WO2019233941A1 - Tetrahydro-1 h-pyrazino[2,1 -ajisoindolylquinoline compounds for the treatment of autoimmune disease - Google Patents

Tetrahydro-1 h-pyrazino[2,1 -ajisoindolylquinoline compounds for the treatment of autoimmune disease Download PDF

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Publication number
WO2019233941A1
WO2019233941A1 PCT/EP2019/064323 EP2019064323W WO2019233941A1 WO 2019233941 A1 WO2019233941 A1 WO 2019233941A1 EP 2019064323 W EP2019064323 W EP 2019064323W WO 2019233941 A1 WO2019233941 A1 WO 2019233941A1
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Prior art keywords
methyl
amino
tetrahydro
pyrazino
carbonitrile
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Ceased
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PCT/EP2019/064323
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English (en)
French (fr)
Inventor
Fabian Dey
Hong Shen
Hongtao Xu
Hongying Yun
Ge Zou
Wei Zhu
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F Hoffmann La Roche AG
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F Hoffmann La Roche AG
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Publication date
Priority to CN201980035182.7A priority Critical patent/CN112204028B/zh
Priority to KR1020207034855A priority patent/KR20210018818A/ko
Priority to MX2020012827A priority patent/MX2020012827A/es
Priority to CA3098291A priority patent/CA3098291A1/en
Priority to BR112020024782-0A priority patent/BR112020024782A2/pt
Priority to PE2020001875A priority patent/PE20210131A1/es
Priority to JP2020567772A priority patent/JP7374130B2/ja
Priority to EP19729220.4A priority patent/EP3802539B1/en
Priority to US16/972,556 priority patent/US12157746B2/en
Application filed by F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG
Priority to CR20200584A priority patent/CR20200584A/es
Priority to AU2019280728A priority patent/AU2019280728A1/en
Priority to SG11202011137SA priority patent/SG11202011137SA/en
Publication of WO2019233941A1 publication Critical patent/WO2019233941A1/en
Priority to CONC2020/0014677A priority patent/CO2020014677A2/es
Priority to IL279144A priority patent/IL279144A/en
Priority to PH12020552092A priority patent/PH12020552092A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • 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
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
    • 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
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

