WO2009100326A1 - Abca-1 elevating compounds and the use thereof - Google Patents
Abca-1 elevating compounds and the use thereof Download PDFInfo
- Publication number
- WO2009100326A1 WO2009100326A1 PCT/US2009/033385 US2009033385W WO2009100326A1 WO 2009100326 A1 WO2009100326 A1 WO 2009100326A1 US 2009033385 W US2009033385 W US 2009033385W WO 2009100326 A1 WO2009100326 A1 WO 2009100326A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- optionally substituted
- formula
- amino
- hydroxycyclopentyl
- compound
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 207
- 230000003028 elevating effect Effects 0.000 title description 2
- 230000014509 gene expression Effects 0.000 claims abstract description 33
- 201000010099 disease Diseases 0.000 claims abstract description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
- 241000124008 Mammalia Species 0.000 claims abstract description 16
- 208000029078 coronary artery disease Diseases 0.000 claims abstract description 14
- 230000001965 increasing effect Effects 0.000 claims abstract description 9
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 5
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 5
- 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 5
- 206010003230 arteritis Diseases 0.000 claims abstract description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 5
- 230000004054 inflammatory process Effects 0.000 claims abstract description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 5
- -1 2-hydroxycyclopentyl Chemical group 0.000 claims description 117
- 238000000034 method Methods 0.000 claims description 67
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 125000001072 heteroaryl group Chemical group 0.000 claims description 49
- 239000001257 hydrogen Substances 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
- 150000002431 hydrogen Chemical group 0.000 claims description 30
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 125000002947 alkylene group Chemical group 0.000 claims description 20
- SSYDTHANSGMJTP-UHFFFAOYSA-N oxolane-3,4-diol Chemical compound OC1COCC1O SSYDTHANSGMJTP-UHFFFAOYSA-N 0.000 claims description 20
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
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- LEMPDBGMVQACNJ-DACRQWOZSA-N (2s,3s,4r,5r)-2-[(2,6-dimethylphenyl)sulfanylmethyl]-5-[6-[[(1r,2r)-2-hydroxycyclopentyl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound CC1=CC=CC(C)=C1SC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(N[C@H]4[C@@H](CCC4)O)=C3N=C2)O1 LEMPDBGMVQACNJ-DACRQWOZSA-N 0.000 claims 1
- BSAMEZHSDCQXNK-DIJFLQFKSA-N (2s,3s,4r,5r)-2-[(2-chlorophenyl)sulfanylmethyl]-5-[6-[[(1r,2r)-2-hydroxycyclopentyl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1CCC[C@H]1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CSC=2C(=CC=CC=2)Cl)O1 BSAMEZHSDCQXNK-DIJFLQFKSA-N 0.000 claims 1
- IZRXENCTXNMAMI-ITRGSPHASA-N (2s,3s,4r,5r)-2-[(2-fluorophenyl)sulfanylmethyl]-5-[6-[(2-hydroxycyclopentyl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound OC1CCCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CSC=2C(=CC=CC=2)F)O1 IZRXENCTXNMAMI-ITRGSPHASA-N 0.000 claims 1
- UVTWDVFIDCVWCH-CPIJZORTSA-N (2s,3s,4r,5r)-2-[(3-fluorophenyl)sulfanylmethyl]-5-[6-[[(1r,2r)-2-hydroxycyclopentyl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1CCC[C@H]1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CSC=2C=C(F)C=CC=2)O1 UVTWDVFIDCVWCH-CPIJZORTSA-N 0.000 claims 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K31/5375—1,4-Oxazines, e.g. morpholine
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Abstract
Description
Claims
Priority Applications (4)
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CA2714516A CA2714516A1 (en) | 2008-02-07 | 2009-02-06 | Abca-1 elevating compounds and the use thereof |
EP09708992A EP2259790A1 (en) | 2008-02-07 | 2009-02-06 | Abca-1 elevating compounds and the use thereof |
JP2010546046A JP2011511802A (en) | 2008-02-07 | 2009-02-06 | Compounds that increase ABCA-1 and methods of using such compounds |
CN200980111878XA CN101983062A (en) | 2008-02-07 | 2009-02-06 | Abca-1 elevating compounds and the use thereof |
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US2701608P | 2008-02-07 | 2008-02-07 | |
US61/027,016 | 2008-02-07 |
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WO2009100326A1 true WO2009100326A1 (en) | 2009-08-13 |
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PCT/US2009/033385 WO2009100326A1 (en) | 2008-02-07 | 2009-02-06 | Abca-1 elevating compounds and the use thereof |
