided with such an adapter
DE19633268A1 (de) 1996-08-19 1998-02-26 Hoechst Ag Polymere Gallensäure-Resorptionsinhibitoren mit gleichzeitiger Gallensäure-Adsorberwirkung
GB9704208D0 (en) 1997-02-28 1997-04-16 Glaxo Group Ltd Chemical compounds
PL336415A1 (en) 1997-03-11 2000-06-19 Searle & Co Combined therapy employing ileic bile acid transport inhibiting benzothiepins as well as a hmg co-enzyme reductase inhibitors
US6635280B2 (en) 1997-06-06 2003-10-21 Depomed, Inc. Extending the duration of drug release within the stomach during the fed mode
WO1998055107A1 (en) 1997-06-06 1998-12-10 Depomed, Inc. Gastric-retentive oral drug dosage forms for controlled release of highly soluble drugs
AU7552198A (en) 1997-06-11 1998-12-30 Sankyo Company Limited Benzylamine derivatives
AUPO763197A0 (en) 1997-06-30 1997-07-24 Sigma Pharmaceuticals Pty Ltd Health supplement
US5900233A (en) 1997-10-16 1999-05-04 Day; Charles E. Epichlorohydrin and 1-(3-aminopropyl) imidazole copolymer and its use in treating irritable bowel syndrome
US20030153541A1 (en) 1997-10-31 2003-08-14 Robert Dudley Novel anticholesterol compositions and method for using same
ATE234829T1 (de) 1997-12-19 2003-04-15 Searle & Co Verfahren zu herstellung von enantiomerisch- anreicherte tetrahydrobenzothiepin oxyden
GB9800428D0 (en) 1998-01-10 1998-03-04 Glaxo Group Ltd Chemical compounds
US6346527B1 (en) 1998-04-24 2002-02-12 Fujisawa Pharmaceutical Co., Ltd. Guanidine derivatives
US6221897B1 (en) 1998-06-10 2001-04-24 Aventis Pharma Deutschland Gmbh Benzothiepine 1,1-dioxide derivatives, a process for their preparation, pharmaceuticals comprising these compounds, and their use
EP1103552A4 (en) 1998-08-07 2003-01-15 Takeda Chemical Industries Ltd BENZOTHIEPINE DERIVATIVES, METHOD FOR THEIR PRODUCTION AND THEIR USE
JP2002533415A (ja) 1998-12-23 2002-10-08 ジー．ディー．サール エルエルシー 心臓血管に適用するための回腸胆汁酸輸送阻害剤およびニコチン酸誘導体の組み合わせ
KR20020002367A (ko) 1998-12-23 2002-01-09 윌리암스 로저 에이 심혈관 징후를 위한 조합물
WO2000038727A1 (en) 1998-12-23 2000-07-06 G.D. Searle Llc Combinations of ileal bile acid transport inhibitors and fibric acid derivatives for cardiovascular indications
PT1140190E (pt) 1998-12-23 2003-02-28 Searle Llc Combinacoes de inibidores do transporte ileal dos acidos biliares e agentes sequestrantes dos acidos biliares usadas para problemas cardiovasculares
JP2002533412A (ja) 1998-12-23 2002-10-08 ジー．ディー．サール エルエルシー 心臓血管に適用するための回腸胆汁酸輸送阻害剤およびコレステリルエステル転送タンパク質阻害剤の組み合わせ
JP2002536440A (ja) 1999-02-12 2002-10-29 ジー．ディー．サール エルエルシー 回腸胆汁酸輸送およびタウロコール酸塩取り込みの阻害剤としての活性を有する新規１，２−ベンゾチアゼピン
DE19916108C1 (de) 1999-04-09 2001-01-11 Aventis Pharma Gmbh Mit Zuckerresten substituierte 1,4-Benzothiazepin-1,1-dioxidderivate, Verfahren zu deren Herstellung und deren Verwendung
US6287609B1 (en) 1999-06-09 2001-09-11 Wisconsin Alumni Research Foundation Unfermented gel fraction from psyllium seed husks
AU1302301A (en) 1999-11-08 2001-06-06 Sankyo Company Limited Nitrogenous heterocycle derivatives
GB9927088D0 (en) 1999-11-17 2000-01-12 Secr Defence Use of poly(diallylamine) polymers
JP2003523336A (ja) 2000-02-18 2003-08-05 メルク エンド カムパニー インコーポレーテッド 糖尿病及び脂質障害のためのアリールオキシ酢酸
SE0000772D0 (sv) 2000-03-08 2000-03-08 Astrazeneca Ab Chemical compounds
WO2001068096A2 (en) 2000-03-10 2001-09-20 Pharmacia Corporation Combination therapy for the prophylaxis and treatment of hyperlipidemic conditions and disorders
US6586434B2 (en) 2000-03-10 2003-07-01 G.D. Searle, Llc Method for the preparation of tetrahydrobenzothiepines
US6638498B2 (en) 2000-06-30 2003-10-28 Semorex Inc. Molecularly imprinted polymers for the treatment and diagnosis of medical conditions
US20020183307A1 (en) 2000-07-26 2002-12-05 Tremont Samuel J. Novel 1,4-benzothiazephine and 1,5-benzothiazepine compounds as inhibitors of apical sodium co-dependent bile acid transport and taurocholate uptake
FR2812886B1 (fr) 2000-08-08 2002-11-08 Assist Publ Hopitaux De Paris Depistage d'un nouveau syndrome hepatique et ses applications
SE0003766D0 (sv) 2000-10-18 2000-10-18 Astrazeneca Ab Novel formulation
EG26979A (en) 2000-12-21 2015-03-01 Astrazeneca Ab Chemical compounds
WO2002053548A1 (fr) 2000-12-27 2002-07-11 Banyu Pharmaceutical Co.,Ltd. Derives de la benzothiazepine
