JP2009537540A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2009537540A5 JP2009537540A5 JP2009511053A JP2009511053A JP2009537540A5 JP 2009537540 A5 JP2009537540 A5 JP 2009537540A5 JP 2009511053 A JP2009511053 A JP 2009511053A JP 2009511053 A JP2009511053 A JP 2009511053A JP 2009537540 A5 JP2009537540 A5 JP 2009537540A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- group
- carbons
- rar
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102000003702 retinoic acid receptors Human genes 0.000 claims description 125
- 108090000064 retinoic acid receptors Proteins 0.000 claims description 125
- 125000000217 alkyl group Chemical group 0.000 claims description 109
- 239000005557 antagonist Substances 0.000 claims description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 59
- 229940125425 inverse agonist Drugs 0.000 claims description 57
- 150000003839 salts Chemical class 0.000 claims description 48
- 229910052799 carbon Inorganic materials 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000000126 substance Substances 0.000 claims description 37
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 26
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 241000124008 Mammalia Species 0.000 claims description 21
- 238000002512 chemotherapy Methods 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 19
- 125000001624 naphthyl group Chemical group 0.000 claims description 19
- 238000001959 radiotherapy Methods 0.000 claims description 18
- 206010043554 thrombocytopenia Diseases 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000001544 thienyl group Chemical group 0.000 claims description 14
- 208000004235 neutropenia Diseases 0.000 claims description 13
- LHUPKWKWYWOMSK-UHFFFAOYSA-N 4-[2-[4-(4-ethylphenyl)-2,2-dimethylthiochromen-6-yl]ethynyl]benzoic acid Chemical group C1=CC(CC)=CC=C1C1=CC(C)(C)SC2=CC=C(C#CC=3C=CC(=CC=3)C(O)=O)C=C12 LHUPKWKWYWOMSK-UHFFFAOYSA-N 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 230000003247 decreasing effect Effects 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
- 102100023606 Retinoic acid receptor alpha Human genes 0.000 claims description 11
- 102100033909 Retinoic acid receptor beta Human genes 0.000 claims description 11
- 102100033912 Retinoic acid receptor gamma Human genes 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 102000005962 receptors Human genes 0.000 claims description 11
- 108020003175 receptors Proteins 0.000 claims description 11
- 108091008726 retinoic acid receptors α Proteins 0.000 claims description 11
- 108091008761 retinoic acid receptors β Proteins 0.000 claims description 11
- 108091008760 retinoic acid receptors γ Proteins 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 210000000440 neutrophil Anatomy 0.000 claims description 10
- 125000002971 oxazolyl group Chemical group 0.000 claims description 10
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
- 210000001185 bone marrow Anatomy 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 230000003394 haemopoietic effect Effects 0.000 claims description 8
- BUGXGZOGQGUTBC-UHFFFAOYSA-N 4-[[3-bromo-4-ethoxy-5-(4-methylbenzoyl)benzoyl]amino]benzoic acid Chemical group CCOC1=C(Br)C=C(C(=O)NC=2C=CC(=CC=2)C(O)=O)C=C1C(=O)C1=CC=C(C)C=C1 BUGXGZOGQGUTBC-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000005389 trialkylsiloxy group Chemical group 0.000 claims description 6
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 6
- 206010065553 Bone marrow failure Diseases 0.000 claims description 5
- 208000007502 anemia Diseases 0.000 claims description 5
- 201000002364 leukopenia Diseases 0.000 claims description 5
- 231100001022 leukopenia Toxicity 0.000 claims description 5
