JP2017536395A - E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 - Google Patents
E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 Download PDFInfo
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- 210000000434 stratum corneum Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical class [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005985 thienyl[1,3]dithianyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012745 toughening agent Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005580 triphenylene group Chemical group 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/207—Cyclohexane rings not substituted by nitrogen atoms, e.g. kasugamycins
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
- C07H3/06—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
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- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
R1は、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、
R2は、−OH、−NH2、−OC(=O)Y1、−NHC(=O)Y1、および−NHC(=O)NHY1基から選択され、ここで、Y1は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、C2〜8ハロアルキニル、C6〜18アリール、およびC1〜13ヘテロアリール基から選択され、
R3は、−CN、−CH2CN、および−C(=O)Y2基から選択され、ここで、Y2は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、−OZ1、−NHOH、−NHOCH3、−NHCN、および−NZ1Z2基から選択され、ここで、Z1およびZ2は、同じでも異なっていてもよく、独立して、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、Z1およびZ2は、一緒になって環を形成していてもよく、
R4は、C3〜8シクロアルキル基から選択され、
R5は、独立して、H、ハロ、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、ただし、少なくとも1つのR5はHでないことを条件とし、
nは、1〜4の範囲の整数から選択され、
Lは、リンカー基から選択される)
のヘテロ二官能性阻害剤、式(I)のプロドラッグ、および前述のもののいずれかの薬学的に許容される塩が開示される。
E−セレクチンおよびCXCR4ケモカイン受容体が役割を果たす疾患を処置するため、ならびに循環血液への放出後の細胞の滞留を促進するための化合物、組成物、および方法が本明細書で開示される。化合物は、in vitroおよびin vivoで様々な使用を有する。
R1は、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、
R2は、−OH、−NH2、−OC(=O)Y1、−NHC(=O)Y1、および−NHC(=O)NHY1基から選択され、ここで、Y1は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、C2〜8ハロアルキニル、C6〜18アリール、およびC1〜13ヘテロアリール基から選択され、
R3は、−CN、−CH2CN、および−C(=O)Y2基から選択され、ここで、Y2は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、−OZ1、−NHOH、−NHOCH3、−NHCN、および−NZ1Z2基から選択され、ここで、Z1およびZ2は、同じでも異なっていてもよく、独立して、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、Z1およびZ2は、一緒になって環を形成していてもよく、
R4は、C3〜8シクロアルキル基から選択され、
各R5は、独立して、H、ハロ、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、ただし、少なくとも1つのR5はHでないことを条件とし、
nは、1〜4の範囲の整数から選択され、
Lは、リンカー基から選択される)
のヘテロ二官能性阻害剤、式(I)のプロドラッグ、および前述のもののいずれかの薬学的に許容される塩が提供される。
定義
化合物合成手順
ヘテロ二官能性化合物を特徴付けるための方法
医薬組成物および医薬組成物を使用する方法
E−セレクチンおよびCXCR4ケモカイン受容体のヘテロ二官能性阻害剤
(化合物9および16)
例示的な式(I)のヘテロ二官能性化合物を、実施例1〜2に記載されているように、および図1に記載されている例示的合成スキームに示されているように合成した。
(実施例2)
SDF−1誘発性化学走性の阻害を評価するCXCR4アッセイ
E−セレクチン活性−結合アッセイ
E−セレクチンのアンタゴニストをスクリーニングし、特徴づける阻害アッセイは競合的結合アッセイであり、このアッセイからIC50値を決定することができる。37℃で2時間のインキュベーションにより、E−セレクチン/Igキメラを96ウェルマイクロタイタープレート内に固定化した。非特異性の結合を減少させるために、ウシ血清アルブミンを各ウェルに添加し、室温で2時間インキュベートした。プレートを洗浄し、ビオチン化した、sLeaポリアクリルアミドのコンジュゲートの存在下、ストレプトアビジン/西洋わさびペルオキシダーゼと共に試験化合物の段階希釈物をウェルに添加し、室温で2時間インキュベートした。
CXCR4アッセイ − 環状AMPの阻害
(実施例5)
腫瘍関連線維芽細胞へのリンパ管および血管内皮移動の阻害
(実施例6)
PDAC細胞のリンパ単層への結合の阻害
(実施例7)
前立腺がんモデル
Claims (31)
- 式(I):
R1は、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、
R2は、−OH、−NH2、−OC(=O)Y1、−NHC(=O)Y1、および−NHC(=O)NHY1基から選択され、ここで、Y1は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、C2〜8ハロアルキニル、C6〜18アリール、およびC1〜13ヘテロアリール基から選択され、
R3は、−CN、−CH2CN、および−C(=O)Y2基から選択され、ここで、Y2は、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、−OZ1、−NHOH、−NHOCH3、−NHCN、および−NZ1Z2基から選択され、ここで、Z1およびZ2は、同じでも異なっていてもよく、独立して、H、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、Z1およびZ2は、一緒になって環を形成していてもよく、
R4は、C3〜8シクロアルキル基から選択され、
各R5は、独立して、H、ハロ、C1〜8アルキル、C2〜8アルケニル、C2〜8アルキニル、C1〜8ハロアルキル、C2〜8ハロアルケニル、およびC2〜8ハロアルキニル基から選択され、ただし、少なくとも1つのR5はHでないことを条件とし、
nは、1〜4の範囲の整数から選択され、
Lは、リンカー基から選択される)
の化合物、式(I)のプロドラッグ、および前述のもののいずれかの薬学的に許容される塩から選択される少なくとも1つの化合物。 - R1が、C1〜8アルキル基から選択される、請求項1に記載の少なくとも1つの化合物。
- R1が、エチルおよびメチルから選択される、請求項2に記載の少なくとも1つの化合物。
- R1がエチルである、請求項3に記載の少なくとも1つの化合物。
- R2が、−OH、−NH2、−OC(=O)Y1、および−NHC(=O)Y1から選択され、ここで、Y1が、C1〜8アルキル、C6〜18アリール、およびC1〜13ヘテロアリール基から選択される、先行する請求項のいずれかに記載の少なくとも1つの化合物。
- R2が、
- R3が、−C(=O)Y2から選択され、ここで、Y2が、−OZ1、−NHOH、−NHOCH3、および−NZ1Z2基から選択され、ここで、Z1およびZ2が、同じでも異なっていてもよく、独立して、H、およびC1〜8アルキルから選択され、Z1およびZ2が、一緒になって環を形成していてもよい、先行する請求項のいずれかに記載の少なくとも1つの化合物。
- R3が−C(=O)OHである、請求項7に記載の少なくとも1つの化合物。
- R4が、
- 少なくとも1つのR5がハロである、先行する請求項のいずれかに記載の少なくとも1つの化合物。
- 少なくとも1つのR5がブロモである、請求項10に記載の少なくとも1つの化合物。
- nが1である、請求項10または11のいずれか一項に記載の少なくとも1つの化合物。
- 式(Ia)の化合物:
- 式(Ib)の化合物:
- 以下の式:
- 以下の式:
- 以下の式:
- 以下の式:
- 前記リンカー基が−C(=O)NH(CH2)2NH−である、請求項1から18のいずれか一項に記載の少なくとも1つの化合物。
- 前記リンカー基が−CH2NHCH2−である、請求項1から18のいずれか一項に記載の少なくとも1つの化合物。
- 前記リンカー基が−C(=O)NHCH2−である、請求項1から18のいずれか一項に記載の少なくとも1つの化合物。
- 以下の式:
- 以下の式:
-
-
- 請求項1から23のいずれか一項に記載の少なくとも1つの化合物および少なくとも1つの追加の薬学的に許容される成分を含む組成物。
- がんの処置および/または予防のための方法であって、ここで、前記がんの細胞は原発部位を離れることができ、前記方法は、がんの処置および/または予防を必要とする対象に、請求項1から25のいずれか一項に記載の少なくとも1つの化合物の有効量および任意選択で少なくとも1つの追加の薬学的に許容される成分を投与するステップを含む方法。
- がん細胞をある部位から血流へ動員し、前記がん細胞を前記血流中に滞留させることが望まれるがんの処置および/または予防のための方法であって、それを必要とする対象に、請求項1から25のいずれか一項に記載の少なくとも1つの化合物の有効量および任意選択で少なくとも1つの追加の薬学的に許容される成分を投与するステップを含む方法。
- 細胞を循環血液に放出し、前記細胞の前記血液中の滞留を促進するための方法であって、それを必要とする対象に、請求項1から25のいずれか一項に記載の少なくとも1つの化合物の有効量および任意選択で少なくとも1つの追加の薬学的に許容される成分を投与するステップを含む方法。
- 腫瘍転移の処置および/または予防のための方法であって、それを必要とする対象に、請求項1から25のいずれか一項に記載の少なくとも1つの化合物の有効量および任意選択で少なくとも1つの追加の薬学的に許容される成分を投与するステップを含む方法。
