RU2239455C2 - Фармацевтические композиции, содержащие агонист или антагонист аденозинового рецептора - Google Patents
Фармацевтические композиции, содержащие агонист или антагонист аденозинового рецептора Download PDFInfo
- Publication number
- RU2239455C2 RU2239455C2 RU2002109228/15A RU2002109228A RU2239455C2 RU 2239455 C2 RU2239455 C2 RU 2239455C2 RU 2002109228/15 A RU2002109228/15 A RU 2002109228/15A RU 2002109228 A RU2002109228 A RU 2002109228A RU 2239455 C2 RU2239455 C2 RU 2239455C2
- Authority
- RU
- Russia
- Prior art keywords
- group
- adenosine
- active ingredient
- iodobenzyl
- alkyl
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 28
- 239000000556 agonist Substances 0.000 title abstract description 14
- 108050000203 Adenosine receptors Proteins 0.000 title abstract description 10
- 102000009346 Adenosine receptors Human genes 0.000 title abstract description 10
- 239000005557 antagonist Substances 0.000 title description 9
- 230000000694 effects Effects 0.000 claims abstract description 65
- 230000035755 proliferation Effects 0.000 claims abstract description 54
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims abstract description 44
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims abstract description 44
- 239000003814 drug Substances 0.000 claims abstract description 37
- 229940079593 drug Drugs 0.000 claims abstract description 34
- 201000002364 leukopenia Diseases 0.000 claims abstract description 32
- 231100001022 leukopenia Toxicity 0.000 claims abstract description 32
- 238000011282 treatment Methods 0.000 claims abstract description 31
- 239000000203 mixture Substances 0.000 claims abstract description 20
- 231100000331 toxic Toxicity 0.000 claims abstract description 18
- 230000002588 toxic effect Effects 0.000 claims abstract description 18
- 230000028327 secretion Effects 0.000 claims abstract description 13
- 230000012010 growth Effects 0.000 claims abstract description 8
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 102
- 239000004480 active ingredient Substances 0.000 claims description 93
- 210000004027 cell Anatomy 0.000 claims description 61
- IPSYPUKKXMNCNQ-PFHKOEEOSA-N (2s,3s,4r,5r)-5-[2-chloro-6-[(3-iodophenyl)methylamino]purin-9-yl]-3,4-dihydroxy-n-methyloxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NC)O[C@H]1N1C2=NC(Cl)=NC(NCC=3C=C(I)C=CC=3)=C2N=C1 IPSYPUKKXMNCNQ-PFHKOEEOSA-N 0.000 claims description 52
- 229960005305 adenosine Drugs 0.000 claims description 51
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 49
- HUJXGQILHAUCCV-MOROJQBDSA-N 3-iodobenzyl-5'-N-methylcarboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NC)O[C@H]1N1C2=NC=NC(NCC=3C=C(I)C=CC=3)=C2N=C1 HUJXGQILHAUCCV-MOROJQBDSA-N 0.000 claims description 47
- -1 nitro, hydroxyl Chemical group 0.000 claims description 42
- 210000002798 bone marrow cell Anatomy 0.000 claims description 41
- 210000000265 leukocyte Anatomy 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 206010028980 Neoplasm Diseases 0.000 claims description 30
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 29
- 239000002246 antineoplastic agent Substances 0.000 claims description 28
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- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
