CN1278725A - 茚并[1,2-c]-、萘并[1,2-c]-和苯并[6,7]芳庚并[1,2-c]吡唑类衍生物 - Google Patents
茚并[1,2-c]-、萘并[1,2-c]-和苯并[6,7]芳庚并[1,2-c]吡唑类衍生物 Download PDFInfo
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- 230000008054 signal transmission Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000009923 sugaring Methods 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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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
- A61K31/33—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
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61P17/06—Antipsoriatics
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- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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Abstract
Description
实施例 | 起始的烯酮(mg) | 2N的NaOH水溶液(μl) | 100个体积H2O2水溶液(μl) |
l1 | 2—(2—吡啶基亚甲基)—1—四氢萘酮(51.2mg) | 108.8 | 44.5×2 |
12 | 2—(3—吡啶基亚甲基)—1—四氢萘酮(49.3mg) | 104.8 | 42.9×2 |
13 | 2—(4—氟代亚苄基)—1—二氢茚酮(50.1mg) | 105.1 | 43.0×2 |
14 | 2—亚苄基—1—苯并环庚酮(50.3mg) | 101.3 | 41.4×2 |
15 | 2—(2—噻吩基亚甲基)—1—苯并环庚酮(51.9ng) | 102.0 | 41.7×2 |
16 | 2—(4—甲氧基亚苄基)—1—四氢萘酮(50.2mg) | 95.0 | 38.8×2 |
17 | 2—(2—氯代亚苄基)—1—四氢萘酮(50.4mg) | 93.8 | 38.4×2 |
18 | 2—(3—氯代亚苄基)—1—四氢萘酮(49.6mg) | 92.3 | 37.8×2 |
19 | 2—(4—氯代亚苄基)—1—四氢萘酮(51.7mg) | 96.2 | 39.4×2 |
20 | 2—(4—异丙基亚苄基)—1—四氢萘酮(50.4mg) | 91.2 | 37.3×3 |
21 | 2—亚胡椒基—1—四氢萘酮(50.5mg) | 90.7 | 37.1×3 |
22 | 6—甲氧基—2—(4—甲基亚苄基)—1—四氢萘酮(51.8mg) | 93.0 | 38.1×3 |
23 | 2—(4—三氟甲基亚苄基)—1—二氢茚酮(49.3mg) | 85.5 | 35.0×2 |
24 | 2—(2,4—二氯亚苄基)—1—二氢茚酮(51.9mg) | 89.7 | 36.7×2 |
25 | 2—(2,3—二甲氧基亚苄基)—1—四氢萘酮(49.6mg) | 84.3 | 34.5×3 |
26 | 6—甲氧基—2—(4—甲氧基亚苄基)—1—四氢萘酮(50.6mg) | 86.0 | 35.2×3 |
27 | 2—(3,5—二甲氧基亚苄基)—1—四氢萘酮(48.8mg) | 82.9 | 33.9×3 |
28 | 5,6—二甲氧基—2—(4—甲氧基亚苄基)—1—二氢茚酮(51.5mg) | 83.0 | 33.93×3 |
实施例 | 10%NH2NH2.H2O的体积μl | 在100℃下加热的时间 |
11 | 212.0 | 38h |
12 | 204.1 | 38h |
13 | 204.8 | 6h |
14 | 197.3 | 38h |
15 | 198.7 | 22h |
16 | 185.0 | 38h |
17 | 182.7 | 38h |
18 | 179.8 | 38h |
19 | 187.4 | 38h |
20 | 177.6 | 22h |
21 | 176.7 | 38h |
22 | 181.3 | 38h |
23 | 166.6 | 6h |
24 | 174.8 | 38h |
25 | 164.1 | 38h |
26 | 167.4 | 22h |
27 | 161.5 | 38h |
28 | 161.6 | 6h |
实施例 | MF | MW | 实测 MH+ | 保留时间(分钟) | 终质量 |
11 | C16H13N3 | 247 | 是 | 4.26 | 15.9mg |
12 | C16H13N3 | 247 | 是 | 3.74 | 10.4mg |
13 | C16H11FN2 | 250 | 是 | 4.60 | 24.9mg |
14 | C18H16N2 | 260 | 是 | 5.10 | 15.8mg |
15 | C16H14N2S | 266 | 是 | 5.07 | 24.1mg |
16 | C18H16N2O | 276 | 是 | 4.75 | 23.6mg |
17 | C17H13ClN2 | 280.5 | 是 | 5.03 | 4.2mg |
18 | C17H13ClN2 | 280.5 | 是 | 5.38 | 16.7mg |
19 | C17H13ClN2 | 280.5 | 是 | 5.40 | 15.7mg |
20 | C20H20N2 | 288 | 是 | 5.87 | 15.0mg |
21 | C18H14N2O2 | 290 | 是 | 4.70 | 11.9mg |
22 | C19H18N2O | 290 | 是 | 5.06 | 7.6mg |
23 | C17H11F3N2 | 300 | 是 | 5.32 | 3.9mg |
24 | C16H10Cl2N2 | 301 | 是 | 5.45 | 5.1mg |
25 | C19H18N2O2 | 306 | 是 | 4.77 | 10.4mg |
26 | C19H18N2O2 | 306 | 是 | 4.64 | 9.8mg |
27 | C19H18N2O2 | 306 | 是 | 4.91 | 11.7mg |
28 | C19H18N2O3 | 322 | 是 | 3.93 | 29.1mg |
实施例 | n | Ar | R1 | R2 | R4 | R5 | R6 | |
1 | 1 | 3—吡啶基 | H | H | H | H | H | H |
2 | 1 | 4—吡啶基 | H | H | H | H | H | H |
3 | 2 | 2—噻吩基 | H | H | H | H | H | H |
