NZ751063A - Heterocyclic compounds useful in the treatment of disease - Google Patents
Heterocyclic compounds useful in the treatment of disease Download PDFInfo
- Publication number
- NZ751063A NZ751063A NZ751063A NZ75106314A NZ751063A NZ 751063 A NZ751063 A NZ 751063A NZ 751063 A NZ751063 A NZ 751063A NZ 75106314 A NZ75106314 A NZ 75106314A NZ 751063 A NZ751063 A NZ 751063A
- Authority
- NZ
- New Zealand
- Prior art keywords
- phenyl
- substituted
- ethoxycarbonylamino
- methyl
- isoxazolyl
- Prior art date
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 65
- 201000010099 disease Diseases 0.000 title claims abstract description 59
- 238000011282 treatment Methods 0.000 title abstract description 7
- 150000002391 heterocyclic compounds Chemical class 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 362
- 230000001419 dependent effect Effects 0.000 claims abstract description 18
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 7
- 230000004761 fibrosis Effects 0.000 claims abstract description 7
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims abstract description 3
- 208000033679 diabetic kidney disease Diseases 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 260
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 225
- 239000000203 mixture Substances 0.000 claims description 165
- -1 phenylethoxycarbonyl-amino Chemical group 0.000 claims description 150
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 139
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 131
- 229910052799 carbon Inorganic materials 0.000 claims description 130
- 125000003118 aryl group Chemical group 0.000 claims description 107
- 125000001072 heteroaryl group Chemical group 0.000 claims description 107
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 103
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 99
- 125000002947 alkylene group Chemical group 0.000 claims description 84
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 82
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 80
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims description 75
- 235000019260 propionic acid Nutrition 0.000 claims description 73
- 229910052739 hydrogen Inorganic materials 0.000 claims description 70
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 70
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 59
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 57
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims description 49
- 125000000732 arylene group Chemical group 0.000 claims description 48
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 47
- 238000009472 formulation Methods 0.000 claims description 43
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 40
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 39
- 229910052736 halogen Inorganic materials 0.000 claims description 35
- 150000002367 halogens Chemical class 0.000 claims description 35
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 26
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000005549 heteroarylene group Chemical group 0.000 claims description 20
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 20
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 19
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 18
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 17
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 12
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- 150000000022 5-membered heteroarenes Chemical class 0.000 claims description 10
- AXLOCHLTNQDFFS-BESJYZOMSA-N azastene Chemical compound C([C@H]1[C@@H]2CC[C@@]([C@]2(CC[C@@H]1[C@@]1(C)C2)C)(O)C)C=C1C(C)(C)C1=C2C=NO1 AXLOCHLTNQDFFS-BESJYZOMSA-N 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- HWZWUADHPSYTOD-UHFFFAOYSA-N ClC1=C(C=CC=C1)C(C)OC(=O)NCC=1C(=NOC1)C1=CC=C(C(=O)NC2(CC2)C(=O)O)C=C1 Chemical compound ClC1=C(C=CC=C1)C(C)OC(=O)NCC=1C(=NOC1)C1=CC=C(C(=O)NC2(CC2)C(=O)O)C=C1 HWZWUADHPSYTOD-UHFFFAOYSA-N 0.000 claims description 8
- PLFFWDRLKHNCFO-UHFFFAOYSA-N ClC1=C(C=CC=C1)C(C)OC(=O)NCC=1C(=NOC1)C1=CC=C(C(=O)NC2C(C3=CC=CC=C3C2)C(=O)O)C=C1 Chemical compound ClC1=C(C=CC=C1)C(C)OC(=O)NCC=1C(=NOC1)C1=CC=C(C(=O)NC2C(C3=CC=CC=C3C2)C(=O)O)C=C1 PLFFWDRLKHNCFO-UHFFFAOYSA-N 0.000 claims description 8
- 208000017169 kidney disease Diseases 0.000 claims description 8
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 8
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000006627 ethoxycarbonylamino group Chemical group 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 5
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 claims description 5
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 4
- 208000019423 liver disease Diseases 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 2
- 125000006747 (C2-C10) heterocycloalkyl group Chemical group 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- WRGQSWVCFNIUNZ-GDCKJWNLSA-N 1-oleoyl-sn-glycerol 3-phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)(O)=O WRGQSWVCFNIUNZ-GDCKJWNLSA-N 0.000 claims 2
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims 1
- 102000004137 Lysophosphatidic Acid Receptors Human genes 0.000 abstract description 13
- 108090000642 Lysophosphatidic Acid Receptors Proteins 0.000 abstract description 13
- 210000004185 liver Anatomy 0.000 abstract description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 abstract description 6
- 208000027866 inflammatory disease Diseases 0.000 abstract description 6
- 208000003251 Pruritus Diseases 0.000 abstract description 5
- 208000022873 Ocular disease Diseases 0.000 abstract description 4
- 206010039710 Scleroderma Diseases 0.000 abstract description 4
- 210000002216 heart Anatomy 0.000 abstract description 4
- 210000003734 kidney Anatomy 0.000 abstract description 4
- 210000004072 lung Anatomy 0.000 abstract description 4
- 208000002193 Pain Diseases 0.000 abstract description 3
- BBDSWHRPUYCMKX-PLEWWHCXSA-N 3-cyclopropyl-2-[[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]methoxy]propanoic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1COC(C(O)=O)CC1CC1 BBDSWHRPUYCMKX-PLEWWHCXSA-N 0.000 abstract 1
- 201000007737 Retinal degeneration Diseases 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 210000005036 nerve Anatomy 0.000 abstract 1
- 230000004258 retinal degeneration Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 242
- 238000000034 method Methods 0.000 description 240
- 238000004128 high performance liquid chromatography Methods 0.000 description 97
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- 125000004432 carbon atom Chemical group C* 0.000 description 82
- 125000001424 substituent group Chemical group 0.000 description 79
- 239000000243 solution Substances 0.000 description 71
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 62
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- XGRLSUFHELJJAB-JGSYTFBMSA-M sodium;[(2r)-2-hydroxy-3-[(z)-octadec-9-enoyl]oxypropyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)([O-])=O XGRLSUFHELJJAB-JGSYTFBMSA-M 0.000 description 46
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
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- 125000002993 cycloalkylene group Chemical group 0.000 description 37
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 31
- 125000004122 cyclic group Chemical group 0.000 description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 25
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- 125000004429 atom Chemical group 0.000 description 22
- 230000001404 mediated effect Effects 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 125000003342 alkenyl group Chemical group 0.000 description 21
- 125000005842 heteroatom Chemical group 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 125000003545 alkoxy group Chemical group 0.000 description 20
- 229910052757 nitrogen Inorganic materials 0.000 description 20
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
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- 125000004474 heteroalkylene group Chemical group 0.000 description 18
- 125000004076 pyridyl group Chemical group 0.000 description 18
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 125000000304 alkynyl group Chemical group 0.000 description 16
- 229910052717 sulfur Inorganic materials 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 125000006588 heterocycloalkylene group Chemical group 0.000 description 15
- 229940002612 prodrug Drugs 0.000 description 15
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- 125000000547 substituted alkyl group Chemical group 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
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- IUDCMLWYSNYDCW-UHFFFAOYSA-N OC(NC1=NOC(CC2=CC=C(CCl)C=C2)=C1)=O Chemical compound OC(NC1=NOC(CC2=CC=C(CCl)C=C2)=C1)=O IUDCMLWYSNYDCW-UHFFFAOYSA-N 0.000 description 13
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- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 12
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- 239000012267 brine Substances 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
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- 150000002148 esters Chemical class 0.000 description 10
- 229910052731 fluorine Inorganic materials 0.000 description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
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- 125000002877 alkyl aryl group Chemical group 0.000 description 9
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- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 9
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- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
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- DZIQUZJSNSZOCH-UHFFFAOYSA-N methyl 2-phenylpropanoate Chemical compound COC(=O)C(C)C1=CC=CC=C1 DZIQUZJSNSZOCH-UHFFFAOYSA-N 0.000 description 8
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- DICSCDORHVSQHS-HXUWFJFHSA-N 1-[4-[4-[2,5-dimethyl-4-[[(1r)-1-phenylethoxy]carbonylamino]pyrazol-3-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NN(C)C=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 DICSCDORHVSQHS-HXUWFJFHSA-N 0.000 description 7
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- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Heterocyclic compounds are described that are lysophosphatidic acid receptor ligands that are useful in the treatment of lysophosphatidic acid receptor-dependent diseases and conditions, including but not limited to diseases involving fibrosis, such as fibrosis of the heart, kidney, liver and lung, and scleroderma; inflammatory diseases such as diabetic nephropathy and inflammatory bowel disease; ocular diseases such as dieases involving retinal degeneration; nerve diseases such as pruritus and pain. Non-limiting examples of those compounds include (RS)-3-Cyclopropyl-2-{ 4-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-benzyloxy} -propionic acid.
Description
TITLE
Heterocyclic Compounds Useful in the Treatment of Disease
CROSS REFERENCE TO RELATED APPLICATIONS
[1] This application claims the benefit of U.S. Provisional Patent Application Serial
No. 61/801,426, filed March 15, 2013, U.S. Provisional Patent Application Serial No.
61/801,231, filed March 15, 2013, U.S. Provisional Patent Application Serial No.
61/827,409, filed May 24, 2013, the entire contents of which are hereby incorporated
by reference herein.
STATEMENT OF GOVERNMENT INTEREST
This invention was made with government support under Grants DK092005
and CA174019 awarded by the National Institutes of Health. The US government has
certain rights in the invention.
FIELD OF THE INVENTION
[3] The present invention relates to compounds having pharmacological activity, to
processes for preparation of such compounds, to pharmaceutical compositions
comprising them, and to their use in therapy and prophylaxis of disease in a subject in
need thereof, in particular for human and veterinarian treatments of pain, pruritus,
cancer, inflammation and fibrotic diseases.
BACKGROUND OF THE INVENTION
Lysophospholipids affect fundamental cellular functions that include proliferation,
differentiation, survival, migration, adhesion, invasion, and morphogensis. Abnormal
functions influence many biological processes leading to disease that include, but are
not limited to fibrotic disease, inflammation, cancer and peripheral nerve injury.
Lysophosphatidic acid (LPA) is a lysophospholipid that has been shown to act through
specific G protein-coupled receptors (GPCRs) in an autocrine and paracrine fashion.
Antagonists of the LPA receptors find use in the treatment of diseases, disorders or
conditions in which LPA plays a role.
Agents that interact with the lysophosphatidic acid receptors [LPARs] to reduce
signal transduction through those receptors (i.e., by competitive or noncompetitive
inhibition or acting as inverse agonists) reduce manifestations of the diseases described
herein. Diseases and conditions whose etiology, progression or persistence is effected
by in whole or in part by signaling through the lysophosphatidic acid receptor subtype 1
(LPA1R) are considered LPA-dependent. New agents having therapeutic utility for
treating those LPA-dependent and other conditions and diseases described herein are
needed.
SUMMARY OF THE INVENTION
Disclosed herein are compounds that inhibit the physiological activity of
lysophosphatidic acid (LPA), and therefore, are useful as agents for the treatment or
prevention of diseases in which inhibition of the physiological activity of LPA is useful.
In one aspect, those compounds are useful for the treatment of fibrosis of organs
(e.g., liver, kidney, lung, heart and the like), liver diseases (e.g., acute hepatatis, chronic
hepatitis, liver fibrosis, liver cirrhosis, portal hypertension, regenerative failure,
nonalcoholic steatohepatitis (NASH), liver hypofunction, hepatic blood flow disorder, and
the like), cell proliferative disease such as cancers (including but not limited to solid
tumor, solid tumor metastasis, vascular fibroma, myeloma, multiple myeloma, Kaposi's
sarcoma, leukemia, chronic lymphocytic leukemia (CLL), invasive metastasis of cancer
cell, and the like), inflammatory diseases (including but not limited to psoriasis,
nephropathy, pneumonia and the like), gastrointestinal tract disease (including but not
limited to (irritable bowel syndrome (lBS), inflammatory bowel disease (IBD), abnormal
pancreatic secretion, and the like), renal disease, urinary tract-associated disease
(including but not limited to benign prostatic hyperplasia or symptoms associated with
neuropathic bladder disease, spinal cord tumor, hernia of intervertebral disk, spinal
canal stenosis, symptoms derived from diabetes, lower urinary tract disease (including
but not limited to obstruction of lower urinary tract, and the like), inflammatory disease of
lower urinary tract, (including but not limited to dysuria, frequent urination, and the like),
pancreas disease, abnormal angiogenesis-associated disease (including but not limited
to arterial obstruction and the like), scleroderma, brain-associated disease (including but
not limited to cerebral infarction, cerebral hemorrhage, and the like), nervous system
diseases (including but not limited to neuropathic pain, peripheral neuropathy, pruritus
and the like), ocular disease (including but not limited to age-related macular
degeneration (AMD), diabetic retinopathy, proliferative vitreo-retinopathy (PVR),
cicatricial pemphigoid, glaucoma filtration surgery scarring, and the like).
[8] The compounds of the invention include compounds of Formula I that have the
structure:
2 1 A
A B L L R Formula I
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
-C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
L is absent or optionally substituted C -C alkylene, optionally substituted C -C
1 6 3 6
cycloalkylene, optionally substituted C -C fluoroalkylene, optionally substituted C -C
1 6 1 6
heteroalkylene, or -UV-Z-, wherein -UV- is defined by -OW-, -WO-, -N(R )W-, -WN(R )-,
-N(R )C(=O)-, -SW-, -S(=O) W-, or -C(=O)N(R )-, wherein W is optionally substituted C -
C alkylene or optionally substituted C -C cycloalkylene or W is -C(R ) -, Z is optionally
3 3 6 2
substituted C -C alkylene, optionally substituted C -C cycloalkylene or C -C
1 6 3 6 1 6
fluoroalkylene or Z is -C(R ) -; and n is 0, 1, or 2;
L is absent, or optionally substituted C -C alkylene, optionally substituted C -C
1 6 3 6
cycloalkylene, C -C fluoroalkylene, optionally substituted C -C heteroalkylene, -O-, -S-,
1 6 1 6
-S(=O)-, -S(=O) -, -N(R )-, -C(=O)-, or -C(=O)N(R )-;
wherein R is -H or -optionally substituted C -C alkyl, or has the structure of one
O O O
Ring A is a 5 or 6 membered heteroarene having the structure of one of:
C C R R
R R C
D D C C
R R R
R R R
N C N
R D R
R R R
,
wherein the dashed line indicates the point of attachment of Ring A to Ring B;
wherein one of R and R is -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl,
1 4 1 4
C -C cycloalkyl, or C -C fluoroalkyl,
3 6 1 4
C D F G F G
and the other R or R is -N(R )C(=O)XCH(R )-CY, -N(R )C(=O)XC(R ) -CY,
F F G F G
-N(R )C(=O)X-CY, -C(=O)-N(R )-CH(R )X-CY, or -C(=O)-N(R )-C(R ) X-CY, wherein X
is absent, -O-, -NH- or -CH -;
R is -H, C -C alkyl or C -C fluoroalkyl;
1 4 1 4
R is -H or C -C alkyl;
G E G
R is independently selected R , or one R is C -C alkylne and is taken
together with CY and the the carbon atom to which R and CY is attached to define a
substituted or unsubstituted carbocycle or a substituted or unsubstituted heterocycle,
and the other R , if present, is as defined for R ;
CY is optionally substituted C -C alkyl, optionally substituted C -C cycloalkyl,
1 6 3 10
optionally substituted C -C heterocycloalkyl, optionally substituted aryl, or optionally
2 10
substituted heteroaryl, wherein if CY is substituted then CY is substituted with 1, 2, or 3
independently selected R ,
H J J
wherein each R is independently -H, halogen, -CN, -NO , -OH, -OR , -SR ,
J J J J L J J J
-S(=O)R , -S(=O) R , -N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , OC(=O)R , -C(=O)OR ,
2 2 2 2
J L L L J L J J
-OC=O)OR , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) , -N(R )C(=O)N(R ) , -N(R )C(=O)R ,
2 2 2 2
-N(R )C(=O)OR , C -C alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C alkoxy, or C -
1 4 1 4 1 4 1 4 1
C heteroalkyl;
wherein each R is independently optionally substituted C -C alkyl, optionally
substituted C -C heteroalkyl, optionally substituted C -C fluoroalkyl, optionally
1 6 1 6
substituted C -C cycloalkyl, optionally substituted heterocycloalkyl, optionally
substituted aryl, optionally substituted heteroaryl, -C -C alkylene-(optionally substituted
C -C cycloalkyl), -C -C alkylene-(optionally substituted heterocycloalkyl), -C -C
3 6 1 4 1 4
alkylene-(optionally substituted aryl), or -C -C alkylene-(optionally substituted
heteroaryl), and
wherein R is independently -H, optionally substituted C -C alkyl, optionally
substituted C -C heteroalkyl, optionally substituted C -C fluoroalkyl, optionally
1 6 1 6
substituted C -C cycloalkyl, optionally substituted heterocycloalkyl, optionally
substituted aryl, optionally substituted heteroaryl, -C -C alkylene-(optionally substituted
C -C cycloalkyl), -C -C alkylene-( optionally substituted heterocycloalkyl), -C -C
3 6 1 4 1 4
alkylene-(optionally substituted aryl), or -C -C alkylene-(optionally substituted
heteroaryl),
H L L L L
or when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or
2 2 2 2 2
J L L L
-N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle,
L L 2 L
[26] or when W is -C(R ) -, or Z is -C(R ) - each R is independently -H or C -C alkyl,
2 1 6
or the R groups independently are C -C alkyl which are taken together with the carbon
atom to which they are attached to define a carbocycle;
Ring B is a optionally substituted C -C cycloalkylene, optionally substituted C -
3 10 2
C heterocycloalkylene, optionally substituted arylene, or optionally substituted
heteroarylene, wherein if ring B is substituted then ring B is substituted with 1,2, or 3
independently selected R , wherein R is as previously defined; and
Ring C is absent or optionally substituted C -C cycloalkylene, optionally
3 10
substituted C -C heterocycloalkylene, optionally substituted arylene, or optionally
2 10
substituted heteroarylene, where if ring C is substituted then ring C is substituted with 1,
2, or 3 independently selected R , wherein R is as previously defined;
[29] wherein when Ring B is substituted or unsubstituted arylene, Ring C is absent,
2 1 J D
L is absent, L is -UV-Z-, wherein -UV- is -N(R )-C(=O), R is
F G G F C
-N(R )-C(=O)XCH(R )-CY, wherein X is -O-, R is -CH and R is -H, and R is -H, -CH
or -CF ,
or when Ring B is optionally substituted arylene and Ring C is substituted or
unsubstituted arylene or is substituted or unsubstituted C -C cycloalkylene, or Ring B
3 10
is substituted or unsubstituted C -C cycloalkylene and Ring C is substituted or
3 10
unsubstituted arylene, L is absent, L is C -C alkylene,
C A B
and R is -H or -CH and R is -CO H or -CO R ,
3 2 2
then Ring A has the structure of one of:
R N N
D N D
D D C C D
R R R R
E N N
N R D
N D R N
C D C R
[33] ,
and when Ring B is C -C heterocycloalkylene, Ring C is substituted or
2 10
2 1 C A
unsubstituted arylene, L is absent, L is C -C alkylene, R is -CH and R is -CO H or
1 6 3 2
-CO2R , then Ring A has the structure of one of:
R N N
C E N
D D D
N C N
C D C
R R R
Other compounds of the invention have the structures indicated by the
numbered embodiment and claims herein.
DETAILED DESCRIPTION OF THE INVENTION
Definitions
[38] As used herein and unless otherwise stated or implied by context, terms that are
used herein have the meanings defined below. Unless otherwise contraindicated or
implied, e.g., by including mutually exclusive elements or options, in these definitions
and throughout this specification, the terms "a" and "an" mean one or more and the term
"or" means and/or where permitted by context. Thus, as used in the specification and
the appended claims, the singular forms "a," "an" and "the" include plural referents
unless the context clearly dictates otherwise.
At various locations in the present disclosure, e.g., in any disclosed
embodiments or in the claims, reference is made to compounds, compositions, or
methods that “comprise” one or more specified components, elements or steps.
Invention embodiments also specifically include those compounds, compositions,
compositions or methods that are or that consist of or that consist essentially of those
specified components, elements or steps. The terms "comprising", "consist of" and
"consist essentially of" have their normally accepted meanings under U.S. patent law
unless otherwise specifically stated. The term “comprised of” is used interchangeably
with the term “comprising” and are stated as equivalent terms. For example,
disclosed compositions, devices, articles of manufacture or methods that "comprise"
a component or step are open and they include or read on those compositions or
methods plus an additional component(s) or step(s). Similarly, disclosed
compositions, devices, articles of manufacture or methods that "consist of" a
component or step are closed and they would not include or read on those
compositions or methods having appreciable amounts of an additional component(s)
or an additional step(s). Furthermore, use of the term "including" as well as other
forms, such as "include", "includes," and "included," is not limiting. The section
headings used herein are for organizational purposes only and are not to be
construed as limiting the subject matter described. Unless otherwise indicated,
conventional methods of mass spectroscopy, NMR, HPLC, protein chemistry,
biochemistry, recombinant DNA techniques and pharmacology are employed.
"Bond" or "single bond" as used herein means a chemical bond between two
atoms, or two moieties when the atoms joined by the bond are considered to be part of
larger substructure. As explicitly stated or implied by context, when a group described
herein is a bond, the referenced group is absent thereby allowing a bond to be formed
between the remaining identified groups.
"Membered ring" as used herein means any cyclic structure. The term
"membered" is meant to denote the number of skeletal atoms that constitute the ring.
Thus, by way of example and not limitation, those membered rings include cyclohexyl,
pyridinyl, pyranyl and thiopyranyl, which are 6-membered rings and cyclopentyl, pyrrolyl,
furanyl, and thienyl, which are 5-membered rings.
"Moiety" as used herein means a specific segment, fragment or functional group
of a molecule or compound. Chemical moieties are sometimes indicated as chemical
entities that are embedded in or appended (i.e., a substituent or variable group) to a
molecule or compound.
“Alkyl” as used herein is a collection of carbon atoms that are covalently linked
together in normal, secondary, tertiary or cyclic arrangements, i.e., in a linear,
branched, cyclic arrangement or some combination thereof. An alkyl substituent to a
structure is that chain of carbon atoms that is covalently attached to the structure
through a sp carbon of the substituent. The alkyl substituents, as used herein,
contains one or more saturated moieties or groups and may additionally contain
unsaturated alkyl moieties or groups, i.e., the substituent may comprise one, two,
three or more independently selected double bonds or triple bonds of a combination
thereof, typically one double or one triple bond if such unsaturated alkyl moieties or
groups are present .
Unsaturated alkyl moieties or groups include moieties or groups as described
below for alkenyl, alkynyl, cycloalkyl, and aryl moieties. Saturated alkyl moieties
contain saturated carbon atoms (sp ) and no aromatic, sp or sp carbon atoms. The
number of carbon atoms in an alkyl moiety or group can vary and typically is 1 to
about 50, e.g., about 1-30 or about 1-20, unless otherwise specified, e.g., C alkyl or
C1-C8 alkyl means an alkyl moiety containing 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms
and C alkyl or C1-C6 means an alkyl moiety containing 1, 2, 3, 4, 5 or 6 carbon
atoms.
[45] When an alkyl substituent, moiety or group is specified, species may include
methyl, ethyl, 1-propyl (n-propyl), 2-propyl (iso-propyl, -CH(CH ) ), 1-butyl (n-butyl), 2-
methylpropyl (iso-butyl, -CH CH(CH ) ), 2-butyl (sec-butyl, -CH(CH )CH CH ), 2-
2 3 2 3 2 3
methylpropyl (t-butyl, -C(CH ) ), amyl, isoamyl, sec-amyl and other linear, cyclic
and branch chain alkyl moieties. Unless otherwise specified, alkyl groups can
contain species and groups described below for cycloalkyl, alkenyl, alkynyl groups,
aryl groups, arylalkyl groups, alkylaryl groups and the like.
Cycloalkyl as used here is a monocyclic, bicyclic or tricyclic ring system
composed of only carbon atoms. The term "cycloalkyl" encompasses a monocyclic or
polycyclic aliphatic, non-aromatic radical, wherein each of the atoms forming the ring
(i.e. skeletal atoms) is a carbon atom. The number of carbon atoms in an cycloalkyl
substituent, moiety or group can vary and typically is 3 to about 50, e.g., about 1-30 or
about 1-20, unless otherwise specified, e.g., C alkyl or C3-C8 alkyl means an
cycloalkyl substituent, moiety or group containing 3, 4, 5, 6, 7 or 8 carbon atoms and C
alkyl or C3-C6 means an cycloalkyl substituent, moiety or group containing 3, 4, 5 or 6
carbon atoms. Cycloalkyl substituents, moieties or groups will typically have 3, 4, 5, 6,
7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms and may contain exo or
endo-cyclic double bonds or endo-cyclic triple bonds or a combination of both wherein
the endo-cyclic double or triple bonds, or the combination of both, do not form a cyclic
conjugated system of 4n + 2 electrons; wherein the bicyclic ring system may share one
(i.e., spiro ring system) or two carbon atoms and the tricyclic ring system may share a
total of 2, 3 or 4 carbon atoms, typically 2 or 3.
Unless otherwise specified, cycloalkyl substituents, moieties or groups can
contain moieties and groups described for alkenyl, alkynyl, aryl, arylalkyl, alkylaryl
and the like and can contain one or more other cycloalkyl moieties. Thus, cycloalkyls
may be saturated, or partially unsaturated. Cycloalkyls may be fused with an aromatic
ring, and the points of attachment to the aromatic ring are at a carbon or carbons of
the cycloalkyl substituent, moiety or group that is not an aromatic ring carbon atom.
Cycloalkyl groups include groups having from 3 to 10 ring atoms. Cycloalkyl
substituents, moieties or groups include cyclopropyl, cyclopentyl, cyclohexyl,
adamantly or other cyclic all carbon containing moieties. Cycloalkyls further include
cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptyl and cyclooctyl. Cycloalkyl groups
may be substituted or unsubstituted. Depending on the substituent structure, a
cycloalkyl substituent can be a monoradical or a diradical (i.e., an cycloalkylene, such
as, but not limited to, cyclopropan-1,1-diyl, cyclobutan-1,1-diyl, cyclopentan-1,1-diyl,
cyclohexan-1,1-diyl, cyclohexan-1,4-diyl, cycloheptan-1,1-diyl, and the like). When
cycloalkyl is used as a Markush group (i.e., a substituent) the cycloalkyl is attached to
a Markush formula with which it is associated through a carbon involved in a cyclic
carbon ring system carbon of the cycloalkyl group that is not an aromatic carbon.
"Alkylamine" as used herein means an -N(alkyl) H group, moiety or substituent
where x and y are independently selected from the group x=1, y=1 and x=2, y=O.
Alkylamine includes those -N(alkyl) H groups wherein x=2 and y=0 and the alkyl groups
taken together with the nitrogen atom to which they are attached form a cyclic ring
system.
"Heteroalkylene" as used herein means an alkylene (i.e. alkanediyl) group,
moiety or substituent in which one or more skeletal atoms of the alkyl are selected from
an atom other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus or combinations
thereof. Heteroalkylene includes C -C heteroalkylene or C -C heteroalkylene.
1 6 1 4
Exemplary heteroalkylenes include, but are not limited to, -OCH -, -OCH(CH )-,
-OC(CH ) -, -OCH CH -, -CH O-, -CH(CH )O-, C(CH ) O-, -CH CH O-, -CH OCH -, -
3 2 2 2 2 3 3 2 2 2 2 2
CH OCH CH -, -CH CH OCH -, -SCH -, -SCH(CH )-, -SC(CH ) -, -SCH CH -, -CH S-, -
2 2 2 2 2 2 2 3 3 2 2 2 2
CH(CH )S-, -C(CH ) S-, -CH CH S-, -CH SCH -,-CH SCH CH -, -CH CH SCH -, -
3 3 2 2 2 2 2 2 2 2 2 2 2
S(=O) CH -, -S(=O) CH(CH )-, -S(=O) C(CH ) -, -S(=O) CH CH -, -CH S(=O) -,
2 2 2 3 2 3 2 2 2 2 2 2
-CH(CH )S(=O) -, -C(CH ) S(=O) -, -CH CH S(=O) -, -CH S(=O) CH -,
3 2 3 2 2 2 2 2 2 2 2
-CH2S(=O)2CH2CH2-, CH2CH2S(=O)2CH2-, -NHCH2-, -NHCH(CH3)-, -NHC(CH3)2-,
-NHCH CH -, -CH NH-, -CH(CH )NH-, -C(CH ) NH-, -CH CH NH-, -CH NHCH -,
2 2 2 3 3 2 2 2 2 2
-CH NHCH CH -, -CH CH NHCH -, and the like.
2 2 2 2 2 2
"Carboxylic acid bioisostere" as used herein means a functional group, moiety or
substituent that exhibits similar physical, biological and/or chemical properties as a
carboxylic acid moiety. By way of example and not limitation, carboxylic acid
bioisosteres include,
O N S
CN O N
F C CF
OH OH
“Alkenyl” as used herein means a substituent, moiety or group that comprises
one or more double bond moities (e.g., -CH=CH-) or 1, 2, 3, 4, 5 or 6 or more,
typically 1, 2 or 3 such moieties and can include an aryl moiety or group such as
benzene, and additionally comprises linked normal, secondary, tertiary or cyclic
carbon atoms, i.e., linear, branched, cyclic or any combination thereof unless the
alkenyl moiety is a vinyl moiety (e.g., -CH=CH ). An alkenyl moiety, group or
substituent with multiple double bonds may have the double bonds arranged
contiguously (i.e. a 1,3 butadienyl moiety) or non-contiguously with one or more
intervening saturated carbon atoms or a combination thereof, provided that a cyclic,
contiguous arrangement of double bonds do not form a cyclically conjugated system
of 4n + 2 electrons (i.e., aromatic). The number of carbon atoms in an alkenyl group
or moiety can vary and typically is 2 to about 50, e.g., about 2-30 or about 2-20,
unless otherwise specified, e.g., C alkenyl or C2-8 alkenyl means an alkenyl moiety
containing 2, 3, 4, 5, 6, 7 or 8 carbon atoms and C alkenyl or C2-6 alkenyl means
an alkenyl moiety containing 2, 3, 4, 5 or 6 carbon atoms. Alkenyl moieties or groups
will typically have 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20
carbon atoms.
When an alkenyl moiety, group or substituent is specified, species include, by
way of example and not limitation, any of the alkyl or cycloalkyl, groups moieties or
substituents described herein that has one or more double bonds, methylene (=CH ),
methylmethylene (=CH-CH ), ethylmethylene (=CH-CH -CH ), =CH-CH -CH -CH ,
3 2 3 2 2 3
vinyl (-CH=CH ), allyl, 1-methylvinyl, butenyl, iso-butenyl, 3-methylbutenyl, 1-
pentenyl, cyclopentenyl, 1-methyl-cyclopentenyl, 1-hexenyl, 3-hexenyl, cyclohexenyl
and other linear, cyclic and branched chained all carbon containing moieties
containing at least one double bond. When alkenyl is used as a Markush group (i.e.,
a substituent) the alkenyl is attached to a Markush formula with which it is associated
through an unsaturated carbon of a double bond of the alkenyl moiety or group
unless specified otherwise.
[53] “Alkynyl” as used herein means a substituent, moiety or group that comprises
one or more triple bond moieties (i.e., -C=C-), e.g., 1, 2, 3, 4, 5, 6 or more, typically 1
or 2 triple bonds, optionally comprising 1, 2, 3, 4, 5, 6 or more double bonds, with the
remaining bonds (if present) being single bonds and comprising linked normal,
secondary, tertiary or cyclic carbon atoms, i.e., linear, branched, cyclic or any
combination thereof, unless the alkynyl moiety is ethynyl. The number of carbon
atoms in an alkenyl moiety or group can vary and typically is 2 to about 50, e.g.,
about 2-30 or about 2-20, unless otherwise specified, e.g., C alkynyl or C2-8
alkynyl means an alkynyl moiety containing 2, 3, 4, 5, 6, 7 or 8 carbon atoms. Alkynyl
groups will typically have 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or
20 carbon atoms.
When an alkynyl moiety or group is specified, species include, by way of
example and not limitation, any of the alkyl moieties, groups or substituents described
herein that has one or more double bonds, ethynyl, propynyl, butynyl, iso-butynyl, 3-
methylbutynyl, 1-pentynyl, cyclopentynyl, 1-methyl-cyclopentynyl, 1-hexynyl, 3-
hexynyl, cyclohexynyl and other linear, cyclic and branched chained all carbon
containing moieties containing at least one triple bond. When an alkynyl is used as a
Markush group (i.e., a substituent) the alkynyl is attached to a Markush formula with
which it is associated through one of the unsaturated carbons of the alkynyl functional
group.
[55] "Aromatic" as used herein refers to a planar ring having a delocalized pi-electron
system containing 4n+2 pi electrons, where n is a positive integer. Aromatic rings can
be formed from five, six, seven, eight, nine, ten, or more than ten atoms. Aromatics are
optionally substituted. The term "aromatic" includes both carboxcylic aryl ("aryl", e.g.,
phenyl) and heterocyclic aryl (or "heteroaryl" or "heteroaromatic") groups (e.g., pyridine).
The term includes monocyclic or fused-ring polycyclic (i.e., rings which share adjacent
pairs of carbon atoms) groups.
[56] ”Aryl” as used here means an aromatic ring system or a fused ring system with
no ring heteroatoms comprising 1, 2, 3 or 4 to 6 rings, typically 1 to 3 rings, wherein the
rings are composed of only carbon atoms; and refers to a cyclically conjugated system
of 4n + 2 electrons (Huckel rule), typically 6, 10 or 14 electrons some of which may
additionally participate in exocyclic conjugation (cross-conjugated (e.g., quinone). Aryl
substituents, moieties or groups are typically formed by five, six, seven, eight, nine, or
more than nine, carbon atoms. Aryl substituents, moieties or groups are optionally
substituted. Exemplary aryls include C -C aryls such as phenyl and naphthalenyl and
6 10
phenanthryl. Depending on the structure, an aryl group can be a monoradical or a
diradical (i.e., an arylene group). Exemplary arylenes include, but are not limited to,
phenyl-1,2-ene, phenyl-1,3-ene, and phenyl-1,4-ene. When aryl is used as a Markush
group (i.e., a substituent) the aryl is attached to a Markush formula with which it is
associated through an aromatic carbon of the aryl group.
“Arylalkyl” as used herein means a substituent, moiety or group where an aryl
moiety is bonded to an alkyl moiety, i.e., -alkyl-aryl, where alkyl and aryl groups are
as described above, e.g., -CH -C H or -CH CH(CH )-C H . When arylalkyl is used as
2 6 5 2 3 6 5
a Markush group (i.e., a substituent) the alkyl moiety of the arylalkyl is attached to a
Markush formula with which it is associated through a sp carbon of the alkyl moiety.
“Alkylaryl” as used herein means a substituent, moiety or group where an
alkyl moiety is bonded to an aryl moiety, i.e., -aryl-alkyl, where aryl and alkyl groups
are as described above, e.g., -C H -CH or -C H -CH CH(CH ). When alkylaryl is
6 4 3 6 4 2 3
used as a Markush group (i.e., a substituent) the aryl moiety of the alkylaryl is
attached to a Markush formula with which it is associated through a sp carbon of the
aryl moiety.
“Substituted alkyl”, “substituted cycloalkyl”, "substituted alkenyl", "substituted
alkynyl", substituted alkylaryl”, “substituted arylalkyl”, “substituted heterocycle”,
“substituted aryl” and the like as used herein mean an alkyl, alkenyl, alkynyl, alkylaryl,
arylalkyl heterocycle, aryl or other group or moiety as defined or disclosed herein that
has a substituent(s) that replaces a hydrogen atom(s) or a substituent(s) that
interrupts a carbon atom chain. Alkenyl and alkynyl groups that comprise a
substituent(s) are optionally substituted at a carbon that is one or more methylene
moieties removed from the double bond.
“Optionally substituted alkyl”, “optionally substituted alkenyl", “optionally
substituted alkynyl", “optionally substituted alkylaryl”, “optionally substituted arylalkyl”,
“optionally substituted heterocycle”, “optionally substituted aryl”, “optionally
substituted heteroaryl“, “optionally substituted alkylheteroaryl”, “optionally substituted
heteroarylalkyl” and the like as used herein mean an alkyl, alkenyl, alkynyl, alkylaryl,
arylalkyl heterocycle, aryl, heteroaryl, alkylheteroaryl, heteroarylalkyl, or other
substituent, moiety or group as defined or disclosed herein that has a substituent(s)
that optionally replaces a hydrogen atom(s) or a substituent(s) that interrupts a
carbon atom chain. Such substituents are as described herein. For a phenyl moiety,
the arrangement of any two substituents present on the aromatic ring can be ortho
(o), meta (m), or para (p). An optionally substituted fluoroalkyl is an alkyl or cycloalkyl
moiety, typically a linear alkyl, wherein one or more hydrogen atoms is replaced by
fluorine and at least one other atom other than carbon and fluorine.
An optionally substituted or substituted substituent, moiety or group includes
those having one or more additional group(s) that replace its hydrogen atom(s)
individually and independently selected from alkyl, cycloalkyl, aryl, heteroaryl,
heteroalicyclic, hydroxy, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide,
alkylsulfone, arylsulfone, cyano, halo, nitro, haloalkyl, fluoroalkyl, fluoroalkoxy, and
amino, including mono- and di-substituted amino groups, and the protected derivatives
thereof. By way of example and not limitation an optional substituent(s) may be halide, -
CN, -NO , or LsRs, wherein each Ls is independently selected from a bond, -O-, -
C(=O)-, -C(=O)O-, -S-, -S(=O)-, -S(=O) -, -NH-, -NHC(=O)-, -C(=O)NH-, S(=O) NH-, -
NHS(=O) , -OC(=O)NH-, -NHC(=O)O-, or -(C -C alkylene)-; and each Rs is selected
2 1 6
from -H, alkyl, fluoroalkyl, heteroalkyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl.
The protecting groups that may form the protective derivatives of the above substituents
may be found in sources such as Greene and Wuts, above. Optional substituents
include those selected from the group consisting of halogen, -CN, -NH , -OH, -N(CH ) ,
2 3 2
alkyl, fluoroalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy,
aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, and arylsulfone,
those selected from the group consisting of halogen, -CN, -NH , -OH, NH(CH ),
-N(CH ) , -CO H, -CO alkyl, -C(=O)NH , -C(=O)NHalkyl, -C(=O)N(alkyl) , -S(=O) NH ,
3 2 2 2 2 2 2 2
-S(=O) NH(alkyl), -S(=O) N(alkyl) , alkyl, cycloalkyl, fluoroalkyl, heteroalkyl, alkoxy,
2 2 2
fluoroalkoxy, -S-alkyl and-S(=0) alkyl or those selected from the group consisting of
halogen, -CN, -NH , -OH, -NH(CH ), -N(CH ) , -CH , -CH CH , -CF , -OCH , and -OCF .
2 3 3 2 3 2 3 3 3 3
Typically, an optionally substituted, substituent, moiety or group is substituted with one
or two of the preceding groups, or more typically with one of the preceding groups. An
optional substituent on an aliphatic carbon atom (acyclic or cyclic, saturated or
unsaturated carbon atoms, excluding aromatic carbon atoms) further includes oxo (=O).
“Heterocycle” or “heterocyclic” as used herein means a cycloalkyl or aromatic
ring system wherein one or more, typically 1, 2 or 3, but not all of the carbon atoms
comprising the ring system are replaced by a heteroatom which is an atom other than
carbon, including, N, O, S, Se, B, Si, P, typically N, O or S wherein two or more
heteroatoms may be adjacent to each other or separated by one or more carbon
atoms, typically 1-17 carbon atoms, 1-7 atoms or 1-3 atoms. Heterocycles includes
heteroaromatic rings (also known as heteroaryls) and heterocycloalkyl rings (also
known as heteroalicyclic groups) containing one to four heteroatoms in the ring(s),
where each heteroatom in the ring(s) is selected from O, S and N, wherein each
heterocyclic group has from 4 to 10 atoms in its ring system, and with the proviso that
the any ring does not contain two adjacent O or S atoms.
Non-aromatic heterocyclic, substituents, moieties or groups (also known as
heterocycloalkyls) have at least 3 atoms in their ring system, and aromatic
heterocyclic groups have at least 5 atoms in their ring system and include benzo-
fused ring systems. Heterocyclics with 3, 4, 5, 6 and 10 atoms include aziridinyl
azetidinyl, thiazolyl, pyridyl and quinolinyl, respectively. Nonaromatic heterocyclic
substituents, moieties or groups are pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl,
tetrahydrothienyl, oxazolidinonyl, tetrahydropyranyl, dihydropyranyl,
tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, piperazinyl,
aziridinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl,
oxazepinyl, diazepinyl, thiazepinyl, 1,2,3,6-tetrahydropyridinyl, pyrrolinyl, pyrrolin-
3-yl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl,
dithiolanyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazolidinyl, imidazolinyl,
imidazolidinyl, 3-azabicyclo[3.1.0)hexanyl, 3azabicyclo[4.1.0)heptanyl, 3H-indolyl and
quinolizinyl. Aromatic heterocyclic includes, by way of example and not limitation,
pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl,
isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl,
benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl,
pyridazinyl,triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl,
benzofurazanyl, benzo-thiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl,
quinoxalinyl, naphthyridinyl, and furopyridinyl. Non-aromatic heterocycles may be
substituted with one or two oxo (=O) moieties, and includes pyrrolidinone.
[64] When heterocycle is used as a Markush group (i.e., a substituent) the
heterocycle is attached to a Markush formula with which it is associated through a
carbon or a heteroatom of the heterocycle, where such an attachment does not result
in an unstable or disallowed formal oxidation state of that carbon or heteroatom. A
heterocycle that is C-linked is bonded to a molecule through a carbon atom include
moieties such as -(CH ) -heterocycle where n is 1, 2 or 3 or -C<heterocycle where C<
represents a carbon atom in a heterocycle ring. A heterocycle that is N-linked is a
nitrogen containing heterocycle that is bonded a heterocycle ring nitrogen sometimes
described as -N<heterocycle where N< represents a nitrogen atom in a heterocycle
ring. Thus, nitrogen-containing heterocycles may be C-linked or N-linked and include
pyrrole substituents, which may be pyrrolyl (N-linked) or pyrrolyl (C-linked),
imidazole substituents, which may be imidazolyl or imidazolyl (both N-linked) or
imidazolyl, imidazolyl or imidazolyl (all C-linked).
“Heteroaryl” as used herein means an aryl ring system wherein one or more,
typically 1, 2 or 3, but not all of the carbon atoms comprising the aryl ring system are
replaced by a heteroatom which is an atom other than carbon, including, N, O, S, Se,
B, Si, P, typically, oxygen (-O-), nitrogen (-NX-) or sulfur (-S-) where X is -H, a
protecting group or C optionally substituted alkyl, wherein the heteroatom
participates in the conjugated system either through pi-bonding with an adjacent atom
in the ring system or through a lone pair of electrons on the heteroatom and may be
optionally substituted on one or more carbons or heteroatoms, or a combination of
both, in a manner which retains the cyclically conjugated system.
[66] Heterocycles and heteroaryls, include, by way of example and not limitation,
heterocycles and heteroaryls described in Paquette, Leo A.; "Principles of Modern
Heterocyclic Chemistry" (W. A. Benjamin, New York, 1968), particularly Chapters 1,
3, 4, 6, 7, and 9; "The Chemistry of Heterocyclic Compounds, A series of
Monographs" (John Wiley & Sons, New York, 1950 to present), in particular Volumes
13, 14, 16, 19, and 28; and J. Am. Chem. Soc. 1960, 82:5545-5473 particularly 5566-
5573). Examples of heteroaryls include by way of example and not limitation pyridyl,
thiazolyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, purinyl, imidazolyl,
benzofuranyl, indolyl, isoindoyl, quinolinyl, isoquinolinyl, benzimidazolyl, pyridazinyl,
pyrazinyl, benzothiopyran, benzotriazine, isoxazolyl, pyrazolopyrimidinyl, quinoxalinyl,
thiadiazolyl, triazolyl and the like. Heterocycles that are not heteroaryls include, by
way of example and not limitation, tetrahydrothiophenyl, tetrahydrofuranyl, indolenyl,
piperidinyl, pyrrolidinyl, 2-pyrrolidonyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl,
decahydroquinolinyl, octahydroisoquinolinyl, 2H-pyrrolyl, 3H-indolyl, 4H-quinolizinyl,
imidazolidinyl, imidazolinyl, pyrazolidinyl, piperazinyl, quinuclidinyl, morpholinyl,
oxazolidinyl and the like.
Other heteroaryls include, by way of example and not limitation, the following
moieties:
N N O
N S O N
N N N
Monocyclic heteroaryls include, by way of example and not limitation,
pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl,
isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl,
thiadiazolyl, and furazanyl. Heteroaryls include those substituents, moieties or groups
containing 0-3 N atoms, 1-3 N atoms or 0-3 N atoms, 0-1 O atoms and 0-1 S atoms.
A heteroaryl may be monocyclic or bicyclic. The ring system of a heteroaryls ring
typically contains 1-9 carbons (i.e., C -C heteroaryl). Monocyclic heteroaryls include
C -C heteroaryls. Monocyclic heteroaryls include those having 5-membered or 6-
membered ring systems. Bicyclic heteroaryls include C -C heteroaryls. Depending
on the structure, a heteroaryl group can be a monoradical or a diradical (i.e., a
heteroarylene group).
"Heterocycloalkyl" or “heteroalicyclic” as used herein means a cycloalkyl group,
moiety or substituent wherein at least on carbon of the cycloalkyl chain is replaces with
a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur. The
heterocycloalkyl may be fused with an aryl or heteroaryl. Heterocycloalkyls, also
referred to as non-aromatic heterocycles, include by way of example and not limitation:
O O O O O
S N N N O O O
N N O O N
N N N
O O S
Heterocycloalkyl includes, by way of example and not limitation, oxazolidinonyl,
pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl,
tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, and indolinyl.
Heteroalicyclics further includes all ring forms of carbohydrates, including but not limited
to monosaccharides, disaccharides and oligosaccharides. Typically, a heterocycloalkyl
is a C -C heterocycloalkyl and includes C -C heterocycloalkyl. A heterocycloalkyl
2 10 4 10
may contain 0-2 N atoms, 0-2 O atoms or 0-1 S atoms.
[71] “Heteroarylalkyl” as used herein means a substituent, moiety or group where
a heteroaryl moiety is bonded to an alkyl moiety, i.e., -alkyl-heteroaryl, where alkyl
and heteroaryl groups are as described above. When heteroarylalkyl is used as a
Markush group (i.e., a substituent) the alkyl moiety of the heteroarylalkyl is attached
to a Markush formula with which it is associated through a sp carbon of the alkyl
moiety.
“Alkylheteroaryl” as used herein means a substituent, moiety or group where
a heteroaryl moiety is bonded to an alkyl moiety, i.e., -heteroaryl-alkyl, where
heteroaryl and alkyl groups are as described above. When heteroarylalkyl is used as
a Markush group (i.e., a substituent) the heteroaryl moiety of the heteroarylalkyl is
attached to a Markush formula with which it is associated through a sp carbon or
heteroatom of the alkyl moiety.
“Halogen” or “halo” as used herein means fluorine, chlorine, bromine or iodine.
"Haloalkyl" as used herein means an alkyl substituent moiety or group in which
one or more of its hydrogen atoms are replaced by one or more independently selected
halide atoms. Haloalkyl includes C -C haloalkyl. Example but non-limiting C -C
1 4 1 4
haloalkyls are -CH Cl, CH Br, -CH I, -CHBrCl, -CHCl-CH Cl and –CHCl-CH I.
2 2 2 2 2
"Haloalkylene" as used herein means an alkylene substituent, moiety or group in
which one or more hydrogen atoms are replaced by one or more halide atoms.
Haloalkylene includes C -C haloalkylenes or C -C haloalkylenes.
1 6 1 4
[76] "Fluoroalkyl" as used herein means an alkyl in which one or more hydrogen
atoms are replaced by a fluorine atom. Fluoroalkyl includes C -C and C -C
1 6 1 4
fluoroalkyls. Example but non-limiting fluoroalkyls include -CH F, -CH F and -CF and
3 2 2 3
perfluroalkyls.
"Fluoroalkylene" as used herein means an alkylene in which one or more
hydrogen atoms are replaced by a fluorine atom. Fluoroalkylene includes C -C
fluoroalkylenes or C -C fluoroalkylenes.
The term "heteroalkyl" refers to an alkyl group in which one or more skeletal
atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen,
sulfur, phosphorus or combinations thereof. In one aspect, a heteroalkyl is a C1-C6
heteroalkyl.
“Protecting group” as used here means a moiety that prevents or reduces the
ability of the atom or functional group to which it is linked from participating in
PR PR
unwanted reactions. Non-limiting examples are for -OR , wherein R is a
PR PR
protecting group for the oxygen atom found in a hydroxyl, while for -C(O)-OR , R
PR PR
may be a carboxylic acid protecting group; for -SR , R may be a protecting group
PR PR PR
for sulfur in thiols and for -NHR or -N(R )2-, at least one of R is a nitrogen atom
protecting group for primary or secondary amines. Hydroxyl, amine, ketones and
other reactive groups may require protection against reactions taking place
elsewhere in the molecule. The protecting groups for oxygen, sulfur or nitrogen
atoms are usually used to prevent unwanted reactions with electrophilic compounds,
such as acylating agents. Typical protecting groups for atoms or functional groups
are given in Greene (1999), “Protective groups in organic synthesis, 3 ed.”, Wiley
Interscience.
