HRP20211965T1 - Novi selektivni inhibitori jak1 i njihova upotreba - Google Patents
Novi selektivni inhibitori jak1 i njihova upotreba Download PDFInfo
- Publication number
- HRP20211965T1 HRP20211965T1 HRP20211965TT HRP20211965T HRP20211965T1 HR P20211965 T1 HRP20211965 T1 HR P20211965T1 HR P20211965T T HRP20211965T T HR P20211965TT HR P20211965 T HRP20211965 T HR P20211965T HR P20211965 T1 HRP20211965 T1 HR P20211965T1
- Authority
- HR
- Croatia
- Prior art keywords
- compound
- imidazo
- nrr
- pyridin
- pharmaceutically acceptable
- Prior art date
Links
- 229940124639 Selective inhibitor Drugs 0.000 title 1
- 101150079478 jak1 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 34
- 150000003839 salts Chemical class 0.000 claims 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 9
- 238000000034 method Methods 0.000 claims 9
- 125000001475 halogen functional group Chemical group 0.000 claims 8
- 201000010099 disease Diseases 0.000 claims 7
- 239000012453 solvate Substances 0.000 claims 7
- 125000001424 substituent group Chemical group 0.000 claims 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 4
- JVWXVJOIUKQBOJ-NWDGAFQWSA-N 2-[(2R,5S)-5-(4-methyl-12-oxa-3,5,8-triazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,10-pentaen-3-yl)oxan-2-yl]acetonitrile Chemical compound CC1=NC=2C(=C3C(=NC=2)C=CO3)N1[C@H]1CC[C@@H](OC1)CC#N JVWXVJOIUKQBOJ-NWDGAFQWSA-N 0.000 claims 4
- 208000027866 inflammatory disease Diseases 0.000 claims 4
- UDGHPISWLBXGGY-WDEREUQCSA-N 2-[(2R,5S)-5-[4-(hydroxymethyl)-12-oxa-3,5,8-triazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,10-pentaen-3-yl]oxan-2-yl]acetonitrile Chemical compound OCC1=NC=2C(=C3C(=NC=2)C=CO3)N1[C@H]1CC[C@@H](OC1)CC#N UDGHPISWLBXGGY-WDEREUQCSA-N 0.000 claims 3
- ZFQNHUSKKDBFHY-GRYCIOLGSA-N 2-[(2R,5S)-5-[4-[(1R)-1-hydroxyethyl]-12-oxa-3,5,8-triazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,10-pentaen-3-yl]oxan-2-yl]acetonitrile Chemical compound O[C@H](C)C1=NC=2C(=C3C(=NC=2)C=CO3)N1[C@H]1CC[C@@H](OC1)CC#N ZFQNHUSKKDBFHY-GRYCIOLGSA-N 0.000 claims 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- -1 oxonium tetrafluoroborate Chemical compound 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 239000003054 catalyst Substances 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 238000005984 hydrogenation reaction Methods 0.000 claims 2
- 230000001613 neoplastic effect Effects 0.000 claims 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 1
- ABAUJVSEICFAOS-NWDGAFQWSA-N 2-[(2R,5S)-5-(4-ethyl-12-oxa-3,5,8-triazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,10-pentaen-3-yl)oxan-2-yl]acetonitrile Chemical compound C(C)C1=NC=2C(=C3C(=NC=2)C=CO3)N1[C@H]1CC[C@@H](OC1)CC#N ABAUJVSEICFAOS-NWDGAFQWSA-N 0.000 claims 1
- UDGHPISWLBXGGY-QWRGUYRKSA-N 2-[(2S,5S)-5-[4-(hydroxymethyl)-12-oxa-3,5,8-triazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,10-pentaen-3-yl]oxan-2-yl]acetonitrile Chemical compound OCC1=NC=2C(=C3C(=NC=2)C=CO3)N1[C@H]1CC[C@H](OC1)CC#N UDGHPISWLBXGGY-QWRGUYRKSA-N 0.000 claims 1
