ZA200207004B - Novel aryl fructose-1,6-bisphosphatase inhibitors. - Google Patents

Novel aryl fructose-1,6-bisphosphatase inhibitors. Download PDF

Info

Publication number: ZA200207004B
Authority: ZA; South Africa
Prior art keywords: group; aryl; substituted; atoms; alkyl
Prior art date: 2000-03-08

Application number

ZA200207004A

Other languages

English (en)

Inventor

Brett C Bookser

Qun Dang

K Raja Reddy

Original Assignee

Metabasis Therapeutics Inc

Priority date (The priority date 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 date listed.)

2000-03-08

Filing date

2002-08-30

Publication date

2003-12-01

2002-08-30 Application filed by Metabasis Therapeutics Inc filed Critical Metabasis Therapeutics Inc

2003-12-01 Publication of ZA200207004B publication Critical patent/ZA200207004B/en

Links

125000003118 aryl group Chemical group 0.000 title claims description 298
239000003112 inhibitor Substances 0.000 title claims description 21
108010017464 Fructose-Bisphosphatase Proteins 0.000 title claims description 8
102000012195 Fructose-1,6-bisphosphatases Human genes 0.000 title claims 4
125000000217 alkyl group Chemical group 0.000 claims description 228
125000001072 heteroaryl group Chemical group 0.000 claims description 205
125000004429 atom Chemical group 0.000 claims description 195
125000004122 cyclic group Chemical group 0.000 claims description 158
125000003710 aryl alkyl group Chemical group 0.000 claims description 155
125000005842 heteroatom Chemical group 0.000 claims description 135
125000003107 substituted aryl group Chemical group 0.000 claims description 109
125000002723 alicyclic group Chemical group 0.000 claims description 105
229910052760 oxygen Inorganic materials 0.000 claims description 103
229910052717 sulfur Inorganic materials 0.000 claims description 94
150000001875 compounds Chemical class 0.000 claims description 93
229910052799 carbon Inorganic materials 0.000 claims description 86
229910052757 nitrogen Inorganic materials 0.000 claims description 84
229940002612 prodrug Drugs 0.000 claims description 50
239000000651 prodrug Substances 0.000 claims description 50
-1 perhaloalkyl Chemical group 0.000 claims description 48
125000002947 alkylene group Chemical group 0.000 claims description 46
229910052698 phosphorus Inorganic materials 0.000 claims description 45
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 35
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
125000004432 carbon atom Chemical group C* 0.000 claims description 27
125000005647 linker group Chemical group 0.000 claims description 27
238000000034 method Methods 0.000 claims description 27
239000000203 mixture Substances 0.000 claims description 27
125000004437 phosphorous atom Chemical group 0.000 claims description 27
101710099475 3'-phosphoadenosine 5'-phosphate phosphatase Proteins 0.000 claims description 25
101710196411 Fructose-1,6-bisphosphatase Proteins 0.000 claims description 25
101710186733 Fructose-1,6-bisphosphatase, chloroplastic Proteins 0.000 claims description 25
101710109119 Fructose-1,6-bisphosphatase, cytosolic Proteins 0.000 claims description 25
101710198902 Fructose-1,6-bisphosphate aldolase/phosphatase Proteins 0.000 claims description 25
150000003839 salts Chemical class 0.000 claims description 25
239000000126 substance Substances 0.000 claims description 25
125000004423 acyloxy group Chemical group 0.000 claims description 24
125000002252 acyl group Chemical group 0.000 claims description 23
125000005843 halogen group Chemical group 0.000 claims description 22
125000003342 alkenyl group Chemical group 0.000 claims description 21
206010012601 diabetes mellitus Diseases 0.000 claims description 21
229910052739 hydrogen Inorganic materials 0.000 claims description 21
125000000304 alkynyl group Chemical group 0.000 claims description 20
125000002541 furyl group Chemical group 0.000 claims description 20
125000006413 ring segment Chemical group 0.000 claims description 20
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 20
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 17
125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims description 17
150000001721 carbon Chemical group 0.000 claims description 17
201000010099 disease Diseases 0.000 claims description 17
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
239000011574 phosphorus Substances 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 16
PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims description 16
241001465754 Metazoa Species 0.000 claims description 15
125000001188 haloalkyl group Chemical group 0.000 claims description 15
150000002367 halogens Chemical class 0.000 claims description 15
125000005041 acyloxyalkyl group Chemical group 0.000 claims description 14
239000003814 drug Substances 0.000 claims description 14
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 13
125000002877 alkyl aryl group Chemical group 0.000 claims description 13
125000006165 cyclic alkyl group Chemical group 0.000 claims description 13
125000000623 heterocyclic group Chemical group 0.000 claims description 13
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WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 9
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201000001421 hyperglycemia Diseases 0.000 claims description 7
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
230000001965 increasing effect Effects 0.000 claims description 6
238000002360 preparation method Methods 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
201000001320 Atherosclerosis Diseases 0.000 claims description 4
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125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
125000003373 pyrazinyl group Chemical group 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000001543 furan-2,5-diyl group Chemical group O1C(=CC=C1*)* 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
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125000000168 pyrrolyl group Chemical group 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 12
125000005275 alkylenearyl group Chemical group 0.000 claims 8
238000004519 manufacturing process Methods 0.000 claims 6
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201000009104 prediabetes syndrome Diseases 0.000 claims 5
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims 4
208000008589 Obesity Diseases 0.000 claims 3
125000006365 alkylene oxy carbonyl group Chemical group 0.000 claims 3
230000002440 hepatic effect Effects 0.000 claims 3
235000020824 obesity Nutrition 0.000 claims 3
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims 3
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102100028701 General vesicular transport factor p115 Human genes 0.000 claims 1
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208000007345 glycogen storage disease Diseases 0.000 claims 1
125000001786 isothiazolyl group Chemical group 0.000 claims 1
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125000006362 methylene amino carbonyl group Chemical group [H]N(C([*:2])=O)C([H])([H])[*:1] 0.000 claims 1
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239000008194 pharmaceutical composition Substances 0.000 claims 1
230000002265 prevention Effects 0.000 claims 1
125000003226 pyrazolyl group Chemical group 0.000 claims 1
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125000000335 thiazolyl group Chemical group 0.000 claims 1
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125000001769 aryl amino group Chemical group 0.000 description 4
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230000007823 neuropathy Effects 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3826—Acyclic unsaturated acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
- C07F9/6539—Five-membered rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom

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General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Diabetes (AREA)
Animal Behavior & Ethology (AREA)
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General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
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Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Hematology (AREA)
Obesity (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Plural Heterocyclic Compounds (AREA)
Medicinal Preparation (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

ZA200207004A 2000-03-08 2002-08-30 Novel aryl fructose-1,6-bisphosphatase inhibitors. ZA200207004B (en)

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US18775000P	2000-03-08	2000-03-08

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US (2)	US6919322B2 (no)
EP (2)	EP1607401A1 (no)
JP (1)	JP2003525944A (no)
KR (1)	KR20020079988A (no)
CN (2)	CN1516705A (no)
AT (1)	ATE350385T1 (no)
AU (2)	AU2001245532B2 (no)
BR (1)	BR0109062A (no)
CA (1)	CA2401706A1 (no)
CZ (1)	CZ20023018A3 (no)
DE (1)	DE60125734T2 (no)
HK (1)	HK1051865A1 (no)
HU (1)	HUP0300344A3 (no)
IL (2)	IL151248A0 (no)
MX (1)	MXPA02008722A (no)
NO (1)	NO20024240L (no)
PL (1)	PL357251A1 (no)
RU (1)	RU2002126616A (no)
SK (1)	SK12722002A3 (no)
WO (1)	WO2001066553A2 (no)
ZA (1)	ZA200207004B (no)