“Ester” as used herein means a substituent, moiety or group that contains a
-C(O)-O- structure (i.e., ester functional group) wherein the carbon atom of the
structure is not directly connected to another heteroatom and is directly connected to
-H or another carbon atom. Typically, esters comprise or consist of an organic moiety
containing 1-50 carbon atoms, 1-20 carbon atoms or 1-8 carbon atoms and 0 to 10
independently selected heteroatoms (e.g., O, S, N, P, Si), typically 0-2 where the
organic moiety is bonded through the -C(O)-O- structure and include ester moieties
such as organic moiety-C(O)-O-. The organic moiety usually comprises one or more
of any of the organic groups described herein, e.g., C alkyl moieties, C alkenyl
1-20 2-20
moieties, C alkynyl moieties, aryl moieties, C heterocycles or substituted
2-20 3-8
derivatives of any of these, e.g., comprising 1, 2, 3, 4 or more substituents, where
each substituent is independently chosen. Exemplary, non-limiting substitutions for
hydrogen or carbon atoms in these organic groups are as described above for
substituted alkyl and other substituted moieties and are independently chosen. The
substitutions listed above are typically substituents that one can use to replace one or
more carbon atoms, e.g., -O- or -C(O)-, or one or more hydrogen atom, e.g., halogen,
-NH or -OH. Exemplary esters include by way of example and not limitation, one or
more independently selected acetate, propionate, isopropionate, isobutyrate,
butyrate, valerate, isovalerate, caproate, isocaproate, hexanoate, heptanoate,
octanoate, phenylacetate esters or benzoate esters. When ester is used as a
Markush group (i.e., a substituent) the single bonded oxygen of the ester functional
group is attached to a Markush formula with which it is associated.
“Acetal”, “thioacetal”, "ketal", "thioketal" and the like as used herein means a
moiety, group or substituent comprising or consisting of a carbon to which is bonded
two of the same or different heteroatoms wherein the heteroatoms are independently
selected S and O. For acetal the carbon has two bonded oxygen atoms, a hydrogen
atom and an organic moiety. For ketal, the carbon has two bonded oxygen atoms
and two independently selected organic moieties where the organic moiety is as
described herein alkyl or optionally substituted alkyl group. For thioacetals and
thioketals one or both of the oxygen atoms in acetal or ketal, respectively, is replaced
by sulfur. The oxygen or sulfur atoms in ketals and thioketals are sometimes linked by
an optionally substituted alkyl moiety. Typically, the alkyl moiety is an optionally
substituted C alkyl or branched alkyl structure such as -C(CH ) -, -CH(CH )-, -CH -,
1-8 3 2 3 2
-CH -CH -, -C[(C2-C4 alkyl) ] - or –[CH(C2-C4 alkyl)] -. Some of these
2 2 2 1, 2, 3 1, 2, 3
moieties can serve as protecting groups for an aldehyde or ketone include, by way of
example and not limitation, acetals for aldehydes and ketals for ketones and contain
-O-CH -CH -CH -O- or -O-CH -CH -O- moieties that form a spiro ring with the
2 2 2 2 2
carbonyl carbon, and can be removed by chemical synthesis methods or by
metabolism in cells or biological fluids.
“Ether” as used herein means an organic moiety, group or substituent that
comprises or consists of 1, 2, 3, 4 or more -O- moieties, usually 1 or 2, wherein no two -
O- moieties are immediately adjacent (i.e., directly attached) to each other. Typically,
ethers comprise an organic moiety containing 1-50 carbon atoms, 1-20 carbon atoms or
1-8 carbon atoms and 0 to 10 independently selected heteroatoms (e.g., O, S, N, P, Si),
typically 0-2. An ether moiety, group or substituent includes organic moiety-O- wherein
the organic moiety is as described herein for alkyl or optionally substituted alkyl group.
When ether is used as a Markush group (i.e., a substituent) the oxygen of the ether
functional group is attached to a Markush formula with which it is associated. When
ether is a used as substituent in a Markush group it is sometimes designated as an
"alkoxy" group. Alkoxy includes C1-C4 ether substituents such as, by way of example
and not limitation, methoxy, ethoxy, propoxy, iso-propoxy and butoxy. Ether further
includes those substituents, moieties or groups that contain one (excluding ketal) or
more -OCH CH O-, moieties in sequence (i.e., polyethylene or PEG moieties).
“Carbonate” as used here means a substituent, moiety or group that contains
a -O-C(=O)-O- structure (i.e., carbonate functional group). Typically, carbonate
groups as used here comprise or consist of an organic moiety containing 1-50 carbon
atoms, 1-20 carbon atoms or 1-8 carbon atoms and 0 to 10 independently selected
heteroatoms (e.g., O, S, N, P, Si), typically 0-2, bonded through the -O-C(=O)-O-
structure, e.g., organic moiety-O-C(=O)-O-. When carbonate is used as a Markush
group (i.e., a substituent) one of the singly bonded oxygen atoms of the carbonate
functional group is attached to a Markush formula with which it is associated.
“Carbamate” or “urethane” as used here means a substituent, moiety or group
PR PR
that contains a -O-C(=O)N(R )-, -O-C(=O)N(R ) , -O-C(=O)NH(optionally
substituted alkyl) or -O-C(=O)N(optionally substituted alkyl) - structure (i.e.,
carbamate functional group) where R and optionally substituted alkyl are
independently selected and R are independently -H, a protecting group or an
organic moiety as described for ester, alkyl or optionally substituted alkyl. Typically,
carbamate groups as used here comprise or consist of an organic moiety containing
about 1-50 carbon atoms, 1-20 carbon atoms or 1-8 carbon atoms and 0 to 10
independently selected heteroatoms (e.g., O, S, N, P, Si), typically 0-2, bonded
PR PR
through the -O-C(=O)-NR - structure, e.g., organic moiety-O-C(=O)-NR - or -O-
C(=O)-NR -organic moiety. When carbamate is used as a Markush group (i.e., a
substituent) the singly bonded oxygen (O-linked) or nitrogen (N-linked) of the
carbamate functional group is attached to a Markush formula with which it is
associated. The linkage of the carbamate substituent is either explicitly stated (N- or
O-linked) or implicit in the context to which this substituent is referred.
For any substituent group or moiety described by a given range of carbon atoms,
the designated range means that any individual number of carbon atoms is described.
Thus, reference to, e.g., “C1-C4 optionally substituted alkyl”, “C2-6 alkenyl optionally
substituted alkenyl”, “C3-C8 optionally substituted heterocycle” specifically means that a
1, 2, 3 or 4 carbon optionally substituted alkyl moiety as defined herein is present, or a
2, 3, 4, 5 or 6 carbon alkenyl, or a 3, 4, 5, 6, 7 or 8 carbon moiety comprising a
heterocycle or optionally substituted alkenyl moiety as defined herein is present. All
such designations are expressly intended to disclose all of the individual carbon atom
groups and thus “C1-C4 optionally substituted alkyl” includes, e.g., 3 carbon alkyl, 4
carbon substituted alkyl and 4 carbon alkyl, including all positional isomers and the like
are disclosed and can be expressly referred to or named. For esters, carbonates and
carbamates defined by a given range of carbon atoms, the designated range includes
the carbonyl carbon of the respective functional group. Thus a C1 ester refers to a
formate ester and a C2 ester refers to an acetate ester. The organic substitutents,
moieties and groups described herein, and for other any other moieties described
herein, usually will exclude unstable moieties except where such unstable moieties are
transient species that one can use to make a compound with sufficient chemical stability
for the one or more of the uses described herein. Substituents, moieties or groups by
operation of the definitions herein that results in those having a pentavalent carbon are
specifically excluded.
“LPA-dependent”, “LPA-mediated” or like terms as used herein means a disease
or condition whose etiology, progression or persistence is effected by in whole or in part
by signaling through one or more lysophosphatidic acid receptor subtypes, including by
way of example and not limitation lysophosphatidic acid receptor subtypes 1-6 (LPARs).
LPA-dependent or LPA-mediated diseases and conditions include but not limited to
fibrosis of organs (e.g., liver, kidney, lung, heart and the like), liver diseases (e.g., acute
hepatatis, chronic hepatitis, liver fibrosis, liver cirrhosis, portal hypertension,
regenerative failure, nonalcoholic steatohepatitis (NASH), liver hypofunction, hepatic
blood flow disorder, and the like), cell proliferative disease (e.g., cancers, including but
not limited to solid tumor, solid tumor metastasis, vascular fibroma, myeloma, multiple
myeloma, Kaposi's sarcoma, leukemia, chronic lymphocytic leukemia (CLL), invasive
metastasis of cancer cell, and the like), inflammatory disease (e.g., psoriasis,
nephropathy, pneumonia and the like), gastrointestinal tract disease (e.g., irritable bowel
syndrome (lBS), inflammatory bowel disease (IBD), abnormal pancreatic secretion, and
the like), renal disease, urinary tract-associated disease (e.g., benign prostatic
hyperplasia or symptoms associated with neuropathic bladder disease), spinal cord
tumor, hernia of intervertebral disk, spinal canal stenosis, symptoms derived from
diabetes, lower urinary tract disease (e.g., obstruction of lower urinary tract, and the
like), inflammatory disease of lower urinary tract (e.g., dysuria, frequent urination, and
the like), pancreas disease, abnormal angiogenesis-associated disease (e.g., arterial
obstruction and the like), scleroderma, brain-associated disease (e.g., cerebral
infarction, cerebral hemorrhage, and the like), nervous system diseases (e.g.,
neuropathic pain, peripheral neuropathy, pruritus and the like), ocular disease (e.g.,
age-related macular degeneration (AMD), diabetic retinopathy, proliferative vitreo-
retinopathy (PVR), cicatricial pemphigoid, glaucoma filtration surgery scarring, and the
like).
“LPA1R selective agents”, LPA1R selective compounds” and like terms as used
herein means agents or compounds that interact with the lysophosphatidic acid subtype
1 receptor in preference to the lysophosphatidic acid receptor 2-6. Typically, that
preference is manifested by 10-fold stronger binding affinity of the agent to LPA1R in
comparison to other known LPARs as measured by experimentally determined K
values.
"Pharmaceutically acceptable formulation" as used herein means a composition
comprising an active pharmaceutical ingredient, such as a compound having the
formula of I-VI in addition to one or more pharmaceutically acceptable excipients or
refers to a composition prepared from an active pharmaceutical ingredient and one or
more pharmaceutically acceptable excipients, wherein the composition is suitable for
administration to a subject, such as a human or an animal, in need thereof. For a
pharmaceutically acceptable formulation to be suitable for administration to a human the
formulation must have biological activity for treating or preventing a disease or condition
disclosed herein or an expectation must exist that the formulation would have a desired
activity towards an “intent to treat” disease or condition. Typically, the “intent to treat”
disease or condition is a lysophosphatidic acid receptor-mediated condition or disease.
More typically the disease or condition to be treated or prevented is a lysophosphatidic
acid lysophosphatidic acid type 1 receptor-mediated disease or condition. A
pharmaceutically acceptable formulation that is suitable for administration to an animal
does not necessarily require a biological activity for treating or preventing a disease or
condition, and may be administered to the animal in order to evaluate a potential
pharmacological or biological activity of a Formula I-XII compound. Those formulations
must therefore be suitable for treating or preventing a disease or condition disclosed
herein in an animal in need thereof or is suitable for evaluating a pharmacological or
biological activity of a Formula I-XII compound. Compositions that are suitable only for
use in vitro assays or which contain a vehicle, component or excipient in an amount not
permitted in a drug product are specifically excluded from the definition of a
pharmaceutically acceptable formulation.
[89] The pharmaceutically acceptable formulation may be comprised of, or be
prepared from, one, two or more Formula I-XII compounds, typically one or two, and one
or more pharmaceutically acceptable excipients. More typically, the formulations will
consist essentially of or consist of a single Formula I-XII compound and one or more
pharmaceutically acceptable excipients. Other formulations may be comprised of,
consist essentially of, or consist of one, two or more Formula I-XII compounds and one
two or more compounds in current use for treating lysophosphatidic acid
lysophosphatidic acid type 1 receptor-mediated disease or condition disclosed herein
and one or more pharmaceutically acceptable excipients. Typically those formulations
will consist essentially of or consist of a single Formula I-XII compound, a single
compound in current use for treating a lysophosphatidic acid lysophosphatidic acid type
1 receptor-mediated disease or condition and one or more pharmaceutically acceptable
excipients.
"Solid formulation" as used herein refers to a pharmaceutically acceptable
formulation comprising at least one Formula I-XII compound and one or more
pharmaceutically acceptable excipients in solid form(s) wherein the formulation is in a
unit dosage form suitable for administration of a solid. The dosage units include tablets,
capsules, caplets, gelcaps, suspensions and other dosage units typically associated
with parenteral or enteral (oral) administration of a solid.
"Liquid formulation" as used herein refers to a pharmaceutically acceptable
formulation wherein at least one Formula I-XII compound has been admixed or
contacted with one or more pharmaceutically acceptable excipients, wherein at least
one of the excipients is in liquid form in proportions required for a liquid formulation, i.e.,
such that a majority of the mass amount of the Formula I-XII compound(s) is dissolved
into the non-solid excipient. Dosage units containing a liquid formulation include syrups,
gels, ointments and other dosage units typically associated with parenteral or enteral
administration of a pharmaceutical formulation to a subject in need thereof in liquid form.
[92] “Prevent, “preventing” and like terms as used herein takes on its normal and
customary meaning in the medical arts and therefore does not require that each
instance to which the term refers be avoided with certainty.
Numbered embodiments
The following embodiments exemplify the invention and are not meant to limit
the invention in any manner. In certain embodiments, the compounds presented herein
possess one or more stereocenters and each center independently exists in either the R
or S configuration. The compounds presented herein include all diastereomeric,
enantiomeric, and epimeric forms as well as the appropriate mixtures thereof.
Stereoisomers are obtained, if desired, by methods such as, stereoselective synthesis
and/or the separation of stereoisomers by chiral chromatographic columns. The
methods and formulations described herein include the use of pharmaceutically
acceptable salts of compounds having the structure of Formulas (I-VI), as well as active
metabolites of these compounds having the same type of activity. In some situations,
compounds may exist as tautomers. All tautomers are included within the scope of the
compounds presented herein. In specific embodiments, the compounds described
herein will exist as salts, including pharmaceutically acceptable salts. The salt forms
- - - -
include inorganic addition salts such as F Cl , Br , I and sulfate salts and organic
addition salts such as mesylate, besylate, tosylate, citrate, succinate, fumarate and
malonate. In other embodiments, the compounds described herein exist as quaternary
ammonium salts.
1. A compound of Formula I having the structure
A B L
L R Formula I
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR , -
2 2 2
C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
L is absent or substituted or unsubstituted C -C alkylene, substituted or
unsubstituted C -C fluoroalkylene, substituted or unsubstituted C -C cycloalkylene,
1 6 3 8
substituted or unsubstituted C -C heteroalkylene, or -UV-Z-, wherein -UV-is defined by
J J J J
-OW-, -WO-, -N(R )W-, -WN(R )-, -N(R )C(=O)-, -SW-, -S(=O)nW-, or -C(=O)N(R )-,
wherein W is substituted or unsubstituted C -C alkylene, or W is -C(R ) -; Z is
1 3 2
substituted or unsubstituted C -C alkylene, substituted or unsubstituted C -C
1 6 3 8
cycloalkylene, or C -C fluoroalkylene or Z is -C(R ) -; and n is 0, 1, or 2;
1 6 2
L is absent, or substituted or unsubstituted C -C alkylene, substituted or
unsubstituted C -C cycloalkylene, C -C fluoroalkylene, substituted or unsubstituted C -
3 8 1 6 3
C cycloalkylene, substituted or unsubstituted C -C heteroalkylene, -O-, -S-, -SO-, -
8 1 6
SO -, -NR -, -C(=O)-, or -C(=O)N(R )-;
wherein R is substituted or unsubstituted C -C alkyl, or has the structure of one
O O O
O O O
[101] Ring A is a 5 or 6 membered heteroarene having the structure of one of:
R N N
C R R
R R C
C D D
D D C
R R R R R
N C N
R D C R
R R R
wherein the dashed line indicates the point of attachment of Ring A to Ring B;
wherein one of R and R is -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl,
1 4 1 4
C -C cycloalkyl, or C -C fluoroalkyl,
3 6 1 4
C D F G F G
[104] and the other R or R is -NR C(=O)XCH(R )-CY, -N(R )C(=O)XC(R ) -CY, or -
F F G F G
NR C(=O)X-CY, -C(=O)-N(R )-CH(R )X-CY, or -C(=O)-N(R )-C(R ) X-CY,
wherein X is absent, -O-, -NH- or -CH2-;
R is -H, -C -C alkyl or -C -C fluoroalkyl,
1 4 1 4
R is -H or C -C alkyl, and
G E G
[108] R is independently selected R or one R is C -C alkyl and is taken together
with CY and the the carbon atom to which R and CY is attached to define a substituted
or unsubstituted carbocycle or substituted or unsubstituted heterocycle and the other
R , if present, is as defined for R ;
wherein CY is substituted or unsubstituted C -C alkyl, substituted or
unsubstituted C -C cycloalkyl, substituted or unsubstituted C -C heterocycloalkyl,
3 10 2 10
substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein if
CY is substituted then CY is substituted with 1, 2, or 3 independently selected R ,
H J J J
R is independently -H, halogen, -CN, -NO , -OH, -OR , -SR , -S(=O)R ,
J J J L J J J J
-S(=O) R , -N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , OC(=O)R , -CO R , -OCO R ,
2 2 2 2 2 2
L L L J L J J
-N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) , N(R )C(=O)N(R ) , -N(R )C(=O)R ,
2 2 2 2
-N(R )C(=O)OR , C -C alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C alkoxy, or C -
1 4 1 4 1 4 1 4 1
C heteroalkyl,
wherein each R is independently substituted or unsubstituted C -C alkyl,
substituted or unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C
1 6 1 6
fluoroalkyl, substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene-(substituted or
unsubstituted aryl), and -C -C alkylene-(substituted or unsubstituted heteroaryl), and
[112] wherein each R is independently -H, C -C alkyl, C -C heteroalkyl, C -C
1 6 1 6 1 6
fluoroalkyl, substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene(substituted or
unsubstituted aryl), or -C -C alkylene-(substituted or unsubstituted heteroaryl), or
H L L L L
when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or
2 2 2 2 2
J L L L
-N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle,
L L L
[114] or when W or Z is -C(R ) - each R is independently -H, C -C alkyl, or the R
2 1 6
groups independently are C -C alkyl which are taken together with the carbon atom to
which they are attached to define a carbocycle;
Ring B is substituted or unsubstituted C -C cycloalkylene, substituted or
3 10
unsubstituted C -C heterocycloalkylene, substituted or unsubstituted arylene, or
2 10
substituted or unsubstituted heteroarylene, where if ring B is substituted then ring B is
substituted with 1,2, or 3 independently selected R , wherein R is as previously
defined; and
Ring C is absent or substituted or unsubstituted C -C cycloalkylene, substituted
3 10
or unsubstituted C -C heterocycloalkylene, substituted or unsubstituted arylene, or
2 10
substituted or unsubstituted heteroarylene, wherein if ring C is substituted then ring C is
substituted with 1, 2, or 3 independently selected R , wherein R is as previously
defined,
wherein when Ring B is substituted or unsubstituted arylene, Ring C is absent,
2 1 J D
L is absent, L is -UV-Z, wherein -UV- is -N(R )-C(=O), R is
F G G F C
-N(R )C(=O)XCH(R )-CY, wherein X is -O-, R is -CH and R is -H, and R is -H, -CH
or -CF ,
[118] or when Ring B is substituted or unsubstituted arylene and Ring C is substituted
or unsubstituted arylene or is substituted or unsubstituted C -C cycloalkylene, or Ring
3 10
B is substituted or unsubstituted C -C cycloalkylene and Ring C is substituted or
3 10
unsubstituted arylene, L is absent, L is C -C alkylene,
C A B
and R is -H or -CH and R is -CO H or -CO R
3 2 2 ,
[120] then Ring A has the structure of one of:
R N N
C R R
R R C
D D C C
R R R
R R R
E N N
N R D
N D R
C D C R
R R R
and when Ring B is C -C heterocycloalkylene, Ring C is substituted or
2 10
2 1 C A
unsubstituted arylene, L is absent, L is C -C alkylene, R is -CH and R is -CO H or
1 6 3 2
-CO R
[123] then Ring A has the structure of one of:
R N N
C E N
E N N
N D R
C D C
R R R
In some embodiments R is -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl,
1 4 1 4
D F G F
C -C cycloalkyl, or C -C fluoroalkyl and R is -N(R )-C(=O)XCH(R )-CY, -N(R )-
3 6 1 4
G F F G
-C(=O)XC(R ) -CY or -N(R )-C(=O)X-CY, wherein R and each R independently are -H
or C -C alkyl.
In some embodiments R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH ,
2 2 2
-C(=O)NHR , C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere.
2 2 2 3
A B B
[127] In preferred embodiments R is -CO H, -CO R , -CN, or -C(=O)NHSO R ,
2 2 2
wherein R is substituted or unsubstituted C -C alkyl or has the structure of one of:
O O O
In some embodiments L is absent or substituted or unsubstituted C1-C6
alkylene, C -C fluoroalkylene, or substituted or unsubstituted C -C heteroalkylene.
1 6 1 6
[130] In some preferred embodiments L is absent or substituted or unsubstituted C -
C alkylene or -UV-Z-, wherein -UV- is defined by -OW-, -WO-, -N(R )W-, -WN(R )-,
-N(R )C(=O)-, -SW-, -S(=O) W-, or -C(=O)N(R )-, wherein W is substituted or
unsubstituted C -C alkylene, Z is substituted or unsubstituted C -C alkylene or C -C
1 3 1 6 1 6
fluoroalkylene; and n is 0,1, or 2.
[131] In particularly preferred embodiments L is -CH -,
, dimethylmethane (i.e., -C(CH ) -), or -UV-Z- wherein -UV-is defined by -
WO-, -WN(R )-, or -C(=O)N(R )-, wherein W is substituted or unsubstituted C -C
alkylene; and Z is substituted or unsubstituted C -C alkylene.
In some embodiments L is absent, or substituted or unsubstituted C -C
alkylene, C1-C6 fluoroalkylene, substituted or unsubstituted C1-C6 heteroalkylene, -O-,
-S-, -S(=O)-, S(=O) -, -N(R )-, or -C(=O)-.
In some preferred embodiments L is absent, -O-, -S-, -S(=O)-, S(=O) -, -N(R )-,
or -C(=O)-.
In some embodiments Ring A is a 5 or 6 membered heteroarene having one of
the structures of:
C C R R
R R C
D D C C
R R R
R R R
N C N
R D R
R R R
In some embodiments, Formula I compounds have R defined as -H, -CN, -F,
-Cl, -Br, -I, -OC -C alkyl, C -C alkyl, C -C cycloalkyl, or C -C fluoroalkyl.
1 4 1 4 3 6 1 4
In more preferred embodiments, Formula I compounds have R defined as -H,
-F, -CN, -CH3, or -CF3.
In some embodiments, Formula I compounds have R defined as -N(R )C(=O)-
G F G F
XCH(R )-CY, -N(R )C(=O)XC(R ) -CY, or -N(R )C(=O)X-CY, wherein X is absent, -O-,
-NH- or -CH -, wherein R is -H or C -C alkyl and X, CY and R are as previously
2 1 4
defined.
[140] In more preferred embodiments, Formula I compounds have R defined as
F G F G F
-N(R )C(=O)OCH(R )-CY, -N(R )C(=O)NHC(R )-CY, or -N(R )C(=O)CH2-CY, wherein
R is -H or C -C alkyl and X, CY and R are as previously defined.
In some embodiments, Formula I compounds have R defined as -H or C -C
alkyl, C -C cycloalkyl or C -C fluoroalkyl.
1 6 1 4
[142] In more preferred embodiments, Formula I compounds have R defined as -H, -
CH , cyclopropyl or -CF .
In some embodiments, Formula I compounds have R defined as H, C1-C4 alkyl
or C -C cycloalkyl.
In more preferred embodiments, Formula I compounds have R defined as -H.
[145] In some embodiments of Formula I compounds one R is -C -C alkyl and is
taken together with CY and the the carbon atom to which R and CY is attached to
define a substituted or unsubstituted carbocycle or a substituted or unsubstituted
heterocycle and the other R , if present is -H.
In other embodiments of Formula I compounds R is independently -H or C -C
alkyl.
In some embodiments of Formula I compounds Ring B is substituted or
unsubstituted C -C cycloalkylene, substituted or unsubstituted C -C
3 10 2 10
heterocycloalkylene, a substituted or unsubstituted arylene, or substituted or
unsubstituted heteroarylene, wherein if ring B is substituted then ring B is substituted
with 1, 2, or 3 independently selected R .
In some embodiments of Formula I compounds Ring C is substituted or
unsubstituted C -C cycloalkylene, substituted or unsubstituted C -C
3 10 2 10
heterocycloalkylene, a substituted or unsubstituted arylene, or substituted or
unsubstituted heteroarylene, wherein if ring C is substituted then ring C is substituted
with 1, 2, or 3 independently selected R .
In some embodiments of Formula I compounds CY is substituted or
unsubstituted C -C alkyl, substituted or unsubstituted C -C cycloalkyl, substituted or
1 6 3 10
unsubstituted C -C heterocycloalkyl, substituted or unsubstituted aryl, or substituted or
2 10
unsubstituted heteroaryl, wherein if CY is substituted then CY is substituted with 1, 2, or
3 idependently selected R .
In some preferred embodiments Ring A has the structure of one of:
C C R R
C R R
[151] .
Particularly preferred Formula I compounds have Ring B and Ring C each
independently defined as 1,4-substituted aryl or heteroaryl, R is -CO H, R is -F or
D F G E F G
-CN, R is -NR C(=O)OCH(R )-CY, R is -CH , and R , R , and CY are as previously
defined.
[153] Other particularly preferred Formula I compounds have Ring B defined as 1,4-
substituted aryl or heteroaryl, L is -UV-Z- wherein -UV-is defined by -WO-, -WN(R )-, or
-C(=O)N(R )-, wherein W is CH , Z is substituted or unsubstituted C -C alkylene, R is
2 1 6
D F G E C F G
-CO H, R is -N(R )C(=O)OCH(R )-CY, R is -CH , and R , R , R , and CY are as
previously defined.
[154] 2. The compound of embodiment 1 wherein Ring A has the structureof one of:
D N D
C R R
3. The compound of embodiment 1 or 2 wherein R is -H, -CN, -F, -CH , or
-CF .
4. The compound of embodiment 1, 2 or 3 wherein R is -F or -CN.
[158] 5. The compound of embodiment 1, 2, 3 or 4 wherein L , is absent.
6 The compound of embodiment 1, 2, 3, 4 or 5 wherein L , when present, is a
geminally substituted alkyl, cycloalkyl or heterocycloalkyl group, or is UV-Z-,
J J J
wherein -UV-is defined by -OW-, -WO-, -N(R )W-, -WN(R )-, -N(R )C(=O)-, -SW-,
-S(=O) W-, or -C(=O)N(R )-, wherein W is substituted or unsubstituted C -C alkylene or
n 1 3
L L L
W is -C(R ) -, wherein R independenly are -H or C -C alkyl or the two R are
2 1 4
independenly C -C alkyl taken together with the carbon to which R is attached to
define a carbocycle, Z is substituted or unsubstituted C -C alkylene or C -C
1 6 1 6
fluoroalkylene; and n is 0, 1, or 2.
7. The compound of embodiments 6 wherein L , when present, is -CH -,
or dimethylmethane, or -UV-Z- wherein -UV- is defined by -WO-, -WN(R )-, or -
C(=O)N(R )-, wherein W is -CH -, Z is substituted or unsubstituted C -C alkylene.
2 1 6
8. The compound of any one of embodiments 1-7 wherein R is -H.
9. The compound of any one of embodiments 1-8 wherein R is -CH .
10. The compound of any one of embodiments 1-9 wherein CY is substituted or
unsubstituted substituted phenyl.
11. The compound of any one of embodiments 1-10 wherein R is -H, halogen, -
J J J J L
CN, -NO , -OH,-OR , -SR , -S(=O)R , -S(=O) R , -N(R ) , C -C alkyl, C -C fluoroalkyl,
2 2 2 1 4 1 4
C -C fluoroalkoxy, C -C alkoxy, and C -C heteroalkyl.
1 4 1 4 1 4
12. The compound of any one of embodiments 1-11 wherein R are
independently selected from -H, halogen or substituted or unsubstituted C -C alkyl or
substituted C -C alkoxy.
13. The compound of any one of embodiments 1-12 wherein R is independently
-H, -Cl, -F, -CH , -CF -OCH or -OCF .
3 3, 3 3
14. A compound of Formula II having the structure:
A B L R Formula II
or a pharmaceutically acceptable salt or prodrug thereof
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
C(=O)NHSO2R or -C(=O)NHCH2CH2SO3H or a carboxylic acid isostere,
R is optionally substituted C -C alkyl or has the structure of one of:
O O O
[172] ;
L is absent or optionally substituted C -C alkylene; optionally substituted C -C
1 6 1 6
fluoroalkylene, or optionally substituted C -C heteroalkylene or -UV-Z-, wherein -UV-is
J J J
defined by -OW-, -WO-, -N(R )W-, -WN(R )-, -N(R )C(=O)-, -SW-, -S(=O) W-, or
-C(=O)N(R )-, wherein W is optionally substituted C -C alkylene or W is -C(R ) -, Z is
1 3 2
optionally substituted C -C alkylene or C -C fluoroalkylene or Z is -C(R ) -; and n is 0,
1 6 1 6 2
1, or 2;
Ring A is a 5 or 6 membered heteroarene having the structure of one of:
D N D
D D C C
R R R
R R R
E N N
N D R
C D C
R R R
wherein R is -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl, C -C cycloalkyl,
1 4 1 4 3 6
or C -C fluoroalkyl;
D F G F G F
R is -N(R )C(=O)XCH(R )-CY, -N(R )C(=O)XC(R ) -CY, or -N(R )C(=O)X-CY;
where X is absent, -O-, -NH- or -CH -;
R is -H or C -C alkyl, C -C cycloalkyl or C -C fluoroalkyl;
1 4 1 6 1 4
R is -H, C -C alkyl or C -C cycloalkyl;
1 4 1 6
G E G
[180] R is independently selected R , or one of R is C1-C4 alkyl and is taken
together with CY and the the carbon atom to which R and CY are attached to define a
substituted or unsubstituted carbocycle or a substituted or unsubstituted heterocycle
and the other R , if present, is as defined for R ;
Ring B is optionally substituted C -C cycloalkylene, optionally substituted C -
3 10 2
C heterocycloalkylene, optionally substituted arylene, or optionally substituted
heteroarylene, where if ring B is substituted then ring B is substituted with 1, 2, or 3
independntly selected R ;
Ring C is absent or optionally substituted C -C cycloalkylene, optionally
3 10
substituted C -C heterocycloalkylene, optionally substituted arylene, or optionally
2 10
substituted heteroarylene, wherein if ring C is substituted then ring C is substituted with
1, 2, or 3 independently selected R ;
CY is optionally substituted C -C alkyl, optionally substituted C -C cycloalkyl,
1 6 3 10
optionally substituted C -C heterocycloalkyl, optionally substituted aryl, or optionally
2 10
substituted heteroaryl, wherein if CY is substituted then CY is substituted with 1, 2, or 3
independently selected R , or
[184] wherein each R is independently selected -H, halogen, -CN, -NO , -OH, -OR , -
J J J J J L J J
SR , -S(=O)R , -S(=O) R , -N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , -OC(=O)R ,
2 2 2 2
J J L L L J L
-C(=O)OR , -OC(=O)OR , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) , -N(R )C(=O)N(R ) , -
2 2 2 2
J J J J
N(R )C(=O)R , -N(R )C(=O)OR , C -C alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C
1 4 1 4 1 4 1 4
alkoxy, or C -C heteroalkyl, and
[185] wherein R is optionally substituted C1-C6 alkyl, optionally substituted C1-C6
heteroalkyl, optionally substituted C -C fluoroalkyl, optionally substituted C -C
1 6 3 6
cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally
substituted heteroaryl, -C -C alkylene-(optionally substituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(optionally substituted heterocycloalkyl), -C -C alkylene-(substituted or
unsubstituted aryl), or -C -C alkylene-(optionally substituted heteroaryl), and
each R is independently -H, optionally substituted C1-C6 alkyl, optionally
substituted C -C heteroalkyl, optionally substituted C -C fluoroalkyl, optionally
1 6 1 6
substituted C -C cycloalkyl, optionally substituted heterocycloalkyl, optionally
substituted aryl, optionally substituted heteroaryl, -C -C alkylene-(optionally substituted
C -C cycloalkyl), -C -C alkylene-(optionally substituted heterocycloalkyl), -C -C
3 6 1 4 1 4
alkylene-(optionally substituted aryl), or -C -C alkylene-(optionally substituted
heteroaryl), or
H L L L L
when R is -S(=O)2N(R )2, -N(R )2, -C(=O)N(R )2, -OC(=O)N(R )2 or
J L L L
-N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define an optionally substituted heterocycle,
L L L
or when W or Z is -C(R ) -, each R is independently -H or C -C alkyl, or the R
2 1 6
groups independently are C -C alkyl which are taken together with the carbon atom to
which they are attached to define a carbocycle;
[189] wherein when Ring B is substituted or unsubstituted arylene, Ring C is absent,
1 J D
L is -UV-Z, wherein -UV- is -N(R )-C(=O), R is
F G G F C
-N(R )C(=O)XCH(R )-CY, wherein X is -O-, R is -CH and R is -H, and R is -H, -CH
or -CF , or when Ring B is substituted or unsubstituted arylene and Ring C is substituted
or unsubstituted arylene or is substituted or unsubstituted C -C cycloalkylene, or Ring
3 10
B is substituted or unsubstituted C -C cycloalkylene and Ring C is substituted or
3 10
unsubstituted arylene and L is C -C alkylene,
C A B
and R is -H or -CH and R is -CO H or -CO R ,
3 2 2
then Ring A has the structure of one of:
D N D
C C R R
R R C
C D D
D D C
R R R R
N C N
C R D C R
R R R
and when Ring B is C2-C10 heterocycloalkylene, Ring C is substituted or
1 C A B
unsubstituted arylene, L is C -C alkylene, R is -CH and R is -CO H or -CO R ,
1 6 3 2 2
[194] then Ring A has the structure of one of:
N C D N
C R D C R
R R R
In preferred embodiments Ring A has the structure of one of:
R N N
D N D
Particularly preferred Formula II compounds have Ring B and Ring C defined
A D F G
each as 1,4-substituted aryl or heteroaryl, R is CO H, and R is -N(R )C(=O)OCH(R )-
Particularly preferred Formula II compounds have Ring B defined as 1,4-
substituted aryl or heteroaryl, L is -UV-Z-, wherein -UV-is defined by -WO-, -WN(R )-, or
-C(=O)N(R )-, wherein W is -CH -, Z is substituted or unsubstituted C -C alkylene, R is
2 1 6
D F G
-CO H, R is -N(R )C(=O)OCH(R )-CY.
15. A compound of Formula III having the structure:
Formula III
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
[202] wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
R is substituted or unsubstituted C -C alkyl or has the structure of one of
O O O
O O O
L is absent or is substituted or unsubstituted C1-C6 alkylene, C1-C6
fluoroalkylene; or substituted or unsubstituted C -C heteroalkylene or -UV-Z- wherein -
J J J
UV-is defined by -OW-, -WO-, -N(R )W-, -WN(R )-, -N(R )C(=O)-, -SW-, -S(=O) W-, or
-C(=O)N(R )-, wherein W is substituted or unsubstituted C -C alkylene or W is -C(R ) -,
1 3 2
Z is substituted or unsubstituted C -C alkylene or C -C fluoroalkylene; and n is 0,1, or
1 6 1 6
[206] Ring A is a 5-6 membered heteroarenes having one the structure of one of:
D N D
D C D
R R R R
N C D N
R D C R
R R R
wherein R is -H, -CN, -F, -Cl, -Br, -I, -OC1-C4 alkyl, C1-C4 alkyl, C3-C6 cycloalkyl,
or C1-C4 fluoroalkyl;
D F G F G F
R is -N(R )C(=O)XCH(R )-CY, -N(R )C(=O)XC(R ) -CY, or -N(R )C(=O)X-CY.
wherein X is absent, -O-, -NH- or -CH -;
R is -H or C -C alkyl, C -C cycloalkyl or C -C fluoroalkyl;
1 4 1 6 1 4
R -H, C -C alkyl or C -C cycloalkyl;
1 4 1 6
G E G
R is independently selected R , or one R is -C -C alkyl and is taken together
with CY and the the carbon atom to which R and CY is attached to define a substituted
or unsubstituted carbocycle or a substituted or unsubstituted heterocycle and the other
R , if present, is as defined for R ;,
1 2 3
A , A and A are independently =NH-, -N=, =CH- or -CH=;,
Ring C is absent or substituted or unsubstituted C -C cycloalkylene, substituted
3 10
or unsubstituted C -C heterocycloalkylene, substituted or unsubstituted arylene, or
2 10
substituted or unsubstituted heteroarylene, wherein if ring C is substituted then ring C is
substituted with 1, 2, or 3 independently selected R ;
CY is substituted or unsubstituted C -C alkyl, substituted or unsubstituted C -
1 6 3
C10 cycloalkyl, substituted or unsubstituted C2-C10 heterocycloalkyl, substituted or
unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein if CY is
substituted then CY is substituted with 1, 2, or 3 R ;
H J J
wherein each R is independently -H, halogen, -CN, -NO , -OH, -OR , -SR , -
J J J J L J J J
S(=O)R , -S(=O) R , -N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , -OC(=O)R , -C(=O)OR ,
2 2 2 2
J L L L J L J J
-OC(=O)OR , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) , N(R )C(=O)N(R ) , -N(R )C(=O)R ,
2 2 2 2
-NR C(=O)OR , C -C alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C alkoxy, or C -C
1 4 1 4 1 4 1 4 1 4
heteroalkyl;
each R is independently substituted or unsubstituted C -C alkyl, substituted or
unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl,
1 6 1 6
substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene-(substituted or
unsubstituted aryl), or C1-C4 alkylene-(substituted or unsubstituted heteroaryl);
each R is independently -H, substituted or unsubstituted C -C alkyl, substituted
or unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl,
1 6 1 6
substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl,
substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -C -C
alkylene-(substituted or unsubstituted cycloalkyl), -C -C alkylene-(substituted or
unsubstituted heterocycloalkyl), -C -C alkylene(substituted or unsubstituted aryl), or
-C -C alkylene-(substituted or unsubstituted heteroaryl), or
H L L L L
when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or
2 2 2 2 2
J L L L
N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle, or
L L L
[219] when W or Z is -C(R )2-, each R is independently -H or C1-C6 alkyl, or the R
groups independently are C -C alkyl which are taken together with the carbon atom to
which they are attached to define a carbocycle;
1 2 3 1
wherein when A , A and A are =CH- or -CH=, Ring C is absent, L is -UV-Z,
J D F G G
wherein -UV- is -N(R )C(=O), R is -N(R )C(=O)XCH(R )-CY, wherein X is -O-, R is -
CH and R is -H, and R is -H, -CH or -CF ,
3 3 3
or when Ring C is substituted or unsubstituted arylene or substituted or
unsubstituted C -C cycloalkylene
3 10
C A B
and R is -H or -CH and R is -CO H or -CO R
3 2 2 ,
then Ring A has the structure of one of:
R N N
D N D
D C D D
R R R R
N C D N
C R D C R
R R R
and when Ring C is substituted or unsubstituted arylene, L is C -C alkylene, R
is -CH and R is -CO H or -CO R
3 2 2 ,
then Ring A has the structure of one of:
D N D
C E N
D R R
N R D
N C D N
C D C R
R R R
In preferred embodiments Ring A has the structure of one of:
R N N
D N D
C C R
C R R
Particularly preferred Formula III compounds have Ring C is defined as 1,4-
A D F G 1
substituted phenyl or pyridyl, R is -CO H, and R is -N(R )C(=O)OCH(R )-CY; L is
-UV-Z- wherein -UV- is defined by -WO-, -WN(R )-, or -C(=O)N(R )-, wherein W is
-CH -, Z is substituted or unsubstituted C -C alkylene, R is -CO H, and R is
2 1 6 2
-N(R )C(=O)OCH(R )-CY.
16. A compound of Formula IV having the structure:
A L R Formula IV
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
-C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
R is optionally substituted -C -C alkyl or has the structure of one of:
O O O O
1 J J
L is -UV-Z-, wherein -UV-is defined by -OW-, -WO-, -N(R )W-, -WN(R )-,
-N(R )C(=O)-, -SW-, -S(=O) W-, or -C(=O)N(R )-, wherein W is substituted or
unsubstituted C -C alkylene or W is -C(R ) -, Z is substituted or unsubstituted C -C
1 3 2 1 6
alkylene or substituted or unsubstituted C1-C6 fluoroalkylene or Z is -C(R )2-; and n is 0,
1, or 2;
A is independently =N- or =CH-;
Ring A is a 5 or 6 membered heteroarene having one of the structures of:
R N N
C R R
R R C
C D D
D D C
R R R R
E N N
N R D
N C D N
C D C R
R R R
,
wherein R is -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl, C -C cycloalkyl,
1 4 1 4 3 6
or C -C fluoroalkyl;
D F G F G F
R is -N(R )C(=O)XCH(R )-CY, -N(R )C(=O)XC(R ) -CY, or -N(R )C(=O)X-CY,
wherein X is absent, -O-, -NH- or -CH -;
R is -H or C1-C4 alkyl, C3-C6 cycloalkyl or C1-C4 fluoroalkyl;
R is -H, C -C alkyl or C -C cycloalkyl;
1 4 3 6
G E G
[243] R is independently selected R , or one R is -C -C alkyl and is taken together
with CY and the carbon atom to which R and CY is attached to define a substituted or
unsubstituted carbocycle or a substituted or unsubstituted heterocycle, and the other
R , if present, is as defined for R ;
CY is C -C alkyl, a substituted or unsubstituted C -C cycloalkyl, a substituted
1 6 3 10
or unsubstituted C -C heterocycloalkyl, a substituted or unsubstituted aryl, or a
2 10
substituted or unsubstituted heteroaryl, wherein if CY is substituted then CY is
substituted with 1, 2, or 3 R ;
H J J
wherein each R is independently -H, halogen, -CN, -NO , -OH, -OR , -SR ,
J J J J L J J O J
-S(=O)R , -S(=O) R , -N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , -OC(=O)R , -C(=O) R ,
2 2 2 2
J L L L J L J J
-OC(=O)OR , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) , N(R )C(=O)N(R ) , -N(R )C(=O)R ,
2 2 2 2
-N(R )C(=O)OR , C -C alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C alkoxy, or C -
1 4 1 4 1 4 1 4 1
C heteroalkyl;
wherein R is independently substituted or unsubstituted C -C alkyl, substituted
or unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl,
1 6 1 6
substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene-(substituted or
unsubstituted aryl), or C -C alkylene-(substituted or unsubstituted heteroaryl); and
[247] each R is independently -H, substituted or unsubstituted C -C alkyl, substituted
or unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl,
1 6 1 6
substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl,
substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -C -C
alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C alkylene-(substituted or
3 6 1 4
unsubstituted heterocycloalkyl), -C -C alkylene-(substituted or unsubstituted aryl), or
-C -C alkylene-(substituted or unsubstituted heteroaryl),
H L L L L
or when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or
2 2 2 2 2
J L L L
-N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C1-C6 alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle,
L L L
or when W or Z is -C(R ) -, each R is independently -H or C -C alkyl, or the R
2 1 6
groups independently are C -C alkyl which are taken together with the carbon atom to
which they are attached to define a carbocycle,
H L L L L
or when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or
2 2 2 2 2
J L L L
-N(R )C(=O)N(R ) , each R is independently is -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle,
L L L
or when W is -C(R ) -, each R is independently -H, C -C alkyl, or the R groups
2 1 6
independently are C1-C6 alkyl which are taken together with the carbon atom to which
they are attached to define a carbocycle;
1 1 J D F
wherein A is =CH-, L is -UV-Z, wherein -UV- is -N(R )-C(=O), R is -N(R )-
G G F C
C(=O)XCH(R )-CY, wherein X is -O-, R is -CH and R is -H, and R is -H, -CH or -
CF ,
C A B
and R is -H or -CH and R is -CO H or CO R
3 2 2 ,
[254] then Ring A has the structure of one of:
D N D
C C R R
R R C
D D C C
R R R
R R R
N R D
N C D N
C D C R
R R R
In preferred embodiments Ring A has the structure of one of:
R N N
D N D
C C R R
C R R
Particularly preferred Formula IV compounds have L defined as -UV-Z-, wherein
-UV -is defined by -WO-, -WN(R )-, or -C(=O)N(R )-, wherein W is -CH -, Z is substituted
A D F G
or unsubstituted C -C alkylene, R is -CO H, and R is -N(R )C(=O)OCH(R )-CY.
1 6 2
17. A compound of Formula V having the structure:
A L R Formula V
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere,
2 2 2 3
[262] wherein R is optionally substituted C -C alkyl or has the structure of one of
O O O
1 J J
L is -UV-Z-, wherein -UV-is defined by -OW-, -WO-, -N(R )W-, -WN(R )-, -
N(R )C(=O)-, -SW-, -S(=O)nW-, or -C(=O)N(R )-, wherein W is substituted or
unsubstituted C -C alkylene or W is -C(R ) -, Z is substituted or unsubstituted C -C
1 3 2 1 6
alkylene or substituted or unsubstituted C -C fluoroalkylene or Z is -C(R ) -; and n is 0,
1 6 2
1, or 2;
A is =N- or =CH-;
Ring A is a 5 membered heteroarene having the structure of one of:
R N N
C R R C
R R C
C R E
E N N
D C D D
C D R D
R R R
[268] wherein R is -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl, C -C cycloalkyl,
1 4 1 4 3 6
or C -C fluoroalkyl;
D F G F G F
R is -N(R )C(=O)XCH(R )-CY, -N(R )C(=O)XC(R ) -CY, or -N(R )C(=O)X-CY;
wherein X is absent, -O-, -NH- or -CH -;
R is -H or C -C alkyl, C -C cycloalkyl or C -C fluoroalkyl;
1 4 3 6 1 4
[271] R is -H, C -C alkyl or -C -C cycloalkyl;
1 4 3 6
G E G
R is independently selected R , or one R is -C1-C4 alkyl and is taken together
with CY and the carbon atom to which R and CY is attached to define a substituted or
unsubstituted carbocycle or a substituted or unsubstituted heterocycle, and the other
R , if present, is as defined for R ;
[273] CY is substituted or unsubstituted C -C alkyl, substituted or unsubstituted C -
1 6 3
C cycloalkyl, substituted or unsubstituted C -C heterocycloalkyl, substituted or
2 10
unsubstituted aryl, or a substituted or unsubstituted heteroaryl, wherein if CY is
substituted then CY is substituted with 1, 2, or 3 independently selected R ;
H J J J
R is independently -H, halogen, -CN, -NO , -OH,-OR , -SR , -S(=O)R , -
J J J L J J J
S(=O) R , -N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , -OC(=O)R , -C(=O)OR , -
2 2 2 2
J L L L J L J J
OC(=O)OR , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) , NR C(=O)N(R ) , -NR C(=O)R ,
2 2 2 2
-NR C(=O)OR , C -C alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C alkoxy,and C -
1 4 1 4 1 4 1 4 1
C heteroalkyl;
wherein each R is independently substituted or unsubstituted C -C alkyl,
substituted or unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C
1 6 1 6
fluoroalkyl, substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene-(substituted or
unsubstituted aryl), or C -C alkylene-(substituted or unsubstituted heteroaryl);
[276] wherein each R is independently -H, substituted or unsubstituted C -C alkyl,
substituted or unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C
1 6 1 6
fluoroalkyl, substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene(substituted or
unsubstituted aryl), or -C -C alkylene-(substituted or unsubstituted heteroaryl),
H L L L L
or when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or -
2 2 2 2 2
J L L L
N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle,
L L L
or when W or Z is -C(R ) -, each R is independently -H or C -C alkyl, or the R
2 1 6
groups independently are C -C alkyl which are taken together with the carbon atom to
which they are attached to define a carbocycle.
1 1 C
wherein when A is =CH-, L is -UV-Z, wherein -UV- is -NHC(=O)-, and R is -H,
-CH or -CF , then Ring A has the structure of one of:
R N N
N D R
C R R
R R C
R D R
R R D
Particularly preferred Formula V compounds have L defined as UV-Z- wherein
-UV-is defined by -WO-, -WN(R )-, or -C(=O)N(R )-, wherein W is -CH -, Z is substituted
A D F G
or unsubstituted C -C alkylene, R is -CO H, and R is -N(R )C(=O)OCH(R )-CY.
