IL206914A - Substituted spirocyclic piperidine derivatives as histamine-3 (h3) receptor ligands - Google Patents
Substituted spirocyclic piperidine derivatives as histamine-3 (h3) receptor ligandsInfo
- Publication number
- IL206914A IL206914A IL206914A IL20691410A IL206914A IL 206914 A IL206914 A IL 206914A IL 206914 A IL206914 A IL 206914A IL 20691410 A IL20691410 A IL 20691410A IL 206914 A IL206914 A IL 206914A
- Authority
- IL
- Israel
- Prior art keywords
- alkyl
- compound according
- optionally substituted
- disorders
- methyl
- Prior art date
Links
- 150000003053 piperidines Chemical class 0.000 title abstract description 4
- 239000003446 ligand Substances 0.000 title description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 208000035475 disorder Diseases 0.000 claims abstract description 29
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 11
- 201000003631 narcolepsy Diseases 0.000 claims abstract description 11
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims abstract description 10
- 208000008589 Obesity Diseases 0.000 claims abstract description 9
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 9
- 235000020824 obesity Nutrition 0.000 claims abstract description 9
- 208000020016 psychiatric disease Diseases 0.000 claims abstract description 9
- 208000030814 Eating disease Diseases 0.000 claims abstract description 6
- 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 6
- 208000018522 Gastrointestinal disease Diseases 0.000 claims abstract description 6
- 206010061218 Inflammation Diseases 0.000 claims abstract description 6
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 6
- 208000019022 Mood disease Diseases 0.000 claims abstract description 6
- 208000002193 Pain Diseases 0.000 claims abstract description 6
- 230000004075 alteration Effects 0.000 claims abstract description 6
- 230000037007 arousal Effects 0.000 claims abstract description 6
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- 230000004634 feeding behavior Effects 0.000 claims abstract description 6
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- 150000001875 compounds Chemical class 0.000 claims description 122
- 125000000217 alkyl group Chemical group 0.000 claims description 85
- 239000000203 mixture Substances 0.000 claims description 74
- -1 oxazolyi Chemical group 0.000 claims description 62
- 125000004432 carbon atom Chemical group C* 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- 229910052731 fluorine Inorganic materials 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 24
- 102220496571 MAGUK p55 subfamily member 3_R20A_mutation Human genes 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 150000001413 amino acids Chemical class 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000004122 cyclic group Chemical group 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 12
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
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- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 claims description 4
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- 238000000034 method Methods 0.000 abstract description 35
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 254
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 82
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- 239000000047 product Substances 0.000 description 52
- 239000000243 solution Substances 0.000 description 42
- 239000012267 brine Substances 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
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- 238000003786 synthesis reaction Methods 0.000 description 24
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- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000010410 layer Substances 0.000 description 20
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- 229910052794 bromium Inorganic materials 0.000 description 19
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 102000005962 receptors Human genes 0.000 description 17
- 108020003175 receptors Proteins 0.000 description 17
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 16
- 235000001014 amino acid Nutrition 0.000 description 16
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 14
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
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- 241000282414 Homo sapiens Species 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
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- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005306 thianaphthenyl group Chemical group 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- 239000000196 tragacanth Substances 0.000 description 1
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- 230000009466 transformation Effects 0.000 description 1
