ZA200509496B - Aza spiro alkane derivatives as inhibitors of metalloproteases - Google Patents
Aza spiro alkane derivatives as inhibitors of metalloproteases Download PDFInfo
- Publication number
- ZA200509496B ZA200509496B ZA200509496A ZA200509496A ZA200509496B ZA 200509496 B ZA200509496 B ZA 200509496B ZA 200509496 A ZA200509496 A ZA 200509496A ZA 200509496 A ZA200509496 A ZA 200509496A ZA 200509496 B ZA200509496 B ZA 200509496B
- Authority
- ZA
- South Africa
- Prior art keywords
- octane
- azaspiro
- carbonyl
- hydroxy
- carboxamide
- Prior art date
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- -1 Aza spiro alkane Chemical class 0.000 title claims description 179
- 102000005741 Metalloproteases Human genes 0.000 title claims description 46
- 108010006035 Metalloproteases Proteins 0.000 title claims description 46
- 239000003112 inhibitor Substances 0.000 title description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 193
- 150000001875 compounds Chemical class 0.000 claims description 154
- 125000000217 alkyl group Chemical group 0.000 claims description 134
- 125000000623 heterocyclic group Chemical group 0.000 claims description 102
- 229910052739 hydrogen Inorganic materials 0.000 claims description 95
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 94
- 229910020008 S(O) Inorganic materials 0.000 claims description 93
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 83
- 229910052799 carbon Inorganic materials 0.000 claims description 75
- 239000001257 hydrogen Substances 0.000 claims description 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 47
- 201000010099 disease Diseases 0.000 claims description 46
- 125000001188 haloalkyl group Chemical group 0.000 claims description 42
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
- 125000005884 carbocyclylalkyl group Chemical group 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 36
- 229910052717 sulfur Inorganic materials 0.000 claims description 34
- 125000002947 alkylene group Chemical group 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 33
- 239000000126 substance Substances 0.000 claims description 33
- 230000000694 effects Effects 0.000 claims description 32
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 241000124008 Mammalia Species 0.000 claims description 19
- 229910052794 bromium Inorganic materials 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 17
- 229910052740 iodine Inorganic materials 0.000 claims description 17
- 102000004190 Enzymes Human genes 0.000 claims description 16
- 108090000790 Enzymes Proteins 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 201000011510 cancer Diseases 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 239000011159 matrix material Substances 0.000 claims description 12
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 101150018425 Cr1l gene Proteins 0.000 claims description 10
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 229910052722 tritium Inorganic materials 0.000 claims description 10
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 125000005026 carboxyaryl group Chemical group 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
- 102000004127 Cytokines Human genes 0.000 claims description 8
- 108090000695 Cytokines Proteins 0.000 claims description 8
- 125000004450 alkenylene group Chemical group 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 8
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 229940002612 prodrug Drugs 0.000 claims description 8
- 239000000651 prodrug Substances 0.000 claims description 8
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 7
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 7
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
- 239000003102 growth factor Substances 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000003003 spiro group Chemical group 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000004562 2,3-dihydroindol-1-yl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 102100026802 72 kDa type IV collagenase Human genes 0.000 claims description 3
- 206010027654 Allergic conditions Diseases 0.000 claims description 3
- 102100032584 Cleft lip and palate transmembrane protein 1-like protein Human genes 0.000 claims description 3
- 201000004624 Dermatitis Diseases 0.000 claims description 3
- 101000627872 Homo sapiens 72 kDa type IV collagenase Proteins 0.000 claims description 3
- 101000942452 Homo sapiens Cleft lip and palate transmembrane protein 1-like protein Proteins 0.000 claims description 3
- 101000577881 Homo sapiens Macrophage metalloelastase Proteins 0.000 claims description 3
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 claims description 3
- 101000990915 Homo sapiens Stromelysin-1 Proteins 0.000 claims description 3
- 102100027998 Macrophage metalloelastase Human genes 0.000 claims description 3
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 claims description 3
- 102100030416 Stromelysin-1 Human genes 0.000 claims description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 239000002207 metabolite Substances 0.000 claims description 3
- 231100000915 pathological change Toxicity 0.000 claims description 3
- 230000036285 pathological change Effects 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 208000017520 skin disease Diseases 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- KVIOIFKWKBDGAV-UHFFFAOYSA-N 58881-41-7 Chemical compound C1=CC=C2N3C(=O)C4=CC5=CC=CC=C5N4C(=O)C3=CC2=C1 KVIOIFKWKBDGAV-UHFFFAOYSA-N 0.000 claims description 2
- GSKUWIIZGNYADX-UHFFFAOYSA-N 6-(3,3-dimethyl-4-phenylpiperidine-1-carbonyl)-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC1(C)CN(C(=O)C2C(CC3(CC3)CN2)C(=O)NO)CCC1C1=CC=CC=C1 GSKUWIIZGNYADX-UHFFFAOYSA-N 0.000 claims description 2
- UABYCZDRWCCXEH-UHFFFAOYSA-N 6-[3-(4-fluorophenyl)pyrrolidine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC(CC2)C=2C=CC(F)=CC=2)C(C(=O)NO)CC21CC2 UABYCZDRWCCXEH-UHFFFAOYSA-N 0.000 claims description 2
- BTSAYUXHVBBREL-UHFFFAOYSA-N 6-[4-(1,3-benzothiazol-6-yl)-3,6-dihydro-2h-pyridine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC=C(CC2)C=2C=C3SC=NC3=CC=2)C(C(=O)NO)CC21CC2 BTSAYUXHVBBREL-UHFFFAOYSA-N 0.000 claims description 2
- KCWMUHJNFPZUTL-UHFFFAOYSA-N 6-[4-(2,5-dimethylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC1=CC=C(C)C(C=2CCN(CC=2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 KCWMUHJNFPZUTL-UHFFFAOYSA-N 0.000 claims description 2
- NWXRXUXLEIZQEQ-UHFFFAOYSA-N 6-[4-(2,5-dimethylphenyl)piperidine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC1=CC=C(C)C(C2CCN(CC2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 NWXRXUXLEIZQEQ-UHFFFAOYSA-N 0.000 claims description 2
- GCJMGSWNBUFEMB-UHFFFAOYSA-N 6-[4-(2-fluorophenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-n-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CC=C(CC2)C=2C(=CC=CC=2)F)N(C)CC21CC2 GCJMGSWNBUFEMB-UHFFFAOYSA-N 0.000 claims description 2
- GRIWYPFXSXJHPV-UHFFFAOYSA-N 6-[4-(4-cyano-2-methylphenyl)piperazine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC1=CC(C#N)=CC=C1N1CCN(C(=O)C2C(CC3(CC3)CN2)C(=O)NO)CC1 GRIWYPFXSXJHPV-UHFFFAOYSA-N 0.000 claims description 2
- NRXKROAITOCGQE-UHFFFAOYSA-N 6-[4-(4-cyano-2-methylphenyl)piperidine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC1=CC(C#N)=CC=C1C1CCN(C(=O)C2C(CC3(CC3)CN2)C(=O)NO)CC1 NRXKROAITOCGQE-UHFFFAOYSA-N 0.000 claims description 2
- JLFCWOIZNQXZMP-UHFFFAOYSA-N 6-[4-(4-cyano-3,5-dimethylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC1=C(C#N)C(C)=CC(C=2CCN(CC=2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 JLFCWOIZNQXZMP-UHFFFAOYSA-N 0.000 claims description 2
- AMQJQMSSIWTWBM-UHFFFAOYSA-N 6-[4-(4-cyano-3-ethylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1=C(C#N)C(CC)=CC(C=2CCN(CC=2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 AMQJQMSSIWTWBM-UHFFFAOYSA-N 0.000 claims description 2
- IAXKVCUYRYEDNF-UHFFFAOYSA-N 6-[4-(4-cyano-3-propan-2-ylphenyl)piperidine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1=C(C#N)C(C(C)C)=CC(C2CCN(CC2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 IAXKVCUYRYEDNF-UHFFFAOYSA-N 0.000 claims description 2
- QLLYPSNNVCGGCP-UHFFFAOYSA-N 6-[4-(4-fluorophenyl)-3-hydroxypiperidine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC(O)C(CC2)C=2C=CC(F)=CC=2)C(C(=O)NO)CC21CC2 QLLYPSNNVCGGCP-UHFFFAOYSA-N 0.000 claims description 2
- UJNMOBDVOPCGRG-UHFFFAOYSA-N 6-[4-(4-tert-butylphenyl)piperazine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1CCN(C(=O)C2C(CC3(CC3)CN2)C(=O)NO)CC1 UJNMOBDVOPCGRG-UHFFFAOYSA-N 0.000 claims description 2
- SOQIZDSFYBDPLX-UHFFFAOYSA-N 6-[4-[3-(dimethylamino)phenyl]piperidine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CN(C)C1=CC=CC(C2CCN(CC2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 SOQIZDSFYBDPLX-UHFFFAOYSA-N 0.000 claims description 2
- 108091007504 ADAM10 Proteins 0.000 claims description 2
- 102000036664 ADAM10 Human genes 0.000 claims description 2
- 101001011906 Homo sapiens Matrix metalloproteinase-14 Proteins 0.000 claims description 2
- 102100030216 Matrix metalloproteinase-14 Human genes 0.000 claims description 2
- 150000005829 chemical entities Chemical class 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- DAWQVDWNIUMYHC-UHFFFAOYSA-N methyl 7-(hydroxycarbamoyl)-6-(3-phenyl-2,5-dihydropyrrole-1-carbonyl)-5-azaspiro[2.5]octane-5-carboxylate Chemical compound C1C(C(=O)NO)C(C(=O)N2CC(=CC2)C=2C=CC=CC=2)N(C(=O)OC)CC21CC2 DAWQVDWNIUMYHC-UHFFFAOYSA-N 0.000 claims description 2
- NJCBPLQYZDLBCA-UHFFFAOYSA-N n-hydroxy-5-methyl-6-(4-phenylpiperazine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCN(CC2)C=2C=CC=CC=2)N(C)CC21CC2 NJCBPLQYZDLBCA-UHFFFAOYSA-N 0.000 claims description 2
- LJHSTHSXZKLQLX-UHFFFAOYSA-N n-hydroxy-5-methyl-6-(4-pyridin-4-ylpiperidine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCC(CC2)C=2C=CN=CC=2)N(C)CC21CC2 LJHSTHSXZKLQLX-UHFFFAOYSA-N 0.000 claims description 2
- YTYGLBZOTUHMOU-UHFFFAOYSA-N n-hydroxy-5-methyl-6-[4-(2-methylquinolin-4-yl)piperazine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCN(CC2)C=2C3=CC=CC=C3N=C(C)C=2)N(C)CC21CC2 YTYGLBZOTUHMOU-UHFFFAOYSA-N 0.000 claims description 2
- SMJTUKFSFPUWGN-UHFFFAOYSA-N n-hydroxy-5-methylsulfonyl-6-(3-phenyl-2,5-dihydropyrrole-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CC(=CC2)C=2C=CC=CC=2)N(S(=O)(=O)C)CC21CC2 SMJTUKFSFPUWGN-UHFFFAOYSA-N 0.000 claims description 2
- LGGDFZFWWHOSDJ-UHFFFAOYSA-N n-hydroxy-6-(3-phenylpiperidine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC(CCC2)C=2C=CC=CC=2)C(C(=O)NO)CC21CC2 LGGDFZFWWHOSDJ-UHFFFAOYSA-N 0.000 claims description 2
- MITLEGOYVUMBJH-UHFFFAOYSA-N n-hydroxy-6-(4-phenylpiperidine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CCC(CC2)C=2C=CC=CC=2)C(C(=O)NO)CC21CC2 MITLEGOYVUMBJH-UHFFFAOYSA-N 0.000 claims description 2
- XSWDPZGYAZCNCU-UHFFFAOYSA-N n-hydroxy-6-(4-thiophen-2-ylpiperidine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CCC(CC2)C=2SC=CC=2)C(C(=O)NO)CC21CC2 XSWDPZGYAZCNCU-UHFFFAOYSA-N 0.000 claims description 2
- UKESPHCVYSOWDM-UHFFFAOYSA-N n-hydroxy-6-(4-thiophen-3-ylpiperidine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CCC(CC2)C2=CSC=C2)C(C(=O)NO)CC21CC2 UKESPHCVYSOWDM-UHFFFAOYSA-N 0.000 claims description 2
- RYIHTKZBIMRJAY-UHFFFAOYSA-N n-hydroxy-6-[3-(2-methylphenyl)pyrrolidine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC1=CC=CC=C1C1CN(C(=O)C2C(CC3(CC3)CN2)C(=O)NO)CC1 RYIHTKZBIMRJAY-UHFFFAOYSA-N 0.000 claims description 2
- GNEWHNGFPDKYIF-UHFFFAOYSA-N n-hydroxy-6-[4-(2-methoxyphenyl)piperazine-1-carbonyl]-5-methyl-5-azaspiro[2.5]octane-7-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(C(=O)C2N(CC3(CC3)CC2C(=O)NO)C)CC1 GNEWHNGFPDKYIF-UHFFFAOYSA-N 0.000 claims description 2
- KOMKRCPIGPQIAH-UHFFFAOYSA-N n-hydroxy-6-[4-(2-methylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC1=CC=CC=C1C1=CCN(C(=O)C2C(CC3(CC3)CN2)C(=O)NO)CC1 KOMKRCPIGPQIAH-UHFFFAOYSA-N 0.000 claims description 2
- GWMGMMDQSZPJSX-UHFFFAOYSA-N n-hydroxy-6-[4-(3-methoxyphenyl)piperidine-1-carbonyl]-5-methyl-5-azaspiro[2.5]octane-7-carboxamide Chemical compound COC1=CC=CC(C2CCN(CC2)C(=O)C2N(CC3(CC3)CC2C(=O)NO)C)=C1 GWMGMMDQSZPJSX-UHFFFAOYSA-N 0.000 claims description 2
- BBKTWOFCSVWCHV-UHFFFAOYSA-N n-hydroxy-6-[4-(3-propan-2-yloxyphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC(C)OC1=CC=CC(C=2CCN(CC=2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 BBKTWOFCSVWCHV-UHFFFAOYSA-N 0.000 claims description 2
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- PPIGHWKFSKHWHU-UHFFFAOYSA-N 6-[4-(4-cyano-2-methylphenyl)piperidine-1-carbonyl]-n-hydroxy-5-methylsulfonyl-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC1=CC(C#N)=CC=C1C1CCN(C(=O)C2N(CC3(CC3)CC2C(=O)NO)S(C)(=O)=O)CC1 PPIGHWKFSKHWHU-UHFFFAOYSA-N 0.000 claims 1
- LTBJBSGNZKJCSD-UHFFFAOYSA-N 6-[4-(4-cyano-3,5-dimethylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-n-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CC=C(CC2)C=2C=C(C)C(C#N)=C(C)C=2)N(C)CC21CC2 LTBJBSGNZKJCSD-UHFFFAOYSA-N 0.000 claims 1
- IBFXUEJHWPQQKI-UHFFFAOYSA-N 6-[4-(4-cyano-3-ethylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-n-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1=C(C#N)C(CC)=CC(C=2CCN(CC=2)C(=O)C2N(CC3(CC3)CC2C(=O)NO)C)=C1 IBFXUEJHWPQQKI-UHFFFAOYSA-N 0.000 claims 1
- UZCLBPDNCDSRPC-UHFFFAOYSA-N 6-[4-(4-cyano-3-ethylphenyl)piperidine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1=C(C#N)C(CC)=CC(C2CCN(CC2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 UZCLBPDNCDSRPC-UHFFFAOYSA-N 0.000 claims 1
- FUSLOGDAJWSVIZ-UHFFFAOYSA-N 6-[4-(4-cyano-3-methylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1=C(C#N)C(C)=CC(C=2CCN(CC=2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 FUSLOGDAJWSVIZ-UHFFFAOYSA-N 0.000 claims 1
- CFUMDKKCRYAVIE-UHFFFAOYSA-N 6-[4-(4-cyano-3-methylphenyl)piperidine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1=C(C#N)C(C)=CC(C2CCN(CC2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 CFUMDKKCRYAVIE-UHFFFAOYSA-N 0.000 claims 1
- ZTPMLWROXBOVCY-UHFFFAOYSA-N 6-[4-(4-cyanophenyl)-3-methylpiperidine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC1CN(C(=O)C2C(CC3(CC3)CN2)C(=O)NO)CCC1C1=CC=C(C#N)C=C1 ZTPMLWROXBOVCY-UHFFFAOYSA-N 0.000 claims 1
- QJIIWWVCIAYSDY-UHFFFAOYSA-N 6-[4-(4-ethylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1=CC(CC)=CC=C1C1=CCN(C(=O)C2C(CC3(CC3)CN2)C(=O)NO)CC1 QJIIWWVCIAYSDY-UHFFFAOYSA-N 0.000 claims 1
- HEHOUKDONSUWEZ-UHFFFAOYSA-N 6-[4-(4-ethylphenyl)piperidine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1=CC(CC)=CC=C1C1CCN(C(=O)C2C(CC3(CC3)CN2)C(=O)NO)CC1 HEHOUKDONSUWEZ-UHFFFAOYSA-N 0.000 claims 1
- QXLREXZKQQOKBW-UHFFFAOYSA-N 6-[4-[3-(dimethylamino)phenyl]-3,6-dihydro-2h-pyridine-1-carbonyl]-n-hydroxy-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CN(C)C1=CC=CC(C=2CCN(CC=2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 QXLREXZKQQOKBW-UHFFFAOYSA-N 0.000 claims 1
- WRSAGYKATANPLQ-UHFFFAOYSA-N C1N(C(O)=O)C(C(=O)N2CC(=CC2)C=2C=CC=CC=2)C(C(=O)NO)CC21CC2 Chemical compound C1N(C(O)=O)C(C(=O)N2CC(=CC2)C=2C=CC=CC=2)C(C(=O)NO)CC21CC2 WRSAGYKATANPLQ-UHFFFAOYSA-N 0.000 claims 1
- 101150065749 Churc1 gene Proteins 0.000 claims 1
- 102100038239 Protein Churchill Human genes 0.000 claims 1
- KZMZXWVOUIOSBN-XEVCZEQESA-N [(3r)-oxolan-3-yl] 7-(hydroxycarbamoyl)-6-(4-phenylpiperazine-1-carbonyl)-5-azaspiro[2.5]octane-5-carboxylate Chemical compound C1N(C(=O)O[C@H]2COCC2)C(C(=O)N2CCN(CC2)C=2C=CC=CC=2)C(C(=O)NO)CC21CC2 KZMZXWVOUIOSBN-XEVCZEQESA-N 0.000 claims 1
- JKJLJEBJWDHPEQ-HDYDNRTBSA-N [(3s)-oxolan-3-yl] 7-(hydroxycarbamoyl)-6-(3-phenyl-2,5-dihydropyrrole-1-carbonyl)-5-azaspiro[2.5]octane-5-carboxylate Chemical compound C1N(C(=O)O[C@@H]2COCC2)C(C(=O)N2CC(=CC2)C=2C=CC=CC=2)C(C(=O)NO)CC21CC2 JKJLJEBJWDHPEQ-HDYDNRTBSA-N 0.000 claims 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
- 125000004125 inden-2-yl group Chemical group [H]C1=C(*)C([H])([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims 1
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims 1
- SQVQBJWUXHRCPY-UHFFFAOYSA-N methyl 3-[1-[7-(hydroxycarbamoyl)-5-azaspiro[2.5]octane-6-carbonyl]-3,6-dihydro-2h-pyridin-4-yl]-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(C=2CCN(CC=2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 SQVQBJWUXHRCPY-UHFFFAOYSA-N 0.000 claims 1
- JTOMTJCMJZDLMC-UHFFFAOYSA-N methyl 3-[1-[7-(hydroxycarbamoyl)-5-azaspiro[2.5]octane-6-carbonyl]piperidin-4-yl]-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(C2CCN(CC2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 JTOMTJCMJZDLMC-UHFFFAOYSA-N 0.000 claims 1
- CFTBWPWIDMZYPS-UHFFFAOYSA-N methyl 3-[1-[7-(hydroxycarbamoyl)-5-azaspiro[2.5]octane-6-carbonyl]piperidin-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2CCN(CC2)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=C1 CFTBWPWIDMZYPS-UHFFFAOYSA-N 0.000 claims 1
- PKZDHFHJTARYOB-UHFFFAOYSA-N methyl 4-[1-[7-(hydroxycarbamoyl)-5-azaspiro[2.5]octane-6-carbonyl]piperidin-4-yl]-3-methylbenzoate Chemical compound CC1=CC(C(=O)OC)=CC=C1C1CCN(C(=O)C2C(CC3(CC3)CN2)C(=O)NO)CC1 PKZDHFHJTARYOB-UHFFFAOYSA-N 0.000 claims 1
- VJISDWDORJKIJA-UHFFFAOYSA-N methyl 6-[4-(3,5-difluorophenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-7-(hydroxycarbamoyl)-5-azaspiro[2.5]octane-5-carboxylate Chemical compound C1C(C(=O)NO)C(C(=O)N2CC=C(CC2)C=2C=C(F)C=C(F)C=2)N(C(=O)OC)CC21CC2 VJISDWDORJKIJA-UHFFFAOYSA-N 0.000 claims 1
- ZEWFEUNCAANMBD-UHFFFAOYSA-N methyl 6-[4-(3,5-dimethylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-7-(hydroxycarbamoyl)-5-azaspiro[2.5]octane-5-carboxylate Chemical compound C1C(C(=O)NO)C(C(=O)N2CC=C(CC2)C=2C=C(C)C=C(C)C=2)N(C(=O)OC)CC21CC2 ZEWFEUNCAANMBD-UHFFFAOYSA-N 0.000 claims 1
- IVOHKGYMHLYKEE-UHFFFAOYSA-N methyl 6-[4-(3-ethylbenzimidazol-5-yl)piperidine-1-carbonyl]-7-(hydroxycarbamoyl)-5-azaspiro[2.5]octane-5-carboxylate Chemical compound C1=C2N(CC)C=NC2=CC=C1C(CC1)CCN1C(=O)C(N(C1)C(=O)OC)C(C(=O)NO)CC21CC2 IVOHKGYMHLYKEE-UHFFFAOYSA-N 0.000 claims 1
- VDWUMLKWSKKGLE-GTPINHCMSA-N methyl 7-(hydroxycarbamoyl)-6-[(3r)-3-phenylpyrrolidine-1-carbonyl]-5-azaspiro[2.5]octane-5-carboxylate Chemical compound C1C(C(=O)NO)C(C(=O)N2C[C@H](CC2)C=2C=CC=CC=2)N(C(=O)OC)CC21CC2 VDWUMLKWSKKGLE-GTPINHCMSA-N 0.000 claims 1
- NXIZZISCXRJDCG-UHFFFAOYSA-N n-hydroxy-5-methyl-6-(1,3,4,9-tetrahydropyrido[3,4-b]indole-2-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CC3=C(C4=CC=CC=C4N3)CC2)N(C)CC21CC2 NXIZZISCXRJDCG-UHFFFAOYSA-N 0.000 claims 1
- IVUBTIOWUAUIBW-UHFFFAOYSA-N n-hydroxy-5-methyl-6-(3-phenyl-2,5-dihydropyrrole-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CC(=CC2)C=2C=CC=CC=2)N(C)CC21CC2 IVUBTIOWUAUIBW-UHFFFAOYSA-N 0.000 claims 1
- ZWKCGAISWMUFQY-UHFFFAOYSA-N n-hydroxy-5-methyl-6-(4-quinolin-4-ylpiperazine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCN(CC2)C=2C3=CC=CC=C3N=CC=2)N(C)CC21CC2 ZWKCGAISWMUFQY-UHFFFAOYSA-N 0.000 claims 1
- PUGGTXIREZKGIO-GTPINHCMSA-N n-hydroxy-5-methyl-6-[(3r)-3-phenylpyrrolidine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2C[C@H](CC2)C=2C=CC=CC=2)N(C)CC21CC2 PUGGTXIREZKGIO-GTPINHCMSA-N 0.000 claims 1
- RCCOOIGIASZBRH-UHFFFAOYSA-N n-hydroxy-5-methyl-6-[4-(2-methylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CC=C(CC2)C=2C(=CC=CC=2)C)N(C)CC21CC2 RCCOOIGIASZBRH-UHFFFAOYSA-N 0.000 claims 1
- IFCGQSILNJBQFK-UHFFFAOYSA-N n-hydroxy-5-methyl-6-[4-(2-phenylethyl)piperazine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCN(CCC=3C=CC=CC=3)CC2)N(C)CC21CC2 IFCGQSILNJBQFK-UHFFFAOYSA-N 0.000 claims 1
- KUOGINGKNMWXPI-UHFFFAOYSA-N n-hydroxy-5-methyl-6-[4-(2-pyridin-4-ylethyl)piperidine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCC(CCC=3C=CN=CC=3)CC2)N(C)CC21CC2 KUOGINGKNMWXPI-UHFFFAOYSA-N 0.000 claims 1
- WZXRIUAHQVRGMN-UHFFFAOYSA-N n-hydroxy-5-methyl-6-[4-(3-methylphenyl)piperazine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCN(CC2)C=2C=C(C)C=CC=2)N(C)CC21CC2 WZXRIUAHQVRGMN-UHFFFAOYSA-N 0.000 claims 1
- YHUOQZUOPVQNFS-UHFFFAOYSA-N n-hydroxy-5-methyl-6-[4-(3-propan-2-ylphenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound CC(C)C1=CC=CC(C=2CCN(CC=2)C(=O)C2N(CC3(CC3)CC2C(=O)NO)C)=C1 YHUOQZUOPVQNFS-UHFFFAOYSA-N 0.000 claims 1
- HWYXQQHSVVQKCL-UHFFFAOYSA-N n-hydroxy-5-methyl-6-[4-(4-nitrophenyl)-3,6-dihydro-2h-pyridine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CC=C(CC2)C=2C=CC(=CC=2)[N+]([O-])=O)N(C)CC21CC2 HWYXQQHSVVQKCL-UHFFFAOYSA-N 0.000 claims 1
- MDJPVLFXEDTVGR-UHFFFAOYSA-N n-hydroxy-5-methyl-6-[4-(4-nitrophenyl)piperazine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCN(CC2)C=2C=CC(=CC=2)[N+]([O-])=O)N(C)CC21CC2 MDJPVLFXEDTVGR-UHFFFAOYSA-N 0.000 claims 1
- MZSWTBHXSNTHFG-UHFFFAOYSA-N n-hydroxy-5-methyl-6-[4-(pyridin-4-ylmethyl)piperazine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCN(CC=3C=CN=CC=3)CC2)N(C)CC21CC2 MZSWTBHXSNTHFG-UHFFFAOYSA-N 0.000 claims 1
- HJNKYGBTSGQBDU-UHFFFAOYSA-N n-hydroxy-5-methyl-6-[4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCN(CC2)C=2N=CC(=CC=2)C(F)(F)F)N(C)CC21CC2 HJNKYGBTSGQBDU-UHFFFAOYSA-N 0.000 claims 1
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- HCZJXYYEIHQWMV-UHFFFAOYSA-N n-hydroxy-6-(3-pyridin-2-ylpyrrolidine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC(CC2)C=2N=CC=CC=2)C(C(=O)NO)CC21CC2 HCZJXYYEIHQWMV-UHFFFAOYSA-N 0.000 claims 1
- ZXJFQRTXVSTUJW-UHFFFAOYSA-N n-hydroxy-6-(3-pyridin-3-ylpyrrolidine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC(CC2)C=2C=NC=CC=2)C(C(=O)NO)CC21CC2 ZXJFQRTXVSTUJW-UHFFFAOYSA-N 0.000 claims 1
- LHXLSUALNIDHOW-UHFFFAOYSA-N n-hydroxy-6-(3-pyridin-4-ylpyrrolidine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC(CC2)C=2C=CN=CC=2)C(C(=O)NO)CC21CC2 LHXLSUALNIDHOW-UHFFFAOYSA-N 0.000 claims 1
- IIFOFXDCTPOHEY-UHFFFAOYSA-N n-hydroxy-6-(4-hydroxy-4-phenylpiperidine-1-carbonyl)-5-methyl-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1C(C(=O)NO)C(C(=O)N2CCC(O)(CC2)C=2C=CC=CC=2)N(C)CC21CC2 IIFOFXDCTPOHEY-UHFFFAOYSA-N 0.000 claims 1
- ZFHJWQWVJPMAIW-UHFFFAOYSA-N n-hydroxy-6-(4-phenylpiperazine-1-carbonyl)spiro[2.5]octane-7-carboxamide Chemical compound C1CC(C(=O)N2CCN(CC2)C=2C=CC=CC=2)C(C(=O)NO)CC21CC2 ZFHJWQWVJPMAIW-UHFFFAOYSA-N 0.000 claims 1
- MEOYYTAHWRZMBY-UHFFFAOYSA-N n-hydroxy-6-(4-pyridin-3-yl-3,6-dihydro-2h-pyridine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC=C(CC2)C=2C=NC=CC=2)C(C(=O)NO)CC21CC2 MEOYYTAHWRZMBY-UHFFFAOYSA-N 0.000 claims 1
- WKXJTIRHKXJRGQ-UHFFFAOYSA-N n-hydroxy-6-(4-pyridin-4-ylpiperazine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CCN(CC2)C=2C=CN=CC=2)C(C(=O)NO)CC21CC2 WKXJTIRHKXJRGQ-UHFFFAOYSA-N 0.000 claims 1
- ODKMAVOSNXZPQA-UHFFFAOYSA-N n-hydroxy-6-(4-thiophen-2-yl-3,6-dihydro-2h-pyridine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC=C(CC2)C=2SC=CC=2)C(C(=O)NO)CC21CC2 ODKMAVOSNXZPQA-UHFFFAOYSA-N 0.000 claims 1
- FPUYDCQZFLZTBP-UHFFFAOYSA-N n-hydroxy-6-(4-thiophen-3-yl-3,6-dihydro-2h-pyridine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC=C(CC2)C2=CSC=C2)C(C(=O)NO)CC21CC2 FPUYDCQZFLZTBP-UHFFFAOYSA-N 0.000 claims 1
- JRBOTYKEXLBUNY-UHFFFAOYSA-N n-hydroxy-6-(5-phenyl-2,3,4,7-tetrahydroazepine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2CC=C(CCC2)C=2C=CC=CC=2)C(C(=O)NO)CC21CC2 JRBOTYKEXLBUNY-UHFFFAOYSA-N 0.000 claims 1
- ZUTRYIUMUJHVMH-UHFFFAOYSA-N n-hydroxy-6-(5-phenylmethoxy-2,3-dihydroindole-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1NC(C(=O)N2C3=CC=C(OCC=4C=CC=CC=4)C=C3CC2)C(C(=O)NO)CC21CC2 ZUTRYIUMUJHVMH-UHFFFAOYSA-N 0.000 claims 1
- KGFYMTHGZVZNMX-GTPINHCMSA-N n-hydroxy-6-[(3r)-3-phenylpyrrolidine-1-carbonyl]spiro[2.5]octane-7-carboxamide Chemical compound C1CC(C(=O)N2C[C@H](CC2)C=2C=CC=CC=2)C(C(=O)NO)CC21CC2 KGFYMTHGZVZNMX-GTPINHCMSA-N 0.000 claims 1
- WINKWOOQYMWFHE-CRYBEJKASA-N n-hydroxy-6-[(3s,4r)-3-methyl-4-phenylpyrrolidine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide Chemical compound C1([C@@H]2CN(C[C@H]2C)C(=O)C2C(CC3(CC3)CN2)C(=O)NO)=CC=CC=C1 WINKWOOQYMWFHE-CRYBEJKASA-N 0.000 claims 1
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Description
AZA SPIRO ALKANE DERIVATIVES
AS INHIBITORS OF METALLOPROTEASES
The present invention relates to aza spiro alkane compounds which are useful in treating diseases, pathologic conditions and disorders associated with metalloprotease activity, including activity of sheddases and adamalysins (ADAMs).