1 6 2
18. A compound of Formula VI having the structure:
A Formula VI
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
-C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere, wherein
2 2 2 3
R is optionally substituted C -C alkyl or has the structure of one of:
O O O
[286] ;
1 J J
L is UV-Z- wherein -UV-is defined by -OW-, -WO-, -N(R )W-, -WN(R )-,
-N(R )C(=O)-, -SW-, -S(=O) W-, or -C(=O)N(R )-, wherein W is substituted or
unsubstituted C -C alkylene or W is -C(R ) -, Z is substituted or unsubstituted C -C
1 3 2 1 6
alkylene or substituted or unsubstituted C -C fluoroalkylene or Z is -C(R ) -; and n is 0,
1 6 2
1, or 2;
A is independently =N- or =CH-;
Ring A is a 5 membered heteroarene having one of the structures of:
D N D
C R C
C R R
D C C R
R R R
D R R
wherein R is defined as -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl, C -C
1 4 1 4 3 6
cycloalkyl, or C -C fluoroalkyl;
D F G
wherein R is the -N(R )C(=O)CH(R )-CY substituent of Formula VI wherein CY
is phenyl substituted with one R ;
G E G
R is independently selected R , or one R is -C1-C4 alkyl and is taken together
with CY and the carbon atom to which R and CY is attached to define a substituted or
unsubstituted carbocycle or a substituted or unsubstituted heterocycle, and the other
R , if present, is as defined for R ;
R is -H, -C -C alkyl or -C -C cycloalkyl;
1 4 3 6
H J J
R is independently selected from -H, halogen, -CN, -NO2, -OH, -OR , -SR , -
J J J J L J J J
S(=O)R , -S(=O) R , -N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , OC(=O)R , -CO R ,
2 2 2 2 2
J L L L J L
-OC(=O)OR , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) , N(R )C(=O)N(R ) ,
2 2 2 2
J J J J
-N(R )C(=O)R , -N(R )C(=O)OR , C -C alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -
1 4 1 4 1 4 1
C alkoxy,and C -C heteroalkyl;
4 1 4
wherein R is substituted or unsubstituted C -C alkyl, substituted or
unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl,
1 6 1 6
substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene-(substituted or
unsubstituted aryl), or C -C alkylene-(substituted or unsubstituted heteroaryl);
[296] wherein each R is independently -H, substituted or unsubstituted C -C alkyl,
substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C1-C6
fluoroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted cycloalkyl), -C -C alkylene-
1 4 1 4
(substituted or unsubstituted heterocycloalkyl), -C -C alkylene(substituted or
unsubstituted aryl), or -C -C alkylene-(substituted or unsubstituted heteroaryl),
H L L L L
or when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or
2 2 2 2 2
J L L L
N(R )C(=O)N(R )2, each R is independently -H or C1-C6 alkyl, or the R groups
independently are C1-C6 alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle,
L L L
or when W or Z is -C(R ) -, each R is independently -H or C -C alkyl, or the R
2 1 6
groups independently are C -C alkyl which are taken together with the carbon atom to
which they are attached to define a carbocycle.
In preferred embodiments Ring A has the structure of one of:
D N D
C C R
Particularly preferred Formula VI compounds have L as -UV-Z- wherein -UV- is
-C(=O)NH-, -CH O- or -CH NH-, Z is substituted -CH-, and R is -CO H.
2 2 2
19. A compound of Formula VII having the structure of:
A N z
Formula VII
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
wherein R is -CO2H, -CO2R , -CN, tetrazolyl, -C(=O)NH2, -C(=O)NHR ,
-C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
R is optionally substituted C -C alkyl or has the structure of one of:
O O O
[306]
A is independently =N- or =CH-;
Ring A has the structure of one of :
C C R R
R is -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl, C -C cycloalkyl, or C -C
1 4 1 4 3 6 1 4
fluoroalkyl;
D F G
wherein R is the -N(R )C(=O)CH(R )-CY substituent of Formula VII wherein CY
is phenyl substituted with one R ;
E F G
R , R and R independently are -H or C -C alkyl;
Z is -C(R ) -;
H J J J
[314] R is independently -H, halogen, -CN, -NO , -OH,-OR , -SR , -S(=O)R , -
J J J L J J J J
S(=O)2R , -N(R )S(=O)2R , -S(=O)2N(R )2, -C(=O)R , -OC(=O)R , -CO2R , -OCO2R , -
L L L J L J J J J
N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) , NR C(=O)N(R ) , -NR C(=O)R , -NR C(=O)OR ,
2 2 2 2
C -C alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C alkoxy,and C -C heteroalkyl;
1 4 1 4 1 4 1 4 1 4
R is substituted or unsubstituted C -C alkyl, substituted or unsubstituted C -C
1 6 1 6
heteroalkyl, C -C fluoroalkyl, substituted or unsubstituted C -C cycloalkyl, substituted
1 6 3 6
or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or
unsubstituted heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl),
1 4 3 6
-C -C alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene-
1 4 1 4
(substituted or unsubstituted aryl), or C -C alkylene-(substituted or unsubstituted
heteroaryl);
[316] R is -H, substituted or unsubstituted C -C alkyl, substituted or unsubstituted C -
1 6 1
C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl, substituted or
6 1 6
unsubstituted C -C cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted
or unsubstituted aryl, substituted or unsubstituted heteroaryl, -C -C alkylene-
(substituted or unsubstituted C -C cycloalkyl), -C -C alkylene-(substituted or
3 6 1 4
unsubstituted heterocycloalkyl), -C -C alkylene(substituted or unsubstituted aryl), or
-C -C alkylene-(substituted or unsubstituted heteroaryl),
H L L L L
or when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or
2 2 2 2 2
J L L L
-N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle,
or each R in Z is independently -H or C -C alkyl, or the R groups
independently are C -C alkyl which are taken together with the carbon atom to which
they are attached to define a carbocycle.
In some embodiments, Formula VII compounds have R defined as -H, C -C
H J L
alkyl or C -C cycloalkyl and each R R and R are as previously defined;
In particularly preferred Formula VII compounds R is -CO H.
20. A compound of Formula VIII having the structure:
A N z
Formula VIII
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
-C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
R is optionally substituted C1-C4 alkyl or has the structure of one of:
O O O
[326] A is =N- or =CH-;
Ring A has the structure of one of:
D N D
C C R R
R -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl, C -C cycloalkyl, or C -C
1 4 1 4 3 6 1 4
fluoroalkyl;
D F G
[330] wherein R is the -N(R )C(=O)CH(R )-CY substituent of Formula VII wherein CY
is phenyl substituted with one R ;
R and R independently are -H or C -C alkyl or C -C cycloalkyl;
1 4 3 6
R is -H or C -C alkyl or is C -C alkyl that is taken together with the the R
1 4 1 4
pheny moiety of the Ring A R substituent and the carbon atom to which R and said
phenyl moiety is attached to define a carbocycle;
W is -C(R ) -;
Z is -C(R ) -;
H J J J J
R is -H, halogen, -CN, -NO , -OH,-OR , -SR , -S(=O)R , -S(=O) R , -
J J L J J J J L
N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , -OC(=O)R , -CO R , -OCO R , -N(R ) , -
2 2 2 2 2 2
L L J L J J J J
C(=O)N(R ) , -OC(=O)N(R ) , NR C(=O)N(R ) , -NR C(=O)R , -NR C(=O)OR , C -C
2 2 2 1 4
alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C alkoxy,and C -C heteroalkyl;
1 4 1 4 1 4 1 4
R is substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6
heteroalkyl, is substituted or unsubstituted C -C fluoroalkyl, substituted or unsubstituted
C -C cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or
unsubstituted aryl, substituted or unsubstituted heteroaryl, -C -C alkylene-(substituted
or unsubstituted C -C cycloalkyl), -C -C alkylene-(substituted or unsubstituted
3 6 1 4
heterocycloalkyl), -C -C alkylene-(substituted or unsubstituted aryl), or C -C alkylene-
1 4 1 4
(substituted or unsubstituted heteroaryl);
R independently are -H, substituted or unsubstituted C -C alkyl, substituted or
unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl,
1 6 1 6
substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene(substituted or
unsubstituted aryl), or -C1-C4 alkylene-(substituted or unsubstituted heteroaryl),
H L L L L
[338] or when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or -
2 2 2 2 2
J L L L
N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle,
or each R is in W or Z independently -H or C -C alkyl, or the R groups
independently are C -C alkyl which are taken together with the carbon atom to which
they are attached to define a carbocycle.
In some embodiments, Formula VIII compounds have R defined as -H, C -C
alkyl or C -C cycloalkyl.
In particularly preferred Formula VIII compounds R is -CO H and R is -H.
[342] 21. A compound of Formula IX having the structure:
A O z
Formula IX
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
[345] R is optionally substituted C -C alkyl or has the structure of one of:
O O O
Ring has the structure of one of:
R N N
C C R
R - H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl, C -C cycloalkyl, or C -C
1 4 1 4 3 6 1 4
fluoroalkyl;
D F G
wherein R is the -N(R )C(=O)CH(R )-CY substituent in Formula IX wherein CY
is phenyl substituted with one R ;
E F G E
[351] R , R and R independently are -H, C -C alkyl or C -C cycloalkyl or R and
1 4 1 6
R independenly are -H, C -C alkyl or C -C cycloalkyl and R is C -C alkyl that is
1 4 1 6 1 4
taken together with the the R pheny moiety of the Ring A R substituent and the carbon
atom to which R and said phenyl moiety is attached to define a carbocycle;
H J J J
R is independently -H, halogen, -CN, -NO , -OH,-OR , -SR , -S(=O)R , -
J J J L J J J J
S(=O) R , -N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , -OC(=O)R , -CO R , -OCO R , -
2 2 2 2 2 2
L L L J L J J J J
N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) , NR C(=O)N(R ) , -NR C(=O)R , -NR C(=O)OR ,
2 2 2 2
C -C alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C alkoxy,and C -C heteroalkyl;
1 4 1 4 1 4 1 4 1 4
R is substituted or unsubstituted C -C alkyl, substituted or unsubstituted C -C
1 6 1 6
heteroalkyl, substituted or unsubstituted C -C fluoroalkyl, substituted or unsubstituted
C3-C6 cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or
unsubstituted aryl, substituted or unsubstituted heteroaryl, -C -C alkylene-(substituted
or unsubstituted C -C cycloalkyl), -C -C alkylene-(substituted or unsubstituted
3 6 1 4
heterocycloalkyl), -C -C alkylene-(substituted or unsubstituted aryl), or C -C alkylene-
1 4 1 4
(substituted or unsubstituted heteroaryl);
[354] W is -C(R ) -;
Z is -C(R ) -;
R independently are -H, substituted or unsubstituted C -C alkyl, substituted or
unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl,
1 6 1 6
substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C1-C4 alkylene(substituted or
unsubstituted aryl), or -C -C alkylene-(substituted or unsubstituted heteroaryl),
or each R in W or Z independently are C -C alkyl which are taken together with
the carbon atom to which they are attached to define a carbocycle.
In preferred Formula IX compounds R is -CO H.
22. A compound of Formula X having the structure:
Formula X
A L R
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
R is optionally substituted C1-C4 alkyl or has the structure of one of:
[364] L is absent or optionally substituted C -C alkylene; C -C fluoroalkylene; or
1 6 1 6
optionally substituted C -C heteroalkylen or L , when present is -CH -, , or
1 6 2
disubstituted dimethylmethane.
A is =N- or =CH-;
Ring A has the structure of one of::
D N D
D D C C
R R R
R R R
E N N
N R D
N C D N
C D C R
R R R
[367]
R is -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl, C -C cycloalkyl, or C -C
1 4 1 4 3 6 1 4
fluoroalkyl;
D F G F G F
R is -NR C(=O)XCH(R )-CY, -NR C(=O)XC(R ) -CY, or –NR C(=O)X-CY;
where X is absent, -O-, -NH- or -CH -;
E F G E
[370] R , R and R independently are -H or C -C alkyl or C -C cycloalkyl or R and
1 4 3 6
R independently are -H, C -C alkyl or C -C cycloalkyl and one R is C -C alkyl and is
1 4 1 6 1 4
taken together with CY and the carbon atom to which R and CY are attached to define
a substituted or unsubstituted carbocycle or a substituted or unsubstituted heterocycle,
and the other R , if present, is as defined for R ;
H J J J J
[371] R is -H, halogen, -CN, -NO , -OH,-OR , -SR , -S(=O)R , -S(=O) R , -
J J L J J J J L
N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , -OC(=O)R , -CO R , -OCO R , -N(R ) , -
2 2 2 2 2 2
L L J L J J J J
C(=O)N(R ) , -OC(=O)N(R ) , NR C(=O)N(R ) , -NR C(=O)R , -NR C(=O)OR , C -C
2 2 2 1 4
alkyl, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, C1-C4 alkoxy,and C1-C4 heteroalkyl;
R is substituted or unsubstituted C -C alkyl, substituted or unsubstituted C -C
1 6 1 6
heteroalkyl, substituted or unsubstituted C -C fluoroalkyl, substituted or unsubstituted
C -C cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or
unsubstituted aryl, substituted or unsubstituted heteroaryl, -C -C alkylene-(substituted
or unsubstituted C -C cycloalkyl), -C -C alkylene-(substituted or unsubstituted
3 6 1 4
heterocycloalkyl), -C -C alkylene-(substituted or unsubstituted aryl), or C -C alkylene-
1 4 1 4
(substituted or unsubstituted heteroaryl);
R independently are -H, substituted or unsubstituted C -C alkyl, substituted or
unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl,
1 6 1 6
substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene(substituted or
unsubstituted aryl), or -C -C alkylene-(substituted or unsubstituted heteroaryl),
H L L L L
[374] or when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or -
2 2 2 2 2
J L L L
N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle;
CY is substituted or unsubstituted C -C alkyl, substituted or unsubstituted C -
1 6 3
C cycloalkyl, substituted or unsubstituted C -C heterocycloalkyl, substituted or
2 10
unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein if CY is
substituted then CY is substituted with 1, 2, or 3 R ,
1 C A B
wherein when L is not absent and R is -H or -CH3 and R is -CO2H or -CO2R ,
then Ring A has the structure of one of:
R N N
D N D
C D D
D D C
R R R
N C N
C D C
R R R
[377] ,
In preferred embodiments Ring A has the structure of one of:
R N N
D N D
C C R R
23. A compound of Formula XI having the structure:
Formula XI
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
[382] wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
R is optionally substituted C -C alkyl or has the structure of one of:
O O O
L is absent or optionally substituted C -C alkylene; C -C fluoroalkylene; or
1 6 1 6
optionally substituted C1-C6 heteroalkylene or L , when present is -CH2-, , or
disubstituted dimethylmethane.
A is =N- or =CH-;
Ring A has the structure of one of:
D N D
C C R R
C R R
[389] R is -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, C -C alkyl, C -C cycloalkyl, or C -C
1 4 1 4 3 6 1 4
fluoroalkyl;
D F G F G F
R is -N(R )C(=O)XCH(R )-CY, -N(R )C(=O)XC(R ) -CY, or -N(R )C(=O)X-CY;
where X is absent, -O-, -NH- or -CH -;
E F G E
R , R and R independently are -H or C -C alkyl or C -C cycloalkyl or R and
1 4 3 6
R independently are -H or C -C alkyl or C -C cycloalkyl and one R is C -C alkyl and
1 4 1 6 1 4
is taken together with CY and carbon atom to which R and CY are attached to define a
substituted or unsubstituted carbocycle or a substituted or unsubstituted heterocycle,
and the other R , if present, is as defined for R ;
H J J J J
R is -H, halogen, -CN, -NO , -OH,-OR , -SR , -S(=O)R , -S(=O) R , -
J J L J J J J L
N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , -OC(=O)R , -CO R , -OCO R , -N(R ) , -
2 2 2 2 2 2
L L J L J J J J
C(=O)N(R ) , -OC(=O)N(R ) , NR C(=O)N(R ) , -NR C(=O)R , -NR C(=O)OR , C -C
2 2 2 1 4
alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C alkoxy,and C -C heteroalkyl;
1 4 1 4 1 4 1 4
[393] R is substituted or unsubstituted C -C alkyl, substituted or unsubstituted C -C
1 6 1 6
heteroalkyl, substituted or unsubstituted C -C fluoroalkyl, substituted or unsubstituted
C -C cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or
unsubstituted aryl, substituted or unsubstituted heteroaryl, -C -C alkylene-(substituted
or unsubstituted C -C cycloalkyl), -C -C alkylene-(substituted or unsubstituted
3 6 1 4
heterocycloalkyl), -C -C alkylene-(substituted or unsubstituted aryl), or C -C alkylene-
1 4 1 4
(substituted or unsubstituted heteroaryl);
R independently are -H, substituted or unsubstituted C -C alkyl, substituted or
unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl,
1 6 1 6
substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene(substituted or
unsubstituted aryl), or -C -C alkylene-(substituted or unsubstituted heteroaryl),
H L L L L
or when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or -
2 2 2 2 2
J L L L
N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle,
CY is C1-C6 alkyl, a substituted or unsubstituted C3-C10 cycloalkyl, a substituted
or unsubstituted C -C heterocycloalkyl, a substituted or unsubstituted aryl, or a
2 10
substituted or unsubstituted heteroaryl, wherein if CY is substituted then CY is
substituted with 1, 2, or 3 R ,
1 C A B
wherein when L is not absent and R is -H or -CH and R is -CO H or -CO R
3 2 2 ,
then Ring A has the structure of one of:
R N N
D N D
C R R
[399] In particularly preferred Formula XI compounds R is -CO2H, and R is
-NR C(=O)OCH(R )-CY.
24. A compound of Formula XII having the structure:
Formula XII
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
[403] R is optionally substituted C -C alkyl or has the structure of one of:
O O O
L is absent or optionally substituted C -C alkylene; C -C fluoroalkylene; or
1 6 1 6
optionally substituted C -C heteroalkylene, or L , when present is –CH -, , or
1 6 2
disubstituted dimethylmethane.
[406] A is =N- or =CH-;
Ring A has the structure of one of:
C R R
R is - H, -CN, -F, -Cl, -Br,- I, -OC -C alkyl, C -C alkyl, C -C cycloalkyl, or C -
1 4 1 4 3 6 1
C fluoroalkyl;
D F G
[410] wherein R is the -N(R )C(=O)CH(R )-CY substituent in Formula XII wherein CY
is phenyl substituted with one R ;
E F G E
R , R and R independently are -H or C -C alkyl or C -C cycloalkyl or R and
1 4 3 6
R independently are -H or C -C alkyl or C -C cycloalkyl and one R is -C -C alkyl and
1 4 1 6 1 4
is taken together with the R pheny moiety of the Ring A R substituent and the carbon
atom to which R and said phenyl moiety is attached to define a substituted or
unsubstituted carbocycle or a substituted or unsubstituted heterocycle, and the other
R , if present, is as defined for R ;
H J J J J
R is -H, halogen, -CN, -NO , -OH,-OR , -SR , -S(=O)R , -S(=O) R , -
J J L J J J J L
N(R )S(=O) R , -S(=O) N(R ) , -C(=O)R , -OC(=O)R , -CO R , -OCO R , -N(R ) , -
2 2 2 2 2 2
L L J L J J J J
C(=O)N(R ) , -OC(=O)N(R ) , NR C(=O)N(R ) , -NR C(=O)R , -NR C(=O)OR , C -C
2 2 2 1 4
alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C alkoxy,and C -C heteroalkyl;
1 4 1 4 1 4 1 4
[413] R is substituted or unsubstituted C -C alkyl, substituted or unsubstituted C -C
1 6 1 6
heteroalkyl, substituted or unsubstituted C -C fluoroalkyl, substituted or unsubstituted
C -C cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or
unsubstituted aryl, substituted or unsubstituted heteroaryl, -C -C alkylene-(substituted
or unsubstituted C -C cycloalkyl), -C -C alkylene-(substituted or unsubstituted
3 6 1 4
heterocycloalkyl), -C -C alkylene-(substituted or unsubstituted aryl), or C -C alkylene-
1 4 1 4
(substituted or unsubstituted heteroaryl);
R independently are -H, substituted or unsubstituted C -C alkyl, substituted or
unsubstituted C -C heteroalkyl, substituted or unsubstituted C -C fluoroalkyl,
1 6 1 6
substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene(substituted or
unsubstituted aryl), or -C -C alkylene-(substituted or unsubstituted heteroaryl),
H L L L L
or when R is -S(=O) N(R ) , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) or -
2 2 2 2 2
J L L L
N(R )C(=O)N(R ) , each R is independently -H or C -C alkyl, or the R groups
2 1 6
independently are C -C alkyl which are taken together with the N atom to which they
are attached to define a substituted or unsubstituted heterocycle,
1 C A B
wherein when L is not absent and R is -H or -CH3 and R is -CO2H or -CO2R ,
then Ring A has the structure of one
C R R
R R C
[417] .
In particularly preferred Formula XII compounds R is -CO H.
25. A composition comprising, essentially consisting of or consisting of one or
more compounds of Formula I-XII and one or more excipients.
In preferred embodiments the composition comprises, consists essentially of, or
consists of one compound of Formula I-XII and one or more excipients.
In other preferred embodiments the composition is a pharmaceutically
acceptable formulation comprising, consisting essentially of, or consisting of one
compound of Formula I-XII and one or more pharmaceutically acceptable excipients.
26. A compound of Formula I-XII or a pharmaceutically acceptable salt or
prodrug thereof wherein the binding affinity of the compound to lysophosphatidic acid
receptor-1 (LPA1R) is between about 10 µM and 1 pM or less
27. The compound of embodiment 19 wherein the compound is a selective
lysophosphatidic acid receptor-1 (LPA1R) compound.
28. A compound of Formula I-XII or a pharmaceutically acceptable salt, or
prodrug thereof wherein the compound is a selective lysophosphatidic acid receptor-1
(LPA1R) compound.
29. The compound of embodiment 20, 21 or 22 wherein the compound is a
selective lysophosphatidic acid receptor-1 (LPA1R) compound wherein the binding
affinity (i.e., K ) of the LPA1R compound is between about 1 µM and 1 pM or less. In
preferred embodiments the K is 100 nM or less, more preferably 10 nM or less.
30. A compound of Table 1.
31. The compound of embodiment 30 wherein the compound is 1-(4-{4-[1-(2-
Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-
cyclopropane-carboxylic acid, 2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)-indancarboxylic acid, 2-(S)-(4-{4-[(R,S)(2-
Chloro-phenyl)-ethoxy-carbonylamino]methyl-isoxazolyl}-benzoylamino) phenyl
acetic acid, 2-(R)- (4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino) phenyl propanoic acid, 2(R)-[[4-[3-methyl((R)
phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]phenyl-propanoic acid, 2(S)-
[[4-[3-methyl((R)-phenylethoxycarbonyl-amino)isoxazolyl]benzoyl]amino]phenyl-
propanoic acid, (R){4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzoylamino}phenyl-propionic acid, (S){4-[3-Methyl((S)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzoylamino}phenyl-propionic acid, (R)(4-{4-
[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-
3-phenyl-propionic acid , (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)(4-fluoro-phenyl)-propionic acid , (R)(4-Chloro-
phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)-propionic acid , (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(3,4-difluoro-phenyl)-
propionic acid , (R)(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic acid , (R)(4-
Bromo-phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(2-fluoro-phenyl)-
propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)p-tolyl-propionic acid, (R)(4-{4-[(R)(2-Chloro-
phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(4-
trifluoromethyl-phenyl)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(4-cyano-phenyl)-
propionic acid, (R)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)cyclopropyl-propionic acid,
32. The compound of embodiment 30 wherein the compound is (R)[[4-[2,5-dimethyl-
4-((R)phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]phenyl-propanoic
acid, (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino](4-fluorophenyl)propanoic acid, (R)- 3-(4-bromophenyl)[[4-[2,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, (R)- 3-(4-chlorophenyl)[[4-[2,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid or (R)- 3-(3,4-difluorophenyl)[[4-
[2,5-dimethyl((R)phenylethoxycarbonyl-amino)pyrazol
yl]benzoyl]amino]propanoic acid.
33. The compound of embodiment 30 wherein the compound is 2-[4-[4-[2,5-
dimethyl(1-phenylethoxycarbonylamino)pyrazolyl]phenyl]phenyl]acetic, 2-[4-[4-[4-
[1-(2-chloro-phenyl)ethoxycarbonylamino]-2,5-dimethyl-pyrazolyl]phenyl]phenyl]acetic
acid, 2-[4-[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-2,5-dimethyl-pyrazol
yl]phenyl]-phenyl] acetic acid, 2-[4-[4-[4-[1-(2,6-difluorophenyl)ethoxycarbonylamino]-
2,5-dimethyl-pyrazolyl]-phenyl]phenyl]acetic acid, 2-[4-[4-[4-[1-(2-
methoxyphenyl)ethoxycarbonyl-amino]-2,5-di-methyl-pyrazolyl]phenyl]phenyl]acetic
acid, 1-[4-[4-[2,5-dimethyl(1-phenylethoxy-carbonylamino)pyrazol
yl]phenyl]phenyl]cyclopropanecarboxylic acid, 1-[4-[6-[2,5-di-methyl(1-
phenylethoxycarbonylamino)pyrazolyl]pyridyl]phenyl]cyclo-propane carboxylic
acid, 1-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-2,5-dimethyl-pyrazol
yl]phenyl]phenyl]cyclopropanecarboxylic acid, 1-[4-[4-[4-[1-(2-fluorophenyl)-
ethoxycarbonyl-amino]-2,5-dimethyl-pyrazolyl]phenyl]phenyl]cyclopropanecarboxylic
acid, 1-[4-[4-[4-[1-(2,6-difluorophenyl)ethoxycarbonylamino]-2,5-dimethyl-pyrazol
yl]phenyl]phenyl]cyclo-propanecarboxylic acid, 1-[4-[4-[4-[1-(2-methoxyphenyl)ethoxy-
carbonylamino]-2,5-dimethyl-pyrazolyl]phenyl]phenyl]cyclopropanecarboxylic acid, 2-
[4-[4-[2,5-dimethyl(1-phenyl-ethoxycarbonylamino)pyrazolyl]phenyl]phenyl]
methyl-propanoic acid, 2-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-2,5-dimethyl-
pyrazolyl]phenyl]phenyl]methyl-propanoic acid, 2-[4-[4-[4-[1-(2-
fluorophenyl)ethoxycarbonyl-amino]-2,5-dimethyl-pyrazolyl]phenyl]phenyl]methyl-
propanoic acid, 2-[4-[4-[4-[1-(2,6-difluorophenyl)ethoxycarbonyl-amino]-2,5-dimethyl-
pyrazolyl]phenyl]phenyl]methyl-propanoic acid or 2-[4-[4-[4-[1-(2-
methoxyphenyl)ethoxycarbonylamino]-2,5-dimethyl-pyrazolyl]phenyl]-phenyl]
methyl-propanoic acid.
34. The compound of embodiment 30 wherein the compound is (R)[[4-[1,5-
dimethyl((R)phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]phenyl-
propanoic acid, (R)[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino](4-fluorophenyl)propanoic acid, (R)- 3-(4-bromophenyl)[[4-[1,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, ((R)- 3-(4-chlorophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid or (R)- 3-(3,4-difluorophenyl)[[4-
[1,5-dimethyl((R)phenylethoxycarbonyl-amino)pyrazol
yl]benzoyl]amino]propanoic acid.
35. The compound of embodiment 30 wherein the compound is (R)- 2-(4-{5-[(R)-
1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-pyrazolyl}-benzoylamino)
phenyl-propionic acid.
[431] 36. The compound of embodiment 30 wherein the compound is (R){4-[3-
Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzylamino}phenyl-
propionic acid, (R)(2-Fluoro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R){4-[3-Methyl
((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzylamino}(4-trifluoromethyl-
phenyl)-propionic acid, (R)Cyclopropyl{4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R)(2-Chloro-
phenyl){4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzylamino}-propionic acid, (R)(4-Chloro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R)- 2-(4-{4-[(R)(2-
Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)phenyl-
propionic acid, (R)- 2-(4-{4-[(R)_1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzylamino)(2-fluoro-phenyl)-propionic acid, (R)- 2-(4-{4-[(R)(2-
Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)(4-
trifluoromethyl-phenyl)-propionic acid, (R)- 3-(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-
phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)-propionic acid or
(R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzylamino)cyclopropyl-propionic acid.
37. The compound of embodiment 30 wherein the compound is 2-{4-[3-Methyl
((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}phenyl-propionic acid,
2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}
phenyl-propionic acid, (RS)Cyclopropyl{4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-propionic acid or (RS)Cyclopropyl
{4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-propionic
acid.
38. The compound of embodiment 30 wherein the compound is 2-[4-[4-[5-[1-(2-
chlorophenyl)ethoxycarbonylamino]cyano-pyrazolyl]phenyl]phenyl]acetic acid, (R)-
1-[4-[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazolyl]phenyl]phenyl]cyclo-
propane carboxylic acid, (R)[4-[4-[2,5-dimethyl(1-
phenylethoxycarbonylamino)pyrazolyl]phenyl]phenyl]cyclopropane carboxylic acid,
(R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonyl-amino]fluoro-pyrazolyl}fluoro-
biphenylyl)-cyclopropanecarboxylic acid, (R)(4'-{5-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]fluoro-pyrazolyl}fluoro-biphenylyl)-cyclo-
propanecarboxylic acid, (R)(2-Chloro-4'-{5-[1-(2-chloro-phenyl)-
ethoxycarbonylamino]fluoro-pyrazolyl}-biphenylyl)-cyclopropanecarboxylic acid,
(R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazolyl}methyl-
biphenylyl)-cyclopropanecarboxylic acid, (R)(4'-{5-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]fluoro-pyrazolyl}-biphenylyl)-cyclopropanecarboxylic acid,
(R)- 1-{4'-[5-(1-Phenyl-ethoxycarbonylamino)trifluoromethyl-pyrazolyl]-biphenyl
yl}-cyclopropanecarboxylic acid, (R){2-Fluoro-4'-[5-(1-phenyl-ethoxycarbonylamino)-
4-trifluoromethyl-pyrazolyl]-biphenylyl}-cyclopropanecarboxylic acid or (R)(4-{5-
[5-(1-Phenyl-ethoxycarbonylamino)-pyrazolyl]-pyridinyl}-phenyl)-
cyclopropanecarboxylic acid.
39. The compound of embodiment 30 wherein the compound is 2-[[4-[3-methyl-
4-(1-phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]phenyl-propanoic acid,
3-cyclopropyl[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]-propanoic acid, 2-[[4-[3-methyl(1-
phenylethoxycarbonylamino)isoxazolyl]benzoyl]-amino]phenoxy-propanoic acid, 2-
[[4-[3-methyl(1-phenylethoxycarbonylamino)-isoxazolyl]benzoyl]amino]phenyl-
butanoic acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxy-carbonylamino]methyl-isoxazol
yl]benzoyl]amino]phenyl-propanoic acid, 2-[[4-[4-[1-(2-
chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]
cyclopropyl-propanoic acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-
isoxazolyl]-benzoyl]amino]phenyl-butanoic acid, 2-[[4-[4-[1-(2-
chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]phenoxy-
propanoic acid, 2-[[4-[4-[1-(2-fluorophenyl)-ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]phenyl-butanoic acid, 2-[[4-[4-[1-(2-
fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]phenoxy-
propanoic acid, 3-cyclopropyl[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]
methyl-isoxazolyl]benzoyl]amino]propanoic acid, 2-[[4-[4-[1-(2-fluorophenyl)ethoxy-
carbonylamino]methyl-isoxazolyl]benzoyl]amino]phenyl-propanoic acid, 3-(4-
methoxyphenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]benzoyl]-
amino]propanoic acid, 3-(4-fluorophenyl)[[4-[3-methyl(1-
phenylethoxycarbonylamino)-isoxazolyl]benzoyl]amino]propanoic acid, 3-(2,6-
difluorophenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid, 3-(3-cyano-phenyl)[[4-[3-methyl(1-
phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]-propanoic acid, 3-(2-
chlorophenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)-isoxazol
yl]benzoyl]amino]propanoic acid, 3-(4-chlorophenyl)[[4-[3-methyl(1-
phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]propanoic acid, 2-[[4-[3-
methyl(1-phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino][4-
(trifluoromethyl)phenyl]-propanoic acid, 3-(4-hydroxyphenyl)[[4-[3-methyl(1-
phenylethoxycarbonylamino)-isoxazolyl]benzoyl]amino]propanoic acid, 3-(3,4-
difluorophenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid, 3-(4-bromo-phenyl)[[4-[3-methyl(1-
phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]-propanoic acid, 2-[[4-[3-
methyl(1-phenylethoxycarbonylamino)isoxazolyl]benzoyl]-amino][4-
(trifluoromethoxy)phenyl]propanoic acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxy-
carbonylamino]methyl-isoxazolyl]benzoyl]amino](4-methoxyphenyl)propanoic
acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino](4-fluorophenyl)propanoic acid, 2-[[4-[4-[1-(2-
chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino](2,6-
difluorophenyl)propanoic acid, 2-[[4-[4-[1-(2-chloro-phenyl)ethoxycarbonylamino]
methyl-isoxazolyl]benzoyl]amino](3-cyanophenyl)-propanoic acid, 3-(2-
chlorophenyl)[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid, 3-(4-chlorophenyl)[[4-[4-[1-(2-
chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]propanoic
acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino][4-(trifluoromethyl)phenyl]propanoic acid, 2-[[4-[4-[1-(2-
chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino](4-
hydroxyphenyl)propanoic acid, 3-(4-bromo-phenyl)[[4-[4-[1-(2-
chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]-amino]propanoic
acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino](3,4-difluorophenyl)propanoic acid, 2-[[4-[4-[1-(2-chlorophenyl)-
ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino][4-(trifluoromethoxy)-
phenyl]propanoic acid, 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-
isoxazolyl]benzoyl]amino](4-methoxyphenyl)propanoic acid, 3-(4-fluorophenyl)
[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid, 3-(2,6-difluorophenyl)[[4-[4-[1-(2-
fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]propanoic
acid, 3-(3-cyanophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxy-carbonylamino]methyl-
isoxazolyl]benzoyl]amino]propanoic acid, 3-(2-chlorophenyl)[[4-[4-[1-(2-
fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-propanoic
acid, 3-(4-chlorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-
isoxazolyl]benzoyl]amino]propanoic acid, 2-[[4-[4-[1-(2-fluorophenyl)ethoxy-
carbonylamino]methyl-isoxazolyl]benzoyl]amino][4-(trifluoromethyl)phenyl]-
propanoic acid, 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino](4-hydroxyphenyl)propanoic acid, 3-(3,4-difluorophenyl)[[4-[4-[1-
(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]propanoic
acid, 3-(4-bromophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-
isoxazolyl]benzoyl]amino]propanoic acid, 2-[[4-[4-[1-(2-
fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino][4-
(trifluoromethoxy)phenyl]propanoic acid, (±)-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonyl-
amino]methyl-isoxazolyl}-benzoylamino)-acetic acid, (±)(4-{4-[1-(2-Chloro-
phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)methyl-
propionic acid, (±)(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol-
5-yl}-benzoylamino)-propionic acid, (±)(4-{4-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)hydroxy-propionic acid,
(±)(4-{4-[1-(2-Chloro-phenyl)ethoxycarbonyl-amino]methyl-isoxazolyl}-benzoyl)-
pyrrolidinecarboxylic acid or (±)(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)-propionic acid.
[435] 40. The compound of embodiment 30 wherein the compound is 2-{p-[3-Fluoro
(1-phenylethoxycarbonylamino)isoxazolyl]benzoylamino}phenylpropionic acid, 2-
(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}benzoylamino)
phenyl-propionic acid, 3-Cyclopropyl{p-[3-fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]-benzoylamino}propionic acid, 2-(p-{4-[1-(o-
Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}benzoylamino)
cyclopropylpropionic acid, 2-[({p-[3-Fluoro(1-phenylethoxy-carbonylamino)
isoxazolyl]phenyl}methyl)amino]phenylpropionic acid, 2-{[(p-{4-[1-(o-
Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}phenyl)methyl]amino}
phenylpropionic acid, 3-Cyclopropyl[({p-[3-fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methyl)amino]propionic acid, 2-{[(p-{4-[1-(o-
Chlorophenyl)ethoxycarbonyl-amino]fluoroisoxazolyl}phenyl)methyl]amino}
cyclopropylpropionic acid, 2-({p-[3-Fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methoxy)phenylpropionic acid, 2-[(p-{4-[1-(o-
Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}phenyl)-methoxy]
phenylpropionic acid, 3-Cyclopropyl({p-[3-fluoro(1-phenylethoxycarbonyl-amino)
isoxazolyl]phenyl}methoxy)propionic acid or 2-[(p-{4-[1-(o-Chlorophenyl)ethoxy-
carbonylamino]fluoroisoxazolyl}phenyl)methoxy]cyclopropylpropionic acid.
41. The compound of embodiment 30 wherein the compound is 2-Benzyl{5-[3-
fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}propionic acid, 2-
Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridyl-
amino)propionic acid, 2-(Cyclopropylmethyl){5-[3-fluoro(1-phenylethoxycarbonyl-
amino)isoxazolyl]pyridylamino}propionic acid, 3-(5-{4-[1-(o-Chlorophenyl)ethoxy-
carbonylamino]fluoroisoxazolyl}pyridylamino)(cyclopropylmethyl)propionic
acid, 2-Benzyl{5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}-propionic acid, 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]
fluoroisoxazolyl}pyridyloxy)propionic acid 2-Benzyl(5-{4-[1-(o-
chlorophenyl)ethoxycarbonyl-amino]fluoroisoxazolyl}pyridyloxy)propionic acid,
2-(Cyclopropylmethyl){5-[3-fluoro(1-phenylethoxycarbonyl-amino)isoxazolyl]
pyridyloxy}propionic acid, 3-(5-{4-[1-(o-Chlorophenyl)ethoxy-carbonylamino]fluoro
isoxazolyl}pyridyloxy)(cyclo-propylmethyl)propionic acid, 2-{5-[3-Fluoro(1-
phenylethoxycarbonylamino)isoxazolyl]pyridylamino}phenyl-propionic acid, 2-(5-
{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridylamino)
phenylpropionic acid, 3-Cyclopropyl{5-[3-fluoro(1-phenylethoxy-carbonylamino)
isoxazolyl]pyridylamino}propionic acid, 2-(5-{4-[1-(o-Chlorophenyl)-
ethoxycarbonylamino]fluoroisoxazolyl}pyridylamino)cyclopropyl-propionic
acid, 2-{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
phenyl-propionic acid, 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroiso-
xazolyl}pyridyloxy)phenylpropionic acid, 3-Cyclopropyl{5-[3-fluoro(1-phenyl-
ethoxy-carbonylamino)isoxazolyl]pyridyloxy}propionic acid, 2-(5-{4-[1-(o-Chloro-
phenyl)-ethoxycarbonylamino]fluoroisoxazolyl}pyridyloxy)
cyclopropylpropionic acid, 2-{p-[3-fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]benzoylamino}phenylpropionic acid , 2-(p-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}benzoyl-amino)
phenylpropionic acid, 3-cyclopropyl{p-[3-fluoro(1-phenylethoxycarbonyl-amino)
isoxazolyl]benzoylamino}propionic acid, 2-(p-{4-[1-(o-chlorophenyl)ethoxy-
carbonylamino]fluoroisoxazolyl}benzoylamino)cyclopropylpropionic acid, 2-[({p-
[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methyl)amino]phenyl-
propionic acid, 2-{[(p-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}-
phenyl)methyl]amino}phenylpropionic acid, 3-cyclopropyl[({p-[3-fluoro(1-phenyl-
ethoxycarbonylamino)isoxazolyl]phenyl}methyl)amino]propionic acid, 2-{[(p-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}phenyl)methyl]amino}cyclo-
propylpropionic acid, 2-({p-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]-
phenyl}methoxy)phenylpropionic acid, 2-[(p-{4-[1-(o-chlorophenyl)ethoxycarbonyl-
amino]fluoroisoxazolyl}phenyl)methoxy]phenylpropionic acid, 3-cyclopropyl
({p-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methoxy)propionic
acid, 2-[(p-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]fluoro
isoxazolyl}phenyl)methoxy]cyclopropylpropionic acid, 2-benzyl{5-[3-fluoro(1-
phenylethoxycarbonylamino)isoxazolyl]pyridylamino}propionic acid, 2-benzyl(5-
{4-[1-(o-chlorophenyl)ethoxy-carbonylamino]fluoroisoxazolyl}
pyridylamino)propionic acid, 2-(cyclopropyl-methyl){5-[3-fluoro(1-
phenylethoxycarbonylamino)isoxazolyl]pyridylamino}-propionic acid, 3-(5-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridyl-amino)
(cyclopropylmethyl)propionic acid, 2-benzyl{5-[3-fluoro(1-phenylethoxy-
carbonylamino)isoxazolyl]pyridyloxy}propionic acid, 2-benzyl(5-{4-[1-(o-chloro-
phenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridyloxy)propionic acid, 2-
(cyclo-propylmethyl){5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}-propionic acid, 3-(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]fluoro
isoxazolyl}pyridyloxy)(cyclopropylmethyl)propionic acid, 2-{5-[3-fluoro(1-
phenylethoxycarbonyl-amino)isoxazolyl]pyridylamino}phenylpropionic acid, 2-(5-
{4-[1-(o-chlorophenyl)-ethoxycarbonylamino]fluoroisoxazolyl}pyridylamino)
phenylpropionic acid, 3-cyclopropyl{5-[3-fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]pyridylamino}-propionic acid, 2-(5-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridylamino)
cyclopropylpropionic acid, 2-{5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]-
2-pyridyloxy}phenylpropionic acid, 2-(5-{4-[1-(o-chlorophenyl)ethoxy-carbonylamino]-
3-fluoroisoxazolyl}pyridyloxy)phenyl-propionic acid, 3-cyclopropyl{5-[3-fluoro-
4-(1-phenylethoxycarbonylamino)iso-xazolyl]pyridyloxy}propionic acid or 2-(5-{4-
[1-(o-chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridyloxy)
cyclopropylpropionic acid.
42. The compound of embodiment 30 wherein the compound is 2-{p-[3-Cyano
(1-phenylethoxycarbonylamino)isoxazolyl]benzoylamino}phenylpropionic acid, 2-
(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}benzoylamino)
phenyl-propionic acid, 2-{p-[3-Cyano(1-phenylethoxycarbonylamino)
isoxazolyl]benzoyl-amino}cyclopropylpropionic acid, 2-(p-{4-[1-(o-
Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}benzoylamino)
cyclopropylpropionic acid, 2-[({p-[3-Cyano(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methyl)amino]phenylpropionic acid, 2-{[(p-{4-[1-(o-
Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}phenyl)methyl]-amino}
phenylpropionic acid, 2-[({p-[3-Cyano(1-phenylethoxycarbonylamino)iso-
xazolyl]phenyl}methyl)amino]cyclopropylpropionic acid, 2-{[(p-{4-[1-(o-Chlorophenyl)-
ethoxycarbonylamino]cyanoisoxazolyl}phenyl)methyl]amino}
cyclopropylpropionic acid, 2-({p-[3-Cyano(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methoxy)phenylpropionic acid, 2-[(p-{4-[1-(o-
Chlorophenyl)ethoxycarbonylamino]cyanoiso-xazolyl}phenyl)methoxy]
phenylpropionic acid, 2-({p-[3-Cyano(1-phenylethoxycarbonyl-amino)
isoxazolyl]phenyl}methoxy)cyclopropylpropionic acid or 2-[(p-{4-[1-(o-Chloro-
phenyl)ethoxycarbonylamino]cyanoisoxazolyl}phenyl)methoxy]
cyclopropylpropionic acid.
43. A compound of embodiment 30 wherein the compound is 2-Benzyl{5-[3-
cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}propionic acid, 2-
Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}
pyridylamino)-propionic acid, 3-{5-[3-Cyano(1-phenylethoxycarbonylamino)
isoxazolyl]pyridyl-amino}(cyclopropylmethyl)propionic acid, 3-(5-{4-[1-(o-
Chlorophenyl)ethoxycarbonyl-amino]cyanoisoxazolyl}pyridylamino)
(cyclopropylmethyl)propionic acid, 2-Benzyl{5-[3-cyano(1-
phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}propionic acid, 2-Benzyl(5-{4-
[1-(o-chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridyloxy)propionic
acid, 3-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
(cyclopropylmethyl)propionic acid, 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonyl-amino]
cyanoisoxazolyl}pyridyloxy)(cyclopropylmethyl)propionic acid, 2-{5-[3-Cyano
(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}phenylpropionic acid, 2-
(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridyl-amino)-
3-phenylpropionic acid, 2-{5-[3-Cyano(1-phenylethoxycarbonylamino)iso-xazolyl]-
2-pyridylamino}cyclopropylpropionic acid, 2-(5-{4-[1-(o-Chlorophenyl)ethoxy-
carbonylamino]cyanoisoxazolyl}pyridylamino)cyclopropylpropionic acid, 2-{5-
[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
phenylpropionic acid, 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano
isoxazolyl}pyridyloxy)phenylpropionic acid, 2-{5-[3-Cyano(1-
phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}cyclopropylpropionic acid, 2-
(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridyloxy)
cyclopropylpropionic acid, 2-{p-[3-cyano(1-phenyl-ethoxycarbonylamino)
isoxazolyl]benzoylamino}phenylpropionic acid, 2-(p-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}benzoylamino)
phenylpropionic acid, 2-{p-[3-cyano(1-phenylethoxycarbonylamino)
isoxazolyl]benzoylamino}cyclo-propylpropionic acid, 2-(p-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]cyanoiso-xazolyl}benzoylamino)
cyclopropylpropionic acid, 2-[({p-[3-cyano(1-phenylethoxy-carbonylamino)
isoxazolyl]phenyl}methyl)amino]phenylpropionic acid, 2-{[(p-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}phenyl)methyl]amino}
phenyl-propionic acid, 2-[({p-[3-cyano(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}-methyl)amino]cyclopropylpropionic acid, 2-{[(p-{4-[1-(o-
chlorophenyl)ethoxycarbonyl-amino]cyanoisoxazolyl}phenyl)methyl]amino}
cyclopropylpropionic acid, 2-({p-[3-cyano(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methoxy)phenylpropionic acid, 2-[(p-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}phenyl)-methoxy]
phenylpropionic acid, 2-({p-[3-cyano(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methoxy)cyclopropylpropionic acid, 2-[(p-{4-[1-(o-
chlorophenyl)ethoxy-carbonylamino]cyanoisoxazolyl}phenyl)methoxy]
cyclopropylpropionic acid, 2-benzyl{5-[3-cyano(1-phenylethoxycarbonylamino)
isoxazolyl]pyridylamino}-propionic acid, 2-benzyl(5-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridylamino)propionic
acid, 3-{5-[3-cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
(cyclopropylmethyl)propionic acid, 3-(5-{4-[1-(o-chloro-phenyl)ethoxycarbonylamino]
cyanoisoxazolyl}pyridylamino)(cyclopropylmethyl)-propionic acid, 2-benzyl{5-
[3-cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}propionic acid, 2-
benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}
pyridyloxy)propionic acid, 3-{5-[3-cyano(1-phenylethoxycarbonyl-amino)
isoxazolyl]pyridyloxy}(cyclopropylmethyl)propionic acid, 3-(5-{4-[1-(o-chloro-
phenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridyloxy)(cyclopropylmethyl)-
propionic acid, 2-{5-[3-cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl-
amino}phenylpropionic acid, 2-(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]
cyanoisoxazolyl}pyridylamino)phenylpropionic acid, 2-{5-[3-cyano(1-
phenylethoxy-carbonylamino)isoxazolyl]pyridylamino}cyclopropylpropionic acid,
2-(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridylamino)-
3-cyclopropyl-propionic acid, 2-{5-[3-cyano(1-phenylethoxycarbonylamino)
isoxazolyl]pyridyloxy}phenylpropionic acid, 2-(5-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]cyanoiso-xazolyl}pyridyloxy)
phenylpropionic acid, 2-{5-[3-cyano(1-phenylethoxycarbonyl-amino)isoxazolyl]
pyridyloxy}cyclopropylpropionic acid or 2-(5-{4-[1-(o-chlorophenyl)-
ethoxycarbonylamino]cyanoisoxazolyl}pyridyloxy)cyclopropylpropionic acid.