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2001
- 2001-03-07 KR KR1020027011737A patent/KR20020079988A/ko not_active Application Discontinuation
- 2001-03-07 EP EP05015039A patent/EP1607401A1/en not_active Withdrawn
- 2001-03-07 EP EP01918456A patent/EP1265907B9/en not_active Expired - Lifetime
- 2001-03-07 AU AU2001245532A patent/AU2001245532B2/en not_active Ceased
- 2001-03-07 MX MXPA02008722A patent/MXPA02008722A/es active IP Right Grant
- 2001-03-07 HU HU0300344A patent/HUP0300344A3/hu unknown
- 2001-03-07 CN CNA018090214A patent/CN1516705A/zh active Pending
- 2001-03-07 IL IL15124801A patent/IL151248A0/xx active IP Right Grant
- 2001-03-07 AU AU4553201A patent/AU4553201A/xx active Pending
- 2001-03-07 JP JP2001565369A patent/JP2003525944A/ja not_active Withdrawn
- 2001-03-07 BR BR0109062-3A patent/BR0109062A/pt not_active Application Discontinuation
- 2001-03-07 CN CNA2005100720821A patent/CN1699383A/zh active Pending
- 2001-03-07 RU RU2002126616/04A patent/RU2002126616A/ru unknown
- 2001-03-07 US US09/801,933 patent/US6919322B2/en not_active Expired - Lifetime
- 2001-03-07 WO PCT/US2001/007452 patent/WO2001066553A2/en active IP Right Grant
- 2001-03-07 CA CA002401706A patent/CA2401706A1/en not_active Abandoned
- 2001-03-07 PL PL01357251A patent/PL357251A1/xx not_active Application Discontinuation
- 2001-03-07 DE DE60125734T patent/DE60125734T2/de not_active Expired - Fee Related
- 2001-03-07 SK SK1272-2002A patent/SK12722002A3/sk unknown
- 2001-03-07 CZ CZ20023018A patent/CZ20023018A3/cs unknown
- 2001-03-07 AT AT01918456T patent/ATE350385T1/de not_active IP Right Cessation
2002
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- 2002-08-30 ZA ZA200207004A patent/ZA200207004B/en unknown
- 2002-09-05 NO NO20024240A patent/NO20024240L/no not_active Application Discontinuation
2003
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2005
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Also Published As

Publication number	Publication date
BR0109062A (pt)	2002-11-26
KR20020079988A (ko)	2002-10-21
WO2001066553A2 (en)	2001-09-13
CN1699383A (zh)	2005-11-23
NO20024240D0 (no)	2002-09-05
RU2002126616A (ru)	2004-03-20
HK1051865A1 (en)	2003-08-22
EP1607401A1 (en)	2005-12-21
US7371739B2 (en)	2008-05-13
EP1265907B1 (en)	2007-01-03
CN1516705A (zh)	2004-07-28
US20050176684A1 (en)	2005-08-11
US6919322B2 (en)	2005-07-19
HUP0300344A2 (hu)	2003-06-28
EP1265907A2 (en)	2002-12-18
PL357251A1 (en)	2004-07-26
WO2001066553A3 (en)	2002-03-14
US20020040014A1 (en)	2002-04-04
MXPA02008722A (es)	2004-05-05
JP2003525944A (ja)	2003-09-02
IL151248A0 (en)	2003-04-10
EP1265907B9 (en)	2007-05-09
HUP0300344A3 (en)	2007-05-29
CA2401706A1 (en)	2001-09-13
ATE350385T1 (de)	2007-01-15
CZ20023018A3 (cs)	2003-01-15
AU4553201A (en)	2001-09-17
NO20024240L (no)	2002-11-08
SK12722002A3 (sk)	2003-04-01
AU2001245532B2 (en)	2005-08-11
DE60125734D1 (en)	2007-02-15
DE60125734T2 (de)	2007-10-25
IL151248A (en)	2007-06-17

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