4 | 1 | 苯基 | H | H | H | H | H | H |
5 | 1 | 苯基(取代) | H | H | H | 3—OCH3 | H | H |
6 | 1 | 苯基(取代) | H | H | H | 4—OCH3 | H | H |
7 | 1 | 苯基(取代) | H | H | H | 4—CH3 | H | H |
8 | 1 | 2—噻吩基 | 6—OCH3 | H | H | H | H | H |
9 | 1 | 2—呋喃基 | H | H | H | H | H | H |
10 | 1 | 2—噻吩基 | H | H | H | H | H | H |
11 | 2 | 2—吡啶基 | H | H | H | H | H | H |
12 | 2 | 3—吡啶基 | H | H | H | H | H | H |
13 | 1 | 苯基(取代) | H | H | H | H | H | H |
14 | 3 | 苯基 | H | H | H | H | H | H |
15 | 3 | 2—噻吩基 | H | H | H | H | H | H |
16 | 2 | 苯基(取代) | H | H | H | 4—OCH3 | H | H |
17 | 2 | 苯基( 取代) | H | H | H | 2—Cl | H | H |
18 | 2 | 苯基(取代) | H | H | H | 3—Cl | H | H |
19 | 2 | 苯基(取代) | H | H | H | 4—Cl | H | H |
20 | 2 | 苯基(取代) | H | H | H | 4—isoPr | H | H |
21 | 2 | 苯基(取代) | H | H | H | 3.4—OCH2O— | H | |
22 | 2 | 苯基(取代) | 7—OCH3 | H | H | 4—CH3 | H | H |
23 | 2 | 苯基(取代) | H | H | H | 4—CF3 | H | H |
24 | 1 | 苯基(取代) | H | H | H | 2—Cl | 4—Cl | H |
25 | 2 | 苯基(取代) | H | H | H | 2—OCH3 | 3—OCH3 | H |
26 | 2 | 苯基(取代) | 7—OCH3 | H | H | 4—OCH3 | H | H |
27 | 2 | 苯基(取代) | H | H | H | 3—OCH3 | 5—OCH3 | H |
28 | 1 | 苯基(取代) | 6—OCH3 | 7—OCH3 | H | 4—OCH3 | H | H |
29 | 1 | 3—噻吩基 | H | H | H | H | H | H |
试验 | 化合物的IC50 |
KDR | 0.20μM |
flt—1 | >50.0μM |
Lck | >50.0μM |
TIE2 | >50.0μM |
ZAP70 | >50.0μM |
EGFR | >50.0μM |
PKC | ≥20μM |
雌激素受体 | >10.0μM(<10%inh@,10μM) |
式Ⅰ的化舍物,其中 | 细胞VEGF诱导的KDR磷酸化IC50 |
R1是氢,R2是氢,R3是氢,n=1和Ar是2—噻吩基 | 3.0μM |
式Ⅰ的化合物,其中 | VEGF刺激的细胞分裂IC50 |
R1是氢,R2是氢,R3是氢,n=1和Ar是2—噻吩基 | 2.0μM |
Claims (10)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US6118297P | 1997-10-06 | 1997-10-06 | |
US60/061,182 | 1997-10-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1278725A true CN1278725A (zh) | 2001-01-03 |
Family
ID=22034166
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN98811122A Pending CN1278725A (zh) | 1997-10-06 | 1998-10-06 | 茚并[1,2-c]-、萘并[1,2-c]-和苯并[6,7]芳庚并[1,2-c]吡唑类衍生物 |
Country Status (12)
Country | Link |
---|---|
US (1) | US6451834B1 (zh) |
EP (1) | EP1023063B1 (zh) |
JP (1) | JP2001518501A (zh) |
CN (1) | CN1278725A (zh) |
AT (1) | ATE249217T1 (zh) |
AU (1) | AU9691198A (zh) |
CA (1) | CA2304565A1 (zh) |
DE (1) | DE69818083T2 (zh) |
DK (1) | DK1023063T3 (zh) |
ES (1) | ES2206997T3 (zh) |
PT (1) | PT1023063E (zh) |
WO (1) | WO1999017769A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN101677990B (zh) * | 2008-02-01 | 2012-09-26 | 延世大学校产学协力团 | 用于抑制血管发生的药物组合物 |
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Publication number | Priority date | Publication date | Assignee | Title |
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US6162810A (en) * | 1997-11-17 | 2000-12-19 | The Regents Of The University Of California | Inadone and tetralone compounds for inhibiting cell proliferation |
KR20010042868A (ko) | 1998-04-21 | 2001-05-25 | 블레어 큐. 퍼거슨 | 항암제 및 증식 억제제로서의5-아미노인데노[1,2-c]피라졸-4-온 |
PT1073435E (pt) * | 1998-04-30 | 2004-10-29 | Abbott Gmbh & Co Kg | Derivados triciclicos substituidos de pirazole com actividade de proteina-quinase |
EP1126842A2 (en) * | 1998-11-06 | 2001-08-29 | Basf Aktiengesellschaft | Inhibition of the formation of vascular hyperpermeability |