Most tissues exist in a highly regulated dynamic equilibrium wherein new tissue is formed and existing tissue is degraded and eliminated. The degradation of the extracellular matrix (ECM), including connective tissue and basement membranes, is effected by the metalloproteinases which are released from connective tissue and invading inflammatory cells. “Excessive unregulated activity of these enzymes can result in undesirable tissue destruction and their activity is regulated at the transcription level, by controlled activation of the latent proenzyme and, after translation, by intracellular specific inhibitory factors such as TIMP ("Tissue Inhibitors of MetalloProteinase™) or by more general proteinase inhibitors such as a2- macroglobulins.
Several structurally related metalloproteases (MPs) are known to play an important role in the breakdown of structural proteins. These metalloproteases typically act on the intercellular matrix, and thus are involved in tissue breakdown and remodeling. Such proteins have been referred to as metalloproteases or MPs. There are several different families of MPs, classified by sequence homology. Several families of known MPs, as well as examples thereof, are disclosed in the art.
These MPs include Matrix-Metallo Proteases [MMPs], zinc metalloproteases, many of the membrane bound metalloproteases, TNF converting enzymes, angiotensin-converting enzymes (ACEs), disintegrins, including ADAMs (See Wolfsberg et al, 131 J. Cell Bio. 275-78
October, 25 1995), and the enkephalinases. Examples of MPs include human skin fibroblast collagenase, human skin fibroblast gelatinase, human sputum collagenase, aggrecanse and gelatinase, and human stromelysin. Collagenase, stromelysin, aggrecanase and related enzymes are thought to be important in mediating the symptomatology of a number of diseases.
Zinc proteases are subdivided according to the primary structure of their catalytic sites and include gluzincin, metzincin, inuzincin, carboxypeptidase, and DD carboxypeptidase subgroups (Hooper NM, 1994, FEBS Lett, 354:1-6). The metzincin subgroup is further divided into serralysins, astacins, matrixins, and adamalysins (Stocker W and Bode Ww, 1995, Curr
Opin Struct Biol, 5:383-390).
The matrixins include the matrix metalloproteases, or MMPs. MMPs constitute a family of structurally similar zinc-containing metalloproteases, which are involved in the remodeling and degradation of extracellular matrix proteins, both as part of normal physiological processes and in pathological conditions. For a review see Bode, W et al., 1996,
Adv Exp Med Biol, 389:1-11. Connective tissue, extracellular matrix constituents and basement membranes are the biological materials that provide rigidity, differentiation, attachment sites and, in some cases, elasticity to biological systems. Connective tissues components include, for example, collagen, elastin, proteoglycans, fibronectin and laminin that form the scaffold for all human tissues. Under normal conditions, connective tissue turnover and/or repair processes are controlled and in equilibrium. The loss of this balance, for whatever reason, leads to a number of disease states. Inhibition of the enzymes responsible loss of equilibrium provides a control mechanism for this tissue decomposition and, therefore, a treatment for these diseases. The uncontrolled breakdown of connective tissue by metalloproteases is a feature of many pathological conditions.
Besides a role in the regulation of extracellular matrix, there is also evidence to suggest that MMPs mediate the migration of inflammatory cells into tissues (Moscatelli D and Rifkin
DB, 1988, Biochim Biophys Acta, 948: 67-85). Several reports have demonstrated that various
MMPs can activate a variety of important non-matrix proteins, including cytokines, chemokines, integrins, and antimicrobial peptides (see Parks WC, 2002, J Clin Invest, 110:613-4). Many of the human MMPs are over expressed in human tumors and are associated with peritumor tissue degradation and metastasis formation. Another important function of certain MMPs is to activate various enzymes, including other MMPs, by cleaving the pro-domains from their protease domains. Thus some MMPs act to regulate the activities of other MMPs, so that over-production of one MMP may lead to excessive proteolysis of extracellular matrix by another. It has also been reported that MMPs can cleave and thereby inactivate the endogenous inhibitors of other proteinases such as elastase (Winyard PG et al., 1991, FEBS Letts, 279: 91-94). Inhibitors of MMPs could thus influence the activity of other destructive proteinases by modifying the level of their endogenous inhibitors. In addition, increasing or maintaining the levels of an endogenous or administered serine protease inhibitor supports the treatment and prevention of diseases such as emphysema, pulmonary diseases, inflammatory diseases and diseases of aging such as loss of skin or organ stretch and resiliency. Thus, MMPs should not be viewed solely as proteinases of ECM catabolism, but rather as extracellular processing enzymes involved in regulating cell-cell and cell-ECM signaling events.
The adamalysins include the reprolysins, snake venom metalloproteases and the
ADAMs. The ADAMs (a disintegrin and metalloprotease domain) are a family of type I transmembrane glycoproteins that are important in diverse biologic processes, such as cell adhesion and the proteolytic shedding of cell surface receptors. ADAM family members have been identified from mammalian and nonmammalian sources, including Xenopus, Drasophila, and Caenorhabditis elegans. Members of the family have a modular design, characterized by the presence of metalloprotease and integrin receptor-binding activities, and a cytoplasmic domain that in many family members specifies binding sites for various signal-transducing proteins. The ADAMs family has been implicated in the control of membrane fusion, cytokine, growth factor and growth factor receptor shedding, and cell migration, as well as processes such as muscle development, fertilization, neurogenesis, and cell fate determination.
Loss of regulation can lead to disease and pathology. Pathologies such as infertility, inflammation and cancer have been shown to involve ADAMS family members. For a review, see Wolfsberg TG and White JM, 1998, ADAM metalloproteinases. In Handbook of
Proteolytic Enzymes (Barrett AJ, Rawlings ND and Woessner JF eds), p.1310-1313, Academic
Press, London as well as Seals DF and Courtneidge SA, 2003, Genes and Development, 17:7- 30.
Some specific examples of important ADAM metalloproteases include the TNFa- converting enzyme, TACE or ADAMI7, that is currently an important target for anti- inflammatory drugs (Moss ML et al., 2001, Drug Discov Today, 6:417-426 and Black RA, 2002, Int J Biochem Cell Biol, 34:1-5). Other members of the family are also likely to be good therapeutic targets. ADAMS has been reported to be expressed almost exclusively in cells of the immune system, particularly B-cells, monocytes, eosinophils and granulocytes. ADAMS therefore represents a therapeutic target for human immunological-based diseases. ADAMIS is found in human aortic smooth muscle and cultured umbilical vein endothelial cells. While
ADAMIS5 is not expressed in normal blood vessels, it has been detected in developing atherosclerotic lesions (Herren B et al., 1997, FASEB J, 11:173-1 80), and has also been shown to be upregulated in osteoarthritic versus normal human cartilage (Bohm BB et al., 1999,
Arthritis Rheum, 42:1946-1950). Thus ADAMI15 may play a role in atherosclerosis and cartilage degeneration diseases. The lymphocyte- specific expression of the ADAM28 } suggests that it may have an important immunological function.
Excessive production of IgE is believed to be a major mediator of allergic responses.
CD23, the low affinity receptor for IgE, is subject to ADAM type metalloprotease-dependent proteolytic release of soluble extracellular fragments, which have been shown to cause upregulation of IgE production and induction of inflammatory cytokines (see Novak N et al, 2001, Curr Opin Immunol, 13:721-726 and Mayer RJ et al., 2002, Inflamm Res, 51:85-90).
Increased levels of soluble CD23 have been observed in allergic asthma, in chronic B- lymphocytic leukemia and in rheumatoid arthritis. Inhibition of the enzyme(s) responsible for
CD23 processing may offer a therapeutic approach for the treatment of various immune based diseases. ADAM metalloproteases also appear to be responsible for the release or shedding of soluble receptors (for example, CD30 and receptors for TNF), adhesion molecules (for example, L-selectin, ICAM-1, fibronectin), growth factors and cytokines (for example Fas ligand, TGF-a, EGF, HB-EGF, SCF IL-6, IL-1, TSH and M-CSF), and growth factor receptors (for example EGFR family members, such as Her-2 and Her-4, which have been implicated in the pathogenesis of different types of cancer (Yarden Y and Sliwkowski MX, 2001, Nature
Reviews 2:127-137). For example, Her-2 is over expressed in 25-30% of human breast cancers and is associated with an increased risk of relapse and death (Slamon DJ et al, 1987,
Science, 235:177-182). ADAMI17 has recently been shown to be critical for the regulated shedding of Her4 (Rio C et al, 2000, J Biol Chem, 275:10379-10387). The protease responsible for Her-2 cleavage, known as Her-2 sheddase, is an unknown MMP that may also be a member of the ADAM family (Codony-Servat J et al, 1999, Cancer Res 59:1196-1201).
Modulation of this activity might therefore have an important role in the modulation of human disease. For a review of the sheddase activity of ADAMs see Moss ML and Lambert MH, 2002, Essays Biochem, 38:141-153.
ADAM-TS proteases have been identified as members of the ADAM family. These proteins are novel in that they contain unique thrombospondin (TS) type I motifs in addition to some of the structurally conserved domains of other ADAM family members. The ADAMTSs are also distinguished from the ADAMSs by their lack of cysteine-rich, EGF-like, transmembrane, and cytoplasmic domains. ADAM-TS proteins have also been shown to be associated with a number of pathological or human disease states. For example, ADAMTS-1 is a tumor-selective gene expressed in colon tumor cells and is also an inflammation-associated protein. A human ortholog of ADAMTS-1, known as METH-1, and the related protein
METH-2 have been recently shown to have antiangiogenic activity, and these or other
ADAMTS family members may play important roles in regulating vascular development.
ADAMTS-2 has been implicated in the normal development of the skin. This enzyme was long known as procollagen N-proteinase, a proteinase that proteolytically removes amino peptides in the processing of type I and type II procollagens to collagens, and it was shown to be deficient in the skin of individuals with the inherited connective tissue disorder type VIC
Ehlers-Danros syndrome. ADAMTS-4 and ADAMTS-11 are known as aggrecanase-1 and -2 because of their ability to cleave specific sites in aggrecan, a proteoglycan that maintains the mechanical properties of cartilage. Progressive degradation and depletion of aggrecan has been implicated in degenerative joint diseases such as osteoarthritis and inflammatory joint diseases such as rheumatoid arthritis. For a review of the ADAM-TS metalloproteases see Tang BL, 2001, Int J Biochem Cell Biol, 33:33-44 and Kaushal GP and SV Shah, 2000, J Clin Invest 105:1335-1337.
The metalloproteases are one of the older classes of proteinases and are found in bacteria, fungi as well as in higher organisms. Many enzymes contain the sequence HEXXH, which provides two histidine ligands for the zinc whereas the third ligand is either a glutamic acid (thermolysin, neprilysin, alanyl aminopeptidase) or a histidine (astacin). Other families exhibit a distinct mode of binding of the Zn atom. Metalloproteases have therefore been isolated from a number of prokaryotic and eukaryotic sources. Acidic metalloproteases have been isolated from broad-banded copperhead and rattlesnake venoms. Neutral metalloproteases, specifically those having optimal activity at neutral pH have, for example; been isolated from Aspergillus sojae. Alkaline metalloproteases, for example, have been isolated from Pseudomonas aeruginosa and the insect pathogen Xenorhabdus luminescens.
Inhibition of microbial metalloproteases may lead to growth inhibition and represent an antibiotic strategy. Inhibition of metalloproteases associated with snake vemom or insect toxicity may also lead to new therapeutic strategies.
Potential therapeutic indications of MP inhibitors have been discussed in the literature.
See for example, U.S. Pat. No. 6,500,847 (Bayer Corporation), U.S. Pat. No. 6,268,379 (DuPont Pharmaceuticals Company), U.S. Pat. No. 5,968,795 (Bayer Corporation), U.S. Pat.
No. 5,892,112 (Glycomed Incorporated and The University of Florida), and U.S. Pat. No. 5,872,152 (British Biotech Pharmaceuticals Limited). Some examples where inhibition of metalloprotease activity would be of benefit include: a) osteoarthritis, b) rheumatic diseases and conditions such as autoimmune disease, rheumatoid arthritis, c) septic arthritis, d) cancer including tumor growth, tumor metastasis and angiogenesis, €) periodontal diseases, f) corneal, epidermal or gastric ulceration (ulcerative conditions can result in the cornea as the result of alkali burns or as a result of infection by Pseudomonas aeruginosa, Acanthamoeba, Herpes simplex and vaccinia viruses), g) proteinuria, h) various cardiovascular and pulmonary diseases such as atherosclerosis, thrombotic events, atheroma, hemodynamic shock, unstable angina, restenosis, heart failure, i) aneurysmal diseases including those of the aorta, heart or brain, j) birth control, k) dystrophobic epidermolysis bullosa, I) degenerative cartilage loss following traumatic joint injury, m) osteopenias and other diseases of abnormal bone loss including osteoporosis, n) tempero mandibular joint disease, 0) pulmonary diseases such as chronic obstructive pulmonary disease, p) demyelinating diseases of the nervous system such as multiple sclerosis, q) metabolic diseases including diabetes (with enhanced collagen degradation) and obesity mediated by insulin resistance, macular degeneration and diabetic retinopathy mediated by angiogenesis, cachexia, premature skin aging, r) impaired wound healing including burns, s) decubital ulcers, t) acute and chronic neurodegenerative disorders including stroke, spinal cord and traumatic brain injury, amyotrophic lateral sclerosis, cerebral amyloid angiopathy, CNS injuries in AIDS, Parkinson's disease, Alzheimer's disease,
Huntington's diseases, prion diseases, myasthenia gravis, and Duchenne's muscular dystrophy, u) pain, v) autoimmune encephalomyelitis and w) diseases linked to TNFa production and/or signaling such as a wide variety of inflammatory and/or immunomodulatory diseases, including acute rheumatic fever, rheumatoid arthritis, multiple sclerosis, allergy, periodontal diseases, hepatitis, bone resorption , sepsis, gram negative sepsis, septic shock, endotoxic shock, toxic shock syndrome, systemic inflammatory response syndrome, inflammatory bowel diseases including Crohn's disease and ulcerative colitis, Jarisch-Herxheimer reactions, asthma, adult respiratory distress syndrome, acute pulmonary fibrotic diseases, pulmonary sarcoidosis, allergic respiratory diseases, silicosis, coal worker's pneumoconiosis, alveolar injury, hepatic failure, liver disease during acute inflammation, severe alcoholic hepatitis, malaria including
Plasmodium falciparum malaria and cerebral malaria, congestive heart failure, damage following heart disease, arteriosclerosis including atherosclerosis, Alzheimer’s disease, acute . encephalitis, brain injury, pancreatitis including systemic complications in acute pancreatitis, impaired wound healing and immune responses in infection inflammation and cancer, myelodysplastic syndromes, systemic lupus erythematosus, biliary cirrhosis, non-insulin dependent diabetes mellitus, bowel necrosis, psoriasis, cachexia and anorexia, radiation injury, and toxicity following administration of monoclonal antibodies such as OKT3, host-versus- graft reactions including ischemia reperfusion injury and allograft rejections including those of the kidney, liver, heart, and skin, lung allograft rejection including chronic hung allograft rejection (obliterative bronchitis), as well as complications due to total hip replacement, infectious diseases including Mycobacterial infection, meningitis, Helicobacter pylori infection during peptic ulcer disease, Chaga's disease resulting from Trypanosoma Cruzi infection, effects of Shiga-like toxin resulting from E. coli infection, the effects of enterotoxin A resulting from Staphylococcus infection, meningococcal infection, and infections from
Borrelia burgdorferi, Treponema pallidum, cytomegalovirus, influenza virus, Sendai virus,
Theiler's encephalomyelitis virus, and the human immunodeficiency virus (HIV). Defective injury repair processes also occur. This can produce improper wound healing leading to weak repairs, adhesions and scarring. These latter defects can lead to disfigurement and/or permanent disabilities as with post-surgical adhesions.
Matrix metalloprotease inhibitors are useful in treating diseases caused, at least in part, by breakdown of structural proteins. Though a variety of inhibitors have been prepared, there is a continuing need for potent matrix metalloprotease inhibitors useful in treating such diseases.
Applicants have found that, surprisingly, the compounds of the present invention are potent metalloprotease inhibitors.
The present invention provides a compound of Formula I or II:
Ca “HF
X
R;, D 1
Ry! Y— p>
Rg” © BC
R
1 or enantiomer, diastercomer, prodrug, solvate, metabolite, or pharmaceutically acceptable salt thereof, wherein constituent members are provided hereinbelow.
The present invention further provides compositions comprising a compound of
Formulaloranda pharmaceutically acceptable carrier.
The present invention further provides a method for treating a disease associated with unwanted metalloprotease activity.
The present invention further provides a method for treating a disease modulated by a metalloprotease in a mammalian subject, wherein the disease is selected from the group consisting of arthritis, cancer, cardiovascular disorders, skin disorders, inflammation and allergic conditions.
The present invention further provides a method for treating cancer, including but not limited to breast cancer, in a mammal.
The present invention further provides a method of inhibiting pathological changes mediated by elevated levels of matrix metalloproteases in mammals comprising administering to said mammal in need thereof a therapeutically effective amount of a compound of the invention.
The present invention further provides a method for treating a disease associated with unwanted TNF-a. converting enzyme activity.
The present invention further provides a method for treating a disease associated with unwanted matrix metalloprotease activity wherein said matix metalloprotease is selected from the group consisiting of MMP12, MMP14, MMP3, MMP2, and MMP9 in a mammalian subject.
The present invention further provides a method for treating a disease associated with unwanted activity of Her-2 sheddase, growth factor sheddases, or cytokine sheddases in a mammalian subject.
The present invention further provides a method for treating a disease associated with activity of Her-2 sheddase ina mammal.
The present invention further provides a method for treating a disease associated with unwanted ADAM10, ADAMI, or ADAMI17 activity in a mammalian subject.
The instant invention provides, inter alia, compounds and pharmaceutical compositions of matter for treating pathological conditions which are associated with metalloprotease activity such as the rapid, unregulated breakdown of extracellular matrix tissue by MMPs including, but not limited to, MMP 12 and MMP 13. Some of these conditions include rheumatoid arthritis, osteoarthritis, septic arthritis, corneal, epidermal or gastric ulceration;
periodontal disease, proteinuria, coronary thrombosis associated with atherosclerotic plaque rupture and bone disease. The compounds of the invention are also useful for treating cancer including, for example, tumor metastasis and angiogenesis which also appears to be associated withe metalloprotease activity. Also, since the cycle of tissue damage and response is associated with a worsening of the disease state, limiting metalloprotease-induced tissue damage due to elevated levels of the proteinases with the compounds of the instant invention can be a generally useful therapeutic approach to many of these debilitating diseases and others. The compounds of the invention are also inhibitors TNFa converting enzyme and sheddases including Her-2 sheddase and HB-EGF sheddase and other growth factor and cytokine sheddases.
The present invention provides a compound of Formula I or II: v_N “PC
R, D
I
Ry’ YM p>
Rg” © BE.