- 炎症性疾患の処置および/または予防のための方法であって、ここで、細胞の接着または移動が前記疾患において生じており、前記方法は、炎症性疾患の処置および/または予防を必要とする対象に、請求項1から25のいずれか一項に記載の少なくとも1つの化合物の有効量および任意選択で少なくとも1つの追加の薬学的に許容される成分を投与するステップを含む方法。
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Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SI3227310T1 (sl) | 2014-12-03 | 2019-11-29 | Glycomimetics Inc | Heterobifunkcionalni inhibitorji e-selektinov in receptorjev kemokina CXCR4 |
CN109069486A (zh) | 2015-12-14 | 2018-12-21 | X4 制药有限公司 | 治疗癌症的方法 |
US11291678B2 (en) | 2016-03-02 | 2022-04-05 | Glycomimetics, Inc | Methods for the treatment and/or prevention of cardiovascular disease by inhibition of E-selectin |
WO2017177230A1 (en) | 2016-04-08 | 2017-10-12 | X4 Pharmaceuticals, Inc. | Methods for treating cancer |
EP3497131B1 (en) * | 2016-08-08 | 2022-03-09 | GlycoMimetics, Inc. | Combination of t-cell checkpoint inhibitors with inhibitors of e-selectin or cxcr4, or with heterobifunctional inhibitors of both e-selectin and cxcr4. |
US11072625B2 (en) | 2016-10-07 | 2021-07-27 | Glycomimetics, Inc. | Highly potent multimeric e-selectin antagonists |
CA3054605A1 (en) | 2017-03-15 | 2018-09-20 | Glycomimetics, Inc. | Galactopyranosyl-cyclohexyl derivatives as e-selectin antagonists |
JP7275131B2 (ja) * | 2017-11-30 | 2023-05-17 | グリコミメティクス, インコーポレイテッド | 骨髄浸潤リンパ球を動員する方法、およびその使用 |
JP7304863B2 (ja) * | 2017-12-29 | 2023-07-07 | グリコミメティクス, インコーポレイテッド | E-セレクチンおよびガレクチン-3のヘテロ二機能性阻害剤 |
EP3761994A1 (en) | 2018-03-05 | 2021-01-13 | GlycoMimetics, Inc. | Methods for treating acute myeloid leukemia and related conditions |
EP3893936A2 (en) | 2018-12-10 | 2021-10-20 | GlycoMimetics, Inc. | Methods of treating hiv and aids and the elimination of latent reservoirs of hiv infection using selectin, galectin, and siglec antagonists |
US11845771B2 (en) | 2018-12-27 | 2023-12-19 | Glycomimetics, Inc. | Heterobifunctional inhibitors of E-selectin and galectin-3 |
WO2020150263A1 (en) | 2019-01-14 | 2020-07-23 | Magnani John L | Selectin or galectin antagonists for treating cytokine release syndrome and crs-induced neurotoxicity |
KR20220012246A (ko) | 2019-04-24 | 2022-02-03 | 글리코미메틱스, 인크. | E-셀렉틴, 갈렉틴-3, 및/또는 cxcr4 케모카인 수용체의 갈락토오스 연결된 다량체성 글리코모방체 억제제 |
WO2021011435A1 (en) | 2019-07-12 | 2021-01-21 | Magnani John L | Methods for use of gene expression as an indicator of e-selectin inhibitor efficacy and clinical outcome for multiple tumor types |
EP4003367A1 (en) | 2019-07-31 | 2022-06-01 | GlycoMimetics, Inc. | Use of e-selectin antagonists to enhance the survival of reconstituted, bone marrow-depleted hosts |
US20230147312A1 (en) | 2020-03-27 | 2023-05-11 | Glycomimetics, Inc. | Treatment of acute respiratory distress syndrome and related conditions with antagonists of e-selectin |
US20230165882A1 (en) | 2020-05-31 | 2023-06-01 | Glycomimetics, Inc. | Compounds and methods for reduction of cancer cell burden and protection of normal hematopoiesis |
BR112022025480A2 (pt) | 2020-06-14 | 2023-01-17 | Glycomimetics Inc | Composições e métodos para superar a resistência mediada por microambiente por meio de direcionamento de e-selectina |
WO2023014690A1 (en) | 2021-08-03 | 2023-02-09 | Glycomimetics, Inc. | Compositions and methods for overcoming microenvironment-mediated resistance via e-selectin targeting |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002543126A (ja) * | 1999-05-03 | 2002-12-17 | スミスクライン・ビーチャム・コーポレイション | Cxcr−4受容体アンタゴニスト−トロンボポエチン模倣物 |
JP2012525393A (ja) * | 2009-05-01 | 2012-10-22 | グリコミメティックス インコーポレイテッド | E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 |
WO2013096926A1 (en) * | 2011-12-22 | 2013-06-27 | Glycomimetics, Inc. | E-selectin antagonist compounds, compositions, and methods of use |
Family Cites Families (236)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL7409399A (nl) | 1973-07-19 | 1975-01-21 | Rhone Poulenc Sa | Werkwijze ter bereiding van thermostabiele har- sen en voorwerpen geheel of gedeeltelijk be- staande uit deze harsen. |
US4471057A (en) | 1981-06-30 | 1984-09-11 | The Wistar Institute | Detection of colorectal carcinoma |
DK17885D0 (da) | 1985-01-14 | 1985-01-14 | Karlsson Karl Anders | Antiviralt middel |
US4876199A (en) | 1985-04-04 | 1989-10-24 | Fred Hutchinson Cancer Research Center | Hybridomas producing monoclonal antibodies to mono-, di-, and trifucosylated type 2 chain |
US4851511A (en) | 1986-01-30 | 1989-07-25 | Fred Hutchinson Cancer Research Center | Monoclonal antibody that specifically binds to disialosyl Lea |
US4925796A (en) | 1986-03-07 | 1990-05-15 | Massachusetts Institute Of Technology | Method for enhancing glycoprotein stability |
ATE94395T1 (de) | 1986-05-09 | 1993-10-15 | Pulverer Gerhard | Verwendung von spezifischen monosacchariden zur herstellung eines arzneimittels zur verhinderung von metastasen maligner tumore. |
US5538724A (en) | 1987-08-11 | 1996-07-23 | The Board Of Trustees For The Leland Stanford Junior Univ. | Method of control leukocyte extravasation |
US5079353A (en) | 1987-12-02 | 1992-01-07 | Chembiomed, Ltd. | Sialic acid glycosides, antigens, immunoadsorbents, and methods for their preparation |
US5632991A (en) | 1988-11-14 | 1997-05-27 | Brigham & Women's Hospital | Antibodies specific for E-selectin and the uses thereof |
EP0381310A1 (en) | 1989-01-30 | 1990-08-08 | The Biomembrane Institute | Monoclonal antibodies directed to tumor-associated gangliosides and fucogangliosides and method for production thereof |