US6462036B1 (en) * | 1998-11-06 | 2002-10-08 | Basf Aktiengesellschaft | Tricyclic pyrazole derivatives |
CZ20011563A3 (cs) * | 1998-11-06 | 2003-02-12 | Basf Aktiengesellschaft | Tricyklické pyrazolové deriváty |
GB9911053D0 (en) * | 1999-05-12 | 1999-07-14 | Pharmacia & Upjohn Spa | 4,5,6,7-tetrahydroindazole derivatives process for their preparation and their use as antitumour agents |
GB9918057D0 (en) * | 1999-07-30 | 1999-10-06 | Univ Bristol | Therapeutic agents |
US20040048844A1 (en) | 1999-10-20 | 2004-03-11 | Bristol-Myers Squibb Pharma Company | Acylsemicarbazides as cyclin dependent kinase inhibitors useful as anti-cancer and anti-proliferative agents |
US6291504B1 (en) | 1999-10-20 | 2001-09-18 | Dupont Pharmaceuticals Company | Acylsemicarbazides and their uses |
YU54202A (sh) | 2000-01-18 | 2006-01-16 | Agouron Pharmaceuticals Inc. | Jedinjenja indazola, farmaceutske smeše i postupci za stimulisanje i inhibiranje ćelijske proliferacije |
HN2001000008A (es) | 2000-01-21 | 2003-12-11 | Inc Agouron Pharmaceuticals | Compuesto de amida y composiciones farmaceuticas para inhibir proteinquinasas, y su modo de empleo |
WO2001079198A1 (en) | 2000-04-18 | 2001-10-25 | Agouron Pharmaceuticals, Inc. | Pyrazoles for inhibiting protein kinase |
MXPA03001189A (es) | 2000-08-09 | 2004-05-14 | Agouron Pharma | Compuestos de pirazol-tiazol, composiciones farmaceuticas que los contienen y su uso para inhibir las cinasas dependientes de ciclinas. |
BR0113258A (pt) | 2000-08-18 | 2003-07-15 | Agouron Pharma | Compostos, pró-drogas, metabólitos ou sais, métodos de tratamento de condição doentia em mamìferos, mediada pela atividade de proteìna cinase e métodos de modulação ou inibição da atividade de um receptor de proteìna cinase |
AU2002228849A1 (en) * | 2000-12-08 | 2002-06-18 | Bristol-Myers Squibb Pharma Company | Semicarbazides and their uses as cyclin dependent kinase inhibitors |
CA2450954A1 (en) * | 2001-06-20 | 2003-01-03 | Imclone Systems Incorporated | Method of treating atherosclerosis and other inflammatory diseases |
EP1444207A2 (en) | 2001-09-19 | 2004-08-11 | Pharmacia Corporation | Substituted pyrazolyl-compounds for the treatment of inflammation |
US6831093B2 (en) * | 2002-01-22 | 2004-12-14 | The Regents Of The University Of California | Non-steroidal ligands for the glucocorticoid receptor, compositions and uses thereof |
PL374062A1 (en) | 2002-05-15 | 2005-09-19 | Janssen Pharmaceutica N.V. | N-substituted tricyclic 3-aminopyrazoles as pdfg receptor inhibitors |
US7320986B2 (en) | 2003-03-07 | 2008-01-22 | Abbott Labortories | Fused tri and tetra-cyclic pyrazole kinase inhibitors |
MXPA05009576A (es) * | 2003-03-07 | 2005-12-12 | Abbott Lab | Inhibidores de pirazol-quinasa triciclicos y tetraciclicos, fundidos. |
CN1914179A (zh) * | 2003-11-13 | 2007-02-14 | 詹森药业有限公司 | 用于生物分子靶标识别的固定的n-取代的三环3-氨基吡唑类 |
CA2583177A1 (en) * | 2004-10-13 | 2006-04-27 | Ptc Therapeutics, Inc. | Compounds for nonsense suppression, and methods for their use |
SI1869020T1 (sl) | 2005-03-29 | 2011-02-28 | Icos Corp | Derivati heteroaril uree, ki so uporabni za inhibicijo chk1 |