Raz
I or enantiomer, diastereomer, prodrug, solvate, metabolite, or pharmaceutically acceptable salt thereof, wherein:
A is CWOH, CWNHOH, CWNHORs;, N(OH)CHO, N(OH)CWR;, SH, SR; or hydantoinyl;
B is (CHym (CH),C=W, (CRR):NRs, NRs(CRR9m (CRR)O(CRaR)s, (CRaR9)xS(CReRg)r, O(C=W)NRs, O, N, NRs, S(O)m, S, C(O)NRs(CRaR 9s, C(O) CR4R9a, or combinations thereof’,
G is (CHa)s (CH2.C=W, (CRaR).NRs, NRs(CRaRom (CRR9O(CR4R):, (CRaR)sS(CRaR9), O(C=W)NRy, O, N, NRs, S(O)m, S, C(O)NRg(CR4R 9», C(OXCR4R(), or combinations thereof;
D is oxygen or sulfur;
X is absent, (CH), Ci.10 alkylene substituted with 0 to 3 Re, Cao alkenylene substituted with 0 to 2 Re, N, O, NRs, S(O), C=O, NRsC(O); NR,C(0)O, NRsC(O)NRs,
C(0)0, OC(0), S(O)mNRs, NR:S(O)ms NRsS(O)mNR:» (CRRYNRs, NRy(CRaRg), or combinations thereof;
Y is absent, (CH), Cio alkylene substituted with 0 to 3 Rs, C20 alkenylene substituted with 0 to 2 Ry, N, O, NRs, S(O)ms C=0, NR,C(0), NR,C(0)O, NR, C(O)NRb,
C(0)0, OC(0), S(O)nNRo, NRyS(O)m: NR,S(O)mNRs, (CRRONRs, NRy(CRaR9), or combinations thereof;
M is CO or S(O);
U is absent, Ci.10 alkylene substituted with 0 to 5 R,, Ca.19 alkenylene substituted with 0 to 2 Re, N, O, NRs, NRsC(0), NR«C(0)O, NRsC(O)NRy, NR,S(O)m, NRyS(O)NRy or combinations thereof;
V is absent, H, Cj.13 carbocyclyl substituted with 0-5 Re or heterocyclyl substituted with 0-5 Re;
U’ is absent, Cy.10 alkylene substituted with 0 to 5 Re, Cz-10 alkenylene substituted with 0 to 2 R,, N, O, NRsS(O)w, C=0, NRyC(0), NR,C(0)O, NR;C(O)NRs, C(0)O, 0C(0),
S(O)» NRy, NRsS(0)m, NRS(O)NRs or combinations thereof;
V’ is H, C3 alkyl, NRgRc, C3.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 R,;
R, and R. are each, independently, H, T, C,salkylene-T, C,salkenylene-T, Co. salkynylene-T, C(O)NR(CRy'Re’)-T, C(OYO(CRy'R:)rT, S(0)(CRo’R)+-T, (CRy’Re)~O- (CRy'R.)T, OH, Cl, F, Br, I, CN, NO2, NRR", COR", COOR™, ORY, CONR'R",
NRICONRR". OCONR'RY, NRICOR?, SO;NR'RY, NR'SO:R", NR'SO,;NR'R', OSO,NR'R",
SOR", Cs haloalkyl, Cs.13 carbocyclyl, heterocyclyl, carbocyclylalkyl, or heterocyelylalkyl, wherein each of said carbocyclyl, heterocyclyl, carbocyclylatkyl, and heterocyleylalkyl groups is optionally substituted by one or more C..3 alkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, carboxy alkyl ester, carboxy aryl ester, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylsulfonyl, arylsulfinyl, alkylsulfonyl or arylsufonyl;
R, and R. are each, independently, H, T, Ci¢alkylene-T, Ci.salkenylene-T,
Cyalkynylene-T, C(O)NRJ'(CRRy')T, C(O)O(CRy'R(’)-T, C(O)CRy'R)-T,
S(O)(CRy’R:")r-T, (CR’Ry")~0O-(CR:’Ry’)~T, C(NR,'R,’)=N-CN) or
C(NR,’R)(=CHNOy);
Ry and Ry are each, independently, H, Cy alkyl, Cy alkenyl, Cas alkynyl, T, Cu. calkylene-T, Csalkenylene-T, C,.calkynylene-T, C(O)NR,'(CR'Ry')~T, C(O)O(CRy'R:)-~T,
S(0),(CRy'Re)T or (CR’Ry)-0-(CRe’Re')~T, OH, CL F, Br, 1, CN, NOz, NRR", COR",
COOR™, OR", CONR'RY, R'NCONR'R", OCONR'R', R'NCORY, SO;NR'RY, NR'SOR",
NR'SO,NRRY, OSO:NRR, SO,RY, Cis haloalkyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, heterocyclylalkyl, carbocyclyloxy or heterocarbocyclyloxy, wherein each of said carbocyclyl, heterocyclyl, carbocyclylalkyl, heterocyclylalkyl, carbocyclyloxy or heterocarbocyclyloxy groups is optionally substituted by one or more C,.3 alkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, carboxy alkyl ester, carboxy aryl ester, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylsulfonyl, arylsulfinyl, alkylsulfony! or arylsufonyl;
T is H, Ci.10 alkyl substituted with 0 to 5 Ry’; Ca.10 alkenyl substituted with 0 to 5 Ry’,
Cp.10 alkynyl substituted with 0 to 5 Ry’, Cis carbocyclyl substituted with 0-3 Ry’, heterocyclyl substituted with 0-5 Ry’;
R,’, Ry’ and R" are each, independently, H, Ci alkyl, Ca.¢ alkenyl, C26 alkynyl, OH,
CL F, Br, I, CN, NO,, NRIRP, COR™, COOR™, OR", CONR'RY, RINCONR'R", OCONR'R",
RINCOR". SO,NRRY, NR'SO,R®, NR'SO,NRR', OSO,NR'RY, SO,RY, Cs haloalkyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, heterocyclylalkyl, carbocyclyloxy or heterocarbocyclyloxy, wherein each of said carbocyclyl, heterocyclyl, carbocyclylalkyl, heterocyclylalkyl, carbocyclyloxy or heterocarbocyclyloxy groups is optionally substituted by one or more C,.g alkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, carboxy alkyl ester, carboxy aryl ester, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylsulfonyl, arylsulfinyl, alkylsulfonyl or arylsufonyl;
R, is hydrogen, Ci alkyl, SR10, OR1o or NR;1Ri2;
R; is hydrogen, C1. alkyl, SRyq, ORy0 or NRiR12;
Rj is: @) Ch.10 alkyl, Cz.3 alkenyl or C.3 alkynyl; (i) Cs.3 carbocyclyl optionally substituted with one or more substituents selected from halogen, Ci. alkyl, SRi3, NRiiRiz, OR, heterocyclyl, aryl, =S, =O, CN, NO, NRgRg’,
COR,, RNC(O)NR,R;’, OC(O)NR,R,’, C(O)ORy, C(O)NR,Ry’, or R,NC(0)0;
(iii) aryl optionally substituted with one or more substituents selected from halogen,
Cis alkyl, SR;3, NRjRi2, ORy3, heterocyclyl, aryl, =S, =O, CN, NO, NRgRp’, COR,,
R,NC(ONRRy, OC(O)NR,R,’, C(O)YOR,, C(O)NR,Ry’, or R,NC(0)0; (iv) heterocyclyl optionally substituted with one or more substituents selected from halogen, C1. alkyl, SRy3, NR1iR12, OR, heterocyclyl, aryl, =S, =0, CN, NO;, NRgRg’, COR,
R,NC(O)NR,R,’, OC(O)NR,R,’, C(O)ORy, C(O)NR,R,’, and RNC(0)O; (v) NRyu(CHz)NR;4Ris; OF (vi) NRjeRiz
R4 and Rs are each, independently, H, halogen, T, C;alkylene-T, Caalkynylene-T,
C(O)NR,’(CR’Ry"),-T, CO(CRyR<)r-T, C(OYO(CRs’Re)-T, S(O)(CRs'Re’)~T, (CR'Ry)r-
O-(CR¢’Ry’)~T, NRy1Ri2, SRys or ORs; : Ry is H, halogen, T, Cjealkylene-T, Cjsalkynylene-T, C(O)NR,’(CR¢'Ry’)~T,
CO(CRyRs)rT, C(O)O(CRyR:)-T, S(O)(CRy’R:)-T, or (CRRy’)-O-(CRRo)~T,
NR11Ri12, SRys, or ORs;
Rs’ is H, halogen, T, Cisalkylene-T, Cj¢alkynylene-T, C(ONR,'(CR¢’Ry’)r-T,
CO(CRyR:)-T, C(O)O(CRy'R:)rT, S(O)(CRy'Rc)-T, or (CRIRy’)-O-(CR'Rs’)~T,
NRyRi, SRus, or ORus; or Ry’ and Rs’ together with the atoms to which they are attached form a ring selected from Cs.13 carbocyclyl and 3-14 membered heterocyclyl;
W is oxygen or sulfur;
Rg and Ry are each, independently, hydrogen, Cy. alkyl, Cz. alkenyl or Cy alkynyl;
Ry is H, Cj.19 alkylene-T, C,.j9 alkenylene-T, and C;.10 alkynylene-T, (CRy’R:),O(CRs'R) AT, - (CRy’R:)/NR,(CRy’RS) T, (CRy'Ro),C(O)CRy’R.’) T, (CRy'Ro),C(O)O(CRy'RS’) ~T, (CRy’Rc),OC(O)CRy'R.) ~T, (CRy’Ro)C(O)NRS’(CRy'RS) + T, (CRy’Re)NRSC(O)(CRy'Re) + T, (CRy’Ro)/OC(O)O(CRy'R.’) ~T, (CRy’Ro)/OC(O)NRJ(CRy'RS’) »-T, (CRy’R)NR,’C(O)O(CRy’R) T, (CRy’R)NRC(ONR,(CRy'R") -T, (CRy'R):S(O)(CRy'R:) T,
(CRy’Re)SONRS(CRyRS) ~T, (CRy' RNR’ SO(CRy'R.) ~T, Or (CRy'Ro), SO:NR,’SOCRy’RS) ~T;
Ryo is H or Ci-Cs alkyl;
Ry; and Ry; are each, independently, hydrogen or C;-Cs alkyl, or Ry; and Rp together with the N atom to which they are attached form a 3-14 member heterocyclic ring;
Ry; is Ci-Cs alkyl, Ci-Cs haloalkyl, Cs-13 carbocyclyl, carbocyclylalkyl, heterocyclyl, ° heterocyclylalkyl, each of which is optionally substituted by one or more halo, C14 alkyl, C14 alkoxy, Ci« haloalkyl, Ci4 haloalkoxy, CN, NO, OH, COOH, amino, alkylamino, or dialkylamino;
Rus and Rys are each, independently, hydrogen, Ci.10 alkyl, Cs.13 carbocyclyl substituted with one or more heterocyclyl, or Rs and Rs together with the N atom to which they are attached form a 3-14 membered heterocyclic system;
Ry and Ry; are each, independently, hydrogen, C-Cio alkyl, C3-Ci3 carbocyelyl, aryl,
C3-Cy3 carbocyclylalkyl or arylalkyl, wherein said C;-Cio alkyl, C3-Cis carbocyclyl, aryl,
Cs.13 carbocyclylalkyl or arylalkyl are each optionally substituted with one or more halo, C14 alkyl, Cy haloalkyl, ORi7’, SR,7’, COOR;7’, amino, alkylamino, dialkylamino or heterocyclyl; or Ris and Ry7 together with the N atom to which they are attached form a 3-14 membered heterocycle substituted with 0-5 Ro, or are substituted by one or more heterocyclyl, heterocyclylalkyl, C3-Cis carbocyclyl or carbocyclylalkyl, wherein said heterocyclyl, heterocyclylalkyl, C3-Ci3 carbocyclyl or carbocyclylalkyl are each optionally substituted by one or more Rg;
Ri7 is H, Ci alkyl, C14 haloalkyl, Cs.;3 carbocyclyl, carbocyclylalkyl, heterocyclyl or heterocyclylalkyl, wherein said C;.3 carbocyclyl, carbocyclylalkyl, heterocyclyl or heterocyclylalkyl are each optionally substituted by halo or Cy alkyl;
Rg is C;6 alkyl;
R, is halogen, Cy. alkyl, Cys alkyloxyalkyl, Ci.6 haloalkyl, SRy3, NRjR12, OH, ORy3,
C;.13 carbocyclyl, heterocyclyl, aryl, =S, =0, CN, NO;, NRgRp’, CORy, NRgC(O)NRgRg’,
OC(O)NRgRp’, C(O)NRgRp’, C(O)OR, NRgC(O)OR, or NRgC(O)R,, or two Rq together with a carbon atom to which they are both attached form a Cs.13 carbocycle;
Rg, Rg’, Ry, and R,’ are each, independently, H, C)4 alkyl, phenyl or benzyl;
R! and R" are each, independently, H, C1.¢ alkyl or Cs.(3 carbocyclyl;
R™ and RY are each, independently, H, C1 alkyl, haloalkyl, carbocyclyl, heterocyclyl, carbocyclylalkyl or heterocyclylalkyl, wherein said carbocyclyl, heterocyclyl, carbocyclylalkyl or heterocyclylalkyl are each optionally substituted by one or more halo,
C4 alkyl or C4 alkoxy;
RY is C6 alkyl, haloalkyl, carbocyclyl or heterocyclyl; j=1,2,30r4 i=0,10r2; =2,3,4,5,6,70r8, n=0,1,2,3,4,56,7,8,9,10, 11 or 12; m=0,1o0r2; p=1or2; and =0,1,2,3,40r5S.
The spiro ring is preferably a stable chemical entity.
In some embodiments, NRg and NR; have no N-N or N-O bonds.
In some embodiments, A is CWNHOH, CWNHOR;s, N(OHYCHO or N(QHYCWRe.
In some embodiments, A is CWNHOH or CWNHOR:s.
In some embodiments, A is C(O)NHOH.
In some embodiments, B is (CHp)s (CH2).C=W, (CR4R)sNRs, NRg(CRaRop, (CR&R)-O(CReR Dy, (CR4R)AS(CRaR Dr, O(C=W)NRg, O, NRs, S(O)m, S, C(O)NR¢(CReR 9s or
C(OXCReR pn.
In some embodiments, B is (CHa), (CH2),C=W, (CR4Re)sNRs, NRg(CRRon
O(C=W)NRj, O, NRg, S(O)m, S, C(O)NRg(CR¢Rg}» or C(OXCR4Ro)n-
In some embodiments, B is (CHj)s (CH2),C=W, (CR4Rf):NRs, NR3(CR4R1)n,
O(C=W)NRg, C(O)NRs(CRaR9)» or C(O)(CRaR)n.
In some embodiments, B is (CHy),, (CH2),C=W, (CR4R¢).NRs or NRs(CRaR¢).
In some embodiments, B is (CHa).
In some embodiments, B is CHa.
In some embodiments, G is (CHz)n, (CH2),C=W, (CR4RQsNRs, NRs(CR4Rn, (CRaR)sO(CR4R),, (CR4RD:S(CR4R),, O(C=W)NRs, O, NRs, S(O), S, C(O)NRs(CR4R 9) or
C(O)(CRaR 9).
In some embodiments, G is (CH2),, (CH),C=W, (CR4Rf)»NRs, NRg(CR4Rf)n,
O(C=W)NRg, O, NR3, S(O)m, S, C(O)NR3(CR4R9);, or C(O)(CR4R Dn.
In some embodiments, G is (CH), (CH2)sC=W, (CR4Rp,NRs, NRs(CR¢R¢)n,
O(C=W)NR3, C(O)NRs(CR4Rg), or CCOXCRgR on.
In some embodiments, G is (CH), (CH2),.C=W, (CRaR)sNRs, NRg(CR¢R On
In some embodiments, G is (CHz)».
In some embodiments, G is CHa.
In some embodiments, B and G are both CH.
In some embodiments, D is oxygen.
In some embodiments, X is (CHa), Cio alkylene substituted with 0 to 3 Ra, NRs,
S(O)m, C=0, NR,C(0), NRsC(0)O, NR:C(O)NRs, C(0)0, OC(0), S(O)mNRy, NRsS(O)m,
NRsS(O)NRs, or (CReRo)NRs, NRo(CRaR9)-
In some embodiments, X is (CHz);, NR, (CRaRg)NRs or NRp(CR4Rg).
In some embodiments, X is (CHz);, (CReRONRs or NRy(CR4R9),.
In some embodiments, X is CH2NRG, CH,CH, or NR,CH;CHa. .
In some embodiments, X is CH2NRy.
In some embodiments, Y is absent, (CH), Ci.10 alkylene substituted with 0 to 3 R,,
NEy, S(O)ms C=O, NR,C(O), NRsC(0)0, NRiC(O)NRs, C(0)0, OC(0), S(O}nNRs,
NRS(O)m, NRyS(O)NRs, or (CRRANRy, NRy(CR4R 9).
In some embodiments, Y is absent, (CHz);, NR, (CR4RONRy or NRy(CRyRy);.
In some embodiments, Y is absent, (CHz);, (CR:RQNRs or NRs(CR4R9);-
In some embodiments, Y is absent, CHa, CH2NRy, CH,CH, or NR,CH:CHa.
In some embodiments, Y is absent or CHa.
In some embodiments, Y is CH,.
In some embodiments, R; is H.
In some embodiments, R; is H.
In some embodiments, Ry is H.
In some embodiments, Ry’ is H.
In'some embodiments, Rs’ is H.
In some embodiments, Rj is NRj6R17.
In some embodiments, M is CO.
In some embodiments, U is absent.
In some embodiments, V is heterocyclyl substituted with 0-5 Re.
In some embodiments, V is azetidin-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, piperindin-1yl, piperazin-1-yl, pyrrolidin-1-yl, isoquinol-2-yl, pyridin-1-yl, 3,6-dihydropyridin-1-yl, 2,3- dihydroindol-1-yl, 1,3,4,9-tetrahydrocarbolin-2-yl, thieno[2,3-c]pyridin-6-yl, 3,4,10,10a- tetrahydro-1H-pyrazino[1,2-a}indol-2-yl, 1,2,4,4a,5,6-hexahydro-pyrazino[1,2-a] quinolin-3-yl, pyrazino[1,2-a]quinolin-3-yl, diazepan-1-yl, 1,4,5,6-tetrahydro-2H-benzo[f]isoquinolin-3-yl,
1,4,4a,5 ,6,10b-hexahydro-2H-benzo[f]isoquinolin-3-yl, 3,3a,8,8a-tetrahydro-1H-2-aza- cyclopenta[a}inden-2-yl, or 2,3,4,7-tetrahydro-1H-azepin-1-yl, azepan-1-yl. : In some embodiments, U? is absent, O or C.j0 alkylene substituted with 0 to 5 Ra.
In some embodiments, U’ is absent.
In some embodiments, V’ is Cs.13 carbocyclyl substituted with 0-5 Re or heterocyclyl substituted with 0-5 R..
In some embodiments, V’ is Cs.13 carbocyclyl substituted with 0-5 Re.
In some embodiments, V’ is phenyl substituted with 0-5 Re.
In some embodiments, V’ is phenyl substituted with 0-5 T, Cy.salkylene-T, (CRy’R.)~
O-(CRy'R.’),-T, OH, CL, F, Br, I, CN, NO,, OR", CONR'R" or NR'COR".
In some embodiments, V’ is phenyl.
In some embodiments, V is heterocyclyl substituted with 0-5 R..
In some embodiments, V’ is thiazolyl, benzothiazolyl, thienyl, quinolinyl, pyridinyl, pyarazinyl, benzimidazolyl, indazolyl, 3,6-dihydropyridinyl, piperidinyl or 2,3-dihydro- benzofuran-5-yl.
In some embodiments, U’ is O or C.jo alkylene and V’ is Cj.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 Re.
In some embodiments, M is CO, U is absent, V is heterocyclyl substituted with 0-5 R,
U’ is absent, and V’ is Cs.,3 carbocyclyl substituted with 0-5 R, or heterocyclyl substituted with 0-5 Re.
In some embodiments, M is CO, U is absent, V is absent, U’ is absent and V’ is NRyR..
In some embodiments, R, and R. are each, independently, H, !
Cisalkylene-T, C(ONR,(CR:'Ry’)~T, ~~ C(O)O(CRy'R:)~T, ~~ C(O)CRy'R.),-T,
S(O)(CRy’R:")-T, (CR:’Ry’)~O-(CR’Ry)~T, C(NR,'R,’)(=N-CN) or
C(NR.'Ry’)(=CHNO).
In some embodiments, R, and R. are each, independently, H,
Cis alkyl, C(O)NR,’(CR:'Ry’)-T, C(O)O(CR»'R:’)~T, S(O)(CRy’R’)-T, (CR'Ry’),-O- (CR:'Ry")~T, CANRy’R,"}(=N-CN) or CINR’Ra"}(=CHNO).
In some embodiments, Ry is H, C4 alkyl, C(OXCRs’R.’)-T, C(O)O(CRy’R;’)-T,
S(0)x(CRy'R.)-T or (CRRy")-O-(CR'Ry’)-T.
In some embodiments, Ry is H.
In some embodiments, Ry, is C4 alkyl.
In some embodiments, Ry, is C(OXCRy’R.’)~T.
In some embodiments, R;, is C(O)O(CRy’R.’),-T.
In some embodiments, Ry is S(O)(CRy’Rc")~T.
In some embodiments, Rp is (CR’Ry)~O-(CR:’Ry’)~T.
In some embodiments, Re is H or C;4 alkyl.
In some embodiments, R. is H, T, C)salkylene-T, C(O)NR,’(CRy’R:")-T, (CRy’RS)- 0-(CRs'R.’),-T, OH, Cl, F, Br, I, CN, NO,, OR", NR'R", CONRRY, NR'COR", SO,NR'R",
Cs haloalkyl, Cs.13 carbocyclyl, heterocyclyl, carbocyclylalkyl, or heterocyclylalkyl, wherein each of said carbocyelyl, heterocyclyl, carbocyclylalkyl, and heterocylcylalkyl groups is optionally substituted by one or more Ci. alkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, carboxy alkyl ester, carboxy aryl ester, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulfonyl, aminosulfonyl, alkylaminosulfony!, dialkylaminosulfonyl, arylsulfonyl, arylsulfinyl, alkylsulfonyl or arylsufonyl.
In some embodiments, wherein R. is H, Cis alkyl, OH, CL F, Br, 1, CN, NO,, methoxy, ethoxy, n-propoxy, isopropoxy, phenoxy, benzyloxy, amino, (Ci4 alkyl)amino, (Ca. g)dialkylamino, C(O)O(C14 alkyl), CONH;, CONH(Ci4 alkyl), CON(Ci4 alkyl, Cis haloalkyl, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzyl, or phenethyl.
In some embodiments, Ry is C(O)NR.(CRSRy’)-T, C(O)O(CRy’R.’)~-T or
S(0)(CRy’R:’)-T.
In some embodiments, Rs’ is C(O)NR,’(CRRy)T, C(O)O(CRy'R.)-T or
S(O)(CRy'R)-T.
In some embodiments, 7 is 0, 1 or 2.
In some embodiments, nis 0, 1 or 2.
In some embodiments, j is 1 or 2.
In some embodiments, said compound has Formula II.
In some embodiments, the compound has Formula II wherein:
A is CWNHOH,
B is (CH (CH).C=W, (CReR9sNRs, NRs(CRsRon, (CR4ROAO(CRaRor, (CR4R)sS(CR4Rp)r, OC(O)NRs, O, NRg, S(O)m , S, C(O)NRg(CR4R2)» or C(OXCRaR9)n;
G is (CHz)s (CH2.C=W, (CR&RO:NR;, NRg(CR4R9n, (CR4R):O(CRaR), (CR4R)nS(CR4R1), OC(O)NRs, O, NRg, S(O) , S, C(O)NRs(CR4R9)» or C(O)(CR4R)r;
X is absent, (CHa), Ci-10 alkylene substituted with 0 to 3 Re, 0, NR, S(O)m; C=0,
NR,C(0), NR:C(0)O, NRC(O)NRs, C(0)Q, OC(0), S(O)aNRy, NRuS(O)ms NRsS(O)NRs, (CR4RNRs or NRy(CR4R 1); :
Y is absent, (CHyp);, Ci.10 alkylene substituted with 0 to 3 Re, O, NR, S(O)m, C=0,
NR,C(0), NRsC(0)0, NR,C(O)NRs, C(0)O, 0OC(0), S(O)sNRy, NRsS(O)ms NRsS(O)NRw, (CR4RNRs or NRy(CRaR1);
Mis CO;
U is absent, Cy. alkylene substituted with 0 to 5 Ry, O, NRy, S(O)ms C=0, NR,C(O),
NRsC(0)0, NR,C(O)NRs, C(0)0, OC(0), S(0)nNRs, NRsS(O)n or NR,S(O)NRp;
V is absent, C3.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0- 5Re;
U’ is absent, Cy.10 alkylene substituted with 0 to 5 Re, O, NRS(O)m, C=0, NR,C(O),
NR:C(0)0, NRyC(O)NRs, C(0)O, OC(0), S(0)aNRs, NRsS(O)m, or NRsS(O)NRs;
V’ is H, Cs alkyl, NRyRc, Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 Re;
R| is hydrogen;
R; is hydrogen;
Rj is NRieR17;
Ry’ is H, C(O)NR,(CRRy")~T, C(O)O(CRs'Re")-T or S(O)(CR'R)-T:
Rs’ is H, C(O)NR,'(CR.'Ry’)~T, C(O)O(CRs'Ry)T or S(O),(CRs'R:")-T; and
W is oxygen.
In some embodiments, the compound has Formula II wherein:
A is C(O)NHOH;
B is (CH (CH)WC=W, (CRR):NRs, NRs(CRRon (CRaR)-O(CRaRDr (CR4R)S(CR4R¢), OC(O)NR3, O, NR3, S(O)m , S, C(O)NRg(CR4Rg) or C(OXCRaR 1);
G is (CHpm (CH.C=W, (CRRJNRs, NRs(CRRom (CRRDO(CRRr (CRaR)»S(CR4R),, OC(O)NRs, O, NRg, S(O)m , S, C(O)NRs(CRR)n Or C(O)XCR4Ron;
X is absent, (CHa);, NR, (CRgR;NRy, or NRy(CReRg);;
Y is absent, (CHa), NR, (CR¢R9;NRs or NRy(CRR 1);
Mis CO;
U is absent;
V is absent, Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-
SR :
U’ is absent, Cj.1 alkylene substituted with 0 to 5 Rq, O, NRpS(O)m, C=0, NR:C(0),
NR;C(0)O0, NRyC(O)NRs, C(0)0, OC(0), S(O)mNRs, NRsS(O)m, or NRpS(O)NRy;
V’ is H, Ci. alkyl, NRyRc, Cs.13 carbocyclyl substituted with 0-5 Re or heterocyclyl substituted with 0-5 Re;
Ry, and R, are each, independently, H, C(O)O(CRy’R")-T or S(O) (CRy’R)-T5
Ry and Ry are each, independently, H or C16 alkyl,;
R; is hydrogen;
R; is hydrogen;
Rj is NRygR17;
Ry’ is H, C(O)NRy’(CR.’Ry)~T, C(OYO(CRs’Re’),-T or S(0),(CRy’R:")~T; and
Rs’ is H, C(O)NR,’(CRo’Ry’)-T, C(O)O(CRy'R<")~T or S(0);(CRs Re") T;
In some embodiments, the compound has Formula II wherein:
A is C(O)NHOH;
B is (CHa (CH2AC=W, (CRR).NRs, NRg(CRaRon (CReRIZO(CReRor, (CRaRO»S(CR4Ry),, OC(O)NRs, O, NRg, S(O) , S, C(O)NRs(CReR9), or C(O)CRuR);
G is (CHps (CH2AC=W, (CRaR9NRs, NRs(CRR9nm (CReRI-O(CRR9r (CRR)»S(CR4RQr, OC(O)NRg, O, NR, S(O)w , S, C(O)NRs(CRaR9)» or C(OXCR4R)n;
X is absent, (CHz);, NRy, (CRaReyNRs or NRy(CR4R 9);
Y is absent, (CH,);, NRy, (CRaRQyNR;, or NRy(CR4R¢);;
Mis CO;
U is absent;
V is absent, Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-
SR;
U’ is absent, C.1o alkylene substituted with 0 to 5 Ry, O, NRpS(O)s, C=0, NR,C(O),
NR;C(0)O0, NRyC(O)NRy, C(0)0, OC(0), S(O)mNRp, NRpS(O)m, or NRpS(O)NRy;
V’ is H, Cis alkyl, NRyR., Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 Re;
Ry and R. are each, independently, H, C(O)O(CRs'R.’)T or S(O),(CRv’R.)T;
C(OXCRy’Rs)rT, (CR'Ry)~0-(CR’Ry")~T, C(O)NR.(CR:'Ry’)~T, C(NRy’Ra")(=N-CN) or C(NR.’Ra’)(=CHNO);
Rq4 and R¢ are each, independently, H or C,4 alkyl;
R,’ is H or C4 alkyl;
Ry’ and R,’ are each, independently, H, C15 alkyl, OH, Cl, F, Br, I, CN, NO, NRIRY,
OR or haloalkyl;
R, is hydrogen;
R; is hydrogen;
Re’ is H, C(O)NR,’(CR:'Ry")-T, C(O)O(CRy'R)-T or S(O)(CRy'R)T;,
Rs’ is H, C(O)NR,’(CR:’Ry’)-T, C(O)O(CRy'R.’)~T or S(O), (CRu'R:’)T; j=1lor2;
I=2,30r4; n=0,1,2,3 or4; and r=0,1or2.
In some embodiments, the compound has Formula II wherein:
A is CONHOH;
B is (CHa (CH)AC=W, (CRRONRs, NRs(CRRm (CRR9:O(CRdRor, (CR4R9»S(CRaRy), OC(O)NRs, O, NRs, S(O)w , S, C(O)NRs(CR4R9)n or C(OXCRaR 9m;
G is (CH (CH).C=W, (CRR)-NRs, NRs(CRR9n (CRRIO(CRR9), (CR4R»S(CRaRy), OC(O)NRs, O, NRs, S(O) , S, C(O)NRs(CR4R 9), or C(O)(CR4R 1s;
X is absent, (CH); CH,NR; or NR,CH,CHy;
Y is absent, (CH,);, CH2NRy, or NRyCH,CHj;
Mis CO;
U is absent;
V is heterocyclyl substituted with 0-5 Re;
U’ is absent, C;.jo alkylene substituted with 0 to 5 R,, or O;
V’ is H, C,.3 alkyl, NRgR., Cs.13 carbocyclyl substituted with 0-5 R. or beterocyclyl substituted with 0-5 R.;
Ry is H, C(O)O(CRy'R.’),~T or S(O),(CRy’Rc")-T; C(OXCRy'R:’)~T, (CR:’Ry’)-O- (CRI'Ry")~T, C(O)NR,’(CR:'Ry)»-T, CONRy'RyW=N-CN) or CONR4"R.")(=CHNO2);
Ris H, T, Ci¢alkylene-T, C,.salkenylene-T or Casalkynylene-T;
Rq and Ry are each, independently, H or Cs alkyl;
R,’ is H or Cy alkyl;
Ry’ and R,’ are each, independently, H, Ci. alkyl, OH, CI, F, Br, I, CN, NO;, NRRY,
OR" or haloalkyl;
R, is hydrogen;
R; is hydrogen;
Ry’ is H;
Rs’ is H; j=lor2;
I=2,30r4, n=0,1,2,3 or4; and r=0,1o0r2.