US5464778A (en) | 1989-03-08 | 1995-11-07 | Board Of Regents Of The University Of Oklahoma | Glycoprotein ligand for P-selectin and methods of use thereof |
US5272263A (en) | 1989-04-28 | 1993-12-21 | Biogen, Inc. | DNA sequences encoding vascular cell adhesion molecules (VCAMS) |
DE69021456T2 (de) | 1989-05-23 | 1996-02-15 | Otsuka Pharma Co Ltd | Monoklonale Antikörper gegen aktivierte endotheliale Zellen. |
US6033665A (en) | 1989-09-27 | 2000-03-07 | Elan Pharmaceuticals, Inc. | Compositions and methods for modulating leukocyte adhesion to brain endothelial cells |
US6001988A (en) | 1990-06-11 | 1999-12-14 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands to lectins |
US6280932B1 (en) | 1990-06-11 | 2001-08-28 | Gilead Sciences, Inc. | High affinity nucleic acid ligands to lectins |
US5576305A (en) | 1990-06-15 | 1996-11-19 | Cytel Corporation | Intercellular adhesion mediators |
US5753631A (en) | 1990-06-15 | 1998-05-19 | Cytel Corporation | Intercellular adhesion mediators |
AU8007791A (en) | 1990-06-15 | 1992-01-07 | Cytel Corporation | Intercellular adhesion mediators |
US6391857B1 (en) | 1990-06-18 | 2002-05-21 | Stanford University | Methods and compositions for endothelial binding |
US6387884B1 (en) | 1990-06-18 | 2002-05-14 | Stanford University | Leukocyte homing modulation |
EP0544815A1 (en) | 1990-07-17 | 1993-06-09 | The Board Of Regents Of The University Of Oklahoma | Peptides from the GMP-140 lectinbindingdomain and selectin binding ligands on carbonhydrates |
US5211937A (en) | 1990-07-30 | 1993-05-18 | Glycomed Incorporated | Method of determining a site of inflammation utilizing elam-1 ligands |
US5143712A (en) | 1990-07-30 | 1992-09-01 | Glycomed Incorporated | Method of determining a site of inflammation utilizing elam-1 ligands |
US5648344A (en) | 1990-07-30 | 1997-07-15 | Glycomed Incorporated | Methods of treating inflammation using selection binding compounds |
US5789573A (en) | 1990-08-14 | 1998-08-04 | Isis Pharmaceuticals, Inc. | Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2 |
NZ240316A (en) | 1990-10-25 | 1996-12-20 | Univ Michigan | Compound for treating disease mediated by the elaboration of elam-1 on endothelial cells |
WO1992009293A1 (en) | 1990-11-23 | 1992-06-11 | The General Hospital Corporation | Inhibition of cell adhesion protein-carbohydrate interactions |
US5151360A (en) | 1990-12-31 | 1992-09-29 | Biomembrane Institute | Effect of n,n,n-trimethylsphingosine on protein kinase-c activity, melanoma cell growth in vitro, metastatic potential in vivo and human platelet aggregation |
US6309639B1 (en) | 1991-02-05 | 2001-10-30 | The Board Of Regents Of The University Of Oklahoma | Method for inhibiting an inflammatory response using antibodies to P-selectin glycoprotein ligand |
US6124267A (en) | 1991-02-05 | 2000-09-26 | Southpac Trust Internationals, Inc. | O-glycan inhibitors of selectin mediated inflammation derived from PSGL-1 |
US6121233A (en) | 1991-04-19 | 2000-09-19 | John L. Magnani | Methods for the inhibition of cancer metastasis mediated by endothelial adhesion molecules |
EP0584229B1 (en) | 1991-05-06 | 2003-07-23 | Genentech, Inc. | A selectin ligand |
US5318890A (en) | 1991-05-06 | 1994-06-07 | The Regents Of The University Of California | Assays for inhibitors of leukocyte adhesion |
US5646123A (en) | 1991-06-10 | 1997-07-08 | Alberta Research Council | Time dependent administration of oligosaccharide glycosides related to blood group determinants having a type I or type II core structure in reducing inflammation in a sensitized mammal arising form exposure to an antigen |
US5352670A (en) | 1991-06-10 | 1994-10-04 | Alberta Research Council | Methods for the enzymatic synthesis of alpha-sialylated oligosaccharide glycosides |
US5580858A (en) | 1991-06-10 | 1996-12-03 | Alberta Research Council | Immunosuppressive and tolerogenic modified Lewisx compounds |
JPH07507040A (ja) | 1991-09-10 | 1995-08-03 | セントコー,インコーポレイテッド | セレクチンによって介在される炎症のペプチド阻害剤 |
US5268364A (en) | 1991-12-12 | 1993-12-07 | The Biomembrane Institute | Method for inhibiting selectin-dependent adhesion of leukocytes and platelets by O-glycosylation modification |
CA2104099A1 (en) | 1991-12-18 | 1993-06-19 | George A. Heavner | Peptide inhibitors of inflammation mediated by selectins |
US5643873A (en) | 1992-05-06 | 1997-07-01 | Affymax Technologies N.V. | Peptides and compounds that bind selectins including endothelial leukocyte adhesion molecule 1 |
US5591835A (en) | 1992-06-29 | 1997-01-07 | Glycomed Incorporated | Substituted lactose derivatives |
CA2100412A1 (en) | 1992-07-15 | 1994-01-16 | Yutaka Yamada | Glycolipid derivatives |
WO1994005310A1 (en) | 1992-09-08 | 1994-03-17 | Centocor, Inc. | Peptide inhibitors of cellular adhesion |
US5519008A (en) | 1992-09-10 | 1996-05-21 | Glycomed Incorporated | Derivatives of triterpenoid acids as inhibitors of cell-adhesion molecules ELAM-1 (E-selectin) and LECAM-1 (L-selectin) |
AU4859793A (en) | 1992-09-11 | 1994-04-12 | Regents Of The University Of California, The | Sulfated ligands for l-selectins and use of chlorates and or sulfatases for the treatment of inflammation |
US5695752A (en) | 1992-09-11 | 1997-12-09 | The Regents Of The University Of California | Treating inflammation via the administration of specific sulfatase enzymes and/or sulfation inhibitor |