44. A compound of embodiment 30 wherein the compound is 2-Benzyl{5-[3-
methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}propionic acid, 2-
Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}
pyridylamino)-propionic acid, 2-(Cyclopropylmethyl){5-[3-methyl(1-
phenylethoxycarbonylamino)isoxazolyl]pyridylamino}propionic acid, 3-(5-{4-[1-(o-
Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)
(cyclopropylmethyl)propionic acid, 2-Benzyl{5-[3-methyl(1-
phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}propionic acid, 2-Benzyl(5-{4-
[1-(o-chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyl-oxy)propionic
acid, 2-(Cyclopropylmethyl){5-[3-methyl(1-phenylethoxycarbonylamino)
isoxazolyl]pyridyloxy}propionic acid, 3-(5-{4-[1-(o-
Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)
(cyclopropylmethyl)propionic acid, 2-{5-[3-Methyl(1-phenylethoxycarbonylamino)
isoxazolyl]pyridylamino}phenylpropionic acid, 2-(5-{4-[1-(o-
Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)
phenylpropionic acid, 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methyl
isoxazolyl}pyridylamino)cyclopropylpropionic acid, 2-{5-[3-Methyl(1-
phenylethoxy-carbonylamino)isoxazolyl]pyridyloxy}phenylpropionic acid, 2-(5-
{4-[1-(o-Chloro-phenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)
phenylpropionic acid, 3-Cyclopropyl{5-[3-methyl(1-phenylethoxycarbonylamino)
isoxazolyl]pyridyl-oxy}propionic acid, 2-(5-{4-[1-(o-
Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)
cyclopropylpropionic acid, 2-benzyl{5-[3-methyl(1-phenyl-ethoxycarbonylamino)
isoxazolyl]pyridylamino}propionic acid, 2-benzyl(5-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)propionic
acid, 2-(cyclopropylmethyl){5-[3-methyl(1-phenylethoxycarbonylamino)
isoxazolyl]pyridylamino}propionic acid, 3-(5-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)
(cyclopropylmethyl)propionic acid, 2-benzyl{5-[3-methyl(1-
phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}propionic acid, 2-benzyl(5-{4-
[1-(o-chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)propionic
acid, 2-(cyclopropylmethyl){5-[3-methyl(1-phenylethoxycarbonylamino)
isoxazolyl]pyridyloxy}propionic acid, 3-(5-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)
(cyclopropylmethyl)propionic acid, 2-{5-[3-methyl(1-phenyl-ethoxycarbonylamino)
isoxazolyl]pyridylamino}phenylpropionic acid, 2-(5-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)phenyl-
propionic acid, 3-cyclopropyl{5-[3-methyl(1-phenylethoxycarbonylamino)
isoxazolyl]pyridylamino}propionic acid, 2-(5-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)
cyclopropylpropionic acid, 2-{5-[3-methyl(1-phenylethoxy-carbonylamino)
isoxazolyl]pyridyloxy}phenylpropionic acid, 2-(5-{4-[1-(o-chloro-
phenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)phenylpropionic
acid, 3-cyclopropyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}-propionic acid, 2-(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]methyl
isoxazolyl}pyridyloxy)cyclopropylpropionic acid, 3-{p-[3-methyl(1-
phenylethoxycarbonylamino)isoxazolyl]benzoylamino}phenylbutyric acid, 4-
cyclopropyl{p-[3-methyl(1-phenyl-ethoxycarbonylamino)
isoxazolyl]benzoylamino}butyric acid, 3-[({p-[3-methyl(1-phenyl-
ethoxycarbonylamino)isoxazolyl]phenyl}methyl)amino]phenylbutyric acid, 4-cyclo-
propyl[({p-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methyl)-
amino]butyric acid, 3-({p-[3-methyl(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}-methoxy)phenylbutyric acid, 4-cyclopropyl({p-[3-methyl(1-
phenylethoxycarbonyl-amino)isoxazolyl]phenyl}methoxy)butyric acid, 3-{5-[3-methyl-
4-(1-phenylethoxycarbonyl-amino)isoxazolyl]pyridylamino}phenylbutyric acid, 4-
cyclopropyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}butyric acid, 3-{5-[3-methyl(1-phenylethoxycarbonylamino)
isoxazolyl]pyridyloxy}phenylbutyric acid, 4-cyclo-propyl{5-[3-methyl(1-
phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}butyric acid
45. A compound of embodiment 30 wherein the compound is 2-[[4-[1,5-dimethyl(1-
phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino](4-methoxyphenyl)propanoic
acid, 2-[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]
(4-fluorophenyl)propanoic acid, 3-(2,6-difluorophenyl)[[4-[1,5-dimethyl(1-
phenylethoxy-carbonylamino)pyrazolyl]benzoyl]amino]propanoic acid, 3-(3-
cyanophenyl)[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]propanoic acid, 3-(2-chlorophenyl)[[4-[1,5-dimethyl(1-
phenylethoxycarbonylamino)pyrazolyl]benzoyl]-amino]propanoic acid, 3-(4-
chlorophenyl)[[4-[1,5-dimethyl(1-phenylethoxycarbonyl-amino)pyrazol
yl]benzoyl]amino]propanoic acid, 2-[[4-[1,5-dimethyl(1-phenylethoxy-
carbonylamino)pyrazolyl]benzoyl]amino][4-(trifluoromethyl)phenyl]propanoic acid,
2-[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino](4-
hydroxyphenyl)propanoic acid, 3-(3,4-difluorophenyl)[[4-[1,5-dimethyl(1-
phenylethoxy-carbonylamino)pyrazolyl]benzoyl]amino]propanoic acid, 3-(4-
bromophenyl)[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]propanoic acid, 2-[[4-[1,5-dimethyl(1-
phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino][4-(trifluoro-
methoxy)phenyl]propanoic acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-
dimethyl-pyrazolyl]benzoyl]amino](4-methoxyphenyl)propanoic acid, 2-[[4-[4-[1-(2-
chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazolyl]benzoyl]amino](4-
fluoro-phenyl)propanoic acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-
dimethyl-pyrazolyl]benzoyl]amino](2,6-difluorophenyl)propanoic acid, 2-[[4-[4-[1-(2-
chloro-phenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazolyl]benzoyl]amino](3-
cyanophenyl)-propanoic acid, 3-(2-chlorophenyl)[[4-[4-[1-(2-
chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazolyl]benzoyl]amino]propanoic
acid, 3-(4-chlorophenyl)[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-
pyrazolyl]benzoyl]amino]propanoic acid, 2-[[4-[4-[1-(2-
chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazolyl]benzoyl]-amino][4-
(trifluoromethyl)phenyl]propanoic acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxy-
carbonylamino]-1,5-dimethyl-pyrazolyl]benzoyl]amino](4-hydroxyphenyl)propanoic
acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]-amino](3,4-difluorophenyl)propanoic acid, 3-(4-bromophenyl)[[4-[4-[1-
(2-chloro-phenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino]propanoic acid, 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-
dimethyl-pyrazolyl]benzoyl]amino][4-(trifluoromethoxy)phenyl]propanoic acid, 2-[[4-
[4-[1-(2-fluorophenyl)ethoxycarbonyl-amino]-1,5-dimethyl-pyrazolyl]benzoyl]amino]
(4-methoxyphenyl)propanoic acid, 3-(4-fluorophenyl)[[4-[4-[1-(2-
fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazolyl]benzoyl]amino]propanoic
acid, 3-(2,6-difluorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxy-carbonylamino]-1,5-
dimethyl-pyrazolyl]benzoyl]amino]propanoic acid, 3-(3-cyanophenyl)[[4-[4-[1-(2-
fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazolyl]benzoyl]amino]-propanoic
acid, 3-(2-chlorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-
pyrazolyl]benzoyl]amino]propanoic acid, 3-(4-chlorophenyl)[[4-[4-[1-(2-
fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazolyl]benzoyl]amino]propanoic
acid, 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino][4-(trifluoromethyl)phenyl]propanoic acid, 2-[[4-[4-[1-(2-
fluorophenyl)ethoxycarbonyl-amino]-1,5-dimethyl-pyrazolyl]benzoyl]amino](4-
hydroxyphenyl)propanoic acid, 3-(3,4-difluorophenyl)[[4-[4-[1-(2-
fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazolyl]benzoyl]amino]propanoic
acid, 3-(4-bromophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxy-carbonylamino]-1,5-dimethyl-
pyrazolyl]benzoyl]amino]propanoic acid, 2-[[4-[4-[1-(2-
fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazolyl]benzoyl]amino][4-
(trifluoromethoxy)phenyl]propanoic acid, 2-{p-[1-methylmethyl(1-phenylethoxy-
carbonylamino)-1h-pyrazolyl]benzoylamino}phenylpropionic acid, 3-cyclopropyl
{p-[1-methylmethyl(1-phenylethoxycarbonylamino)-1h-pyrazolyl]benzoylamino}-
propionic acid, 2-(p-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]methylmethyl-1h-
pyrazolyl}benzoylamino)phenylpropionic acid, 2-(p-{4-[1-(o-chlorophenyl)ethoxy-
carbonylamino]methylmethyl-1h-pyrazolyl}benzoylamino)
cyclopropylpropionic acid, 2-[({p-[1-methylmethyl(1-phenylethoxycarbonylamino)-
1h-pyrazolyl]phenyl}-methyl)amino]phenylpropionic acid, 3-cyclopropyl[({p-[1-
methylmethyl(1-phenyl-ethoxycarbonylamino)-1h-pyrazol
yl]phenyl}methyl)amino]propionic acid, 2-{[(p-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]methylmethyl-1h-pyrazolyl}phenyl)methyl]-
amino}phenylpropionic acid, 2-{[(p-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]
methylmethyl-1h-pyrazolyl}phenyl)methyl]amino}cyclopropylpropionic acid, 2-
({p-[1-methylmethyl(1-phenylethoxycarbonylamino)-1h-pyrazol
yl]phenyl}methoxy)phenyl-propionic acid, 3-cyclopropyl({p-[1-methylmethyl(1-
phenylethoxycarbonylamino)-1h-pyrazolyl]phenyl}methoxy)propionic acid, 2-[(p-{4-[1-
(o-chlorophenyl)ethoxycarbonyl-amino]methylmethyl-1h-pyrazol
yl}phenyl)methoxy]phenylpropionic acid, 2-[(p-{4-[1-(o-
chlorophenyl)ethoxycarbonylamino]methylmethyl-1h-pyrazolyl}phenyl)-
methoxy]cyclopropylpropionic acid, 3-{p-[1-methylmethyl(1-
phenylethoxycarbonyl-amino)-1h-pyrazolyl]benzoylamino}phenylbutyric acid, 4-
cyclopropyl{p-[1-methylmethyl(1-phenylethoxycarbonylamino)-1h-pyrazol
yl]benzoylamino}butyric acid, 3-[({p-[1-methylmethyl(1-
phenylethoxycarbonylamino)-1h-pyrazolyl]phenyl}methyl)amino]phenylbutyric acid,
4-cyclopropyl[({p-[1-methylmethyl(1-phenylethoxycarbonyl-amino)-1h-pyrazol
yl]phenyl}methyl)amino]butyric acid, 3-({p-[1-methylmethyl(1-
phenylethoxycarbonylamino)-1h-pyrazolyl]phenyl}methoxy)phenylbutyric acid or
4-cyclopropyl({p-[1-methylmethyl(1-phenylethoxycarbonylamino)-1h-pyrazol
yl]phenyl}methoxy)butyric acid.
[440] 46. A compound of embodiment 30 wherein the compound is 2-[4-[4-[4-cyano
(1-phenylethoxycarbonylamino)pyrazolyl]phenyl]phenyl]acetic acid, 1-[4-[4-[4-cyano-
-(1-phenylethoxycarbonylamino)pyrazolyl]phenyl]phenyl]cyclopropanecarboxylic
acid, 1-[4-[4-[5-[1-(2-chlorophenyl)ethoxycarbonylamino]cyano-pyrazol
yl]phenyl]phenyl]cyclo-propanecarboxylic acid, 2-[4-[4-[4-cyano(1-
phenylethoxycarbonylamino)pyrazolyl]-phenyl]phenyl]methyl-propanoic acid, 2-[4-
[4-[5-[1-(2-chlorophenyl)ethoxycarbonyl-amino]cyano-pyrazolyl]phenyl]phenyl]
methyl-propanoic acid, 1-{4'-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]biphenylyl}cyclopropanecarboxylic acid, 1-(4'-{5-[1-(o-
Chlorophenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}biphenylyl)-
cyclopropanecarboxylic acid, 1-{3-Fluoro-4'-[4-fluoro(1-phenylethoxycarbonylamino)-
1H-pyrazolyl]biphenylyl}cyclopropanecarboxylic acid, 1-(4'-{5-[1-(o-
Chlorophenyl)ethoxy-carbonylamino]fluoro-1H-pyrazolyl}fluoro
biphenylyl)cyclopropanecarboxylic acid, 1-{2-Fluoro-4'-[4-fluoro(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]biphenylyl}-cyclopropanecarboxylic
acid, 1-(4'-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}
fluorobiphenylyl)cyclopropanecarboxylic acid, 1-(2-Chloro-4'-{5-[1-(o-
chlorophenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}
biphenylyl)cyclopropane-carboxylic acid, 1-(4-{p-[4-Fluoro(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]-phenyl}tolyl)cyclopropanecarboxylic acid,
1-[4-(p-{5-[1-(o-Chlorophenyl)ethoxycarbonyl-amino]fluoro-1H-pyrazol
yl}phenyl)tolyl]cyclopropanecarboxylic acid, 1-(p-{5-[5-(1-Phenylethoxycarbonylamino)-
1H-pyrazolyl]pyridyl}phenyl)cyclopropanecarboxylic acid, 1-[p-(5-{5-[1-(o-
Chlorophenyl)ethoxycarbonylamino]-1H-pyrazolyl}pyridyl)-
phenyl]cyclopropanecarboxylic acid, 1-(p-{5-[4-Methyl(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}phenyl)cyclopropanecarboxylic
acid, 1-[p-(5-{5-[1-(o-Chloro-phenyl)ethoxycarbonylamino]methyl-1H-pyrazolyl}
pyridyl)phenyl]cyclopropane-carboxylic acid, 1-(2-Fluoro{5-[5-(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}phenyl)cyclopropanecarboxylic
acid, 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonyl-amino]-1H-pyrazolyl}pyridyl)
fluorophenyl]cyclopropanecarboxylic acid, 1-(3-Fluoro{5-[5-(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}phenyl)cyclopropane-carboxylic
acid, 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]-1H-pyrazolyl}pyridyl)
fluorophenyl]cyclopropanecarboxylic acid, 1-(p-{5-[4-Methyl(1-phenylethoxy-
carbonylamino)-1H-pyrazolyl]pyridyl}phenyl)cyclopropanecarboxylic acid, 1-(p-{5-
[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropane-carboxylic acid, 1-[p-(5-{5-[1-(o-
Chlorophenyl)ethoxycarbonylamino]methyl-1H-pyrazolyl}
pyridyl)phenyl]cyclopropanecarboxylic acid, 1-(2-Fluoro{5-[4-methyl(1-phenyl-
ethoxycarbonylamino)-1H-pyrazolyl]pyridyl}phenyl)cyclopropanecarboxylic acid, 1-
[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]methyl-1H-pyrazolyl}pyridyl)-
2-fluorophenyl]cyclopropanecarboxylic acid, 1-(3-Fluoro{5-[4-methyl(1-
phenylethoxy-carbonylamino)-1H-pyrazolyl]pyridyl}phenyl)cyclopropanecarboxylic
acid, 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]methyl-1H-pyrazolyl}
pyridyl)fluoro-phenyl]cyclopropanecarboxylic acid, 1-(p-{5-[4-Fluoro(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}phenyl)cyclopropanecarboxylic
acid, 1-[p-(5-{5-[1-(o-Chloro-phenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}
pyridyl)phenyl]cyclopropane-carboxylic acid, 1-(2-Fluoro{5-[4-fluoro(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}phenyl)cyclopropanecarboxylic
acid, 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxy-carbonylamino]fluoro-1H-pyrazolyl}
pyridyl)fluorophenyl]cyclopropanecarboxylic acid, 1-(3-Fluoro{5-[4-fluoro(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}phenyl)cyclopropanecarboxylic
acid, 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonyl-amino]fluoro-1H-pyrazolyl}
pyridyl)fluorophenyl]cyclopropanecarboxylic acid, 1-(p-{5-[4-Cyano(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}phenyl)cyclo-propanecarboxylic
acid, 1-[p-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano-1H-pyrazolyl}
pyridyl)phenyl]cyclopropanecarboxylic acid, 1-(4-{5-[4-Cyano(1-phenyl-
ethoxycarbonylamino)-1H-pyrazolyl]pyridyl}fluorophenyl)cyclopropanecarboxylic
acid, 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano-1H-pyrazolyl}
pyridyl)fluorophenyl]cyclopropanecarboxylic acid, 1-(4-{5-[4-Cyano(1-
phenylethoxy-carbonylamino)-1H-pyrazolyl]pyridyl}fluorophenyl)cyclopropane-
carboxylic acid or 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano-1H-
pyrazolyl}pyridyl)fluorophenyl]cyclopropanecarboxylic acid.
47. A compound of embodiment 30 wherein the compound is 3-phenyl[[4-[5-
(1-phenylethoxycarbonylamino)oxazolyl]benzoyl]amino]propanoic acid, 3-cyclopropyl-
2-[[4-[5-(1-phenylethoxycarbonylamino)oxazolyl]benzoyl]amino]propanoic acid, 4-
phenyl[[4-[5-(1-phenylethoxycarbonylamino)oxazolyl]benzoyl]amino]butanoic acid,
3-phenoxy[[4-[5-(1-phenylethoxycarbonylamino)oxazolyl]benzoyl]amino]propanoic
acid, 3-Phenyl[({p-[5-(1-phenylethoxycarbonylamino)-1,3-oxazolyl]phenyl}methyl)-
amino]propionic acid, 3-Cyclopropyl[({p-[5-(1-phenylethoxycarbonylamino)-1,3-
oxazolyl]phenyl}-methyl)amino]propionic acid, 3-Phenyl({p-[5-(1-
phenylethoxycarbonyl-amino)-1,3-oxazolyl]phenyl}methoxy)propionic acid, 4-Phenyl-
3-({p-[5-(1-phenylethoxy-carbonylamino)-1,3-oxazolyl]phenyl}methoxy)butyric acid or
4-Cyclopropyl({p-[5-(1-phenylethoxycarbonyl-amino)-1,3-oxazol
yl]phenyl}methoxy)butyric acid.
48. A compound of embodiment 30 wherein the compound is 2-[[4-[1-methyl
(1-phenylethoxycarbonylamino)imidazolyl]benzoyl]amino]phenyl-propanoic acid, 3-
cyclopropyl[[4-[1-methyl(1-phenylethoxycarbonylamino)imidazolyl]benzoyl]-
amino]propanoic acid, 2-[[4-[1-methyl(1-phenylethoxycarbonylamino)imidazol
yl]benzoyl]amino]phenyl-butanoic acid, 2-[[4-[1-methyl(1-phenylethoxycarbonyl-
amino)imidazolyl]benzoyl]amino]phenoxy-propanoic acid, 2-[({p-[1-Methyl(1-
phenylethoxycarbonylamino)-1H-imidazolyl]phenyl}methyl)amino]phenylpropionic
acid, 3-Cyclopropyl[({p-[1-methyl(1-phenylethoxycarbonylamino)-1H-imidazol
yl]phenyl}methyl)amino]propionic acid, 2-({p-[1-Methyl(1-
phenylethoxycarbonylamino)-1H-imidazolyl]phenyl}methoxy)phenylpropionic acid,
3-Cyclopropyl({p-[1-methyl(1-phenylethoxycarbonylamino)-1H-imidazol
yl]phenyl}methoxy)propionic acid, 3-[({p-[1-Methyl(1-phenylethoxycarbonylamino)-1H-
imidazolyl]phenyl}methyl)amino]phenylbutyric acid, 4-Cyclopropyl[({p-[1-methyl-
-(1-phenylethoxycarbonylamino)-1H-imidazolyl]phenyl}methyl)amino]butyric acid, 3-
({p-[1-Methyl(1-phenylethoxycarbonyl-amino)-1H-imidazolyl]phenyl}methoxy)
phenylbutyric acid or 4-Cyclopropyl({p-[1-methyl(1-phenylethoxycarbonylamino)-
1H-imidazolyl]phenyl}methoxy)butyric acid.
49. A compound of embodiment 30 wherein the compound is 2-[[4-[1,2-dimethyl-
3-oxo(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]phenyl-propanoic
acid, 3-cyclopropyl[[4-[1,2-dimethyloxo(1-phenylethoxycarbonylamino)pyrazol-
4-yl]benzoyl]amino]propanoic acid, 2-[[4-[1,2-dimethyloxo(1-phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]phenyl-butanoic acid, 2-[[4-[1,2-dimethyloxo
(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]phenoxy-propanoic acid,
2-[({p-[1,2-Dimethyloxo(1-phenylethoxycarbonylamino)-1,2-dihydropyrazolyl]-
phenyl}-methyl)amino]phenylpropionic acid, 3-Cyclopropyl[({p-[1,2-dimethyloxo-
-(1-phenylethoxycarbonylamino)-1,2-dihydropyrazol
yl]phenyl}methyl)amino]propionic acid, 2-({p-[1,2-Dimethyloxo(1-
phenylethoxycarbonylamino)-1,2-dihydropyrazolyl]-phenyl}methoxy)
phenylpropionic acid, 3-Cyclopropyl({p-[1,2-dimethyloxo(1-
phenylethoxycarbonylamino)-1,2-dihydropyrazolyl]phenyl}methoxy)propionic acid, 3-
[({p-[1,2-Dimethyloxo(1-phenylethoxycarbonylamino)-1,2-dihydropyrazolyl]-
phenyl}-methyl)amino]phenylbutyric acid, 4-Cyclopropyl[({p-[1,2-dimethyloxo
(1-phenyl-ethoxycarbonylamino)-1,2-dihydropyrazolyl]phenyl}methyl)amino]butyric
acid, 3-({p-[1,2-Dimethyloxo(1-phenylethoxycarbonylamino)-1,2-dihydropyrazol
yl]-phenyl}-methoxy)phenylbutyric acid or 4-Cyclopropyl({p-[1,2-dimethyloxo
(1-phenylethoxy-carbonylamino)-1,2-dihydropyrazolyl]phenyl}methoxy)butyric acid.
[444] 50. A compound of embodiment 30 wherein the compound is 3-phenyl[[4-[5-
(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]propanoic acid, 3-
cyclopropyl[[4-[5-(1-phenylethoxycarbonylamino)pyrimidin
yl]benzoyl]amino]propanoic acid, 4-phenyl[[4-[5-(1-
phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]butanoic acid, 3-phenoxy
[[4-[5-(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]-propanoic acid, 3-
Phenyl[({p-[5-(1-phenylethoxycarbonylamino)pyrimidinyl]phenyl}-methyl)-
amino]propionic acid, 3-Cyclopropyl[({p-[5-(1-phenylethoxycarbonylamino)
pyrimidinyl]-phenyl}methyl)amino]propionic acid, 3-Phenyl({p-[5-(1-phenylethoxy-
carbonylamino)pyrimidinyl]phenyl}methoxy)propionic acid, 3-Cyclopropyl({p-[5-(1-
phenylethoxycarbonyl-amino)pyrimidinyl]phenyl}methoxy)propionic acid, 4-Phenyl
[({p-[5-(1-phenylethoxy-carbonylamino)pyrimidinyl]phenyl}methyl)amino]butyric acid,
4-Cyclopropyl[({p-[5-(1-phenylethoxycarbonylamino)
pyrimidinyl]phenyl}methyl)amino]-butyric acid, 4-Phenyl({p-[5-(1-
phenylethoxycarbonylamino)pyrimidinyl]phenyl}-methoxy)butyric acid, 4-Cyclopropyl-
3-({p-[5-(1-phenylethoxycarbonylamino)pyrimidinyl]phenyl}methoxy)butyric acid, 2-
[[4-[6-methyl(1-phenylethoxycarbonyl-amino)pyrimidinyl]benzoyl]amino]phenyl-
propanoic acid, 3-cyclopropyl[[4-[6-methyl(1-phenylethoxycarbonylamino)-
pyrimidinyl]benzoyl]amino]propanoic acid, 2-[[4-[6-methyl(1-phenylethoxycarbonyl-
amino)pyrimidinyl]benzoyl]amino]phenyl-butanoic acid or 2-[[4-[6-methyl(1-
phenyl-ethoxycarbonylamino)pyrimidinyl]benzoyl]-amino]phenoxy-propanoic acid.
51. A compound of embodiment 30 wherein the compound is 3-phenyl[[4-[4-
(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]propanoic acid, 3-
cyclopropyl[[4-[4-(1-phenylethoxycarbonylamino)pyrimidin
yl]benzoyl]amino]propanoic acid, 4-phenyl[[4-[4-(1-
phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]butanoic acid or 3-phenoxy
[[4-[4-(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]-propanoic acid,
[446] 52. A compound of embodiment 30 wherein the compound is 3-phenyl[[4-[3-
(1-phenylethoxycarbonylamino)pyrazinyl]benzoyl]amino]propanoic acid, 3-
cyclopropyl[[4-[3-(1-phenylethoxycarbonylamino)pyrazin
yl]benzoyl]amino]propanoic acid, 4-phenyl[[4-[3-(1-
phenylethoxycarbonylamino)pyrazinyl]benzoyl]amino]butanoic acid or 3-phenoxy
[[4-[3-(1-phenylethoxycarbonylamino)pyrazinyl]benzoyl]amino]propanoic acid.
53. A compound of embodiment 30 wherein the compound is 1-{p-[3-Methyl
(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}piperidinecarboxylic acid, (1-{p-
[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}piperidyl)acetic acid,
1-(1-{p-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidyl)cyclo-propanecarboxylic acid, [1-(1-{p-[3-Methyl(1-
phenylethoxycarbonylamino)isoxazolyl]-phenyl}piperidyl)cyclopropyl]acetic acid, 1-
{5-[3-Methyl(1-phenylethoxycarbonyl-amino)isoxazolyl]pyridyl}
piperidinecarboxylic acid, (1-{5-[3-Methyl(1-phenyl-ethoxycarbonylamino)
isoxazolyl]pyridyl}piperidyl)acetic acid, 1-(1-{5-[3-Methyl(1-
phenylethoxycarbonylamino)isoxazolyl]pyridyl}piperidyl)cyclopropanecarboxylic
acid, [1-(1-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)cyclopropyl]acetic acid, 1-{p-[3-Fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}piperidinecarboxylic acid, (1-{p-[3-Fluoro(1-
phenylethoxycarbonyl-amino)isoxazolyl]phenyl}piperidyl)acetic acid, 1-(1-{p-[3-
Fluoro(1-phenylethoxy-carbonylamino)isoxazolyl]phenyl}
piperidyl)cyclopropanecarboxylic acid, [1-(1-{p-[3-Fluoro(1-
phenylethoxycarbonylamino)isoxazolyl]phenyl}piperidyl)cyclopropyl]acetic acid, 1-
{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}piperidine-
carboxylic acid, (1-{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyl}piperidyl)acetic acid, 1-(1-{5-[3-Fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]pyridyl}piperidyl)cyclopropanecarboxylic acid, [1-(1-{5-[3-Fluoro(1-
phenylethoxy-carbonylamino)isoxazolyl]pyridyl}piperidyl)cyclopropyl]acetic acid,
1-{p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidinecarboxylic acid, (1-{p-[3-Cyano(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}piperidyl)acetic acid, 1-(1-{p-[3-Cyano(1-
phenylethoxycarbonylamino)isoxazolyl]phenyl}piperidyl)cyclo-propanecarboxylic
acid, [1-(1-{p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]-phenyl}
piperidyl)cyclopropyl]acetic acid, 1-{5-[3-Cyano(1-phenylethoxycarbonyl-amino)
isoxazolyl]pyridyl}piperidinecarboxylic acid, (1-{5-[3-Cyano(1-phenyl-
ethoxycarbonylamino)isoxazolyl]pyridyl}piperidyl)acetic acid, 1-(1-{5-[3-Cyano-
4-(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid, [1-(1-{5-[3-Cyano(1-
phenylethoxycarbonylamino)isoxazolyl]pyridyl}piperidyl)cyclopropyl]acetic acid,
1-{p-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}piperidinecarboxylic
acid, (1-{p-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}piperidyl)acetic
acid, 1-(1-{p-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)cyclopropanecarboxylic acid, [1-(1-{p-[5-(1-Phenylethoxycarbonyl-amino)-1H-
pyrazolyl]phenyl}piperidyl)cyclopropyl]acetic acid, 1-{5-[5-(1-Phenylethoxy-
carbonylamino)-1H-pyrazolyl]pyridyl}piperidinecarboxylic acid, (1-{5-[5-(1-
Phenyl-ethoxycarbonylamino)-1H-pyrazolyl]pyridyl}piperidyl)acetic acid, 1-(1-{5-
[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid, [1-(1-{5-[5-(1-Phenylethoxycarbonylamino)-1H-
pyrazolyl]pyridyl}piperidyl)-cyclopropyl]acetic acid, 1-{p-[4-Methyl(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}piperidinecarboxylic acid, (1-{p-
[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}piperidyl)acetic
acid, 1-(1-{p-[4-Methyl(1-phenylethoxy-carbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)cyclopropanecarboxylic acid, [1-(1-{p-[4-Methyl(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}piperidyl)cyclopropyl-]acetic
acid, 1-{5-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidinecarboxylic acid, (1-{5-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazol-
1-yl]pyridyl}piperidyl)acetic acid, 1-(1-{5-[4-Methyl(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid, [1-(1-{5-[4-Methyl(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}piperidyl)cyclopropyl]acetic
acid, 1-{p-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidine-carboxylic acid, (1-{p-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazol-
1-yl]phenyl}piperidyl)acetic acid, 1-(1-{p-[4-Fluoro(1-phenylethoxycarbonylamino)-
1H-pyrazolyl]phenyl}piperidyl)cyclopropanecarboxylic acid, [1-(1-{p-[4-Fluoro(1-
phenylethoxy-carbonylamino)-1H-pyrazolyl]phenyl}piperidyl)cyclopropyl]acetic
acid, 1-{5-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidinecarboxylic acid, (1-{5-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazol-
1-yl]pyridyl}piperidyl)acetic acid, 1-(1-{5-[4-Fluoro(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid, [1-(1-{5-[4-Fluoro(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}piperidyl)cyclopropyl]acetic
acid, 1-{p-[4-Cyano(1-phenyl-ethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidinecarboxylic acid, (1-{p-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazol-
1-yl]phenyl}piperidyl)acetic acid, 1-(1-{p-[4-Cyano(1-phenylethoxycarbonylamino)-
1H-pyrazolyl]phenyl}piperidyl)cyclopropane-carboxylic acid, [1-(1-{p-[4-Cyano
(1-phenylethoxycarbonylamino)-1H-pyrazolyl]-phenyl}piperidyl)cyclopropyl]acetic
acid, 1-{5-[4-Cyano(1-phenylethoxycarbonyl-amino)-1H-pyrazolyl]pyridyl}
piperidinecarboxylic acid, (1-{5-[4-Cyano(1-phenyl-ethoxycarbonylamino)-1H-pyrazol-
1-yl]pyridyl}piperidyl)acetic acid, 1-(1-{5-[4-Cyano(1-
phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}piperidyl)cyclopropane-
carboxylic acid or [1-(1-{5-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]-
2-pyridyl}piperidyl)cyclopropyl]acetic acid.
54. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of Table 1 and one or more pharmaceutically
acceptable excipients.
55. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 31 and one or more pharmaceutically
acceptable excipients.
56. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 32 and one or more pharmaceutically
acceptable excipients.
57. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 33 and one or more pharmaceutically
acceptable excipients.
58. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 34 and one or more pharmaceutically
acceptable excipients.
59. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 35 and one or more pharmaceutically
acceptable excipients.
[454] 60. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 36 and one or more pharmaceutically
acceptable excipients.
61. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 37 and one or more pharmaceutically
acceptable excipients.
62. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 38 and one or more pharmaceutically
acceptable excipients.
63. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 39 and one or more pharmaceutically
acceptable excipients.
64. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 40 and one or more pharmaceutically
acceptable excipients.
[459] 65. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 41 and one or more pharmaceutically
acceptable excipients.
66. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 42 and one or more pharmaceutically
acceptable excipients.
67. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 43 and one or more pharmaceutically
acceptable excipients.
68. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 44 and one or more pharmaceutically
acceptable excipients.
69. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 45 and one or more pharmaceutically
acceptable excipients.
70. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 46 and one or more pharmaceutically
acceptable excipients.
71. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 47 and one or more pharmaceutically
acceptable excipients.
[466] 72. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 48 and one or more pharmaceutically
acceptable excipients.
73. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 49 and one or more pharmaceutically
acceptable excipients.
74. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 50 and one or more pharmaceutically
acceptable excipients.
75. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 51 and one or more pharmaceutically
acceptable excipients.
76. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 52 and one or more pharmaceutically
acceptable excipients.
[471] 77. A pharmaceutically acceptable formulation comprising, consisting essentially
of, or consisting of a compound of embodiment 53 and one or more pharmaceutically
acceptable excipients.
78. A method comprising administering an effective amount of a Formula I-XII
compound to a subject having a LPA-dependent or LPA-mediated disease or condition.
[473] 79. The method of embodiment 78 wherein the LPA-dependent or LPA-mediated
disease or condition is a disease with fibrosis of the organs.
80. The method of embodiment 79 wherein the fibrosis is of the liver, kidney,
lung, heart, eye and the like.
81. The method of embodiment 78 wherein the LPA-dependent or LPA-mediated
disease or condition is chronic pain
82. The method of embodiment 78 wherein the LPA-dependent or LPA-mediated
disease or condition is pruritus.
83. The method of embodiment 78 wherein the LPA-mediated disease is a
proliferative disease including cancer (solid tumor, solid tumor metastasis, vascular
fibroma, myeloma, multiple myeloma, Kaposi's sarcoma, leukemia, chronic lymphocytic
leukemia (CLL) and the like) and invasive metastasis of cancer cell, including ovarian,
breast and triple negative breast cancer and the like,
84. The method of embodiment 78 wherein the LPA-mediated disease is an
inflammatory disease including psoriasis, nephropathy, pneumonia and the like,
[479] 85. The method of embodiment 78 wherein the LPA-mediated disease is a
gastrointestinal disease such as inflammatory bowel disease,
86. The method of embodiment 78 wherein the LPA-mediated disease is an
ocular disease including age-related macular degeneration (AMD), diabetic retinopathy,
proliferative vitreoretinopathy (PVR), cicatricial pemphigoid, glaucoma filtration surgery
scarring, uveitis and the like,
87. The method of embodiment 78 wherein the LPA-mediated disease is a liver
disease including acute hepatitis, chronic hepatitis, liver fibrosis, liver cirrhosis,
cholestatic pruritus, portal hypertension, regenerative failure, nonalcoholic
steatohepatitis (NASH), liver hypofunction, hepatic blood flow disorder, and the like,
[482] 88. The method of embodiment 78 wherein the LPA-mediated disease is a renal
disease including chronic kidney disease, end stage renal disease, uremic pruritus,
nephropathy including diabetic nephropathy and the like,
89. The method of embodiment 78 wherein the LPA-mediated disease is a skin
disease including scleroderma, skin scarring, atopic dermatitis, psoriasis and the like,
[484] 90. The method of any one of embodiments 78-89 wherein the subject is a
human.
91. The method of any one of embodiments 78-90 wherein the compound is
selected from Table 1.
92. The method of any one of embodiments 78-90 wherein the compound is 1-
(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-
cyclo-propanecarboxylic acid, 2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonyl-amino]
methyl-iso-xazolyl}-benzoylamino)-indancarboxylic acid, 2-(S)- (4-{4-[(R,S)(2-
Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino) phenyl
acetic acid, 2-(R)- (4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-iso-
xazolyl}-benzoylamino) phenyl propanoic acid, 2(R)-[[4-[3-methyl((R)phenyl-
ethoxycarbonylamino)isoxazolyl]benzoyl]amino]phenyl-propanoic acid, 2(S)-[[4-[3-
methyl((R)-phenylethoxycarbonyl-amino)isoxazolyl]benzoyl]amino]phenyl-
propanoic acid, (R){4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzoylamino}phenyl-propionic acid, (S){4-[3-Methyl((S)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzoylamino}phenyl-propionic acid, (R)(4-{4-
[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-
3-phenyl-propionic acid , (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)(4-fluoro-phenyl)-propionic acid , (R)(4-Chloro-
phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)-propionic acid , (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(3,4-difluoro-phenyl)-
propionic acid , (R)(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic acid , (R)(4-
Bromo-phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(2-fluoro-phenyl)-
propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)p-tolyl-propionic acid, (R)(4-{4-[(R)(2-Chloro-
phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(4-
trifluoromethyl-phenyl)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(4-cyano-phenyl)-
propionic acid, (R)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)cyclopropyl-propionic acid , (R)[[4-[2,5-dimethyl
((R)phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]phenyl-propanoic
acid, (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino](4-fluorophenyl)propanoic acid, (R)- 3-(4-bromophenyl)[[4-[2,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, (R)- 3-(4-chlorophenyl)[[4-[2,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)- 3-(3,4-difluorophenyl)[[4-[2,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, (R)[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]phenyl-propanoic acid, (R)[[4-[1,5-dimethyl((R)
phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino](4-fluorophenyl)propanoic
acid, (R)- 3-(4-bromophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid, ((R)- 3-(4-chlorophenyl)[[4-[1,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, (R)- 3-(3,4-difluorophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)- 2-(4-{5-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-pyrazolyl}-benzoylamino)phenyl-propionic acid,
(R){4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzylamino}
phenyl-propionic acid, (R)(2-Fluoro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R){4-[3-Methyl
((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzylamino}(4-trifluoromethyl-
phenyl)-propionic acid, (R)Cyclopropyl{4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R)(2-Chloro-
phenyl){4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzylamino}-propionic acid, (R)(4-Chloro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R)- 2-(4-{4-[(R)(2-
Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)phenyl-
propionic acid, (R)- 2-(4-{4-[(R)_1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzylamino)(2-fluoro-phenyl)-propionic acid, (R)- 2-(4-{4-[(R)(2-
Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)(4-
trifluoromethyl-phenyl)-propionic acid, (R)- 3-(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-
phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)-propionic acid, (R)-
2-(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzylamino)cyclopropyl-propionic acid, 2-{4-[3-Methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzyloxy}phenyl-propionic acid, 2-{4-[3-Methyl-
4-((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}phenyl-propionic
acid, (RS)Cyclopropyl{4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazol-
-yl]-benzyloxy}-propionic acid, (RS)Cyclopropyl{4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-propionic acid, 2-[4-[4-[5-[1-(2-
chlorophenyl)ethoxycarbonylamino]cyano-pyrazolyl]phenyl]phenyl]acetic acid, (R)-
1-[4-[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazolyl]phenyl]phenyl-
cyclopropane carboxylic acid, (R)[4-[4-[2,5-dimethyl(1-
phenylethoxycarbonylamino)-pyrazolyl]phenyl]phenyl]cyclopropane carboxylic acid,
(R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonyl-amino]fluoro-pyrazolyl}fluoro-
biphenylyl)-cyclopropanecarboxylic acid, (R)(4'-{5-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]fluoro-pyrazolyl}fluoro-biphenylyl)-cyclo-
propanecarboxylic acid, (R)(2-Chloro-4'-{5-[1-(2-chloro-phenyl)-
ethoxycarbonylamino]fluoro-pyrazolyl}-biphenylyl)-cyclopropanecarboxylic acid,
(R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazolyl}methyl-
biphenylyl)-cyclopropanecarboxylic acid, (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxy-
carbonylamino]fluoro-pyrazolyl}-biphenylyl)-cyclopropanecarboxylic acid, (R)- 1-
{4'-[5-(1-Phenyl-ethoxycarbonylamino)trifluoromethyl-pyrazolyl]-biphenylyl}-
cyclo-propanecarboxylic acid, (R){2-Fluoro-4'-[5-(1-phenyl-ethoxycarbonylamino)
trifluoro-methyl-pyrazolyl]-biphenylyl}-cyclopropanecarboxylic acid, (R)(4-{5-[5-
(1-Phenyl-ethoxycarbonylamino)-pyrazolyl]-pyridinyl}-phenyl)-
cyclopropanecarboxylic acid,
93. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 31.
[488] 94. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 32.
95. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 33.
96. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 34.
97. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 35.
98. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 36.
[493] 99. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 37.
100. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 38.
101. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 39.
102. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 40.
103. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 41.
[498] 104. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 42.
105. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 43.
106. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 44.
107. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 45.
108. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 46.
[503] 109. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 47.
110. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 48.
111. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 49.
[506] 112. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 50.
113. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 51.
114. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 52.
115. The method of any one of embodiments 78-90 wherein the compound is
selected from embodiment 53.
116. A composition comprising, consisting essentially of or consisting of one or
more compounds of Formula (I-XII) and one or more agents currently used to treat a
LPA -dependent or LPA -mediated disease or a disease or condition described herein.
117. A pharmaceutically acceptable formulation comprising, consisting
essentially of or consisting of one or more compounds of Formula (I-XII), one or more
agents currently used to treat a LPA -dependent or LPA -mediated disease and one or
more pharmaceutically acceptable excipients.
[512] 118. A method comprising administering in combination with or co-administrating
a compound of Formula (I-XII) to a subject with a LPA-dependent or LPA-mediated
disease or condition and a currently used agent to treat a LPA -dependent or LPA -
mediated disease
The one or more additional therapeutically active agents other than compounds
of Formula (I-XII) are selected from: corticosteroids, immunosuppressants, analgesics,
anti-cancer agents, anti-inflammatories, chemokine receptor antagonists,
bronchodilators, leukotriene receptor antagonists, leukotriene formation inhibitors,
platelet activating factor receptor antagonists, monoacylglycerol kinase inhibitors,
phospholipase A inhibitors, phospholipase A inhibitors, and lysophospholipase D
(lysoPLD) inhibitors, autotaxin inhibitors, decon-gestants, mast cell stabilizers,
antihistamines, mucolytics, anticholinergics, antitussives, expectorants, and ß-2
agonists.
In preferred embodiments the currently used agent(s) are selected from those
described in the Merck Index known to affect lysophosphatidic acid receptor signaling.
In other preferred embodiments the Formula (I-XII) compound is selected from Table 1.
In other embodiments, therapies which combine a compound of Formula (I-XII),
with currently used agents that act on differing signalling pathways to the LPA synthesis
or signalling pathway so as to provide complementary clinical outcomes, are
encompassed herein for treating LPA-dependent or LPA-mediated diseases or
conditions.
Examples of additional therapeutic agents include, but are not limited to, any of
the following: gossypol, genasense, polyphenol E, Chlorofusin, all trans-retinoic acid
(ATRA), bryostatin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), 5-
aza-2'-deoxycytidine, all trans retinoic acid, doxorubicin, vincristine, etoposide,
gemcitabine, imatinib, geldanamycin, 17-N-Allylamino-17 -Demethoxygeldanamycin (17
-AAG), flavopiridol, LY294002, bortezomib, trastuzumab, BAY 11-7082, PKC412, or PD
184352, TaxolTM (paclitaxel), and analogs ofTaxol™, such as Taxotere™, U0126,
PD98059, PD184352, PD0325901, ARRY-142886, SB239063, SP600 125, BAY 43-
9006, wortmannin, or LY294002, Adriamycin, Dactinomycin, Bleomycin, Vinblastine,
Cisplatin, acivicin; aclarubicin; acodazole hydrochloride; acronine; adozelesin;
aldesleukin; altretamine; ambomycin; ametantrone acetate; amino glutethimide;
amsacrine; anastrozole; anthramycin; asparaginase; asperlin; azacitidine; azetepa;
azotomycin; batimastat; benzodepa; bicalutamide; bisantrene hydrochloride; bisnafide
dimesylate; bizelesin; bleomycin sulfate; brequinar sodium; bropirimine; busulfan;
cactinomycin; calusterone; caracemide; carbetimer; carboplatin; carmustine; carubicin
hydrochloride; carzelesin; cedefingol; chlorambucil; cirolemycin; cladribine; crisnatol
mesylate; cyclophosphamide; cytarabine; dacarbazine; daunorubicin hydrochloride;
decitabine; dexormaplatin; deazaguanine; deazaguanine mesylate; diaziquone;
doxorubicin; doxorubicin hydrochloride; droloxifene; droloxifene citrate; dromostanolone
propionate; duazomycin; edatrexate; eflornithine hydrochloride; elsamitrucin; enloplatin;
enpromate; epipropidine; epirubicin hydrochloride; erbulozole; esorubicin hydrochloride;
estramustine; estramustine phosphate sodium; etanidazole; etoposide; etoposide
phosphate; etoprine; fadrozole hydrochloride; fazarabine; fenretinide; floxuridine;
fludarabine phosphate; fluorouracil; flurocitabine; fosquidone; fostriecin sodium;
gemcitabine; gemcitabine hydrochloride; hydroxyurea; idarubicin hydrochloride;
ifosfamide; iimofosine; interleukin II (including recombinant interleukin II, or rIL2),
interferon alfa-2a; interferon alfa-2b; interferon alfa-n1; interferon alfa-n3; interferon
beta-l a; interferon gamma-l b; iproplatin; irinotecan hydrochloride; lanreotide acetate;
letrozole; leuprolide acetate; liarozole hydrochloride; lometrexol sodium; lomustine;
losoxantrone hydrochloride; masoprocol; maytansine; mechlorethamine hydrochloride;
megestrol acetate; melengestrol acetate; melphalan; menogaril; mercaptopurine;
methotrexate; methotrexate sodium; metoprine; meturedepa; mitindomide; mitocarcin;
mitocromin; mitogillin; mitomalcin; mitomycin; mitosper; mitotane; mitoxantrone
hydrochloride; mycophenolic acid; nocodazoie; nogalamycin; ormaplatin; oxisuran;
pegaspargase; peliomycin; pentamustine; peplomycin sulfate; perfosfamide;
pipobroman; piposulfan; piroxantrone hydrochloride; plicamycin; plomestane; porfimer
sodium; porfiromycin; prednimustine; procarbazine hydrochloride; puromycin; puromycin
hydrochloride; pyrazofurin; riboprine; rogletimide; safingol; safingol hydrochloride;
semustine; simtrazene; sparfosate sodium; sparsomycin; spiro germanium
hydrochloride; spiromustine; spiroplatin; streptonigrin; streptozotocin; sulofenur;
talisomycin; tecogalan sodium; tegafur; teloxantrone hydrochloride; temoporfm;
teniposide; teroxirone; testolactone; thiamiprine; thioguanine; thiotepa; tiazofurin;
tirapazamine; toremifene citrate; trestolone acetate; triciribine phosphate; trimetrexate;
trimetrexate glucuronate; triptorelin; tubulozole hydrochloride; uracil mustard; uredepa;
vapreotide; verteporfin; vinblastine sulfate; vincristine sulfate; vindesine; vindesine
sulfate; vinepidine sulfate; vinglycinate sulfate; vinleurosine sulfate; vinorelbine tartrate;
vinrosidine sulfate; vinzolidine sulfate; vorozole; zeniplatin; zinostatin; zorubicin
hydrochloride, mechloroethamine, cyclophosphamide, chlorambucil, meiphalan, etc.),
ethylenimine, hexamethlymelamine, thiotepa, busulfan), carmustine, lomusitne,
semustine, streptozocin, ortriazenes, dacarbazine, methotrexate, fluorouracil,
floxouridine, Cytarabine, mercaptopurine, thioguanine, pentostatin,
hydroxyprogesterone caproate, megestrol acetate, medroxyprogesterone acetate,
estrogens, diethlystilbestrol, ethinyl estradiol, tamoxifen), testosterone propionate,
fluoxymesterone, flutamide, leuprolide, cisplatin, carboblatin, mitoxantrone),
procarbazine, mitotane, amino glutethimide, Erbulozole, Dolastatin 10, Mivobulin
isethionate, Vincristine, NSC-639829, Discodermolide, ABT -751, Altorhyrtin A and
Altorhyrtin C), Spongistatins 1-9, Cemadotin hydrochloride, Epothilone A, Epothilone B,
Epothilone C, Epothilone D, Epothilone E, Epothilone F, Epothilone B N-oxide,
Epothilone AN-oxide, 16-aza-epothilone B, 21aminoepothilone B, 21-hydroxyepothilone
D, 26-fluoroepothilone, Auristatin PE, Soblidotin, Cryptophycin 52, Vitilevuamide,
Tubulysin A, Canadensol, Centaureidin, Oncocidin Al Fijianolide B, Laulimalide,
Narcosine, Nascapine, Hemiasterlin, Vanadocene acetylacetonate, Indanocine
Eleutherobins (such as Desmethyleleutherobin, Desacetyleleutherobin, lsoeleutherobin
A, and Z-Eleutherobin), Caribaeoside, Caribaeolin, Halichondrin B, Diazonamide A,
Taccalonolide A, Diozostatin, (-)-Phenylahistin, Myoseverin B, Resverastatin phosphate
sodium, Aprepitant, cannabis, marinol, dronabinol, erythropoetin-a, Filgrastim, rituximab,
natalizumab, cyclophosphamide, penicillamine, cyclosporine, nitrosoureas, cisplatin,
carboplatin, oxaliplatin, methotrexate, azathioprine, mercaptopurine, pyrimidine
analogues, protein synthesis inhibitors, dactinomycin, anthracyclines, mitomycin C,
bleomycin, mithramycin, Atgam® Thymoglobuline®, OKT3®, basiliximab, daclizumab,
cyclosporin, tacrolimus, sirolimus, Interferons, opioids, infliximab, etanercept,
adalimumab, golimumab, leflunomide, sulfasalazine, hydroxychloroquinine, minocycline,
rapamicin, mycophenolic acid, mycophenolate mofetil, FTY720, Cyclosporin A (CsA) or
tacrolimus (FK506), aspirin, salicylic acid, gentisic acid, choline magnesium salicylate,
choline salicylate, choline magnesium salicylate, choline salicylate, magnesium
salicylate, sodium salicylate, diflunisal, carprofen, fenoprofen, fenoprofen calcium,
flurobiprofen, ibuprofen, ketoprofen, nabutone, ketolorac, ketorolac tromethamine,
naproxen, oxaprozin, diclofenac, etodolac, indomethacin, sulindac, tolmetin,
meclofenamate, meclofenamate sodium, mefenamic acid, piroxicam, meloxicam,
valdecoxib, parecoxib, etoricoxib, lumiracoxib, betamethasone, prednisone,
alclometasone, aldosterone, amcinonide, beclometasone, betamethasone, budesonide,
ciclesonide, clobetasol, clobetasone, clocortolone, cloprednol, cortisone, cortivazol,
deflazacort, deoxycorticosterone, desonide, desoximetasone, desoxycortone,
dexamethasone, diflorasone, diflucortolone, difluprednate, fluclorolone, fludrocortisone,
fludroxycortide, flumetasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin,
fluocortolone, fluorometholone, fluperolone, fluprednidene, fluticasone, formocorta1,
halcinonide, halometasone, hydrocortisone/cortisol, hydrocortisone aceponate,
hydrocortisone buteprate, hydrocortisone butyrate, lotepredno1, medrysone,
meprednisone, methylprednisolone, methylprednisolone aceponate, mometasone
furoate, paramethasone, prednicarbate, prednisone/prednisolone, rimexolone,
tixocortol, triamcinolone, ulobetasol, pioglitazone, clofibrate, fenofibrate gemfibrozil, folic
acid, isbogrel, ozagrel, ridogrel, dazoxiben, lovastatin, simvastatin, pravastatin,
fluvastatin, atorvastatin, nisvastatin, and rosuvastatin, edaravone, vitamin C,
TROLOX , citicoline and minicycline, (2R)propyloctanoic acid, propranolol, nadolol,
timolol, pindolol, labetalol, metoprolol, atenolol, esmolol and acebutolol, memantine,
traxoprodil, tirofiban lamifiban, argatroban, enalapril, cyclandelate, losartan, valsartan,
candesartan, irbesartan, telmisartan, olmesartan mepyramine (pyrilamine), antazoline,
diphenhydramine, carbinoxamine, doxylamine, clemastine, dimenhydrinate,
pheniramine, chlorphenamine (chlorpheniramine), dexchlorpheniramine,
brompheniramine, triprolidine, cetirizine, cyclizine, chlorcyclizine, hydroxyzine,
meclizine, loratadine, desloratidine, promethazine, alimemazine (trimeprazine),
cyproheptadine, azatadine, ketotifen, acrivastine, astemizole, cetirizine, mizolastine,
terfenadine, azelastine, epinastine, levocabastine, olopatadine, levocetirizine,
fexofenadine, rupatadine, bepotastine), mucolytics, anticholinergics, antitussives,
analgesics, expectorants, albuterol, ephedrine, epinephrine, fomoterol, metaproterenol,
terbutaline, budesonide, ciclesonide, dexamethasone, flunisolide, fluticasone
propionate, triamcinolone acetonide, ipratropium bromide, pseudoephedrine,
theophylline, montelukast, pranlukast, tomelukast, zafirlukast, ambrisentan, bosentan,
enrasentan, sitaxsentan, tezosentan, iloprost, treprostinil, pirfenidone, epinephrine,
isoproterenol, orciprenaline, xanthines, zileuton.