US6506921B1 (en) 2001-06-29 2003-01-14 Virginia Tech Intellectual Properties, Inc. Amine compounds and curable compositions derived therefrom
US20040077625A1 (en) 2001-07-25 2004-04-22 Tremont Samuel J. Novel 1,4-benzothiazepine and 1,5-benzothiazepine compounds as inhibitors of apical sodium codependent bile acid transport abd taurocholate uptake
US20040038862A1 (en) 2001-07-30 2004-02-26 Goodwin Bryan James Identification of new therapeutic targets for modulating bile acid synthesis
AU2002332638A1 (en) 2001-09-12 2003-03-24 G.D. Searle Llc Method for the preparation of crystalline tetrahydrobenzothiepines
BR0213501A (pt) 2001-11-02 2004-08-24 Searle Llc Compostos de benzotiepina mono- e di-fluorada como inibidores de transporte de ácido biliar co-dependente de sódio apical (asbt) e captação de taurocolato
TW200300349A (en) 2001-11-19 2003-06-01 Sankyo Co A 4-oxoqinoline derivative
GB0314079D0 (en) 2003-06-18 2003-07-23 Astrazeneca Ab Therapeutic agents
SE0104334D0 (sv) 2001-12-19 2001-12-19 Astrazeneca Ab Therapeutic agents
GB0229931D0 (en) 2002-12-21 2003-01-29 Astrazeneca Ab Therapeutic agents
WO2003059378A2 (en) 2001-12-29 2003-07-24 Novo Nordisk A/S Combined use of a glp-1 compound and another drug for treating dyslipidemia
US20040014806A1 (en) 2002-03-08 2004-01-22 Pharmacia Corporation Methods and compositions for lowering levels of blood lipids
US7312208B2 (en) 2002-08-28 2007-12-25 Asahi Kasei Pharma Corporation Quaternary ammonium compounds
WO2004076657A2 (en) 2003-02-28 2004-09-10 Mcgill University Cell and enzyme compositions for modulating bile acids, cholesterol and triglycerides
GB0307918D0 (en) 2003-04-05 2003-05-14 Astrazeneca Ab Therapeutic use
WO2005036971A1 (en) 2003-10-16 2005-04-28 Techcom Group, Llc Reduced digestible carbohydrate food having reduced blood glucose response
KR20070026392A (ko) 2004-02-27 2007-03-08 아사히 가세이 파마 가부시키가이샤 신규 벤조티아제핀 및 벤조티에핀 화합물
US20050197376A1 (en) 2004-03-02 2005-09-08 Fujisawa Pharmaceutical Co. Ltd. Concomitant drugs
EP1593671A1 (en) 2004-03-05 2005-11-09 Graffinity Pharmaceuticals AG DPP-IV inhibitors
TWI415635B (zh) 2004-05-28 2013-11-21 必治妥施貴寶公司 加衣錠片調製物及製備彼之方法
US20050287178A1 (en) 2004-06-23 2005-12-29 Steed Barrie L Diagnosis and treatment of heavy gallbladder densities
US20090131395A1 (en) 2005-05-05 2009-05-21 Microbia, Inc. Biphenylazetidinone cholesterol absorption inhibitors
EP1928499B1 (en) 2005-09-20 2011-06-29 Novartis AG Use of a dpp-iv inhibitor to reduce hypoglycemic events
WO2007120592A1 (en) 2006-04-10 2007-10-25 Merck & Co., Inc. Cgrp antagonist salt
US8048413B2 (en) 2006-05-17 2011-11-01 Helene Huguet Site-specific intestinal delivery of adsorbents, alone or in combination with degrading molecules
DE502007006208D1 (de) 2006-11-14 2011-02-17 Sanofi Aventis Deutschland Neue 1,4-benzothiepin-1,1-dioxidderivate mit verbesserten eigenschaften, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung
DE102006053637B4 (de) 2006-11-14 2011-06-30 Sanofi-Aventis Deutschland GmbH, 65929 Neue mit Fluor substituierte 1,4-Benzothiepin-1,1-Dioxidderivate, diese Verbindungen enthaltende Arzneimittel und deren Verwendung
DE102006053635B4 (de) 2006-11-14 2011-06-30 Sanofi-Aventis Deutschland GmbH, 65929 Neue mit Benzylresten substituierte 1,4-Benzothiepin-1,1-Dioxidderivate, diese Verbindungen enthaltende Arzneimittel und deren Verwendung
DE102006053636B4 (de) 2006-11-14 2008-09-18 Sanofi-Aventis Deutschland Gmbh Neue mit Cyclohexylresten substituierte 1,4-Benzothiepin-1,1-Dioxidderivate und deren Verwendung
AU2008209566C1 (en) 2007-01-19 2013-02-14 Intercept Pharmaceuticals, Inc. 23-substituted bile acids as TGR5 modulators and methods of use thereof
ATE476176T1 (de) 2007-03-02 2010-08-15 Farnam Co Inc Wachsähnliches material enthaltende tabletten mit verzögerter freisetzung
BRPI0918499A2 (pt) 2008-09-02 2015-12-01 Usv Ltd polímeros reticulados
WO2010062861A2 (en) 2008-11-26 2010-06-03 Satiogen Pharmaceuticals, Inc. Bile acid recycling inhibitors for treatment of obesity and diabetes
FR2943342B1 (fr) 2009-03-20 2011-03-04 Servier Lab Nouveaux derives de benzothiadiazepines,leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
WO2011075539A2 (en) 2009-12-18 2011-06-23 Satiogen Pharmaceuticals, Inc. Treatment of obesity or diabetes with bile acid sequestrants