- 238000004519 manufacturing process Methods 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 18
- 102000005962 receptors Human genes 0.000 claims description 17
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- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 14
- 230000002265 prevention Effects 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 230000010261 cell growth Effects 0.000 claims description 13
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 11
- 230000002159 abnormal effect Effects 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
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- 150000003833 nucleoside derivatives Chemical group 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 230000004069 differentiation Effects 0.000 claims description 7
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- 239000002593 adenosine A3 receptor agonist Substances 0.000 claims description 6
- 150000003931 anilides Chemical group 0.000 claims description 6
- MWEQTWJABOLLOS-UHFFFAOYSA-L disodium;[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical compound O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP([O-])(=O)OP(O)([O-])=O)C(O)C1O MWEQTWJABOLLOS-UHFFFAOYSA-L 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 5
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 5
- 230000009471 action Effects 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 229940122216 Adenosine A3 receptor agonist Drugs 0.000 claims description 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 4
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
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- 125000000101 thioether group Chemical group 0.000 claims description 3
- XTPOZVLRZZIEBW-SCFUHWHPSA-N (2r,3r,4s,5r)-2-[6-[2-(4-aminophenyl)ethylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=CC(N)=CC=C1CCNC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 XTPOZVLRZZIEBW-SCFUHWHPSA-N 0.000 claims description 2
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims description 2
- 125000003853 4-amino-3-iodobenzyl group Chemical group [H]N([H])C1=C(I)C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
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- 208000008784 apnea Diseases 0.000 claims description 2
- 125000002648 azanetriyl group Chemical group *N(*)* 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000005030 pyridylthio group Chemical group N1=C(C=CC=C1)S* 0.000 claims description 2
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 2
- FDEACFAXFCKCHZ-MOROJQBDSA-N (2s,3s,4r,5r)-5-(6-amino-2-hex-1-ynylpurin-9-yl)-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound C12=NC(C#CCCCC)=NC(N)=C2N=CN1[C@@H]1O[C@H](C(=O)NCC)[C@@H](O)[C@H]1O FDEACFAXFCKCHZ-MOROJQBDSA-N 0.000 claims 15
- 238000009472 formulation Methods 0.000 claims 5
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 4
- 229930024421 Adenine Natural products 0.000 claims 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims 2
- 229960000643 adenine Drugs 0.000 claims 2
- WHYVKEGFJPLEJZ-UHFFFAOYSA-N n-[(3-iodophenyl)methyl]-7h-purin-6-amine Chemical compound IC1=CC=CC(CNC=2C=3NC=NC=3N=CN=2)=C1 WHYVKEGFJPLEJZ-UHFFFAOYSA-N 0.000 claims 2
- UMMMZHIKPLYIHG-LPWJYYESSA-N (1s,2r,3s,4r)-4-(6-amino-2-chloropurin-9-yl)cyclopentane-1,2,3-triol Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1C[C@H](O)[C@@H](O)[C@H]1O UMMMZHIKPLYIHG-LPWJYYESSA-N 0.000 claims 1