[517] 119. The method of embodiments 116-118 wherein the subject is a human.
120. The method of embodiments 116-119 wherein the Formula I-XII
compound(s) are selected from Table 1.
121. The method of embodiments 116-119 wherein the Formula I-XII
compound(s) are selected from the group consisting of 1-(4-{4-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-cyclo-propanecarboxylic
acid, 2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)-indancarboxylic acid, 2-(S)- (4-{4-[(R,S)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino) phenyl acetic acid, 2-(R)-
(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino) phenyl propanoic acid, 2(R)-[[4-[3-methyl((R)
phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]phenyl-propanoic acid, 2(S)-
[[4-[3-methyl((R)-phenylethoxycarbonyl-amino)isoxazolyl]benzoyl]amino]phenyl-
propanoic acid, (R){4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzoylamino}phenyl-propionic acid, (S){4-[3-Methyl((S)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzoylamino}phenyl-propionic acid, (R)(4-{4-
[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-
3-phenyl-propionic acid , (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)(4-fluoro-phenyl)-propionic acid , (R)(4-Chloro-
phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)-propionic acid , (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(3,4-difluoro-phenyl)-
propionic acid , (R)(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic acid , (R)(4-
Bromo-phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(2-fluoro-phenyl)-
propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)p-tolyl-propionic acid, (R)(4-{4-[(R)(2-Chloro-
phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(4-
trifluoromethyl-phenyl)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(4-cyano-phenyl)-
propionic acid, (R)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)cyclopropyl-propionic acid , (R)[[4-[2,5-dimethyl
((R)phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]phenyl-propanoic
acid, (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino](4-fluorophenyl)propanoic acid, (R)- 3-(4-bromophenyl)[[4-[2,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, (R)- 3-(4-chlorophenyl)[[4-[2,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)- 3-(3,4-difluorophenyl)[[4-[2,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, (R)[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]phenyl-propanoic acid, (R)[[4-[1,5-dimethyl((R)
phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino](4-fluorophenyl)propanoic
acid, (R)- 3-(4-bromophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)- 3-(4-chlorophenyl)[[4-[1,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, (R)- 3-(3,4-difluorophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)- 2-(4-{5-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-pyrazolyl}-benzoylamino)phenyl-propionic acid,
(R){4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzylamino}
phenyl-propionic acid, (R)(2-Fluoro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R){4-[3-Methyl
((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzylamino}(4-trifluoromethyl-
phenyl)-propionic acid, (R)Cyclopropyl{4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R)(2-Chloro-
phenyl){4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzylamino}-propionic acid, (R)(4-Chloro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R)- 2-(4-{4-[(R)(2-
Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)phenyl-
propionic acid, (R)- 2-(4-{4-[(R)_1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzylamino)(2-fluoro-phenyl)-propionic acid, (R)- 2-(4-{4-[(R)(2-
Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)(4-
trifluoromethyl-phenyl)-propionic acid, (R)- 3-(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-
phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)-propionic acid, (R)-
2-(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzylamino)cyclopropyl-propionic acid, 2-{4-[3-Methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzyloxy}phenyl-propionic acid, 2-{4-[3-Methyl-
4-((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}phenyl-propionic
acid, (RS)Cyclopropyl{4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazol-
-yl]-benzyloxy}-propionic acid, (RS)Cyclopropyl{4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-propionic acid, 2-[4-[4-[5-[1-(2-
chlorophenyl)ethoxy-carbonylamino]cyano-pyrazolyl]phenyl]phenyl]acetic acid,
(R)[4-[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]phenyl]cyclo-propane carboxylic acid, (R)[4-[4-[2,5-dimethyl(1-
phenylethoxycarbonylamino)pyrazolyl]phenyl]phenyl]-cyclopropane carboxylic acid,
(R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonyl-amino]fluoro-pyrazolyl}fluoro-
biphenylyl)-cyclopropanecarboxylic acid, (R)(4'-{5-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]fluoro-pyrazolyl}fluoro-biphenylyl)-cyclo-
propanecarboxylic acid, (R)(2-Chloro-4'-{5-[1-(2-chloro-phenyl)-
ethoxycarbonylamino]fluoro-pyrazolyl}-biphenylyl)-cyclopropanecarboxylic acid,
(R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazolyl}methyl-
biphenylyl)-cyclopropane-carboxylic acid, (R)(4'-{5-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]fluoro-pyrazolyl}-biphenylyl)-cyclopropanecarboxylic acid,
(R)- 1-{4'-[5-(1-Phenyl-ethoxycarbonyl-amino)trifluoromethyl-pyrazolyl]-biphenyl
yl}-cyclopropanecarboxylic acid, (R){2-Fluoro-4'-[5-(1-phenyl-ethoxycarbonylamino)-
4-trifluoromethyl-pyrazolyl]-biphenylyl}-cyclopropanecarboxylic acid, (R)(4-{5-[5-
(1-Phenyl-ethoxycarbonylamino)-pyrazolyl]-pyridinyl}-phenyl)-
cyclopropanecarboxylic acid,
[520] 122. The method of embodiments 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 31.
123. The method of embodiments 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 32.
124. The method of embodiments 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 33.
125. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 34.
126. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 35.
[525] 127. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 36.
128. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 37.
129. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 38.
130. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 39.
131. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 40.
132. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 41.
[531] 133. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 42.
134. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 43.
135. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 44.
136. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 45.
137. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 46.
[536] 138. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 47.
139. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 48.
140. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 49.
141. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 50.
142. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 51.
[541] 143. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 52.
144. The method of embodiment 116-119 wherein the Formula I-XII
compound(s) are selected from embodiment 53.
145. The composition of embodiment 116 where the currently used agent is a
mast cell stabilizing agent
146. The composition of embodiment 116 where the currently used agent is a
platelet activating factor receptor antagonist,
147. The composition of embodiment 145 where the mast cell stabilizing agent is
cromoglicate, nedocromil, azelastine, bepotastine, epinastine, ketotifen, olopatadine and
rupatadine.
148. The composition of embodiment 146 where the platelet activating factor
receptor antagonist is rupatadine, SM-12502, CV-3988 and WEB 2170.
1A. A compound wherein the compound has the structure of Formula I
A B L Formula I
[548]
or a pharmaceutically acceptable salt or prodrug thereof,
A B B
wherein R is -CO H, -CO R , -CN, tetrazolyl, -C(=O)NH , -C(=O)NHR ,
2 2 2
-C(=O)NHSO R or -C(=O)NHCH CH SO H or a carboxylic acid isostere;
2 2 2 3
wherein R is -H or -C -C alkyl, or has the structure of one of:
O O O
L is absent or substituted or unsubstituted C -C alkylene, substituted or
unsubstituted C -C cycloalkylene, C -C fluoroalkylene, substituted or unsubstituted C -
3 6 1 6 1
C heteroalkylene, or -UV-Z-, wherein -UV- is defined by -OW-, -WO-, -N(R )W-,
J J J
-WN(R )-, -N(R )C(=O)-, -SW-, -S(=O) W- or -C(=O)N(R )-, wherein W is substituted or
unsubstituted C -C alkylene or substituted or unsubstituted C -C cycloalkylene or W is
1 3 3 6
-C(R ) -, and wherein Z is substituted or unsubstituted C -C alkylene, substituted or
2 1 6
unsubstituted C -C cycloalkylene, or C -C fluoroalkylene or Z is -C(R ) -; wherein n is
3 6 1 6 2
0, 1, or 2;
[553] L is absent, or substituted or unsubstituted C -C alkylene, substituted or
unsubstituted C -C cycloalkylene, C -C fluoroalkylene, substituted or unsubstituted C -
3 6 1 6 1
C heteroalkylene, -O-, -S-, -S(=O)-, -S(=O) -, -N(R )-, -C(=O)-, or -C(=O)N(R )-;
Ring A is a 5-6 membered heteroarene selected from one of:
R N N
R R R R
E N N
N R D
N C N
C D C R
R R R
wherein the dashed line indicates the point of attachment of Ring A to Ring B;
wherein one of R and R is -H, -CN, -F, -Cl, -Br, -I, -OC -C alkyl, -C -C alkyl, -C -C
1 4 1 4 3 6
C D F G
cycloalkyl, or -C -C fluoroalkyl, and the other R or R is -N(R )-C(=O)XCH(R )-CY, -
F G F F G
N(R )-C(=O)XC(R ) -CY, -N(R )-C(=O)X-CY, -C(=O)-N(R )-CH(R )X-CY, -C(=O)-
F G F
N(R )-C(R ) X-CY, or -C(=O)X-N(R )-X-CY, wherein X is absent, -O-, -NH- or -CH -;
E F G
R is -H, -C -C alkyl or -C -C fluoroalkyl; R is -H or C -C alkyl; R is
1 4 1 4 1 4
independently selected R , or one R is -C -C alkyl and is taken together with the
carbon atom to which R is attached and the carbon or heteroatom to which CY is
attached to define a substituted or unsubstituted carbocycle or a substituted or
unsubstituted heterocycle, and the other R , if present, is as defined for R ;
CY is substituted or unsubstituted C -C alkyl, substituted or unsubstituted C -
1 6 3
C cycloalkyl, substituted or unsubstituted C -C heterocycloalkyl, substituted or
2 10
unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein if CY is
substituted then CY is substituted with 1, 2, or 3 independently selected R ;
[559] wherein each R is independently selected from -H, halogen, -CN, -NO , -OH,
J J J J J J L J J
-OR , -SR , -S(=O)R , -S(=O)2R , -N(R )S(=O)2R , -S(=O)2N(R )2, -C(=O)R , OC(=O)R ,
J J L L L J L
-CO R , -OCO R , -N(R ) , -C(=O)N(R ) , -OC(=O)N(R ) , -N(R )C(=O)N(R ) , -
2 2 2 2 2 2
J J J J
N(R )C(=O)R , -N(R )C(=O)OR , C -C alkyl, C -C fluoroalkyl, C -C fluoroalkoxy, C -C
1 4 1 4 1 4 1 4
alkoxy, and C -C heteroalkyl, wherein each R is independently substituted or
unsubstituted C -C alkyl, substituted or unsubstituted C -C heteroalkyl, C -C
1 6 1 6 1 6
fluoroalkyl, substituted or unsubstituted C -C cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, -C -C alkylene-(substituted or unsubstituted C -C cycloalkyl), -C -C
1 4 3 6 1 4
alkylene-(substituted or unsubstituted heterocycloalkyl), -C -C alkylene-(substituted or
unsubstituted aryl), or -C -C alkylene-(substituted or unsubstituted heteroaryl);
wherein each R is independently -H, substituted or unsubstituted C -C alkyl,
substituted or unsubstituted C -C heteroalkyl, C -C fluoroalkyl, substituted or
1 6 1 6
unsubstituted C -C cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted
or unsubstituted aryl, substituted or unsubstituted heteroaryl, -C -C alkylene-
(substituted or unsubstituted cycloalkyl), -C -C alkylene-(substituted or unsubstituted
heterocycloalkyl), -C -C alkylene(substituted or unsubstituted aryl), or -C -C alkylene-
1 4 1 4
H L L
(substituted or unsubstituted heteroaryl), or when R is -S(=O) N(R ) , -N(R ) , -
2 2 2
L L F L L
C(=O)N(R ) , -OC(=O)N(R ) or -N(R )C(=O)N(R ) , each R is independently -H or C -
2 2 2 1
C alkyl, or the R groups independently are C -C alkyl which are taken together with
6 1 6
the N atom to which they are attached to define a substituted or unsubstituted
L L L
heterocycle, or when W is -C(R ) - or Z is -C(R ) -, each R is independently -H, C -C
2 2 1 6
alkyl, or the R groups independently are C -C alkyl which are taken together with the
carbon atom to which they are attached to define a carbocycle;
Ring B is substituted or unsubstituted C -C cycloalkylene, substituted or
3 10
unsubstituted C -C heterocycloalkylene, substituted or unsubstituted arylene, or
2 10
substituted or unsubstituted heteroarylene, where if ring B is substituted then ring B is
substituted with 1, 2, or 3 independently selected R , wherein R is as previously
defined;
Ring C is absent or substituted or unsubstituted C -C cycloalkylene, substituted
3 10
or unsubstituted C -C heterocycloalkylene, substituted or unsubstituted arylene, or
2 10
substituted or unsubstituted heteroarylene, where if ring C is substituted then ring C is
substituted with 1, 2, or 3 independently selected R , wherein R is as previously
defined,
wherein when Ring B is substituted or unsubstituted arylene, Ring C is absent,
2 1 J D F G
L is absent, L is -UV-Z-, wherein -UV- is -N(R )-C(=O), R is -N(R )-C(=O)XCH(R )-
G F C
CY, wherein X is -O-, R is -CH and R is -H, and R is -H, -CH or -CF ,
3 3 3
or when Ring B is substituted or unsubstituted arylene and Ring C is substituted
or unsubstituted arylene or is substituted or unsubstituted C -C cycloalkylene, or Ring
3 10
B is substituted or unsubstituted C -C cycloalkylene and Ring C is substituted or
3 10
unsubstituted arylene, L is absent, L is C -C alkylene,
C A B
[565] and R is -H or -CH and R is -CO H or CO R
3 2 2 ,
then Ring A has the structure of one of::
D N D
C R R
R R C
C D D
D D C
R R R R
E N N
N C N
C D C R
R R R
and when Ring B is C -C heterocycloalkylene, Ring C is substituted or
2 10
2 1 C A
unsubstituted arylene, L is absent, L is C -C alkylene, R is -CH and R is -CO H or
1 6 3 2
CO R then Ring A has the structure of one of:
R N N
C E N
N R D
N C D N
C D C
2A. The compound of embodiment 1A wherein R is -H, -CN, -F, -Cl, -Br, -I, -
OC -C alkyl, -C -C alkyl, -C -C cycloalkyl, or -C -C fluoroalkyl and R is -N(R )-
1 4 1 4 3 6 1 4
G F G F F
C(=O)XCH(R )-CY, -N(R )-C(=O)XC(R ) -CY, -N(R )-C(=O)X-CY, wherein R and each
R independently are -H or C -C alkyl.
3A. The compound of embodiment 2A wherein Ring A is selected from one of:
D N D
C R R
R R C
C D D
D D C
R R R
R R R
N D R
C D C R
R R R
D F G C
wherein R is -N(R )-C(=O)XCH(R )-CY, and R is -H, -CH or -CF ,
Ring B is substituted or unsubstituted arylene or substituted or unsubstituted
heteroarylene, Ring C is absent; L is absent; L is -UV-Z-, wherein -UV- is -OW-, -WO-,
J J J J
-N(R )W-, -WN(R )-, -N(R )C(=O)-, -SW-, -S(=O)nW-, or -C(=O)N(R )-, wherein W is
substituted or unsubstituted C -C alkylene; and n is 0, 1, or 2; or Ring B and Ring C
independently are substituted or unsubstituted arylene or substituted or unsubstituted
arylene L is absent, L is C -C alkylene.
[575] 4A. The compound of embodiment 2A wherein Ring A has the structure of one
of :
R N N
C E N
N R D
N C D N
C D C
wherein Ring B is substituted or unsubstituted arylene and Ring C is substituted
or unsubstituted arylene or is substituted or unsubstituted C -C cycloalkylene, or Ring
3 10
B is substituted or unsubstituted C -C cycloalkylene and Ring C is substituted or
3 10
unsubstituted arylene, L is absent and L is C -C alkylene.
5A. The compound of embodiment 2A wherein L is absent and L is C -C
alkylene, or substituted or unsubstituted C3-C6 cycloalkylene, substituted or
unsubstituted C -C heteroalkylene or L and Ring C are absent and L is -UV-Z-,
J J J
wherein -UV- is defined by -OW-, -WO-, -N(R )W-, -WN(R )-, -N(R )C(=O)-, -SW-, -
S(=O) W-, or -C(=O)N(R )-, wherein W is substituted or unsubstituted C -C alkylene;
n 1 3
and n is 0, 1, or 2.
6A. The compound of embodiment 5A wherein L is -UV-Z- wherein -UV- is
J J J
defined by -OW-, -WO-, -N(R )W-, -WN(R )- or -C(=O)N(R )-, wherein W is substituted
or unsubstituted C1-C3 alkylene.
[580] 7A. The compound of embodiment 5A wherein L is -UV-Z-, wherein -UV- is
defined by -WO-, -WN(R )- or -C(=O)N(R )-, wherein W is substituted or unsubstituted
C -C alkylene, and L is absent.
8A. The compound of embodiment 7A wherein Z is substituted or unsubstituted
C -C alkylene.
[582] 9A. The compound of embodiment 7A wherein Z is substituted or unsubstituted
C -C alkylene and R is -CO H or -CO R .
1 6 2 2
10A. The compound of embodiment 7A, wherein L is -UV-Z-, wherein -UV- is
defined by -C(=O)N(R )-, wherein R is -H or -CH .
11A. The compound of embodiment 7A wherein L is UV-Z-, wherein -UV-, is
defined by -WO-.
12A. The compound of embodiment 7A wherein L is UV-Z-, wherein -UV-, is
defined by - WN(R )-, wherein R is -H or -CH .
13A. The compound of embodiment 2A wherein L is absent or a substituted or
unsubstituted substituted C -C alkylene or a substituted or unsubstituted C
1 4 3
cycloalkylene (i.e., cyclopropyl-di-yl).
14A. The compound of embodiment 2 wherein L is -CH -, or
-C(CH ) -.
15A. The compound of embodiment 2 wherein Ring A has the structure of one
R N N
C C R R
C D F G
wherein R is -H, -CN, -CH , or -CF , R is -N(R )C(=O)XCH(R )-CY, -
F G F 1
N(R )C(=O)XC(R ) -CY, or -N(R )C(=O)X-CY and L is -UV-Z- wherein -UV- is defined
by -WO -, -WN(R )- or -C(=O)N(R )-.
16A. The compound of embodiment 15A wherein R is -H, -CH or -CF and R
is -N(R )C(=O)XCH(R )-CY.
D F G
17A. The compound of embodiment 15A wherein R is -N(R )C(=O)XCH(R )-
F G F
CY, wherein -X- is -N(R )- or -O-; and wherein R and each R , independently selected,
are -H or -CH .
18A. The compound of embodiment 17A wherein R is -CH , in the R or S
configuration, and CY is substituted or unsubstituted phenyl or substituted or
unsubstituted heteroaryl.
D F G
[594] 19A. The compound of embodiment 17A wherein R is -N(R )C(=O)OCH(R )-
CY, wherein CY is unsubstituted or substituted phenyl, wherein substituted phenyl is
phenyl that is substituted with one or two of independently selected R .
20A. The compound of embodiment 17A, wherein R is -N(R )C(=O)OCH(CH )-
CY, wherein R is -H, and wherein CY is unsubstituted phenyl.
[596] 21A. The compound of embodiment 17A, wherein R is -N(R )-C(=O)OCH(CH )-
CY, wherein R is -H, and wherein CY is substituted phenyl, wherein substituted phenyl
is phenyl that is substituted with one or two of independently selected R , wherein R
are halogens.
22A. The compound of embodiment 21A, wherein R is -NH-C(=O)OCH(CH )-
CY wherein CY is substituted phenyl, wherein substituted phenyl is phenyl that is
substituted with one R , wherein R is -F, -Cl or -Br.
23A. The compound of embodiment 21A, wherein R is -NH-C(=O)OCH(CH )-
CY, wherein CY is substituted phenyl, wherein substituted phenyl is phenyl that is
substituted with one R , wherein R is -Cl.
24A. The compound of embodiment 19A, wherein R is -NH-C(=O)OCH(CH )-
CH O
[H, Halogen]
CY having the structure of .
25A. The compound of claim 19A wherein R is -NH-C(=O)OCH(CH )-CY
wherein the methyl group in R is in the R configuration.
26A. The compound of any one of embodiments 5-25 wherein Ring A has the
structure of: , wherein L is absent and Ring B is substituted or unsubstituted
arylene, or substituted or unsubstituted heteroarylene,
provided that when Ring C is not absent and L is C -C alkylene, or Ring C is
1 J D
absent and L is -UV-Z, wherein -UV- is -N(R )-C(=O), and R has the structure of -
F G F G F A
N(R )-C(=O)XCH(R )-CY, -N(R )-C(=O)XC(R ) -CY or -N(R )-C(=O)X-CY,and R is -
CO H, then R is other than -H, -CH and -CF .
2 3 3
[603] 27A. The compound of embodiment 26A wherein R is -H, -CH3 or -CF3, and R
is -NH-C(=O)OCH(R )-CY, wherein R is -H or -CH , in the R or S configuration, and -
CY is substituted or unsubstituted phenyl.
28A. The compound of embodiment 26A wherein L and Ring C are absent,
Ring B is substituted or unsubstituted arylene, or substituted or unsubstituted
heteroarylene, and L is -UV-Z-, wherein -UV-, is defined by -WO-, -WN(R )- or -
C(=O)N(R )-.
29A. The compound of embodiment 26A wherein L and Ring C are absent,
Ring B is substituted or unsubstituted arylene, or substituted or unsubstituted
1 J J
heteroarylene, and L is -UV-Z-, wherein -UV-, is defined by -WN(R )- or -C(=O)N(R )-,
wherein R is -H or -CH .
30A. The compound of embodiment 29A wherein L is -UV-Z-, wherein -UV- is
defined by -C(=O)NH-, and wherein Z is substituted or unsubstituted C1-C6 alkylene.
31A. The compound of embodiment 29A wherein L is -UV-Z-, wherein -UV- is
defined by -WO-, wherein W is substituted or unsubstituted C -C alkylene, and wherein
Z is substituted or unsubstituted C -C alkylene.
32A. The compound of embodiment 29A wherein L is -UV-Z-, wherein -UV- is
defined by -W-NH-, wherein W is substituted or unsubstituted C -C alkylene, and
wherein Z is substituted or unsubstituted C -C alkylene.
33A. The compound of embodiment 26A wherein L is -UV-Z-, wherein -UV- is
J J J
defined by -WO-, -WN(R )- or -C(=O)N(R ), wherein R is -H or -CH , and wherein Z is
substituted or unsubstituted C -C alkylene, wherein the alkylene is -CH(CH -
1 6 2
cyclopropyl)-, -CH(CH -aryl) or -CH(CH -heteroaryl), wherein the aryl or heteroaryl is
substituted or unsubstituted.
34A. The compound of embodiment 33A wherein L is -UV-Z-, wherein -UV- is
defined by -C(=O)NH-, -WO- or -W-NH-, wherein -W- is -CH -.
35A. The compound of embodiment 33A wherein R is -CO H or -CO R .
36A. The compound of embodiment 33A wherein L is -UV-Z-, wherein -UV- is
defined by -CH O-, -CH -NH- or -C(=O)NH-, wherein Z is substituted or unsubstituted
C -C alkylene, wherein the alkylene is -CH(CH -cyclopropyl)-, -CH(CH -aryl) or -
1 6 2 2
CH(CH2-heteroaryl), wherein the aryl or heteroaryl is unsubstituted or substituted with 1,
2, or 3 independently selected substituted or unsubstituted C -C alkyl or halogen.
37A. The compound of embodiment 36A wherein said substituted or
unsubstituted C -C alkyl or halogen substituent or substituents of the aryl or heteroaryl
of -CH(CH -aryl) or -CH(CH -heteroaryl) are selected from the group consisting of -CH ,
2 2 3
-CF , -F, -Cl or -Br.
38A. The compound of embodiment 33A, wherein L is -UV-Z- and wherein R is
1 A A
-CO H to which Z is attached to define -L -R (i.e., -UV-Z-R ), wherein -UV- is defined
by -C(=O)NH-, -WO- or -W-NH-, wherein -W- is -CH -, and Z is -CH(CH -aryl), wherein
the aryl is substituted or unsubstituted, having the structure of one of
[H, Cl]
[H, F, Cl, CH , CF ]
O OH
O OH
[H, F]
[H, F, Cl, Br, CH , CF ]
O OH
39A. The compound of embodiment 36A wherein the -CH(CH -aryl) substituent
of Z in the -L -R is in the R configuration.
40A. The compound of embodiment 33A wherein L is -UV-Z- and wherein R is
1 A A
-CO H to which Z is attached to define -L -R (i.e., -UV-Z-R ), wherein -UV- is defined
by -C(=O)NH-, -WO- or -W-NH-, wherein -W- is -CH -, and Z is -CH(CH -cyclopropyl)-,
having the structure of
O OH O
O OH
O OH
41A. The compound of embodiment 1A, 2A, 3A, or 4A, wherein the compound
has the structure of Formula III
Formula III
C L R
A 1 2 3
, wherein A , A and A are
independently -N=, =N-, =CH- or -CH=.
42A. The compound of embodiment 41A wherein Ring A wherein Ring A has the
C C R
C R R
structure of one of: ,
1 D F G F
wherein when L is C -C alkylene, R is -N(R )-C(=O)XCH(R )-CY, -N(R )-
G F G A B C
C(=O)XC(R ) -CY, wherein R is -H, R is -H or -CH ; R is -CO H or CO R , and R is
2 3 2 2
-H or -CH , then Ring A has the structure of one of:
R N N
43A. The compound of embodiment 41A, wherein Ring A wherein Ring A has
R N N
D N D
C C R R
C R R
the structure of one of: ,
wherein Ring C is a substituted or unsubstituted arylene or heteroarylene, L is
A B D F G F
C1-C6 alkylene, R is -CO2H or CO2R , R is -N(R )-C(=O)XCH(R )-CY, -N(R )-
G F G C
C(=O)XC(R )2-CY, wherein R is -H, R is -CH3 and CY is substituted phenyl and R is -
is -CN, -F, -Cl, -Br, -I, -OC -C alkyl, -C -C alkyl, -C -C cycloalkyl, or -C -C fluoroalkyl.
1 4 2 4 3 6 2 4
[623] 44A. The compound of embodiment 41A, wherein Ring A has the structure of
one of:
R N N
D N D
C C R R
C R R
, wherein Ring C is
a substituted or unsubstituted arylene or heteroarylene, L is C -C alkylene, R is -
B D F G F G
CO H or -CO R , R is -N(R )-C(=O)XCH(R )-CY, -N(R )-C(=O)XC(R ) -CY, wherein X
2 2 2
F G C
is -O-, R is -CH , R is -H or -CH and CY is substituted phenyl and R is - is -H, -CN, -
F, -Cl, -Br, -I, -OC -C alkyl, -C -C alkyl, -C -C cycloalkyl, or -C -C fluoroalkyl.
1 4 1 4 3 6 1 4
45A. The compound of embodiment 1A, 2A or 5A wherein the compound has the
A L R
Formula IV
structure of Formula IV , wherein Ring A has the
N E N
R N N
D N D
structure of one of: ,
1 D F G 1
wherein A is =N- or =C-; R is -NR C(=O)OCH(R )-CY; L is -UV-Z-, wherein -UV- is
J J F G
defined by -C(=O)N(R )-, wherein R is -H or -CH3; R and R independently are -H or -
CH ; and R is -CO H or -CO R .
3 2 2
46A. The compound of embodiment 2A wherein the compound has the structure
of Formula VII
Formula VI
, wherein Ring A is a 5 membered
heteroarene having one of the structures of:
R N N
D N D
C C R R
C R R
, wherein R is the -
N(R )C(=O)CH(R )-CY substituent of Formula VI wherein CY is phenyl substituted with
H C A B F G
one R , and R is -H, -CH , CF or -F; R is -CO H or -CO R ; and R and R
3 3 2 2
independently are -H or -CH ; and R independently are -H, halogen, -CH or -CF .
3 3 3
47A. The compound of embodiment 2A wherein the compound has the structure
of Formula VII
A N z
Formula VII
., wherein A is =CH- or =N-;Ring A is
a 5 membered heteroarene having the structure of one of:
C C R
C R R
, wherein R is the
-N(R )C(=O)CH(R )-CY substituent of Formula VII wherein CY is phenyl substituted
H C A B E F
with one R ; and R is -H, -CH , CF or -F; R is -CO H or -CO R ; R and R
3 3 2 2
independently are -H or C -C alkyl; R is -H or -CH ; R independently are -H, halogen,
1 4 3
L L L
-CH or -CF ; and Z is -C(R ) , wherein one R is -H and the other R is -H or C -C
3 3 2 1 4
alkyl.
48A The compound of embodiment 2A wherein the compound has the structure
Formula VIII
of Formula VIII ,wherein A is =CH-
or =N-; wherein Ring A is a 5 membered heteroarene having the structure of one of
R N N
D N D
C C R R
C R R
, wherein R is the -
N(R )C(=O)CH(R )-CY substituent of Formula VII wherein CY is phenyl substituted with
H A B L E F
one R ; R is -CO H or -CO R ; W is -C(R ) - or ; R and R independently are
2 2 2
-H or C1-C4 alkyl; R is -H or -CH3; R independently are -H, halogen, -CH3 or -CF3; and
L L L
Z is -C(R )2, wherein one R is -H and the other R is -H or C1-C4 alkyl.
49A. The compound of embodiment 2A wherein the compound has the structure
A O z
Formula IX
of Formula IX , wherein A is =CH-
or =N-; wherein Ring A is a 5 membered heteroarene having the structure of one of
R N N
D N D
D F G
[632] wherein R is the -N(R )C(=O)CH(R )-CY substituent of Formula VII wherein CY
H A B
is phenyl substituted with one R ;R is -CO H or -CO R ;
L E F
wherein W is -C(R ) - or ; R and R independently are -H or C -C
2 1 4
G H L
alkyl; R is -H or -CH ; R independently are -H, halogen, -CH or -CF ; and Z is -C(R ) ,
3 3 3 2
wherein one R is -H and the other R is -H or C -C alkyl.
50A. The compound of embodiment 2A wherein the compound has the structure
Formula XII
of Formula IX ,wherein
A is =CH- or =N-; wherein Ring A is a 5 membered heteroarene having the structure of
R N N
C C R R
one of , wherein R is the
-N(R )C(=O)CH(R )-CY substituent of Formula VII wherein CY is phenyl substituted
H A B L E F
with one R ; R is -CO H or -CO R ; wherein W is -C(R ) - or ; R and R
2 2 2
independently are -H or C -C alkyl; R is -H or -CH ; R independently are -H, halogen,
1 4 3
L L L
-CH or -CF ; and Z is -C(R ) , wherein one R is -H and the other R is -H or C -C
3 3 2 1 4
alkyl.
[635] 51A The compound of embodiment 2A wherein the compound is selected from
Table 1.
52A. The compound of embodiment 51A wherein the compound is 1-(4-{4-[1-(2-
Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-
cyclopropanecarboxylic acid, 2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)-indancarboxylic acid, 2-(S)-(4-{4-[(R,S)(2-
Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino) phenyl
acetic acid, 2-(R)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino) phenyl propanoic acid, 2(R)-[[4-[3-methyl((R)
phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]phenyl-propanoic acid, 2(S)-
[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]
phenyl-propanoic acid, (R)[[4-[2,5-dimethyl((R)
phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]phenyl-propanoic acid, (R)
[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]
phenyl-propanoic acid, (R)[[4-[2,5-dimethyl((R)
phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino](4-fluorophenyl)propanoic
acid, (R)[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino](4-fluorophenyl)propanoic acid, (R)- 3-(4-bromophenyl)[[4-[2,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, (R)- 3-(4-bromophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)- 3-(4-chlorophenyl)[[4-[2,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, (R)- 3-(4-chlorophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)- 3-(3,4-difluorophenyl)[[4-[2,5-
dimethyl((R)phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic
acid, (R)- 3-(3,4-difluorophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)(4-{4-[(R)(2-chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)cyclopropyl-propionic
acid, (R){4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzoylamino}phenyl-propionic acid, (S){4-[3-Methyl((S)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzoylamino}phenyl-propionic acid, (R)(4-{4-
[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-
3-phenyl-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)(4-fluoro-phenyl)-propionic acid, (R)(4-Chloro-
phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(3,4-difluoro-phenyl)-
propionic acid, (R)(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic acid, (R)(4-
Bromo-phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)-propionic acid, (R)(4-Bromo-phenyl)(4-{4-[(R)(2-
chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic
acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)(2-fluoro-phenyl)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)p-tolyl-propionic acid,
(R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)(4-trifluoromethyl-phenyl)-propionic acid, (R)(4-{4-[(R)(2-Chloro-
phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)(4-cyano-
phenyl)-propionic acid, (R)- 2-(4-{5-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-pyrazolyl}-benzoylamino)phenyl-propionic acid, (R){4-[3-Methyl((R)
phenyl-ethoxycarbonylamino)-isoxazolyl]-benzylamino}phenyl-propionic acid, (R)-
3-(2-Fluoro-phenyl){4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzylamino}-propionic acid, (R){4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-
isoxazolyl]-benzylamino}(4-trifluoromethyl-phenyl)-propionic acid, (R)
Cyclopropyl{4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzylamino}-propionic acid, (R)(2-Chloro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R)(4-Chloro-
phenyl){4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzylamino}-propionic acid, (R)- 2-(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)phenyl-propionic acid,
(R)- 2-(4-{4-[(R)_1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzylamino)(2-fluoro-phenyl)-propionic acid, (R)- 2-(4-{4-[(R)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)(4-trifluoromethyl-phenyl)-
propionic acid, (R)- 3-(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)-propionic acid, (R)(4-{4-
[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)
cyclopropyl-propionic acid, 2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-
isoxazolyl]-benzyloxy}phenyl-propionic acid, (RS)Cyclopropyl{4-[3-methyl
((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-propionic acid, (RS)
Cyclopropyl{4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzyloxy}-propionic acid, 2-[4-[4-[5-[1-(2-chlorophenyl)ethoxycarbonylamino]cyano-
pyrazolyl]phenyl]phenyl]acetic acid, (R)[4-[4-[1,5-dimethyl(1-
phenylethoxycarbonylamino)pyrazolyl]phenyl]phenyl]cyclopropane carboxylic acid,
(R)[4-[4-[2,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]phenyl]cyclopropane carboxylic acid, (R)(4'-{5-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]fluoro-pyrazolyl}fluoro-biphenylyl)-
cyclopropanecarboxylic acid, (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]
fluoro-pyrazolyl}fluoro-biphenylyl)-cyclopropanecarboxylic acid, (R)(2-Chloro-
4'-{5-[1-(2-chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazolyl}-biphenylyl)-
cyclopropanecarboxylic acid, (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]
fluoro-pyrazolyl}methyl-biphenylyl)-cyclopropanecarboxylic acid, (R)(4'-{5-[1-
(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazolyl}-biphenylyl)-
cyclopropanecarboxylic acid, (R)- 1-{4'-[5-(1-Phenyl-ethoxycarbonylamino)
trifluoromethyl-pyrazolyl]-biphenylyl}-cyclopropanecarboxylic acid, (R){2-Fluoro-
4'-[5-(1-phenyl-ethoxycarbonylamino)trifluoromethyl-pyrazolyl]-biphenylyl}-
cyclopropanecarboxylic acid, (R)(4-{5-[5-(1-Phenyl-ethoxycarbonylamino)-pyrazol
yl]-pyridinyl}-phenyl)-cyclopropanecarboxylic acid.
53A. A compound of any one of embodiments 1A-52A for preparation of
mendicant for treating a LPA-dependent disease or condition.
The compounds of Table 1 are exemplary of the invention but not limiting,
wherein compounds 57-458 are prepared according to the appropriately modified
procedures of the examples for preparation of compounds 1-458.