US6277975B1 (en) | 1992-10-23 | 2001-08-21 | Genetics Institute, Inc. | Fusions of P-selectin ligand protein and polynucleotides encoding same |
US5843707A (en) | 1992-10-23 | 1998-12-01 | Genetics Institute, Inc. | Nucleic acid encoding a novel P-selectin ligand protein |
EP0601417A3 (de) | 1992-12-11 | 1998-07-01 | Hoechst Aktiengesellschaft | Physiologisch verträglicher und physiologisch abbaubarer, Kohlenhydratrezeptorblocker auf Polymerbasis, ein Verfahren zu seiner Herstellung und seine Verwendung |
US5710123A (en) | 1992-12-18 | 1998-01-20 | Centocor, Inc. | Peptide inhibitors of selectin binding |
DK0695189T3 (da) | 1992-12-29 | 1999-08-09 | Genentech Inc | Behandling af inflammatorisk tarmsygdom med IFN-gammainhibitorer |
US5412123A (en) | 1993-02-08 | 1995-05-02 | Glycomed Incorporated | Anthraquinone and anthracene derivatives as inhibitors of the cell-adhesion molecules of the immune system |
JP2716657B2 (ja) | 1993-02-26 | 1998-02-18 | 株式会社ディ・ディ・エス研究所 | 接着分子elam‐1に特異的結合能を有する化合物 |
US5763413A (en) | 1993-03-04 | 1998-06-09 | Mect Corporation | Lewis-associated compound, process for producing the same, and anti-inflammatory |
US5527890A (en) | 1993-04-16 | 1996-06-18 | Glycomed Incorporated | Derivatives of triterpenoid acids and uses thereof |
DE69326255T2 (de) | 1993-05-05 | 1999-12-30 | Affymax Tech Nv | Elam-1 bindende peptide und zusammensetzungen |
HUT74506A (en) | 1993-05-14 | 1997-01-28 | Cytel Corp | Sialyl lewis-x analogues as inhibitors of cellular adhesion |
US5527785A (en) | 1993-05-14 | 1996-06-18 | The Regents Of The University Of California | Selectin receptor modulating compositions |
SE9301677L (sv) | 1993-05-14 | 1994-11-18 | Kurt G I Nilsson | Syntesmetod |
US5854218A (en) | 1993-05-14 | 1998-12-29 | Cytel Corporation | Sialyl Lex analogues as inhibitors of cellular adhesion |
US5811404A (en) | 1993-05-14 | 1998-09-22 | Cytel Corporation | Sialyl Lex analogues as inhibitors of cellular adhesion |
JP3662021B2 (ja) | 1993-05-17 | 2005-06-22 | アーヴァント イミュノセラピューティクス インコーポレイテッド | 補体関連蛋白質および炭水化物よりなる組成物、ならびに該組成物の製法および使用方法 |
US5856300A (en) | 1994-05-12 | 1999-01-05 | T Cell Sciences, Inc. | Compositions comprising complement related proteins and carbohydrates, and methods for producing and using said compositions |
US5976540A (en) | 1993-05-17 | 1999-11-02 | T Cell Sciences, Inc. | Compositions comprising complement related proteins and carbohydrates, and methods for producing and using said compositions |
US5646248A (en) | 1993-06-08 | 1997-07-08 | La Jolla Cancer Research Foundation | E-selection binding soluble lamp-1 polypeptide |
US5750508A (en) | 1993-06-16 | 1998-05-12 | Glycomed Incorporated | Sialic acid/fucose based medicaments |
US5837689A (en) | 1993-06-16 | 1998-11-17 | Glycomed Incorporated | Sialyl lewis-x mimetics containing naphthyl backbones |
US5658880A (en) | 1993-06-16 | 1997-08-19 | Glycomed Incorporated | Sialic acid/fucose based medicaments |
US5789385A (en) | 1993-06-16 | 1998-08-04 | Glycomed Incorporated | Sialyl Lewisx mimetics containing phenyl backbones |
US5679321A (en) | 1993-06-17 | 1997-10-21 | Glycomed Incorporated | Sialic acid/fucose based medicaments |
DK76193D0 (da) | 1993-06-25 | 1993-06-25 | Astra Ab | Kulhydratderivater |
US5559103A (en) | 1993-07-21 | 1996-09-24 | Cytel Corporation | Bivalent sialyl X saccharides |
US5508387A (en) | 1993-08-04 | 1996-04-16 | Glycomed Incorporated | Selectin binding glycopeptides |
US5827837A (en) | 1993-08-20 | 1998-10-27 | The Regents Of The University Of California | Polyanion anti-inflammatory agents |
US5464815A (en) | 1993-09-08 | 1995-11-07 | Genentech, Inc. | Inhibition of heparin-binding |
WO1995010296A1 (en) | 1993-10-12 | 1995-04-20 | Glycomed Incorporated | A library of glyco-peptides useful for identification of cell adhesion inhibitors |
US5783693A (en) | 1993-11-19 | 1998-07-21 | The Regents Of The University Of California | Methods for synthesizing sulfated disaccharide inhibitors of selectins |
WO1995014787A1 (en) | 1993-11-22 | 1995-06-01 | Centocor, Inc. | Peptide inhibitors of selecting binding |
US5663151A (en) | 1994-03-04 | 1997-09-02 | Bristol-Myers Squibb Company | Sulfated α-glycolipid derivatives as cell adhesion inhibitors |
DE4408248A1 (de) | 1994-03-11 | 1995-09-14 | Hoechst Ag | Physiologisch verträgliche und physiologisch abbaubare Kohlenhydrat-Mimetika, ein Verfahren zur Herstellung und ihre Verwendung |
EP0671409A3 (de) | 1994-03-11 | 1996-06-12 | Hoechst Ag | Malonsäurederivate mit antiadhäsiven Eigenschaften. |
US5444050A (en) | 1994-04-29 | 1995-08-22 | Texas Biotechnology Corporation | Binding of E-selectin or P-selectin to sialyl Lewisx or sialyl-Lewisa |
HUT77345A (hu) | 1994-04-29 | 1998-03-30 | Texas Biotechnology Corporation | E-szelektin, P-szelektin vagy L-szelektin szialil-Lewis x-hez vagy szialil-Lewis a-hoz kapcsolódását gátló mannopiranoziloxi-bifenil származékok és ezeket tartalmazó gyógyszerkészítmények |
US5486536A (en) | 1994-08-15 | 1996-01-23 | The Regents Of The University Of Michigan | Sulfatides as anti-inflammatory compounds |
JPH0899989A (ja) | 1994-09-30 | 1996-04-16 | Akira Hasegawa | 新規糖脂質誘導体およびその製造用中間体 |
DE4436164A1 (de) | 1994-10-10 | 1996-04-11 | Hoechst Ag | Neue Kohlenhydratkonjugate als Inhibitoren der Zelladhäsion |