- OZCCPYHYSIPRDM-PAPYEOQZSA-N (1s,2r,3s,4r)-4-[6-amino-2-(2-phenylethylamino)purin-9-yl]cyclopentane-1,2,3-triol Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](O)C3)O)C=NC=2C(N)=NC=1NCCC1=CC=CC=C1 OZCCPYHYSIPRDM-PAPYEOQZSA-N 0.000 claims 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 125000006681 (C2-C10) alkylene group Chemical group 0.000 claims 1
- NFHVNDANLVCJHE-UHFFFAOYSA-N 2-chloro-n-[(3-iodophenyl)methyl]-9-(oxolan-2-yl)purin-6-amine Chemical compound C=12N=CN(C3OCCC3)C2=NC(Cl)=NC=1NCC1=CC=CC(I)=C1 NFHVNDANLVCJHE-UHFFFAOYSA-N 0.000 claims 1
- ATOXAERIKXFYQV-UHFFFAOYSA-N 2-chloro-n-[(3-iodophenyl)methyl]-9-methylpurin-6-amine Chemical compound N1=C(Cl)N=C2N(C)C=NC2=C1NCC1=CC=CC(I)=C1 ATOXAERIKXFYQV-UHFFFAOYSA-N 0.000 claims 1
- OJUZWXZBQQALOH-UHFFFAOYSA-N 2-n-hexyl-6-n-[(3-iodophenyl)methyl]-9-methylpurine-2,6-diamine Chemical compound C=12N=CN(C)C2=NC(NCCCCCC)=NC=1NCC1=CC=CC(I)=C1 OJUZWXZBQQALOH-UHFFFAOYSA-N 0.000 claims 1
- APXSDGLADFOEDD-UHFFFAOYSA-N 4-[6-[(3-iodophenyl)methylamino]purin-9-yl]butanenitrile Chemical compound IC1=CC=CC(CNC=2C=3N=CN(CCCC#N)C=3N=CN=2)=C1 APXSDGLADFOEDD-UHFFFAOYSA-N 0.000 claims 1
- XBNTWQABLLKTFL-UHFFFAOYSA-N 6-n-[(3-iodophenyl)methyl]-2-n,2-n,9-trimethylpurine-2,6-diamine Chemical compound C=12N=CN(C)C2=NC(N(C)C)=NC=1NCC1=CC=CC(I)=C1 XBNTWQABLLKTFL-UHFFFAOYSA-N 0.000 claims 1
- IKLSILSIWVEUSQ-UHFFFAOYSA-N 6-n-[(3-iodophenyl)methyl]-2-n,9-dimethylpurine-2,6-diamine Chemical compound C=12N=CN(C)C2=NC(NC)=NC=1NCC1=CC=CC(I)=C1 IKLSILSIWVEUSQ-UHFFFAOYSA-N 0.000 claims 1
- AZPDSYNWGWXMJJ-UHFFFAOYSA-N 6-n-[(3-iodophenyl)methyl]-9-methyl-2-n-propylpurine-2,6-diamine Chemical compound C=12N=CN(C)C2=NC(NCCC)=NC=1NCC1=CC=CC(I)=C1 AZPDSYNWGWXMJJ-UHFFFAOYSA-N 0.000 claims 1
- CRCODYWJYJOVSH-UHFFFAOYSA-N 6-n-[(3-iodophenyl)methyl]-9-methylpurine-2,6-diamine Chemical compound N1=C(N)N=C2N(C)C=NC2=C1NCC1=CC=CC(I)=C1 CRCODYWJYJOVSH-UHFFFAOYSA-N 0.000 claims 1
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- ISRXYCXDEAVHOY-UHFFFAOYSA-N n-[(3-iodophenyl)methyl]-2-methoxy-9-methylpurin-6-amine Chemical compound C=12N=CN(C)C2=NC(OC)=NC=1NCC1=CC=CC(I)=C1 ISRXYCXDEAVHOY-UHFFFAOYSA-N 0.000 claims 1
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| IL13368099A IL133680A0 (en) | 1999-09-10 | 1999-12-23 | Pharmaceutical compositions comprising an adenosine receptor agonist or antagonist |
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Cited By (1)
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| RU2391103C2 (ru) * | 2004-10-15 | 2010-06-10 | Си Ви Терапьютикс, Инк. | Способ предупреждения и лечения ремоделирования дыхательных путей и воспаления легких с применением антагонистов аденозиновых рецепторов a2b |
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| IL121272A (en) * | 1997-07-10 | 2000-06-01 | Can Fite Technologies Ltd | Pharmaceutical compositions comprising adenosine and their use for treating or preventing leukopenia |
| AU8181701A (en) | 2000-06-21 | 2002-01-02 | Hoffmann La Roche | Benzothiazole derivatives |
| JP4012070B2 (ja) * | 2001-01-16 | 2007-11-21 | カン−フィテ・バイオファーマ・リミテッド | ウイルスの複製を阻害するためのアデノシンａ３受容体アゴニストの使用 |
| US20020115635A1 (en) * | 2001-02-21 | 2002-08-22 | Pnina Fishman | Modulation of GSK-3beta activity and its different uses |