ES2552657T3 (es) 2010-05-26 2015-12-01 Satiogen Pharmaceuticals, Inc. Inhibidores del reciclado de ácidos biliares y saciógenos para el tratamiento de diabetes, obesidad, y afecciones gastrointestinales inflamatorias
ES2687027T3 (es) 2010-11-04 2018-10-23 Albireo Ab Inhibidores de ibat para el tratamiento de enfermedades hepáticas
US20120114588A1 (en) 2010-11-08 2012-05-10 Albireo Ab Ibat inhibitors for treatment of metabolic disorders and related conditions
WO2012064268A1 (en) 2010-11-08 2012-05-18 Albireo Ab Ibat inhibitors for treatment of metabolic disorders and related conditions
DK2637646T3 (en) 2010-11-08 2016-08-29 Albireo Ab PHARMACEUTICAL COMBINATION CONTAINING AN IBAT inhibitor and a bile acid binder
AU2012328526B2 (en) 2011-10-28 2017-05-25 Shire Human Genetic Therapies, Inc. Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases
JP5663699B2 (ja) 2012-05-07 2015-02-04 キッセイ薬品工業株式会社 ピラゾール誘導体及びその医薬用途
CA2907230A1 (en) 2013-03-15 2014-09-18 Lumena Pharmaceuticals, Inc. Bile acid recycling inhibitors for treatment of primary sclerosing cholangitis and inflammatory bowel disease
JO3301B1 (ar) 2013-04-26 2018-09-16 Albireo Ab تعديلات بلورية على إيلوبيكسيبات
CN106659726A (zh) 2014-06-25 2017-05-10 Ea制药株式会社 固体制剂及其着色防止或着色减少方法
CA2952405A1 (en) 2014-06-25 2015-12-30 Ea Pharma Co., Ltd. Solid formulation and method for stabilizing the same
EP3012252A1 (en) 2014-10-24 2016-04-27 Ferring BV Crystal modifications of elobixibat
US9684018B2 (en) 2014-11-19 2017-06-20 Texas Instruments Incorporated Current sense circuit that operates over a wide range of currents
CN108601739B (zh) 2016-02-09 2022-01-04 阿尔比里奥公司 考来烯胺丸剂及其制备方法
KR101844184B1 (ko) 2017-07-21 2018-04-02 씨제이헬스케어 주식회사 아미노알킬벤조티아제핀 유도체의 용도
CA3091338A1 (en) 2018-03-09 2019-09-12 Elobix Ab Process for the preparation of elobixibat
CN112449637B (zh) 2018-06-05 2024-03-19 阿尔比里奥公司 苯并硫杂(二)氮杂环庚三烯化合物及其作为胆汁酸调节剂的用途
PL3810581T3 (pl) 2018-06-20 2025-04-28 Albireo Ab Modyfikacje kryształu odewiksibatu
US11801226B2 (en) 2018-06-20 2023-10-31 Albireo Ab Pharmaceutical formulation of odevixibat
AU2019350487A1 (en) 2018-09-27 2021-05-13 Albireo Energy, Llc System, apparatus and hybrid VAV device with multiple heating coils
EP3923943B1 (en) 2019-02-12 2024-07-31 Mirum Pharmaceuticals, Inc. Genotype and dose-dependent response to an asbti in patients with bile salt export pump deficiency
US20220105218A1 (en) 2019-02-15 2022-04-07 The Board Of Trustees Of The Leland Standford Junior University Methods and systems for reducing a pathogen population
WO2020194531A1 (ja) 2019-03-26 2020-10-01 国立大学法人東北大学 血中尿毒症物質の低減剤
JP7696898B2 (ja) 2019-12-04 2025-06-23 アルビレオ・アクチボラグ ベンゾチア（ジ）アゼピン化合物及び胆汁酸モジュレータとしてのそれらの使用
IL293379B2 (en) 2019-12-04 2026-04-01 Albireo Ab Benzothia(dia)azepine compounds and their use as bile acid modulators
US11014898B1 (en) 2020-12-04 2021-05-25 Albireo Ab Benzothiazepine compounds and their use as bile acid modulators
WO2021110884A1 (en) 2019-12-04 2021-06-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
EP4069247B1 (en) 2019-12-04 2025-03-26 Albireo AB Benzothiadiazepine compounds and their use as bile acid modulators
ES2973355T3 (es) 2019-12-04 2024-06-19 Albireo Ab Compuestos de benzotia(di)azepina y su uso como moduladores del ácido biliar
EP4188541B1 (en) * 2020-08-03 2024-12-25 Albireo AB Benzothia(di)azepine compounds and their use as bile acid modulators
CA3196488A1 (en) 2020-11-12 2022-05-19 Albireo Ab Odevixibat for treating progressive familial intrahepatic cholestasis (pfic)
WO2022101379A1 (en) 2020-11-12 2022-05-19 Albireo Ab Odevixibat for treating progressive familial intrahepatic cholestasis (pfic)
BR112023010799A2 (pt) 2020-12-04 2023-10-03 Albireo Ab Compostos de benzotia(di)azepina e seus usos como moduladores de ácidos biliares
TW202313579A (zh) 2021-06-03 2023-04-01 瑞典商艾爾比瑞歐公司 苯并噻(二)氮呯(benzothia(di)azepine)化合物及其作為膽酸調節劑之用途
EP4511038A1 (en) 2022-04-22 2025-02-26 Albireo AB Subcutaneous administration of an asbt inhibitor
KR20250022025A (ko) 2022-06-09 2025-02-14 알비레오 에이비 간염 치료
CN119487013A (zh) 2022-07-05 2025-02-18 阿尔比里奥公司 苯并硫杂(二)氮杂环庚三烯化合物及其作为胆汁酸调节剂的用途
CN120379676A (zh) 2022-11-03 2025-07-25 阿尔比里奥公司 治疗阿拉杰里综合征(algs)
AU2023390975A1 (en) 2022-12-09 2025-06-05 Albireo Ab Asbt inhibitors in the treatment of renal diseases