US5686426A (en) | 1994-11-17 | 1997-11-11 | Bristol-Myers Squibb Company | Dicarboxymethylated glycolipid derivatives as cell adhesion inhibitors |
US6492332B1 (en) | 1995-12-12 | 2002-12-10 | Omeros Corporation | Irrigation solution and methods for inhibition of tumor cell adhesion, pain and inflammation |
US5639734A (en) | 1994-12-20 | 1997-06-17 | Esko; Jeffrey D. | Disaccharide inflammation inhibitors and uses thereof |
CN1176644A (zh) | 1994-12-28 | 1998-03-18 | 住友制药株式会社 | 路易斯x衍生物及其制备方法 |
US20020040008A1 (en) | 1995-01-24 | 2002-04-04 | Wagner Denisa D. | Method for treating and preventing atherosclerosis |
US5527936A (en) | 1995-02-17 | 1996-06-18 | E. I. Du Pont De Nemours And Company | Hydrosilylation of unsaturated compounds |
GB9504065D0 (en) | 1995-03-01 | 1995-04-19 | Pharmacia Spa | Poly-pyrrolecarboxamidonaphthalenic acid derivatives |
US6506770B1 (en) | 1996-06-06 | 2003-01-14 | Anormed, Inc. | Antiviral compounds |
GB9511357D0 (en) | 1995-06-06 | 1995-08-02 | Johnson Matthey Plc | Improved antiviral compounds |
AU6155896A (en) | 1995-06-07 | 1996-12-30 | Cytel Corporation | Humanized antibodies to e-selectin |
US5736533A (en) | 1995-06-07 | 1998-04-07 | Neose Technologies, Inc. | Bacterial inhibition with an oligosaccharide compound |
NZ311686A (en) | 1995-06-29 | 2000-01-28 | Novartis Ag | Diglycosylated 1,2-diols as mimetics of sialyl-lewis x and sialyl-lewis a |
CZ290072B6 (cs) | 1995-06-29 | 2002-05-15 | Texas Biotechnology Corporation | Di- a trivalentní malé molekuly selektinových inhibitorů |
US5876715A (en) | 1995-08-17 | 1999-03-02 | The Biomembrane Institute | Antibodies that bind novel carbohydrate ligands (myelorollins) that cause E-selectin dependent cell rolling, and uses thereof |
DE19532902A1 (de) | 1995-09-06 | 1997-03-13 | Hoechst Ag | Neuartige Glycomimetika als Selektin-Antagonisten und daraus hergestellte entzündungshemmend wirkende Arzneimittel |
DE19537334A1 (de) | 1995-10-09 | 1997-04-10 | Hoechst Ag | Antiadhäsive Piperidin- und Pyrrolidin-Carbonsäuren |
AU7445796A (en) | 1995-10-18 | 1997-05-07 | Cytel Corporation | Sialyl lex analogues as inhibitors of cellular adhesion |
US5919769A (en) | 1995-10-26 | 1999-07-06 | Kanebo, Ltd | Fucose derivatives, drugs containing the same as active ingredient, and intermediates for producing the same |
US5747463A (en) | 1995-11-13 | 1998-05-05 | Bristol-Myers Squibb Company | Malonate derivatives of glycolipids as cell adhesion inhibitors |
JPH09176047A (ja) | 1995-12-25 | 1997-07-08 | Unitika Ltd | 外用医薬製剤 |
DE19602355A1 (de) | 1996-01-24 | 1997-07-31 | Hoechst Ag | Mehrfach fucosylierte Dicarbonsäuren mit antiadhäsiven Eigenschaften |
EP0886639B1 (en) | 1996-01-30 | 2008-05-28 | GlycoMimetics, Inc. | SIALYL-LEWISa AND SIALYL-LEWISx EPITOPE ANALOGUES |
EP0886640B1 (en) | 1996-01-30 | 2007-03-21 | GlycoMimetics, Inc. | SIALYL-LEWISa AND SIALYL-LEWISx EPITOPE ANALOGUES |
US5710023A (en) | 1996-03-01 | 1998-01-20 | Genetics Institute, Inc. | IL-13 cytokine receptor chain |
EP0902681B1 (en) | 1996-03-01 | 2002-05-22 | The Regents of the University of California | Inhibition of selectin binding |
US6344545B1 (en) | 1996-06-14 | 2002-02-05 | Progenics Pharmaceuticals, Inc. | Method for preventing HIV-1 infection of CD4+ cells |
US5654412A (en) | 1996-05-29 | 1997-08-05 | Glycomed Incorporated | Processes for the synthesis of sialyl Lewisx compounds |
CA2197058A1 (en) | 1996-06-05 | 1997-12-06 | Avery B. Nathens | Anti-inflammatory agent |
US5919768A (en) | 1996-06-26 | 1999-07-06 | Texas Biotechnology Corporation | Di- and trivalent small molecule selectin inhibitors |
PL331286A1 (en) | 1996-08-08 | 1999-07-05 | Novartis Ag | Modified oligosaccharides |
US5830871A (en) | 1996-10-28 | 1998-11-03 | The Scripps Research Institute | Inhibitors of E-, P- and L-selectin binding |
GB9618520D0 (en) | 1996-09-05 | 1996-10-16 | Chiroscience Ltd | Compounds and their therapeutic use |
US6592872B1 (en) | 1996-09-17 | 2003-07-15 | The United States Of America As Represented By The Department Of Health And Human Services | Targeting antigens to the MHC class I processing pathway with an anthrax toxin fusion protein |
ATE358492T1 (de) | 1996-09-27 | 2007-04-15 | Univ Columbia | Behandlung einer ischämischen störung und zur verbesserung des infarktergebnis |
US6110897A (en) | 1996-10-10 | 2000-08-29 | Glycorex Ab | Antiinflammatory cell adhesion inhibitors |
WO1998021334A2 (en) | 1996-11-13 | 1998-05-22 | Morphogenesis, Inc. | Antibody mg1 recognizing a small subset of human hematopoietic cells |
US6235309B1 (en) | 1997-02-28 | 2001-05-22 | The Regents Of The University Of California | Inhibition of cell-cell binding by lipid assemblies |
US6120751A (en) | 1997-03-21 | 2000-09-19 | Imarx Pharmaceutical Corp. | Charged lipids and uses for the same |
SE9701127D0 (sv) | 1997-03-26 | 1997-03-26 | Karolinska Innovations Ab | Antigenic fusionprotein carrying GALal, 3GAL epitopes |
JP3720520B2 (ja) | 1997-03-27 | 2005-11-30 | タカラバイオ株式会社 | 糖と標的物との相互作用の測定方法 |
US6413760B1 (en) | 1997-04-15 | 2002-07-02 | Genetics Institute, Inc. | Highly purified mocarhagin cobra venom protease polynucleotides endcoding same and related proteases and therapeutic uses thereof |
US5916910A (en) | 1997-06-04 | 1999-06-29 | Medinox, Inc. | Conjugates of dithiocarbamates with pharmacologically active agents and uses therefore |