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US (1) | US20090203689A1 (en) |
EP (1) | EP2259790A1 (en) |
JP (1) | JP2011511802A (en) |
KR (1) | KR20100117105A (en) |
CN (1) | CN101983062A (en) |
CA (1) | CA2714516A1 (en) |
WO (1) | WO2009100326A1 (en) |
Cited By (6)
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Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002046181A2 (en) * | 2000-12-07 | 2002-06-13 | Cv Therapeutics, Inc. | Abca-1 elevating compounds against coronary artery disease or atherosclerosis |
US20030050275A1 (en) * | 2001-07-13 | 2003-03-13 | Elfatih Elzein | Partial and full agonists of A1 adenosine receptors |
WO2007067817A1 (en) * | 2005-12-07 | 2007-06-14 | Cv Therapeutics, Inc. | Abca1 elevating compounds |
US20070185051A1 (en) * | 2002-07-11 | 2007-08-09 | Arvinder Dhalla | Partial and full agonists of A1 adenosine receptors |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3845770A (en) * | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
US4326525A (en) * | 1980-10-14 | 1982-04-27 | Alza Corporation | Osmotic device that improves delivery properties of agent in situ |
US5364620A (en) * | 1983-12-22 | 1994-11-15 | Elan Corporation, Plc | Controlled absorption diltiazem formulation for once daily administration |
US5023252A (en) * | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
US5001139A (en) * | 1987-06-12 | 1991-03-19 | American Cyanamid Company | Enchancers for the transdermal flux of nivadipine |
US4992445A (en) * | 1987-06-12 | 1991-02-12 | American Cyanamid Co. | Transdermal delivery of pharmaceuticals |
US4902514A (en) * | 1988-07-21 | 1990-02-20 | Alza Corporation | Dosage form for administering nilvadipine for treating cardiovascular symptoms |
GB9525432D0 (en) * | 1995-12-13 | 1996-02-14 | Amp Great Britain | Capacitively ground electrode for piezo-electric film |
US6835563B1 (en) * | 1999-06-18 | 2004-12-28 | Cv Therapeutics | Compositions and methods for increasing cholesterol efflux and raising HDL ATP binding cassette transporter protein ABC1 |
US6995285B2 (en) * | 2000-12-07 | 2006-02-07 | Cv Therapeutics, Inc. | ABCA-1 elevating compounds |
US6900219B2 (en) * | 2002-04-04 | 2005-05-31 | Cv Therapeutics, Inc. | ABCA-1 elevating compounds |
US6853563B1 (en) * | 2003-07-28 | 2005-02-08 | System General Corp. | Primary-side controlled flyback power converter |
WO2007002867A1 (en) * | 2005-06-28 | 2007-01-04 | Cv Therapeutics, Inc. | Abca1 elevating compounds |
-
2009
- 2009-02-06 KR KR1020107019763A patent/KR20100117105A/en not_active Application Discontinuation
- 2009-02-06 US US12/367,062 patent/US20090203689A1/en not_active Abandoned
- 2009-02-06 CA CA2714516A patent/CA2714516A1/en not_active Abandoned
- 2009-02-06 JP JP2010546046A patent/JP2011511802A/en not_active Withdrawn
- 2009-02-06 CN CN200980111878XA patent/CN101983062A/en active Pending
- 2009-02-06 EP EP09708992A patent/EP2259790A1/en not_active Withdrawn
- 2009-02-06 WO PCT/US2009/033385 patent/WO2009100326A1/en active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002046181A2 (en) * | 2000-12-07 | 2002-06-13 | Cv Therapeutics, Inc. | Abca-1 elevating compounds against coronary artery disease or atherosclerosis |
US20030050275A1 (en) * | 2001-07-13 | 2003-03-13 | Elfatih Elzein | Partial and full agonists of A1 adenosine receptors |
US20070185051A1 (en) * | 2002-07-11 | 2007-08-09 | Arvinder Dhalla | Partial and full agonists of A1 adenosine receptors |
WO2007067817A1 (en) * | 2005-12-07 | 2007-06-14 | Cv Therapeutics, Inc. | Abca1 elevating compounds |
Non-Patent Citations (2)
Title |
---|
DHALLA ARVINDER K ET AL: "A(1) adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents", AMERICAN JOURNAL OF PHYSIOLOGY: ENDOCRINOLOGY AND METABOLISM, AMERICAN PHYSIOLOGICAL SOCIETY, BETHESDA, MD, US, vol. 292, no. 5, 1 May 2007 (2007-05-01), pages E1358 - E1363, XP008090212, ISSN: 0193-1849 * |
DHALLA ARVINDER K; SANTIKUL MELISSA; SMITH MICHELLE; BELARDINELLI LUIZ: "Anti-diabetic effects of CVT-3619, metformin and pioglitazone alone and combined in ZDF rats", DIABETES, vol. 56, no. Suppl.1, June 2007 (2007-06-01), pages A132, XP009100468 * |
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Also Published As
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CA2714516A1 (en) | 2009-08-13 |
KR20100117105A (en) | 2010-11-02 |
US20090203689A1 (en) | 2009-08-13 |
EP2259790A1 (en) | 2010-12-15 |
CN101983062A (en) | 2011-03-02 |
JP2011511802A (en) | 2011-04-14 |
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