In some embodiments, the compound has Formula II wherein:
A is CONHOH;
B is (CHa)n, (CH2)sC=W, (CRaR)»NRg or NRs(CR4R9);
G is (CHa)n, (CH2)/C=W, (CRaR9):NRg or NRg(CRaR 1);
X is absent, (CHy), CHaNRy, or NR;CH,CHy;
Y is absent, (CH,);, CHoNRy, or NRyCH2CHy;
Mis CO;
U is absent;
V is heterocyclyl substituted with 0-5 Re;
U’ is absent, C).jp alkylene substituted with 0 to 5 Rs, or O;
V’ is H, Cs alkyl, NRyR,, Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 R,;
Ry is H, C(O)O(CRy’R.’),~T or S(0),(CRy’R:’)-T; C(O)CRo'Re’)r-T, (CR:’Ry’)-O- (CR’Ry)~T, C(O)NR,’(CRc'Ry’)-T, CNR. Ra" ¥=N-CN) or CNR,’Rs’)(=CHNO);
Ris H, T, C,alkylene-T, C,.galkenylene-T or C,¢alkynylene-T,
R4 and Re are each, independently, H or Cy alkyl;
R,’ is Hor Cig alkyl;
Ry’ and R,’ are each, independently, H, Cy alkyl, OH, Cl, F, Br, I, CN, NO, NR'R",
ORY or haloalkyl;
R; is hydrogen;
R; is hydrogen;
Ry is H;
Rs’ is H; j=lor2;
E=2,30r4; n=0,1,2,30r4;and r=0,1or2.
In some embodiments, the compound has Formula II wherein:
A is CONHOH;
B is (CHa)n;
G is (CHy)s;
X is absent, (CH), CH;NR; or NR,CH,CH;;
Y is absent, (CH,);, CH,NRy or NRyCH2CHy;
Mis CO;
U is absent;
V is heterocyclyl substituted with 0-5 Re;
U’ is absent, C.1o alkylene substituted with 0 to 5 R,, or O;
V’ is H, C,.3 alkyl, NRgR,, Cs.13 carbocyclyl substituted with 0-5 Re or heterocyclyl substituted with 0-5 Re;
Ry is H, C(O)O(CRy'Re)-T or S(0)s(CRy'R:")~T; C(OXCRo'Re)r-T, (CR:'Ry’)-O- (CR:’Ry’)~T, C(O)NRy’(CR. Ry’) T, CINRy’Re")(=N-CN) or C(NRJR,")(=CHNO,);
Reis H, T, Cisalkylene-T, C,.salkenylene-T or C; ¢alkynylene-T;
R,’ is H or C; 4 alkyl;
Ry’ and R,’ are each, independently, H, Cy alkyl, OH, Cl, F, Br, I, CN, NO,, NR'R",
OR" or haloalkyl;
R} is hydrogen;
R; is hydrogen;
Ry’ is H;
Rs’ is H; j=1lor2;
I=2,30r4, n=0,1,2,3o0r4; and r=0,1or2.
In some embodiments, the compound has Formula IT wherein:
A is CONHOH;
B is CH;
G is CH;
X is CHoNRy;
Y is (CHa);
Mis CO;
U is absent;
V is azetidin-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, piperindin-1yl, piperazin-1-yl, pyrrolidin-1-yl, isoquinol-2-yl, pyridin-1-y, 3,6-dihydropyridin-1-y}, 2,3-dihydroindol-1-y}, 1,3 ,4,9-tetrahydrocarbolin-2-yl, thieno[2,3-c]pyridin-6-yl, 3,4,10,10a-tetrahydro-1H- pyrazino[1,2-a]indol-2-y1, 1,2,4,4a,5 6-hexahydro-pyrazinof 1,2-a]quinolin-3-yl, pyrazino[1,2- a]quinolin-3-yl, diazepan-1-yl, 1,4,5,6-tetrahydro-2H-benzo[flisoquinolin-3-yl, 1,4,4a,5,6,10b- hexahydro-2H-benzo(flisoquinolin-3-yl, 3,3a,8,8a-tetrahydro- 1H-2-aza-cyclopentafa]inden-2- yl, or 2,3,4,7-tetrahydro-1H-azepin-1-yl, azepan-1-yl; :
U’ is absent;
VV? is Cs.13 carbocyclyl substituted with 0-5 Re;
Ry is H, C(Q)O(CRy’R.’)-T or C(OXCRs'R<")-T;
R,’ is H or Cys alkyl;
Ry’ and R.’ are both H;
R; is hydrogen;
R; is hydrogen;
Ry is H;
Rs’ is H; j=1lor2; and r=0,1or2.
In some embodiments, the compound has Formula II wherein:
A is CONHOH;
Bis CHy;
G is CHy;
X is CH;NRy,;
Y is (CHa);
Mis CO;
U is absent;
V is piperindin-1y}, piperazin-1-yl, pyrrolidin-1-yl, pyridin-1-yl or 3,6-dihydropyridin- 1-yL;
U’ is absent;
V’ is C3.13 aryl substituted with 0-5 Re;
Ry is H, C(O)O(CRy'R.’),-T or C(OXCRy'R:’)-T'
Ry’ and R;’ are both Hj
R) is hydrogen;
Ry, is hydrogen;
Ry is H;
Rs’ is H; jis 1 or2;and ris0,1or2.
In some embodiments, the compound has Formula II wherein:
A is CONHOH;
B is CHy;
Gis CH;
X is CHzNRw; :
Y is (CHa); '
Mis CO;
U is absent;
V is piperindin-1y}, piperazin-1-yl, pyrrolidin-1-yl, pyridin-1-yl or 3,6-dihydropyridin- 1-yl;
U’ is absent;
V’ is phenyl substituted with 0-3 Re;
Ry is H, C(O)O(CRy'R")+-T or C(OXCRy'Re')-T; :
Ry’ and R;’ are both H;
R| is hydrogen;
R; is hydrogen;
Ry’ is H;
Rs’ is H; jis 1lor2;and ris 0,1or2.
At various places in the present specification substituents of compounds of the invention are disclosed in groups or in ranges. It is specifically intended that the invention include each and every individual subcombination of the members of such groups and ranges.
For example, the term “Ci. alkyl” is specifically intended to individually disclose methyl, ethyl, C3 alkyl, C4 alkyl, Cs alkyl, and Cs alkyl.
For compounds of the invention in which a variable appears more than once, each variable can be a different moiety selected from the Markush group defining the variable. For example, where a structure is described having two R! groups that are simultaneously present on the same compound; the two R groups can represent different moieties selected from the
Markush group defined for R.
It is further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, can also be provided in combination ina single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination.
As used herein, the term “alkyl” is meant to refer to a saturated hydrocarbon group which is straight-chained or branched. Example alkyl groups include methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, t-butyl), pentyl (¢.g., n- pentyl, isopentyl, neopentyl), and the like. An alkyl group can contain from 1 to about 20, from 2 to about 20, from 1 to about 10, from 1 to about 8, from 1 to about 6, from 1 to about 4, or from 1 to about 3 carbon atoms. )
As used herein, “alkenyl” refers to an alkyl group having one or more double carbon- carbon bonds. Example alkenyl groups include ethenyl, propenyl, cyclohexenyl, and the like.
As used herein, “alkynyl” refers to an alkyl group having one or more triple carbon- carbon bonds. Example alkynyl groups include ethynyl, propynyl, and the like.
As used herein, “haloalkyl” refers to an alkyl group having one or more halogen substituents. Example haloalkyl groups include CF, CFs, CHF, CCl, CHCl, C2Cls, and the like. An alkyl group in which all of the hydrogen atoms are replaced with halogen atoms can be referred to as “perhaloalkyl.”
As used herein, “alkylene” or “alkylenyl” refers to a bivalent alkyl group. An example alkylene group is methylene or ethylene.
As used herein, “alkenylene” or “alkenylenyl” refers to a bivalent alkenyl group .
As used herein, “carbocyclyl” groups are saturated (i.e., containing no double or triple bonds) or unsaturated (i.e., containing one or more double or triple bonds) cyclic hydrocarbon moieties. Carbocyclyl groups can be mono- or polycyclic (e.g., having 2, 3 or 4 fused rings) or spirocyclic. Example carbocyclyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, 1,3-cyclopentadienyl, cyclohexenyl, norbornyl, norpinyl, norcarnyl, adamantyl, phenyl, and the like. Carbocyclyl groups can be aromatic (e-g., “aryl”) or non-aromatic (e.g., “cycloalkyl”). In some embodiments, carbocyclyl groups can have from about 3 to about 30 carbon atoms, about 3 to about 20, about 3 to about 10, or about 3 to about 7 carbon atoms.As used herein, “aryl” refers to an aromatic carbocyelyl group including monocyclic or polycyclic (e.g. having 2, 3 or 4 fused rings) aromatic hydrocarbons such as, for example, phenyl, naphthyl, anthracenyl, phenanthrenyl, indanyl, indenyl, and the like. In some embodiments, aryl groups have from 6 to about 20 carbon atoms.
As used herein, “cycloalkyl” refers to non-aromatic carbocyclyl groups including cyclized alkyl, alkenyl, and alkynyl groups. Cycloalkyl groups can include bi- or polycyclic (e.g., having 2, 3 or 4 fused rings) ring systems as well as spiro ring systems. Example cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, norbornyl, norpinyl, norcarnyl, adamantyl, and the like. Also included in the definition of cycloalkyl are moieties that have one or more aromatic rings fused (i.e. having a bond in common with) to the cycloalkyl ring, for example, benzo derivatives of pentane, pentene, hexane, and the like.
As used herein, “heterocyclyl” or “heterocycle” refers to a saturated or unsaturated carbocyclyl group wherein one or more of the ring-forming carbon atoms of the carbocyclyl group is replaced by a heteroatom such as O, S, or N. Heterocyclyl groups can be aromatic (e.g., “heteroaryl”) or non-aromatic (e.g., “heterocycloalkyl”). Heterocyclyl groups can also correspond to hydrogenated and partially hydrogenated heteroaryl groups. Heterocyclyl groups can be characterized as having 3-14 ring-forming atoms. In some embodiments, heterocyclyl groups can contain, in addition to at least one heteroatom, from about 1 to about 20, about 2 to about 10, or about 2 to about 7 carbon atoms and can be attached through a carbon atom or heteroatom. In further embodiments, the heteroatom can be oxidized (e.g., have an oxo or sulfindo substituent) or a nitrogen atom can be quaternized. Examples of heterocyclyl groups include morpholino, thiomorpholino, piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, 2,3-dihydrobenzofuryl, 1,3-benzodioxole, benzo-1,4-dioxane, piperidinyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidiny], and the like, as well as any of the groups listed below for “heteroaryl” and “heterocycloalkyl.” Further example heterocycles include pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, ~~ 3,6-dihydropyridyl, 1,2,3,6-tetrahydropyridyl, 1,2,5,6- tetrahydropyridyl, piperidonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl,
tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thia- diazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, xanthenyl, octahydro- isoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4- oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzo-thiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, deca-hydroquinolinyl, 2H,6H-1,5,2dithiazinyl, dihydrofuro{2,3- btetrahydrofuran, furanyl, furazanyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl and isoxazolyl. Further examples of heterocycles include azetidin-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, piperindin-1yl, piperazin-1-yl, pyrrolidin-1-yl, isoquinol-2-yl, pyridin-1-yl, 3,6-dihydropyridin-1-yl, 2,3-dihydroindol-1-yl, 1,3,4,9-tetrahydrocarbolin-2-yl, thieno[2,3-c]pyridin-6-yl, 3,4,10,10a-tetrahydro-1H- pyrazino[1,2-a}indol-2-yl, 1,2,4,4a,5,6-hexahydro-pyrazino[1,2-a]quinolin-3-yl, pyrazino{1,2- a]quinolin-3-yl, diazepan-1-yl, 1,4,5,6-tetrahydro-2H-benzo[f]isoquinolin-3-yl, 1,4,4a,5,6,10b- hexahydro-2H-benzo[f]isoquinolin-3-yl, 3,3a,8,8a-tetrahydro-1H-2-aza-cyclopenta[a]inden-2- yl, and 2,3,4,7-tetrahydro-1H-azepin-1-yl, azepan-1-yl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles.
As used herein, “heteroaryl” groups are aromatic heterocyclyl groups and include monocyclic and polycyclic (e.g., having 2, 3 or 4 fused rings) aromatic hydrocarbons that have at least one heteroatom ring member such as sulfur, oxygen, or nitrogen. Heteroaryl groups include, without limitation, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furyl, quinolyl, isoquinolyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrryl, oxazolyl, benzofuryl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 1,2,4- thiadiazolyl, isothiazolyl, benzothienyl, purinyl, carbazolyl, benzimidazolyl, indolinyl, and the like. In some embodiments, the heteroaryl group has from 1 to about 20 carbon atoms, and in further embodiments from about 3 to about 20 carbon atoms. In some embodiments, the heteroaryl group contains 3 to about 14, 3 to about 7, or § to 6 ring-forming atoms. In some embodiments, the heteroaryl group has 1 to about 4, 1 to about 3, or 1 to 2 heteroatoms.
As used herein, “heterocycloalkyl” refers to non-aromatic heterocyclyl groups including cyclized alkyl, alkenyl, and alkynyl groups where one or more of the ring-forming carbon atoms is replaced by a heteroatom such as an O, N, or S atom. Example heterocycloalkyl” groups include morpholino, thiomorpholino, piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, 2,3-dihydrobenzofuryl, 1,3-benzodioxole, benzo-1,4-dioxane, piperidinyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, and the like. Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings fused (i.e., having a bond in common with) to the nonaromatic heterocyclic ring, for example phthalimidyl, naphthalimidyl, and benzo derivatives of heterocycles such as indolene and isoindolene groups. In some embodiments, the heterocycloalkyl group has from 1 to about 20 carbon atoms, and in further embodiments from about 3 to about 20 carbon atoms. In some embodiments, the heterocycloalkyl group contains 3 to about 14, 3 to about 7, or 5 to 6 ring-forming atoms. In some embodiments, the heterocycloalkyl group has 1 to about 4, 1 to about 3, or 1 to 2 heteroatoms. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 triple bonds.
As used herein, “halo” or “halogen” includes fluoro, chloro, bromo, and iodo.
As used herein, “alkoxy” refers to an -O-alkyl group. Example alkoxy groups include methoxy, ethoxy, propoxy (e.g., D-propoxy and isopropoxy), t-butoxy, and the like.
As used herein, “aryloxy” refers to an -O-aryl group. An example aryloxy group is phenoxy.
As used here, “haloalkoxy” refers to an —O-haloalky] group. An example haloalkoxy group is OCF.
As used herein, “carbocyclylalkyl” refers to an alkyl moiety substituted by a carbocyclyl group. Example carbocyclylalkyl groups include “aralkyl” (alkyl substituted by aryl (“arylalkyl”) and “cycloalkylalkyl” (alkyl substituted by cycloalkyl). In some embodiments, carbocyclylalkyl groups have from 4 to 24 carbon atoms.
As used herein, “heterocyclylalkyl” refers to an alkyl moiety substituted by a heterocarbocyclyl group. Example heterocarbocyclylalkyl groups include “heteroarylalkyl” (alkyl substituted by heteroaryl) and “heterocycloalkylalkyl” (alkyl substituted by heterocycloalkyl). In some embodiments, heterocyclylalkyl groups have from 3 to 24 carbon atoms in addition to at least one ring-forming heteroatom.
As used herein, “amino” refers to an NH group. «Alkylamino” refers to an amino group substituted by an alkyl group and “dialkylamino” refers to an amino group substituted by two alkyl groups.
As used herein, “aminocarbonyl” refers to CONHa.
As used herein, “alkylaminocarbonyl” refers to CONH(alkyl).
As used herein, “alkylaminocarbonyl” refers to CON(alkyl.
As used herein, “carboxy” or “carboxyl” refers to COOH.
As used herein, “carboxy alkyl ester” refers to COO-alkyl.
As used herein, “carboxy aryl ester” refers to COO-aryl.
As used herein, “hydroxy” refers to OH.
As used herein, “mercapto” refers to SH.
As used herein, “sulfinyl” refers to SO.
As used herein, “sulfonyl” refers to SOx. )
As used herein, “aminosulfony!” refers to SO;NHa.
As used herein, “alkylaminosulfonyl” refers to SO,NH(alkyl).
As used herein, “dialkylaminosulfony!” refers to SO:N(alkyl),.
As used herein, “arylsulfonyl” refers to SOz-aryl.
As used herein, “arylsulfiny]” refers to SO-aryl. :
As used herein, “alkylsulfonyl” refers to SO,-alkyl.
As used herein, “alkylsulfinyl” refers to SO-alkyl.
As used herein, “combinations thereof” is meant to refer to concatenation of two or more moieties recited for a given variable. For example, “CHz, NH, CO, and combinations thereof” would include CH,;NH, CH;CO, CONH, CH,NHCO, and other stable combinations.
Unless otherwise indicated, the compounds provided in the above formula are meant to include pharmaceutically acceptable salts, prodrugs, enantiomers, diastereomers, racemic mixtures, crystalline forms, non-crystalline forms, amorphous forms, hydrates and solvates thereof.
The term “pharmaceutically acceptable salt” is meant to refer to salts of the active compounds which are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the present invention contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suiteble inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. When compounds of the present invention contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either peat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, phosphoric, partially neutralized phosphoric acids, sulfuric, partially neutralized sulfuric, hydroiodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like. Certain specific compounds of the present invention may contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts.
The neutral forms of the compounds of the present invention may be regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents, but otherwise the salts are equivalent to the parent form of the compound for the purposes of the present invention.
As noted above, some of the compounds of the present invention possess chiral or asymmetric carbon atoms (optical centers) or double bonds; the racemates, diastereomers, geometric isomers and individual optical isomers are all intended to be encompassed within the scope of the present invention.
Compounds of the invention can also include all isotopes of atoms occurring in the intermediates or final compounds. Isotopes include those atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium.
Compounds of the invention can also include tautomeric forms, such as keto-enol tautomers. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution.
Some of the compounds of the invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are intended to be encompassed within the scope of the present invention. Certain compounds of the present invention may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present invention and are intended to be within the scope of the present invention. :
In addition to salt forms, the present invention provides compounds may be in a prodrug form. Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention. Additionally, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex-vivo environment. For example, prodrugs can be slowly converted to the compounds of the present invention when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent.
In some embodiments, the present invention provides a compound selected from:
N-hydroxy-5-methyl-6-{ [4-(3-methylphenyl)piperezin-1-yl]carbonyl} -5- azaspiro[2.5]octane-7-carboxamide; :
N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-5-methyl-6-({4-[3(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6- {[4-(2-methylphenyl)piperazin-1-yl]carbony1}-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-chlorophenyl)piperazin-1-yl]carbonyl} -N-hydroxy-5-methyl-5- azaspiro[2.5)octane-7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(2-methyl-4-nitrophenyl)piperazin-1-yljcarbonyl} -5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-phenylpiperidin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-6-[(4-hydroxy-4-phenylpiperidin-1-yl)carbony!]-5-methyl-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-quinolin-2-ylpiperazin-1-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2,3-dichlorophenyl)piperazin-1-yljcarbonyl}-N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-quinolin-4-ylpiperazin-1-ylcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-{ [4-(2-methylquinolin-4-yl)piperazin-1 -yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(2-phenylethyl)piperazin-1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-pyridin-4-ylpiperidin- 1-yl)carbonyl]-5-azaspiro[2.5]octane- 7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(4-nitrophenyl)piperazin-1 -yi]carbonyl}-3- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{ [4-(2-methoxyphenyl)piperazin-1 -yl]carbonyl}-5-methyl-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-phenoxypiperidin-1-yl)carbonyl] -5-azaspiro[2.5]octane-7- carboxamide; 6-3 4-dihydroisoquinolin-2(1H)-ylcarbonyl)-N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; 6-(4,7-dihydrothieno [2,3-c]pyridin-6(5H)-ylcarbonyl)-N-hydroxy-5-methyl-3- azaspiro[2.5]octane-7-carboxamide; 6-[(3-benzylpyrrolidin-1-yl)carbonyl]-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-5-methyl-6-[(4-pyridin-2-ylpiperazin-1-yl)carbonyl]-5-azaspiro[2. 5]octane- 7-carboxamide;
N-hydroxy-5-methyl-6- { [4-(2-pyridin-4-ylethyl)piperidin-1-yl] carbonyl}-5- azaspiro[2.5)octane-7-carboxamide;
N-hydroxy-5-methyl-6-({4-[5~(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)- 5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-({4-[3-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} carbonyl)- 5-azaspiro[2.5]octane-7-carboxamide; 6-(1,4"-bipiperidin-1'-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-5-methyl-6-{[4-(pyridin-2-ylmethyl)piperazin-1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; .
N-hydroxy-5-methyl-6-{[4-(pyridin-4-ylmethyl)piperazin-1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-{ [4-(pyridin-3-ylmethyl)piperazin-1 -yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-{ [4-(2-methylphenyl)-3 ,6-dihydropyridin-1(2H)-y1] carbonyl}- 5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(3 -methylphenyl)piperazin-1-yljcarbonyl} -5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-5-methyl-6-(1,3 4.9-tetrahydro-2H-B-carbolin-2-ylcarbonyl)-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-S5-methyl-6-[(9-methyl- 1 3,4,9-tetrahydro-2H-B-carbolin-2-yl)carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; : 6-{[4-(2-fluorophenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2-chlorophenyl)-3,6-dihydropyridin-1(2H)-ylJcarbonyl}-N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4~(4-nitropheny!)-3,6-dihydropyridin-1 (2H)-yl]carbonyl }-N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-phenyl-3,6-dihydropyridin-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2-methyl-4-nitrophenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-5- methyl-5-azaspiro[2.5]octane-7-carboxamide; : N(7)-hydroxy-N(6),5-dimethyl-N(6)-(3-phenylpropyl)-5-azaspiro[2.5]octane-6,7- dicarboxamide;
N(7)-hydroxy-N(6)-isobutyl-5-methyl-5-azaspiro [2.5]octane-6,7-dicarboxamide;
N-hydroxy-5-methyl-6-{[4-(2-nitrophenyl)piperazin-1-yl]carbonyl}-3- azaspiro[2.5]octane-7-carboxamide;
N(7)-hydroxy-N(6)-isobutyl-N(6),5-dimethyl-5-azaspiro[2.5]octane-6,7- dicarboxamide;
N(7)-hydroxy-5-methyl-N(6)-(2-phenoxyethyl)-5-azaspiro[2.5Joctane-6,7- dicarboxamide;
N(7)-hydroxy-N(6)-[2-(4-methoxyphenyl)ethyl]-5-methyl-S-azaspiro[2.5]octane-6,7- dicarboxamide;
N(7)-hydroxy-5-methyl-N(6)-(4-phenylbutyl)-5-azaspiro[2.5}octane-6,7- dicarboxamide;
N(7)-hydroxy-5-methyl-N(6)-[3-(2-oxopyrrolidin-1-yl)propyl]-5-azaspiro[2.5]octane- 6,7-dicarboxamide;
N-hydroxy-5-methyl-6-[(10a)-3,4,10,10a-tetrahydropyrazino(1,2-alindol-2(1H)- ylcarbonyl]-5-azaspiro[2.5]octane-7-carboxamide; (5,6-trans)-N-hydroxy-5-{ [4-(2-methyl-4-nitrophenyl)piperazin-1- yl]carbonyl}spiro[2.5]octane-6-carboxamide; : (5,6-trans)-N-hydroxy-6-{[4-(3 -methylphenyl)piperazin-1- yl]carbonyl}spiro [2.5]octane-5-carboxamide; ! ¢ ,6-trans)-N-hydroxy-5-[(4-phenyl-3,6-dihydropyridin-1 (2H)- yl)carbonyl]spiro [2.5]octane-6-carboxamide; (5,6-trans)-N-hydroxy-5-{[4-(3-methylphenyl)piperazin-1- yl]carbonyl}spiro[2.5)octane-6-carboxamide; (5.6-trans)-N-hydroxy-6-[(4-phenyl-3,6-dihydropyridin-1(2H)- ylcarbonyl]spiro[2.5]octane-5-carboxamide;
N-hydroxy-6-(3,4,10,10a-tetrahydropyrazino[ 1,2-a]indol-2(1 H)-ylcarbonyl)-5- azaspiro[2.5]octane-7-carboxamide; 6-(1,2,4,4a,5,6-hexahydro-3H-pyrazino[ 1,2-a]quinolin-3 -ylcarbonyl)-N-hydroxy-3- methyl-5-azaspiro[2.5]octane-7-carboxamide;
Methyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridin-1(ZH)- yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate;
Benzyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridin-1(2H)- yl)carbony}}-5-azaspiro[2.5]octane-5-carboxylate;
N-Hydroxy-5-(methylsulfonyl)-6-{(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[3-(3-methoxyphenyl)piperidin-1-yl]carbonyl}-5-methyl-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-{[3-(2-phenylethyl)pyrrolidin-1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(3-methoxyphenyl)piperidin-1-yl]carbonyl}-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-[3-(aminocarbonyl)phenyl]-3,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy- 5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(2-methoxyphenylpiperidin-1-yl] carbonyl}-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(3-fluoro-2-methylphenylpiperazin-1-y1] carbonyl}-N-hydroxy-5- azaspiro[2.S]octane-7-carboxamide;
N-hydroxy-6-{[4-(2-methyl-3 -nitrophenyl)piperazin-1-yl] carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; 6.3.6 inycro-3,4"bipyrdin-QED-ylcarbonyD)-N-hydroxy--azaspiro(2.Soctane-T carboxamide;
N(7)-hydroxy-N(6)-(4-methoxyphenyl)-N(6)-methyl-5-azaspiro [2.5]octane-6,7- dicarboxamide;
N-hydroxy-6-{[4-(3-methoxyphenyl)piperazin-1-yljcarbonyl} -5-methyl-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(3 —chlorophenyl)piperazin-1 -yl]carbonyl} N-hydroxy-5-methyl-5- azaspiro[2.5}octane-7-carboxamide;
N-hydroxy-6-{(4-phenyl-1 ,A-diazepan-1 -yl)carbonyl]-5-azaspiro [2.5]octane-7- carboxamide;
N-hydroxy-6-{[3-methyl-4-(3 -methylphenyl)piperazin-1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
Nehydroxy-6-{[4-(3-methoxyphenyl)piperidin-1-yllcarbonyl}-S-azaspiro[2.Sjoctanc-7- carboxamide;
N-hydroxy-6-{(3-phenylpyrrolidin-1-yl)carbonyl] spiro[2.5]octane-5-carboxamide;
N-hydroxy-6-[(4-isobutyrylpiperazin-1 -yl)carbonyl] -5-azaspiro[2.5]octane-7- carboxamide; / 6-{ [4-(4-cyano-2-methylphenyl)-3 ,6-dihydropyridin-1 (2H)-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide;
N(7)-Hydroxy-5-methyl-N(6)- {4-[(2-methylquinolin-4-ylymethoxy]phenyl} -5- azaspiro[2.5]octane-6,7-dicarboxamide;
N(7)-Hydroxy-N(6)- {4-[(2-methylquinolin-4-ylymethoxy]phenyl}-5- azaspiro[2.5]octane-6,7-dicarboxamide; 6-{[4-(4-cyanophenyl)piperazin-1-yljcarbonyl}-N-hydroxy-5-azaspiro(2.5]octane-7- carboxamide;
N-hydroxy-7-[(4-phenylpiperidin-1-yl)carbonyl]-S-azaspiro[2.5]octane-6-carboxamide;
N-hydroxy-6-[(4-phenylpiperidin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
N-Hydroxy-6-{(4-phenylpiperazin-1-yljcarbonyl}-5-azaspiro[2.5}octane-7- carboxamide; ’
N-hydroxy-6-({4-[3-(methoxymethyl)phenyl]piperidin-1-y1} carbonyl)-5- azaspiro[2.5]octane-7-carboxamide;
Methyl 3-[14{7-[(hydroxyamino)carbonyl]-5-azaspiro[2.5oct-6- yl}carbonyl)piperidin-4-yl]benzoate; 6-[(3-Cyclohexylpyrrolidin-1 -yl)carbonyl]-N-hydroxy-5 -azaspiro[2.5]octane-7- carboxamide;
N-Hydroxy-6-{[4-(3 -isopropylphenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4~(3-isopropylphenyl)piperidin-1-ylJcarbonyl}-5 -azaspiro[2.5]octane- 7-carboxamide;
N-hydroxy-6-{[4-(4-propylphenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(4-cthylphenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; )
N-Hydroxy-6-{[4-(4-ethylphenyl)piperidin-1-yl]carbonyl} -S-azaspiro[2.5]octane-7- carboxamide; 6-{[4-(4-cyano-2-methylphenyl)piperazin-1-yl] carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide;
N-Hydroxy-6-{[4-(3-isopropoxyphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-Hydroxy-6-{[4-(3-methylphenyl)-3,6-dihydropyridin-1(2H)-yl] carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-Hydroxy-6-{[4-(3-methylphenyl)piperidin-1-ylJcarbonyl}-5-azaspiro[2.5]octane-7- carboxamide; 6-{[4-(4-tert-butylphenyl)piperazin- 1-yl]carbonyl} -N-hydroxy-5-azaspiro[2.5]octane- 7-carboxamide;
N-Hydroxy-6-[(4-pyridin-4-ylpiperazin-1-y[)carbonyl]-5-azaspiro[2.5]octane-7- carboxamide; 6-[(3-Benzylpiperidin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-6-[(5-methoxy-2,3-dihydro-1H-indol-1-yl)carbonyl}-5-azaspiro[2.5]octane- 7-carboxamide;
N-hydroxy-6-({ 5-[(2-methylquinolin-4-yl)methoxy] -2,3-dihydro-1H-indol-1- yl}carbonyl)-5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-({5- [(2-methylquinolin-4-yl)methoxy] -2,3-dihydro-1H-indol-1- yl}carbonyl)-5-azaspiro[2.5]octane-7 carboxamide; 6-{[5-(benzyloxy)-2,3~dihydro-1H-indol-1-yl]carbonyl}-N-hydroxy-3- azaspiro[2.5]octane-7-carboxamide; 6-(1,3-dihydro-1 'H-spiro[indene-2,4'-piperidin]-1 -ylcarbonyl)-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(3 -isopropoxyphenyl)piperidin-1 -yl]carbonyl} -5-azaspiro[2.5]octane- 7-carboxamide;
Methyl 4-[1{7-[(Rydroxyamino)carbonyl]-5-azaspiro[2.5}oct-6-yl} carbonyl)-1.2,3,6- tetrahydropyridin-4-yl]-3-methylbenzoate;
N-hydroxy-6-{[4-(2-methyl-4-nitrophenyl)-3,6-dihydropyridin-1(2H)-yljcarbonyl} -5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2-ctbylphenyl)piperidin-1-yljcarbonyl}-N-hydroxy-S-azaspiro[2.5]octane-7- carboxamide;
Methyl 4-[1<({7-[(hydroxyamino)carbonyl]-5-azaspiro[2.5]oct-6- yl} carbonyl)piperidin-4-yl]-3-methylbenzoate; 6-{[4-(2,3-dihydro-1-benzofuran-5-yl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}-N- hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{ [4-(3-isopropylpheny!)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-5- methyl-5-azaspiro[2.5]octane-7-carboxamide;
N-Hydroxy-6-{[(3R)-3-phenylpyrrolidin-1-yl] carbonyl }-5-azaspiro[2.5]octane-7- carboxamide;
N-Hydroxy-6-{[(3S)-3-phenylpyrrolidin-1 -yljcarbonyl}-5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-6-({3- [3~(trifluoromethyl)phenyl]pyrrolidin-1 -yl}carbonyl)-5- azaspiro[2.5]octane-7-carboxamide; : 6-{[3-(3-chlorophenyl)pyrrolidin-1-ylJcarbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide; 6-{[3-(3-fluorophenyl)pyrrolidin-1 -yl]carbonyl}-N-hydroxy-5-azaspiro{2.5] octane-7- carboxamide; 6-{[3-(4-fluorophenyl)pyrrolidin-1-yl]carbonyl} -N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide;
3s \ 6-{[3-(4-chlorophenyl)pyrrolidin-1-yllcarbonyl}-N-hydroxy-5-azaspiro[2. Sjoctane-7 - carboxamide;
N-hydroxy-6-({3-[4-(trifluoromethyl)phenyl]pyrrolidin-1-yl} carbonyl)-5- azaspiro[2.5]octane-7-carboxamide; 6-{[3-(4-methoxyphenyl)pyrrolidin-1-yl carbonyl }-N-hydroxy-5-azaspiro[2.S]octane- 7-carboxamide; 6-{[3-(4-phenoxyphenyl)pyrrolidin-1-yljcarbonyl} -N-hydroxy-5-azaspiro[2. S]octane- 7-carboxamide;
N-hydroxy-6-{[4-(3-methoxyphenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbony!}-3- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(4-cyano-3-methylphenyl)-3,6-dihydropyridin-1(2H)-yl carbonyl} -5- azaspiro[2.5]octane-7-carboxamide; 6-{[3-(3-methoxyphenyl)pyrrolidin-1-yl] carbonyl }-N-hydroxy-5-azaspiro[2.5]octane- ~ 7-carboxamide;
N-hydroxy-6-[(3-pyridin-4-ylpyrrolidin-1-y)carbonyl]-5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-6-{[4~(3,5-dimethylpheny})-3,6-dihydropyridin-1(2H)-yl]carbonyl} -5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(3-trifluoromethoxyphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl}- 5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[S-(methoxymethyl)-4-pheny}-3,6-dihydropyridin-1(2H)-y]] carbonyl }- 5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-(1,4,5,6-tetrahydrobenzo[flisoquinolin-3(2H)-ylcarbonyl)-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(5-methoxy-2-methylphenyl)-3,6-dihydropyridin-1(2H)- yl}carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(4-methoxy-2-methylphenyl)-3,6-dihydropyridin-1(2H)- yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide; 6-[(4-cyano-4-phenylpiperidin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2.5] octane-7- carboxamide;
Ethyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3 ,6-dihydropyridin-1(2H)- yl)carbonyl}-5-azaspiro[2.5]octane-5-carboxylate;
Propyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridin-1(2H)- yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate;
Isopropy! 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3 _6-dihydropyridin-1(2H)- yl)carbonyl)-5-azaspirof2.5]octane-5-carboxylate;
Isobutyl 7-{(hydroxyamino)carbonyl]-6-[(4-pheny1-3,6-dibydropyridia-1(2ED)- yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; and
N-hydroxy-6-[(5 -methyl-4-phenyl-3 6-dihydropyridin-1(2H)-y!)carbonyl]-5- azaspiro[2.5]octane-7 carboxamide.