Definitions

  • n 1, 2, 3 or 4;
  • the“ds-isomers” refers to a mixture of
  • R 5 is H, piperazinyl, halogen, Ci -6 alkyl, halopyrrolidinylamino or hydroxypyrrolidinylCi- 6alkyl amino;
  • R 4 is H
  • halopyrrolidinyloxy hydroxy(Ci- 6 alkyl)-l ,4-diazepanyl; hydroxy(Ci -6 alkylamino)pyrrolidinyl; hydroxy- 1 ,4-diazepanyl; hydroxypyrrolidinylCi ⁇ alkylamino; morpholinylC i _ 6 alkylammo;
  • a further embodiment of present invention is (vi) a compound of formula (I) or (la) or (lb) according to any one of (i) to (v), or a pharmaceutically acceptable salt thereof, wherein R 1
  • R 4 is H
  • Another embodiment of present invention is (ii’) a compound of fonnula (la),
  • R 3 is H; R 4 is H;
  • azetidinyl amino amino; azetidinyloxy; piperazinyl; piperidinyl or pyrrolidinyl which is once or twice substituted by substituents independently selected from amino, hydroxy, hydroxyCi- 6alkyl, Ci -6 alkoxy and C ⁇ alkyl amino;
  • R 2 is Ci- 6 alkyl
  • R 5 is H or piperazinyl
  • R 4 is H
  • X is halogen or leaving group, for example, OTf or OMs; m is 0, 1, 2, or 3; n is 1, 2, 3 or 4; m+n ⁇ 4; R 7 and R 8 are protecting groups, for example, R 7 is Boc and R 8 is benzyl; R 9 is alkylsilyl, for example, trimethylsilyl.
  • the amide coupling of protected amino acid (II) and silylamine (III) can be achieved using coupling reagents, such as HATU and DIPEA, to afford intermediate (IV).
  • coupling reagents such as HATU and DIPEA
  • R 7 is removed by selective deprotection, the amide bond in the resulting intermediate (V) can be reduced under reductive conditions, such as treatment of LAH, to afford diamine (VI).
  • Buchwald-Hartwig animation conditions ref: Acc. Chem. Res. 1998, 31, 805-818; Chem. Rev. 2016, 116, 12564-12649; Topics in Current Chemistry, 2002, 219, 131-209; and references cited therein
  • a catalyst such as Ruphos Pd-G2
  • a base such as Cs 2 C0 3
  • the resulting compound of formula (XII) can be submitted to nucleophilic aromatic substitution conditions (e.g. heating with halide (XIII) in the presence of DIEPA in DMSO), or Buchwald-Hartwig amination conditions (e.g. heating with halide (XIII) in the presence of a catalyst, such as Ruphos Pd-G2, and a base, such as Cs 2 C0 3 , to afford compound of formula (I).
  • the compound of formula (XII) may contain a protecting group, e.g. Boc, which will be removed before affording the final compound of formula (I).
  • Example 3 (19.7 mg) was obtained.
  • Step 2 preparation of 4- [(4/?, 10/>5 -4-methy l-8-piperazin-l -yl-3,4,6,1 Ob-tetrahydro- l/ -pyrazino [2, l-a]isoindoI-2-yl] pyrazolo [1,5-a] pyridine-7-carbonitriIe (Example 5)
  • Step 2 preparation of tert- butyl 4-
  • Step 3 preparation of tert- butyl (3/?)-4-[(4/?, 10M , )-2-(8-cyano-5-quinolyI)-4-methyl- 3 ,4, 6,1 Ob-tetrahydro-l//-pyrazino [2, 1-a] isoindol-8-yl] -3-(hydroxymethyl)-piperazine- 1- carboxylate (compound 10c)
  • Example 14 (7.2 mg) was obtained.
  • Example 25 (9.4 mg) was obtained.
  • Example 30 (46 mg) was obtained.
  • Example 41 The title compound was prepared in analogy to the preparation of Example 10 by using tert-butyl 3a-methoxy-l,2,3,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate instead of tert- butyl (3/ )-3-(hydiOxymethyl)piperazine-l -carboxyl ate.
  • Example 41 (8.8 mg) was obtained.
  • Example 45A (18 mg) was obtained. MS: calc’d 455 [(M+H) + ], measured 455 [(M+H)']. ' H NMR (400 MHz, METHANOL-7 ⁇ ) d ppm 'll NMR (400
  • Example 46 (35 mg) was obtained. MS: calc’d 443 [(M+H) + ], measured 443 [(M+H) ].
  • Example 48 (8.8 mg) was obtained.
  • Example 49 (58 mg) was obtained. MS: calc’d 443 [(M+H) + ], measured 443 [(M+H) + ]. !
  • Example 50 (5.4 mg) was obtained.
  • Example 56A (24 mg) was obtained.
  • Example 60 (70 mg) was obtained.
  • Example 61 (61 mg) was obtained. MS: ealc’d 455 [(M+H) + ], measured 455 [(M+H) + J.

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  • 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)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
PCT/EP2019/064323 2018-06-05 2019-06-03 Tetrahydro-1 h-pyrazino[2,1 -ajisoindolylquinoline compounds for the treatment of autoimmune disease Ceased WO2019233941A1 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
US16/972,556 US12157746B2 (en) 2018-06-05 2019-06-03 Tetrahydro-1H-pyrazino[2,1-a]isoindolylquinoline compounds for the treatment of autoimmune disease
MX2020012827A MX2020012827A (es) 2018-06-05 2019-06-03 Compuestos tetrahidro-1h-pirazino[2,1-a]isoindolilquinolina para el tratamiento de enfermedades autoinmunes.
CR20200584A CR20200584A (es) 2018-06-05 2019-06-03 Compuestos tetrahidro-1h-pirazino [2,1-a] isoindolilquinolina para el tratamiento de enfermedades autoinmunes
BR112020024782-0A BR112020024782A2 (pt) 2018-06-05 2019-06-03 compostos de tetra-hidro-1h-pirazino[2,1-a]isoindolilquinolina para o tratamento de doença autoimune
PE2020001875A PE20210131A1 (es) 2018-06-05 2019-06-03 COMPUESTOS TETRAHIDRO-1H-PIRAZINO[2,1-a]ISOINDOLILQUINOLINA PARA EL TRATAMIENTO DE ENFERMEDADES AUTOINMUNES
JP2020567772A JP7374130B2 (ja) 2018-06-05 2019-06-03 自己免疫疾患治療用の新規なテトラヒドロ－１Ｈ－ピラジノ［２，１－ａ］イソインドリルキノリン化合物
EP19729220.4A EP3802539B1 (en) 2018-06-05 2019-06-03 Tetrahydro-1h-pyrazino[2,1-a]isoindolylquinoline compounds for the treatment of autoimmune disease
CN201980035182.7A CN112204028B (zh) 2018-06-05 2019-06-03 用于治疗自身免疫性疾病的四氢-1H-吡嗪并[2,1-a]异吲哚基喹啉化合物
CA3098291A CA3098291A1 (en) 2018-06-05 2019-06-03 Tetrahydro-1 h-pyrazino[2,1 -ajisoindolylquinoline compounds for the treatment of autoimmune disease
KR1020207034855A KR20210018818A (ko) 2018-06-05 2019-06-03 자가면역 질환의 치료를 위한 테트라하이드로-1H-피라지노[2,1-a]이소인돌릴퀴놀린 화합물
AU2019280728A AU2019280728A1 (en) 2018-06-05 2019-06-03 Tetrahydro-1 H-pyrazino[2,1 -ajisoindolylquinoline compounds for the treatment of autoimmune disease
SG11202011137SA SG11202011137SA (en) 2018-06-05 2019-06-03 Tetrahydro-1 h-pyrazino[2,1 -ajisoindolylquinoline compounds for the treatment of autoimmune disease
CONC2020/0014677A CO2020014677A2 (es) 2018-06-05 2020-11-26 Compuestos tetrahidro-1h-pirazino[2,1-a]isoindolilquinolina para el tratamiento de enfermedades autoinmunes
IL279144A IL279144A (en) 2018-06-05 2020-12-01 Tetrahydro-1H-pyrazino[2,1-azisoindolylquinoline compounds for the treatment of immune system disease
PH12020552092A PH12020552092A1 (en) 2018-06-05 2020-12-04 Tetrahydro-1h-pyrazino[2,1-a]isoindolylquinoline compounds for the treatment of autoimmune disease

