NZ565494A - Xanthine derivatives as selective HM74A agonists - Google Patents
Xanthine derivatives as selective HM74A agonistsInfo
- Publication number
- NZ565494A NZ565494A NZ565494A NZ56549406A NZ565494A NZ 565494 A NZ565494 A NZ 565494A NZ 565494 A NZ565494 A NZ 565494A NZ 56549406 A NZ56549406 A NZ 56549406A NZ 565494 A NZ565494 A NZ 565494A
- Authority
- NZ
- New Zealand
- Prior art keywords
- chloro
- dione
- purine
- dihydro
- butyl
- Prior art date
Links
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 title abstract description 30
- 101000843809 Homo sapiens Hydroxycarboxylic acid receptor 2 Proteins 0.000 title description 26
- 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 title description 24
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 title description 8
- 239000000556 agonist Substances 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 287
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 21
- 125000003118 aryl group Chemical group 0.000 claims abstract description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 18
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 14
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 14
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 13
- 206010003210 Arteriosclerosis Diseases 0.000 claims abstract description 12
- 208000011775 arteriosclerosis disease Diseases 0.000 claims abstract description 12
- 208000006575 hypertriglyceridemia Diseases 0.000 claims abstract description 12
- 206010019280 Heart failures Diseases 0.000 claims abstract description 11
- 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 11
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 11
- 208000008589 Obesity Diseases 0.000 claims abstract description 11
- 235000020824 obesity Nutrition 0.000 claims abstract description 11
- 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 10
- 208000000103 Anorexia Nervosa Diseases 0.000 claims abstract description 10
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims abstract description 10
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 10
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 10
- 208000029078 coronary artery disease Diseases 0.000 claims abstract description 10
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- 208000022831 chronic renal failure syndrome Diseases 0.000 claims abstract description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 8
- 208000020832 chronic kidney disease Diseases 0.000 claims abstract description 7
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 156
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 146
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 124
- 229910052757 nitrogen Inorganic materials 0.000 claims description 72
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
- 239000000460 chlorine Substances 0.000 claims description 43
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 30
- 229960003512 nicotinic acid Drugs 0.000 claims description 19
- 235000001968 nicotinic acid Nutrition 0.000 claims description 19
- 239000011664 nicotinic acid Substances 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
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- 238000004519 manufacturing process Methods 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 9
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 150000003536 tetrazoles Chemical class 0.000 claims description 5
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 239000005864 Sulphur Substances 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
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- 229940125753 fibrate Drugs 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
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- 125000005647 linker group Chemical group 0.000 claims description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 2
- 208000022531 anorexia Diseases 0.000 claims 1
- 206010061428 decreased appetite Diseases 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 309
- 239000000203 mixture Substances 0.000 description 270
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 260
- -1 alkeny! Chemical group 0.000 description 162
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 149
- 239000000243 solution Substances 0.000 description 136
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 116
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 115
- 239000007787 solid Substances 0.000 description 114
- 238000000034 method Methods 0.000 description 111
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 108
- 239000000047 product Substances 0.000 description 104
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 82
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- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 78
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
- 238000005160 1H NMR spectroscopy Methods 0.000 description 65
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 63
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- 229910001868 water Inorganic materials 0.000 description 62
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 55
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 49
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 47
- 239000012044 organic layer Substances 0.000 description 46
- 239000012267 brine Substances 0.000 description 44
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 44
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 41
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
- 238000000746 purification Methods 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
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- 238000006243 chemical reaction Methods 0.000 description 30
- 239000000377 silicon dioxide Substances 0.000 description 30
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- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- FAIAJSOSTNJZCI-UHFFFAOYSA-N purine-2,6-dione Chemical compound O=C1NC(=O)C2=NC=NC2=N1 FAIAJSOSTNJZCI-UHFFFAOYSA-N 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 23
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
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- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 19
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- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 18
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
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- Endocrinology (AREA)
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- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0516464A GB0516464D0 (en) | 2005-08-10 | 2005-08-10 | Novel compounds |
| GB0607736A GB0607736D0 (en) | 2006-04-19 | 2006-04-19 | Novel compounds |
| GB0614569A GB0614569D0 (en) | 2006-07-21 | 2006-07-21 | Novel compounds |
| PCT/EP2006/007865 WO2007017261A1 (en) | 2005-08-10 | 2006-08-08 | Xanthine derivatives as selective hm74a agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ565494A true NZ565494A (en) | 2011-06-30 |
Family
ID=37189397
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ565494A NZ565494A (en) | 2005-08-10 | 2006-08-08 | Xanthine derivatives as selective HM74A agonists |
Country Status (28)
| Country | Link |
|---|---|
| US (3) | US20100179128A1 (enExample) |
| EP (3) | EP1912992A1 (enExample) |
| JP (2) | JP2009504592A (enExample) |
| KR (2) | KR20080038396A (enExample) |
| AR (1) | AR055369A1 (enExample) |
| AT (1) | ATE487719T1 (enExample) |
| AU (2) | AU2006278215A1 (enExample) |
| BR (2) | BRPI0615145A2 (enExample) |
| CA (2) | CA2618963A1 (enExample) |
| CR (2) | CR9749A (enExample) |
| CY (1) | CY1111757T1 (enExample) |
| DE (1) | DE602006018151D1 (enExample) |
| DK (1) | DK1912991T3 (enExample) |
| EA (2) | EA014556B1 (enExample) |
| ES (1) | ES2401128T3 (enExample) |
| HR (1) | HRP20100725T1 (enExample) |
| IL (2) | IL189083A0 (enExample) |
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| DE602007010312D1 (de) | 2006-06-23 | 2010-12-16 | Incyte Corp | Purinonderivate als hm74a-agonisten |
| BRPI0713619A2 (pt) | 2006-06-23 | 2013-01-15 | Incyte Corp | composto ou prà-droga ou sal farmaceuticamente aceitÁvel do mesmo, composiÇço, e, uso do composto. |
| JP2010500300A (ja) | 2006-08-08 | 2010-01-07 | サノフィ−アベンティス | アリールアミノアリール−アルキル−置換イミダゾリジン−２，４−ジオン、それらの製造法、それらの化合物を含有する薬剤、およびそれらの使用 |
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| DE102007063671A1 (de) | 2007-11-13 | 2009-06-25 | Sanofi-Aventis Deutschland Gmbh | Neue kristalline Diphenylazetidinonhydrate, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| WO2010003624A2 (en) | 2008-07-09 | 2010-01-14 | Sanofi-Aventis | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
| AU2009324811B2 (en) | 2008-12-08 | 2013-01-24 | Glaxosmithkline Llc | Novel compounds |
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- 2006-08-08 HR HR20100725T patent/HRP20100725T1/hr unknown
- 2006-08-08 WO PCT/EP2006/007865 patent/WO2007017261A1/en not_active Ceased
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- 2006-08-08 EP EP06763016A patent/EP1912991B1/en not_active Not-in-force
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