US6193973B1 (en) | 1997-08-22 | 2001-02-27 | B. David Tuttle | Dietary supplement for boosting energy and increasing muscular strength |
US5948628A (en) | 1997-09-05 | 1999-09-07 | The Board Of Regents Of The University Of Oklahoma | Methods of screening for compounds which mimic galectin-1 |
US7018637B2 (en) | 1998-02-23 | 2006-03-28 | Aventis Pasteur, Inc | Multi-oligosaccharide glycoconjugate bacterial meningitis vaccines |
WO1999043356A1 (en) | 1998-02-25 | 1999-09-02 | Hsc Research Development Limited Partnership | Antibiotic-ligand conjugates and methods of use thereof |
WO1999043353A2 (en) | 1998-02-26 | 1999-09-02 | Boehringer Ingelheim Pharmaceuticals, Inc. | Combination anti-selectin and immunosuppressant therapy |
CA2245224A1 (en) | 1998-08-14 | 2000-02-14 | Jiang-Hong Giong | Chemokine receptor antagonists and chemotherapeutics |
US6458777B1 (en) | 1998-03-13 | 2002-10-01 | Mucosal Therapeutics Llc | Methods and compositions for treating and preventing mucositis |
US6365365B1 (en) | 1998-03-20 | 2002-04-02 | The Regents Of The University Of California | Method of determining whether an agent modulates glycosyl sulfotransferase-3 |
US6265192B1 (en) | 1998-03-20 | 2001-07-24 | The Regents Of The University Of California | Glycosly sulfortransferase-3 |
US6037333A (en) | 1998-05-07 | 2000-03-14 | Trustees Of Tufts College | Microbe-inhibiting compositions |
CA2330611A1 (en) | 1998-05-22 | 1999-12-02 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules and therapies based thereon |
EP1087996B1 (en) | 1998-06-16 | 2007-01-17 | The Board of Regents of The University of Oklahoma | Glycosulfopeptides and methods of synthesis and use thereof |
US6004815A (en) | 1998-08-13 | 1999-12-21 | The Regents Of The University Of California | Bacteria expressing nonsecreted cytolysin as intracellular microbial delivery vehicles to eukaryotic cells |
JP4553488B2 (ja) | 1998-09-21 | 2010-09-29 | 大塚製薬株式会社 | カルボキシメチルガラクトース誘導体 |
US6960566B1 (en) | 1998-11-06 | 2005-11-01 | The Wister Institute of Anatomy and Biology | Compositions and methods for treatment of cancer |
DE69941031D1 (de) | 1998-11-12 | 2009-08-06 | Novolytics Inc | Zusammensetzungen und verfahren zur erzeugung von gefässeokklusion |
GB9904387D0 (en) | 1999-02-25 | 1999-04-21 | Pharmacia & Upjohn Spa | Antitumour synergistic composition |
US6515117B2 (en) | 1999-10-12 | 2003-02-04 | Bristol-Myers Squibb Company | C-aryl glucoside SGLT2 inhibitors and method |
US6887842B1 (en) | 1999-11-19 | 2005-05-03 | The Board Of Trustees Of The Leland Stanford Junior University | Modulating a pharmacokinetic property of a drug by administering a bifunctional molecule containing the drug |
US7204981B2 (en) | 2000-03-28 | 2007-04-17 | Eli Lilly And Company | Methods of treating diseases with activated protein C |
NZ553687A (en) | 2000-03-30 | 2010-03-26 | Whitehead Biomedical Inst | RNA sequence-specific mediators of RNA interference |
US6683056B2 (en) | 2000-03-30 | 2004-01-27 | Bristol-Myers Squibb Company | O-aryl glucoside SGLT2 inhibitors and method |
US20020031508A1 (en) | 2000-05-19 | 2002-03-14 | Wagner Denisa D. | Methods for diagnosing and treating hemostatic disorders by modulating P-selectin activity |
US20020165178A1 (en) | 2000-06-28 | 2002-11-07 | Christian Schetter | Immunostimulatory nucleic acids for the treatment of anemia, thrombocytopenia, and neutropenia |
WO2002022820A1 (en) | 2000-09-12 | 2002-03-21 | Genetics Institute, Llc | Inhibition of stenosis or restenosis by p-selectin antagonists |
AU2440802A (en) | 2000-10-18 | 2002-04-29 | Massachusetts Inst Technology | Methods and products related to pulmonary delivery of polysaccharides |
WO2002040049A2 (en) | 2000-11-14 | 2002-05-23 | The General Hospital Corporation | Blockade of t cell migration into epithelial gvhd target tissues |
US7422733B2 (en) | 2000-11-29 | 2008-09-09 | Bracco International B.V. | Linkable sialyl Lewis X analogs |
US20020132220A1 (en) | 2000-12-27 | 2002-09-19 | Berens Kurt L. | Use of selectin antagonists in organ preservation solutions |
BR0208474A (pt) | 2001-03-28 | 2006-02-21 | Harvard College | método para fornecer um antìgeno alvo ao citossol de uma célula, polipeptìdeo isolado, dna isolado, vetor, composição farmacêutica, métodos para gerar uma resposta imune mediana por célula em um mamìfero, para produzir uma proteìna, e para medir uma resposta imune mediada por célula, e, kit para medir respostas imunes mediadas por célula in vitro |
US20030198639A1 (en) | 2002-04-16 | 2003-10-23 | Frenette Paul S. | Methods of treating sickle cell disease |
US7087212B2 (en) | 2001-08-17 | 2006-08-08 | Mallinckrodt, Inc | Multicomponent assemblies having enhanced binding properties for diagnosis and therapy |
AU2002337913A1 (en) | 2001-10-19 | 2003-04-28 | Richard D. Cummings | Glycosulfopeptide inhibitors and methods of use thereof |
WO2003049684A2 (en) | 2001-12-07 | 2003-06-19 | Centocor, Inc. | Pseudo-antibody constructs |
WO2003055876A1 (en) | 2001-12-21 | 2003-07-10 | Anormed Inc. | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
US20030186942A1 (en) | 2002-01-16 | 2003-10-02 | Crooks Peter A. | Compounds of use in the treatment of epilepsy, seizure, and electroconvulsive disorders |