Compounds of the invention further include: 6.(1.4,48,5,6,10b-hexehydrobenzo[flisoquinolin-3(2H)-ylcarbonyl)-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-fluorophenyl)-3 -hydroxypiperidin-1-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-(3 ,3a,8,8a-tetrahydroindeno[1 2-c]pyrrol-2(1H)-ylcarbonyl)-3- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(4-phenyl-1,3 -thiazol-2-yl)piperidin-1-yi]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(4-tert-Buty}-1,3-thiazol-2-yDpiperidin- 1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-[(4-methyl-4-phenylpiperidin-1 -yD)carbonyl}-5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-6-{[4-(4-ethyl-1 3-thiazol-2-yl)piperidin-1-ylJcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[(trans)-3-methyl-4-phenylpyrrolidin-1-yljcarbonyl} -5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2-fluorophenyl)piperazin-1-yljcarbonyl} -N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide; 6-{[4-(3,5-dimethylphenyl)-3 ,6~dihydropyridin-1(2H)-yl] carbonyl}-N-hydroxy-5- methyl-5-azaspiro[2.5]octane-7-carboxamide;
Tetrahydro-2H-pyran-4-yl-7-((hydroxyamino)carbonyl)6-((4-phenylpiperazin-1- yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate;
Ethyl 7-((hydroxyamino)carbonyl) )-6-((4-phenylpiperazin-1-yl)carbonyl-5- azaspiro(2,5)octane-5-carboxylate;
Methyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5- azaspiro[2.5]octane-5-carboxylate;
N-hydroxy-6-{(4-pyrazin-2-ylpiperazin-1-yDcarbony]-5-szaspiro[2.Sloctane-7- carboxamide;
N-hydrory-6-{(4-quinolin-2-yipiperazin- 1-yDearbony]-5-ezaspiro[2. Sloctasne-7 - carboxamide;
N-hydroxy-6-{[3-(5,6,7 $-tetrahydronaphthalen-2-ylpyrrolidin-1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6- {{3R)-3 -phenylpyrrolidin-1 -yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
Methyl J-[(bydroxyamino)carbonyl]-6- {[(3R)-3-phenylpyrrolidin-1-yllearbonyl} -5- azaspiro[2.5]octane-5-carboxylate;
N-hydroxy-6-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-5-azaspirof2. Sloctane-7 - carboxamide;
Nehydroxy-6-(3-pyridin-2-ylpyrrolidin-1-yl)carbonyi]-5-azaspiro[2.S]octane-- carboxamide;
N-hydroxy-6-[(3-methyl-3-phenylpyrrolidin-1-yl)carbonyl]-5-azaspiro[2.S]octanc-7- carboxamide;
N-hydroxy-6-(3-phenylazetidin-1-yl)carbonyl]-S-azaspiro[2. S]octane-7-carboxamide;
N-hydroxy-5-methyl-6- [(3-methyl-3 -phenylpyrrolidin-1 -yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-5-methyl-6-[(3-phenylazetidin-1 _yl)carbonyl]-5-azaspiro[2.5]octane-7 - carboxamide; 6-(1,3 32,4,5,9b-hexahydro-2H-benzo[e]isoindol-2-ylcarbonyl)-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[3-(2-naphthylpyrrolidin-1-yl]carbonyl}-5-azaspiro[2. Sjoctane-7- carboxamide;
N-hydroxy-6-{[4-(2-thienyl)-3,6-dihydropyridin-1(2H)-ylJcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[3-(3-thienyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[ 2. SJoctane-7- carboxamide;
N-hydroxy-6-{[3-(2-thienyl)pyrrolidin-1-y1] carbonyl} -5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-6-{[4-(2-thienyl)piperidin-1-yl] carbonyl}-5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-6-{[3-(2-methylphenyl)pyrrolidin-1-yl]carbonyl} -5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-6-{[3-(4-methylphenylpyrrolidin-1-yl}carbonyl} -5-azaspiro[2.5}octane-7- carboxamide; 5-acetyl-N-hydroxy-6- [(4-phenyl-3 ,6-dihydropyridin-1 (2H)-yl)carbonyl}-5- azaspiro[2.5)octane-7-carboxamide;
Nehydroxy-6-{[4-(-thieny))-3,6-dihydropyridin-1(2H)-yllearbonyl}-5- azaspiro [2.5]octane-7-carboxamide;
N-hydroxy-6-[(3-phenylpiperidin-1 -yl)carbonyl]-5-azaspiro[2 .5]octane-7-carboxamide;
N-hydroxy-6-{[4-(3-thienyl)piperidin-1-yl]carbonyl} -5-azaspiro[2.5]octane-7- carboxamide;
Methyl 6-{[4-(3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-ylJcarbonyl}-7- [(hydroxyamino)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; 6-{[4-(3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl}-N-hydroxy-3- (methylsulfonyl)-5-azaspiro[2.5]octane-7-carboxamide; 6-{[4-(3,5-difluorophenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4~(3,5-dichlorophenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-[3,5-bis(trifluoromethyl)phenyl]-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}-N- hydroxy-5-azaspiro[2.5]octane-7 -carboxamide;
N-hydroxy-5 -(methylsulfonyl)-6-[(4-phenylpiperazin-1 -yl)carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; 5-formyl-N-hydroxy-6-[(4-phenylpiperazin-1 -yl)carbonyl]-5-azaspiro[2.5}octane-7- carboxamide; 6-{[4-(3,5-difluorophenyl)piperidin-1-yljcarbonyl} “N-hydroxy-5-azaspiro[2.5]octane- 7-carboxamide; 6-{[4-(2,5-dimethylphenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2,4,5-trimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-[(4-biphenyl-3-ylpiperidin-1-yl)carbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide;
6-[(4~dibenzo[b,d]furan-4-ylpiperidin-1-yl)carbonyl]-N-hydroxy-3- azaspiro[2.5)octane-7-carboxamide; 6-{[4-(2,5-dimethylphenyl)piperidin-1-yl]carbonyl} -N-hydroxy-5-azaspiro[2.5]octane- 7-carboxamide; 6-{ [4-(2,4,5-trimethylphenyl)piperidin-1-yl]carbonyl} -N-hydroxy-3- azaspiro[2.5]octane-7-carboxamide;
Methyl 3-[1-({7-[(hydroxyamino)carbonyl] -5-azaspiro[2.5)oct-6-y1} carbonyl)-1 ,2,3,6- tetrahydropyridin-4-yl]-4-methylbenzoate; 6-[(5 -phenyl-2,3,4,7-tetrahydro-1H-azepin-1 -yl)carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-[3-(dimethylamino)phenyl}-3 ,6-dihydropyridin-1 (2H)-yl}carbonyl}-N-hydroxy- 5-azaspiro[2.5]octane-7-carboxamide;
Methyl 3-[1 -({7-{(bydroxyamino)carbonyl]-5-azaspiro[2.5]oct-6- yl}carbonyl)piperidin-4-yl]-4-methylbenzoate; 6-[(5-phenylazepan-1-yl)carbonyl] -N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide; 6-({4- [3-(dimethylamino)phenyl]piperidin-1-yl} carbonyl)-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2-methylphenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; \ 6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl] -N-hydroxy-5-azaspiro[2.5]octane- 7-carboxamide; 6-{[4-(4-cyano-2-methylphenyl)piperidin-1-yl] carbonyl }-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide;; 6-[(3,3-dimethyl-4-phenyl-3,6-dihydropyridin-1 (2H)-yl)carbonyl]-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-[(3,3-dimethyl-4-phenylpiperidin-1-yl)carbonyl] -N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide;
N-hydroxy-5-(methylsulfonyl)-6-[(3-phenyl-2,5 -dihydro-1H-pyrrol-1-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide;
Methyl 7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1- yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate;
N-hydroxy-5-methyl-6-[(3-phenyl-2,5-dihydro- 1H-pyrrol-1-yl)carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3 -methylphenyl)piperidin-1-yl] carbonyl}-N-hydroxy-5- azaspiro[2.5)octane-7-carboxamide; 6.([4-[3-(benzyloxy)phenyl]-3,6-dibydropyridin-1(2H)-yl]carbonyl}-N-hydroxy->- azaspiro[2.5]octane-7-carboxamide; 6-{[4-[3-ethylphenyl]-3 6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-3- azaspiro[2.5]octane-7-carboxamide; 6-{[4-[3-(ethyloxy)phenyl]-3 ,6-dihydropyridin-1(2H)-yljcarbonyl} -N-hydroxy-35- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(3-cthylphenyl)piperidin-1 -yl]carbonyl} -N-hydroxy-5-azaspiro [2.5]octane-7- carboxamide; 6. {[4-(3-cthoxyphenyDpiperidin-1-yljcarbonyl}-N-hydroxy-5-azaspiro[2. Sjoctane-7- carboxamide; 6-{[4-(3-cyclopropylpheny1)-3,6-dihydropyridin-1(2H)-ylJcarbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-methoxy-3,5-dimethylphenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}-N- hydroxy-5-azaspiro[2.5]octane-7-carboxamide; 6-{[4-(3,5 -dimethyl-4-methoxyphenyl)piperidin-1-yl] carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3-ethylphenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3-ethylphenyl)piperidin-1 -yljcarbonyl}-N-hydroxy-5- azaspiro[2.5)octane-7-carboxamide; 6-{[4-(4-cyano-3 ,5-dimethylphenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N- hydroxy-5-azaspiro [2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3,5-dimethylphenyl)piperidin-1-yl]carbonyl} <N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(1,3-benzothiazol-6-yl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(1 methyl 1H-benzimidazol-6-yl)-3,6-dihydropyridin-1(2H)- yl]carbonyl}-5-azaspiro[2.5}octane-7-carboxamide;
N-hydroxy-6-{[4-(1 -methyl-1H-benzimidazol-6-yl)piperidin-1-yljcarbonyl}-5- azaspiro[2.5)octane-7-carboxamide; 6-{[4-(4-cyano-3-isopropylphenyl)-3,6-dihydropyridin-1(2HD)-yl carbonyl} -N-hydroxy- 5-azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3-isopropylphenyl)piperidin-1-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3-cthylphenyl)-3,6-dihydropyridin-1(2H)-yl]earbonyl} -N-hydroxy-3- methyl-5-azaspiro[2.5}octane-7 -carboxamide; 6-{[4~(4-cyano-3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl}-N- hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(1-ethy}-1H-benzimidazol-6-y)-3,6-dihydropyridin-1(2H)- yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(1-methyl-1H-indazol-5-y1)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}- 5-azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(1 -ethyl-1H-benzimidazol-6-yl)piperidin-1-yljcarbonyl}-3- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(1-methyl-1H-indazo}-5-yl)piperidin-1-yl] carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
N-hydroxy-6-{[4-(1-ethyl-1E-indazol-5-yl)-3,6-dihydropyridin-1(2ED-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;
Tetrahydro-2H-pyran-4-yl 6-{[4-(1 -ethyl-1H-benzimidazol-6-yl)piperidin-1- yl] carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2.5)octane-5-carboxylate;
Methyl 6-{[4-(1-ethyl-1H-benzimidazol-6-yl)-3,6-dihydropyridin-1(2H)-yl]carbonyl} - 7-[(hydroxyamino)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; 6-{[4-(1-ethyl-1H-benzimidazol-6-y1)-3,6-dihydropyridin-1(2H)-yl] carbonyl} -N- hydroxy-5-(methylsulfonyl)-S-azaspiro[2.5]octane-7-carboxamide;
Methyl 6-{[4-(1-ethyl-1H-benzimidazol-6-yl)piperidin-1-yl]carbonyl}-7- [(hydroxyamino)carbonyl]-5-azaspirof2.5]octane-5-carboxylate;
Claims (1)
- What is claimed is:1. A compound of Formula I or II: vy MN > Te X R, D I Rs _B Y % p> Rs” © BE Ra jit enantiomer, diastereomer, prodrug, solvate, metabolite, or pharmaceutically acceptable salt thereof, wherein: A is CWOH, CWNHOH, CWNHOR;, N(OH)CHO, N(OH)CWR¢, SH, SR; or hydantoinyl; B is (CHy)n (CH:.C=W, (CRRNRs, NRg(CRRon, (CRR)-O(CR4R9)r, (CRR).S(CRaR9),, O(C=W)NRs, O, N, NRs, S(O)m, S, C(O)NRg(CR4R9)n, C(O)(CRaR¢)m, OF combinations thereof; G is (CH) (CH.C=W, (CRR9uNRs, NRe(CRaROn (CR4R):O(CRaR 1), (CRR).S(CRaR7),, O(C=W)NRs, O, N, NRs, S(O) S, C(O)NRs(CRaR)n, C(O)(CRaR), OF combinations thereof; D is oxygen or sulfur; X is absent, (CH,), Ci.1o alkylene substituted with 0 to 3 Rs, Caio alkenylene substituted with 0 to 2 Ra, N, O, NRy, S(O)m, C=0, NRyC(O), NR,C(0)0O, NRyC(O)NRb, C(0)0, OC(0), S(O)mNRs, NRpS(O)m, NRpS(O)mNRw, (CR4Rg)NRy, NRy(CR4Ry);, or combinations thereof, Y is absent, (CHa), Ci.10 alkylene substituted with 0 to 3 Rg, Caio alkenylene substituted with 0 to 2 Rs, N, O, NRp, S(O), C=0, NR+C(0), NRC(0)O, NR,C(O)NRy, C(0)0, OC(0), S(O)mNRs, NRoS(O)m, NRsS(0)mNRs, (CRRNRp, NRy(CR4Rg), or combinations thereof;M is CO or S(O); U is absent, Ci.10 alkylene substituted with 0 to 5 R,, Ca.10 alkenylene substituted with 0 to 2 Rs, N, O, NRp, NRyC(0), NRsC(0)O, NRyC(O)NRp, NRsS(O)m, NRy,S(O)NRy or combinations thereof; V is absent, H, Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 Re; U’ is absent, C.10 alkylene substituted with 0 to 5 Ry, C-10 alkenylene substituted with 0 to 2 Rs, N, O, NRsS(O)m, C=0, NRyC(O), NR,C(0)0, NRyC(O)NRs, C(0)O, 0C(0), S(O)mNRsp, NRpS(O)m, NRpS(O)NR; or combinations thereof; Vv’ is H, Ci. alkyl, NRgRe, C313 carbocyclyl substituted with 0-5 R, or heterocyclyl substituted with 0-5 Re;R. and R. are each, independently, H, T, C,.salkylene-T, C,.salkenylene-T, Cs. salkynylene-T, C(O)NR,’(CRy’R)-T, C(0)O(CRy’Re),-T, S(O)p(CRu'R:")-T, (CRy'R.")-O- (CRyR:)-T, OH, Cl, F, Br, I, CN, NO;, NRR", COR", COORY, ORY, CONRR, NRICONR'RY, OCONR'RY, NRICOR", SO,NR'R", NR'SO,R", NR'SO;NR'R", OSO,NRR, SO,RY, Ci. haloalkyl, Cs.13 carbocyclyl, heterocyclyl, carbocyclylalkyl, or heterocyclylalkyl, wherein each of said carbocyclyl, heterocyclyl, carbocyclylalkyl, and heterocylcylalkyl groups is optionally substituted by one or more Cs alkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, carboxy alkyl ester, carboxy aryl ester, +- aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylsulfonyl, arylsulfinyl, alkylsulfonyl or arylsufonyl; R, and R. are each, independently, H, T, Cialkylene-T, Cssalkenylene-T, Crealkynylene-T, C(O)NR.(CRCRy)-T, C(O)O(CRy'Re)-T, C(O) (CRy’R")-T, S(0)p(CRy’R)-T, (CR’Ry’)-O~(CRRp")~T, C(NR,’R.")(=N-CN) or C(NR,’R,’)(=CHNO); Ry and Ry are each, independently, H, Ci alkyl, C6 alkenyl, C4 alkynyl, T, Ci. calkylene-T, C;.galkenylene-T, C;salkynylene-T, C(O)NR,’(CR.’Ry)-T, C(0)O(CRs’R:")r-T, S(O),(CRy’R.’),-T or (CRe'Ry)-0-(CR:'Ry")~T, OH, Cl, F, Br, I, CN, NO, NR'RY, COR", COORY, ORY, CONR'R", RINCONR'RY, OCONR'R, RINCOR", SO,NR'R", NR'SOR", NRISO,NRRY, OSO,NRR'", SO,RY, Cis haloalkyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, heterocyclylalkyl, carbocyclyloxy or heterocarbocyclyloxy, wherein each of said carbocyclyl, heterocyclyl, carbocyclylalkyl, heterocyclylalkyl, carbocyclyloxy or heterocarbocyclyloxy groups is optionally substituted by one or more C13 alkyl, alkoxy, halo,haloalkyl, haloalkoxy, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, carboxy alkyl ester, carboxy aryl ester, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylsulfonyl, arylsulfinyl, alkylsulfonyl or arylsufonyl; T is H, Ci.10 alkyl substituted with 0 to 5 Ry’; Cz-10 alkenyl substituted with 0 to 5 Ry’,C,.10 alkynyl substituted with 0 to 5 Ry’, Css carbocyclyl substituted with 0-3 Ry’, heterocyclyl substituted with 0-5 Rv’R., Ry’ and R;’ are each, independently, H, C16 alkyl, Cp.6 alkenyl, Ca.6 alkynyl, OH, CL F, Br, I, CN, NO, NR'RY, COR", COOR", ORY, CONR'RY, R'INCONR'RY, OCONR'R', RINCORY, SO;NRR", NR'SOR", NR'SO;NRR', OSO,NRRY, SO,RY, Cis haloalkyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, heterocyclylalkyl, carbocyclyloxy or heterocarbocyclyloxy, wherein each of said carbocyclyl, heterocyclyl, carbocyclylalkyl, heterocyclylalkyl, carbocyclyloxy or heterocarbocyclyloxy groups is optionally substituted by one or more Cg alkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, carboxy alkyl ester, carboxy aryl ester, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylsulfonyl, arylsulfinyl, alkylsulfonyl or arylsufonyl; R, is hydrogen, Ci. alkyl, SRio, ORyp OF NRiuiR12; R; is hydrogen, Ci. alkyl, SRig, ORyp or NRii1R12; Rj; is: 6) C,.10 alkyl, C1. alkenyl or C,.g alkynyl; (ii) Cs. carbocyclyl optionally substituted with one or more substituents selected from halogen, Cy alkyl, SRy3, NR;jR12, ORs, heterocyclyl, aryl, =S, =O, CN, NO, NRgRy’, COR,, RNC(O)NRR,’, OC(O)NRRy’, C(O)OR,, C(O)NRR,’, or RNC(O)O; (ili) aryl optionally substituted with one or more substituents selected from halogen, Cis alkyl, SRi3, NRuRyz, ORs, heterocyclyl, aryl, =S, =0, CN, NO,, NRgRy’, COR, R,NC(O)NR,R,’, OC(O)NR,R,’, C(O)OR,, C(O)NR,R,’, or RyNC(0)O; (iv) heterocyclyl optionally substituted with one or more substituents selected from halogen, C1. alkyl, SR;3, NR11R 1, ORs, heterocyclyl, aryl, =S, =0, CN, NO, NRgRg’, COR,, R,NC(O)NR,R,’, OC(O)NR,R,’, C(O)OR,, C(O)NR,R,’, and R,NC(0)0; (v) NRj4(CH2)INRy4Rs; or (vi) NRyRi7R4 and Rs are each, independently, H, halogen, T, C,¢alkylene-T, C,-¢alkynylene-T, C(O)NR,’(CR’Ry)+-T, CO(CRoRe)-T, C(0)O(CRy'Re)-T, S(0)(CRs’R)-T, (CRRy')r 0-(CR.'Ry)~T, NRiR12, SR; or ORs;Ry is H, halogen, T, Cicalkylene-T, C,.¢alkynylene-T, C(O)NR,'(CR:’Ry’)-T, CO(CRyRe)-T, C(O)O(CRyR)-T, S(0),(CRy'R:")-T, oF (CRJRy)-O-CRRy)-T, NR, R12, SRis, or ORs;Rs is H, halogen, T, Cisalkylene-T, C,¢alkynylene-T, C(O)NR,’(CR:'Ry")-T, COCRsRe)T, COOCRYR),T, SOpCRR)T, or (CRIRe)-O-(CRR), NRyjR12, SRis, or ORs;or Ry’ and Rs’ together with the atoms to which they are attached form a ring selected from Cs.13 carbocyclyl and 3-14 membered heterocyclyl;W is oxygen or sulfur; Rg and Ry are each, independently, hydrogen, Ci. alkyl, C23 alkenyl or Cp.g alkynyl; Rg is H, C).10 alkylene-T, Ca.10 alkenylene-T, and Ca.10 alkynylene-T, (CRy'R)O(CRs’'Re’) + T, (CRy’R)NRS’(CRo'RS) Ts (CRy’R),C(O)(CRy'RS’) ~T, (CRy'Ro).C(O)O(CRyRS) ~T, (CRy’Ro)OC(OXCRy'RS) ~T, (CRy’R).C(O)NR,'(CRy'R:") ~T, (CRy’R)NR,’C(O)(CRy'R.) ~T, (CRy’R.),0C(O)O(CRy’Rs") -T, (CRy'Rc),OC(O)NR,’(CRy'RS") ~T, (CRs’Ro)NRy’C(O)O(CRy'R.") ~T, (CRs'Ro) NR," C(O)NR,’(CRy'R:") ~T, (CRy’Ro)S(O)(CRy'R<) + T, (CRy’Rc)SO;NRy’(CRu'Re)) Ts (CRy’Re) NR,’ SO2(CRy’R.) ~T, or (CRy’R),SO:NRy’SO2(CRyR:) + T; Ryo is H or C;-Cg alkyl; Ry; and Ry; are each, independently, hydrogen or C;-Cg alkyl, or Ry; and Ry2 together with the N atom to which they are attached form a 3-14 member heterocyclic ring; Ry; is C1-Cs alkyl, C;-Ce haloalkyl, Cs.13 carbocyclyl, carbocyclylalkyl, heterocyclyl, heterocyclylalkyl, each of which is optionally substituted by one or more halo, Ci. alkyl, Ci4 alkoxy, Ci haloalkyl, Cia haloalkoxy, CN, NO,, OH, COOH, amino, alkylamino, or dialkylamino; Ris and Ry; are each, independently, hydrogen, Ci-10 alkyl, Cs.13 carbocyclyl substituted with one or more heterocyclyl, or Ris and R;s together with the N atom to which they are attached form a 3-14 membered heterocyclic system; Ris and Ry; are each, independently, hydrogen, C;-Co alkyl, C3-Ci3 carbocyclyl, aryl, C3-Cy3 carbocyclylalkyl or arylalkyl, wherein said C;-Cyo alkyl, C3-Ci3 carbocyclyl, aryl,Cj.13 carbocyclylalkyl or arylalkyl are each optionally substituted with one or more halo, C14 alkyl, C14 haloalkyl, OR;7’, SR,;’, COOR;7’, amino, alkylamino, dialkylamino or heterocyclyl; or Ry and Ry; together with the N atom to which they are attached form a 3-14 membered heterocycle substituted with 0-5 Ry or are substituted by one or more heterocyclyl, heterocyclylalkyl, Cs3-Cis carbocyclyl or carbocyclylalkyl, wherein said heterocyclyl, heterocyclylalkyl, C3-Ci3 carbocyclyl or carbocyclylalkyl are each optionally substituted by one or more Rg; Ri?’ is H, C14 alkyl, Ci4 haloalkyl, Cs.13 carbocyclyl, carbocyclylalkyl, heterocyclyl or heterocyclylalkyl, wherein said Ci.i3 carbocyclyl, carbocyclylalkyl, heterocyclyl or heterocyclylalkyl are each optionally substituted by halo or C14 alkyl; Ris is Ci alkyl; Ry is halogen, Cy alkyl, Ca.3 alkyloxyalkyl, Ci. haloalkyl, SRj3, NRiR12, OH, ORs,Cs.3 carbocyclyl, heterocyclyl, aryl, =S, =0, CN, NO, NRgRg’, COR,, NRC(O)NRgRg’, OC(O)NRgRy’, C(O)NRgRy’, C(O)OR,, NRC(O)OR, or NRgC(O)Ry, or two Rg together with a carbon atom to which they are both attached form a Cs.13 carbocycle; Rp, Rg’, Ry, and Ry’ are each, independently, H, C4 alkyl, phenyl or benzyl; R! and RY are each, independently, H, Cy.s alkyl or Ca.13 carbocyclyl; R™ and RY are each, independently, H, Cs alkyl, haloalkyl, carbocyclyl, heterocyclyl, carbocyclylalkyl or heterocyclylalkyl, ‘wherein said carbocyclyl, heterocyclyl, carbocyclylalkyl or heterocyclylalkyl are each optionally substituted by one or more halo, C4 alkyl or C;4 alkoxy; RY is Cy. alkyl, haloalkyl, carbocyclyl or heterocyclyl; j=1,2,3 0r4; i=0,1o0r2; =2,3,4,5,6,70r8; n=0,1,2,3,4,5,6,7,8,9,10,11 or 12;m=0,1or2; p=1or2;and r=0,1,2,3,40r5; with the provisos: : a) the spiro ring is a stable chemical entity; and b) NR; and NR, have no N-N or N-O bonds.2. The compound of claim 1 wherein A is CWNHOH, CWNHORs, N(OH)CHO or N(OH)CWRs.3. The compound of claim 1 wherein A is CWNHOH or CWNHOR:s. 4, The compound of claim 1 wherein A is C(O)NHOH.5. The compound of claim 1 wherein B is (CHy). (CH2).C=W, (CR4R¢)sNRs, NRg(CReR9)n (CRaR)SO(CRRDr, (CRaROnS(CRaR9)r, O(C=W)NR;, O, NR;s, S(O)m S, C(O)NRg(CR4R), or C(O) (CRsR 1)».6. The compound of claim 1 wherein B is (CH), (CH2).C=W, (CR4R):NRs, NRg(CR¢Rn O(C=W)NRs, O, NRg, S(O)m, S, C(O)NRg(CR¢R¢)» or C(O)(CRaR 1).7. The compound of claim 1 wherein B is (CH) (CH2).C=W, (CR4R)sNRs, NR3(CRgR on, O(C=W)NR3, C(O)NRg(CRRy)» or C(OXCR¢Ron.8. The compound of claim 1 wherein B is (CHa)s, (CH),C=W, (CR4Rg:NRg or NRg(CRaR).9. The compound of claim 1 wherein B is (CH2)n.10. The compound of claim 1 wherein B is CHa.11. The compound of claim 1 wherein G is (CHj)n, (CH2).C=W, (CR4Rg).NRg, NRs(CRaR9n (CRRD.O(CRRp,, (CRR)-S(CR4R9),, O(C=W)NRs, O, NRs, S(O)m, S, C(O)NRg(CR4Rp)s or C(O)(CR4R 9).12. The compound of claim 1 wherein G is (CHp)» (CH2).C=W, (CR4R9)-NRs, NRg(CR¢R 9m O(C=W)NRs, O, NR3, S(O)m, S, C(O)NRg(CRaR on OF C(O)(CR4RD)m-13. The compound of claim 1 wherein G is (CH (CHp):.C=W, (CRaR)nNRs, NRg(CRaR a, O(C=W)NRs, C(O)NRg(CR4R on OF C(O) CReR14. The compound of claim 1 wherein G is (CHm (CH).C=W, (CRgR9):NRs, NRg(CRaR Dn.15. The compound of claim 1 wherein G is (CH2)n-16. The compound of claim 1 wherein G is CHa.17. The compound of claim 1 wherein B and G are both CHa.18. The compound of claim 1 wherein D is oxygen.19. The compound of claim 1 wherein X is (CHa), C110 alkylene substituted with 0 to 3 Ra, NRy, S(O)m C=0, NRsC(0), NR,C(0)O, NRyC(O)NRs, C(0)0, OC(0), S(O)mNRs, NR,S(O)ms NRsS(O)NRy, OF (CR4R)NRs, NRu(CRaR¢);-50. The compound of claim 1 wherein X is (CHz);, NRs, (CRaRNRs or NRu(CReR);-91. The compound of claim 1 wherein X is (CHa), (CRaReNRy OF NRu(CR4Ry)92. The compound of claim 1 wherein X is CH2NR, CH,CH; or NR,CH,CHa.23. The compound of claim 1 wherein Y is absent, (CHy);, Ci-10 alkylene substituted with 0 to 3 Rg NRb, S(O)m: C=0, NR+C(O), NR,C(0)0, NRC(O)NRs, C(O)0, 0C(0), S(0)nNRs, NRS(0)m NRpS(O)NR, or (CRaR)NRy, NRy(CRaR 0):74. The compound of claim 1 wherein Y is absent, (CHa);, NRu, (CRgR)NR} or NRy(CR4Ry);.75. The compound of claim 1 wherein Y is absent, (CHy)y, (CRRONR;, or NRp(CRgRe);.26. The compound of claim 1 wherein Y is absent, CH,, CH;NR;,, CH,CH, or NR,CHCH,.27. The compound of claim 1 wherein Y is absent or CHa.98. The compound of claim 1 wherein Y is CHa.29. The compound of claim 1 wherein R; is H.30. The compound of claim 1 wherein R; is H.31. The compound of claim 1 wherein Ry is H.32. The compound of claim 1 wherein Rs’ is H.33. The compound of claim 1 wherein Rs’ is H.34. The compound of claim 1 wherein Rj is NRjeR17.35. The compound of claim 1 wherein M is CO.36. The compound of claim 1 wherein U is absent.37. The compound of claim 1 wherein V is heterocyclyl substituted with 0-5 Re.38. The compound of claim 1 wherein V is azetidin-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, piperindin-lyl, piperazin-1-yl, pyrrolidin-1-yl, isoquinol-2-yl, pyridin-1-yl, ~~ 3,6- dihydropyridin-1-yl, 2,3-dihydroindol-1-yl, 1,3,4,9-tetrahydrocarbolin-2-yl, thieno[2,3- c]pyridin-6-yl, 3,4,10,1 Oa-tetrahydro- 1H-pyrazino[1,2-a]indol-2-yl, 1 ,2,4,4a,5,6-hexahydro- pyrazino[1,2-ajquinolin-3-yl, pyrazino[ 1,2-a}quinolin-3-yl, diazepan-1-yl, 1,4,5,6-tetrahydro- 2H-benzo(flisoquinolin-3-yl, 1,4,4a,5,6,10b-hexahydro-2H-benzo[f]isoquinolin-3-yl,3,3a,8,8a-tetrahydro-1H-2-aza-cyclopenta[a]inden-2-yl, or 2,3 4,7-tetrahydro-1H-azepin-1-yl, azepan-1-yl.39. The compound of claim 1 wherein U’ is absent, O or Cj.jo alkylene substituted with 0 toRa.40. The compound of claim 1 wherein U’ is absent.41. The compound of claim 1 wherein V’ is Cs.13 carbocyclyl substituted with 0-5 Re or heterocyclyl substituted with 0-5 Re.42. The compound of claim 1 wherein V” is C3.13 carbocyclyl substituted with 0-5 Re.43. The compound of claim 1 wherein V” is phenyl substituted with 0-5 Re. 44, The compound of claim 1 wherein V’ is phenyl substituted with 0-5 T, C;.salkylene-T, (CRy’R),-0~(CRy’'R."),-T, OH, CL F, Br, I, CN, NO, OR", CONR'R" or NR'COR".45. The compound of claim 1 wherein V’ is phenyl.46. The compound of claim 1 wherein V” is heterocyclyl substituted with 0-5 Re.47. The compound of claim 1 wherein V* is thiazolyl, benzothiazolyl, thienyl, quinolinyl, pyridinyl, pyarazinyl, benzimidazolyl, indazolyl, 3,6-dihydropyridinyl, piperidinyl or 2,3- dihydro-benzofuran-5-yl.48. The compound of claim 1 wherein U’ is O or Ci.jp alkylene and V’ is Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 Re.49. The compound of claim 1 wherein M is CO, U is absent, V is heterocyclyl substituted with 0-5 R,, U’ is absent, and V’ is Cj.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 R..50. The compound of claim 1 wherein M is CO, U is absent, V is absent, U’ is absent and V’ is NRpR..51. The compound of claim 1 wherein Ry, and R, are each, independently, H, Cisalkylene-T, C(O)NR,'(CRRy)rT, C(OYO(CRy'R)-T, C(O)(CRy’R)-T, S(O)(CRo'R:)--T, (CR.'Ry)-O-(CR’Ry’)~T, C(NR.’R,")(=N-CN) or C(NR.'R,")(=CHNO,).52. The compound of claim 1 wherein Rp, and R. are each, independently, H, Cy alkyl, C(O)NR.’(CR:'Ry’)-T, C(O)O(CRy'R)T, S(O)/(CRy'R:")T, (CR:’Ry)-O- (CRSRy)-T, C(NR,’R,)(=N-CN) or C(NR¢’R,")(=CHNO,).53. The compound of claim 1 wherein Rp is H, Cis alkyl, C(O) (CRy’'R)-T, C(O)O(CRy'R)-T,s S(0)(CRy'R.’)~T or (CR:’Ryp")~O-(CR:’Ry)~T.54. The compound of claim 1 wherein Ry is H.55. The compound of claim 1 wherein Ry, is C14 alkyl.56. The compound of claim 1 wherein Ry is C(OXCRy'R:’)-T.57. The compound of claim 1 wherein Ry is C(O)O(CRy'R)~T.58. The compound of claim 1 wherein Ry is S(O),(CRy’R:")-T.59. The compound of claim 1 wherein Ry is (CR'Rp’)-O-(CR:’Ry’)~T.60. The compound of claim 1 wherein Re is H or C4 alkyl.61. The compound of claim 1 wherein Re is H, T, C,.salkylene-T, C(O)NR, (CRy'R.’)T, (CRy'R)-O-(CRy’Re)-T, OH, CL F, Br, I, CN, NO, ORV, NRR", CONR'R", NR'COR", SO,NRR, C3 haloalkyl, Cs.3 carbocyclyl, heterocyclyl, carbocyclylalkyl, or heterocyclylalkyl, wherein each of said carbocyclyl, heterocyclyl, carbocyclylalkyl, and heterocylcylalkyl groups is optionally substituted by one or more Ci. alkyl, alkoxy, halo,haloalkyl, haloalkoxy, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, carboxy alkyl ester, carboxy aryl ester, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulfonyl, aminosulfonyl, alkylaminosuifonyl, dialkylaminosulfonyl, arylsulfonyl, arylsulfinyl, alkylsulfonyl or arylsufonyl.62. The compound of claim 1 wherein R. is H, Ci alkyl, OH, Cl, F, Br, I, CN, NO, methoxy, ethoxy, n-propoxy, iSopropoxy, phenoxy, benzyloxy, amino, (C4 alkyl)amino, (Ca- g)dialkylamino, C(0)O(Ci4 alkyl), CONH,;, CONH(Ci4 alkyl), CON(Ci.4 alkyl), Cis haloalkyl, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzyl, or phenethyl.63. The compound of claim 1 wherein Ry’ is C(ONR.(CRRy)-T, C(O)O(CRy’R.)-T or S(O),(CRy'R:),-T.64. The compound of claim 1 wherein Rs’ is C(O)NRy(CR:'Ry’)-T, C(O)O(CRy'R)-T or S(0),(CRy’Rc’)-T.65. The compound of claim 1 wherein ris 0, 1 or 2.66. The compound of claim 1 wherein nis 0, 1 or 2.67. The compound of claim 1 wherein; is 1 or 2.68. The compound of claim 1 having Formula II.69. The compound of claim 1 having Formula II wherein: A is CWNHOH, B is (CHps (CH2.C=W, (CRaR):NRs, NRg(CRaRn, (CRaR1):O(CRaR9)r, (CR4R)AS(CR4Ry)r, OC(O)NRg, O, NRg, $(O)n , S, C(O)NRg(CR4R¢)n or C(O)(CReR1)n; G is (CHa)n (CH2.C=W, (CRsRp):NRs, NRs(CRaRpn, (CR4R)O(CR4R9)r, (CRR),S(CRR9),, OC(O)NRs, O, NRs, S(O) , S, C(O)NR3(CR4R 1)» or C(OXCRaR pn; X is absent, (CHz);, Ci.10 alkylene substituted with 0 to 3 Re, O, NRy, S(O)m, C=0, NR,C(O), NRyC(0)O, NR;C(O)NRs, C(0)0, OC(0), S(O)mNR., NRS(0)m, NRpS(O)NRs, (CRaRe)NR;, or NRy(CRgRy);;Y is absent, (CHz), Cio alkylene substituted with 0 to 3 Ra, O, NRs, S(0)n C=O, NR;C(0), NRyC(0)O, NR:C(O)NRy, C(0)O, 0C(0), S(O)mNRw, NRS(0)ms NRuS(O)NRps (CR4Rg)NRy or NRu(CR4R1);; = Mis CO; U is absent, Ci.10 alkylene substituted with 0 to 5 Rs, O, NRy, S(O)m, C=0, NR,C(O), NR,C(0)0, NR;C(O)NRs, C(0)0, 0C(0), S(O)mwNRp, NRyS(O)m or NR,S(O)NRe; V is absent, C3.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0- 5Re; 1’ is absent, C;.jo alkylene substituted with 0 to 5 Rs, O, NRyS(0)m, C=0, NR, C(0), NR,C(0)0, NRyC(O)NRs, C(0)0, 0C(0), S(O)mNRs, NR;S(0)m, or NRsS(O)NRw; V’ is H, C.3 alkyl, NRuR¢, C313 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 Re; R, is hydrogen; R, is hydrogen; Rj; is NRjeR17; Re’ is H, C(O)NR,(CRe'Ry"),~T, C(O)O(CRs’R<)-T or S(O),(CRy’R:)~T; Rs’ is H, C(O)NR,’(CR'Ry’)~-T, C(OYO(CRy'R<™)-T or S(0)(CRy’'R.")~T; and W is oxygen.70. The compound of claim 1 having Formula II wherein: A is C(O)NHOH; B is (CH)wm (CH2.C=W, (CR&R):NRs, NRg(CRaRn (CRR)O(CR4Ry)r, (CR4R)»S(CRGR7), OC(O)NRs, O, NRs, S(O)m » S, C(O)NRg(CR4R), or C(O)(CRaR 9); G is (CH (CHWC=W, (CRaRp):NRs, NR (CRaR9)n, (CRaRD-O(CReR1)r, (CReR)-S(CR4Ry),, OC(O)NRs, O, NRg, S(O) » S, C(O)NRg(CRaR1), or C(O)(CRaR 9); X is absent, (CHy);, NR, (CRaR)NRs or NRy(CR4R 1); Y is absent, (CHz);, NRy, (CRaRe) NR or NRu(CR4aR1); Mis CO; U is absent; V is absent, Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0- 5Re; U’ is absent, C,.10 alkylene substituted with 0 to 5 R,, 0, NRpS(O)m, C=O, NR, C(O), NR,C(0)0O, NRsC(O)NRy, C(0)0, OC(0), S(O)mNRs, NRS(O)m> or NRpS(O)NR;V’ is H, Cig alkyl, NRRc, Ci.13 carbocyclyl substituted with 0-5 Re or heterocyclyl substituted with 0-5 Re; Ry, and R; are each, independently, H, C(O)O(CRy'R.’)T or S(0)(CRy'R)r-T; Rg and Rare each, independently, H or C6 alkyl; R; is hydrogen; R; is hydrogen; Rs is NRigRi17;R. is H, C(O)NR,’(CR:'Ry)-T, C(O)O(CRy'R<"),-T or S(0)(CRy’R;")~T; and Rs’ is H, C(O)NR.’(CR'Ry')~T, C(O)O(CRy’R.’)~T or S(O)s(CRs'R)-T;71. The compound of claim 1 having Formula II wherein: A is C(O)NHOH; B is (CH)m (CH:).C=W, (CRR9NRs, NRg(CR&Ron, (CRR)-O(CReR 9), (CRGR)»S(CR4R9),, OC(O)NRs, O, NRg, S(O)n , S, C(O)NRg(CRaR), OF C(OXCRaR 0); G is (CHp)m (CH2.C=W, (CReR)NRg, NRs(CRRDn (CR&R)-O(CR4R 9), (CRR)»S(CR4R9);, OC(O)NRg, O, NRg, S(O) , S, C(O)NR3(CReRy), or C(OXCRaR)n; X is absent, (CHz);, NRs, (CReR{NRs, or NRo(CRaR1)s; Y is absent, (CHz);, NRy, (CR4R)NRy or NRu(CRaRg); M is CO; U is absent; V is absent, C3.13 carbocyclyl substituted with 0-5 Re or heterocyclyl substituted with 0- 5Re; U? is absent, Cy.10 alkylene substituted with 0 to 5 Re, O, NRS(0)n, C=0, NRsC(0), NR,C(0)O, NR,C(O)NRy, C(0)O, 0C(0), S(0)mNRp, NRS(O)m, or NRpS(O)NRy; V’is H, Ci alkyl, NRyR., Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 Re; R, and R. are each, independently, H, C(O)O(CRy’'R.’)+T or S(O) (CRy'RS)-T; C(O)(CRy’R)-T, (CRyRy")-O-(CRe’Ry)~T, C(O)NRy’(CR:'Ry)r-T, C(NR«’R:")(=N-CN) or CINR,’Ry’)(=CHNO); R, and Ry are each, independently, H or Cis alkyl; R,’ is H or C4 alkyl; Ry’ and Ry are each, independently, H, Cy. alkyl, OH, CL F, Br, I, CN, NO,, NR'RY, ORY or haloalkyl; R, is hydrogen;Rg is hydrogen; Ry’ is H, C(O)NR,’(CR<'Ry")r-T, C(O)O(CRy'RS),-T or S(O)(CRy'Re)rT; Rs’ is H, C(O)NR,'(CRe'Ry)-T, C(O)O(CRy'R),-T or S(O) (CRy' Re) T: j=lor2; I=2,30r4; n=0,1,2,3o0r4; and r=0,1o0r2.72. The compound of claim 1 having Formula II wherein: A is CONHOH; B is (CHpm (CH2AC=W, (CRRINRs, NRs(CRRJn (CRaR0O(CRaR)r, (CRR.S(CRaRy),, OC(O)NRg, O, NRs, S(O) » S, C(O)NR(CRRIn or C(O)(CR¢R on; G is (CHpm (CHAC=W, (CR&R)NRs, NRg(CRiRd)m (CRaRD-O(CRaR9)r, (CReR)»S(CRaR9)r, OC(O)NRs, O, NRs, S(O) S, C(O)NRg(CR4R)» or C(O)(CRaR0)r; X is absent, (CHa), CH2NR, or NRpCH,CHz; Y is absent, (CHz);, CH2NRy or NR,CH,CHz; Mis CO; U is absent; V is heterocyclyl substituted with 0-5 Re; U’ is absent, Ci.10 alkylene substituted with 0 to 5 R,, or O; V’ is H, Ci. alkyl, NRyR., Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 Re; Ry is H, C(O)O(CRy’R),-T or S(O)(CRy’R")T; C(O)(CRy’R:)+-T, (CR'Ry’)-0-(CR.’Ry")~T, C(OINR,’(CR’Ry")-T, C(NR,’Ra")(EN-CN) or C(NR,’R,')(=CHNO.);R. is H, T, Ci.¢alkylene-T, Cz-salkenylene-T or C,-salkynylene-T; Ry and Ry are each, independently, H or Cy.6 alkyl;R.’ is H or Cys alkyl; R,’ and R.’ are each, independently, H, C, alkyl, OH, CL F, Br, I, CN, NO», NR'R", OR" or haloalkyl; R, is hydrogen; R; is hydrogen; Ry is H; Rs’ is H; j=1lor2;I=2,30r4; n=0,1,2,3or4; and r=0,1o0r2.73. The compound of claim 1 having Formula IT wherein: A is CONHOH; B is (CHz)m (CH2),C=W, (CReR0)-NRg Or NRg(CR4R¢); G is (CHz)n, (CH2),C=W, (CReR0):NRs or NRg(CR4R 9); X is absent, (CH), CH2NR, or NRpCH,CHy; Y is absent, (CHy);, CH2NR, or NRyCH,CHz; Mis CO; U is absent; V is heterocyclyl substituted with 0-5 Re; U’ is absent, C1.10 alkylene substituted with 0 to 5 Ry, or 0; V’ is H, C3 alkyl, NRyR¢, Cs.13 carbocyclyl substituted with 0-5 R. or heterocyclyl substituted with 0-5 Re; R, is H, C(O)O(CRy'R:),-T or S(O),(CRy’Re)r-T; C(O)CRy’Re)-T, (CR'Ry™),-O-(CR.’Ry")~T, C(O)NRy’ (CR. 'Ry"),-T, CANRy'Ry")(=N-CN) or C(NR4’R4")(=CHNO,);R. is H, T, Ci¢alkylene-T, Cy.galkenylene-T or C;.salkynylene-T; Rg and Ry are each, independently, H or C1.¢ alkyl; R,’ is H or Cys alkyl; R,’ and R.’ are each, independently, H, Cy alkyl, OH, CL, F, Br, I, CN, NO, NRRY, OR™ or haloalkyl; R, is hydrogen; R; is hydrogen; Ry’ is H; Rs’ is H; j=1lor2; I=2,30r4, n=0,1,2,3 or 4; and r=0,1or2.74. The compound of claim 1 having Formula II wherein: A is CONHOH;B is (CHz)n; Gis (CH2)m X is absent, (CHy); CH:NR; or NRyCH;CHy; Y is absent, (CHy);, CHoNR; or NR,CH,CH;; Mis CO; U is absent; V is heterocyclyl substituted with 0-5 Re; 1’ is absent, Ci.jp alkylene substituted with 0 to 5 Re, or O; V’ is H, Cig alkyl, NRsRq, Ci.13 carbocyclyl substituted with 0-5 Re or heterocyclyl substituted with 0-5 Re; R, is H, C(O)O(CRy'R:)rT or S(O)(CRy'Re)-T; C(O)(CRy'Re)+-T, (CRRy’)-O- (CR<’Ry)~T, C(O)NR,' (CRe'Ry')-T, CNR, 'Ry")(=N-CN) or C@R,’Rs")(=CHNO2);R.is H, T, Ci.¢alkylene-T, C,.salkenylene-T or C,.¢alkynylene-T;R.’ is H or Cys alkyl; Ry’ and Ry’ are each, independently, H, Ci. alkyl, OH, CL, F, Br, I, CN, NO,, NR'R", OR" or haloalkyl; R, is hydrogen; R; is hydrogen, Ry’ is H; Rs’ is H; j=1lor2; I=2,30r4, n=0,1,2,3 ord; and r=0,1o0r2.75. A compound of claim 1 having Formula II wherein: A is CONHOH; Bis CHy; G is CH;; X is CH;NRy; Y is (CH); Mis CO; U is absent;V is azetidin-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, piperindin-1yl, piperazin-1-yl, pyrrolidin-1-yl, isoquinol-2-yl, pyridin-1-yl, 3,6-dihydropyridin-1-yl, 2,3-dihydroindol-1-yl, 1,3,4,9-tetrahydrocarbolin-2-yl, thieno[2,3-c]pyridin-6-yl, 3,4,10,10a-tetrahydro-1H- pyrazino[1,2-a}indol-2-yl, 1,2,4,4a,5,6-hexahydro-pyrazino[1 ,2-a]quinolin-3-y1, pyrazino([1,2- a]quinolin-3-yl, diazepan-1-yl, 1,4,5,6-tetrahydro-2H-benzo[flisoquinolin-3-yl, 1,4,4a,5,6,10b- hexahydro-2H-benzo[f]isoquinolin-3-yl, 3.3a,8,8a-tetrahydro-1H-2-aza-cyclopenta[a]inden-2- yl, or 2,3,4,7-tetrahydro-1H-azepin-1-yl, azepan-1-yl; U’ is absent; V’ is C313 carbocyclyl substituted with 0-5 Re; Ry is H, C(O)O(CRs"Re")+-T or C(O)(CRs'R")-T; R,’ is H or Cys alkyl; Ry’ and R;’ are both H; R; is hydrogen; R;, is hydrogen; Rs’ is H; Rs’ is H; j=1or2; and r=0,1o0r2.76. The compound of claim 1 having Formula II wherein: A is CONHOH,; B is CHy; G is CH; X is CH;NRy,; Y is (CHz);; Mis CO; U is absent; V is piperindin-1yl, piperazin-1-yl, pyrrolidin-1-yl, pyridin-1-yl or 3,6-dihydropyridin- 1-yl; 1’ is absent; V’ is Cs.13 aryl substituted with 0-5 Re; Ry is H, C(O)O(CRy’R.’),~T or C(O)(CRy'R:’),-T; Ry’ and R.’ are both H; R, is hydrogen;R; is hydrogen; Ry is H; ‘Rs’ is H; jis 1or2;and ris0,1or2.77. The compound of claim 1 having Formula II wherein: A is CONHOH; B is CHa; Gis CH; X is CH2NRy; Y is (CHa); Mis CO; U is absent; V is piperindin-1y}, piperazin-1-yl, pyrrolidin-1-yl, pyridin-1-yl or 3,6-dihydropyridin- 1-yl; U’ is absent; V’ is phenyl substituted with 0-3 Re; Ry is H, C(O)O(CRy’R.")~T or C(O}CRy'R:")-T; Ry’ and R.’ are both H; R, is hydrogen; R; is hydrogen; Rs’ is H; Rs’ 1s H; jis 1or2;and ris0,1 or 2.78. A compound according to claim 1 selected from: N-hydroxy-5-methyl-6-{[4-(3-methylphenyl)piperazin-1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7- carboxamide; N-hydroxy-5-methyl-6-( {4-[3-(trifluoromethyl)phenyl] piperazin-1-yl}carbonyl)-S5- azaspiro[2.5]octane-7-carboxamide;N-hydroxy-5-methyl-6-{ [4-(2-methylphenyl)pip erazin-1-yljcarbonyl}-5- azaspiro[2.5] octane-7-carboxamide; 6-{[4-(4-chlorophenyl)piperazin-1 -yl]carbonyl} -N-hydroxy-5-methyl-5- azaspiro [2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6-{ [4-(2-methyl-4-nitrophenyl)piperazin- 1-yl]carbonyl}-5- azaspirof2. 5]octane-7-carboxamide; N-hydroxy-3 -methyl-6-[(4-phenylpiperidin-1 -yl)carbonyl]-5-azaspiro [2.5)octane-7- carboxamide; N-hydroxy-6-[(4-hydroxy-4-phenylpiperidin- 1-yl)carbonyl]-5-methyl-5- azaspiro[2.5] octane-7-carboxamide; N-hydroxy-5-methyl-6-{(4-phenyl-3 ,6-dihydropyridin-1 (2H)-yl)carbonyl]-5- azaspiro[2. 5]octane-7-carboxamide; N-hydroxy-5-methyl-6-[(4-quinolin-2-ylpiperazin-1 -yl)carbonyl]-5- azaspirof2. 5]octane-7-carboxamide; 6-{[4-(2,3 -dichlorophenyl)piperazin-1-yl] carbonyl }-N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6- [(4-quinolin-4-ylpiperazin-1 -yl)carbonyl]-5- azaspiro[2.5] octane-7-carboxamide; N-hydroxy-5-methyl-6-{ [4-(2-methylquinolin-4-yl)piperazin-1 -yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6-{ [4-(2-phenylethyl)piperazin-1 -yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6- [(4-pyridin-4-ylpiperidin-1 -yl)carbonyl]-5-azaspiro[2.5]octane- 7-carboxamide; N-hydroxy-5-methyl-6-{ [4-(4-nitrophenyl)piperazin-1 -yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{ [4-(2-methoxyphenyl)piperazin-1-yl] carbonyl}-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; . N-hydroxy-5-methyl-6-[(4-phenoxypiperidin-1 -yl)carbonyl}-5-azaspiro{2 .5]octane-7- carboxamide; 6-(3,4-dihydroisoquinolin-2(1 H)-ylcarbonyl)-N-hydroxy-5 -methyl-5- azaspiro[2.5]octane-7-carboxamide;6-(4,7-dihydrothieno [2,3-c]pyridin-6(SH)-ylcarbonyl)-N-hydroxy-5-methyl-5- azaspiro[2. S]octane-7-carboxamide; 6-[(3-benzylpyrrolidin-1-yl)c arbonyl]-N-hydroxy-5 -methyl-5-azaspiro[2.5]octane-7- carboxamide; N-hydroxy-5-methyl-6-[(4-pyridin-2-ylpiperazin- 1-yl)carbonyl]-5-azaspiro2. 5)octane- 7-carboxamide; N-hydroxy-5-methyl-6-{ [4-(2-pyridin-4-ylethyl)piperidin-1 -yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6-( {4-[5-(trifluoromethyl)pyridin-2-yl]piperazin- 1-yl}carbonyl)- 5-azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6-({4-{3 -(trifluoromethyl)pyridin-2-yl]piperazin-1 -yl}carbonyl)- 5-azaspiro[2.5]octane-7-carboxamide; 6-(1,4"-bipiperidin-1 '.ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro [2.5]octane-7- carboxamide; N-hydroxy-5-methyl-6-{ [4-(pyridin-2-ylmethyl)piperazin-1 -yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6-{ [4-(pyridin-4-ylmethyl)piperazin-1-yl]carbonyl} -5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6-{[4-(pyridin-3 ~ylmethyl)piperazin-1-yl]jcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6-{[4-(2-methylphenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}- 5-azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(3-methylphenyl)piperazin-1 -yl] carbonyl} -5-azaspiro[2.5]octane-7- carboxamide; : N-hydroxy-5-methyl-6-(1,3,4,9-tetrahydro -2H-B-carbolin-2-ylcarbonyl)-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6-{(9-methyl-1,3 ,4,9-tetrahydro-2H-B-carbolin-2-yl)carbonyl] -5- azaspiro[2.5)octane-7-carboxamide; 6-{[4-(2-fluorophenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2-chlorophenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl} -N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-nitrophenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide;6-{[4-phenyl-3 ,6-dihydropyridin-1(2H)-yl] carbonyl} -N-hydroxy-5-methyl-5- azaspiro[2. 5]octane-7-carboxamide; 6-{ [4-(2-methyl-4-nitrophenyl)-3 ,6-dihydropyridin-1(2H)-yl] carbonyl }-N-hydroxy-5- methyl-5-azaspiro[2. 5]octane-7-carboxamide; N(7)-hydroxy-N(6),5 -dimethyl-N(6)-(3 -phenylpropyl)-5-azaspiro[2. 5]octane-6,7- dicarboxamide; N(7)-hydroxy-N(6)-isobutyl-5-methyl-5-azaspiro 2. 5]octane-6,7-dicarboxamide; N-hydroxy-5-methyl-6-{ [4-(2-nitrophenyl)piperazin-1 -yl]carbonyl}-5- azaspiro[2. 