WO2007025303A2 (en) * | 2005-08-26 | 2007-03-01 | The Regents Of The University Of California | Non-steroidal antiandrogens |
WO2011059784A1 (en) * | 2009-10-29 | 2011-05-19 | Bristol-Myers Squibb Company | Tricyclic heterocyclic compounds |
TWI553010B (zh) * | 2012-04-12 | 2016-10-11 | 財團法人生物技術開發中心 | 雜環吡唑化合物,其製備方法及用途 |
AR097138A1 (es) * | 2013-07-15 | 2016-02-24 | Basf Se | Compuestos plaguicidas |
US10633354B2 (en) | 2016-09-02 | 2020-04-28 | Bristol-Myers Squibb Company | Substituted tricyclic heterocyclic compounds |
US11046646B2 (en) | 2017-08-09 | 2021-06-29 | Bristol-Myers Squibb Company | Alkylphenyl compounds |
WO2019032631A1 (en) | 2017-08-09 | 2019-02-14 | Bristol-Myers Squibb Company | OXIME ETHER COMPOUNDS |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE789948A (fr) * | 1971-10-13 | 1973-04-11 | Sandoz Sa | Nouveaux derives du pyrazole, leur preparation et leur application comme medicaments |
US3843665A (en) * | 1973-04-11 | 1974-10-22 | Sandoz Ag | Process for preparing substituted indeno,naphtho and cyclohepta pyrazoles |
AU658646B2 (en) * | 1991-05-10 | 1995-04-27 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
WO1994014777A1 (en) * | 1992-12-28 | 1994-07-07 | Eisai Co., Ltd. | Heterocyclic carbonic acid derivatives which bind to retinoid receptors (rar) |
WO1996014843A2 (en) * | 1994-11-10 | 1996-05-23 | Cor Therapeutics, Inc. | Pharmaceutical pyrazole compositions useful as inhibitors of protein kinases |
WO1996031510A1 (en) * | 1995-04-03 | 1996-10-10 | Novartis Ag | Pyrazole derivatives and processes for the preparation thereof |
US5593997A (en) | 1995-05-23 | 1997-01-14 | Pfizer Inc. | 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors |
-
1998
- 1998-10-06 DK DK98951011T patent/DK1023063T3/da active
- 1998-10-06 DE DE69818083T patent/DE69818083T2/de not_active Expired - Fee Related
- 1998-10-06 AT AT98951011T patent/ATE249217T1/de not_active IP Right Cessation
- 1998-10-06 CN CN98811122A patent/CN1278725A/zh active Pending
- 1998-10-06 JP JP2000514640A patent/JP2001518501A/ja active Pending
- 1998-10-06 WO PCT/US1998/021258 patent/WO1999017769A1/en active IP Right Grant
- 1998-10-06 PT PT98951011T patent/PT1023063E/pt unknown
- 1998-10-06 EP EP98951011A patent/EP1023063B1/en not_active Expired - Lifetime
- 1998-10-06 AU AU96911/98A patent/AU9691198A/en not_active Abandoned
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- 1998-10-06 ES ES98951011T patent/ES2206997T3/es not_active Expired - Lifetime
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101677990B (zh) * | 2008-02-01 | 2012-09-26 | 延世大学校产学协力团 | 用于抑制血管发生的药物组合物 |
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CA2304565A1 (en) | 1999-04-15 |
EP1023063B1 (en) | 2003-09-10 |
DE69818083D1 (de) | 2003-10-16 |
DK1023063T3 (da) | 2004-01-26 |
EP1023063A1 (en) | 2000-08-02 |
JP2001518501A (ja) | 2001-10-16 |
US6451834B1 (en) | 2002-09-17 |
ES2206997T3 (es) | 2004-05-16 |
PT1023063E (pt) | 2004-02-27 |
DE69818083T2 (de) | 2004-07-08 |
WO1999017769A1 (en) | 1999-04-15 |
AU9691198A (en) | 1999-04-27 |
ATE249217T1 (de) | 2003-09-15 |
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