- -1 1-ademantyl Chemical group 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 238000010322 bone marrow transplantation Methods 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 210000005259 peripheral blood Anatomy 0.000 claims description 4
- 239000011886 peripheral blood Substances 0.000 claims description 4
- 206010040047 Sepsis Diseases 0.000 claims description 3
- 239000000556 agonist Substances 0.000 claims description 3
- 230000036737 immune function Effects 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 230000005855 radiation Effects 0.000 claims description 3
- 238000011084 recovery Methods 0.000 claims description 3
- 210000000130 stem cell Anatomy 0.000 claims description 3
- 238000002054 transplantation Methods 0.000 claims description 3
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical group C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 claims description 2
- 208000030507 AIDS Diseases 0.000 claims description 2
- 201000004384 Alopecia Diseases 0.000 claims description 2
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical group C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 claims description 2
- 208000019838 Blood disease Diseases 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 206010025327 Lymphopenia Diseases 0.000 claims description 2
- 208000000112 Myalgia Diseases 0.000 claims description 2
- 206010033661 Pancytopenia Diseases 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 208000027418 Wounds and injury Diseases 0.000 claims description 2
- 125000005103 alkyl silyl group Chemical group 0.000 claims description 2
- 231100000360 alopecia Toxicity 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 230000006378 damage Effects 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 208000014951 hematologic disease Diseases 0.000 claims description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 2
- 208000018706 hematopoietic system disease Diseases 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 231100001023 lymphopenia Toxicity 0.000 claims description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 claims description 2
- 208000003265 stomatitis Diseases 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 231100000419 toxicity Toxicity 0.000 claims description 2
- 230000001988 toxicity Effects 0.000 claims description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 61
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 3
- 229940096885 Retinoic acid receptor agonist Drugs 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- 125000006725 C1-C10 alkenyl group Chemical group 0.000 claims 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- CWJSHJJYOPWUGX-UHFFFAOYSA-N chlorpropham Chemical compound CC(C)OC(=O)NC1=CC=CC(Cl)=C1 CWJSHJJYOPWUGX-UHFFFAOYSA-N 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000007910 systemic administration Methods 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 238000000034 method Methods 0.000 description 56
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 230000007115 recruitment Effects 0.000 description 3
- 230000006041 cell recruitment Effects 0.000 description 2
- 0 CC(C)(C)c1cc(C(*c2ccc(*)cc2)=O)cc(C(C)(C)C)c1OI(C)C Chemical compound CC(C)(C)c1cc(C(*c2ccc(*)cc2)=O)cc(C(C)(C)C)c1OI(C)C 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80077306P | 2006-05-16 | 2006-05-16 | |
| PCT/US2007/011730 WO2007136653A2 (en) | 2006-05-16 | 2007-05-16 | Use of a rar antagonist or inverse agonist for the treatment of chemotherapy and/or radiation therapy side effects |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009537540A JP2009537540A (ja) | 2009-10-29 |
| JP2009537540A5 true JP2009537540A5 (https=) | 2011-07-21 |
Family
ID=38566762