Patent Citations (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0489423A1 (de) 1990-12-06 1992-06-10 Hoechst Aktiengesellschaft Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindung als Arzneimittel
EP0549967A1 (de) 1991-12-20 1993-07-07 Hoechst Aktiengesellschaft Polymere und Oligomere von Gallensäurederivaten, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
WO1993016055A1 (en) 1992-02-17 1993-08-19 The Wellcome Foundation Limited Hypolipidaemic benzothiazepine compounds
EP0573848A2 (de) 1992-06-12 1993-12-15 Hoechst Aktiengesellschaft Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel
WO1994018183A1 (en) 1993-02-15 1994-08-18 The Wellcome Foundation Limited Hypolipidaemic condensed 1,4-thiazepines
WO1994018184A1 (en) 1993-02-15 1994-08-18 The Wellcome Foundation Limited Hypolipidaemic compounds
EP0624593A2 (de) 1993-05-08 1994-11-17 Hoechst Aktiengesellschaft Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel
EP0624596A2 (de) 1993-05-08 1994-11-17 Hoechst Aktiengesellschaft Tetrazolderivate von Gallebnsäuren, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel
EP0624594A2 (de) 1993-05-08 1994-11-17 Hoechst Aktiengesellschaft Monomere Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel
EP0624595A2 (de) 1993-05-08 1994-11-17 Hoechst Aktiengesellschaft nor-Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel
WO1996005188A1 (en) 1994-08-10 1996-02-22 The Wellcome Foundation Limited Hypolipidemic 1,4-benzothiazepine-1,1-dioxides
WO1996008484A1 (en) 1994-09-13 1996-03-21 Monsanto Company Novel benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
WO1996016051A1 (en) 1994-11-17 1996-05-30 The Wellcome Foundation Limited Hypolipidemic benzothiazepines
EP0864582A2 (en) 1997-03-14 1998-09-16 Hoechst Aktiengesellschaft Hypolipidemic 1,4-benzothiazepine-1,-dioxides
DE19825804A1 (de) 1998-06-10 1999-12-16 Hoechst Marion Roussel De Gmbh 1,4-Benzothiazepin-1,1-dioxidderivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung
EP1173205A1 (en) 1999-04-19 2002-01-23 AstraZeneca AB An oral formulation for ileum administering comprising an inhibitor compound of the ileal bile acid transport
WO2003020710A1 (en) 2001-09-04 2003-03-13 Astrazeneca Ab Benzothiazepine derivatives
WO2003022830A1 (en) 2001-09-07 2003-03-20 Astrazeneca Ab Benzothiepine ileal bile acid transport inhibitors
WO2003022825A1 (en) 2001-09-07 2003-03-20 Astrazeneca Ab Benzothiazepine derivatives for the treatment of hyperlipidemia
WO2003022286A1 (en) 2001-09-08 2003-03-20 Astrazeneca Ab Benzothiazepine and benzothiadiazepine derivatives with ileal bile acid transport (ibat) inhibitory activity for the treatment hyperlipidaemia
WO2003061663A1 (en) 2002-01-26 2003-07-31 Astrazeneca Ab Use of benzothiazepines having activity as inhibitors of ileal bile acid transport for reducing cholesterololemia
WO2003091232A2 (en) 2002-04-25 2003-11-06 Astrazeneca Ab Benzothiadiazepine derivatives, processes for their preparation and pharmaceutical compositions containing them
WO2003106482A1 (en) 2002-06-14 2003-12-24 Astrazeneca Ab Peptides derivatives comprising thiazepine group for the treatment of hyperlipidemic conditions
WO2004006899A1 (en) 2002-07-13 2004-01-22 Astrazeneca Ab Combination of an ibat inhibitor and a metal salt for the treatment of diarrhoea
EP1535913A1 (en) 2002-08-28 2005-06-01 Asahi Kasei Pharma Corporation Novel quaternary ammonium compounds
WO2004076430A1 (en) 2003-02-25 2004-09-10 Astrazeneca Ab Benzothiazepine and benzothiepine derivatives
US20050215882A1 (en) 2004-03-23 2005-09-29 The Regents Of The University Of Michigan Noninvasive method to determine fat content of tissues using MRI
WO2007009656A2 (de) 2005-07-15 2007-01-25 Sanofi-Aventis Deutschland Gmbh Neues 1,4-benzothiazepin-1,1-dioxidderivat mit verbesserten eigenschaften, verfahren zu dessen herstellung, diese verbindung enthaltende arzneimittel und dessen verwendung
WO2007009655A1 (de) 2005-07-15 2007-01-25 Sanofi-Aventis Deutschland Gmbh 1,4-BENZOTHIAZEPIN-l, 1-DIOXIDDERIVAT, VERFAHREN ZU DESSEN HERSTELLUNG, DIESE VERBINDUNG ENTHALTENDE ARZNEIMITTEL UND DESSEN VERWENDUNG ALS HYPOLIPIDÄMIKUM
US9295677B2 (en) 2008-02-26 2016-03-29 Qing Bile Therapeutics Inc. Polyhydroxylated bile acids for treatment of biliary disorders
WO2011137135A1 (en) 2010-04-27 2011-11-03 Glaxosmithkline Llc Chemical compounds
WO2013063526A1 (en) * 2011-10-28 2013-05-02 Lumena Pharmaceuticals, Inc. Bile acid recycling inhibitors for treatment of hypercholemia and cholestatic liver disease
US9872844B2 (en) 2014-02-27 2018-01-23 Nusirt Sciences, Inc. Compositions and methods for the reduction or prevention of hepatic steatosis
EP3210977A2 (en) 2014-10-20 2017-08-30 CJ Healthcare Corporation Novel aminoalkyl benzothiazepine derivative and use thereof
US20160146715A1 (en) 2014-11-21 2016-05-26 Samsung Display Co., Ltd. Dust sensor and electronic product using the same
WO2017138878A1 (en) 2016-02-09 2017-08-17 Albireo Ab Oral cholestyramine formulation and use thereof
WO2017138877A1 (en) 2016-02-09 2017-08-17 Albireo Ab Oral cholestyramine formulation and use thereof
US20180140219A1 (en) 2016-11-23 2018-05-24 Mayo Foundation For Medical Education And Research System and method for generating nonalcoholic fatty liver disease activity score (nas) using magnetic resonance elastography
WO2019032027A1 (en) 2017-08-09 2019-02-14 Albireo Ab CHOLESTYRAMINE TABLETS, ORAL FORMULATIONS OF CHOLESTYRAMINE AND THEIR USE
WO2019032026A1 (en) 2017-08-09 2019-02-14 Albireo Ab CHOLESTYRAMINE GRANULES, ORAL FORMULATIONS OF CHOLESTYRAMINE AND THEIR USE
US20200247769A1 (en) * 2019-02-06 2020-08-06 Albireo Ab Benzothiadiazepine compounds and their use as bile acid modulators
US20200247768A1 (en) * 2019-02-06 2020-08-06 Albireo Ab Benzothiazepine compounds and their use as bile acid modulators
WO2021110886A1 (en) 2019-12-04 2021-06-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2021110887A1 (en) 2019-12-04 2021-06-10 Albireo Ab Benzothiazepine compounds and their use as bile acid modulators
WO2021110883A1 (en) 2019-12-04 2021-06-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2021110885A1 (en) 2019-12-04 2021-06-10 Albireo Ab Benzothiadiazepine compounds and their use as bile acid modulators
WO2022029101A1 (en) 2020-08-03 2022-02-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators

Non-Patent Citations (134)

* Cited by examiner, † Cited by third party
Title
ADAMS ET AL., CLIN CHEM., vol. 51, no. 10, 2005, pages 1867 - 1873
ADAMS ET AL., CLIN. CHEM., vol. 51, no. 10, 2005, pages 1867 - 1873
ALASHKAR ET AL., BLOOD, vol. 126, no. 23, 2015
ALVAREZ ET AL., HUM MOL GENET, vol. 13, no. 20, 2004, pages 2451 - 2460
ANGULO ET AL., HEPATOLOGY, vol. 45, no. 4, 2007, pages 846 - 54
ANZIVINO ET AL., DIG LIVER DIS, vol. 45, no. 3, 2013, pages 226 - 232
ARNELL ET AL., J PEDIATR GASTROENTEROL NUTR, vol. 51, no. 4, 2010, pages 494 - 499
BEAUSEJOUR ET AL., CAN J GASTROENTEROL, vol. 25, no. 6, 2011, pages 311 - 314
BLACKMORE ET AL., J CLIN EXP HEPATOL, vol. 3, no. 2, 2013, pages 159 - 161
BRUNT ET AL., AM J GASTROENTEROL, vol. 94, 1999, pages 2467 - 2474
BRUNT ET AL., AM. J. GASTROENTEROL., vol. 94, 1999, pages 2467 - 2474
CHALASANI ET AL., HEPATOLOGY, vol. 67, no. 1, 2018, pages 1531 - 1545
CHEN ET AL., J PEDIATR, vol. 153, no. 6, 2008, pages 825 - 832
CHEN ET AL., JOURNAL OF PEDIATRICS, vol. 140, no. 1, 2002, pages 119 - 124
CHIANG, J. LIPID RES., vol. 50, 2009, pages 1955 - 1966
COPELAND ET AL., J GASTROENTEROL HEPATOL, vol. 28, no. 3, 2013, pages 560 - 564
DANESE ET AL., PLOS ONE, vol. 12, no. 6, 2017, pages e0179200
DAVIT-SPRAUL ET AL., HEPATOLOGY, vol. 51, no. 5, 2010, pages 1645 - 1655
DAVIT-SPRAUL ET AL., MOL GENET METAB, vol. 113, no. 3, 2014, pages 225 - 229
DENG ET AL., WORLD J GASTROENTEROL, vol. 18, no. 44, 2012, pages 6504 - 6509
DI LASCIO ET AL., ULTRASOUND MED BIOL, vol. 44, no. 8, 2018, pages 1585 - 1596
DIXON ET AL., SCIENTIFIC REPORTS, vol. 7, no. 9214, 2017, pages 11823 - 7
DONG ET AL., MOL. PHARM., vol. 10, 2013, pages 1008 - 1019
DROGE ET AL., J HEPATOL, vol. 67, no. 6, 2017, pages 1253 - 1264
DROGE ET AL., SCI REP, vol. 6, 2016, pages 24827
DROGE ET AL., ZEITSCHRIFT FUR GASTROENTEROLOGIE, vol. 53, no. 12, 2015
ELLINGER ET AL., WORLD J GASTROENTEROL, vol. 23, no. 29, 2017, pages 5295 - 5303
EVASON ET AL., AM J SURG PATHOL, vol. 35, no. 5, 2011, pages 687 - 696
FERREIRA ET AL., PEDIATRIC TRANSPLANTATION, vol. 17, 2013, pages 99
FERSLEW ET AL., DIG DIS SCI, vol. 60, 2015, pages 3318 - 3328
FOLMER ET AL., HEPATOLOGY, vol. 49, no. 2, 2009, pages 1597 - 1605
FRANCALANCI ET AL., DIGESTIVE AND LIVER DISEASE, vol. 42, 2010, pages S329
FRANCALANCI ET AL., LABORATORY INVESTIGATION, vol. 201, 2011, pages 360A - 203
GAO ET AL., SHANDONG YIYAO, vol. 52, no. 10, 2012, pages 14 - 16
GIOVANNONI ET AL., PLOS ONE, vol. 10, no. 12, 2015, pages e0145021
GOLDSCHMIDT ET AL., HEPATOL RES, vol. 46, no. 2, 2016, pages 192 - 200
GRIFFIN ET AL., CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, vol. 2016, 2016
GUNAYDIN, M. ET AL., HEPAT MED, vol. 10, 2018, pages 95 - 104
GUORUI ET AL., LINCHUANG ERKE ZAZHI, vol. 31, no. 10, 2013, pages 905 - 909
HAO ET AL., INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY, vol. 10, no. 3, 2017, pages 3480 - 3487
HARMANCI ET AL., EXPERIMENTAL AND CLINICAL TRANSPLANTATION, vol. 13, 2015, pages 76
HASEGAWA ET AL., ORPHANET J RARE DIS, vol. 9, 2014, pages 89
HAYSHI ET AL., EBIOMEDICINE, vol. 27, 2018, pages 187 - 199
HERBST ET AL., MOL CELL PROBES, vol. 29, no. 5, 2015, pages 291 - 298
HO ET AL., PHARMACOGENET GENOMICS, vol. 20, no. 1, 2010, pages 45 - 57
HOLZ ET AL., HEPATOL COMMUN, vol. 2, no. 2, 2018, pages 152 - 154
HOLZ ET AL., ZEITSCHRIFT FUR GASTROENTEROLOGIE, vol. 54, no. 8, 2016
HSU ET AL., HEPATOL RES, vol. 39, no. 6, 2009, pages 625 - 631
HU ET AL., MOL MED REP, vol. 10, no. 3, 2014, pages 1264 - 1274
IMAGAWA ET AL., J HUM GENET, vol. 63, no. 5, 2018, pages 569 - 577
IMAGAWA ET AL., JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, vol. 63, 2016, pages S51
IMAGAWA ET AL., SCI REP, vol. 7, 2017, pages 41806
ISHAK ET AL., J. HEPATOL., vol. 22, 1995, pages 696 - 699
IVASHKIN ET AL., HEPATOLOGY INTERNATIONAL, vol. 10, no. 1, 2016, pages S461
JANKOWSKA ET AL., J PEDIATR GASTROENTEROL NUTR, vol. 58, no. 1, 2014, pages 92 - 95
JAQUOTOT-HAERRANZ ET AL., REV ESP ENFERM DIG, vol. 105, no. 1, 2013, pages 52 - 54
JERICHO ET AL., JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, vol. 3, pages 368 - 374
JERICHO ET AL., JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, vol. 60, no. 3, 2015, pages 368 - 374
JIRSA ET AL., HEPATOL RES, vol. 30, no. 1, 2004, pages 1 - 3
KAGAWA ET AL., AM J PHYSIOL GASTROINTEST LIVER PHYSIOL, vol. 294, no. 1, 2008, pages G58 - 67
KANG ET AL., J PATHOL TRANSL MED, 16 May 2019 (2019-05-16)
KHOSLA ET AL., AMERICAN JOURNAL OF GASTROENTEROLOGY, vol. 110, 2015, pages S397
KLEINER ET AL., HEPATOLOGY, vol. 41, no. 6, 2005, pages 1313 - 1321
KLOMP ET AL., HEPATOLOGY, vol. 40, no. 1, 2004, pages 27 - 38
KNISELY ET AL., HEPATOLOGY, vol. 44, no. 2, 2006, pages 478 - 86
KOOISTRA ET AL.: "KLIFS: A structural kinase-ligand interaction database", NUCLEIC ACIDS RES, vol. 44, no. D1, 2016, pages D365 - D371
KOSTERSKARPEN, XENOBIOTICA, vol. 38, 2008, pages 1043 - 1071
KRAWCZYK ET AL., ANN HEPATOL, vol. 11, no. 5, 2012, pages 710 - 744