TABLE 1
Cpd Name
1 1-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)-cyclopropanecarboxylic acid
2 2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)-indancarboxylic acid
3 2-(S)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino) phenyl acetic acid
4 2-(R)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino) phenyl propanoic acid
2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]
phenyl-propanoic acid
6 2(S)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]
phenyl-propanoic acid
7 (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]-
3-phenyl-propanoic acid
8 (R)[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]-
3-phenyl-propanoic acid
9 (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]-
3-(4-fluorophenyl)propanoic acid
(R)[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]-
3-(4-fluorophenyl)propanoic acid
11 (R)- 3-(4-bromophenyl)[[4-[2,5-dimethyl((R)phenylethoxycarbonyl-amino)pyrazol-
3-yl]benzoyl]amino]propanoic acid
12 (R)- 3-(4-bromophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-amino)pyrazol-
3-yl]benzoyl]amino]propanoic acid
13 (R)- 3-(4-chlorophenyl)[[4-[2,5-dimethyl((R)phenylethoxycarbonyl-amino)pyrazol-
3-yl]benzoyl]amino]propanoic acid
14 (R)- 3-(4-chlorophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-amino)pyrazol-
3-yl]benzoyl]amino]propanoic acid
(R)- 3-(3,4-difluorophenyl)[[4-[2,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid
16 (R)- 3-(3,4-difluorophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl-
amino)pyrazolyl]benzoyl]amino]propanoic acid
17 (R)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)cyclopropyl-propionic acid
18 (R){4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzoylamino}
phenyl-propionic acid
19 (S){4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzoylamino}
phenyl-propionic acid
(R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)phenyl-propionic acid
21 (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)(4-fluoro-phenyl)-propionic acid
22 (R)(4-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)-propionic acid
23 (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)(3,4-difluoro-phenyl)-propionic acid
24 (R)(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)-propionic acid
(R)(4-Bromo-phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)-propionic acid
26 (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)(2-fluoro-phenyl)-propionic acid
27 (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)p-tolyl-propionic acid
28 (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)(4-trifluoromethyl-phenyl)-propionic acid
29 (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)(4-cyano-phenyl)-propionic acid
(R)- 2-(4-{5-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-pyrazolyl}-
benzoylamino)phenyl-propionic acid
31 (R){4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzylamino}
phenyl-propionic acid
32 (R)(2-Fluoro-phenyl){4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazol
yl]-benzylamino}-propionic acid
33 (R){4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzylamino}
(4-trifluoromethyl-phenyl)-propionic acid
34 (R)Cyclopropyl{4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzylamino}-propionic acid
(R)(2-Chloro-phenyl){4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazol
yl]-benzylamino}-propionic acid
36 (R)(4-Chloro-phenyl){4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazol
yl]-benzylamino}-propionic acid
37 (R)- 2-(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzylamino)phenyl-propionic acid
38 (R)- 2-(4-{4-[(R)_1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzylamino)(2-fluoro-phenyl)-propionic acid
39 (R)- 2-(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzylamino)(4-trifluoromethyl-phenyl)-propionic acid
40 (R)- 3-(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzylamino)-propionic acid
41 (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzylamino)cyclopropyl-propionic acid
42 2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}phenyl-
propionic acid
43 2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}phenyl-
propionic acid
44 (RS)Cyclopropyl{4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzyloxy}-propionic acid
45 (RS)(4-Chloro-phenyl){4-[3-methyl((R)phenyl-ethoxycarbonyloxy)-isoxazol
yl]-benzyloxy}-propionic acid
46 2-[4-[4-[5-[1-(2-chlorophenyl)ethoxycarbonylamino]cyano-pyrazol
yl]phenyl]phenyl]acetic acid
47 (R)[4-[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]phenyl]cyclopropane carboxylic acid
48 (R)[4-[4-[2,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]phenyl]cyclopropane carboxylic acid
49 (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazolyl}fluoro-
biphenylyl)-cyclopropanecarboxylic acid
50 (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazolyl}fluoro-
biphenylyl)-cyclopropanecarboxylic acid
51 (R)(2-Chloro-4'-{5-[1-(2-chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazolyl}-
biphenylyl)-cyclopropanecarboxylic acid
52 (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazolyl}methyl-
biphenylyl)-cyclopropanecarboxylic acid
53 (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazolyl}-biphenyl
yl)-cyclopropanecarboxylic acid
54 (R)- 1-{4'-[5-(1-Phenyl-ethoxycarbonylamino)trifluoromethyl-pyrazolyl]-biphenyl
yl}-cyclopropanecarboxylic acid
55 (R){2-Fluoro-4'-[5-(1-phenyl-ethoxycarbonylamino)trifluoromethyl-pyrazolyl]-
biphenylyl}-cyclopropanecarboxylic acid
56 (R)(4-{5-[5-(1-Phenyl-ethoxycarbonylamino)-pyrazolyl]-pyridinyl}-phenyl)-
cyclopropanecarboxylic acid
57 2-[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]phenyl-
propanoic acid
58 3-cyclopropyl[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid
59 2-[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]phenoxy-
propanoic acid
60 2-[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]phenyl-
butanoic acid
61 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-phenyl-propanoic acid
62 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-cyclopropyl-propanoic acid
63 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
4-phenyl-butanoic acid
64 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-phenoxy-propanoic acid
65 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
4-phenyl-butanoic acid
66 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-phenoxy-propanoic acid
67 3-cyclopropyl[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid
68 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-phenyl-propanoic acid
69 3-(4-methoxyphenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid
70 3-(4-fluorophenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid
71 3-(2,6-difluorophenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid
72 3-(3-cyanophenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid
73 3-(2-chlorophenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid
74 3-(4-chlorophenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid
75 2-[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino][4-
(trifluoromethyl)phenyl]propanoic acid
76 3-(4-hydroxyphenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid
77 3-(3,4-difluorophenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid
78 3-(4-bromophenyl)[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]propanoic acid
79 2-[[4-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino][4-
(trifluoromethoxy)phenyl]propanoic acid
80 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-(4-methoxyphenyl)propanoic acid
81 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-(4-fluorophenyl)propanoic acid
82 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-(2,6-difluorophenyl)propanoic acid
83 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-(3-cyanophenyl)propanoic acid
84 3-(2-chlorophenyl)[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid
85 3-(4-chlorophenyl)[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid
86 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-[4-(trifluoromethyl)phenyl]propanoic acid
87 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-(4-hydroxyphenyl)propanoic acid
88 3-(4-bromophenyl)[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid
89 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-(3,4-difluorophenyl)propanoic acid
90 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-[4-(trifluoromethoxy)phenyl]propanoic acid
91 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-(4-methoxyphenyl)propanoic acid
92 3-(4-fluorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid
93 3-(2,6-difluorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-
isoxazolyl]benzoyl]amino]propanoic acid
94 3-(3-cyanophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid
95 3-(2-chlorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid
96 3-(4-chlorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid
97 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-[4-(trifluoromethyl)phenyl]propanoic acid
98 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-(4-hydroxyphenyl)propanoic acid
99 3-(3,4-difluorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-
isoxazolyl]benzoyl]amino]propanoic acid
100 3-(4-bromophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazol
yl]benzoyl]amino]propanoic acid
101 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]methyl-isoxazolyl]benzoyl]amino]-
3-[4-(trifluoromethoxy)phenyl]propanoic acid
102 2-[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino](4-
methoxyphenyl)propanoic acid
103 2-[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino](4-
fluorophenyl)propanoic acid
104 3-(2,6-difluorophenyl)[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]propanoic acid
105 3-(3-cyanophenyl)[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]propanoic acid
106 3-(2-chlorophenyl)[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]propanoic acid
107 3-(4-chlorophenyl)[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]propanoic acid
108 2-[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino][4-
(trifluoromethyl)phenyl]propanoic acid
109 2-[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino](4-
hydroxyphenyl)propanoic acid
110 3-(3,4-difluorophenyl)[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]propanoic acid
111 3-(4-bromophenyl)[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]propanoic acid
112 2-[[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino][4-
(trifluoromethoxy)phenyl]propanoic acid
113 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino](4-methoxyphenyl)propanoic acid
114 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino](4-fluorophenyl)propanoic acid
115 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino](2,6-difluorophenyl)propanoic acid
116 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino](3-cyanophenyl)propanoic acid
117 3-(2-chlorophenyl)[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-
pyrazolyl]benzoyl]amino]propanoic acid
118 3-(4-chlorophenyl)[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-
pyrazolyl]benzoyl]amino]propanoic acid
119 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino][4-(trifluoromethyl)phenyl]propanoic acid
120 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino](4-hydroxyphenyl)propanoic acid
121 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino](3,4-difluorophenyl)propanoic acid
122 3-(4-bromophenyl)[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-
pyrazolyl]benzoyl]amino]propanoic acid
123 2-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino][4-(trifluoromethoxy)phenyl]propanoic acid
124 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino](4-methoxyphenyl)propanoic acid
125 3-(4-fluorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol-
3-yl]benzoyl]amino]propanoic acid
126 3-(2,6-difluorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-
pyrazolyl]benzoyl]amino]propanoic acid
127 3-(3-cyanophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol-
3-yl]benzoyl]amino]propanoic acid
128 3-(2-chlorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol-
3-yl]benzoyl]amino]propanoic acid
129 3-(4-chlorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol-
3-yl]benzoyl]amino]propanoic acid
130 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino][4-(trifluoromethyl)phenyl]propanoic acid
131 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino](4-hydroxyphenyl)propanoic acid
132 3-(3,4-difluorophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-
pyrazolyl]benzoyl]amino]propanoic acid
133 3-(4-bromophenyl)[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-
pyrazolyl]benzoyl]amino]propanoic acid
134 2-[[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-1,5-dimethyl-pyrazol
yl]benzoyl]amino][4-(trifluoromethoxy)phenyl]propanoic acid
135 2-{p-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]benzoylamino}
phenylpropionic acid
136 2-(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}benzoylamino)
phenylpropionic acid
137 3-Cyclopropyl{p-[3-fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]benzoylamino}propionic acid
138 2-(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}benzoylamino)
cyclopropylpropionic acid
139 2-[({p-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methyl)amino]
phenylpropionic acid
140 2-{[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro
isoxazolyl}phenyl)methyl]amino}phenylpropionic acid
141 3-Cyclopropyl[({p-[3-fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methyl)amino]propionic acid
142 2-{[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro
isoxazolyl}phenyl)methyl]amino}cyclopropylpropionic acid
143 2-({p-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methoxy)
phenylpropionic acid
144 2-[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}phenyl)methoxy]-
3-phenylpropionic acid
145 3-Cyclopropyl({p-[3-fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methoxy)propionic acid
146 2-[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}phenyl)methoxy]-
3-cyclopropylpropionic acid
147 2-{p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]benzoylamino}
phenylpropionic acid
148 2-(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}benzoylamino)
phenylpropionic acid
149 2-{p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]benzoylamino}
cyclopropylpropionic acid
150 2-(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}benzoylamino)
cyclopropylpropionic acid
151 2-[({p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methyl)amino]
phenylpropionic acid
152 2-{[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano
isoxazolyl}phenyl)methyl]amino}phenylpropionic acid
153 2-[({p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methyl)amino]
cyclopropylpropionic acid
154 2-{[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano
isoxazolyl}phenyl)methyl]amino}cyclopropylpropionic acid
155 2-({p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methoxy)
phenylpropionic acid
156 2-[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}phenyl)methoxy]-
3-phenylpropionic acid
157 2-({p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methoxy)
cyclopropylpropionic acid
158 2-[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}phenyl)methoxy]-
3-cyclopropylpropionic acid
159 2-Benzyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
160 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}
pyridylamino)propionic acid
161 2-(Cyclopropylmethyl){5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
162 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)-
2-(cyclopropylmethyl)propionic acid
163 2-Benzyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
164 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}
pyridyloxy)propionic acid
165 2-(Cyclopropylmethyl){5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
166 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)
(cyclopropylmethyl)propionic acid
167 2-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
phenylpropionic acid
168 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)-
3-phenylpropionic acid
169 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)-
3-cyclopropylpropionic acid
170 2-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
phenylpropionic acid
171 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)
phenylpropionic acid
172 3-Cyclopropyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
173 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)
cyclopropylpropionic acid
174 2-Benzyl{5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
175 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}
pyridylamino)propionic acid
176 2-(Cyclopropylmethyl){5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
177 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridylamino)-
2-(cyclopropylmethyl)propionic acid
178 2-Benzyl{5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
179 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}
pyridyloxy)propionic acid
180 2-(Cyclopropylmethyl){5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
181 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridyloxy)
(cyclopropylmethyl)propionic acid
182 2-{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
phenylpropionic acid
183 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridylamino)-
3-phenylpropionic acid
184 3-Cyclopropyl{5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
185 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridylamino)-
3-cyclopropylpropionic acid
186 2-{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
phenylpropionic acid
187 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridyloxy)
phenylpropionic acid
188 3-Cyclopropyl{5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
189 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridyloxy)
cyclopropylpropionic acid
190 2-Benzyl{5-[3-cyano(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
191 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}
pyridylamino)propionic acid
192 3-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
(cyclopropylmethyl)propionic acid
193 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridylamino)-
2-(cyclopropylmethyl)propionic acid
194 2-Benzyl{5-[3-cyano(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
195 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}
pyridyloxy)propionic acid
196 3-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
(cyclopropylmethyl)propionic acid
197 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridyloxy)
(cyclopropylmethyl)propionic acid
198 2-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
phenylpropionic acid
199 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridylamino)-
3-phenylpropionic acid
200 2-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
cyclopropylpropionic acid
201 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridylamino)-
3-cyclopropylpropionic acid
202 2-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
phenylpropionic acid
203 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridyloxy)
phenylpropionic acid
204 2-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
cyclopropylpropionic acid
205 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridyloxy)
cyclopropylpropionic acid
206 2-{p-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]benzoylamino}
phenylpropionic acid
207 2-(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}benzoylamino)
phenylpropionic acid
208 3-Cyclopropyl{p-[3-fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]benzoylamino}propionic acid
209 2-(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}benzoylamino)
cyclopropylpropionic acid
210 2-[({p-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methyl)amino]
phenylpropionic acid
211 2-{[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro
isoxazolyl}phenyl)methyl]amino}phenylpropionic acid
212 3-Cyclopropyl[({p-[3-fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methyl)amino]propionic acid
213 2-{[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro
isoxazolyl}phenyl)methyl]amino}cyclopropylpropionic acid
214 2-({p-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methoxy)
phenylpropionic acid
215 2-[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}phenyl)methoxy]-
3-phenylpropionic acid
216 3-Cyclopropyl({p-[3-fluoro(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methoxy)propionic acid
217 2-[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}phenyl)methoxy]-
3-cyclopropylpropionic acid
218 2-{p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]benzoylamino}
phenylpropionic acid
219 2-(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}benzoylamino)
phenylpropionic acid
220 2-{p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]benzoylamino}
cyclopropylpropionic acid
221 2-(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}benzoylamino)
cyclopropylpropionic acid
222 2-[({p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methyl)amino]
phenylpropionic acid
223 2-{[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano
isoxazolyl}phenyl)methyl]amino}phenylpropionic acid
224 2-[({p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methyl)amino]
cyclopropylpropionic acid
225 2-{[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano
isoxazolyl}phenyl)methyl]amino}cyclopropylpropionic acid
226 2-({p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methoxy)
phenylpropionic acid
227 2-[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}phenyl)methoxy]-
3-phenylpropionic acid
228 2-({p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methoxy)
cyclopropylpropionic acid
229 2-[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}phenyl)methoxy]-
3-cyclopropylpropionic acid
230 2-Benzyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
231 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}
pyridylamino)propionic acid
232 2-(Cyclopropylmethyl){5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
233 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)-
2-(cyclopropylmethyl)propionic acid
234 2-Benzyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
235 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}
pyridyloxy)propionic acid
236 2-(Cyclopropylmethyl){5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
237 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)
(cyclopropylmethyl)propionic acid
238 2-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
phenylpropionic acid
239 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)-
3-phenylpropionic acid
240 3-Cyclopropyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
241 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridylamino)-
3-cyclopropylpropionic acid
242 2-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
phenylpropionic acid
243 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)
phenylpropionic acid
244 3-Cyclopropyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
245 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylisoxazolyl}pyridyloxy)
cyclopropylpropionic acid
246 2-Benzyl{5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
247 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}
pyridylamino)propionic acid
248 2-(Cyclopropylmethyl){5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
249 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridylamino)-
2-(cyclopropylmethyl)propionic acid
250 2-Benzyl{5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
251 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}
pyridyloxy)propionic acid
252 2-(Cyclopropylmethyl){5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
253 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridyloxy)
(cyclopropylmethyl)propionic acid
254 2-{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
phenylpropionic acid
255 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridylamino)-
3-phenylpropionic acid
256 3-Cyclopropyl{5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
257 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridylamino)-
3-cyclopropylpropionic acid
258 2-{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
phenylpropionic acid
259 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridyloxy)
phenylpropionic acid
260 3-Cyclopropyl{5-[3-fluoro(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
261 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoroisoxazolyl}pyridyloxy)
cyclopropylpropionic acid
262 2-Benzyl{5-[3-cyano(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}propionic acid
263 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}
pyridylamino)propionic acid
264 3-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
(cyclopropylmethyl)propionic acid
265 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridylamino)-
2-(cyclopropylmethyl)propionic acid
266 2-Benzyl{5-[3-cyano(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}propionic acid
267 2-Benzyl(5-{4-[1-(o-chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}
pyridyloxy)propionic acid
268 3-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
(cyclopropylmethyl)propionic acid
269 3-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridyloxy)
(cyclopropylmethyl)propionic acid
270 2-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
phenylpropionic acid
271 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridylamino)-
3-phenylpropionic acid
272 2-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
cyclopropylpropionic acid
273 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridylamino)-
3-cyclopropylpropionic acid
274 2-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
phenylpropionic acid
275 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridyloxy)
phenylpropionic acid
276 2-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
cyclopropylpropionic acid
277 2-(5-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyanoisoxazolyl}pyridyloxy)
cyclopropylpropionic acid
278 3-{p-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]benzoylamino}
phenylbutyric acid
279 4-Cyclopropyl{p-[3-methyl(1-phenylethoxycarbonylamino)
isoxazolyl]benzoylamino}butyric acid
280 3-[({p-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methyl)amino]
phenylbutyric acid
281 4-Cyclopropyl[({p-[3-methyl(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methyl)amino]butyric acid
282 3-({p-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}methoxy)
phenylbutyric acid
283 4-Cyclopropyl({p-[3-methyl(1-phenylethoxycarbonylamino)
isoxazolyl]phenyl}methoxy)butyric acid
284 3-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridylamino}
phenylbutyric acid
285 4-Cyclopropyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridylamino}butyric acid
286 3-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridyloxy}
phenylbutyric acid
287 4-Cyclopropyl{5-[3-methyl(1-phenylethoxycarbonylamino)isoxazolyl]
pyridyloxy}butyric acid
288 2-[4-[4-[4-cyano(1-phenylethoxycarbonylamino)pyrazolyl]phenyl]phenyl]acetic acid
289 1-[4-[4-[4-cyano(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]phenyl]cyclopropanecarboxylic acid
290 1-[4-[4-[5-[1-(2-chlorophenyl)ethoxycarbonylamino]cyano-pyrazol
yl]phenyl]phenyl]cyclopropanecarboxylic acid
291 2-[4-[4-[4-cyano(1-phenylethoxycarbonylamino)pyrazolyl]phenyl]phenyl]methyl-
propanoic acid
292 2-[4-[4-[5-[1-(2-chlorophenyl)ethoxycarbonylamino]cyano-pyrazolyl]phenyl]phenyl]-
2-methyl-propanoic acid
293 1-{4'-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
biphenylyl}cyclopropanecarboxylic acid
294 1-(4'-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}
biphenylyl)cyclopropanecarboxylic acid
295 1-{3-Fluoro-4'-[4-fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
biphenylyl}cyclopropanecarboxylic acid
296 1-(4'-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}fluoro
biphenylyl)cyclopropanecarboxylic acid
297 1-{2-Fluoro-4'-[4-fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
biphenylyl}cyclopropanecarboxylic acid
298 1-(4'-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}fluoro
biphenylyl)cyclopropanecarboxylic acid
299 1-{2-Chloro-4'-[4-fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
biphenylyl}cyclopropanecarboxylic acid
300 1-(2-Chloro-4'-{5-[1-(o-chlorophenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}
biphenylyl)cyclopropanecarboxylic acid
301 1-(4'-(4-fluoro(((1-phenylethoxy)carbonyl)amino)-1H-pyrazolyl)methyl-
[1,1'-biphenyl]yl)cyclopropanecarboxylic acid
302 1-(4'-(5-(((1-(2-chlorophenyl)ethoxy)carbonyl)amino)fluoro-1H-pyrazolyl)methyl-
[1,1'-biphenyl]yl)cyclopropanecarboxylic acid
303 1-(p-{5-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropanecarboxylic acid
304 1-[p-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]-1H-pyrazolyl}
pyridyl)phenyl]cyclopropanecarboxylic acid
305 1-(p-{5-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropanecarboxylic acid
306 1-[p-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]methyl-1H-pyrazolyl}
pyridyl)phenyl]cyclopropanecarboxylic acid
307 1-(2-Fluoro{5-[5-(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropanecarboxylic acid
308 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]-1H-pyrazolyl}pyridyl)
fluorophenyl]cyclopropanecarboxylic acid
309 1-(3-Fluoro{5-[5-(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropanecarboxylic acid
310 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]-1H-pyrazolyl}pyridyl)
fluorophenyl]cyclopropanecarboxylic acid
311 1-[p-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]methyl-1H-pyrazolyl}
pyridyl)phenyl]cyclopropanecarboxylic acid
312 1-(2-Fluoro{5-[4-methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropanecarboxylic acid
313 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]methyl-1H-pyrazolyl}pyridyl)-
2-fluorophenyl]cyclopropanecarboxylic acid
314 1-(3-Fluoro{5-[4-methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropanecarboxylic acid
315 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]methyl-1H-pyrazolyl}pyridyl)-
3-fluorophenyl]cyclopropanecarboxylic acid
316 1-(p-{5-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropanecarboxylic acid
317 1-[p-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}
pyridyl)phenyl]cyclopropanecarboxylic acid
318 1-(2-Fluoro{5-[4-fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropanecarboxylic acid
319 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}pyridyl)-
2-fluorophenyl]cyclopropanecarboxylic acid
320 1-(3-Fluoro{5-[4-fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropanecarboxylic acid
321 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]fluoro-1H-pyrazolyl}pyridyl)-
3-fluorophenyl]cyclopropanecarboxylic acid
322 1-(p-{5-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]
pyridyl}phenyl)cyclopropanecarboxylic acid
323 1-[p-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano-1H-pyrazolyl}
pyridyl)phenyl]cyclopropanecarboxylic acid
324 1-(4-{5-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
fluorophenyl)cyclopropanecarboxylic acid
325 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano-1H-pyrazolyl}pyridyl)-
2-fluorophenyl]cyclopropanecarboxylic acid
326 1-(4-{5-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
fluorophenyl)cyclopropanecarboxylic acid
327 1-[4-(5-{5-[1-(o-Chlorophenyl)ethoxycarbonylamino]cyano-1H-pyrazolyl}pyridyl)-
3-fluorophenyl]cyclopropanecarboxylic acid
328 2-{p-[1-Methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]benzoylamino}phenylpropionic acid
329 3-Cyclopropyl{p-[1-methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]benzoylamino}propionic acid
330 2-(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylmethyl-1H-pyrazol
yl}benzoylamino)phenylpropionic acid
331 2-(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylmethyl-1H-pyrazol
yl}benzoylamino)cyclopropylpropionic acid
332 2-[({p-[1-Methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]phenyl}methyl)amino]phenylpropionic acid
333 3-Cyclopropyl[({p-[1-methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]phenyl}methyl)amino]propionic acid
334 2-{[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylmethyl-1H-pyrazol
yl}phenyl)methyl]amino}phenylpropionic acid
335 2-{[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylmethyl-1H-pyrazol
yl}phenyl)methyl]amino}cyclopropylpropionic acid
336 2-({p-[1-Methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]phenyl}methoxy)phenylpropionic acid
337 3-Cyclopropyl({p-[1-methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]phenyl}methoxy)propionic acid
338 2-[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylmethyl-1H-pyrazol
yl}phenyl)methoxy]phenylpropionic acid
339 2-[(p-{4-[1-(o-Chlorophenyl)ethoxycarbonylamino]methylmethyl-1H-pyrazol
yl}phenyl)methoxy]cyclopropylpropionic acid
340 3-{p-[1-Methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]benzoylamino}phenylbutyric acid
341 4-Cyclopropyl{p-[1-methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]benzoylamino}butyric acid
342 3-[({p-[1-Methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]phenyl}methyl)amino]phenylbutyric acid
343 4-Cyclopropyl[({p-[1-methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]phenyl}methyl)amino]butyric acid
344 3-({p-[1-Methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]phenyl}methoxy)phenylbutyric acid
345 4-Cyclopropyl({p-[1-methylmethyl(1-phenylethoxycarbonylamino)-1H-pyrazol
yl]phenyl}methoxy)butyric acid
346 3-phenyl[[4-[5-(1-phenylethoxycarbonylamino)oxazolyl]benzoyl]amino]propanoic
acid
347 3-cyclopropyl[[4-[5-(1-phenylethoxycarbonylamino)oxazol
yl]benzoyl]amino]propanoic acid
348 4-phenyl[[4-[5-(1-phenylethoxycarbonylamino)oxazolyl]benzoyl]amino]butanoic acid
349 3-phenoxy[[4-[5-(1-phenylethoxycarbonylamino)oxazolyl]benzoyl]amino]propanoic
acid
350 3-Phenyl[({p-[5-(1-phenylethoxycarbonylamino)-1,3-oxazol
yl]phenyl}methyl)amino]propionic acid
351 3-Cyclopropyl[({p-[5-(1-phenylethoxycarbonylamino)-1,3-oxazol
yl]phenyl}methyl)amino]propionic acid
352 3-Phenyl({p-[5-(1-phenylethoxycarbonylamino)-1,3-oxazol
yl]phenyl}methoxy)propionic acid
353 4-Phenyl({p-[5-(1-phenylethoxycarbonylamino)-1,3-oxazolyl]phenyl}methoxy)butyric
acid
354 4-Cyclopropyl({p-[5-(1-phenylethoxycarbonylamino)-1,3-oxazol
yl]phenyl}methoxy)butyric acid
355 2-[[4-[1-methyl(1-phenylethoxycarbonylamino)imidazolyl]benzoyl]amino]phenyl-
propanoic acid
356 3-cyclopropyl[[4-[1-methyl(1-phenylethoxycarbonylamino)imidazol
yl]benzoyl]amino]propanoic acid
357 2-[[4-[1-methyl(1-phenylethoxycarbonylamino)imidazolyl]benzoyl]amino]phenyl-
butanoic acid
358 2-[[4-[1-methyl(1-phenylethoxycarbonylamino)imidazolyl]benzoyl]amino]phenoxy-
propanoic acid
359 2-[({p-[1-Methyl(1-phenylethoxycarbonylamino)-1H-imidazol
yl]phenyl}methyl)amino]phenylpropionic acid
360 3-Cyclopropyl[({p-[1-methyl(1-phenylethoxycarbonylamino)-1H-imidazol
yl]phenyl}methyl)amino]propionic acid
361 2-({p-[1-Methyl(1-phenylethoxycarbonylamino)-1H-imidazolyl]phenyl}methoxy)
phenylpropionic acid
362 3-Cyclopropyl({p-[1-methyl(1-phenylethoxycarbonylamino)-1H-imidazol
yl]phenyl}methoxy)propionic acid
363 3-[({p-[1-Methyl(1-phenylethoxycarbonylamino)-1H-imidazol
yl]phenyl}methyl)amino]phenylbutyric acid
364 4-Cyclopropyl[({p-[1-methyl(1-phenylethoxycarbonylamino)-1H-imidazol
yl]phenyl}methyl)amino]butyric acid
365 3-({p-[1-Methyl(1-phenylethoxycarbonylamino)-1H-imidazolyl]phenyl}methoxy)
phenylbutyric acid
366 4-Cyclopropyl({p-[1-methyl(1-phenylethoxycarbonylamino)-1H-imidazol
yl]phenyl}methoxy)butyric acid
367 2-[[4-[1,2-dimethyloxo(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]
phenyl-propanoic acid
368 3-cyclopropyl[[4-[1,2-dimethyloxo(1-phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]propanoic acid
369 2-[[4-[1,2-dimethyloxo(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]
phenyl-butanoic acid
370 2-[[4-[1,2-dimethyloxo(1-phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino]
phenoxy-propanoic acid
371 2-[({p-[1,2-Dimethyloxo(1-phenylethoxycarbonylamino)-1,2-dihydropyrazol
yl]phenyl}methyl)amino]phenylpropionic acid
372 3-Cyclopropyl[({p-[1,2-dimethyloxo(1-phenylethoxycarbonylamino)-1,2-
dihydropyrazolyl]phenyl}methyl)amino]propionic acid
373 2-({p-[1,2-Dimethyloxo(1-phenylethoxycarbonylamino)-1,2-dihydropyrazol
yl]phenyl}methoxy)phenylpropionic acid
374 3-Cyclopropyl({p-[1,2-dimethyloxo(1-phenylethoxycarbonylamino)-1,2-
dihydropyrazolyl]phenyl}methoxy)propionic acid
375 3-[({p-[1,2-Dimethyloxo(1-phenylethoxycarbonylamino)-1,2-dihydropyrazol
yl]phenyl}methyl)amino]phenylbutyric acid
376 4-Cyclopropyl[({p-[1,2-dimethyloxo(1-phenylethoxycarbonylamino)-1,2-
dihydropyrazolyl]phenyl}methyl)amino]butyric acid
377 3-({p-[1,2-Dimethyloxo(1-phenylethoxycarbonylamino)-1,2-dihydropyrazol
yl]phenyl}methoxy)phenylbutyric acid
378 4-Cyclopropyl({p-[1,2-dimethyloxo(1-phenylethoxycarbonylamino)-1,2-
dihydropyrazolyl]phenyl}methoxy)butyric acid
379 3-phenyl[[4-[5-(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]propanoic
acid
380 3-cyclopropyl[[4-[5-(1-phenylethoxycarbonylamino)pyrimidin
yl]benzoyl]amino]propanoic acid
381 4-phenyl[[4-[5-(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]butanoic
acid
382 3-phenoxy[[4-[5-(1-phenylethoxycarbonylamino)pyrimidin
yl]benzoyl]amino]propanoic acid
383 3-Phenyl[({p-[5-(1-phenylethoxycarbonylamino)
pyrimidinyl]phenyl}methyl)amino]propionic acid
384 3-Cyclopropyl[({p-[5-(1-phenylethoxycarbonylamino)
pyrimidinyl]phenyl}methyl)amino]propionic acid
385 3-Phenyl({p-[5-(1-phenylethoxycarbonylamino)pyrimidinyl]phenyl}methoxy)propionic
acid
386 3-Cyclopropyl({p-[5-(1-phenylethoxycarbonylamino)
pyrimidinyl]phenyl}methoxy)propionic acid
387 4-Phenyl[({p-[5-(1-phenylethoxycarbonylamino)
pyrimidinyl]phenyl}methyl)amino]butyric acid
388 4-Cyclopropyl[({p-[5-(1-phenylethoxycarbonylamino)
pyrimidinyl]phenyl}methyl)amino]butyric acid
389 4-Phenyl({p-[5-(1-phenylethoxycarbonylamino)pyrimidinyl]phenyl}methoxy)butyric
acid
390 4-Cyclopropyl({p-[5-(1-phenylethoxycarbonylamino)
pyrimidinyl]phenyl}methoxy)butyric acid
391 2-[[4-[6-methyl(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]phenyl-
propanoic acid
392 3-cyclopropyl[[4-[6-methyl(1-phenylethoxycarbonylamino)pyrimidin
yl]benzoyl]amino]propanoic acid
393 2-[[4-[6-methyl(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]phenyl-
butanoic acid
394 2-[[4-[6-methyl(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]
phenoxy-propanoic acid
395 3-phenyl[[4-[4-(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]propanoic
acid
396 3-cyclopropyl[[4-[4-(1-phenylethoxycarbonylamino)pyrimidin
yl]benzoyl]amino]propanoic acid
397 4-phenyl[[4-[4-(1-phenylethoxycarbonylamino)pyrimidinyl]benzoyl]amino]butanoic
acid
398 3-phenoxy[[4-[4-(1-phenylethoxycarbonylamino)pyrimidin
yl]benzoyl]amino]propanoic acid
399 3-phenyl[[4-[3-(1-phenylethoxycarbonylamino)pyrazinyl]benzoyl]amino]propanoic
acid
400 3-cyclopropyl[[4-[3-(1-phenylethoxycarbonylamino)pyrazin
yl]benzoyl]amino]propanoic acid
401 4-phenyl[[4-[3-(1-phenylethoxycarbonylamino)pyrazinyl]benzoyl]amino]butanoic
acid
402 3-phenoxy[[4-[3-(1-phenylethoxycarbonylamino)pyrazinyl]benzoyl]amino]propanoic
acid
403 1-{p-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidinecarboxylic acid
404 (1-{p-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}piperidyl)acetic
acid
405 1-(1-{p-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidyl)cyclopropanecarboxylic acid
406 [1-(1-{p-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidyl)cyclopropyl]acetic acid
407 1-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidinecarboxylic acid
408 (1-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)acetic acid
409 1-(1-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid
410 [1-(1-{5-[3-Methyl(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)cyclopropyl]acetic acid
411 1-{p-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidinecarboxylic acid
412 (1-{p-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}piperidyl)acetic
acid
413 1-(1-{p-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidyl)cyclopropanecarboxylic acid
414 [1-(1-{p-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidyl)cyclopropyl]acetic acid
415 1-{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidinecarboxylic acid
416 (1-{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)acetic acid
417 1-(1-{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid
418 [1-(1-{5-[3-Fluoro(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)cyclopropyl]acetic acid
419 1-{p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidinecarboxylic acid
420 (1-{p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}piperidyl)acetic
acid
421 1-(1-{p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidyl)cyclopropanecarboxylic acid
422 [1-(1-{p-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]phenyl}
piperidyl)cyclopropyl]acetic acid
423 1-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidinecarboxylic acid
424 (1-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)acetic acid
425 1-(1-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid
426 [1-(1-{5-[3-Cyano(1-phenylethoxycarbonylamino)isoxazolyl]pyridyl}
piperidyl)cyclopropyl]acetic acid
427 1-{p-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}piperidinecarboxylic
acid
428 (1-{p-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}piperidyl)acetic acid
429 1-(1-{p-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)cyclopropanecarboxylic acid
430 [1-(1-{p-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)cyclopropyl]acetic acid
431 1-{5-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}piperidinecarboxylic
acid
432 (1-{5-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}piperidyl)acetic acid
433 1-(1-{5-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid
434 [1-(1-{5-[5-(1-Phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropyl]acetic acid
435 1-{p-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidinecarboxylic acid
436 (1-{p-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)acetic acid
437 1-(1-{p-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)cyclopropanecarboxylic acid
438 [1-(1-{p-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)cyclopropyl]acetic acid
439 1-{5-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidinecarboxylic acid
440 (1-{5-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)acetic acid
441 1-(1-{5-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid
442 [1-(1-{5-[4-Methyl(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropyl]acetic acid
443 1-{p-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidinecarboxylic acid
444 (1-{p-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)acetic acid
445 1-(1-{p-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)cyclopropanecarboxylic acid
446 [1-(1-{p-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)cyclopropyl]acetic acid
447 1-{5-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidinecarboxylic acid
448 (1-{5-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)acetic acid
449 1-(1-{5-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid
450 [1-(1-{5-[4-Fluoro(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropyl]acetic acid
451 1-{p-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidinecarboxylic acid
452 (1-{p-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)acetic acid
453 1-(1-{p-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)cyclopropanecarboxylic acid
454 [1-(1-{p-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]phenyl}
piperidyl)cyclopropyl]acetic acid
455 1-{5-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidinecarboxylic acid
456 (1-{5-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)acetic acid
457 1-(1-{5-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropanecarboxylic acid
458 [1-(1-{5-[4-Cyano(1-phenylethoxycarbonylamino)-1H-pyrazolyl]pyridyl}
piperidyl)cyclopropyl]acetic acid
EXAMPLES
HPLC Methods
[641] HPLC traces for examples synthesized were recorded using a HPLC consisting
of Shimadzu HPLC pumps, degasser and UV detector, equipped with an Agilent 1100
series auto-sampler. A MS detector (APCI) PE Sciex API 150 EX was incorporated for
purposes of recording mass spectral data. HPLC/mass traces were obtained using one
of three chromatographic methods:
[642] Method 1: Column Zorbax C18, size 4.6 mm X 7.5 cm; Solvent A: 0.05 % TFA
in water, Solvent B: 0.05 % TFA in acetonitrile; Flow rate – 0.7 mL/min; Gradient: 5 % B
to 100 % B in 9 min, hold at 100 % B for 4 min and 100 % B to 5 % B in 0.5 min; UV
detector – channel 1 = 220 nm, channel 2 = 254 nm.
Method 2: Column Zorbax C18, size 4.6 mm X 7.5 cm;
Solvent A: 0.05 % TFA in water, Solvent B: 0.05 % TFA in acetonitrile;
Flow rate – 0.7 mL/min; Gradient: 5 % B to 100 % B in 5 min, hold at 100 % B for 2 min
and 100 % B to 5 % B in 0.5 min; UV detector – channel 1 = 220 nm, channel 2 = 254
Method 3: Column SunFire (Waters) C18, size 2.1 mm X 50 mm;
Solvent A: 0.05 % TFA in water, Solvent B: 0.05 % TFA in acetonitrile;
Flow rate – 0.8 mL/min; Gradient: 10 % B to 90 % B in 2.4 min, hold at 90 % B for 1.25
min and 90 % B to 10 % B in 0.25 min, hold at 10 % B for 1.5 min.; UV detector –
channel 1 = 220 nm, channel 2 = 254 nm.
Example 1: 1-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)-cyclopropanecarboxylic acid
Step 1: 2-(4-carboxymethyl-benzoyl)oxo-butyric acid t-butyl ester
t-Butyl acetoacetate (15.1mL, 89.0 mmol) was added to a suspension of magnesium
chloride (8.48g, 89.0 mmol) in dichloromethane (88mL) that had been cooled to 0 C. To
the mixture was added pyridine (13.8mL, 171mmol) and stirring continued for an
additional 15 minutes. 4-(Chlorocarbonyl)benzoic acid methyl ester (17.0g, 85.6 mmol)
in dichloromethane (88mL) was then added dropwise to the reaction. This mixture was
stirred at 0 C for 90minutes and then at room temperature for 90 minutes. At this time
the mixture was treated with 0.2M hydrochloric acid solution (10mL). The organic layer
was diluted with dichloromethane (70mL), washed with 0,2M hydrochloric acid solution
(30mL), separated, dried over anhydrous Na SO , filtered and concentrated in vacuo. A
yellow oil was obtained that was used directly in the next step (17.1g, 68%).
Method 2, Rt 5.4 min. MS (ESI) m/z 321.2 [M + H ].
Step 2: 5-(4-Methoxycarbonyl-phenyl)methyl-isoxazolecarboxylic acid tert-
butyl ester
5-(4-methylcarboxy-phenyl)methyl-isoxazolyl-carboxylic acid t-butyl ester
A mixture of 2-(4-carboxymethyl-benzoyl)oxo-butyric acid t-butyl ester [example 1,
step 1] (7.45g, 23.2 mmol), hydroxylamine hydrochloride (5.17g, 74.4 mmol), ethanol
(46.5mL) and water (32.2mL) was heated at 60-62 C for 2 hours. At this point the
reaction was allowed to cool and the resulting mixture was partitioned between ethyl
acetate and water. The organic layer was dried over anhydrous MgSO , filtered and
concentrated in vacuo. A crude product was obtained that was purified by silica gel
chromatography initially with hexane/ethyl acetate 9/1 as eluting solvent to afford 5-(4-
Methoxycarbonyl-phenyl)methyl-isoxazolecarboxylic acid tert-butyl ester (4.69g,
64%)
Method 2, Rt 6.14 min. MS (ESI) m/z 318.2 [M + H ].
[649] Step 3: 5-(4-Methoxycarbonyl-phenyl)methyl-isoxazolecarboxylic acid5-(4-
Methoxycarbonyl-phenyl)methyl-isoxazolecarboxylic acid tert-butyl ester [Example
1, step 2] (6.35g mg, 20 mmol) was dissolved in dichloromethane (100 mL) and to this
was added trifluoroacetic acid (50mL). The mixture was stirred for 2 hours at room
temperature when the volatiles were removed. The product (5.2g, 99 %) was used as is
in Step 4.
Method 2, Rt 4.08 min. MS (ESI) m/z 262 [M + H ];
Step 4: 1-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol
yl}-benzoic acid methyl ester
5-(4-methylcarboxy-phenyl)methyl-isoxazolyl-carboxylic acid
[Example 1, step 3] (3.91g, 15.0 mmol) was suspended in toluene (120 mL) and to this
was added diisopropylethylamine (3.13mL, 18.0mmol). To the resulting solution was
added diphenylphosphoryl azide (3.56mL, 16.5mmol) and this mixture was heated to
90 C. After 15 minutes, 1-(2-chlorophenyl)-ethanol (2.98mL, 22.5mmol) was added
slowly and heating maintained for 4 hours. The reaction was allowed to cool overnight.
This mixture was diluted with toluene, transferred to a separatory funnel, extracted with
water. The organic layer was dried over anhydrous MgSO , filtered and concentrated in
vacuo to yield a crude product (8.34g). The crude was purified by silica gel
chromatography eluting with a gradient from 30% to 40% ethyl acetate in hexanes to
afford purified product (3.59g, 58%) as three fractions. Method 2, Rt 5.70 min. MS (ESI)
m/z 415.4 [M + H ].
Step 5: 1-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol
yl}-benzoic acid
1-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoic acid methyl ester [Example 1, step 4] (1.5g, 3.62 mmol) was dissolved in
THF/water (1/1: 20mL) and treated with LiOH (5.1mL of a 1M aqueous solution). The
resulting mixture was stirred at room temperature for 3 hours. The reaction was acidified
to pH2, transferred to a separatory funnel, diluted with water and extracted with
dichloromethane. The organic layer was dried over anhydrous MgSO , filtered and
concentrated in vacuo to afford the product (0.8g, 55%). Method 2, Rt 4.77 min. MS
(ESI) m/z 401.3 [M + H ].
Step 6: 1-Aminocyclopropanecarboxylic acid methyl ester
1-Aminocyclopropanecarboxylic acid (202mg, 2mmol) in methanol (4mL) was cooled to
-10 C and to this was added dropwise thionyl chloride (581µL, 8mmol). The mixture was
allowed to warm and was then refluxed for 2 hours. Solvents were evaporated and the
residue redissolved in boiling alcohol. To the cooled solution was added diethyl ether to
the point of turbidity when the mixture was refridgerated for 2 days. The resulting
precipitates afford the product (223mg, 67%) that was used in Step 7.
Step 7: 1-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol
yl}-benzoylamino)-cyclopropanecarboxylic acid methyl ester
To 1-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoic acid [Example 1, step 5] (49.8mg, 0.12 mmol) was added 1-
hydroxybenzotriazole (18mg, 0.13mmol), N-(3-dimethylaminopropyl)-ethylcarbodiimide
(EDCI: 25mg, 0.13 mmol), dichloromethane (2 mL), diisopropylethylamine (52µL, 0.30
mmol), and 1-Aminocyclo-propanecarboxylic acid methyl ester [example 1, step 6](20
mg, 0.13 mmol) and this mixture was stirred overnight. At this point the mixture was
diluted with ethyl acetate (20 mL) and washed with saturated sodium bicarbonate
solution (10 mL), citric acid solution (5 mL) and water. The organic layer was dried over
anhydrous MgSO , filtered and concentrated in vacuo to yield a crude product (101mg).
The residue was purified by preparative TLC, eluting with a 40% mixture of ethyl acetate
in hexane v/v. Following extraction of the purified band, the product was obtained (55
mg, 92%). Method 2, Rt 4.76 min. MS (ESI) m/z 498.4 [M + H ].
[657] Step 8: 1-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol
yl}-benzoylamino)-cyclopropanecarboxylic acid
1-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)-cyclopropanecarboxylic acid methyl ester [example 1, step 7](55mg,
0.11mmol) was dissolved in a 1:1 mixture of THF/water and treated with lithium
hydroxide (8mg, 0.33mmol). The resulting mixture was stirred at room temperature for 2
days. At this point the pH was adjusted to 2 with hydrochloric acid and the mixture was
extracted with ethyl acetate (3x20mL). The organic layer was dried over anhydrous
MgSO , filtered and concentrated in vacuo to yield a crude product (190mg). The
residue was purified by preparative TLC, eluting with a 45% mixture of acetone in
dichloromethane v/v. Following extraction of the purified band, the product was obtained
(22 mg, 41%).
Method 2, Rt 4.30 min. MS (ESI) m/z 484.6 [M + H ].
Example 2: 2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)-indancarboxylic acid
Step 1: 2-Aminoindancarboxylic acid methyl ester
2-Aminoindancarboxylic acid methyl ester was prepared according to a similar
procedure as described for example 1, step 6 from 2-Aminoindancarboxylic acid
hydrochloride (214mg, 1mmol) that was used directly. Yield 155mg (68%)
Step 2: 2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol
yl}-benzoylamino)-indancarboxylic acid methyl ester
2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)-indancarboxylic acid methyl ester was prepared according to a similar
procedure as described for example 1, step 7 from 1-(4-{4-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoic acid [Example 1, step 5] (49.8mg,
0.12 mmol) and 2-aminoindancarboxylic acid methyl ester [example 2, step 1]. Yield
55 mg, (81%). Method 2, Rt 5.49 min. MS (ESI) m/z 574.6 [M + H ].
[662] Step 3: 2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol
yl}-benzoylamino)-indancarboxylic acid
2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-
benzoylamino)-indancarboxylic acid was prepared according to a similar procedure
as described for example 1, step 8 from 2-(4-{4-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-indancarboxylic acid
methyl ester [example 2, step 7](55mg, 0.11mmol).Yield 6 mg, (11%). Method 2, Rt 5.00
min. MS (ESI) m/z 560.3[M + H ].
Example 3 : 2-(S)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino) phenyl acetic acid
[664] Step 1: L-phenylglycine methyl ester was prepared according to a similar
procedure as described for example 1, step 6 from L-phenylglycine (756mg, 5mmol) that
was used directly. Yield 480mg (58%).
Step 2: 2-(S)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino) phenyl acetic acid methyl ester
[666] 2-(S)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol-
-yl}-benzoylamino) phenyl acetic acid methyl ester was prepared according to a similar
procedure as described for example 1, step 7 from 1-(4-{4-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoic acid [Example 1, step 5](
(58.1mg, 0.14 mmol) and L-phenylglycine methyl ester [Example 3, step 1] which was
used without purification. Yield 60mg (76%) Method 2, Rt 5.41 min. MS (ESI) m/z 548.6
[M + H ].
[667] Step 3: 2-(S)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino) phenyl acetic acid
2-(S)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol-
-yl}-benzoylamino) phenyl acetic acid was prepared according to a similar procedure
as described for example 1, step 8 from 2-(S)-(4-{4-[(R,S)(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino) phenyl acetic acid methyl
ester [example 3, step 2](60mg, 0.11 mmol).Yield 4 mg (11%). Method 2, Rt 4.90 min.
MS (ESI) m/z 534.4 [M + H ].
Example 4 : 2-(R)- (4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino) phenyl propanoic acid
[670] Step 1: D-phenylalanine methyl ester
D-phenylalanine methyl ester was prepared according to a similar procedure as
described for example 1, step 6 from D-phenylalanine (1.12g, 7mmol). Yield 650mg
(53%).
Step 2: 2-(R)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino) phenyl propanoic acid methyl ester
2-(R)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol-
-yl}-benzoylamino) phenyl propanoic acid methyl ester was prepared according to a
similar procedure as described for example 1, step 7 from 1-(4-{4-[1-(2-Chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoic acid [Example 1, step 5] (58.1mg,
0.14 mmol) and D-phenylalanine methyl ester [example 4, step 1] to yield the product
(40mg, 49%) which was used directly. Method 2, Rt 5.6 min. MS (ESI) m/z 562.2 [M +
H ].
Step 3: 2-(R)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino) phenyl propanoic acid
[675] 2-(R)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol-
-yl}-benzoylamino) phenyl propanoic acid was prepared according to a similar
procedure as described for example 1, step 8 from 2-(R)-(4-{4-[(R,S)(2-Chloro-
phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino) phenyl propanoic
acid methyl ester [example 4, step 2](40mg, 0.07mmol). Yield 8mg (21%).Method 2, Rt
4.94 min. MS (ESI) m/z 548.5 [M + H ].
Example 5 - 2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]phenyl-propanoic acid
Step 1: 2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol
yl]benzoic acid methyl ester
2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazolyl]benzoic
acid methyl ester was prepared according to a similar procedure as described for
example 1, step 4 from 5-(4-Methoxycarbonyl-phenyl)methyl-isoxazolecarboxylic
acid [Example 1, step 3] (1.55g, 5.9 mmol) and 1-(R)-(+)-phenyl-ethanol. Yield 1.18g
(52%).
Step 2: 2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol
yl]benzoic acid
[680] 2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazolyl]benzoic
acid was prepared according to a similar procedure as described for example 1, step 5
from 2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazolyl]benzoic acid
methyl ester [Example 5, step 1] (1.5g, 3.62 mmol). Yield 1.04g, (91%). Method 3, Rt
2.72 min. MS (ESI) m/z 367.3 [M + H ].
[681] Step 3: 2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]phenyl-propanoic acid methyl ester
2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]phenyl-propanoic acid methyl ester was prepared according to a
similar procedure as described for example 1, step 7 from 2(R)-[[4-[3-methyl((R)
phenylethoxycarbonylamino)isoxazolyl]benzoic acid [Example 5, step 2] (64,7mg,
0.18 mmol) and D-phenylalanine methyl ester [example 4, step 1]. Yield 100 mg, 92%).
Method 3, Rt 3.04 min. MS (ESI) m/z 528.3 [M + H ].
Step 4: 2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]phenyl-propanoic acid (sodium salt)
[684] 2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]phenyl-propanoic acid was prepared according to a similar
procedure as described for example 1, step 8 from 2(R)-[[4-[3-methyl((R)
phenylethoxycarbonylamino)isoxazolyl]benzoyl]amino]phenyl-propanoic acid
methyl ester [example 5, step 3](100mg, 0.19mmol). The crude material (21mg) was
dissolved in methanol and treated with 1N sodium hydroxide (40µL) before drying to
afford the product as its sodium salt (22 mg, 22%). Method 3, Rt 3.04 min. MS (ESI) m/z
514.3 [M + H ].
Example 6: 2(S)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol
yl]benzoyl]amino]phenyl-propanoic acid
[686] The title compound was prepared according to an analagous procedure to that
described for example 5 from 5-(4-Methoxycarbonyl-phenyl)methyl-isoxazole
carboxylic acid [Example 1, step 3] (64.7mg, 0.18mmol) and L-phenylalanine methyl
ester to afford the product as its sodium salt (18mg, 18%).Method 3 Rt 3.05 min. MS
(ESI) m/z 514.3 [M + H ].
Example 7: (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol-
3-yl]benzoyl]amino]phenyl-propanoic acid
[688] Step 1: 5-(4-Methoxycarbonyl-phenyl)-1,3-dimethyl-1H-pyrazolecarboxylic
acid tert-butyl ester and 3-(4-Methoxycarbonyl-phenyl)-1,5-dimethyl-1H-pyrazole
carboxylic acid tert-butyl ester:
4-(2-tert-Butoxycarbonyloxo-butyryl)-benzoic acid methyl ester [Example 1,
Step 1] (crude 76.0 g, 208.8 mmol on 100% purity basis) was dissolved in ethanol (2.2
L). Methyl hydrazine (9.72 g, 210.9 mmol) was added to the above solution dropwise
under stirring at room temperature. The reaction mixture was stirred another 3 hrs at RT
after finishing the addition. The completion of reaction was confirmed by LC/MS. The
solvent was removed under vacuum. The residue was dissolved in EtOAc (700 mL) and
washed with water (2 X 500 mL). The organics were dried over Na SO , filtered and
evaporated. Mixture of products obtained as an oil, which was used in the next step
without further purification. Crude yield 72.6 g. Method 3, Rt 3.12 min. MS (ESI) m/z
331.0 [M + H ].
Step 2: 5-(4-Methoxycarbonyl-phenyl)-1,3-dimethyl-1H-pyrazolecarboxylic
acid and 3-(4-Methoxycarbonyl-phenyl)-1,5-dimethyl-1H-pyrazolecarboxylic acid:
[691] A mixture of 5-(4-Methoxycarbonyl-phenyl)-1,3-dimethyl-1H-pyrazole
carboxylic acid tert-butyl ester and 3-(4-Methoxycarbonyl-phenyl)-1,5-dimethyl-1H-
pyrazolecarboxylic acid tert-butyl ester [Example 7, Step 1] (5.00 g., 15.13 mmol) was
dissolved into CH2Cl2 (120.0 mL) and trifluoroacetic acid (40.0 mL) was added and the
reaction mixture was stirred for 3 h at room temperature. The volatiles were removed
under vacuum. The residue was dissolved into ethyl acetate (50.0 mL). It was then
extracted with saturated aq. Na CO solution (40 mL). Separated aqueous layer was
washed with ethyl acetate (2x20 mL). Then it was treated with 1 M HCl to pH 2. Then it
was extracted with ethyl acetate (2x35 mL), dried (Na SO ), filtered and concentrated to
yield white solid mixture of acids (3.0 g., 72%). TLC on silica plate (15% acetone in
DCM): two fluorescent spots of two isomers Rf: 0.2 and Rf: 0.125. Method 3, Rt 2.94
min. MS (ESI) m/z 275.0 [M + H ];
Step 3: 4-[2,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-2H-pyrazolyl]-
benzoic acid methyl ester and 4-[1,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-
1H-pyrazolyl]-benzoic acid methyl ester:
[693] The mixture of acid isomers [Example 7, Step 2] (6.0 g., 21.88 mmol), was
suspended in anhydrous toluene (180.0 mL), under nitrogen and stirring. Then
diisopropylethyl amine (3.39 g., 26.24 mmol) was added. A clear solution was generated
to which diphenyl phosphoryl azide 7.22 g, 26.24 mmol) was added. The reaction
mixture was heated to 95 C. Then (R)-(+)phenylethyl alcohol (4.008 g, 32.8 mmol)
was added dropwise at 95 C over a period of 40 minutes. Then the reaction mixture
was heated for an additional 5 hr at 95 C, followed by stirring at room temperature
overnight. Next day it was diluted with EtOAc (300 mL), washed with sat. aq. Na CO
solution (200.0 mL) and water (2x500 mL), dried (Na SO ), filtered and concentrated to
yield crude oily carbamate (12.5 g). The crude was purified by column chromatography
(SiO ), initial elution with DCM (250 mL) and then gradient elution Acetone:DCM (2%
acetone in DCM to 10% acetone in DCM). Two pure isomers were obtained. Fast
moving isomer (1.667 g, 19.4%) and slow moving isomer (2.132 g, 24.77%) were
obtained [> 95% by HPLC purity]. A fraction containing a mixture of isomers (0.812 g,
9.4%) was obtained. A) Slow moving spot: Method 3, Rt 2.78 min. MS (ESI) m/z 394.2
[M + H ]; tentatively assigned as (R)- 4-[1,5-Dimethyl(1-phenyl-
ethoxycarbonylamino)-1H-pyrazolyl]-benzoic acid methyl ester.B) Fast moving spot:
Method 3, Rt 2.80 min. MS (ESI) m/z 394.4 [M + H ]; tentatively assigned as (R)- 4-[2,5-
Dimethyl((R)phenyl-ethoxycarbonylamino)-2H-pyrazolyl]-benzoic acid methyl
ester.
Step 4: 4-[2,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-2H-pyrazolyl]-
benzoic acid:
[695] 4-[2,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-2H-pyrazolyl]-benzoic
acid methyl ester [Example 7, Step 3B] (240 mg, 0.61 mmol) was dissolved in
THF/water (2/1 v/v, 2.25 mL) and treated with LiOH (1.2 mL of a 1M aqueous solution, 2
eq.). The resulting mixture was stirred at room temperature overnight. The reaction was
acidified to pH2, diluted with water and extracted with EtOAc (2 X 40 mL). The organic
layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo to afford the
product (180 mg, 78%). Method 3, Rt 2.81 min. MS (ESI) m/z 380.2 [M + H ].
Step 5: (R)- 2-{4-[2,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-2H-
pyrazolyl]-benzoylamino}phenyl-propionic acid methyl ester:
To 4-[2,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-2H-pyrazolyl]-benzoic acid
[Example 7, step 4] (100 mg, 0.26 mmol) was added 1-hydroxybenzotriazole (43 mg,
0.32 mmol), EDCI (67 mg, 0.34 mmol), dimethylformamide (2 mL),
diisopropylethylamine (184 µL, 1.06 mmol), and D-phenylalanine methyl ester [Example
4, Step 1] (86 mg, 0.39 mmol) and this mixture was stirred overnight. At this point the
mixture was diluted with ethyl acetate (20 mL) and washed with 1N sodium hydroxide
solution (10mL), and water. The organic layer was dried over anhydrous MgSO , filtered
and concentrated in vacuo to yield the crude product (193 mg), which was purified by
silica gel chromatography, eluting with an ethyl acetate/dichloromethane gradient to
provide the title compound (95 mg, 68%). > 95% by HPLC purity. Method 3, Rt 2.91
min. MS (ESI) m/z 541.3 [M + H ].
Step 6: (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]phenyl-propanoic acid:
[698] (R)- 2-{4-[2,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-2H-pyrazolyl]-
benzoylamino}phenyl-propionic acid methyl ester [Example 7, step 5] (95 mg, 0.176
mmol) was dissolved in a 2:1 mixture of THF/water (2.25 mL) and treated with 1M
lithium hydroxide solution (2 mL). The resulting mixture was stirred at room temperature
overnight. The pH of the aqueous layer was adjusted to 2 with hydrochloric acid and the
mixture was extracted with ethyl acetate (3x20mL). The organic layer was dried over
anhydrous MgSO , filtered and concentrated in vacuo to yield the crude product (112
mg). The crude material was purified by silica-gel chromatography, eluting with a
dichloromethane/acetone gradient. (90 mg, 97%). Method 3, Rt 2.90 min. MS (ESI) m/z
527.5 [M + H ].
[699] Example 8: (R)[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol-
3-yl]benzoyl]amino]phenyl-propanoic acid
Step 1: 4-[1,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-1H-pyrazolyl]-
benzoic acid:
4-[1,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-1H-pyrazolyl]-benzoic
acid methyl ester [Example 7, Step 3A] (240 mg, 0.61 mmol) was dissolved in
THF/water (2/1 v/v, 2.25 mL) and treated with LiOH (1.2 mL of a 1M aqueous solution, 2
eq.). The resulting mixture was stirred at room temperature overnight. The reaction was
acidified to pH2, transferred to a separatory funnel, diluted with water and extracted with
EtOAc (2 X 40 mL). The organic layer was dried over anhydrous MgSO , filtered and
concentrated in vacuo to afford the product (205 mg, 89%). Purity is 97% by HPLC.
Method 3, Rt 2.43 min. MS (ESI) m/z 380.2 [M + H ].
Step 2: (R)- 2-{4-[1,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-1H-
pyrazolyl]-benzoylamino}phenyl-propionic acid methyl ester:
4-[1,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-1H-pyrazolyl]-benzoic
acid [Example 8, Step 1] (100 mg, 0.26 mmol) was added 1-hydroxybenzotriazole (43
mg, 0.32 mmol), EDCI (67 mg, 0.34 mmol), dimethylformamide (2 mL),
diisopropylethylamine (184 µL, 1.06 mmol), and D-phenylalanine methyl ester [Example
4, Step 1] (86 mg, 0.39 mmol) and this mixture was stirred overnight. At this point the
mixture was diluted with ethyl acetate (20 mL) and washed with 1N sodium hydroxide
solution (10mL), and water. The organic layer was dried over anhydrous MgSO , filtered
and concentrated in vacuo to yield the crude product (150 mg) which was purified by
silica gel chromatography, eluting with a ethyl acetate/dichloromethane gradient to
provide the product (75 mg, 53%). Purity > 97% by HPLC. Method 3, Rt 3.05 min. MS
(ESI) m/z 541.2 [M + H ].
Step 3: (R)[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino]phenyl-propanoic acid:
[705] (R)- 2-{4-[1,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-1H-pyrazolyl]-
benzoylamino}phenyl-propionic acid methyl ester [Example 8, step 2] (75 mg, 0.139
mmol) was dissolved in a 2:1 mixture of THF/water (1.5 mL) and treated with 1M lithium
hydroxide solution (0.28 mL). The resulting mixture was stirred at room temperature
overnight. The pH of the aqueous layer was adjusted to 2 with hydrochloric acid and the
mixture was extracted with ethyl acetate (3x20mL). The organic layer was dried over
anhydrous MgSO , filtered and concentrated in vacuo to yield the product [>95% HPLC
purity] (60 mg, 82%). Method 3, Rt 2.69 min. MS (ESI) m/z 527.5 [M + H ].
Example 9: (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol-
3-yl]benzoyl]amino](4-fluorophenyl)propanoic acid
[707] Step 1: (R)Amino(4-fluoro-phenyl)-propionic acid methyl ester
hydrochloride:
(R)Amino(4-fluoro-phenyl)-propionic acid methyl ester hydrochloride was
prepared according to a similar procedure as described for example 1, step 6 from D
Fluorophenyl alanine (1 g, 5.46 mmol). Yield 900 mg, (71 %). Method 3, Rt 0.54 min.
MS (ESI) m/z 198.3 [M + H ].
Step 2: (R)- 2-{4-[2,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-2H-
pyrazolyl]-benzoylamino}(4-fluoro-phenyl)-propionic acid methyl ester:
(R)- 2-{4-[2,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-2H-pyrazolyl]-
benzoylamino}(4-fluoro-phenyl)-propionic acid methyl ester was prepared according
to a similar procedure as described for example 7, step 5 from (R)- 4-[2,5-Dimethyl(1-
phenyl-ethoxycarbonylamino)-2H-pyrazolyl]-benzoic acid [Example 7, Step 4] (50 mg,
0.132 mmol) and (R)Amino(4-fluoro-phenyl)-propionic acid methyl ester
hydrochloride [Example 9, Step 1]. Yield 59 mg (80%).