- WKNNRZVOWSSOSY-XYPYZODXSA-N C12=C(C3=C(N=C(N3[C@H]3CC[C@@H](CC3)C#N)CO)C=N2)OC=C1 Chemical compound C12=C(C3=C(N=C(N3[C@H]3CC[C@@H](CC3)C#N)CO)C=N2)OC=C1 WKNNRZVOWSSOSY-XYPYZODXSA-N 0.000 claims 1
- HIQALKYWCDEOTH-IJLUTSLNSA-N C12=C(N=CC=3N=C(N(C1=3)[C@H]1CC[C@@H](CC1)C#N)[C@@H](C)O)C=CO2 Chemical compound C12=C(N=CC=3N=C(N(C1=3)[C@H]1CC[C@@H](CC1)C#N)[C@@H](C)O)C=CO2 HIQALKYWCDEOTH-IJLUTSLNSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- WWFMBYPVXNSPOA-JHJVBQTASA-N O1C=CC2=C1C=1N(C(=NC=1C=N2)[C@H](O)C)[C@H]1CC[C@@H](CC1)CC#N Chemical compound O1C=CC2=C1C=1N(C(=NC=1C=N2)[C@H](O)C)[C@H]1CC[C@@H](CC1)CC#N WWFMBYPVXNSPOA-JHJVBQTASA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 claims 1
- LCDCPQHFCOBUEF-UHFFFAOYSA-N pyrrolidine-1-carboxamide Chemical compound NC(=O)N1CCCC1 LCDCPQHFCOBUEF-UHFFFAOYSA-N 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
Classifications
-
- 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
- C07D491/12—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 three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
-
- 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
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662403660P | 2016-10-03 | 2016-10-03 | |
| EP17858944.6A EP3509591B1 (en) | 2016-10-03 | 2017-09-30 | Novel jak1 selective inhibitors and uses thereof |
| PCT/US2017/054668 WO2018067422A1 (en) | 2016-10-03 | 2017-09-30 | Novel jak1 selective inhibitors and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20211965T1 true HRP20211965T1 (hr) | 2022-03-18 |
Family
ID=61831161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20211965TT HRP20211965T1 (hr) | 2016-10-03 | 2017-09-30 | Novi selektivni inhibitori jak1 i njihova upotreba |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US10738060B2 (enExample) |
| EP (1) | EP3509591B1 (enExample) |
| JP (1) | JP7089141B2 (enExample) |
| KR (1) | KR102399848B1 (enExample) |
| CN (2) | CN113214278B (enExample) |
| AU (3) | AU2017339417C1 (enExample) |
| DK (1) | DK3509591T3 (enExample) |
| EA (1) | EA201990523A1 (enExample) |
| ES (1) | ES2901216T3 (enExample) |
| HK (1) | HK1253040A1 (enExample) |
| HR (1) | HRP20211965T1 (enExample) |
| HU (1) | HUE058120T2 (enExample) |
| IL (3) | IL265358B (enExample) |
| MX (1) | MX390005B (enExample) |
| NZ (1) | NZ751284A (enExample) |
| PL (1) | PL3509591T3 (enExample) |
| PT (1) | PT3509591T (enExample) |
| RS (1) | RS62695B1 (enExample) |
| WO (1) | WO2018067422A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ751284A (en) * | 2016-10-03 | 2022-09-30 | Hangzhou Highlightll Pharmaceutical Co Ltd | Novel jak1 selective inhibitors and uses thereof |
| CA3045567A1 (en) * | 2017-01-11 | 2018-07-19 | Leo Pharma A/S | Novel amino-imidazopyridine derivatives as janus kinase inhibitors and pharmaceutical use thereof |
| EA202191170A1 (ru) * | 2018-10-31 | 2021-07-27 | Инсайт Корпорейшн | Комбинированная терапия для лечения гематологических заболеваний |
| PH12021552130A1 (en) * | 2019-03-05 | 2022-08-31 | Incyte Corp | Jak1 pathway inhibitors for the treatment of chronic lung allograft dysfunction |
| TW202102222A (zh) | 2019-03-19 | 2021-01-16 | 美商英塞特公司 | 白斑病之生物標記物 |