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
CNPCT/CN2018/090004 2018-06-05
CN2018090004 2018-06-05
EP18193916.6 2018-09-12
EP18193916 2018-09-12
CN2019086019 2019-05-08
CNPCT/CN2019/086019 2019-05-08

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US (1) US12157746B2 (https=)
EP (1) EP3802539B1 (https=)
JP (1) JP7374130B2 (https=)
KR (1) KR20210018818A (https=)
CN (1) CN112204028B (https=)
AU (1) AU2019280728A1 (https=)
BR (1) BR112020024782A2 (https=)
CA (1) CA3098291A1 (https=)
CL (1) CL2020003065A1 (https=)
CO (1) CO2020014677A2 (https=)
CR (1) CR20200584A (https=)
IL (1) IL279144A (https=)
MA (1) MA52747A (https=)
MX (1) MX2020012827A (https=)
PE (1) PE20210131A1 (https=)
PH (1) PH12020552092A1 (https=)
SG (1) SG11202011137SA (https=)
TW (1) TW202016111A (https=)
WO (1) WO2019233941A1 (https=)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021094301A1 (en) * 2019-11-12 2021-05-20 F. Hoffmann-La Roche Ag Hydropyrazino[1,2-b]isoquinoline compounds for the treatment of autoimmune disease
WO2021099285A1 (en) * 2019-11-19 2021-05-27 F. Hoffmann-La Roche Ag Triazatricycle compounds for the treatment of autoimmune disease
WO2021099284A1 (en) * 2019-11-19 2021-05-27 F. Hoffmann-La Roche Ag Hydro-1h-pyrrolo[1,2-a]pyrazine compounds for the treatment of autoimmune disease
WO2022013136A1 (en) 2020-07-14 2022-01-20 F. Hoffmann-La Roche Ag Hydroisoquinoline or hydronaphthyridine compounds for the treatment of autoimmune disease
WO2022022489A1 (zh) * 2020-07-27 2022-02-03 江苏恒瑞医药股份有限公司 吲哚稠环类衍生物、其制备方法及其在医药上的应用
CN114057759A (zh) * 2020-08-07 2022-02-18 江苏恒瑞医药股份有限公司 稠合四环类衍生物、其制备方法及其在医药上的应用
WO2022111636A1 (zh) 2020-11-26 2022-06-02 江苏恒瑞医药股份有限公司 稠合三环化合物、其制备方法及其在医药上的应用
CN114656363A (zh) * 2022-03-28 2022-06-24 南京林业大学 一种钯催化芳香酯类化合物的合成方法
US12421229B2 (en) 2019-12-03 2025-09-23 Hoffmann-La Roche Inc. Hydropyrido[1,2-α]pyrazine compounds for the treatment of autoimmune disease
US12421240B2 (en) 2019-10-31 2025-09-23 Hoffmann-La Roche Inc. Hydropyrazino[1,2-d][1,4]diazepine compounds for the treatment of autoimmune disease

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023025109A1 (zh) * 2021-08-23 2023-03-02 上海维申医药有限公司 一类Toll样受体抑制剂及其制备和应用

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