Step 3: (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino](4-fluorophenyl)propanoic acid:
(R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol
yl]benzoyl]amino](4-fluorophenyl)propanoic acid was prepared according to a similar
procedure as described for example 7, step 6 from (R)- 2-{4-[2,5-Dimethyl((R)
phenyl-ethoxycarbonylamino)-2H-pyrazolyl]-benzoylamino}(4-fluoro-phenyl)-
propionic acid methyl ester [Example 9, Step 2] (59 mg, 0.11 mmol) to afford the product
55 mg (87%). Method 3, Rt 2.73 min. MS (ESI) m/z 545.4 [M + H ].
Example 10: (R)[[4-[1,5-dimethyl((R)
phenylethoxycarbonylamino)pyrazolyl]benzoyl]amino](4-fluorophenyl)propanoic
acid The title compound was prepared according to an analogous procedure to that
described for example 8 from 4-[1,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-
1H-pyrazolyl]-benzoic acid [Example 8, Step 1] (50 mg, 0.132 mmol) and (R)
Amino(4-fluoro-phenyl)-propionic acid methyl ester hydrochloride [Example 9, Step
1]. Yield 55 mg, (87%). Method 3, Rt 2.69 min. MS (ESI) m/z 545.4 [M + H ].
Example 11: (R)- 3-(4-bromophenyl)[[4-[2,5-dimethyl((R)
phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic acid
[715] Step 1: (R)Amino(4-bromo-phenyl)-propionic acid methyl ester
hydrochloride:
The title compound was prepared using a similar procedure as described for
example 1, step 6 from Dbromophenyl alanine (1 g, 4.1 mmol). Yield 550 mg (46 %).
Method 3, Rt 1.70 min. MS (ESI) m/z 258.1 [M + H ].
[717] Step 2: (R)- 3-(4-bromophenyl)[[4-[2,5-dimethyl((R)
phenylethoxycarbonylamino)-pyrazolyl]benzoyl]amino]propanoic acid
The title compound was prepared according to an analogous procedure to that
described for example 9 (steps 2 & 3) from 4-[2,5-Dimethyl((R)phenyl-
ethoxycarbonylamino)-2H-pyrazolyl]-benzoic acid [Example 7, Step 4] and (R)
Amino(4-bromo-phenyl)-propionic acid methyl ester hydrochloride [Example 11, Step
1]. Yield 30 mg (65%). Method 3, Rt 3.03 min. MS (ESI) m/z 607.4 [M + H ].
Example 12: (R)- 3-(4-bromophenyl)[[4-[1,5-dimethyl((R)
phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic acid The title
compound was prepared according to an analogous procedure to that described for
example 8 from 4-[1,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-1H-pyrazolyl]-
benzoic acid [Example 8, Step 1] (50 mg, 0.132 mmol) and 3-(4-bromo-phenyl)-
propionic acid methyl ester hydrochloride [Example 11, Step 1]. Yield 60 mg, (80%).
Method 3, Rt 3.02 min. MS (ESI) m/z 619.2 [M + H ].
Example 13: (R)- 3-(4-chlorophenyl)[[4-[2,5-dimethyl((R)
phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic acid
Step 1: (R)- 2-Amino(4-chloro-phenyl)-propionic acid methyl ester
hydrochloride:
(R)- 2-Amino(4-chloro-phenyl)-propionic acid methyl ester hydrochloride was
prepared using a similar procedure as described for example 1, step 6 from D
chlorophenyl alanine (1 g, 5 mmol). Yield 940 mg (75 %). Method 3, Rt 0.03 min. MS
(ESI) m/z 214.0 [M + H ].
Step 2: (R,R)- 3-(4-chlorophenyl)[[4-[2,5-dimethyl(1-
phenylethoxycarbonylamino)-pyrazolyl]benzoyl]amino]propanoic acid
The title compound was prepared according to an analogous procedure to that
described for example 9 (steps 2 & 3) from (R)- 4-[2,5-Dimethyl(1-phenyl-
ethoxycarbonylamino)-2H-pyrazolyl]-benzoic acid [Example 7, Step 4] and (R)- 2-
Amino(4-chloro-phenyl)-propionic acid methyl ester hydrochloride [Example 13, Step
1]. Yield 40 mg (55%). Method 3, Rt 2.80 min. MS (ESI) m/z 561.3 [M + H ].
Example 14: (R)- 3-(4-chlorophenyl)[[4-[1,5-dimethyl((R)
phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic acid
[726] The title compound was prepared according to an analogous procedure to that
described for example 8 from 4-[1,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-
1H-pyrazolyl]-benzoic acid [Example 8, Step 1] and (R)- 2-Amino(4-chloro-phenyl)-
propionic acid methyl ester hydrochloride [Example 8, Step 1]. Yield 40 mg
(54%)Method 3, Rt 3.00 min. MS (ESI) m/z 561.3 [M + H ].
[727] Example 15: (R)- 3-(3,4-difluorophenyl)[[4-[2,5-dimethyl((R)
phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic acid
Step 1: (R)- 2-Amino(3,4-difluoro-phenyl)-propionic acid methyl ester
hydrochloride:
(R)- 2-Amino(3,4-difluoro-phenyl)-propionic acid methyl ester hydrochloride
was prepared using a similar procedure as described for example 1, step 6 from D-3,4-
difluorophenyl alanine (1 g, 4.97 mmol). Yield 1.04 g, 83 %). Method 3, Rt 0.16 min. MS
(ESI) m/z 216.0 [M + H ];
Step 2: (R)- 3-(3,4-difluorophenyl)[[4-[2,5-dimethyl((R)
phenylethoxycarbonylamino)-pyrazolyl]benzoyl]amino]propanoic acid:
[731] The title compound was prepared according to an analogous procedure to that
described for example 9 (steps 2 & 3) from (R)- 4-[2,5-Dimethyl(1-phenyl-
ethoxycarbonylamino)-2H-pyrazolyl]-benzoic acid [Example 7, Step 4] (50 mg, 0.132
mmol) and (R)- 2-Amino(3,4-difluoro-phenyl)-propionic acid methyl ester
hydrochloride [Example 15, Step 1]. Yield 30 mg (61%). Method 3, Rt 2.96 min. MS
(ESI) m/z 563.4 [M + H ].
Example 16: (R)- 3-(3,4-difluorophenyl)[[4-[1,5-dimethyl((R)
phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic acid
The title compound was prepared according to an analogous procedure to that
described for example 8 from 4-[1,5-Dimethyl((R)phenyl-ethoxycarbonylamino)-
1H-pyrazolyl]-benzoic acid [Example 8, Step 1] (50 mg, 0.132 mmol) and (R)- 2-
Amino(3,4-difluoro-phenyl)-propionic acid methyl ester hydrochloride [Example 15,
Step 1]. Yield 20 mg (56%). Method 3, Rt 2.71 min. MS (ESI) m/z 563.3 [M + H ].
Example 17: (R)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)cyclopropyl-propionic acid
Step 1: (R)Aminocyclopropylpropionic acid methyl ester hydrochloride:
(R)- 2-Aminocyclopropylpropionic acid methyl ester hydrochloride was
prepared using a similar procedure as described for example 1, step 6 from (R)- 2-
Aminocyclopropylpropionic acid and used directly. Yield 350mg (100%).
Step 2: 4-{4-[1-((R)Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol
yl}-benzoic acid methyl ester
Prepared in analogous fashion as in Example 5 Step 1 using 5-(4-
methoxycarbonyl-phenyl)methyl-isoxazolecarboxylic acid [Example 1, step 3] (3.47
g, 13.28 mmol) and (R)(2-chlorophenyl)-ethanol. Yield = 1.81 g (4.36 mmol, 25 %).
HPLC (254 nm): Method 3 Rt 3.31 min. MS (ESI) m/z 415.5 [M + H ].
Step 3: 4-{4-[1-((RChloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol
yl}-benzoic acid
[740] Prepared in analogous fashion as in Example 5, Step 2 using 4-{4-[1-((R)
chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}-benzoic acid methyl ester
[Example 17, step 2](1.81 g, 4.46 mmol). Yield = 1.70 g (4.25 mmol, 95 %). HPLC (254
nm): Method 3 Rt 3.01 min. MS (ESI) m/z 401.2 [M + H ].
Step 4: (R)(4-{4-[1-((R)Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzoylamino)cyclopropyl-propionic acid
The title compound was prepared according to an analogous procedure to that
described for example 5 from 4-{4-[1-((R)chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (50mg, 0.13 mmol) and (R)- 2-
Aminocyclopropylpropionic acid methyl ester hydrochloride [Example 17, step 1].
Yield 22mg (34%). Method 3, Rt 3.27min. MS (ESI) m/z 512.5 [M + H ].
Example 18: (R){4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazol-
-yl]-benzoylamino}phenyl-propionic acid Step 1: 4-[3-Methyl((S)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzoic acid
4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzoic acid
was prepared in analogous fashion to example 17 [steps & 3] from 5-(4-
methoxycarbonyl-phenyl)methyl-isoxazolecarboxylic acid [Example 1, step 3] (1 g,
3.3 mmol) and (S)(2-chlorophenyl)-ethanol. Yield = 800 mg (2.19 mmol, 60 %). HPLC
(254 nm): Method 3 Rt 2.67 min. MS (ESI) m/z 367.4 [M + H ].
Step 2: (S,R){4-[3-Methyl(1-phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzoylamino}phenyl-propionic acid
The title compound was prepared according to an analogous procedure to that
described for example 5 from (S)[3-Methyl(1-phenyl-ethoxycarbonylamino)-
isoxazolyl]-benzoic acid [Example 18, step 2] (61 mg, 0.12 mmol) and D-
phenylalanine methyl ester hydrochloride. Yield = 30 mg (0.06 mmol, 49 %). HPLC (254
nm): Method 3 Rt 3.05 min. MS (ESI) m/z 514.5 [M + H+].
Example 19: (S){4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazol-
-yl]-benzoylamino}phenyl-propionic acid
The title compound was prepared according to an analogous procedure to that
described for example 18 from 4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-
isoxazolyl]-benzoic acid [Example 18, step 2] (61 mg, 0.12 mmol) and L-
phenylalanine methyl ester hydrochloride. Yield = 22 mg (0.04 mmol, 36 %). HPLC (254
nm): Method 3 Rt 2.87 min. MS (ESI) m/z 514.5 [M + H+].
Example 20: (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)phenyl-propionic acid
[750] The title compound was prepared according to an analogous procedure to that
described for example 17 from 4-{4-[1-((R)Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (60 mg, 0.15 mmol) and D-
phenylalanine methyl ester. Yield = 65 mg (0.12 mmol, 77 %). HPLC (254 nm): Method
3 Rt 2.93 min. MS (ESI) m/z 566.3 [M + H ].
[751] Example 21: (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)(4-fluoro-phenyl)-propionic acid
The title compound was prepared according to an analogous procedure to that
described for example 17 from 4-{4-[1-((R)Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (60 mg, 0.15 mmol) and D
fluorophenylalanine methyl ester. Yield = 65 mg (0.12 mmol, 77 %). HPLC (254 nm):
Method 3 Rt 2.93 min. MS (ESI) m/z 566.3 [M + H ].
Example 22 (R)(4-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic acid
The title compound was prepared according to an analogous procedure to that
described for example 17 from 4-{4-[1-((R)Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (60 mg, 0.15 mmol) and D
chlorophenylalanine methyl ester. Yield = 64 mg (0.11 mmol, 74 %). HPLC (254 nm):
Method 3 Rt 3.11 min. MS (ESI) m/z 583.4 [M + H ].
Example 23: (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)(3,4-difluoro-phenyl)-propionic acid
The title compound was prepared according to an analogous procedure to that
described for example 17 from 4-{4-[1-((R)Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (60 mg, 0.15 mmol) and D-3,4-
difluorophenylalanine methyl ester hydrochloride. Yield = 41 mg (0.07 mmol, 47 %).
HPLC (254 nm): Method 3 Rt 2.96 min. MS (ESI) m/z 584.1 [M + H ].
Example 24: (R)(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic acid
The title compound was prepared according to an analogous procedure to that
described for example 17 from 4-{4-[1-((R)Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (60 mg, 0.15 mmol) and D
chlorophenylalanine methyl ester hydrochloride. Yield = 41 mg (0.07 mmol, 47 %).
HPLC (254 nm): Method 3 Rt 3.06 min. MS (ESI) m/z 584.2 [M + H ].
Example 25: (R)(4-Bromo-phenyl)(4-{4-[(R)(2-chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic acid
The title compound was prepared according to an analogous procedure to that
described for example 17 from 4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (60 mg, 0.15 mmol) and D
bromophenylalanine methyl ester hydrochloride. Yield = 65 mg (0.10 mmol, 35 %).
HPLC (254 nm): Method 3 Rt 3.28 min. MS (ESI) m/z 626.3, 628.4 [M + H ].
Example 26: (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)(2-fluoro-phenyl)-propionic acid
[762] The title compound was prepared according to an analogous procedure to that
described for example 17 from 4-{4-[(R)- 1-(2-chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (60 mg, 0.15 mmol) and D
fluorophenylalanine methyl ester hydrochloride. Yield = 70 mg (0.12 mmol, 52 %). HPLC
(254 nm): Method 3 Rt 3.12 min. MS (ESI) m/z 566.5, 567.8 [M + H ].
[763] Example 27: (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)p-tolyl-propionic acid
The title compound was prepared according to an analogous procedure to that
described for example 17 from 4-{4-[(R)- 1-(4-chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (60 mg, 0.15 mmol) and D
methylphenylalanine methyl ester hydrochloride. Yield = 37 mg (0.07 mmol, 43 %).
HPLC (254 nm): Method 3 Rt 3.13 min. MS (ESI) m/z 562.3 [M + H ].
Example 28: (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)(4-trifluoromethyl-phenyl)-propionic acid
The title compound was prepared according to an analogous procedure to that
described for example 17 from 4-{4-[(R)(4-bromo-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (60 mg, 0.15 mmol) and D
trifluoromethylphenylalanine methyl ester hydrochloride. Yield = 40 mg (0.06 mmol, 44
%). HPLC (254 nm): Method 3 Rt 3.00 min. MS (ESI) m/z 616.2 [M + H ].
Example 29: (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoylamino)(4-cyano-phenyl)-propionic acid
[768] The title compound was prepared according to an analogous procedure to that
described for example 17 from 4-{4-[(R)(4-bromo-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzoic acid [Example 17, step 3] (60 mg, 0.15 mmol) and D
cyanophenylalanine methyl ester hydrochloride. Yield = 17 mg (0.03 mmol, 20 %).
HPLC (254 nm): Method 3 Rt 2.93 min. MS (ESI) m/z 573.2 [M + H ].
[769] Example 30: (R)- 2-(4-{5-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-pyrazolyl}-benzoylamino)phenyl-propionic acid Step 1: 2-(4-Cyano-phenyl)-
4-methyl-2H-pyrazolecarboxylic acid ethyl ester
A solution of trichloroacetyl chloride (12.92 mL, 115.8 mmol) in dichloromethane
(30 mL) was cooled to -10 C under a nitrogen atmosphere. A solution of ethyl propenyl
ether (12.82 mL, 115.8 mmol) and pyridine (9.36 mL, 115.8 mmol) was added dropwise
at a rate to maintain the internal temperature at -10 C. After addition was complete, the
reaction was warmed to room temperature and stirred for 24 hours. The mixture was
filtered and the solids were washed with dichloromethane (50 mL). The filtrates were
evaporated to dryness under vacuum to yield an oil (31.71 g). This material was
dissolved in ethanol (400 mL) and treated with 4- cyanophenylhydrazine hydrochloride
(24.81 g, 139 mmol). The resulting mixture was refluxed for 3 hours and then cooled to
room temperature. The volatiles were evaporated in vacuo, the residue was dissolved in
EtOAc (1 L) and washed with 1 N aqueous HCl solution (2 X 300 mL). The organic layer
was separated, washed with water, dried over anhydrous Na SO , filtered and
concentrated in vacuo to obtain a yellow solid (27.8 g). This was triturated with EtOAc
(130 mL) and the remaining solids removed by filtration (do not contain product). The
filtrates were concentrated to 50 mL volume and the precipitated solids were filtered (do
not contain product). The filtrates were concentrated and purified by silica gel
chromatography, eluting with a 100/0 to 88/12 hexanes/acetone gradient. Collected
fractions containing a mixture of the two isomeric products, which were concentrated to
dryness and triturated with methanol to yield the desired isomer [2-(4-cyano-phenyl)
methyl-2H-pyrazolecarboxylic acid ethyl ester] as a yellow solid (3.77 g, 14.8 mmol,
13%). HPLC (254 nm): Method 3 Rt 2.93 min. MS (ESI) m/z 256.3 [M + H ]. H NMR
(500 MHz, CDCl ) d 7.73 (d, J = 8.5 Hz, 2 H); 7.58 (s, 1 H); 7.52 (d, J = 8.5 Hz, 2 H);
4.27 (q, J = 7.1 Hz, 2 H); 2.35 (s, 3 H); 1.26 (t, J = 7.1 Hz, 3 H).
Step 2: 2-(4-Cyano-phenyl)methyl-2H-pyrazolecarboxylic acid
A stirred solution of 2-(4-Cyano-phenyl)methyl-2H-pyrazolecarboxylic acid
ethyl ester [Example 30, step 1](500 mg, 1.96 mmol) in THF (10 mL) was treated with
LiOH 1 N aqueous solution (10 mL) and the resulting mixture was stirred at room
temperature for 6 hours, after which time analysis by HPLC/MS indicates approximately
60% conversion to product. The reaction mixture was diluted with ethyl acetate (100 mL)
and washed with 1 N aqueous NaOH solution (100 mL). The organic layer contained
unreacted starting material. The aqueous layer was acidified to pH 1 with 1 N HCl
aqueous solution and the resulting suspension was extracted with ethyl acetate (100
mL). The organic layer was separated, dried over anhydrous MgSO , filtered and
concentrated in vacuo to afford the pure product as a white solid (289 mg, 1.27 mmol,
65 %). HPLC (254 nm): Method 3 Rt 2.56 min. MS (ESI) m/z 228.3 [M + H ].
Step 3: [2-(4-Cyano-phenyl)methyl-2H-pyrazolyl]-carbamic acid (R)(2-
chloro-phenyl)-ethyl ester
2-(4-Cyano-phenyl)methyl-2H-pyrazolecarboxylic acid [Example 30, step 2]
(218 mg, 0.96 mmol) was suspended in toluene (10 mL) and treated with
diisopropylethylamine (200 µL, 1.16 mmol),. The resulting solution was treated with
diphenylphosphoryl azide (230 µL, 1.06 mmol) and heated to 65 C. (R)- 1-(2-chloro-
phenyl)-ethanol (227 mg, 1.44 mmol) was added to the reaction mixture and the
temperature was increased to 105 C for 30 minutes, during which time vigorous gas
evolution was observed. The reaction was brought to 65 C and stirred at that
temperature for 4 hours. The reaction was deemed complete by HPLC/MS. After
cooling, the volatiles were removed in vacuo and the crude residue was purified by silica
gel chromatography, eluting with a hexanes/ethyl acetate gradient. Product was isolated
as a white solid (120 mg, 0.31 mmol, 33 %). HPLC (254 nm): Method 3 Rt 3.84 min. MS
(ESI) m/z 381.2 [M + H ].
Step 4: 4-{5-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-pyrazol
yl}-benzoic acid
A solution containing (R)-[2-(4-Cyano-phenyl)methyl-2H-pyrazolyl]-
carbamic acid 1-(2-chloro-phenyl)-ethyl ester (120 mg, 0.32 mmol) and THF (1.5 mL)
was treated with a 1 N aqueous LiOH solution (1.5 mL) and the resulting mixture was
stirred at room temperature for 36 hours, followed by heating to 45 C for 24 hours. The
reaction mixture was diluted with ethyl acetate (50 mL) and washed with 1 N aqueous
NaOH solution (50 mL). The aqueous layer was acidified to pH 1 with 1 N HCl aqueous
solution and the resulting suspension was extracted with ethyl acetate (50 mL). The
organic layer was separated, dried over anhydrous MgSO , filtered and concentrated in
vacuo to afford the pure product as a white solid. Yield = 62 mg (0.16 mmol, 49 %).
HPLC (254 nm): Method 3 Rt 3.14 min. MS (ESI) m/z 399.2 [M + H ].
Step 3: (R)(4-{5-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
pyrazolyl}-benzoylamino)phenyl-propionic acid methyl ester
4-{5-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-pyrazolyl}-
benzoic acid (62 mg, 0.16 mmol), was dissolved in DMF (1.4 mL) and treated with di-
isopropylethylamine (112 µL, 0.62 mmol) under nitrogen. EDCI (40 mg, 0.20 mmol) and
HOBt (26 mg, 0.19 mmol) was added and the resulting mixture was stirred for 30
minutes. D-Phenylalanine methyl ester hydrochloride (50 mg, 0.23 mmol) was added
and the resulting mixture stirred at room temperature overnight. The reaction was
diluted with EtOAc (50 mL) and transferred to a separatory funnel. The organics were
washed with 1 N HCl aqueous solution and brine, dried over anhydrous MgSO , filtered
and concentrated in vacuo. The crude residue was purified by preparative TLC plate
(1000 µm), eluting with a 7:3 v/v hexanes/ethyl acetate mixture. The product was
obtained as a white solid. Yield = 35 mg (0.06 mmol, 39 %). HPLC (254 nm): Method 3
Rt 3.28 min. MS (ESI) m/z 561.3, 563.3 [M + H ].
[779] Step 4: (R)- 2-(4-{5-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
pyrazolyl}-benzoylamino)phenyl-propionic acid
A solution containing (R)(4-{5-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]-
4-methyl-pyrazolyl}-benzoylamino)phenyl-propionic acid methyl ester (35 mg, 0.06
mmol), and THF (1 mL) was treated with a 1 N aqueous LiOH solution (125 µL) and the
resulting mixture was stirred at room temperature for 18 hours. The reaction mixture
was diluted with ethyl acetate (50 mL) and acidified to pH 1 with 1 N HCl aqueous
solution. The organic layer was separated, dried over anhydrous MgSO , filtered and
concentrated in vacuo to afford the pure product as a white solid. Yield = 20 mg (0.04
mmol, 61 %). HPLC (254 nm): Method 3 Rt 3.19 min. MS (ESI) m/z 547.6, 550.6 [M +
H ].
Example 31: (R){4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazol-
-yl]-benzylamino}phenyl-propionic acid
Step 1: 5-(4-Chloromethyl-phenyl)methyl-isoxazolecarboxylic acid tert-butyl
ester
[783] A stirred suspension of MgCl (2.97 g, 31.2 mmol) in dichloromethane (30 mL)
under nitrogen was treated dropwise with tert-butyl acetoacetate (5.17 mL, 31.2 mmol)
and the resulting mixture was cooled to 0 C. The mixture was stirred at that
temperature for 15 minutes and then treated with dropwise addition of pyridine (4.85
mL, 60.0 mmol). After 15 minutes, a solution of 4-(chloromethyl)benzoyl chloride (5.67
g, 30.0 mmol) in dichloromethane (30 mL) was added dropwise. The resulting mixture
was maintained at 0 C for 1 hour and then at room temperature for an additional hour.
The reaction was quenched with careful addition of water (100 mL) and the mixture was
transferred to a separatory funnel. The organic layer was washed with a 1 N HCl
aqueous solution (2 X 100 mL) then dried over anhydrous MgSO , filtered and
concentrated in vacuo. The crude residue was dissolved in ethanol (60 mL) and treated
with a solution of NH2OH.HCl (6.67 g, 96.0 mmol) in water (13 mL). This mixture was
heated to 60 C for 2 hours and at room temperature overnight. A thick white precipitate
formed which was filtered, rinsed with ethanol and air-dried. The mother liquor was
concentrated and cooled to 0 C to yield a second crop of solid which was filtered and
air-dried. Combined yield = 5.82 g (19.0 mmol, 63 %). HPLC (254 nm): Method 3 Rt
3.49 min. MS (ESI) m/z 308.4 [M + H ].
[784] Step 2: 5-(4-Chloromethyl-phenyl)methyl-isoxazolecarboxylic acid
5-(4-Chloromethyl-phenyl)methyl-isoxazolecarboxylic acid tert-butyl ester
(4.61 g, 15.0 mmol) was dissolved in dichloromethane (7.5 mL) and treated with
trifluoroacetic acid (7.5 mL). The resulting mixture was stirred at room temperature for
18 hours, after which time the reaction was deemed complete by HPLC/MS. The
volatiles were removed in vacuo to yield the crude product as a white solid (3.8 g, 15.0
mmol, quant.), which was used as is in the next step.
Step 3: [5-(4-Chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)
phenyl-ethyl ester
5-(4-Chloromethyl-phenyl)methyl-isoxazolecarboxylic acid (3.0 g, 12.0
mmol) was suspended in toluene (120 mL) and treated with triethylamine (2.02 mL, 14.4
mmol). The resulting solution was treated with diphenylphosphoryl azide (2.85 mL, 13.2
mmol) and heated to 65 C. (R)(phenyl)-ethanol (1.9 g, 15.6 mmol) was added to the
reaction mixture and the temperature was increased to 105 C for 30 minutes, during
which time vigorous gas evolution was observed. The reaction was brought to 65 C and
stirred at that temperature for 4 hours. The reaction was deemed complete by
HPLC/MS. After cooling, the volatiles were removed in vacuo and the crude residue was
purified by silica gel chromatography, eluting with a hexanes/ethyl acetate gradient.
Product isolated as a white solid (3.16 g, 8.52 mmol, 71 %). HPLC (254 nm): Method 3
Rt 3.02 min. MS (ESI) m/z 371.2 [M + H ].
[788] Step 4: (R)- 2-{4-[3-Methyl((Rphenyl-ethoxycarbonylamino)-isoxazolyl]-
benzylamino}phenyl-propionic acid methyl ester
A solution containing [5-(4-Chloromethyl-phenyl)methyl-isoxazolyl]-
carbamic acid (R)phenyl-ethyl ester (74 mg, 0.2 mmol), DMF (2 mL) and
triethylamine (224 µL, 1.6 mmol) was treated with D-phenylalanine methyl ester
hydrochloride (173 mg, 0.80 mmol) and heated to 80 C for 3 hours. The reaction was
deemed complete by HPLC/MS. The reaction was cooled, partitioned between EtOAc
and water and transferred to a separatory funnel. The organic layer was washed with
water and brine, dried over anhydrous MgSO , filtered and concentrated in vacuo. The
crude yellow oily residue was purified by silica gel chromatography eluting with a
hexanes/EtOAc gradient. The product was obtained as a colorless film (77 mg, 0.15
mmol, 75 %). HPLC (254 nm): Method 3 Rt 2.67 min. MS (ESI) m/z 514.4 [M + H ].
[790] Step 5: (R){4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzylamino}phenyl-propionic acid
A solution containing (R)- 2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-
isoxazolyl]-benzylamino}phenyl-propionic acid methyl ester (77 mg, 0.15 mmol)
and THF (1.5 mL) was treated with a 1 N aqueous LiOH solution (1.5 mL) and the
resulting mixture was stirred at room temperature for 18 hours. The reaction mixture
was diluted with ethyl acetate (50 mL) and acidified to pH ~ 5 with 1 N HCl aqueous
solution. The organic layer was separated, dried over anhydrous MgSO , filtered and
concentrated in vacuo. The residue was triturated with diethyl ether to afford the pure
product as a white solid (9 mg, 0.018 mmol, 12 %). HPLC (254 nm): Method 3 Rt 2.74
min. MS (ESI) m/z 500.5 [M + H ].
Example 32: (R)(2-Fluoro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid
The title compound was prepared in analogous fashion as in Example 31 using
[5-(4-chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)phenyl-ethyl
ester [Example 31, step 3](100 mg, 0.27 mmol), and Dfluorophenyl-alanine methyl
ester hydrochloride. Yield = 10 mg (0.02 mmol, 7 %). HPLC (254 nm): Method 3 Rt 2.64
min. MS (ESI) m/z 518.4 [M + H ].
Example 33: (R){4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazol-
-yl]-benzylamino}(4-trifluoromethyl-phenyl)-propionic acid
[795] The title compound was prepared in analogous fashion as in Example 31 using
[5-(4-chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)phenyl-ethyl
ester [Example 31, step 3](100 mg, 0.27 mmol), and Dtrifluoromethylphenyl-alanine
methyl ester hydrochloride. Yield = 18 mg (0.03 mmol, 11%). HPLC (254 nm): Method 3
Rt 3.10 min. MS (ESI) m/z 568.5 [M + H ].
[796] Example 34: (R)Cyclopropyl{4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid The title compound
was prepared in analogous fashion as in Example 31 using [5-(4-chloromethyl-phenyl)-
3-methyl-isoxazolyl]-carbamic acid (R)phenyl-ethyl ester [Example 31, step 3](100
mg, 0.27 mmol), and (R)Aminocyclopropylpropionic acid methyl ester
hydrochloride [Example 17, step 1]. Yield = 13 mg (0.03 mmol, 35 %). HPLC (254 nm):
Method 3 Rt 2.82 min. MS (ESI) m/z 464.5 [M + H ].
Example 35: (R)(2-Chloro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid
The title compound was prepared in analogous fashion as in Example 31 using
[5-(4-chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)phenyl-ethyl
ester [Example 31, step 3](100 mg, 0.27 mmol), and Dchlorophenyl-alanine methyl
ester hydrochloride. Yield = 38 mg (0.07 mmol, 27 %). HPLC (254 nm): Method 3 Rt
3.05 min. MS (ESI) m/z 534.2 [M + H ].
Example 36: (R)(4-Chloro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid
[800] The title compound was prepared in analogous fashion as in Example 31 using
[5-(4-chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)phenyl-ethyl
ester [Example 31, step 3](100 mg, 0.27 mmol), and Dchlorophenyl-alanine methyl
ester hydrochloride. Yield = 8 mg (0.01 mmol, 5 %). HPLC (254 nm): Method 3 Rt 3.13
min. MS (ESI) m/z 534.4 [M + H ].
[801] Example 37: (R)- 2-(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzylamino)phenyl-propionic acid
Step 1: [5-(4-Chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)
(2-chloro-phenyl)-ethyl ester
[5-(4-Chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)(2-
chloro-phenyl)-ethyl ester was prepared in analogous fashion as in Example 31, steps
1-3 from 5-(4-chloromethyl-phenyl)methyl-isoxazolecarboxylic acid [Example 31,
step 2](1.95 g, 7.75 mmol) and (R)(2-chlorophenyl)-ethanol (1.82 g, 11.62 mmol).
Yield = 1.33 g (3.28 mmol, 42 %). HPLC (254 nm): Method 3 Rt 3.31 min. MS (ESI) m/z
405.3 [M + H ].
[804] Step 2: (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzylamino)phenyl-propionic acid methyl ester
(R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazol
yl}-benzylamino)phenyl-propionic acid methyl ester was prepared in analogous
fashion as in Example 31, steps 4 from [5-(4-Chloromethyl-phenyl)methyl-isoxazol
yl]-carbamic acid (R)(2-chloro-phenyl)-ethyl ester [Example 37, step 1] (101 mg, 0.25
mmol) and D-phenylalanine methyl ester hydrochloride. Yield = 45 mg (0.08 mmol, 33
%). HPLC (254 nm): Method 3 Rt 2.90 min. MS (ESI) m/z 548.5 [M + H ].
Step 3: (R)- 2-(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-
isoxazolyl}-benzylamino)phenyl-propionic acid
[807] Prepared in analogous fashion as in Example J, Step 5 using the following
reagents and amounts: (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzylamino)phenyl-propionic acid methyl ester [Example 37,
step 2] (45 mg, 0.08 mmol). Yield = 6 mg (0.01 mmol, 14 %). HPLC (254 nm): Method 3
Rt 2.69 min. MS (ESI) m/z 534.3 [M + H ].
Example 38: (R)- 2-(4-{4-[(R)_1-(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzylamino)(2-fluoro-phenyl)-propionic acid
[809] The title compound was prepared in analogous fashion as in Example 31 using
[5-(4-Chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)(2-chloro-
phenyl)-ethyl ester [Example 37, step 1](101 mg, 0.25 mmol), and Dfluorophenyl-
alanine methyl ester hydrochloride. Yield = 30 mg (0.05 mmol, 22 %). HPLC (254 nm):
Method 3 Rt 2.57 min. MS (ESI) m/z 552.3 [M + H ].
[810] Example 39: (R)- 2-(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzylamino)(4-trifluoromethyl-phenyl)-propionic acid
The title compound was prepared in analogous fashion as in Example 31 using
[5-(4-Chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)(2-chloro-
phenyl)-ethyl ester [Example 37, step 1](101 mg, 0.25 mmol), and D
trifluoromethylphenyl-alanine methyl ester hydrochloride. Yield = 38 mg (0.06 mmol, 25
%). HPLC (254 nm): Method 3 Rt 3.06 min. MS (ESI) m/z 602.6 [M + H ].
Example 40: (R)- 3-(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)-
ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)-propionic acid
The title compound was prepared in analogous fashion as in Example 31 using
[5-(4-Chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)(2-chloro-
phenyl)-ethyl ester [Example 37, step 1](101 mg, 0.25 mmol), and Dchlorophenyl-
alanine methyl ester hydrochloride. Yield = 8 mg (0.01 mmol, 5 %). HPLC (254 nm):
Method 3 Rt 2.78 min. MS (ESI) m/z 569.3 [M + H ].
Example 41: (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]
methyl-isoxazolyl}-benzylamino)cyclopropyl-propionic acid
The title compound was prepared in analogous fashion as in Example 31 using
[5-(4-Chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)(2-chloro-
phenyl)-ethyl ester [Example 37, step 1](101 mg, 0.25 mmol), and (R)Amino
cyclopropylpropionic acid methyl ester hydrochloride [Example 17, step 1]. Yield = 8 mg
(0.01 mmol, 3 %). HPLC (254 nm): Method 3 Rt 2.80 min. MS (ESI) m/z 498.4 [M + H ].
Example 42: 2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazol
yl]-benzyloxy}phenyl-propionic acid
Step 1: {p-[3-Methyl((R)phenylethoxycarbonylamino)
isoxazolyl]phenyl}methyl acetate
[818] [5-(4-Chloromethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)phenyl-
ethyl ester [Example 31, step 3] (1g, 2.8mmole) was mixed with potassium acetate (2g,
14mmol) and sodium iodide (0.5g, 2.8mmole) and to this was added N,N-
dimethylacetamide (20mL). The mixture was sonicated and then heated to 80 C for
1.5hrs. The mixture was cooled to room temperature and partitioned between saturated
sodium chloride solution and ethyl acetate. The organic layer was further washed with
water 4 times and then saturated sodium chloride solution before drying over
magnesium sulfate. The filtered solution was evaporated to give a solid that was used
directly. Yield = 0.94 g (2.4 mmol, 87 %). HPLC (254 nm): Method 3 Rt 2.89 min. MS
(ESI) m/z 395.3 [M + H ].
Step 2: [5-(4-Hydroxymethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)-
1-phenyl-ethyl ester
[820] {p-[3-Methyl((R)phenylethoxycarbonylamino)isoxazolyl]phenyl}methyl
acetate [Example 42, step 1](0.94g, 2.4mmole) was dissolved in THF (20mL) and
methanol (20mL) and to this was added potassium carbonate (981mg, 7.1mmole). The
resulting mixture was allowed to stir for 1.5 hours at room temperature when LC/MS
indicated formation of a single product [HPLC (254 nm): Method 3 Rt 2.93 min. MS
(ESI) m/z 353.2 [M + H ]. Solvents were evaporated and the residue was partitioned
between saturated sodium chloride solution and ethyl acetate. The organic phase was
dried over magnesium sulfate, filtered and evaporated to give a residue that was
chromatographed in a gradient of 0-50% ethyl acetate in hexanes to afford the product.
Yield 0.63g (1.79mmole, 74%).
[821] Step 3: Methyldiazo-phenylpropanoate
D-phenylalanine methyl ester hydrochloride (2g, 9.3mmole) was partitioned
between saturated sodium bicarbonate solution and ethyl acetate. The organic phase
was dried over magnesium sulfate, filtered and evaporated to give a residue that was
used directly. D-phenylalanine methyl ester (836mg, 4.7mmole) was dissolved in
chloroform (20mL) and acetic acid (0.055mL, 0.94mmole) was added. The solution was
warmed to reflux with the slow drop wise addition of isoamyl nitrite (0.76mL, 5.6mmole)
which was complete prior to solvent boiling. The mixture was refluxed for a further 30
minutes to afford a yellow solution that was cooled to 0 C. The organic solution was
washed with 1N sulfuric acid (25mL), water (20mL), saturated sodium bicarbonate
solution (25mL), water (25mL) and 1N sulfuric acid (25mL). The organic phase was
dried over magnesium sulfate, filtered and evaporated to give a residue that was
chromatographed in a gradient of 0-5% ethyl acetate in hexanes to afford the product.
Yield 0.65g (3.4 mmole, 72%).
Step 4: 2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzyloxy}phenyl-propionic acid methyl ester
[5-(4-Hydroxymethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)phenyl-
ethyl ester [Example 42, step 2] (100mg, 0.28mmole) and Methyldiazo-
phenylpropanoate [Example 42, step 3] (61mg, 0.39mmole) were suspended in
benzene (3mL) in a screw cap vial. To this was added diRhodium tetraacetate (1mg,
0.002mmole). After 10 minutes at room temperature the vial was heated to 90 C for 1
hour. The mixture was cooled to room temperature and the mixture chromatographed in
a gradient of 0-20% ethyl acetate in hexanes to afford the product. Yield = 52 mg (0.1
mmol, 36%). HPLC (254 nm): Method 3 Rt 3.56 min. MS (ESI) m/z 515.5 [M + H ].
Step 5: 2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-
benzyloxy}phenyl-propionic acid
2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-
3-phenyl-propionic acid methyl ester (52mg, 0.10mmole) was dissolved in 2/1 v/v
THF/water (4.5 mL) and the mixture stirred for 24 hours. The reaction mixture was
diluted with ethyl acetate (50 mL) and washed with saturated sodium bicarbonate
solution. The aqueous layer was acidified to pH ~ 3 with 6 N HCl and extracted with
ethyl acetate. The organic layer was separated, dried over anhydrous MgSO , filtered
and concentrated in vacuo. The residue was co-evaporated with diethyl ether to afford
the pure product as a white solid (22 mg, 0.043 mmol, 44 %). HPLC (254 nm): Method 3
Rt 3.03 min. MS (ESI) m/z 501.5 [M + H ].
Example 43: 2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazol
yl]-benzyloxy}phenyl-propionic acid
[828] Example 43 was prepared in analogous fashion to example 42 from [5-(4-
Hydroxymethyl-phenyl)methyl-isoxazolyl]-carbamic acid (R)phenyl-ethyl ester
[Example 42, step 2] (100mg, 0.28mmole) dissolved in 15% THF in benzene (1.15mL)
using Methyldiazo-phenylpropanoate that was synthesized from L-phenylalanine
methyl ester hydrochloride (2g, 9.3mmole). Yield 20mg (0.04mmole, 14%). HPLC (254
nm): Method 3 Rt 2.96 min. MS (ESI) m/z 501.6 [M + H ].
Example 44: (RS)Cyclopropyl{4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-propionic acid
Step 1: D,Lamino-cyclopropylpropanoic acid methyl ester
Prepared in analogous fashion to Example 1, step 6 from D,Lamino-
cyclopropylpropanoic acid (500mg, 3.87mmole). The crude residue was partitioned
between saturated sodium bicarbonate solution and ethyl acetate. The organic phase
was dried over magnesium sulfate, filtered and evaporated to give a residue that was
used directly. Yield 295mg (2.06mmole, 53%)
Step 2: R,S Methyldiazo-cyclopropylpropanoate
[833] Prepared in analogous fashion to Example 42, step 3 from D,Lamino-
cyclopropylpropanoic acid methyl ester (295mg, 2.06mmole) and used directly. Yield
200mg (1.29mmole, 62%)
Step 3: (RS)Cyclopropyl{4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-propionic acid methyl ester
Prepared in analogous fashion to Example 42, step 4 from [5-(4-Hydroxymethyl-
phenyl)methyl-isoxazolyl]-carbamic acid (R)phenyl-ethyl ester [Example 42,
step 2] (90mg, 0.25mmole) dissolved in 15% THF in benzene (1 mL) and R,S Methyl
diazo-cyclopropylpropanoate [Example 44, step 2] (118mg, 0.75mmole]. Yield 50mg
(0.1mmole, 40%). HPLC (254 nm): Method 3 Rt 2.99 min. MS (ESI) m/z 479.1 [M + H ].
Step 4: : (RS)Cyclopropyl{4-[3-methyl((R)phenyl-
ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-propionic acid
[837] Prepared in analogous fashion to Example 42, step 5 from (RS)Cyclopropyl
{4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-propionic
acid methyl ester [Example 44, step 3] (50mg, 0.1mmole). Yield 21mg (0.1mmole, 40%).
HPLC (254 nm): Method 3 Rt 3.06 min. MS (ESI) m/z 465 [M + H ].
Example 45: (RS)(4-Chloro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonyloxy)-isoxazolyl]-benzyloxy}-propionic acid
Step 1: D,LAmino-3(4-chlorophenyl)propanoic acid methyl ester
Prepared in analogous fashion to Example 1, step 6 from D,LAmino-3(4-
chlorophenyl)propanoic acid (600mg, 3mmole). The crude residue was partitioned
between saturated sodium bicarbonate solution and ethyl acetate. The organic phase
was dried over magnesium sulfate, filtered and evaporated to give a residue that was
used directly. Yield 698mg (3.3mmole, 100%)
Step 2: R,S Methyldiazo-3(4-chlorophenyl)propanoate
Prepared in analogous fashion to Example 42, step 3 from D,LAmino-3(4-
chlorophenyl)propanoic acid methyl ester [Example 45, step 1](698mg, 3.3mmole) and
used directly. Yield 275mg (1.33mmole, 40%)
Step 3: (RS)(4-Chloro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonyloxy)-isoxazolyl]-benzyloxy}-propionic acid methyl ester
Prepared in analogous fashion to Example 42, step 4 from [5-(4-Hydroxymethyl-
phenyl)methyl-isoxazolyl]-carbamic acid (R)phenyl-ethyl ester [Example 42,
step 2] (90mg, 0.25mmole) dissolved in 15% THF in benzene (1 mL) and R,S Methyl
diazo-3(4-chlorophenyl)propanoate [Example 45, step 2] (200mg, 0.89 mmole). Yield
55mg (0.1mmole, 40%). HPLC (254 nm): Method 3 Rt 3.49 min. MS (ESI) m/z 549.6 [M
+ H ].
Step 4: (RS)(4-Chloro-phenyl){4-[3-methyl((R)phenyl-
ethoxycarbonyloxy)-isoxazolyl]-benzyloxy}-propionic acid
Prepared in analogous fashion to Example 42, step 5 from (RS)Cyclopropyl
{4-[3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}-propionic
acid methyl ester [Example 44, step 3] (55mg, 0.1mmole). Yield 20mg (0.04mmole,
37%). HPLC (254 nm): Method 3 Rt 3.26 min. MS (ESI) m/z 535 [M + H ].
[847] Example 46: 2-[4-[4-[5-[1-(2-chlorophenyl)ethoxycarbonylamino]cyano-
pyrazolyl]phenyl]phenyl]acetic acid
Step 1 - 5-amino(4-bromophenyl)pyrazolecarbonitrile
(4-bromophenyl)hydrazine hydrochloride (2.24 g, 10 mmol) was suspended in
ethanol (20 mL) and treated with triethylamine (1.53 mL, 11 mmol). The resulting
solution was then treated with malononitrile (1.22 g, 10 mmol) added portionwise. After
a small exotherm was observed, the reaction was heated to reflux for 1 hour. The
reaction was cooled to room temperature; the solids were collected by vacuum filtration
and rinsed with cold ethanol. The solids were air-dried. Yield = 0.93 g, 3.5 mmol (35 %).
HPLC (254 nm): Method 2, Rt 5.82 min. MS (ESI) m/z 265 [M + H ]; 263 [M + H ]; 184
[(M – Br) + H ].
Step 2 - 1-(2-chlorophenyl)ethyl N-[2-(4-bromophenyl)cyano-pyrazol
yl]carbamate
A solution of 5-amino(4-bromophenyl)pyrazolecarbonitrile [Example 46,
step 1] (26 mg, 0.1 mmol) in CH Cl (1 mL) was treated with triethylamine (28 µL, 0.2
mmol), followed by phosgene (100 µL of a 20 % v/v solution in toluene, 0.2 mmol est.).
The resulting solution was stirred at room temperature for 30 minutes. (+)(2-
chlorophenyl)ethanol (23 mg, 0.15 mmol) was added and the resulting mixture stirred at
room temperature overnight. The reaction was concentrated in vacuo to remove
volatiles, and the residue was purified by chromatography on silica-gel, eluting with a
4:1 mixture of hexanes/ethyl acetate v/v. The product was obtained as a colorless film.
Yield = 27 mg (0.06 mmol, 61 %). HPLC (254 nm): Method 1, Rt 6.31 min. MS (ESI)
+ + 1
m/z 447 [M + H ]; 445 [M + H ]. H NMR (500 MHz, CDCl ) d 7.90 (s, 1 H); 7.57 (d, J =
8.8 Hz, 2 H); 7.37 – 7.35 (m, 1 H); 7.32 (d, J = 8.8 Hz, 2 H); 7.27 (m, 3 H); 6.70 (br, 1
H); 6.14 (q, J = 6.5 Hz, 1 H); 1.54 (d, J = 6.5 Hz, 3 H).
[852] Step 3 - ethyl 2-[4-[4-[5-[1-(2-chlorophenyl)ethoxycarbonylamino]cyano-
pyrazolyl]phenyl]phenyl]acetate
In a pressure vessel, 1-(2-chlorophenyl)ethyl N-[2-(4-bromophenyl)cyano-
pyrazolyl]carbamate [Example 46, step 2] (80 mg, 0.18 mmol) was dissolved in a 2:1
v/v mixture of toluene and ethanol (2 mL) and treated with Na CO (0.6 mL of a 2N
aqueous solution) and [4-(2-ethoxyoxo-ethyl)phenyl]boronic acid (75 mg, 0.36 mmol).
The resulting mixture was degassed under Ar for 15 minutes, then treated with
Pd[Ph P] (8 mg, 0.007 mmol). The vessel was capped and immersed in an oil bath at
80 C, with vigorous magnetic stirring. Reaction was deemed complete after 14 hours.
Reaction cooled to room temperature and partitioned between ethyl acetate and water.
The organic layer was washed with water and brine. The combined aqueous layers
were back-extracted with ethyl acetate. The combined organic layers were dried over
anhydrous MgSO , filtered and concentrated in vacuo. The residue was purified by
chromatography on silica-gel, eluting with a 4:1 mixture of hexanes/ethyl acetate v/v.
The product was obtained as a white solid. Yield = 82 mg (0.16 mmol, 89 %). HPLC
(254 nm): Method 1, Rt 6.94 min. MS (ESI) m/z 529.3 [M + H ]; 485.1 [(M – EtO) + H ].
Step 4 : 2-[4-[4-[5-[1-(2-chlorophenyl)ethoxycarbonylamino]cyano-pyrazol
yl]phenyl]phenyl]acetic acid
Ethyl 2-[4-[4-[5-[1-(2-chlorophenyl)ethoxycarbonylamino]cyano-pyrazol
yl]phenyl]phenyl]acetate [Example 46, step 3] (45 mg, 0.085 mmol) was dissolved in
THF (1 mL) and treated with LiOH (1 mL of a 1M aqueous solution). The resulting
mixture was stirred at room temperature for 2 hours. The reaction was transferred to a
separatory funnel, diluted with water and extracted with ethyl acetate. The organic layer
was discarded and the aqueous layer was brought to pH 2 with a 0.1 N HCl solution.
The product was extracted with ethyl acetate. The organic layer was dried over
anhydrous MgSO4, filtered and concentrated in vacuo to yield a white solid as the pure
product. Yield = 42 mg (0.085 mmol, quantitative). HPLC (254 nm): Method 1, Rt 6.99
+ + 1
min. MS (ESI) m/z 501.3 [M + H ]; 457.2 [(M – CO H) + H ]. H NMR (500 MHz, DMSO-
d ) d 12.39 (br, 1 H); 10.42 (br, 1 H); 8.31 (s, 1 H); 7.82 (d, J = 8.6 Hz, 2 H); 7.67 (d, J =
8.3 Hz, 2 H); 7.56 (d, J = 8.6 Hz, 2 H); 7.43 (d, J = 7.7 Hz, 1 H); 7.39 (d, J = 8.3 Hz, 2
H); 7.33 – 7.29 (m, 3 H); 5.94 (q, J = 6.5 Hz, 1 H); 3.64 (s, 2 H); 1.44 (br, 3 H).
Example 47: (R)[4-[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol-
3-yl]phenyl]phenyl]cyclopropane carboxylic acid
Step 1: 2-(4-Bromo-benzoyl)oxo-butyric acid ethyl ester
Ethyl acetoacetate (1.97mL, 15.6 mmole) was added to a suspension of
magnesium chloride (1.49g, 15.6 mmole) in dichloromethane (15mL) that had been
cooled to 0 C. To the mixture was added pyridine (2.43mL, 30mmole) and stirring
continued for an additional 15 minutes. 4-Bromobenzoyl chloride (3.29g, 15mmole) in
dichloromethane (15mL) was then added to the reaction. This mixture was stirred at 0 C
for 15minutes and then at room temperature for 1 hour. At this time the mixture was
treated with 6N hydrochloric acid solution (20mL). The organic layer was separated,
dried over anhydrous MgSO , filtered and concentrated in vacuo to give a colorless oil
that was used directly in the next step.