AU2003230985A1 (en) | 2002-04-18 | 2003-11-03 | Stephen H. Embury | Method and composition for preventing pain in sickle cell patients |
WO2003097658A2 (en) | 2002-05-16 | 2003-11-27 | Glycomimetics, Inc. | Compounds and methods for inhibiting selectin-mediated function |
CA2490703A1 (en) | 2002-07-03 | 2004-01-15 | Glycomimetics, Inc. | Compositions and methods for diagnosis and therapy of medical conditions involving angiogenesis |
US7556806B2 (en) | 2002-10-11 | 2009-07-07 | University Of Maryland Biotechnology Institute | Carbohydrate-based synthetic vaccines for HIV |
JP2006515306A (ja) | 2002-12-20 | 2006-05-25 | グリコミメティクス, インコーポレイテッド | Pseudomonas細菌感染の処置のためのオリゴ糖およびその結合体 |
US6844125B2 (en) | 2003-03-20 | 2005-01-18 | Kabushiki Kaisha Toshiba | Combination of developing agents, image forming apparatus, and method for forming image |
US7332334B2 (en) | 2003-04-18 | 2008-02-19 | Oklahoma Medical Research Foundation | Hematopoietic stem cells treated by in vitro fucosylation and methods of use |
US20040219158A1 (en) | 2003-05-02 | 2004-11-04 | Glycomimetics, Inc. | Compositions and methods for diagnosis and therapy of medical conditions involving infection with pseudomonas bacteria |
US20050054614A1 (en) | 2003-08-14 | 2005-03-10 | Diacovo Thomas G. | Methods of inhibiting leukocyte accumulation |
US7041226B2 (en) | 2003-11-04 | 2006-05-09 | Lexmark International, Inc. | Methods for improving flow through fluidic channels |
WO2005046597A2 (en) | 2003-11-07 | 2005-05-26 | Brigham And Womens's Hospital, Inc. | Antibodies to cd44 glycoforms and uses thereof |
CA2546784A1 (en) | 2003-11-19 | 2005-06-16 | Glycomimetics, Inc. | Glycomimetic antagonists for both e- and p-selectins |
EP1763533B1 (en) | 2003-11-19 | 2008-01-09 | GlycoMimetics, Inc. | Specific antagonist for both e- and p-selectins |
ES2300877T3 (es) | 2003-12-18 | 2008-06-16 | Unibioscreen S.A. | Derivados de esteroides glucosilados con actividad antimigratoria. |
GB0404434D0 (en) | 2004-02-27 | 2004-03-31 | Novartis Ag | Organic compounds |
US7745421B2 (en) | 2004-05-25 | 2010-06-29 | The Johns Hopkins University | Methods and compositions for treating diseases and disorders associated with Siglec-8 expressing cells |
JP2008504531A (ja) | 2004-06-24 | 2008-02-14 | ザ スクリップス リサーチ インスティテュート | 切断可能なリンカーを有するアレイ |
WO2006017180A2 (en) | 2004-07-09 | 2006-02-16 | Progenics Pharmaceuticals, Inc. | Glycopeptide dimers and uses thereof |
EP1790639B1 (en) | 2004-08-27 | 2014-03-26 | Ono Pharmaceutical Co., Ltd. | Spirocyclic compounds and their use as cxcr4-antagonists |
WO2006062946A2 (en) | 2004-12-06 | 2006-06-15 | University Of Florida Research Foundation, Inc. | Incorporation of bone marrow derived stem cells in tumors |
EP1838320B1 (en) | 2005-01-07 | 2014-07-16 | Emory University | Cxcr4 antagonists for the treatment of medical disorders |
AU2006203826A1 (en) | 2005-01-07 | 2006-07-13 | Emory University | CXCR4 antagonists for the treatment of HIV infection |
CA2598409A1 (en) | 2005-02-17 | 2006-08-24 | Icos Corporation | Phosphoinositide 3-kinase inhibitors for inhibiting leukocyte accumulation |
US20060217303A1 (en) | 2005-03-25 | 2006-09-28 | Wisconsin Alumni Research Foundation | Compounds and Methods for Treating Seizure Disorders |
WO2006127906A1 (en) | 2005-05-25 | 2006-11-30 | Glycomimetics, Inc. | Heterobifunctional compounds for selectin inhibition |
US20060287253A1 (en) | 2005-06-17 | 2006-12-21 | Kriegler Steven M | Compounds and methods for treating seizure disorders |
CA2616166A1 (en) | 2005-07-22 | 2007-02-01 | The Regents Of The University Of California | Heparin compositions and selectin inhibition |
WO2007021721A2 (en) | 2005-08-09 | 2007-02-22 | Glycomimetics, Inc. | Glycomimetic inhibitors of the pa-il lectin, pa-iil lectin or both the lectins from pseudomonas |
US20100003711A1 (en) | 2005-08-15 | 2010-01-07 | The Scripps Research Institute | Methods to identify therapeutic agents |
EP1924260A2 (en) | 2005-08-18 | 2008-05-28 | Novartis AG | Use of cxcr4 binding molecules for the treatment of whim syndrome |
HUE038246T2 (hu) | 2005-09-02 | 2018-10-29 | Glycomimetics Inc | Heterobifunkcionális pan-szelektin inhibitorok |
EP1937308A4 (en) | 2005-09-14 | 2010-09-15 | Univ Maryland Biotech Inst | SYNTHETIC ADDED CARBOHYDRATES AS INGREDIENTS OF MICROBICIDES |
WO2007143052A1 (en) | 2006-06-01 | 2007-12-13 | Glycomimetics, Inc. | Galactosides and thiodigalactosides as inhibitors of pa-il lectin from pseudomonas |
EP2029164B1 (en) | 2006-06-07 | 2015-12-23 | The Board of Trustees of the Leland Stanford Junior University | Anti-leukocyte recruitment therapy for the treatment of seizures and epilepsy |
WO2008002449A2 (en) | 2006-06-23 | 2008-01-03 | Glycomimetics, Inc. | Glycomimetic inhibitors of siglec-8 |
EP2041067A4 (en) | 2006-07-11 | 2009-11-25 | Univ Emory | ANTAGONISTS OF CXCR4 COMPRISING DIAZINE AND TRIAZINE STRUCTURES FOR THE TREATMENT OF MEDICAL DISORDERS |
US20080227799A1 (en) | 2006-07-11 | 2008-09-18 | Liotta Dennis C | CXCR4 Antagonists Including Heteroatoms for the Treatment of Medical Disorders |
WO2008008852A2 (en) | 2006-07-11 | 2008-01-17 | Emory University | Cxcr4 antagonists including heteroatoms for the treatment of medical disorders |
US7998740B2 (en) | 2006-07-18 | 2011-08-16 | Robert Sackstein | Cytokine induction of selectin ligands on cells |