5]octane-7-carboxamide; N(7)-hydroxy-N(6)-isobutyl-N(6),5 -dimethyl-5-azaspiro[2.5]octane-6,7- dicarboxamide; N(7)-hydroxy-5 -methyl-N(6)-(2-phenoxyethyl)-5 -azaspiro[2.5]octane-6,7- dicarboxamide; N(7)-hydroxy-N(6)- [2-(4-methoxyphenyl)ethyl]-5-methyl-5 -azaspiro[2.5]octane-6,7- dicarboxamide; N(7)-hydroxy- 5-methyl-N(6)-(4-phenylbutyl)-5-azaspiro [2.5]octane-6,7- dicarboxamide; N(7)-hydroxy-5 -methy]-N(6)-[3-(2-oxopyrrolidin-1 -yl)propyl]-5-azaspiro[2.5]octane- 6,7-dicarboxamide; N-hydroxy-5-methyl-6-[(10a)-3,4,10,1 0a-tetrahydropyrazino[1,2-aJindol-2(1H)- ylcarbonyl]-5-azaspiro[2. 5)octane-7-carboxamide; (5,6-trans)-N-hydroxy-5-{ [4-(2-methyl-4-nitrophenyl)piperazin-1 - yl]carbonyl}spiro{2.5] octane-6-carboxamide; (5,6-trans)-N-hydroxy-6-{[4-(3 -methylphenyl)piperazin-1- yl]carbonyl}spiro[2. 5]octane-5-carboxamide; (5,6-trans)-N-hydroxy-5-[{(4-phenyl-3 ,6-dihydropyridin-1(2H)- yl)carbonyl]spiro[2. 5]octane-6-carboxamide; (5,6-trans)-N-hydroxy-5-{[4-(3 -methylphenyl)piperazin-1- yl]carbonyl} spirof2. 5]octane-6-carboxamide; (5,6-trans)-N-hydroxy-6-[(4-phenyl-3 ,6-dihydropyridin-1(2H)- yl)carbonyl]spiro[2. 5]octane-5-carboxamide; N-hydroxy-6-(3,4,10,1 0a-tetrahydropyrazino[1,2-a]indol-2(1 H)-ylcarbonyl)-5- azaspiro[2.5]octane-7-carboxamide;6-(1,2,4,4a,5 ,6-hexahydro-3H-pyrazino{1 ,2-a]quinolin-3 -ylcarbonyl)-N-hydroxy-5- methyl-5-azaspiro[2.5]octane-7 -carboxamide; Methyl 7- [(hydroxyamino)carbonyl]-6- [(4-phenyl-3 ,6-dihydropyridin-1(2H)- yl)carbony!}-5-azaspiro [2.5]octane-5 -carboxylate; Benzyl 7-[(hydroxyamino)carbonyl] -6-[(4-phenyl-3 ,6-dihydropyridin-1(2H)- yl)carbonyl]-5-azaspiro[2.5) octane-5-carboxylate; N-Hydroxy-5-(methylsulfonyl)-6- [(4-phenyl-3 ,6-dihydropyridin-1 (2H)-yl)carbonyl]-5- azaspiro[2.5]octane-7 -carboxamide; N-hydroxy-6-{[3-(3 -methoxyphenyl)piperidin-1-y1] carbonyl}-5-methyl-5- azaspiro[2.5] octane-7-carboxamide; N-hydroxy-5-methyl-6-{[3 -(2-phenylethyl)pyrrolidin-1 -yl]Jcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(3 -methoxyphenyl)piperidin-1-yl] carbonyl}-5-methyl-5- azaspiro [2.5]octane-7-carboxamide; 6-{[4-[3 -(aminocarbonyl)phenyl]-3 ,6-dihydropyridin-1 (2H)-y!]carbonyl}-N-hydroxy- 5-azaspiro[2.5]octane-7 -carboxamide; N-hydroxy-6-{ [4-(2-methoxyphenyl)piperidin- 1-yl]carbonyl}-5-methyl-5- azaspiro[2.5] octane-7-carboxamide; 6-{[4-(3-fluoro-2 -methylphenyl)piperazin-1-yl] carbonyl}-N-hydroxy-5- azaspiro[2.5] octane-7-carboxamide; N-hydroxy-6-{ [4-(2-methyl-3-nitrophenyl)piperazin-1 -yl]carbonyl}-5- azaspirof2. 5)octane-7-carboxamide; 6-(3',6'-dihydro-3,4'-bipyridin- 1 '(2'H)-ylcarbonyl)-N-hydroxy-5 -azaspiro[2.5]octane-7- carboxamide; N(7)-hydroxy-N(6)~(4-methoxyphenyl)-N(6)-methyl-5-azaspiro [2.5)octane-6,7- dicarboxamide; N-hydroxy-6-{ [4-(3-methoxyphenyl)piperazin-1 -ylJcarbonyl}-5-methyl-5- azaspiro[2.5] octane-7-carboxamide; 6-{[4-(3-chlorophenyl)piperazin-1 -yljcarbonyl} -N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{(4-phenyl-1,4-diazepan- 1-yl)carbonyl]-5-azaspiro[2. 5]octane-7- carboxamide; N-hydroxy-6-{[3-methyl-4-(3 -methylphenyl)piperazin-1-yl] carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;N-hydroxy-6-{[4-(3 -methoxypheny!)piperidin-1-y1] carbonyl}-5-azaspiro[2. 5]octane-7- carboxamide; N-hydroxy-6-[(3 -phenylpyrrolidin-1 -yl)carbonyl]jspiro[2.5] octane-5-carboxamide; N-hydroxy-6- [(4-isobutyrylpiperazin-1 -yl)carbonyl]-5-azaspiro[2. 5Joctane-7- carboxamide; 6-{ [4-(4-cyano-2-methylphenyl)-3 ,6-dihydropyridin-1(2H)-yl} carbonyl}-N-hydroxy-5- azaspiro(2.5] octane-7-carboxamide; N(7)-Hydroxy-5-methyl-N(6)- {4-[(2-methylquino lin-4-yl)methoxy]phenyl}-5- azaspiro[2.5] octane-6,7-dicarboxamide; N(7)-Hydroxy-N(6)-{4- [(2-methylquinolin-4-yl)methoxylphenyl} -5- azaspiro[2.5] octane-6,7-dicarboxamide; 6-{[4-(4-cyanophenyl)piperazin-1-yl] carbony!}-N-hydroxy-5-azaspiro[2.5] octane-7- carboxamide; N-hydroxy-7-[(4-phenylpiperidin-1 -yl)carbonyl]-5-azaspiro[2.5] octane-6-carboxamide; N-hydroxy-6-[(4-phenylpiperidin-1 -yl)carbonyl]-5-azaspiro[2.5] octane-7-carboxamide; N-Hydroxy-6-[(4-phenylpiperazin-1 -yl)carbonyl]}-5-azaspiro[2. 5]octane-7- carboxamide; N-hydroxy-6-({4- [3-(methoxymethyl)phenyl] piperidin-1-yl}carbonyl)-5- azaspiro[2.5]octane-7-carboxamide; Methyl 3-[1-({7- [(hydroxyamino)carbonyl]-5-azaspiro[2. 5]oct-6- yl} carbonyl)piperidin-4-yl]benzoate; 6-[(3-Cyclohexylpyrrolidin-1 -yD)carbonyl] -N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide; N-Hydroxy-6-{[4-(3-isopropylphenyl)-3 ,6-dihydropyridin-1(2H)-yl] carbonyl}-5- azaspiro[2.5]octane-7 -carboxamide; N-hydroxy-6-{[4-(3 -isopropylphenyl)piperidin-1-yl] carbonyl }-5-azaspiro[2.5]octane- 7-carboxamide; N-hydroxy-6- { [4-(4-propylphenyl)-3,6-dihydropyridin- 1(2H)-yl]carbonyl}-35- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(4-ethylphenyl)-3 ,6-dihydropyridin-1 (2H)-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-Hydroxy-6-{[4-(4-ethylphenyl)piperidin-1 -yl]carbonyl} -5-azaspiro[2.5]octane-7- carboxamide;6-{ [4-(4-cyano-2-methylphenyl)piperazin- 1-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; N-Hydroxy-6-{ [4-(3-isopropoxyphenyl)-3 ,6-dihydropyridin-1 (2H)-yl]carbonyl} -5- azaspiro[2.5]octane-7-carboxamide; N-Hydroxy-6-{[4-(3 -methylphenyl)-3 ,6-dihydropyridin-1 (2H)-ylJcarbonyl}-5- azaspiro[2. 5]octane-7-carboxamide; N-Hydroxy-6-{ [4-(3-methylphenyl)piperidin-1 -yl]carbonyl} -5-azaspiro[2.5]octane-7- carboxamide; 6-{ [4-(4-tert-butylphenyl)piperazin- 1-yl]carbonyl} -N-hydroxy-5-azaspiro[2.5]octane- 7-carboxamide; N-Hydroxy-6- [(4-pyridin-4-ylpiperazin-1 -yl)carbonyl]-5-azaspiro [2.5]octane-7- carboxamide; 6-[(3-Benzylpiperidin-1-yl)carbonyl] N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide; N-hydroxy-6-{(5 -methoxy-2,3-dihydro-1H-indol-1 -yl)carbonyl]-5-azaspiro[2.5]octane- 7-carboxamide; N-hydroxy-6-({5- [(2-methylquinolin-4-yl)methoxy] -2.3-dihydro-1H-indol-1- yl}carbonyl)-5-azaspiro[2.5]octane-7-carboxamide; : N-hydroxy-5-methyl-6-({5-[(2-methylquinolin-4-yl)methoxy] -2,3-dihydro-1H-indol-1- yl} carbonyl)-5-azaspiro[2.5 Joctane-7-carboxamide; 6-{[5-(benzyloxy)-2,3-dihydro-1H-indol-1 -yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-(1,3-dihydro-1 'H-spiro{indene-2,4'-piperidin]-1'-ylcarbonyl)-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{ [4-(3-isopropoxyphenyl)piperidin-1 -yl]carbonyl}-5-azaspiro[2.5]octane- 7-carboxamide; Methyl 4-(1 -({7-[(hydroxyamino)carbonyl]-5-azaspiro [2.5]oct-6-y1}carbonyl)-1,2,3,6- tetrahydropyridin-4-yl]-3-methylbenzoate; N-hydroxy-6-{[4-(2-methyl-4-nitrophenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2-ethylphenyl)piperidin-1-yl] carbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide; Methyl 4-{1 -({7-[(hydroxyamino)carbonyl]-5-azaspiro[2.5]oct-6- yl} carbonyl)piperidin-4-yl}-3-methylbenzoate;6-{[4-(2,3-dihydro-1 -benzofuran-5-yl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N- hydroxy-S-methy]-5-azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(3 -isopropylphenyl)-3 ,6-dihydropyridin-1 (2H)-yl]carbonyl}-5- methyl-5-azaspiro[2.5]octane-7-carboxamide; N-Hydroxy-6-{[(3R)-3-phenylpyrrolidin-1-yljcarbonyl} -5-azaspiro[2.5]octane-7- carboxamide; N-Hydroxy-6-{[(3S)-3 -phenylpyrrolidin-1-yl] carbonyl }-5-azaspiro[2. 5]octane-7- carboxamide; N-hydroxy-6-({3-[3 -(trifluoromethyl)phenyl]pyrrolidin-1 -yl}carbonyl)-5- azaspiro [2.5]octane-7-carboxamide; 6-{[3-(3-chlorophenyl)pyrrolidin-1 -yl]carbonyl} “N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide; 6-{[3-(3-flucrophenyl)pyrrolidin-1 -yl]carbonyl} -N-hydroxy-5-azaspiro [2.5]octane-7- carboxamide; 6-{[3-(4-fluorophenyl)pyrrolidin-1 -yl]carbonyl}-N-hydroxy-5-azaspiro [2.5]octane-7- carboxamide; 6-{[3-(4-chlorophenyl)pyrrolidin-1-yl] carbonyl }-N-hydroxy-5-azaspiro[2. 5]octane-7- carboxamide; N-hydroxy-6-({3- [4~(trifluoromethyl)phenyl]pyrrolidin- 1-yl}carbonyl)-5- azaspiro[2.5]octane-7-carboxamide; 6-{[3-(4-methoxyphenyl)pyrrolidin-1-yl] carbonyl}-N-hydroxy-5-azaspiro[2.5]octane- 7-carboxamide; 6-{[3-(4-phenoxyphenyl)pyrrolidin-1-yl] carbonyl}-N-hydroxy-5-azaspiro[2.5]octane- 7-carboxamide; N-hydroxy-6-{[4-(3 -methoxyphenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{ [4-(4-cyano-3-methylphenyl)-3,6-dihydropyridin- 1(2H)-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; 6-{[3-(3-methoxyphenyl)pyrrolidin-1 -yl]carbonyl}-N-hydroxy-5-azaspiro[2. 5]octane- 7-carboxamide; N-hydroxy-6-[(3-pyridin-4-ylpyrrolidin-1 -yl)carbonyl]-5-azaspiro[2.5]octane-7- carboxamide; N-hydroxy-6-{[4-(3,5-dimethylphenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;N-hydroxy-6-{[4-(3 -trifluoromethoxyphenyl)-3 ,6-dihydropyridin-1 (2H)-yl]carbonyl}- 5-azaspiro[2 .5]octane-7-carboxamide; N-hydroxy-6-{ [5-(methoxymethyl)-4-phenyl-3 6-dihydropyridin-1(2H)-y1] carbonyl}- 5-azaspiro[2.5]octane-7 carboxamide; N-hydroxy-6-(1,4,5 ,6-tetrahydrobenzo[f] isoquinolin-3 (2H)-ylcarbonyl)-5- azaspiro[2.5] octane-7-carboxamide; N-hydroxy-6-{[4-(5 -methoxy-2-methylphenyl)-3 ,6-dihydropyridin-1(2H)- yl]carbonyl}-5-azaspiro[2. 5]octane-7-carboxamide; N-hydroxy-6-{ [4-(4-methoxy-2-methylphenyl)-3 ,6-dihydropyridin-1(2H)- yl]carbonyl}-5-azaspiro[2. 5]octane-7-carboxamide; 6-[(4-cyano-4-phenylpiperidin- 1-yl)carbonyl] -N-hydroxy-5-azaspiro[2. 5]octane-7- carboxamide; Ethyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3 ,6-dihydropyridin-1(2H)- yl)carbonyl}-5-azaspiro[2. 5)octane-5-carboxylate; Propyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridin-1 (2H)- yl)carbonyl]-5-azaspiro [2.5]octane-5-carboxylate; Isopropyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridin-1(2H)- yl)carbonyl]-5-azaspiro[2.5]octane-5 carboxylate; Isobutyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridin-1(2H)- yl)carbonyl]-5-azaspiro[2.5]octane-5 -carboxylate; and N-hydroxy-6-[(5-methyl-4-phenyi-3 ,6-dihydropyridin-1(2H)-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide.79. A compound according to claim 1 selected from: 6-(1,4,4a,5,6,10b-hexahydrobenzo [flisoquinolin-3 (2H)-ylcarbonyl)-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-fluorophenyl)-3-hydroxypiperidin-1 -yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-(3,32,8,8a-tetrahydroindeno[1,2-c] pyrrol-2(1H)-ylcarbonyl)-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(4-phenyl-1,3-thiazol-2-yl)piperidin-1 -yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide,; N-hydroxy-6-{[4-(4-tert-Butyl-1,3-thiazol-2-yl)piperidin-1-ylj carbonyl}-5- azaspiro[2.5]octane-7-carboxamide;N-hydroxy-6-[(4-methyl-4-phenylpiperidin- 1-y})carbonyl]-5-azaspiro[2 .S]octane-7- carboxamide; N-hydroxy-6-{[4-(4-ethyl-1 ,3-thiazol-2-yl)piperidin-1 -yl]jcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{ [(trans)-3-methyl-4-phenylpyrrolidin- 1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; 6-{ [4-(2-fluorophenyl)piperazin-1-yljcarbonyl} -N-hydroxy-5-azaspiro[2. 5Joctane-7- carboxamide; 6-{[4-(3,5-dimethylphenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-5- methyl-5-azaspiro [2.5]octane-7-carboxamide; Tetrahydro-2H-pyran-4-yl-7-((aydroxyamino)carbonyl)-6-((4-phenylpiperazin- 1- yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate; Ethyl 7-((hydroxyamino)carbonyl) )-6-((4-phenylpiperazin-1 -yl)carbonyl-5- azaspiro(2,5)octane-5-carboxylate; Methyl 7-[(hydroxyamino)carbonyl}-6-[(4-phenylpiperazin-1-yl)carbonyl]-5- azaspiro[2.5]octane-5-carboxylate; N-hydroxy-6-[(4-pyrazin-2-ylpiperazin-1 -yl)carbonyl}-5-azaspiro[2.5]octane-7- carboxamide; N-hydroxy-6-[(4-quinolin-2-ylpiperazin-1-yl)carbonyl]-5-azaspiro [2.5)octane-7- carboxamide; N-hydroxy-6-{ [3-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidin- 1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-5-methyl-6-{[(3R)-3 -phenylpyrrolidin-1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; Methyl 7-[(hydroxyamino)carbonyl]-6-{[(3R)-3-phenylpyrrolidin-1 -yl]carbonyl}-5- azaspiro[2.5]octane-5-carboxylate; N-hydroxy-6-[(3-pyridin-3-ylpyrrolidin-1 -yl)carbonyl]-5-azaspiro[2.5]octane-7- carboxamide; N-hydroxy-6-[(3-pyridin-2-ylpyrrolidin-1 -yl)carbonyl]-5-azaspiro[2.5]octane-7- carboxamide; N-hydroxy-6-[(3-methyl-3-phenylpyrrolidin-1 -yl)carbonyl}-5-azaspiro[2.5]octane-7- carboxamide; N-hydroxy-6-[(3-phenylazetidin-1 -yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;N-hydroxy-5 -methyl-6-[(3-methyl-3 -phenylpyrrolidin-1 -ylcarbonyl}-5- azaspiro[2.5)octane-7-carboxamide; N-hydroxy-5 -methyl-6-[(3-phenylazetidin- 1 -yl)carbonyl]-5-azaspiro[2.5}octane-7- carboxamide; 6-(1,3,3a,4,5 9b-hexahydro-2H-benzo[e}isoindol-2-ylcarbonyl)-N-hydroxy-3 - azaspiro[2.5]octane-7 -carboxamide; N-hydroxy-6-{ [3-(2-naphthyl)pyrrolidin-1 -yl]carbonyl}-5-azaspiro [2.5]octane-7- carboxamide; N-hydroxy-6-{[4-(2-thienyl)-3 ,6-dihydropyridin-1(2H)-yl] carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[3-(3 -thienyl)pyrrolidin-1-ylJcarbonyl}-5 -azaspiro[2.5]octane-7- carboxamide; N-hydroxy-6-{[3-(2-thienyl)pyrrolidin-1 -yl]carbonyl}-5-azaspiro[2. 5]octane-7- carboxamide; N-hydroxy-6-{[4-(2-thienyl)piperidin-1 -yl]carbonyl}-5-azaspiro[2.5] octane-7- carboxamide; N-hydroxy-6-{ [3-(2-methylphenyl)pyrrolidin-1-yl] carbonyl}-5-azaspiro[2.5]octane-7- carboxamide; N-hydroxy-6-{ [3-(4-methylphenyl)pyrrolidin-1-yl] carbonyl}-5-azaspiro[2.5]octane-7- carboxamide; 5-acetyl-N-hydroxy-6-[(4-phenyl-3 ,6-dihydropyridin-1(2H)-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(3-thienyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-[(3-phenylpiperidin-1-yl)carbonyl]-5 -azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(3-thienyl)piperidin-1-yl] carbonyl }-5-azaspiro[2.5]octane-7- carboxamide; Methyl 6-{[4-(3 ,5-dimethylphenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-7- [(hydroxyamino)carbonyl]-5-azaspiro[2 .5]octane-5-carboxylate; 6-{[4-(3,5-dimethylpheny1)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-5- (methylsulfonyl)-5-azaspirof2.5]octane-7 -carboxamide; 6-{[4~(3,5-difluorophenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl }-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide;6-{[4-(3,5-dichlorophenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-3- azaspiro[2.5]octane-7-carboxamide; 6-{[4-[3,5 -bis(trifluoromethyl)phenyl] -3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N- hydroxy-5-azaspiro[2. 5]octane-7 -carboxamide; N-hydroxy-5-(methylsulfonyl)-6-[(4-phenylpiperazin-1 -yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; -formyl-N-hydroxy-6-[(4-phenylpiperazin- 1-yl)carbonyl}-5-azaspiro[2. 5Joctane-7- carboxamide; 6-{[4-(3 ,5-difluorophenyl)piperidin-1-yl] carbonyl}-N-hydroxy-5-azaspiro [2.5)octane- 7-carboxamide; 6-{[4-(2,5 -dimethylphenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2,4,5-trimethylphenyl)-3 6-dihydropyridin- 1(2H)-yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-[(4-biphenyl-3-ylpiperidin-1-yl)carbonyl] -N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide; 6-[(4-dibenzo[b,d]furan-4-ylpiperidin-1 -yl)carbonyl]-N-hydroxy-3- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(2,5-dimethylphenyl)piperidin-1-yl] carbonyl }-N-hydroxy-5-azaspiro[2.5]octane- 7-carboxamide; 6-{[4-(2,4,5-trimethylphenyl)piperidin-1-yl] carbonyl }-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; Methyl 3-[1-({7-[(hydroxyamino)carbonyl] -5-azaspiro[2.5]oct-6-yl} carbonyl)-1,2,3,6- tetrahydropyridin-4-yl]-4-methylbenzoate; 6-[(5-phenyl-2,3,4,7-tetrahydro-1H-azepin-1 -yl)carbonyl]-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-[3-(dimethylamino)phenyl]-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy- 5-azaspiro[2.5]octane-7-carboxamide; Methyl 3-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2.5]oct-6- yl} carbonyl)piperidin-4-yl]-4-methylbenzoate; 6-[(5-phenylazepan-1-yl)carbonyl}-N-hydroxy-5-azaspiro[2. 5]octane-7-carboxamide;6-({4-[3-(dimethylamino)phenyl]piperidin-1 -yl}carbonyl)-N-hydroxy-5- azaspiro[2.5]octane-7 -carboxamide; 6-{[4-(2-methylphenyl)-3 ,6-dihydropyridin-1(2H)-yl] carbonyl }-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-[(3-phenyl-2,5-dihydro-1 H-pyrrol-1 _yl)carbony1]-N-hydroxy-5-azaspiro [2.5]octane- 7-carboxamide; 6-{ [4-(4-cyano-2-methylphenyl)piperidin- 1-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5] octane-7-carboxamide; 6-[(3 3-dimethyl-4-phenyl-3,6-dihydropyridin- 1(2H)-yl)carbonyl] -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-[(3,3-dimethyl-4-phenylpiperidin-1 -yl)carbonyl] -N-hydroxy-5-azaspiro [2.5]octane-7- carboxamide; N-hydroxy-5-(methylsulfonyl)-6- [(3-phenyl-2,5-dihydro-1 H-pyrrol-1-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; Methyl 7-[(hydroxyamino)carbonyl]-6-[(3 -phenyl-2,5-dihydro-1H-pyrrol-1- yl)carbonyl]-5-azaspiro[2.5]octane-5 -carboxylate; N-hydroxy-5-methyl-6-[(3-phenyl-2,5 -dihydro-1H-pyrrol-1-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3-methylphenyl)piperidin-1 -yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-[3-(benzyloxy)phenyl}-3 ,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-[3-ethylphenyl]-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-[3-(ethyloxy)phenyl]-3,6-dihydropyridin-1 (2H)-yl]carbony!}-N-hydroxy-5- azaspiro[2.5)octane-7-carboxamide; 6-{[4-(3-ethylphenyl)piperidin-1 -yl]carbonyl}-N-hydroxy-5-azaspiro[2.5] octane-7- carboxamide; 6-{[4-(3-ethoxyphenyl)piperidin-1-yl]carbonyl} -N-hydroxy-5-azaspiro[2.5]octane-7- carboxamide; 6-{[4-(3-cyclopropylphenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-5- azaspiro[2.5)octane-7-carboxamide;6- {[4-(4-methoxy-3 ,5-dimethylphenyl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N- hydroxy-5-azaspiro[2.5]octane-7-carboxamide; 6-{[4-(3, 5-dimethyl-4-methoxyphenyl)piperidin-1-yl} carbonyl} -N-hydroxy-5- azaspiro[2.5)octane-7-carboxamide; 6-{[4-(4-cyano-3-ethylphenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3-ethylphenyl)piperidin-1 -yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl } -N- hydroxy-5-azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3,5-dimethylphenyl)piperidin-1 -yl]carbonyl}-N-hydroxy-3- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(1,3-benzothiazol-6-yl)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(1-methyl-1 H-benzimidazol-6-yl)-3,6-dihydropyridin-1(2H)- yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(1-methyl-1H-benzimidazol-6-yl)piperidin-1-yl] carbonyl }-5- azaspiro[2.5]octane-7-carboxamide; 6- {[4-(4-cyano-3-isopropylphenyl)-3,6-dihydropyridin-1(2H)-yl] carbonyl}-N-hydroxy- 5-azaspiro[2.5)octane-7-carboxamide; 6- {[4-(4-cyano-3-isopropylphenyl)piperidin-1-yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridin-1(2H)-yl] carbonyl} -N-hydroxy-5- methyl-5-azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-3,5-dimethylphenyl)-3,6-dihydropyridin- 1 (2H)-yl]carbonyl }-N- hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(1-ethyl-1H-benzimidazol-6-yl)-3,6-dihydropyridin-1(2H)- yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6- {[4-(1-methyl-1H-indazol-5-yl)-3,6-dihydropyridin-1(2H)-ylJcarbonyl } - 5-azaspiro[2.5]octane-7-carboxamide;N-hydroxy-6-{[4-(1-ethyl-1 H-benzimidazol-6-yl)piperidin-1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(1-methyl-1H-indazol-5-yl)piperidin- 1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[4-(1-ethyl-1H-indazol-5 -y1)-3,6-dihydropyridin-1 (2H)-yl]carbonyl}-5- azaspiro|[2. 