LAM ET AL., AM J PHYSIOL CELL PHYSIOL, vol. 293, no. 5, 2007, pages C1709 - 16
LAM ET AL., J HEPATOL, vol. 44, no. 1, 2006, pages 240 - 242
LANG ET AL., DRUG METAB DISPOS, vol. 34, no. 9, 2006, pages 1582 - 1599
LANG ET AL., PHARMACOGENET GENOMICS, vol. 17, no. 1, 2007, pages 47 - 60
LEDINGHEN V ET AL., J GASTROENTEROL HEPATOL, vol. 31, no. 4, 2016, pages 848 - 855
LEE ET AL., PEDIATR GASTROENTEROL HEPATOL NUTR, vol. 20, no. 2, 2017, pages 114 - 123
LI ET AL., HEPATOLOGY INTERNATIONAL, vol. 11, no. 1, 2017, pages S362
LI ET AL., HEPATOLOGY INTERNATIONAL, vol. 11, no. 1, pages S180
LICHTINGHAGEN ET AL., J HEPATOL, vol. 59, no. 2, 2013, pages 236 - 242
LICHTINGHAGEN R ET AL., J HEPATOL, vol. 59, no. 2, August 2013 (2013-08-01), pages 236 - 42
LIN ET AL., ZHONGGUO DANG DAI ER KE ZA ZHI., vol. 20, no. 9, 2018, pages 758 - 764
LIU ET AL., HEPATOLOGY INTERNATIONAL, vol. 3, no. 1, 2009, pages 184 - 185
LIU ET AL., LIVER INTERNATIONAL, vol. 30, no. 6, 2010, pages 809 - 815
LIU ET AL., PEDIATR INT, vol. 55, no. 2, 2013, pages 138 - 144
LV ET AL., J CLIN TRANSL HEPATOL, vol. 6, no. 2, 2018, pages 217 - 221
MAGGIORE ET AL., J HEPATOL, vol. 53, no. 5, 2010, pages 981 - 6
MASAHATA ET AL., TRANSPLANT PROC, vol. 48, no. 9, 2016, pages 3156 - 3162
MCKAY ET AL., F1000RES, vol. 2, 2013, pages 32
MCPHERSON ET AL., GUT, vol. 59, no. 9, 2010, pages 1265 - 1269
MILOH ET AL., GASTROENTEROLOGY, vol. 130, no. 4, 2006, pages A759 - A760
MIZUOCHI ET AL., CLIN CHIM ACTA, vol. 413, 2012, pages 1301 - 1304
MOGHADAMRAD ET AL., HEPATOLOGY, vol. 57, no. 6, 2013, pages 2539 - 2541
NAGASAKA ET AL., J PEDIATR GASTROENTEROL NUTR, vol. 45, no. 1, 2007, pages 453 - 105
NARCHI ET AL., SAUDI J GASTROENTEROL, vol. 23, no. 5, 2017, pages 303 - 305
NEUMAN ET AL., CAN J GASTROENTEROL HEPATOL, vol. 28, no. 11, 2014, pages 607 - 618
NEUMAN ET AL., CAN. J. GASTROENTEROL. HEPATOL., vol. 28, no. 11, 2014, pages 607 - 618
P.G.M WUTZT.W. GREENE: "Greene's Protective Groups in Organic Synthesis", 2006, JOHN WILEY & SONS
PAINTER ET AL., EUR J HUM GENET, vol. 13, no. 4, 2005, pages 435 - 439
PARK ET AL., WORLD J GASTROENTEROL, vol. 22, no. 20, 2016, pages 4901 - 4907
PAULI-MAGNUS ET AL., HEPATOLOGY, vol. 38, no. 4, 2003, pages 518A
PAULI-MAGNUS ET AL., J HEPATOL, vol. 43, no. 3, 2005, pages 536 - 543
PENG ET AL., ZHONGHUA ER KE ZA ZHI (CHINESE JOURNAL OF PEDIATRICS, vol. 56, no. 6, 2018, pages 440 - 444
PEREZ MJBRIZ O., WORLD J. GASTROENTEROL., vol. 15, no. 14, 2009, pages 1677 - 1689
QIU ET AL., HEPATOLOGY, vol. 65, no. 5, 2017, pages 1655 - 1669
REEDER ET AL., J MAGN RESON IMAGING, vol. 34, no. 4, 2011
RUMBO ET AL., TRANSPLANTATION, vol. 102, no. 7, 2018, pages S848
SATAPATHY SKSANYAL AJ, SEMIN. LIVER DIS., vol. 35, no. 3, 2015, pages 221 - 235
SATTLER ET AL., JOURNAL OF HEPATOLOGY, vol. 66, no. 1, 2017, pages S177
SCHEIMANN ET AL., GASTROENTEROLOGY, vol. 132, no. 4, 2007, pages A452
SHAH ET AL., J PEDIATR GENET, vol. 6, no. 2, 2017, pages 126 - 127
SHAPRIO ET AL., J HUM GENET, vol. 55, no. 5, 2010, pages 308 - 313
SHARMA ET AL., BMC GASTROENTEROL, vol. 18, no. 1, 2018, pages 107
SHARMA ET AL., INDIAN JOURNAL OF GASTROENTEROLOGY, vol. 36, no. 1, 2017, pages A99
SHERRIF ET AL., LIVER INTERNATIONAL: OFFICIAL JOURNAL OF THE INTERNATIONAL ASSOCIATION FOR THE STUDY OF THE LIVER, vol. 33, no. 8, 2013, pages 1266 - 1270
SHIMIZU ET AL., AM J TRANSPLANT, vol. 11, no. 2, 2011, pages 394 - 398
SOHN ET AL., PEDIATR GASTROENTEROL HEPATOL NUTR, vol. 22, no. 2, 2019, pages 201 - 206
SORRENTINO P ET AL., DIG. DIS. SCI., vol. 50, no. 6, 2005, pages 1130 - 1135
SQUIRES ET AL., J PEDIATR GASTROENTEROL NUTR, vol. 64, no. 3, 2017, pages 425 - 430
STINDT ET AL., LIVER INT, vol. 33, no. 10, 2013, pages 1527 - 1735
STOLZ ET AL., ALIMENT PHARMACOL THER, vol. 49, no. 9, 2019, pages 1195 - 1204
STONE ET AL., J BIOL CHEM, vol. 287, no. 49, 2012, pages 41139 - 51
STRAUTNIEKS ET AL., GASTROENTEROLOGY, vol. 134, no. 4, 2008, pages 1203 - 1214
TAKAHASHI ET AL., EUR J GASTROENTEROL HEPATOL, vol. 19, no. 11, 2007, pages 942 - 6
TIBESAR ET AL., CASE REP PEDIATR, vol. 2014, 2014, pages 185923
TOGAWA ET AL., JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, vol. 66, 2018, pages S363
TREEPONGKARUNA ET AL., WORLD J GASTROENTEROL, vol. 15, no. 34, 2009, pages 4339 - 4342
UEGAKI ET AL., INTERN MED, vol. 47, no. 7, 2008, pages 599 - 602
VAN DER WOERD ET AL., HEPATOLOGY, vol. 62, no. 1, 2015, pages 1382 - 1391
VAN DER WOERD ET AL., PLOS ONE, vol. 8, no. 11, 2013, pages e80553
VAN MIL ET AL., GASTROENTEROLOGY, vol. 127, no. 2, 2004, pages 379 - 384
VITALE ET AL., J GASTROENTEROL, vol. 53, no. 8, 2018, pages 945 - 958
WAISBOURD-ZINMAN ET AL., ANN HEPATOL, vol. 16, no. 3, 2017, pages 465 - 468
WANG ET AL., HEPATOL RES, vol. 48, no. 7, 2018, pages 574 - 584
WANG ET AL., PLOS ONE, vol. 11, no. 4, 2016, pages e0153114
WONG ET AL., CLIN CHEM, vol. 54, no. 7, 2008, pages 1141 - 1148
ZARENEZHAD ET AL., HEPATITIS MONTHLY, vol. 17, no. 10, 2017, pages e43500 - 6