JP5298020B2 (ja) | 2006-10-12 | 2013-09-25 | グリコミメティクス, インコーポレイテッド | ヘキソースおよびn−アセチルヘキソサミンの糖模倣体置換 |
US20080306098A1 (en) | 2006-11-06 | 2008-12-11 | Mutz Mitchell W | Pharmacokinetics of protease inhibitors and other drugs |
US20100145032A1 (en) | 2007-01-18 | 2010-06-10 | Suomen Punainen Risti, Veripalelu | Novel carbohydrate profile compositions from human cells and methods for analysis and modification thereof |
CA2677747A1 (en) | 2007-02-09 | 2008-08-21 | Glycomimetics, Inc. | Methods of use of glycomimetics with replacements for hexoses and n-acetyl hexosamines |
US20080261978A1 (en) | 2007-03-08 | 2008-10-23 | Clark Michael P | Chemokine receptor modulators |
US20090054334A1 (en) | 2007-05-23 | 2009-02-26 | Mutz Mitchell W | Combinatorial improvement of bifunctional drug properties |
US8039442B2 (en) | 2007-07-18 | 2011-10-18 | Glycomimetics, Inc. | Compounds and methods for treatment of sickle cell disease or complications associated therewith |
KR20100042654A (ko) | 2007-08-08 | 2010-04-26 | 교와 핫꼬 기린 가부시키가이샤 | 단리된 세포 집단 |
EP2211913A4 (en) | 2007-10-12 | 2010-12-22 | Transmolecular Inc | SYSTEMIC ADMINISTRATION OF CHLOROTOXIN AGENTS FOR THE DIAGNOSIS AND TREATMENT OF TUMORS |
FI20070853A0 (fi) | 2007-11-09 | 2007-11-09 | Glykos Finland Oy | Glykaania sitovat monoklonaaliset vasta-aineet |
AU2008336249B2 (en) | 2007-12-10 | 2015-01-29 | The University Of Queensland | Treatment and prophylaxis |
US8895510B2 (en) | 2008-04-08 | 2014-11-25 | Glycomimetics, Inc. | Pan-selectin inhibitor with enhanced pharmacokinetic activity |
CA2727788A1 (en) | 2008-06-13 | 2009-12-17 | Glycomimetics, Inc. | Treatment of cancers of the blood using selected glycomimetic compounds |
WO2010025416A1 (en) * | 2008-08-29 | 2010-03-04 | Genzyme Corporation | Cxcr4 antagonists for kidney injury |
US20100240773A1 (en) | 2009-03-23 | 2010-09-23 | Kenneth Korzekwa | Multifunctional linkers |
FI20095459A0 (fi) | 2009-04-24 | 2009-04-24 | Suomen Punainen Risti Veripalv | Uusia määritysmenetelmiä |
WO2010132315A1 (en) | 2009-05-13 | 2010-11-18 | Endgenitor Technologies, Inc. | Enhanced hematopoietic stem cell engraftment |
AU2011237629B2 (en) | 2010-04-07 | 2015-09-17 | Glycomimetics, Inc. | Glycomimetic compounds and methods to inhibit infection by HIV |
US8921328B2 (en) | 2010-09-14 | 2014-12-30 | Glycomimetics, Inc. | E-selectin antagonists |
US20130261070A1 (en) | 2010-10-04 | 2013-10-03 | John L. Magnani | Anti-epileptogenic agents |
FI20106031A0 (fi) | 2010-10-06 | 2010-10-06 | Suomen Punainen Risti Veripalv | Menetelmä solujen eristämiseksi ja menetelmällä eristetty solupopulaatio |
WO2012061662A1 (en) | 2010-11-03 | 2012-05-10 | Glycomimetics, Inc. | Glycomimetic-peptidomimetic inhibitors of e-selectins and cxcr4 chemokine receptors |
US8765126B2 (en) | 2011-05-05 | 2014-07-01 | Robert Sackstein | Methods of treating complications and disorders associated with G-CSF administration |
CA2888527A1 (en) | 2012-10-31 | 2014-05-08 | Glycomimetics, Inc. | E-selectin antagonists compounds and methods of use |
WO2014089269A1 (en) | 2012-12-07 | 2014-06-12 | Glycomimetics, Inc. | Compounds, compositions and methods using e-selectin antagonists for mobilization of hematopoietic cells |
WO2014149837A1 (en) | 2013-03-15 | 2014-09-25 | Glycomimetics, Inc. | Compounds and methods to enhance the oral availability of glycomimetics |
CA2925119A1 (en) | 2013-09-30 | 2015-04-02 | Glycomimetics, Inc. | Methods and compositions for treating and/or preventing mucositis |
US20160333043A1 (en) | 2014-01-17 | 2016-11-17 | Glycomimetics, Inc. | E-Selectin Antagonists Modified By Macrocycle Formation to the Galactose |
SI3227310T1 (sl) | 2014-12-03 | 2019-11-29 | Glycomimetics Inc | Heterobifunkcionalni inhibitorji e-selektinov in receptorjev kemokina CXCR4 |
WO2016164394A1 (en) | 2015-04-08 | 2016-10-13 | Glycomimetics, Inc. | 2-halo-galactose-containing selectin antagonists |
US20200171005A9 (en) | 2015-12-02 | 2020-06-04 | Glycomimetics, Inc. | Heterobifunctional Pan-Selectin Antagonists Having a Triazole Linker |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002543126A (ja) * | 1999-05-03 | 2002-12-17 | スミスクライン・ビーチャム・コーポレイション | Cxcr−4受容体アンタゴニスト−トロンボポエチン模倣物 |
JP2012525393A (ja) * | 2009-05-01 | 2012-10-22 | グリコミメティックス インコーポレイテッド | E−セレクチンおよびcxcr4ケモカイン受容体のヘテロ二官能性阻害剤 |
WO2013096926A1 (en) * | 2011-12-22 | 2013-06-27 | Glycomimetics, Inc. | E-selectin antagonist compounds, compositions, and methods of use |
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AU2015355136B2 (en) | 2020-06-25 |
KR102542750B1 (ko) | 2023-06-12 |
EP3227310B1 (en) | 2019-07-31 |
NZ732034A (en) | 2022-03-25 |
PT3227310T (pt) | 2019-11-06 |
CN107108679B (zh) | 2020-10-23 |
EP3227310A4 (en) | 2018-07-25 |
EP3227310A1 (en) | 2017-10-11 |
WO2016089872A1 (en) | 2016-06-09 |
US10519181B2 (en) | 2019-12-31 |
LT3227310T (lt) | 2019-09-10 |
BR112017011446A2 (pt) | 2018-02-27 |
AU2015355136A1 (en) | 2017-06-08 |
DK3227310T3 (da) | 2019-09-30 |
US20170305951A1 (en) | 2017-10-26 |
EP3569609A1 (en) | 2019-11-20 |
CN107108679A (zh) | 2017-08-29 |
PL3227310T3 (pl) | 2020-02-28 |
SI3227310T1 (sl) | 2019-11-29 |
HUE045542T2 (hu) | 2019-12-30 |
CA2968391A1 (en) | 2016-06-09 |
JP6689854B2 (ja) | 2020-04-28 |
CY1122038T1 (el) | 2020-10-14 |
ES2754549T3 (es) | 2020-04-20 |
CA2968391C (en) | 2022-04-26 |
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