| US20040204481A1 (en) * | 2001-04-12 | 2004-10-14 | Pnina Fishman | Activation of natural killer cells by adenosine A3 receptor agonists |
| US7049303B2 (en) | 2001-11-07 | 2006-05-23 | Medical Research Council | Inhibition of viruses |
| US7414036B2 (en) | 2002-01-25 | 2008-08-19 | Muscagen Limited | Compounds useful as A3 adenosine receptor agonists |
| EP1554583B1 (en) * | 2002-10-22 | 2007-08-22 | Can-Fite Biopharma Ltd. | The use of the a3 adenosine receptor as a marker for a disease state |
| US7087761B2 (en) | 2003-01-07 | 2006-08-08 | Hoffmann-La Roche Inc. | Cyclization process for substituted benzothiazole derivatives |
| CN1956983B (zh) | 2004-05-24 | 2010-05-26 | 弗·哈夫曼-拉罗切有限公司 | 4-羟基-4-甲基-哌啶-1-甲酸(4-甲氧基-7-吗啉-4-基-苯并噻唑-2-基)-酰胺 |
| CN103087133B (zh) | 2004-05-26 | 2016-09-14 | 伊诺泰克制药公司 | 嘌呤衍生物作为腺苷a1受体激动剂及其用法 |
| US7825102B2 (en) | 2004-07-28 | 2010-11-02 | Can-Fite Biopharma Ltd. | Treatment of dry eye conditions |
| CN101437526A (zh) | 2004-09-20 | 2009-05-20 | 伊诺泰克制药公司 | 嘌呤衍生物及其用法 |
| JP4633123B2 (ja) | 2004-11-05 | 2011-02-16 | エフ．ホフマン−ラ ロシュ アーゲー | イソニコチン酸誘導体の製造方法 |
| JP2008519029A (ja) * | 2004-11-08 | 2008-06-05 | キャン−ファイト・バイオファーマ・リミテッド | 加速骨吸収の治療的処置 |
| WO2007040565A2 (en) * | 2004-11-22 | 2007-04-12 | King Pharmaceuticals Research & Development, Inc. | Enhancing treatment of cancer and hif-1 mediated disoders with adenosine a3 receptor antagonists |
| DE602006012815D1 (de) | 2005-03-23 | 2010-04-22 | Hoffmann La Roche | Acetylenylpyrazolopyrimidinderivate als mglur2-antagonsten |
| AU2006298829B2 (en) | 2005-09-27 | 2011-03-03 | F. Hoffmann-La Roche Ag | Oxadiazolyl pyrazolo-pyrimidines as mGluR2 antagonists |
| EA015683B1 (ru) | 2005-11-30 | 2011-10-31 | Инотек Фармасьютикалз Корпорейшн | Производные пурина и способы их применения |
| BRPI0621052A2 (pt) * | 2006-01-27 | 2012-07-17 | Can Fite Biopharma Ltd | uso de um agonista de receptor de adenosina a3 (a3ar) |
| WO2008023362A2 (en) * | 2006-08-21 | 2008-02-28 | Can-Fite Biopharma Ltd. | Use of a combination of methotrexate and an a3ar agonist for the treatment of cancer |
| MX2009003750A (es) * | 2006-10-06 | 2009-06-18 | Univ Pennsylvania | Suministro eficiente de antagonistas del receptor de adenosina a3 de especies cruzadas, para reducir la presion intraocular. |
| GB0625100D0 (en) * | 2006-12-15 | 2007-01-24 | Univ Murcia | Epigallocatechin-3-gallate compositions for cancer therapy and chemoprotection |
| US20090088403A1 (en) * | 2007-05-07 | 2009-04-02 | Randy Blakely | A3 adenosine receptors as targets for the modulation of central serotonergic signaling |
| CA2694983A1 (en) * | 2007-07-17 | 2009-01-22 | Combinatorx, Incorporated | Treatments of b-cell proliferative disorders |
| US20090047243A1 (en) * | 2007-07-17 | 2009-02-19 | Richard Rickles | Combinations for the treatment of b-cell proliferative disorders |
| WO2009151569A2 (en) * | 2008-06-09 | 2009-12-17 | Combinatorx, Incorporated | Beta adrenergic receptor agonists for the treatment of b-cell proliferative disorders |
| WO2010027935A1 (en) * | 2008-09-08 | 2010-03-11 | Merck Sharp & Dohme Corp. | Ahcy hydrolase inhibitors for treatment of hyper homocysteinemia |
| JP5849044B2 (ja) | 2009-05-17 | 2016-01-27 | キャン−ファイト バイオファーマ リミテッド | 眼圧低下のためのａ３アデノシン受容体作動薬 |