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12545705B2 (en) 2010-11-04 2026-02-10 Albireo Ab IBAT inhibitors for the treatment of liver diseases
US12187812B2 (en) 2010-11-04 2025-01-07 Albireo Ab IBAT inhibitors for the treatment of liver diseases
US12496282B2 (en) 2017-08-28 2025-12-16 Enanta Pharmaceuticals, Inc. Hepatitis B antiviral agents
US12508234B2 (en) 2018-06-20 2025-12-30 Albireo Ab Pharmaceutical formulation of odevixibat
US12091394B2 (en) 2018-06-20 2024-09-17 Albireo Ab Crystal modifications of odevixibat
US12264159B2 (en) 2018-11-21 2025-04-01 Enanta Pharmaceuticals, Inc. Functionalized heterocycles as antiviral agents
US12187690B2 (en) 2019-02-06 2025-01-07 Albireo Ab Benzothiadiazepine compounds and their use as bile acid modulators
US12202809B2 (en) 2019-12-04 2025-01-21 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
US12060338B2 (en) 2019-12-04 2024-08-13 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
US12024495B2 (en) 2019-12-04 2024-07-02 Albireo Ab Benzothiazepine compounds and their use as bile acid modulators
US12447156B2 (en) 2020-11-12 2025-10-21 Albireo Ab Treating progressive familial intrahepatic cholestasis (PFIC) with IBAT inhibitors
US12134606B2 (en) 2020-12-04 2024-11-05 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
US12365658B2 (en) 2021-06-03 2025-07-22 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2023203248A1 (en) 2022-04-22 2023-10-26 Albireo Ab Subcutaneous administration of an asbt inhibitor
WO2023237728A1 (en) 2022-06-09 2023-12-14 Albireo Ab Treating hepatitis
WO2024177984A1 (en) * 2023-02-20 2024-08-29 Assembly Biosciences, Inc. Benzothia(dia)zepine compounds for treatment of hbv and hdv
WO2024240249A1 (zh) * 2023-05-25 2024-11-28 正大天晴药业集团股份有限公司 一种苯并噻二氮卓化合物及其用途
WO2025043094A1 (en) 2023-08-23 2025-02-27 Assembly Biosciences, Inc. Benzothia(dia)zepine compounds for treatment of hbv and hdv
WO2025146508A1 (en) 2024-01-05 2025-07-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2025146507A1 (en) 2024-01-05 2025-07-10 Albireo Ab Benzothia(di)azepine compounds and their use as bile acid modulators
WO2026038156A1 (en) 2024-08-15 2026-02-19 Assembly Biosciences, Inc. Novel crystalline forms
US12617774B2 (en) 2025-05-30 2026-05-05 Novartis Ag Substituted indole compounds and methods of use thereof