| EP4393492A3 (en) * | 2019-06-06 | 2024-08-07 | Hangzhou Highlightll Pharmaceutical Co., Ltd. | Method for synthesizing furoimidazopyridine compound, polymorphic substance and polymorphic substance of salt |
| KR102785014B1 (ko) | 2019-06-06 | 2025-03-20 | 항저우 하이라이트엘엘 파마슈티컬 씨오., 엘티디. | 푸로이미다조피리딘 화합물의 합성 방법, 푸로이미다조피리딘 화합물의 결정 형태, 및 그의 염의 결정 형태 |
| BR112022023550A2 (pt) | 2020-05-19 | 2023-01-03 | Bayer Cropscience Ag | (tio)amidas azabicíclicas como compostos fungicidas |
| MX2022015625A (es) | 2020-06-10 | 2023-01-11 | Bayer Ag | Heterociclos sustituidos con azabiciclilo como nuevos fungicidas. |
| US20240307396A1 (en) * | 2021-06-07 | 2024-09-19 | The Regents Of The University Of California | Compositions and methods for treating celiac disease |
| AU2022342095A1 (en) * | 2021-09-13 | 2024-06-27 | Hangzhou Highlightll Pharmaceutical Co., Ltd | Methods of treating cns disorders |
| CN114213424B (zh) * | 2021-12-30 | 2023-05-26 | 杭州高光制药有限公司 | 一种呋喃[3，2-b]并吡啶衍生物的合成方法 |
| WO2025224600A1 (en) * | 2024-04-21 | 2025-10-30 | Biohaven Therapeutics Ltd. | Treatment of alpha-synucleinopathies and neuroprotection |
| WO2025248468A1 (en) | 2024-05-28 | 2025-12-04 | Biohaven Therapeutics Ltd. | Use of tyk2/jak1 inhibitors to treat amyloid-related imaging abnormalities (aria) |
| WO2026002028A1 (zh) * | 2024-06-26 | 2026-01-02 | 杭州多域生物技术有限公司 | 稠杂芳环类化合物、其药物组合物及其应用 |
| WO2026032213A1 (zh) * | 2024-08-08 | 2026-02-12 | 普罗思特(南京)生物科技有限公司 | 取代的三环衍生物及其应用 |
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| WO2015184305A1 (en) | 2014-05-30 | 2015-12-03 | Incyte Corporation | TREATMENT OF CHRONIC NEUTROPHILIC LEUKEMIA (CNL) AND ATYPICAL CHRONIC MYELOID LEUKEMIA (aCML) BY INHIBITORS OF JAK1 |
| CN105418620B (zh) | 2014-09-23 | 2018-05-04 | 天津药明康德新药开发有限公司 | 一种4-(叔丁氧羰基)八氢呋喃并[3,2-b]吡啶-6-羧酸的合成方法 |
| WO2016100349A2 (en) | 2014-12-16 | 2016-06-23 | Rugen Holdings (Cayman) Limited | Bicyclic azaheterocyclic compounds as nr2b nmda receptor antagonists |
| WO2016196244A1 (en) | 2015-05-29 | 2016-12-08 | Incyte Corporation | Pyridineamine compounds useful as pim kinase inhibitors |
| CN106432232A (zh) | 2016-09-18 | 2017-02-22 | 苏州汉德创宏生化科技有限公司 | 1‑哌啶‑4‑基‑1,3‑二氢‑咪唑[4,5‑b]吡啶‑2‑酮的合成方法 |
| NZ751284A (en) | 2016-10-03 | 2022-09-30 | Hangzhou Highlightll Pharmaceutical Co Ltd | Novel jak1 selective inhibitors and uses thereof |
| JP7291077B2 (ja) | 2016-12-16 | 2023-06-14 | ヤンセン ファーマシューティカ エヌ．ベー． | Ｊａｋファミリーのキナーゼの低分子阻害物質 |
| CN107216334A (zh) | 2017-06-29 | 2017-09-29 | 上海吉尔多肽有限公司 | 一种6‑氯呋喃[3,2‑b]吡啶的合成方法 |
| KR102785014B1 (ko) | 2019-06-06 | 2025-03-20 | 항저우 하이라이트엘엘 파마슈티컬 씨오., 엘티디. | 푸로이미다조피리딘 화합물의 합성 방법, 푸로이미다조피리딘 화합물의 결정 형태, 및 그의 염의 결정 형태 |
| EP4393492A3 (en) | 2019-06-06 | 2024-08-07 | Hangzhou Highlightll Pharmaceutical Co., Ltd. | Method for synthesizing furoimidazopyridine compound, polymorphic substance and polymorphic substance of salt |
| CN118619944A (zh) | 2019-06-06 | 2024-09-10 | 北京泰德制药股份有限公司 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
| CN114213424B (zh) | 2021-12-30 | 2023-05-26 | 杭州高光制药有限公司 | 一种呋喃[3，2-b]并吡啶衍生物的合成方法 |
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