Step 2: 3-(4-Bromo-phenyl)-1,5-dimethyl-1H-pyrazolecarboxylic acid ethyl
ester and 5-(4-Bromophenyl)-1,3-dimethyl-1H-pyrazolecarboxylic acid ethyl ester
2-(4-Bromo-benzoyl)oxo-butyric acid ethyl ester [example 47, step 1] (4.7g,
15mmole), methylhydrazine (0.79mL,15.1 mmole), p-toluenesulfonic acid (0.15g) were
mixed with ethanol (150mL) and this mixture was heated to 78 C for 2 hours. At this
point the reaction was allowed to cool and the resulting mixture was partitioned between
ethyl acetate and water. The organic layer was dried over anhydrous MgSO , filtered
and concentrated in vacuo. A crude product was obtained that was purified by silica gel
chromatography initially with hexane/ethyl acetate 95/5 as eluting solvent and then with
hexane/ethyl acetate 88/12 to afford 3-(4-Bromo-phenyl)-1,5-dimethyl-1H-pyrazole
carboxylic acid ethyl ester (600mg, 12%) and 5-(4-Bromo-phenyl)-1,3-dimethyl-1H-
pyrazolecarboxylic acid ethyl ester (190mg, 4%).
Step 3: 3-(4-Bromophenyl)-1,5-dimethyl-1H-pyrazolecarboxylic acid
A mixture of 3-(4-Bromophenyl)-1,5-dimethyl-1H-pyrazolecarboxylic acid ethyl
ester [example 47, step 2] (600mg, 1.85 mmole), 1N sodium hydroxide solution
(18.5mL) and dioxane (18.5mL) was stirred at 100 C for 3 hours. Upon cooling the
mixture was acidified to pH 3-4 with 3N hydrochloric acid solution and this was extracted
with ethyl acetate. The organic layer was dried over anhydrous MgSO , filtered and
concentrated in vacuo to yield the product as a solid (422mg, 77%).
Step 4: (R)(phenyl)ethyl N-[2-(4-bromophenyl)-1,5-dimethyl-1H-pyrazol
yl]carbamate
[864] A suspension of 3-(4-Bromophenyl)-1,5-dimethyl-1H-pyrazolecarboxylic acid
[example 47, step 3] (50 mg, 0.17 mmol) in toluene (1mL) and triethylamine (17mg, 0.17
mmole) was treated with diphenylphosphoryl azide (44µL, 0.20 mmole) and the mixture
stirred at 45 C for 3 hours and then 95 C with the evolution of a gas. After 30 minutes
(R)-(+)phenylethanol (25 mg, 0.20 mmole) was added. Heating was continued for a
further 1 hour before the mixture was allowed to cool. The reaction was concentrated in
vacuo and the residue dissolved in ethyl acetate and the solution washed with 0.1M
potassium carbonate solution and then brine. The organic layer was dried over
anhydrous MgSO , filtered and concentrated in vacuo to afford the product (64mg, 91%)
that was used directly in the next step. HPLC (254 nm): Method 3 Rt 3.10 min. MS (ESI)
m/z 416.2, 414.4 [M + H ].
Step 5: 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)phenyl]cyclopropane
carboxylic acid methyl ester.
Methyl 1-(4-bromophenyl)cyclopropanecarboxylate (1g, 3.92 mmole), potassium
acetate (461mg, 4.7 mmole), and bis(pinacolato)diboron (1.19g, 4.70 mmole) were
mixed in dioxane (10mL) and degassed for 10minutes under a stream of argon. [1,1'-
bis(diphenylphosphino)ferrocene]palladium(II) dichloride (32mg) was added and the
mixture was heated at 95 C for 2 hours. At this point the mixture was allowed to cool
and the mixture was partitioned between ethyl acetate and water. The organic layer was
dried over anhydrous MgSO , filtered and concentrated in vacuo. A crude product was
obtained that was purified by silica gel chromatography with hexane/ethyl acetate 95/5
as eluting solvent to afford the product as a white solid (1.02g, 86%).
[867] Step 6: (R)[4-[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]phenyl]cyclopropanecarboxylic acid methyl ester
In a pressure vessel, (R)(phenyl)ethyl N-[2-(4-bromophenyl)-1,5-dimethyl-1H-
pyrazolyl]carbamate [example 47, step 4) (64 mg, 0.16 mmol) was dissolved in a 2:1
v/v mixture of toluene and ethanol (2 mL) and treated with Na CO (0.5 mL of a 2N
aqueous solution) and 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan
yl)phenyl]cyclopropane carboxylic acid methyl ester [Example 47, step 5] (52 mg, 0.17
mmol). The resulting mixture was degassed under argon for 15 minutes, and then
treated with tetrakis (triphenyl-phosphine)palladium(0) (1 mg, 0.006 mmol). The vessel
was capped and immersed in an oil bath at 80 C, with vigorous magnetic stirring
overnight. This reaction was cooled to room temperature and partitioned between ethyl
acetate and water. The organic layer was washed with water and brine. The combined
aqueous layers were back-extracted with ethyl acetate. The combined organic layers
were dried over anhydrous MgSO4, filtered and concentrated in vacuo. This material
was purified by preparative TLC eluting with hexane/ethyl acetate 1/1 v/v to give the
product as a yellow film (10 mg, 13%).
Step 7: (R)[4-[4-[2,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]phenyl]cyclopropanecarboxylic acid
(R)[4-[4-[1,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]phenyl]cyclopropanecarboxylic acid methyl ester [example 47, step 6] (10mg,
0.02 mmole) was dissolved in THF (1 mL) and treated with LiOH (1 mL of a 2M aqueous
solution). The resulting mixture was stirred overnight and then refluxed for 5 hours. The
reaction was cooled and transferred to a separatory funnel, diluted with water and
extracted with ethyl acetate. The organic layer was discarded and the aqueous layer
was brought to pH 1 with a 0.1 N HCl solution when the product was extracted with ethyl
acetate. This organic layer was dried over anhydrous MgSO , filtered and concentrated
in vacuo. A residue was obtained which was triturated with dimethoxyethane. The solids
were filtered and the filtrate evaporated to dryness to yield a residue that was purified by
preparative TLC, eluting with ethyl acetate/hexane 2/1 v/v. The product was obtained as
a white solid (3 mg, 28 %). HPLC (254 nm): Method 3 Rt 3.12 min. MS (ESI) m/z 496.6
[M + H ].
Example 48: (R)[4-[4-[2,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol-
3-yl]phenyl]phenyl]cyclopropane carboxylic acid
Step 1: 5-(4-Bromo-phenyl)-1,3-dimethyl-1H-pyrazolecarboxylic acid
A mixture of 5-(4-Bromo-phenyl)-1,3-dimethyl-1H-pyrazolecarboxylic acid
ethyl ester [example 47, step 2] (190mg, 0.59 mmole), 1N sodium hydroxide solution
(5.9mL) and dioxane (5.9mL) was stirred at 100 C for 1 hour. Upon cooling the mixture
was acidified to pH 3-4 with 3N hydrochloric acid solution and this was extracted with
ethyl acetate. The organic layer was dried over anhydrous MgSO , filtered and
concentrated in vacuo to yield the product as a solid (170mg, 98%).
Step 2: (R)(phenyl)ethyl N-[5-(4-Bromo-phenyl)-1,3-dimethyl-1H-pyrazole
yl]-carbamate
[875] 5-(4-Bromo-phenyl)-1,3-dimethyl-1H-pyrazolecarboxylic acid [example 48,
step 1] (50 mg, 0.17 mmol) was used to prepare (R)(phenyl)ethyl N-[5-(4-Bromo-
phenyl)-1,3-dimethyl-1H-pyrazoleyl]carbamate according to the procedure described
for example 47, step 4 to afford the product (64mg, 91%) that was used in the next step.
HPLC (254 nm): Method 3 Rt 3.03 min. MS (ESI) m/z 416.5 [M + H ].
[876] Step 3: (R)[4-[4-[2,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]-phenyl]cyclopropane carboxylic acid methyl ester
In a pressure vessel, (R)(phenyl)ethyl N-[5-(4-Bromo-phenyl)-1,3-dimethyl-
1H-pyrazoleyl]carbamate [example 48, step 2) (64 mg, 0.16 mmol) was used to
prepare the product as an oil (32 mg, 41%) using a similar procedure to that described
for example 47, step 6
Step 4: (R)[4-[4-[2,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]phenyl]cyclopropane carboxylic acid
(R)[4-[4-[2,5-dimethyl(1-phenylethoxycarbonylamino)pyrazol
yl]phenyl]phenyl]cyclopropane carboxylic acid methyl ester [example 48, step 3] (32mg,
0.06 mmole) was dissolved in THF (3 mL) and treated with LiOH (3 mL of a 2M aqueous
solution). The resulting mixture was stirred overnight and then refluxed for 5 hours. The
reaction was cooled and transferred to a separatory funnel, diluted with water and
extracted with ethyl acetate. The organic layer was discarded and the aqueous layer
was brought to pH 1 with a 0.1 N HCl solution when the product was extracted with ethyl
acetate. This organic layer was dried over anhydrous MgSO , filtered and concentrated
in vacuo. A residue was obtained which was triturated with dimethoxyethane. The solids
were filtered and the filtrate evaporated to dryness to yield a residue that was purified by
preparative TLC, eluting with ethyl acetate/hexane 2/1 v/v. The product was obtained as
a white solid (10 mg, 32 %). HPLC (254 nm): Method 3 Rt 2.92 min. MS (ESI) m/z 496.6
[M + H ].
Example 49: (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-
pyrazolyl}fluoro-biphenylyl)-cyclopropanecarboxylic acid
Step 1: Ethyl (E)(dimethylamino)oxo-butenoate
Ethyl pyruvate (5 g, 43.1 mmol) was dissolved in CH Cl (86 mL) and treated
with dimethylformamide dimethylacetal (5.73 mL, 43.1 mmol). The reaction was stirred
at room temperature for 2 hours and concentrated in vacuo. The crude was used as is in
the next step. Yield = 7.4 g.
Step 2: ethyl 2-(4-bromophenyl)pyrazolecarboxylate
4-Bromophenyl hydrazine hydrochloride (2.0 g, 8.95 mmol) was dissolved in
MeOH (18 mL) and treated with crude ethyl (E)(dimethylamino)oxo-butenoate
[example 3, step 1] (1.54 g, 9.0 mmol). The resulting mixture was stirred at room
temperature for 6 hours. The volatiles were removed in vacuo and the residue was
purified by chromatography on silica-gel, eluting with a 95:5 mixture of hexanes/ethyl
acetate v/v, increasing the polarity to 9:1 over time. Two isomeric products were
isolated: ethyl 2-(4-bromophenyl)pyrazolecarboxylate as an orange solid (0.82 g, 2.78
mmol, 31 %) and ethyl 1-(4-bromophenyl)pyrazolecarboxylate as a red solid (0.44 g,
1.49 mmol, 17 %).
Ethyl 2-(4-bromophenyl)pyrazolecarboxylate: HPLC (254 nm): Method 2 Rt
+ + +
.22 min. MS (ESI) m/z 297 [M + H ]; 294.8 [M + H ]; 252 [(M – EtO) + H ]; 250 [(M –
EtO) + H ]. H NMR (500 MHz, CDCl ) d 7.69 (d, J = 1.9 Hz, 1 H); 7.58 (d, J = 8.7 Hz, 2
H); 7.32 (d, J = 8.7 Hz, 2 H); 7.03 (d, J = 1.9 Hz, 1 H); 4.26 (q, J = 7.1 Hz, 2 H); 1.28 (t,
J = 7.1 Hz, 3 H).
Ethyl 1-(4-bromophenyl)pyrazolecarboxylate: H NMR (500 MHz, CDCl3) d
7.91 (d, J = 2.4 Hz, 1 H); 7.65 (d, J = 7.2 Hz, 2 H); 7.60 (d, J = 7.2 Hz, 2 H); 7.00 (d, J =
2.4 Hz, 1 H); 4.44 (q, J = 7.0 Hz, 2 H); 1.43 (t, J = 7.0 Hz, 3 H).
Step 3: 2-(4-Bromo-phenyl)fluoro-2H-pyrazolecarboxylic acid ethyl ester
[888] Ethyl 2-(4-bromophenyl)pyrazolecarboxylate (1.08 g, 3.68 mmol) was
dissolved in acetonitrile (12 mL) and the resulting mixture was treated with glacial acetic
acid (4.6 mL). To this solution, 1-chloromethylfluoro-1,4-diazoniabicyclo[2.2.2]octane
bis(tetrafluoroborate) (Selectfluor®, 3.91 g, 11.04 mmol) was added in one portion and
the resulting mixture was heated to 105 C for 18 hours. The mixture was cooled to
room temperature and the volatiles were removed in vacuo. The crude residue was
loaded directly onto a silica-gel column and purified by elution with 95:5 mixture of
hexanes/ethyl acetate v/v, increasing the polarity to 9:1 over time. The product was
isolated as a white solid (410 mg, 1.31 mmol, 36 %) and starting material was recovered
(272 mg, 0.93 mmol, 25 %). For 2-(4-Bromo-phenyl)fluoro-2H-pyrazolecarboxylic
acid ethyl ester: HPLC (254 nm): Method 3 Rt 2.97 min. MS (ESI) m/z 313.1 [M + H ].
H NMR (500 MHz, CDCl ) d 7.60 (s, 1 H); 7.58 (d, J = 9 Hz, 2 H); 7.29 (d, J = 9 Hz, 2
H); 4.30 (q, J = 7.1 Hz, 2 H); 1.28 (t, J = 7.1 Hz, 3 H).
Step 4: 2-(4-Bromo-phenyl)fluoro-2H-pyrazolecarboxylic acid
A stirred solution of 2-(4-bromo-phenyl)fluoro-2H-pyrazolecarboxylic acid
ethyl ester (410 mg, 1.31 mmol) in THF (13 mL) was treated with LiOH 1 N aqueous
solution (13 mL) and the resulting mixture was stirred at room temperature overnight.
The reaction was deemed complete by thin layer chromatography and HPLC/MS. The
reaction mixture was partitioned between ethyl acetate and 1 N aqueous HCl solution
(100 mL v/v) and transferred to a separatory funnel. The organic layer was separated
and the aqueous layer was back-extracted with ethyl acetate (30 mL). The combined
organic layers were dried over anhydrous MgSO , filtered and concentrated in vacuo to
afford the pure product as a white solid (347 mg, 1.22 mmol, 93 %). HPLC (254 nm):
Method 3 Rt 2.82 min. MS (ESI) m/z 285.1 [M + H ].
Step 5: (R)-[2-(4-Bromo-phenyl)fluoro-2H-pyrazolyl]-carbamic acid 1-(2-
chloro-phenyl)-ethyl ester
2-(4-Bromo-phenyl)fluoro-2H-pyrazolecarboxylic acid (347 mg, 1.22 mmol)
was suspended in toluene (12 mL) and treated with triethylamine (205 µL, 1.46 mmol).
The resulting solution was treated with diphenylphosphoryl azide (316 µL, 1.46 mmol)
and heated to 65 C. (R)- 1-(2-Chloro-phenyl)-ethanol (230 mg, 1.46 mmol) was added
to the reaction mixture and the temperature was increased to 105 C for 30 minutes,
during which time vigorous gas evolution was observed. The reaction was brought to 65
C and stirred at that temperature for 4 hours. The reaction was deemed complete by
HPLC/MS. After cooling, the volatiles were removed in vacuo and the crude residue was
purified by silica gel chromatography, eluting with a hexanes/ethyl acetate gradient.
Product isolated as a white solid (452 mg, 1.03 mmol, 85 %). HPLC (254 nm): Method 3
Rt 3.16 min. MS (ESI) m/z 440.1 [M + H ].
[893] Step 6: (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-pyrazol-
1-yl}fluoro-biphenylyl)-cyclopropanecarboxylic acid
A stirred suspension of (R)-[2-(4-Bromo-phenyl)fluoro-2H-pyrazolyl]-
carbamic acid 1-(2-chloro-phenyl)-ethyl ester (88 mg, 0.2 mmol), 2:1 v/v toluene/ethanol
(2 mL), 2 M aqueous solution of Na CO (670 µL) and 1-(4-borono
fluorophenyl)cyclopropanecarboxylic acid (45 mg, 0.2 mmol) was degassed under
nitrogen for 10 minutes and treated with Pd[Ph P] (12 mg, 0.01 mmol). The resulting
mixture was immersed in an oil bath with stirring at 90 C for 12 hours. The reaction was
cooled, transferred to a separatory funnel and diluted with ethyl acetate (50 mL). The
mixture was carefully treated with 1 N aqueous HCl solution (20 mL). The organic layer
was separated, washed with brine, dried over anhydrous MgSO , filtered and
concentrated in vacuo. The crude residue was purified by preparative TLC plate (1000
µm), eluting with a 1:1 v/v hexanes/ethyl acetate mixture. The product was obtained as
a tan solid. Yield = 35 mg (35 %). HPLC (254 nm): Method 3, Rt 3.11 min. MS (ESI) m/z
538.3 [M + H ].
Example 50: (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-
pyrazolyl}fluoro-biphenylyl)-cyclopropanecarboxylic acid
[896] The title compound was prepared in analogous fashion as in Example 49 using
(R)-[2-(4-Bromo-phenyl)fluoro-2H-pyrazolyl]-carbamic acid 1-(2-chloro-phenyl)-
ethyl ester (Example 49, Step 5 (88 mg, 0.2 mmol), and 1-[4-(dihydroxyboranyl)
fluorophenyl]-cyclopropanecarboxylic acid. Yield 40 mg (37 %) as a light yellow solid.
HPLC (254 nm): Method 3, Rt 3.14 min. MS (ESI) m/z 538.3 [M + H ].
[897] Example 51: (R)(2-Chloro-4'-{5-[1-(2-chloro-phenyl)-ethoxycarbonylamino]
fluoro-pyrazolyl}-biphenylyl)-cyclopropanecarboxylic acid
The title compound was prepared in analogous fashion as in Example 49 using
(R)-[2-(4-Bromo-phenyl)fluoro-2H-pyrazolyl]-carbamic acid 1-(2-chloro-phenyl)-
ethyl ester (Example 49, Step 5 (88 mg, 0.2 mmol), and 1-[3-chloro
(dihydroxyboranyl)phenyl]-cyclopropanecarboxylic acid. Yield 24 mg (22 %) as a light
yellow solid. HPLC (254 nm): Method 3, Rt 3.40 min. MS (ESI) m/z 554.4 [M + H ].
Example 52: (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-
pyrazolyl}methyl-biphenylyl)-cyclopropanecarboxylic acid
The title compound was prepared in analogous fashion as in Example 49 using
(R)-[2-(4-Bromo-phenyl)fluoro-2H-pyrazolyl]-carbamic acid 1-(2-chloro-phenyl)-
ethyl ester (Example 49, Step 5 (88 mg, 0.2 mmol), and 1-[4-(dihydroxyboranyl)
methylphenyl]cyclo-propanecarboxylic acid. Yield 36 mg (34 %) as a light yellow
solid. HPLC (254 nm): Method 3, Rt 3.19 min. MS (ESI) m/z 534.3 [M + H ].
Example 53: (R)(4'-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]fluoro-
pyrazolyl}-biphenylyl)-cyclopropanecarboxylic acid
The title compound was prepared in analogous fashion as in Example 49 using
(R)-[2-(4-Bromo-phenyl)fluoro-2H-pyrazolyl]-carbamic acid 1-(2-chloro-phenyl)-
ethyl ester (Example 49, Step 5 (88 mg, 0.2 mmol), and 4-(1-
carboxycyclopropyl)phenylboronic acid, pinacol ester. Yield 9 mg (9 %) as a white solid.
HPLC (254 nm): Method 3, Rt 3.20 min. MS (ESI) m/z 520.0 [M + H ].
Example 54: (R)- 1-{4'-[5-(1-Phenyl-ethoxycarbonylamino)trifluoromethyl-
pyrazolyl]-biphenylyl}-cyclopropanecarboxylic acid
Step 1: 2-(4-Bromo-phenyl)iodo-2H-pyrazolecarboxylic acid ethyl ester
Ethyl 2-(4-bromophenyl)pyrazolecarboxylate (Example 49, Step 2, 294 mg,
1.0 mmol) was dissolved in methanol (3 mL) and treated dropwise with iodine
monochloride (115 µL, 2.3 mmol). The resulting mixture was heated to 50 C for 3
hours. Another aliquot of iodine monochloride (120 µL) was added and heating
continued for additional 3 hours. The reaction was deemed complete by HPLC/MS. After
cooling to room temperature, the reaction mixture was diluted with ethyl acetate (30 mL)
and transferred to a separatory funnel. The organic layer was washed successively with
1 N Na2S2O3 aqueous (30 mL) and brine (30 mL). The organic layer was separated,
washed with brine, dried over anhydrous MgSO , filtered and concentrated in vacuo.
The product [2-(4-bromo-phenyl)iodo-2H-pyrazolecarboxylic acid ethyl ester] was
obtained as a pale yellow solid (420 mg, quant.) and used as is in the next step. HPLC
(254 nm): Method 3, Rt 3.33 min. MS (ESI) m/z 421.0, 423.0 [M + H ].
Step 2: 2-(4-Bromo-phenyl)trifluoromethyl-2H-pyrazolecarboxylic acid ethyl
ester
2-(4-Bromo-phenyl)iodo-2H-pyrazolecarboxylic acid ethyl ester (420 mg,
1.0 mmol) was dissolved in DMF (4 mL) and the resulting solution was degassed with
nitrogen for 10 minutes. (1,10-Phenanthroline) (trifluoromethyl) copper (I)
(Trifluoromethylator™, 520 mg, 1.5 mmol) was added in one portion under an inert
atmosphere and the resulting mixture was stirred at 50 C for 18 hours. The reaction
was cooled to room temperature and filtered through a pad of Celite and rinsed
thoroughly with ethyl acetate. The filtrates were washed with 1 N HCl aqueous, brine,
dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product 2-
(4-bromo-phenyl)trifluoromethyl-2H-pyrazolecarboxylic acid ethyl ester was used
as is in the next step (291 mg, 0.80 mmol, 80 %). HPLC (254 nm): Method 3, Rt 3.23
min. MS (ESI) m/z 365.2 [M + H ].
Step 3: 2-(4-Bromo-phenyl)trifluoromethyl-2H-pyrazolecarboxylic acid
2-(4-Bromo-phenyl)trifluoromethyl-2H-pyrazolecarboxylic acid ethyl ester
(291 mg, 0.80 mmol) in THF (8 mL) was treated with LiOH 1 N aqueous solution (8 mL)
and the resulting mixture was stirred at room temperature for 3 hours. The reaction was
deemed complete by thin layer chromatography and HPLC/MS. The reaction mixture
was partitioned between ethyl acetate and 1 N aqueous HCl solution (100 mL v/v) and
transferred to a separatory funnel. The organic layer was separated and the aqueous
layer was back-extracted with ethyl acetate (30 mL). The combined organic layers were
dried over anhydrous MgSO , filtered and concentrated in vacuo to afford the pure
product as a white solid (268 mg, 0.80 mmol, quant.). HPLC (254 nm): Method 3 Rt 2.97
min. MS (ESI) m/z 335.2 [M + H ].
Step 4: (R)- [2-(4-Bromo-phenyl)trifluoromethyl-2H-pyrazolyl]-carbamic
acid 1-phenyl-ethyl ester
[911] 2-(4-Bromo-phenyl)trifluoromethyl-2H-pyrazolecarboxylic acid (268 mg,
0.80 mmol) was suspended in toluene (8 mL) and treated with triethylamine (135 µL,
0.97 mmol). The resulting solution was treated with diphenylphosphoryl azide (209 µL,
0.97 mmol) and heated to 65 C. (R)(phenyl)-ethanol (118 mg, 0.97 mmol) was
added to the reaction mixture and the temperature was increased to 105 C for 30
minutes, during which time vigorous gas evolution was observed. The reaction was
brought to 65 C and stirred at that temperature for 4 hours. The reaction was deemed
complete by HPLC/MS. After cooling, the volatiles were removed in vacuo and the crude
residue was purified by silica gel chromatography, eluting with a hexanes/ethyl acetate
gradient. Product isolated as a white solid (195 mg, 0.43 mmol, 54 %). HPLC (254 nm):
Method 3 Rt 3.23 min. MS (ESI) m/z 454.0, 456.1 [M + H ].
Step 5: (R)- 1-{4'-[5-(1-Phenyl-ethoxycarbonylamino)trifluoromethyl-pyrazol
yl]-biphenylyl}-cyclopropanecarboxylic acid
A stirred suspension of (R)- [2-(4-Bromo-phenyl)trifluoromethyl-2H-pyrazol
yl]-carbamic acid 1-phenyl-ethyl ester (98 mg, 0.22 mmol), 2:1 v/v toluene/ethanol (2.2
mL), 2 M aqueous solution of Na CO (720 µL) and 4-(1-
carboxycyclopropyl)phenylboronic acid, pinacol ester (124 mg, 0.43 mmol) was
degassed under nitrogen for 10 minutes and treated with Pd[Ph P] (12 mg, 0.01 mmol).
The resulting mixture was immersed in an oil bath with stirring at 95 C for 3 hours. The
reaction was cooled, transferred to a separatory funnel and diluted with ethyl acetate
(50 mL). The mixture was carefully treated with 1 N aqueous HCl solution (20 mL). The
organic layer was separated, washed with brine, dried over anhydrous MgSO , filtered
and concentrated in vacuo. The crude residue was purified by preparative TLC plate
(1000 µm), eluting with a 1:1 v/v hexanes/ethyl acetate mixture. The product was
obtained as a tan solid. Yield = 6.8 mg (6 %). HPLC (254 nm): Method 3, Rt 3.21 min.
MS (ESI) m/z 536.3 [M + H ].
Example 55: (R){2-Fluoro-4'-[5-(1-phenyl-ethoxycarbonylamino)
trifluoromethyl-pyrazolyl]-biphenylyl}-cyclopropanecarboxylic acid
The title compound was prepared in analogous fashion as in Example 54
using(R)- [2-(4-Bromo-phenyl)trifluoromethyl-2H-pyrazolyl]-carbamic acid 1-
phenyl-ethyl ester (Example 54, Step 4 (98 mg, 0.22 mmol) and 1-[4-(dihydroxyboranyl)-
3-fluorophenyl]cyclopropanecarboxylic acid. Yield 7 mg (6 %) as a white solid. HPLC
(254 nm): Method 3, Rt 3.11 min. MS (ESI) m/z 554.4 [M + H ]
Example 56: (R)(4-{5-[5-(1-Phenyl-ethoxycarbonylamino)-pyrazolyl]-
pyridinyl}-phenyl)-cyclopropanecarboxylic acid
Step 1: 2-(6-Chloro-pyridinyl)-2H-pyrazolecarboxylic acid ethyl ester
2-(6-Chloro-pyridinyl)-2H-pyrazolecarboxylic acid ethyl ester was prepared
in analogous fashion as in Example 49, Step 2 using (6-chloro-pyridinyl)-hydrazine
hydrochloride (9.89 g, 48.68 mmol; prepared according to WO2005/92856A1) and ethyl
(E)(dimethylamino)oxo-butenoate (7.82 g, 45.68 mmol, Example 49, Step 1).
Yield = 1.35 g (5.38 mmol, 12 %). HPLC (254 nm): Method 3 Rt 2.87 min. MS (ESI) m/z
252.2 [M + H ]. H NMR (500 MHz, CDCl ) d 8.50 (d, J = 3.0 Hz, 1 H); 7.77 (dd, J = 3.0
Hz, J = 8.5 Hz, 1 H); 7.74 (d, J = 2.0 Hz, 1 H); 7.43 (d, J = 8.5 Hz, 1 H); 7.08 (d, J = 2.0
Hz, 1 H); 4.28 (q, J = 7.5 Hz, 2 H); 1.30 (t, J = 7.5 Hz, 3 H).
[919] Step 2: 2-(6-Chloro-pyridinyl)-2H-pyrazolecarboxylic acid hydrochloride
salt
A stirred solution of 2-(6-Chloro-pyridinyl)-2H-pyrazolecarboxylic acid ethyl
ester [Example 56, step 1] (1.35 g, 5.4 mmol) in THF/water 8:2 v/v (35 mL) was treated
with LiOH 1 N aqueous solution (6.5 mL) and the resulting mixture was stirred at room
temperature for 3 hours. The reaction was deemed complete by thin layer
chromatography and HPLC/MS. The reaction mixture was diluted with water (100 mL)
and washed with dichloromethane (60 mL). The aqueous layer was acidified with 1 N
aqueous HCl solution to pH 2 resulting in a white suspension. The solids were filtered,
rinsed with water and air-dried to afford the title compound as a white solid. Yield = 0.90
g (3.46 mmol, 64 %). HPLC (254 nm): Method 3 Rt 2.65 min. MS (ESI) m/z 224.3 [M +
H ].
Step 3: (R)-[2-(6-Chloro-pyridinyl)-2H-pyrazolyl]-carbamic acid 1-phenyl-
ethyl ester
2-(6-Chloro-pyridinyl)-2H-pyrazolecarboxylic acid hydrochloride salt
[Example 56, step 2]( 0.90 g, 4.03 mmol) was suspended in toluene (27 mL) and treated
with di-isoproprylethylamine (1.28 mL, 8.86 mmol). The resulting solution was treated
with diphenylphosphoryl azide (855 µL, 4.83 mmol) and heated to 65 C. (R)- 1-
(phenyl)-ethanol (600 µL, 6.03 mmol) was added to the reaction mixture and the
temperature was increased to 105 C for 30 minutes, during which time vigorous gas
evolution was observed. The reaction was brought to 65 C and stirred at that
temperature for 4 hours. The reaction was deemed complete by HPLC/MS. After
cooling, volatiles were removed in vacuo and the crude residue purified by silica gel
chromatography, eluting with a hexanes/ ethyl acetate gradient. Product isolated as a
white solid. Yield = 0.60 g (1.75 mmol, 44 %). HPLC (254 nm): Method 3 Rt 3.05 min.
MS (ESI) m/z 343.2 [M + H ].
Step 4: (R)(4-{5-[4-Methyl(1-phenyl-ethoxycarbonylamino)-pyrazolyl]-
pyridinyl}-phenyl)-cyclopropanecarboxylic acid methyl ester
A stirred suspension of (R)-[2-(6-Chloro-pyridinyl)-2H-pyrazolyl]-carbamic
acid 1-phenyl-ethyl ester [Example 56, step 3] (240 mg, 0.70 mmol) in 2:1 v/v
toluene/ethanol (7 mL), 2 M aqueous solution of Na CO (1.5 mL) and 1-[4-(4,4,5,5-
tetramethyl-[1,3,2]dioxaborolanyl)-phenyl]-cyclopropanecarboxylic acid methyl ester
(260 mg, 0.84 mmol) was degassed under nitrogen for 10 minutes and treated with
Pd[Ph P] (42 mg, 0.036 mmol). The resulting mixture was immersed in an oil bath with
stirring at 90 C for 15 hours. The reaction was cooled, transferred to a separatory
funnel and diluted with ethyl acetate (50 mL). The mixture was carefully treated with 1 N
aqueous HCl solution (20 mL). The organic layer was separated, washed with brine,
dried over anhydrous MgSO , filtered and concentrated in vacuo. The crude residue
was purified by silica gel chromatography, eluting with a 0-30% hexanes/ethyl acetate
gradient of increasing polarity. The product was obtained as a tan solid. Yield = 136 mg
(0.28 mmol, 40 %). HPLC (254 nm): Method 3 Rt 2.93 min. MS (ESI) m/z 483.4 [M +
H ].
[925] Step 6: (R)(4-{5-[5-(1-Phenyl-ethoxycarbonylamino)-pyrazolyl]-pyridin
yl}-phenyl)-cyclopropanecarboxylic acid
A solution of (R)(4-{5-[4-Methyl(1-phenyl-ethoxycarbonylamino)-pyrazol
yl]-pyridinyl}-phenyl)-cyclopropanecarboxylic acid methyl ester (136 mg, 0.28 mmol)
in a 2:1 v/v mixture of THF/water (3 mL) was treated with a 1 N LiOH aqueous solution
(420 µL) and stirred at ambient temperature for 16 hours. The reaction was brought to
pH 1 by addition of a 1 N HCl aqueous solution. The mixture was extracted with EtOAc
and washed with water. The organic layer was dried over anhydrous Na2SO4, filtered
and concentrated in vacuo. The product was obtained as an off white solid Prepared in
analogous fashion as in Example M1, Step 6 using the following reagents and amounts:
(R)(4-{5-[5-(1-phenyl-ethoxycarbonylamino)-pyrazolyl]-pyridinyl}-phenyl)-
cyclopropanecarboxylic acid methyl ester (136 mg, 0.28 mmol), THF/water 2:1 v/v (3
mL), 1 N aqueous LiOH solution (420 µL). Yield = 15 mg (0.032 mmol, 11 %). HPLC
(254 nm): Method 3 Rt 2.93 min. MS (ESI) m/z 483.3 [M + H ].
Compounds 57-458 of Table 1 and derivatives thereof are prepared from the
according to procedures outlined for compounds 1-56. The heterocyclic amines or
esters required to assemble the corresponding carbamates were prepared based on
methods described in citations 1-24.
Certain isoxazole substitutions are prepared following construction of the
appropriate aryl isoxazole (3, Scheme 1). Direct flurorination or bromination and
cyanation provides arylbromide (4) or acid (5) after palladium catalyzed carbonylation.
Scheme 1
O O A
NH OH O
DMF,DMA
A O A
Br N Br
CO H
Selectfluor 2
CO, PdCl (dppf)
or Br2/HOAc
followed by Zn(CN) ,
R F= F, Br, CN
Pd[PPh ]
3 4 A= Ch, N
Acid (5, scheme 2) may be directly coupled with amines to afford amide
intermediates (6) which may be converted to the carbamate products (7) following acid
hydrolysis, Curtius rearrangement and deprotection with acid.
Scheme 2
CO H
1) LiOH
HBTU, DIEA
z R NH
B 2) DPPA
H N R
OH R
F= F, Br, CN
A= CH, N
3) TFA
The acid (5) may be reduced to alcohol (8) and/or converted to its chloride (9) as
in scheme 3. Alcohols may be converted to their ether analogs (10) by rhodium
catalyzed insertion into diazo intermediates N -z-R , or the amines (11) may be
generated from chlorides (IX)
Scheme 3
CO H
O OH
O Cl
SOCl
BH .THF
H N R , isoamyl nitrite
F= F, Br, CN
1) 2
A= CH, N
H N R
2) N R , Rh OAc
2 2 4
O R O N R
Alternatively the bromides (4) may be directly coupled to alcohols or amines
(UV-Z-R ) whereby U is -OH or –NH2 by thermal or metal catalyzed halide
displacement as in scheme 4. All key intermediates (10-12) may be further modified to
produce final products as described in scheme 1 using acid hydrolysis, Curtius
rearrangement followed by acid deprotection
Scheme 4
V R U
O V B
Example 57. Receptor Binding Assays
Binding affinity of compounds of Formula I-XII were determined based on their
ability to displace tritiated lysophosphatidic acid ([ H]-LPA) from CHO cells expressing
LPA1R in a protocol similar to that described in reference 17. In a 96 well format, CHO
cells expressing human LPA1R [Cerep] were treated with [ H]-LPA (2nM). Test
compounds were added in increasing concentration to each well and incubated at room
temperature for 90 minutes. At this time the plates were washed and the wells counted
for radioactivity. Results were compared to a control in which cells were treated with
[ H]-LPA in the presence of 10µM unlabeled LPA. The specific ligand binding to the
receptors was defined as the difference between the total binding and the nonspecific
binding determined in the presence of an excess of unlabelled ligand. The results were
expressed as a percent of control specific binding ((measured specific binding/control
specific binding) x 100) and as a percent inhibition of control specific binding (100-
((measured specific binding/control specific binding) x 100)) obtained in the presence of
the test compounds. The IC value (concentration causing a half-maximal inhibition of
control specific binding) and Hill coefficient (nH) were determined by non-linear
regression analysis of the competition curve generated with mean replicate values using
Hill equation curve fitting (Y = D + [(A – D)/(1 + (C/C50)nH)], where Y = specific binding,
D = minimum specific binding, A = maximum specific binding, C = compound
concentration, C50 = IC50, and nH = slope factor). This analysis was performed using a
software developed at Cerep (Hill software) and validated by comparison with data
generated by the commercial software SigmaPlot® 4.0 for Windows® (© 1997 by SPSS
Inc.). The inhibition constant (Ki) was calculated using the Cheng Prusoff equation (Ki =
IC50/(1+(L/KD)), where L = concentration of radioligand in the assay, and KD = affinity
of the radioligand for the receptor). A scatchard plot was used to determine the Kd.
Example 58. Calcium Flux Assay
Inhibition of LPA-stimulated Ca flux was used to assess compound potency
using FLIPR technology in a 96 well plate format. The assay buffer used was a modified
Hanks Balanced Salt Solution (HBSS) where HBSS was supplemented to contain
20mM HEPES and 2.5mM Probenecid at pH7.4 (Millipore, GPCR Profiler ). LPA1R
expressing cells (Millipore) were plated and prepared 24 hours prior to assay of test
2+ 2+
articles. Ca ion flux was assessed from fluorescence of a Fluo-based No Wash Ca
dye. Antagonist data are generated from plates with LPA concentrations sufficient to
generate 80% efficacy [EC ]. Percentage inhibition was calculated from a reduction of
efficacy according to concentration of compounds of Formula I-VI. For dose responses
the inhibition data was used to calculate compound IC .
TETRA
The agonist assay was conducted on a FLIPR instrument where the test
compound(s), vehicle controls, and reference agonist were added to the assay plate
after a fluorescence baseline was established. The agonist assay was a total of 180
seconds and was used to assess each compound’s ability to activate each GPCR
assayed. Upon completion of the agonist assay, the assay plate was removed from the
TETRA
FLIPR and incubated at 25°C for seven (7) minutes. After the incubation period, the
TETRA
assay plate was placed back in the FLIPR and the antagonist assay was initiated.
Antagonist Assay: Using EC potency values determined during the agonist
assay, all pre-incubated sample compound wells were challenged with EC
concentration of reference agonist after establishment of a fluorescence baseline. The
antagonist assay was conducted using the same assay plate that was used for the
TETRA
agonist assay. The antagonist assay was conducted on a FLIPR instrument where
9 vehicle controls and EC concentration of reference agonist were added to
appropriate wells. The antagonist assay was a total of 180 seconds and was used to
assess each compound’s ability to inhibit each GPCR assayed.
Data Processing: All assay plate data were subjected to appropriate baseline
corrections. After baseline corrections were applied, maximum fluorescence values
were exported and data processed to calculate percentage activation (relative to Emax
reference agonist and vehicle control values), percentage inhibition (relative to EC80
and vehicle control values), and additional statistical values (i.e. Z’, percentage variation
between replicate data values) to assess the quality of each plate. Where assay plate
data were rejected, additional experiments were conducted. All dose response curves
were generated using GraphPad Prism. The curves were fit by utilizing “Sigmoidal Dose
Response (Variable Slope)” equation where the bottom parameter was fixed to “0.”
Where appropriate, the top parameter was fixed to “100” to better predict potency values
when a full curve was not generated by the concentrations assayed.
Antagonist activity data for representative compounds prepared according to the
synthetic methods disclosed herein are presented in Table 2.
Table 2. In vitro biological data for representative compounds of Formula I-XII
Unless otherwise noted, compounds that were tested had an IC of less than 50 µM in
the LPA1R Ca flux functional assay.
LPA1 R LPA1 R LPA1 R
Example Example Example
Antagonist Antagonist Antagonist
Number Number Number
Activity Activity Activity
1 C 20 A 37 A
2 C 21 A 38 A
3 D 22 A 39 A
4 B 23 A 40 A
A 24 A 41 A
6 D 25 A 42 A
7 D 26 A 43 B
8 D 27 A 44 A
9 D 28 A 45 A
D 29 C 46 C
11 D 30 D 47 B
12 D 30 C 48 C
13 D 31 A 49 A
14 D 31 A 50 A
D 32 A 51 A
16 D 33 A 52 A
17 A 34 A 53 A
18 D 35 A 54 B
19 D 36 A 55 B
56 A
Unless otherwise noted, compounds that were tested had an IC of less than 50
µM in the LPA1R Ca flux functional assay. A = less than 0.3 µM; B = greater than
0.3 µM and less than 1 µM; C = greater than 1 µM and less than 50 µM; D = greater
than 50 µM
CITATIONS
1) Gyorkos A. C., Corrette C. P., ChoS. Y., Turner T. M., Aso K., Kori M.,
Gyoten M., Condroski K. R., Siedem C. S., Boyd S. A. WO2005099688, 2005
2) Maiti, Swarupananda; Sridharan, Vellaisamy; Menendez, J. Carlos;
Journal of Combinatorial Chemistry, 2010 , vol. 12, # 5 p. 713 – 722
3) Takagi M., Nakamura T., Matsuda I., Kiguchi T., Ogawa N., Ozeki H.
US2009/36450 A1, 2009
[4] 4) Lee, Len F.; Schleppnik, Francis M.; Howe, Robert K.; Journal of
Heterocyclic Chemistry, 1985 , vol. 22, p. 1621 – 1630
5) Dehmel, Florian; Abarbri, Mohamed; Knochel, Paul; Synlett, 2000 , # 3
p. 345 – 346
6) Abarbri, Mohamed; Thibonnet, Jerome; Berillon, Kaurent; Dahmel,
Florian; Rottlaender, Mario; Knochel, Paul; Journal of Organic Chemistry, 2000 , vol.
65, # 15 p. 4618 – 4634
7) Gagnon et al.; Canadian Journal of Chemistry, 1953 , vol. 31, p.
673,682
8) Malki, Fatiha; Touati, Abdelkader; Rahal, Said; Moulay, Saad; Asian
Journal of Chemistry, 2011 , vol. 23, # 3 p. 961 – 967
9) Ohata S., Kato K., Toriyabe K., Ito Y., Hamaguchi R., Nakano Y.,
EP2202226 A1, 2010
10) Maekawa T., Hara R., Odaka H., Kimura H., Mizufune H., Fukatsu K.,
WO03099793, 2003
[11] 11) Sam, Sik Kim; Bo, Seung Choi; Jae, Hoon Lee; Ki, Kon Lee; Tae, Hee
Lee; Shin, Hyunik; Young, Ho Kim; Synlett, 2009, # 4 p. 599 – 602
12) Zhu, Yulin; Pan, Yuanjiang; Huang, Shenlin; Synthetic Communications,
2004 , vol. 34, # 17 p. 3167 – 3174
13) Pathak, Vijai Nath; Gupta, Ragini; Varshney, Bindu; Indian Journal of
Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 2008 , vol.
47, # 3 p. 434 – 438
14) Pierre, Fabrice; O'Brien, Sean E.; Haddach, Mustapha; Bourbon,
Pauline; Schwaebe, Michael K.; Stefan, Eric; Darjania, Levan; Stansfield, Ryan; Ho,
Caroline; Siddiqui-Jain, Adam; Streiner, Nicole; Rice, William G.; Anderes, Kenna;
Ryckman, David M.; Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 6
p. 1687 – 1691
15) Boes M., Galley G., Godel T., Hoffmann T., Hunkeler W., Schnider P.,
Stadler H. US6756380, 2004
16) Aissaoui H., Boss C., Hazemann J., Koberstein R., Siegrist R., Sifferlen
T. US2011105491, 2011
[17] 17) An S., Dickens M. A., Bleu T., Hallmark O. G., Goetzl E. J. Biochemical
and Biophysical Research Communications (1997) 231, 619–622
18) P Schenone, P Fossa, G Menozzi, (1991) Journal of Heterocyclic
Chemistry, 1991 , vol. 28, # 2 p. 453 – 457
19) T Kimura, N Ohkawa, A Nakao, T Nagasaki, T Shimozato, (2006).
EP1632488 A1,
20) ND Smith, SP Govek, M Kahraman, JD Julien, JY Nagasawa, KL
Douglas, CL Bonnefous, AG Lai. (2013) WO2013/142266 A1
21) B Cottyn, F Terrier, D Vichard, P Nioche, Pierre; Raman. (2007)
Synlett, # 8 p. 1203 – 1206
[22] 22) SL Buchwald, TD Senecal, W Shu, Wei . (2013) Angewandte Chemie -
International Edition, 2013 , vol. 52, # 38 p. 10035 – 10039.
23) X Guo, W Hu, H Huang, (2007) Angewandte Chemie - International
Edition, 2007 , vol. 46, # 8 p. 1337 – 1339
24) SK Shah, QT Truong, H Qi, WK Hagmann (2005). WO2005044785A1
Claims (3)
1-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}- benzoylamino)-cyclopropanecarboxylic acid, 2-(4-{4-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}- benzoylamino)-indancarboxylic acid, 2-(S)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzoylamino) phenyl acetic acid, 2-(R)-(4-{4-[(R,S)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzoylamino) phenyl propanoic acid, 5 2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol yl]benzoyl]amino]phenyl-propanoic acid, 2(S)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol yl]benzoyl]amino]phenyl-propanoic acid, (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol 10 yl]benzoyl]amino]phenyl-propanoic acid, (R)[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol yl]benzoyl]amino]phenyl-propanoic acid, (R)[[4-[2,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol yl]benzoyl]amino](4-fluorophenyl)propanoic acid, 15 (R)[[4-[1,5-dimethyl((R)phenylethoxycarbonylamino)pyrazol yl]benzoyl]amino](4-fluorophenyl)propanoic acid, (R)(4-bromophenyl)[[4-[2,5-dimethyl((R)phenylethoxycarbonyl- amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)(4-bromophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl- 20 amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)(4-chlorophenyl)[[4-[2,5-dimethyl((R)phenylethoxycarbonyl- amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)(4-chlorophenyl)[[4-[1,5-dimethyl((R)phenylethoxycarbonyl- amino)pyrazolyl]benzoyl]amino]propanoic acid, 25 (R)- 3-(3,4-difluorophenyl)[[4-[2,5-dimethyl((R) phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)- 3-(3,4-difluorophenyl)[[4-[1,5-dimethyl((R) phenylethoxycarbonyl-amino)pyrazolyl]benzoyl]amino]propanoic acid, (R)(4-{4-[(R)(2-chloro-phenyl)-ethoxycarbonylamino]methyl- 30 isoxazolyl}-benzoylamino)cyclopropyl-propionic acid, (R){4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazolyl]- benzoylamino}phenyl-propionic acid, (S){4-[3-Methyl((S)phenyl-ethoxycarbonylamino)-isoxazolyl]- benzoylamino}phenyl-propionic acid, 35 (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzoylamino)phenyl-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzoylamino)(4-fluoro-phenyl)-propionic acid, (R)(4-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)- 5 ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzoylamino)(3,4-difluoro-phenyl)-propionic acid, (R)(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)- ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic acid, 10 (R)(4-Bromo-phenyl)(4-{4-[(R)(2-chloro-phenyl)- ethoxycarbonylamino]methyl-isoxazolyl}-benzoylamino)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzoylamino)(2-fluoro-phenyl)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- 15 isoxazolyl}-benzoylamino)p-tolyl-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzoylamino)(4-trifluoromethyl-phenyl)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzoylamino)(4-cyano-phenyl)-propionic acid, 20 (R)(4-{5-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- pyrazolyl}-benzoylamino)phenyl-propionic acid, (R){4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]- benzylamino}phenyl-propionic acid, (R)(2-Fluoro-phenyl){4-[3-methyl((R)phenyl- 25 thoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R){4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]- benzylamino}(4-trifluoromethyl-phenyl)-propionic acid, (R)Cyclopropyl{4-[3-methyl((R)phenyl-ethoxycarbonylamino)- isoxazolyl]-benzylamino}-propionic acid, 30 (R)(2-Chloro-phenyl){4-[3-methyl((R)phenyl- ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R)(4-Chloro-phenyl){4-[3-methyl((R)phenyl- ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- 35 isoxazolyl}-benzylamino)phenyl-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzylamino)(2-fluoro-phenyl)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzylamino)(4-trifluoromethyl-phenyl)-propionic acid, 5 (R)(2-Chloro-phenyl)(4-{4-[(R)(2-chloro-phenyl)- ethoxycarbonylamino]methyl-isoxazolyl}-benzylamino)-propionic acid, (R)(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl- isoxazolyl}-benzylamino)cyclopropyl-propionic acid, 2-{4-[3-Methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]- 10 benzyloxy}phenyl-propionic acid, or (RS)Cyclopropyl{4-[3-methyl((R)phenyl-ethoxycarbonylamino)- isoxazolyl]-benzyloxy}-propionic acid. 16. The compound of claim 1 wherein the compound is (RS)Cyclopropyl{4- 15 [3-methyl((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzyloxy}- propionic acid, 2(R)-[[4-[3-methyl((R)phenylethoxycarbonylamino)isoxazol- 5-yl]benzoyl]amino]phenyl-propanoic acid, (R){4-[3-Methyl((R)phenyl- ethoxycarbonylamino)-isoxazolyl]-benzylamino}phenyl-propionic acid, (R)-
2-(4-{4-[(R)(2-Chloro-phenyl)-ethoxycarbonylamino]methyl-isoxazolyl}- 20 benzylamino)phenyl-propionic acid and (R)Cyclopropyl{4-[
3-methyl ((R)phenyl-ethoxycarbonylamino)-isoxazolyl]-benzylamino}-propionic acid. 17. Use of a compound of any one of claims 1 – 16 in the manufacture of a 25 medicament for treating a LPA-dependent disease or condition. 18. A compound of any one of claims 1 – 16 for use in treating a lysophosphatidic acid-dependent disease or condition. 30 19. A use or compound according to claim 17 or 18 wherein the lysophosphatidic acid-dependent disease or condition is selected from the group consisting of organ fibrosis, liver disease, and renal disease. 20. A use or a compound according to any one of claims 17 – 19 wherein the disease is selected from diabetic nephropathy or nonalcoholic steatohepatitis (NASH). 5 21. A pharmaceutically acceptable formulation comprising a compound of any one of claims 1 – 16 and one or more pharmaceutically acceptable excipients.
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