Also Published As

Publication number Publication date
CL2023003568A1 (es) 2024-07-05
PL4347575T3 (pl) 2025-10-06
US20220402885A1 (en) 2022-12-22
AU2022285893A1 (en) 2023-11-23
EP4347575B1 (en) 2025-07-23
JP7842787B2 (ja) 2026-04-08
BR112023024850A2 (pt) 2024-02-20
CA3218474A1 (en) 2022-12-08
CN117412955A (zh) 2024-01-16
CO2023016072A2 (es) 2023-12-11
EP4347575A1 (en) 2024-04-10
HUE072404T2 (hu) 2025-11-28
ES3037404T3 (en) 2025-10-01
US12365658B2 (en) 2025-07-22
AU2022285893A9 (en) 2023-11-30
MX2023014153A (es) 2024-01-10
JP2024520677A (ja) 2024-05-24
IL308582A (en) 2024-01-01
AR126076A1 (es) 2023-09-06
EP4347575C0 (en) 2025-07-23
JOP20230302A1 (ar) 2023-11-23
KR20240017844A (ko) 2024-02-08
ZA202400117B (en) 2025-06-25
TW202313579A (zh) 2023-04-01

Similar Documents

Publication Publication Date Title
EP4347575B1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
EP4069360B1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
US11572350B1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
EP4188541B1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
WO2020161216A1 (en) Benzothiazepine compounds and their use as bile acid modulators
WO2022029101A1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
WO2021110885A1 (en) Benzothiadiazepine compounds and their use as bile acid modulators
WO2021110886A1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
WO2021110884A1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
WO2021110883A1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
WO2024008766A1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
AU2020218908A1 (en) Benzothiadiazepine compounds and their use as bile acid modulators
EP4069359A1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
EP4069361A1 (en) Benzothia(di)azepine compounds and their use as bile acid modulators
EP4069247A1 (en) Benzothiadiazepine compounds and their use as bile acid modulators
HK40109960B (en) Benzothia(di)azepine compounds and their use as bile acid modulators
HK40109960A (en) Benzothia(di)azepine compounds and their use as bile acid modulators
EA050593B1 (ru) Соединения бензотиа(ди)азепина и их применение в качестве модуляторов желчных кислот
HK40095619B (en) Benzothia(di)azepine compounds and their use as bile acid modulators
HK40095619A (en) Benzothia(di)azepine compounds and their use as bile acid modulators
HK40082186B (en) Benzothia(di)azepine compounds and their use as bile acid modulators
HK40082186A (en) Benzothia(di)azepine compounds and their use as bile acid modulators
OA21240A (en) Benzothia(di)azepine compounds and their use as bile acid modulators.

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22732489

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 3218474

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2022285893

Country of ref document: AU

Ref document number: 805364

Country of ref document: NZ

Ref document number: AU2022285893

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 308582

Country of ref document: IL

ENP Entry into the national phase

Ref document number: 2022285893

Country of ref document: AU

Date of ref document: 20220603

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: NC2023/0016072

Country of ref document: CO

WWE Wipo information: entry into national phase

Ref document number: MX/A/2023/014153

Country of ref document: MX

Ref document number: 202393031

Country of ref document: EA

Ref document number: 2301007763

Country of ref document: TH

WWE Wipo information: entry into national phase

Ref document number: 12023553263

Country of ref document: PH

Ref document number: 202280038820.2

Country of ref document: CN

Ref document number: P6003110/2023

Country of ref document: AE

WWE Wipo information: entry into national phase

Ref document number: 202317081258

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2023574477

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: DZP2023001878

Country of ref document: DZ

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112023024850

Country of ref document: BR

WWP Wipo information: published in national office

Ref document number: NC2023/0016072

Country of ref document: CO

ENP Entry into the national phase

Ref document number: 20237043618

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 11202308875W

Country of ref document: SG

WWE Wipo information: entry into national phase

Ref document number: 2022732489

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2022732489

Country of ref document: EP

Effective date: 20240103

WWE Wipo information: entry into national phase

Ref document number: 523451701

Country of ref document: SA

ENP Entry into the national phase

Ref document number: 112023024850

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20231128

WWE Wipo information: entry into national phase

Ref document number: 523451701

Country of ref document: SA

WWE Wipo information: entry into national phase

Ref document number: 523451701

Country of ref document: SA

WWE Wipo information: entry into national phase

Ref document number: 523451701

Country of ref document: SA

WWG Wipo information: grant in national office

Ref document number: 2022732489

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 523451701

Country of ref document: SA

WWG Wipo information: grant in national office

Ref document number: MX/A/2023/014153

Country of ref document: MX