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009511053A Pending JP2009537540A (ja) | 2006-05-16 | 2007-05-16 | 化学療法および／または放射線療法の副作用を処置するためのｒａｒアンタゴニストまたはｒａｒインバースアゴニストの使用 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9271946B2 (https=) |
| EP (1) | EP2026778B1 (https=) |
| JP (1) | JP2009537540A (https=) |
| CN (1) | CN101472572B (https=) |
| CA (1) | CA2651487A1 (https=) |
| DK (1) | DK2026778T3 (https=) |
| ES (1) | ES2702128T3 (https=) |
| TR (1) | TR201819157T4 (https=) |
| WO (1) | WO2007136653A2 (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3721880B1 (en) | 2010-09-01 | 2022-02-02 | Thomas Jefferson University | Composition and method for muscle repair and regeneration |
| KR102083046B1 (ko) * | 2012-06-07 | 2020-02-28 | 칠드런＇스 하스피틀 로스 앤젤레스 | 레티노이드 작용제를 이용하여 호중구감소증을 치료하기 위한 방법 |
| US9492431B2 (en) | 2012-11-08 | 2016-11-15 | Yamaguchi University | Therapeutic agent for keratoconjunctive disorders |
| US20140194517A1 (en) * | 2013-01-08 | 2014-07-10 | Io Therapeutics, Inc. | Treatment of Graft-Versus-Host Disease Disorders using RAR Antagonists |
| ES2694831T3 (es) | 2013-05-22 | 2018-12-27 | Yamaguchi University | Inhibidor para trastornos retinocoroideos |
| MX2016010699A (es) | 2014-02-18 | 2017-10-11 | Children's Hospital Los Angeles | Composiciones y metodos para tratar neutropenia. |
| EP3380086B1 (en) | 2015-11-25 | 2021-10-13 | IO Therapeutics, Inc. | Cyp26-resistant rar-alpha selective agonists in the treatment of cancer |
| WO2017201200A1 (en) * | 2016-05-19 | 2017-11-23 | Orphagen Pharmaceuticals, Inc. | Therapeutic compositions containing rar-alpha antagonists |
| JP7023868B2 (ja) | 2016-06-08 | 2022-02-22 | クレメンティア ファーマシューティカルズ，インコーポレイテッド | 異所性骨化を治療するための方法 |
| WO2017214575A1 (en) | 2016-06-10 | 2017-12-14 | Io Therapeutics, Inc. | Receptor selective retinoid and rexinoid compounds and immune modulators for cancer immunotherapy |
| CA3043807A1 (en) | 2016-11-16 | 2018-05-24 | Clementia Pharmaceuticals Inc. | Methods for treating multiple osteochondroma (mo) |
| WO2019014468A1 (en) * | 2017-07-13 | 2019-01-17 | Io Therapeutics, Inc. | RECEPTOR SUBTYPE AND RETINOID COMPOUNDS AND SELECTIVE REXINOIDS OF A FUNCTION IN COMBINATION WITH IMMUNE MODULATORS FOR ANTICANCER IMMUNOTHERAPY |
| US10363272B2 (en) | 2017-08-31 | 2019-07-30 | Io Therapeutics, Inc. | RAR selective agonists in combination with immune modulators for cancer immunotherapy |
| CN113207799B (zh) * | 2021-03-19 | 2022-03-15 | 中山大学 | 一种二型糖尿病小鼠快速心衰模型的构建方法 |
| CN115974860B (zh) * | 2022-12-15 | 2024-09-24 | 复旦大学附属中山医院 | 维甲酸类化合物及其制备方法和用途、含该化合物的药物组合物 |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0638071B1 (en) | 1992-12-28 | 1997-04-09 | Eisai Co., Ltd. | Heterocyclic carbonic acid derivatives which bind to retinoid receptors (rar) |
| US6008204A (en) * | 1995-09-01 | 1999-12-28 | Allergan Sales, Inc. | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
| US5776699A (en) * | 1995-09-01 | 1998-07-07 | Allergan, Inc. | Method of identifying negative hormone and/or antagonist activities |
| US5952345A (en) * | 1995-09-01 | 1999-09-14 | Allergan Sales, Inc. | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
| US6942980B1 (en) * | 1995-09-01 | 2005-09-13 | Allergan, Inc. | Methods of identifying compounds having nuclear receptor negative hormone and/or antagonist activities |
| US6218128B1 (en) * | 1997-09-12 | 2001-04-17 | Allergan Sales, Inc. | Methods of identifying compounds having nuclear receptor negative hormone and/or antagonist activities |
| US5958954A (en) * | 1995-09-01 | 1999-09-28 | Allergan Sales, Inc. | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
| US5877207A (en) * | 1996-03-11 | 1999-03-02 | Allergan Sales, Inc. | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