| WO2011010306A1 (en) | 2009-07-21 | 2011-01-27 | Ramot At Tel-Aviv University Ltd. | A3 adenosine receptor ligands for modulation of pigmentation |
| WO2011074903A2 (ko) * | 2009-12-17 | 2011-06-23 | 이화여자대학교 산학협력단 | Ａ3 아데노신 수용체 효능제를 포함하는 약제학적 조성물 |
| LT2523669T (lt) | 2010-01-11 | 2017-04-25 | Inotek Pharmaceuticals Corporation | Akispūdžio mažinimo būdas, derinys ir rinkinys |
| MX2012010006A (es) | 2010-03-03 | 2013-01-17 | Us Gov Health & Human Serv | Agonistas de a3ar para el tratamiento de uveitis. |
| PH12012501906A1 (en) | 2010-03-26 | 2013-01-14 | Inotek Pharmaceuticals Corp | Method of reducing intraocular pressure in humans using n6 -cyclopentyladenosine (cpa), cpa derivatives or prodrugs thereof |
| WO2011123518A1 (en) | 2010-03-31 | 2011-10-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Adenosine receptor agonists for the treatment and prevention of vascular or joint capsule calcification disorders |
| UA117095C2 (uk) | 2011-12-22 | 2018-06-25 | Аліос Біофарма, Інк. | Нуклеозидна сполука або її фармацевтично прийнятна сіль |
| CN104159589A (zh) * | 2012-01-23 | 2014-11-19 | 坎-菲特生物药物有限公司 | 肝脏状况的治疗 |
| PT2807178T (pt) | 2012-01-26 | 2017-08-08 | Inotek Pharmaceuticals Corp | Polimorfos anidros de nitrato de (2r,3s,4r,5r)-5-(6-(ciclopentilamino)-9h-purin-9-il)-3,4-dihidroxitetrahidrofuran-2-il)}metilo e seus processos de preparação |
| US9441007B2 (en) | 2012-03-21 | 2016-09-13 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| USRE48171E1 (en) | 2012-03-21 | 2020-08-25 | Janssen Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
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| AU2013290418B2 (en) | 2012-07-19 | 2017-08-03 | Chaozhong Cai | Octahydro-cyclopentapyrrolyl antagonists of CCR2 |
| JP6140825B2 (ja) | 2012-08-09 | 2017-05-31 | キャン−ファイト バイオファーマ リミテッドＣａｎ−Ｆｉｔｅ ＢｉｏＰｈａｒｍａ Ｌｔｄ． | 性機能不全の治療に使用するためのａ３アデノシン受容体リガンド |
| NZ630759A (en) | 2013-03-15 | 2017-07-28 | Inotek Pharmaceuticals Corp | Ophthalmic formulations comprising an a1 agonist |
| IL242723B (en) | 2015-11-23 | 2019-12-31 | Can Fite Biopharma Ltd | A3 adenosine receptor ligand for the treatment of ectopic fat accumulation |
| KR102445887B1 (ko) | 2016-04-21 | 2022-09-21 | 아스트로사이트 파마슈티컬스, 인코포레이티드 | 신경계 및 심혈관계 병태 치료를 위한 화합물 및 방법 |
| IL254535A0 (en) * | 2017-09-17 | 2017-11-30 | Can Fite Biopharma Ltd | Adenosine a3 receptor ligand for use in the management of cytokine release syndrome |
| IL276358B2 (en) | 2018-02-09 | 2024-11-01 | Astrocyte Pharmaceuticals Inc | Compounds and methods for treating addiction and related disorders |
| EA202190576A1 (ru) | 2018-09-26 | 2021-09-03 | Астросайт Фармасьютикалс, Инк. | Полиморфные соединения и их применение |
| IL264112A (en) | 2019-01-06 | 2020-07-30 | Fishman Pnina | An a3 adenosine receptor ligand for use for reducing level of adipocytes |
| IT202300014340A1 (it) | 2023-07-10 | 2025-01-10 | Consiglio Nazionale Ricerche | Trattamento di malattie associate alla disfunzione del gene ocrl. |
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| RU2391103C2 (ru) * | 2004-10-15 | 2010-06-10 | Си Ви Терапьютикс, Инк. | Способ предупреждения и лечения ремоделирования дыхательных путей и воспаления легких с применением антагонистов аденозиновых рецепторов a2b |
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