5)octane-7-carboxamide; Tetrahydro-2H-pyran-4-yl 6-{[4-(1-ethyl-1 H-benzimidazol-6-yl)piperidin-1- ylJcarbonyl}-7-[(hydroxyamino)carbonyl] -5-azaspiro[2.5]octane-5-carboxylate; Methyl 6-{[4-(1-ethyl-1H-benzimidazol-6-y1)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}- 7-[(hydroxyamino)carbonyl]-5-azaspiro[2.5]octane-5 -carboxylate; 6-{[4-(1-ethyl-1 H-benzimidazol-6-yl)-3,6-dihydropyridin-1(2H)-yl]carbonyl}-N- hydroxy-5-(methylsulfonyl)-5-azaspiro[2.5]octane-7-carboxamide; Methyl 6-{[4-(1-ethyl-1H-benzimidazol-6-yl)piperidin-1-yl] carbonyl}-7- [(hydroxyamino)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; 6-{[4-(1-ethyl-1H-benzimidazol-6-yl)piperidin-1-yl]carbonyl}-N-hydroxy-5- (methylsulfonyl)-5-azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyano-2-methylphenyl)piperidin-1-yl]carbonyl}-N-hydroxy-5- (methylsulfonyl)-5-azaspiro[2.5]octane-7-carboxamide; Methyl 6-{[4-(4-cyano-2-methylpheny])piperazin-1-yljcarbonyl}-7- [(hydroxyamino)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; 6-{[4-(1-ethyl-1H-benzimidazol-6-yl)piperazin-1-yljcarbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; Methyl 6-{[4-(1-ethyl-1H-benzimidazol-6-yl)piperazin-1-yljcarbonyl}-7- [(hydroxyamino)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; 6-{[4-(1-ethyl-1H-benzimidazol-6-yl)piperazin-1-ylJcarbonyl} -N-hydroxy-5- (methylsulfonyl)-5-azaspiro[2.5]octane-7-carboxamide; Tetrahydro-2H-pyran-4-yl 6-{[4-(4-cyano-2-methylphenyl)piperazin-1-yl]carbonyl}-7- [(hydroxyamino)carbonyl]-5-azaspiro[2.5]octane-S-carboxylate; Tetrahydro-2H-pyran-4-yl 6-{[4-(1-ethyl-1H-benzimidazol-6-yl)piperazin-1- yl]carbonyl}-7-[(hydroxyamino)carbonyl}-5-azaspiro[2.5])octane-5-carboxylate;N-hydroxy-6- [(3-methyl-4-phenylpiperidin-1 -yl)carbonyl]-5-azaspiro[2.5]octane-7- carboxamide; 6-{[5-(aminocarbonyl)-4-phenyl-3 ,6-dihydropyridin-1(2H)-yl] carbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyanophenyl)-S-methyl-3,6-dihydropyridin- 1(2H)-yl]carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(4-cyanophenyl)-3-methylpiperidin-1-yl] carbonyl }-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[5 -methyl-4-(4-nitrophenyl)-3,6-dihydropyridin-1(2H)-yl] carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; N-hydroxy-6-{[5-methyl-4-(3 -nitrophenyl)-3,6-dihydropyridin-1(2H)-yl] carbonyl }-5- azaspiro[2.5]octane-7-carboxamide; 6-[(4-dibenzo[b,d]furan-2-yl-3,6-dihydropyridin-1 (2H)-yl)carbonyl]-N-hydroxy-3- azaspiro[2.5]octane-7-carboxamide; 6-[(4-dibenzo[b,d]furan-2-ylpiperidin-1-yl)carbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; 6-{[4-(3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,6-dihydropyridin-1 (2H)- yl]carbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide; 6-{[4~(3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)piperidin- 1-ylJcarbonyl}-N- hydroxy-5-azaspiro[2.5]octane-7-carboxamide; Isopropy! 7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1- yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; (3S)-tetrahydrofuran-3-yl 7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro- 1H- pyrrol-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; Cyclohexyl 7-[(hydroxyamino)carbonyl}-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1- yl)carbonyl]-5-azaspiro[2.5)octane-5-carboxylate; Tetrahydro-2H-pyran-4-yl 7-[(hydroxyamino)carbonyl}-6-[(3-phenyl-2,5-dihydro-1H- pyrrol-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; N-hydroxy-6-((4-phenylpiperazin-1-yl)carbonyl)spiro(2.5) octane-5-carboxamide; N-hydroxy-6-{[(3R)-3-phenylpyrrolidin-1-yl]carbonyl}spiro[2.5]octane-5- carboxamide; N-hydroxy-6-{[4-(2-methyl-4-nitrophenyl)piperazin- 1-ylJcarbonyl} spiro[2.5]octane- 5- carboxamide;N-hydroxy-6-[(4-phenyl-3 ,6-dihydropyridin-1(2H)-yl)carbonyl}spiro[2.5] octane-5- carboxamide; (3S)-tetrahydrofuran-3-yl 7-{(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1 - yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; (3R)-tetrahydrofuran-3-yl 7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1- yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; 2-Methoxyethyl 7-((hydroxyamino)carbonyl)-6-((4-phenylpiperazin-1 -yl)carbonyl)-5- azaspiro(2,5)octane - 5-carboxylate; N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl] -5-(phenylsulfonyl)-5- azaspiro[2.5]octane-7-carboxamide; Propyl 7-[(hydroxyamino)carbony))-6-[(4-phenylpiperazin-1-yl)carbonyl]-5- azaspiro[2,5]octane-5-carboxylate; Isopropyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5- azaspiro[2.5]octane-5-carboxylate; Methyl 6-{[4-(3,5-difluorophenyl)-3,6-dihydropyridin-1 (2H)-yl]jcarbonyl}-7- [(hydroxyamino)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; Methyl 6-{[4-(3,5-difluorophenyl)-3 ,6-dihydropyridin-1(2H)-yl]carbonyl}-7- [(hydroxyamino)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate; N-hydroxy-6-{[4-(4-isopropylphenyl)piperazin-1-yl}carbonyl}-5 -azaspiro{2.5]octane- 7-carboxamide; 6-{ [4-(3,5-difluorophenyl)piperidin-1-yljcarbonyl}-N-hydroxy-5 -(methylsulfonyl)-5- azaspiro[2.5]octane-7-carboxamide; and 6-{[4-(4,5-dimethyl-1,3-thiazol-2-yl)piperidin-1-yl] carbonyl }-N-hydroxy-5- azaspiro[2.5)octane-7-carboxamide.80. A compound of claim 1 selected from: (6S,7S)-N-hydroxy-5-methyl-6- {[4-(3-methylphenyl)piperazin-1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-S-methyl-6-({4-[3-(trifluoromethyl)phenyl]piperazin-1- yl} carbonyl)-5-azaspiro[2.5]octane-7-carboxamide;(6S,7S)-N-hydroxy-5-methyl-6-{ [4-(2-methylphenyl)piperazin- 1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (68,7S)-6-§ [4-(4-chlorophenyl)piperazin-1 -yljcarbonyl}-N-hydroxy-5 -methyl-5- azaspiro[2.5] octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-{ [4-(2-methyl-4-nitrophenyl)piperazin- 1-yl]carbonyl}- 5-azaspiro[2.5]octane-7-carboxamide; (68,7 S)-N-hydroxy-5-methyl-6-[(4-phenylpiperidin- 1-yl)carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (65,7 S)-N-hydroxy-6-[(4-hydroxy-4-phenylpiperidin-1 -yl)carbonyl]-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5 -methyl-6-[(4-phenyl-3,6-dihydropyridin-1 (2H)-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5 -methyl-6-[(4-quinolin-2-ylpiperazin-1 -yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; (68,78)-6-{[4(2,3-dichlorophenyl)piperazin-1-yl] carbonyl }-N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; (6S ,7S)-N-hydroxy-5-methyl-6-[(4-quinolin-4-ylpiperazin- 1-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-{ [4-(2-methylquinolin-4-yl)piperazin-1 -yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-{ [4-(2-phenylethyl)piperazin-1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6- [(4-pyridin-4-ylpiperidin-1-yl)carbonyl]-5- azaspiro[2.5)octane-7-carboxamide; (6S,78)-N-hydroxy-5-methyl-6-{ [4-(4-nitrophenyl)piperazin-1-yl]carbonyl}-5- . azaspiro[2.5]octane-7-carboxamide; (68,7S)-N-hydroxy-6-{[4-(2-methoxyphenyl)piperazin-1-yl] carbonyl }-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-[(4-phenoxypiperidin-1-yl)carbonyl]-3- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-6-(3,4-dihydroisoquinolin-2( 1H)-ylcarbony!)-N-hydroxy-5-methyl-5- azaspirof2.5]octane-7-carboxamide; and(68 75)-6-(4,7-dihydrothieno[2,3-c]pyridin-6(SH)-ylcarbonyl)-N-hydroxy-5-methy-5- azaspiro[2.5]octane-7-carboxamide.81. A compound of claim 1 selected from: (6S,7S)-6- [(3-benzylpyrrolidin-1-yl)carbonyl]-N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hy droxy-5-methyl-6-[(4-pyridin-2-ylpiperazin-1 -yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-pyridin-4-ylethyl)piperidin-1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (68,78)-N-hydroxy-5-methyl-6-({4-[5 ~(trifluoromethyl)pyridin-2-yl]piperazin-1- yl} carbonyl)-5-azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-({4-[3-(trifluoromethyl)pyridin-2-yl]piperazin-1- yl} carbonyl)-S-azaspiro[2.5]octane-7-carboxamide; (6S,7S)-6-(1,4"-bipiperidin-1'-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2.5]octane- 7-carboxamide; : (6S,7S)-N-hydroxy-5-methyl-6-{ [4-(pyridin-2-ylmethyl)piperazin-1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-{[4-(pyridin-4-ylmethyl)piperazin-1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-{[4-(pyridin-3-ylmethyl)piperazin-1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-methylphenyl)-3,6-dihydropyridin-1(2H)- yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide; (68,7S)-N-hydroxy-6-{[4-(3-methylpheny]l)piperazin-1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; - (68,7S)-N-hydroxy-S-methyl-6-(1,3,4,9-tetrahydro-2H-B-carbolin-2-ylcarbonyl)-S5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-[(9-methyl-1,3,4,9-tetrahydro-2H- B-carbolin-2- yl)carbonyl]-5-azaspirof2.5)octane-7-carboxamide; (6S,7S)-6-{[4-(2-fluorophenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-5- methyl-5-azaspiro[2.5]octane-7-carboxamide; (6S,7S)-6-{[4-(2-chlorophenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl } -N-hydroxy-S5- methyl-5-azaspiro[2.5]octane-7-carboxamide;(68,75)-6-{[4-(4-nitrophenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy-5- methyl-5-azaspiro[2.5]octane-7-carboxamide; (68,78)-6-{[4-phenyl-3 6-dihydropyridin-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5- azaspiro[2.5]octane-7-carboxamide; (68,78)-6-{[4-(2-methyl-4-nitropheny)-3,6-dihydropyridin-1(2FD-ylJearbonyl}-N- hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide; (68,78)-N(7)-hydroxy-N(6),5-dimethyl-N(6)-(3-phenylpropyl)-5-azaspiro [2.5)octane- 6,7-dicarboxamide; and (6S,7S)-N(7)-hydroxy-N(6)-isobutyl-5-methyl-5-azaspiro[2.5]octane-6,7- dicarboxamide.82. A compound of claim 1 selected from: (6S,7S)-6-(1,4,48,5,6,10b-hexahydrobenzofflisoquinolin-3(2H)-yicarbonyl)-N- hydroxy-5-azaspiro[2.5]octane-7-carboxamide; (68,7S)-6-{[4-(4-fluorophenyl)-3-hydroxypiperidin-1-yljcarbonyl}-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-6-(3,3a,8,8a-tetrahydroindeno(1 ,2-c)pyrrol-2(1H)-ylcarbonyl)-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-6-{[4-(4-phenyl-1,3 -thiazol-2-yl)piperidin-1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-6-{[4-(4-tert-Butyl-1,3 -thiazol-2-yl)piperidin-1-yl]carbonyl} -5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-6-[(4-methyl-4-phenylpiperidin-1-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-6-{[4-(4-ethyl-1,3-thiazol-2-yl)piperidin-1-yl]carbonyl} -5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-6-{[(trans)-3-methyl-4-phenylpyrrolidin-1 -yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (68,7S)-6-{[4-(2-fluorophenyl)piperazin-1-yljcarbonyl} -N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-6-{[4-(3,5-dimethylphenyl)-3,6-dihydropyridin-1 (2H)-ylJcarbonyl}-N- hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide; Tetrahydro-2H-pyran-4-yl<(6S,7S)-7<((hydroxyamino)carbonyl)-6-((4- phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate;Ethyl (6S,7S)-7 -((hydroxyamino)carbonyl) }-6-((4-phenylpiperazin-1-yl)carbonyl-5- azaspiro(2,5)octane-5-carboxylate; Methyl (68,7S)-7-[(hydroxyamino)carbonyl] -6-[(4-phenylpiperazin-1-yl)carbonyl]-5 - azaspiro[2.5)octane-5-carboxylate; (6S,7S)-N-hydroxy-6-[(4-pyrazin-2-ylpiperazin-1-yl)carbonyl)-5-azaspiro[2. S]octane- 7-carboxamide; (68 7S)-N-hydroxy-6-[(4-quinolin-2-ylpiperazin-1-yl)carbonyl]-5-azaspiro[2. 3 Joctane- 7-carboxamide; (6S,78)-N-hydroxy-6-{[3-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidin-1- ylJcarbonyl}-5-azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-{ [(3R)-3-phenylpyrrolidin-1-yl]carbonyl}-3- azaspiro[2.5]octane-7-carboxamide; Methyl (68,7S)-7-[(hydroxyamino)carbonyl]-6-{[(3R)-3-phenylpyrrolidin-1- yl]carbonyl}-5-azaspiro[2.5]octane-5-carboxylate; (68,7S)-N-hydroxy-6-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl}-5-azaspiro{2.5]octane- 7-carboxamide; and (68,7S)-N-hydroxy-6-[(3-pyridin-2-ylpyrrolidin-1-yl)carbonyl]-5-azaspiro[2.5] octane- 7-carboxamide.83. A compound of claim 1 selected from: (6S,7S)-N-hydroxy-6- ((3-methyl-3-phenylpyrrolidin-1-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-N-hydroxy-6-[(3-phenylazetidin-1-yl)carbonyl]-5-azaspiro[2.5}octane-7- carboxamide; (6S,7S)-N-hydroxy-5-methyl-6-[(3-methyl-3 -phenylpyrrolidin-1-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; (68,7S)-N-hydroxy-5-methyl-6-[(3-phenylazetidin-1-yl)carbonyl]-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-6-(1,3 ,3a,4,5,9b-hexahydro-2H-benzo[e)isoindol-2-ylcarbonyl)-N-hydroxy-5- azaspiro[2.5]octane-7-carboxamide; (6S,7 S)-N-hydroxy-6-{[3-(2-naphthyl)pyrrolidin-1-yljcarbonyl} -5-azaspiro[2.5]octane- 7-carboxamide; (68,7S)-N-hydroxy-6- {[4-(2-thienyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl} -5- azaspiro[2.5]octane-7-carboxamide;PCT/US2004/012672 (6S,7S)-N-hydroxy-6-{[3-(3-thienyl)pyrrolidin-1-yl]Jcarbonyl} -5-azaspiro[2.5]octane- 7-carboxamide; (6S,7S)-N-hydroxy-6-{[3-(2-thienyl)pyrrolidin-1-yl]carbonyl} -5-azaspiro[2.5]octane- 7-carboxamide; (6S,7S)-N-hydroxy-6-{[4-(2-thienyl)piperidin- 1-yl]carbonyl}-5-azaspirc[2.5]octane-7- carboxamide;(68.7S)-N-hydroxy-6-{[3-(2-methylphenyl)pyrrolidin-1-yljcarbonyl}-5- azaspiro[2.5]octane-7-carboxamide; lo (6S,7S)-N-hydroxy-6-{[3-(4-methylphenyl)pyrrolidin-1-yl]carbonyl}-5- azaspiro[2.5]octane-7-carboxamide; (6S,7S)-5-acetyl-N-hydroxy-6-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5- azaspiro[2.5)octane-7-carboxamide; (6S,7S)-N-hydroxy-6- {[4-(3-thienyl)-3,6-dihydropyridin-1(2H)-yl] carbonyl} -5- azaspiro[2.5]octane-7-carboxamide; ts (6S,7S)-N-hydroxy-6-[(3-phenylpiperidin-1-yl)carbonyl]-5-azaspiro [2.5]octane-7- carboxamide;(6S.7S)-N-hydroxy-6- {[4-(3-thienyl)piperidin-1-yl]carbonyl }-5-azaspiro[2.5] octane-7- carboxamide; Methyl (6S,7S)-6-{[4-(3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl}-7- [(hydroxyamino)carbonyl]-S-azaspiro{2.5]octane-5-carboxylate; (6S,7S)-6-{[4-(3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl}-N- hydroxy-S-(methylsulfonyl)-5-azaspiro[2.5]octane-7-carboxamide; and (6S,7S)-6-{[4-(3,5-diflucrophenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl} -N-hydroxy- S-azaspiro{2.5]octane-7-carboxamide.84. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.85. Use of a compound of claim 1 in the manufacture of a medicament for treating a disease associated with unwanted metalloprotease activity in a mammalian subject.86. Use of a compound of claim 1 in the manufacture of a medicament for treating a disease modulated by a metalloprotease in a mammalian subject, wherein the disease is selected AMENDED SHEET \PCT/US2004/012672 from arthritis, cancer, cardiovascular disorders, skin disorders, inflammation and allergic conditions.87. Use of a compound according to claim 1 in the manufacture of a medicament for treating breast cancer in a mammal.88. Use of a compound according to claim 1 in the manufacture of a medicament for inhibiting pathological changes mediated by elevated levels of matrix metalloproteases in mammals.89. Use of a compound of claim 1 in the manufacture of a medicament for treating a disease associated with unwanted TNF-a converting enzyme activity in a mammalian subject.90. Use of a compound of claim 1 in the manufacture of a medicament for treating a disease associated with unwanted matrix metalloprotease activity wherein said matrix metalloprotease is selected from the group consisting of MMP12, MMP 14, MMP3, MMP2, and MMP9 in a mammalian subject.91. Use of a compound of claim 1 in the manufacture of a medicament for treating a disease associated with unwanted activity of Her-2 sheddase, growth factor sheddases, or cytokine sheddases in a mammalian subject.92. Use of a compound of claim 1 in the manufacture of a medicament for treating a disease associated with activity of Her-2 sheddase in a mammal.93. Use of claim 92 wherein said disease is cancer. 94, Use of claim 93 wherein said cancer is breast cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, colon cancer, gastric cancer, pancreatic cancer or glioma.95. Use of a compound of claim 1 in the manufacture of a medicament for treating a disease associated with unwanted ADAM10, ADAMI15, or ADAMI17 activity in a mammalian subject. AMENDED SHEET \. PCT/US2004/01267296. A substance or composition for use in a method for treating a disease associated with unwanted metalloprotease activity in a mammalian subject, said substance or composition comprising a compound of claim 1, and said method comprising administering to said mammal in need thereof a therapeutically effective amount of said substance or composition.97. A substance or composition for use in a method for treating a disease modulated by a metalloprotease in a mammalian subject, wherein the disease is selected from arthritis, cancer, cardiovascular disorders, skin disorders, inflammation and allergic conditions, said substance or composition comprising a compound according to claim 1, and said method comprising administering to said mammal in need of such treatment a therapeutically effective amount of said substance or composition.98. A substance or composition for use in a method for treating breast cancer in a mammal, said substance or composition comprising a compound according to claim 1, and said method comprising administering to said mammal in need of such treatment a therapeutically effective amount of said substance or composition.99. A substance or composition for use in a method of inhibiting pathological changes mediated by elevated levels of matrix metalloproteases in mammals, said substance or composition comprising a compound according to claim 1, and said method comprising administering to said mammal in need thereof a therapeutically effective amount of said substance or composition.100. A substance or composition for use in a method for treating a disease associated with unwanted TNF-a converting enzyme activity in a mammalian subject, said substance or composition comprising a compound of claim 1, and said method comprising administering to said mammal in need thereof a therapeutically effective amount of said substance or composition.101. A substance or composition for use in a method for treating a disease associated with unwanted matrix metalloprotease activity wherein said matrix metalloprotease is selected from the group consisting of MMP12, MMP14, MMP3, MMP2, and MMP9 in a mammalian subject. said substance or composition comprising a compound of claim 1, and said method AMENDED SHEET \\ PCT/US2004/012672 comprising administering to said mammal in need thereof a therapeutically effective amount of said substance or composition.102. A substance or composition for use in a method for treating a disease associated with unwanted activity of Her-2 sheddase, growth factor sheddases, or cytokine sheddases in a mammalian subject, said substance or composition comprising a compound of claim 1, and said method comprising administering to said mammal in need thereof a therapeutically effective amount of said substance or composition.103. A substance or composition for use in a method for treating a disease associated with activity of Her-2 sheddase in a mammal, said substance or composition comprising a compound according to claim 1, and said method comprising administering to said mammal a therapeutically effective amount of said substance or composition.104. A substance or composition for use in a method of treatment of claim 103, wherein said disease is cancer.105. A substance or composition for use in a method of treatment of claim 104, wherein said cancer is breast cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, colon cancer, gastric cancer, pancreatic cancer or glioma.106. A substance or composition for use in a method for treating a disease associated with unwanted ADAMI10, ADAMIS5, or ADAMI7 activity in a mammalian subject, said substance or composition comprising a compound of claim 1, and said method comprising administering to said mammal in need thereof a therapeutically effective amount of said substance or composition.107. A compound of any one of claims | to 83, substantially as herein described and illustrated.108. A composition of claim 84, substantially as herein described and illustrated. AMENDED SHEET \. PCT/US2004/012672109. Use of any one of claims 85 to 95, substantially as herein described and illustrated.110. A substance or composition for use in a method of treatment of any one of 5S claims 96 to 106, substantially as herein described and illustrated... 111. A new compound, a new composition, a new use of a compound of claim 1, or a substance or composition for a new use in a method of treatment, substantially as herein described. AMENDED SHEET \
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