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- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000002306 tributylsilyl group Chemical group C(CCC)[Si](CCCC)(CCCC)* 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- General Health & Medical Sciences (AREA)
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- Biomedical Technology (AREA)
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- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Otolaryngology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6290908P | 2008-01-30 | 2008-01-30 | |
| PCT/US2009/032195 WO2009097309A1 (en) | 2008-01-30 | 2009-01-28 | Substituted spirocyclic piperidine derivatives as histamine-3 (h3) receptor ligands |
Publications (2)
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|---|---|
| IL206914A0 IL206914A0 (en) | 2010-12-30 |
| IL206914A true IL206914A (en) | 2013-03-24 |
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| IL206914A IL206914A (en) | 2008-01-30 | 2010-07-08 | Substituted spirocyclic piperidine derivatives as histamine-3 (h3) receptor ligands |
Country Status (18)
| Country | Link |
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| US (2) | US8524713B2 (https=) |
| EP (1) | EP2257553B1 (https=) |
| JP (1) | JP5524082B2 (https=) |
| KR (1) | KR20100105789A (https=) |
| CN (1) | CN101932585B (https=) |
| AT (1) | ATE522538T1 (https=) |
| AU (1) | AU2009209235B2 (https=) |
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| UA (1) | UA100877C2 (https=) |
| WO (1) | WO2009097309A1 (https=) |
| ZA (1) | ZA201005136B (https=) |
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| UA95644C2 (ru) * | 2006-07-25 | 2011-08-25 | Сефалон, Инк. | Пиридазиноновые производные, фармацевтическая композиция и способ лечения заболеваний |
| CA2712885A1 (en) | 2008-01-30 | 2009-08-06 | Cephalon, Inc. | Substituted pyridazine derivatives which have histamine h3 antagonist activity |
| WO2009142732A2 (en) * | 2008-05-20 | 2009-11-26 | Cephalon, Inc. | Substituted pyridazinone derivatives as histamine-3 (h3) receptor ligands |
| CA2726588C (en) | 2008-06-03 | 2019-04-16 | Karl Kossen | Compounds and methods for treating inflammatory and fibrotic disorders |
| TWI522361B (zh) | 2010-07-09 | 2016-02-21 | 艾伯維公司 | 作為s1p調節劑的稠合雜環衍生物 |
| TW201206893A (en) | 2010-07-09 | 2012-02-16 | Abbott Healthcare Products Bv | Bisaryl (thio) morpholine derivatives as S1P modulators |
| TW201643169A (zh) | 2010-07-09 | 2016-12-16 | 艾伯維股份有限公司 | 作為s1p調節劑的螺-哌啶衍生物 |
| WO2012077655A1 (ja) * | 2010-12-07 | 2012-06-14 | 塩野義製薬株式会社 | Ｇｐｒ１１９アゴニスト活性を有するスピロ誘導体 |
| CA2827673C (en) | 2011-02-18 | 2020-10-27 | Novartis Pharma Ag | Mtor/jak inhibitor combination therapy |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| MX382781B (es) | 2014-04-02 | 2025-03-13 | Intermune Inc | Piridinonas anti-fibroticas. |
| JP6643764B2 (ja) * | 2016-02-05 | 2020-02-12 | 国立大学法人岐阜大学 | 抗がん剤 |
| US12435078B2 (en) | 2017-09-18 | 2025-10-07 | Gfb (Abc), Llc | Pyridazinones and methods of use thereof |
| CN114728982A (zh) | 2019-10-31 | 2022-07-08 | 逃逸生物有限公司 | 固体形式的s1p-受体调节剂 |
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| GB0313762D0 (en) * | 2003-06-13 | 2003-07-23 | Biofocus Plc | Compound libraries |
| CN101921279A (zh) * | 2003-10-01 | 2010-12-22 | 阿得罗公司 | 螺环杂环衍生物及其应用方法 |
| SE0403160D0 (sv) * | 2004-12-23 | 2004-12-23 | Biovitrum Ab | New compounds |
| US8158791B2 (en) * | 2005-11-10 | 2012-04-17 | Msd K.K. | Aza-substituted spiro derivatives |
| WO2007063385A2 (en) * | 2005-12-01 | 2007-06-07 | Pfizer Products Inc. | Spirocyclic amine histamine-3 receptor antagonists |
| WO2007088462A1 (en) * | 2006-02-01 | 2007-08-09 | Pfizer Products Inc. | Spirochromane antagonists of the h-3 receptor |
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Also Published As
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|---|---|
| EA018537B1 (ru) | 2013-08-30 |
| JP2011510992A (ja) | 2011-04-07 |
| HK1151526A1 (en) | 2012-02-03 |
| CN101932585B (zh) | 2013-07-10 |
| UA100877C2 (ru) | 2013-02-11 |
| EP2257553A1 (en) | 2010-12-08 |
| JP5524082B2 (ja) | 2014-06-18 |
| AU2009209235B2 (en) | 2013-07-18 |
| ZA201005136B (en) | 2013-12-23 |
| EP2257553B1 (en) | 2011-08-31 |
| CN101932585A (zh) | 2010-12-29 |
| AU2009209235A1 (en) | 2009-08-06 |
| MY150062A (en) | 2013-11-29 |
| ES2370378T3 (es) | 2011-12-14 |
| US20100298332A1 (en) | 2010-11-25 |
| WO2009097309A1 (en) | 2009-08-06 |
| EA201070903A1 (ru) | 2011-02-28 |
| KR20100105789A (ko) | 2010-09-29 |
| US20130310389A1 (en) | 2013-11-21 |
| MX2010008382A (es) | 2010-11-25 |
| ATE522538T1 (de) | 2011-09-15 |
| NZ587034A (en) | 2011-12-22 |
| BRPI0905849A2 (pt) | 2015-06-30 |
| US8524713B2 (en) | 2013-09-03 |
| CA2712888A1 (en) | 2009-08-06 |
| IL206914A0 (en) | 2010-12-30 |
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| MM9K | Patent not in force due to non-payment of renewal fees |