| US20030219832A1 (en) * | 1996-03-11 | 2003-11-27 | Klein Elliott S. | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
| US5763635A (en) * | 1996-06-21 | 1998-06-09 | Allergan | Tetrahydronaphthalene derivatives substituted in the 8 position with alkyhidene groups having retinoid and/or retinoid antagonist-like biological activity |
| US5773594A (en) * | 1996-06-21 | 1998-06-30 | Allergan | Alkyl or aryl substituted dihydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity |
| US6555690B2 (en) * | 1996-06-21 | 2003-04-29 | Allergan, Inc. | Alkyl or aryl substituted dihydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity |
| US5739338A (en) * | 1996-11-05 | 1998-04-14 | Allergan | N-aryl substituted tetrahydroquinolines having retinoid agonist, retinoid antagonist or retinoid inverse agonist type biological activity |
| US5728846A (en) * | 1996-12-12 | 1998-03-17 | Allergan | Benzo 1,2-g!-chrom-3-ene and benzo 1,2-g!-thiochrom-3-ene derivatives |
| US6037488A (en) * | 1997-04-19 | 2000-03-14 | Allergan Sales, Inc. | Trisubstituted phenyl derivatives having retinoid agonist, antagonist or inverse agonist type biological activity |
| US5919970A (en) * | 1997-04-24 | 1999-07-06 | Allergan Sales, Inc. | Substituted diaryl or diheteroaryl methanes, ethers and amines having retinoid agonist, antagonist or inverse agonist type biological activity |
| US6521641B1 (en) * | 1998-10-08 | 2003-02-18 | Allergan, Inc. | Male anti-fertility agents |
| US6043381A (en) * | 1999-05-07 | 2000-03-28 | Allergan Sales, Inc. | Process for preparing substituted benzo[1,2-g]-chrom-3-ene, benzo[1,2-g]-thiochrom-3-ene and benzo[1,2-g]-1,2-dihydroquinoline derivatives |
| US6313168B1 (en) * | 1999-12-15 | 2001-11-06 | Allergan Sales, Inc. | Use of retinoid receptor antagonists in the treatment of cartilage and bone pathologies |
| US20020193403A1 (en) * | 2001-05-03 | 2002-12-19 | Allergan Sales, Inc. | Methods of treating hyperlipidemia |
| EP1385546A1 (en) * | 2001-05-08 | 2004-02-04 | MERCK PATENT GmbH | Combination therapy using anti-egfr antibodies and anti-hormonal agents |
| IL152904A0 (en) * | 2002-01-24 | 2003-06-24 | Gamida Cell Ltd | Utilization of retinoid and vitamin d receptor antagonists for expansion of renewable stem cell populations |
| WO2003078567A2 (en) * | 2002-03-18 | 2003-09-25 | Gamida-Cell Ltd. | Methods of inducing differentiation in ex vivo expanded stem cells |
| MXPA04011972A (es) * | 2002-06-04 | 2005-03-31 | Galderma Res & Dev | Nuevos ligandos inhibidores de los receptores rars, su procedimiento de preparacion y su uso en medicina humana asi como en cosmetica. |
| US7105566B2 (en) * | 2002-10-22 | 2006-09-12 | Allergan, Inc. | Methods of treatment during vascular procedures |
| ES2283866T3 (es) * | 2002-11-18 | 2007-11-01 | GALDERMA RESEARCH & DEVELOPMENT | Nuevos ligandos que son antagonistas de los receptores rar, procedimiento de preparacion de estos ligandos y utilizacion de estos ligandos en el campo de la medicina humana y de la cosmetica. |
-
2007
- 2007-05-16 TR TR2018/19157T patent/TR201819157T4/tr unknown
- 2007-05-16 CA CA002651487A patent/CA2651487A1/en not_active Abandoned
- 2007-05-16 EP EP07794936.0A patent/EP2026778B1/en not_active Not-in-force
- 2007-05-16 JP JP2009511053A patent/JP2009537540A/ja active Pending
- 2007-05-16 ES ES07794936T patent/ES2702128T3/es active Active
- 2007-05-16 CN CN2007800222950A patent/CN101472572B/zh not_active Expired - Fee Related
- 2007-05-16 DK DK07794936.0T patent/DK2026778T3/en active
- 2007-05-16 WO PCT/US2007/011730 patent/WO2007136653A2/en not_active Ceased
-
2008
- 2008-11-13 US US12/291,994 patent/US9271946B2/en not_active Expired - Fee Related