NZ518094A - Process for preparing N-acylamino compounds - Google Patents
Process for preparing N-acylamino compoundsInfo
- Publication number
- NZ518094A NZ518094A NZ518094A NZ51809496A NZ518094A NZ 518094 A NZ518094 A NZ 518094A NZ 518094 A NZ518094 A NZ 518094A NZ 51809496 A NZ51809496 A NZ 51809496A NZ 518094 A NZ518094 A NZ 518094A
- Authority
- NZ
- New Zealand
- Prior art keywords
- group
- independently selected
- optionally
- substituted
- mimosa
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 37
- 150000001875 compounds Chemical class 0.000 claims description 431
- 235000011468 Albizia julibrissin Nutrition 0.000 claims description 409
- 241001070944 Mimosa Species 0.000 claims description 409
- 125000000217 alkyl group Chemical group 0.000 claims description 206
- 125000004122 cyclic group Chemical group 0.000 claims description 192
- 238000000034 method Methods 0.000 claims description 141
- -1 ethylenedioxy acetal Chemical class 0.000 claims description 139
- 239000000203 mixture Substances 0.000 claims description 123
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 112
- 125000000623 heterocyclic group Chemical group 0.000 claims description 101
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 64
- 125000003118 aryl group Chemical group 0.000 claims description 61
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 58
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 43
- 230000008569 process Effects 0.000 claims description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 35
- 201000010099 disease Diseases 0.000 claims description 33
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 31
- 125000004432 carbon atom Chemical group C* 0.000 claims description 27
- 230000001404 mediated effect Effects 0.000 claims description 27
- 125000005605 benzo group Chemical group 0.000 claims description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 25
- 125000006413 ring segment Chemical group 0.000 claims description 22
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 238000001727 in vivo Methods 0.000 claims description 20
- 102000004190 Enzymes Human genes 0.000 claims description 16
- 108090000790 Enzymes Proteins 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 238000000338 in vitro Methods 0.000 claims description 14
- 230000002401 inhibitory effect Effects 0.000 claims description 14
- 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 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 238000012360 testing method Methods 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 239000002516 radical scavenger Substances 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- 230000000269 nucleophilic effect Effects 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 8
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 7
- 239000012298 atmosphere Substances 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 7
- LAOZSCRCYVBSJA-UHFFFAOYSA-N 5,5-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CC1(C)C(=O)NC(=O)NC1=O LAOZSCRCYVBSJA-UHFFFAOYSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 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
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- KAHVZNKZQFSBFW-UHFFFAOYSA-N n-methyl-n-trimethylsilylmethanamine Chemical compound CN(C)[Si](C)(C)C KAHVZNKZQFSBFW-UHFFFAOYSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- BADXJIPKFRBFOT-UHFFFAOYSA-N dimedone Chemical group CC1(C)CC(=O)CC(=O)C1 BADXJIPKFRBFOT-UHFFFAOYSA-N 0.000 claims description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 3
- 150000001735 carboxylic acids Chemical class 0.000 claims 2
- 230000003301 hydrolyzing effect Effects 0.000 claims 2
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 claims 1
- 238000010276 construction Methods 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 61
- AUHBCNJHXCDLMK-UHFFFAOYSA-N diazepine-1-carboxamide Chemical class NC(=O)N1C=CC=CC=N1 AUHBCNJHXCDLMK-UHFFFAOYSA-N 0.000 abstract description 6
- 108090000426 Caspase-1 Proteins 0.000 abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 206
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 194
- 102000003810 Interleukin-18 Human genes 0.000 description 139
- 108090000171 Interleukin-18 Proteins 0.000 description 139
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 119
- 239000000243 solution Substances 0.000 description 109
- 125000001424 substituent group Chemical group 0.000 description 93
- 210000004027 cell Anatomy 0.000 description 91
- 239000007787 solid Substances 0.000 description 77
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 64
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 62
- 238000005160 1H NMR spectroscopy Methods 0.000 description 57
- 241000699670 Mus sp. Species 0.000 description 56
- 238000005481 NMR spectroscopy Methods 0.000 description 54
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 51
- 125000001544 thienyl group Chemical group 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
- 101150041968 CDC13 gene Proteins 0.000 description 48
- 235000019439 ethyl acetate Nutrition 0.000 description 48
- 125000001624 naphthyl group Chemical group 0.000 description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 239000002158 endotoxin Substances 0.000 description 40
- 229920006008 lipopolysaccharide Polymers 0.000 description 38
- 238000003556 assay Methods 0.000 description 37
- 125000001041 indolyl group Chemical group 0.000 description 37
- 238000003818 flash chromatography Methods 0.000 description 35
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 34
- 125000004076 pyridyl group Chemical group 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 125000003226 pyrazolyl group Chemical group 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
- 125000001113 thiadiazolyl group Chemical group 0.000 description 31
- 125000000335 thiazolyl group Chemical group 0.000 description 31
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- 125000000842 isoxazolyl group Chemical group 0.000 description 22
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- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/12—1,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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US08/575,641 US6008217A (en) | 1995-12-20 | 1995-12-20 | Inhibitors of interleukin-1β converting enzyme |
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US08/712,878 US5985863A (en) | 1996-09-12 | 1996-09-12 | Compositions and methods for decreasing IGIF and IFN-γ production by administering an ICE inhibitor |
US3149596P | 1996-11-26 | 1996-11-26 | |
US08/761,483 US6204261B1 (en) | 1995-12-20 | 1996-12-06 | Inhibitors of interleukin-1β Converting enzyme inhibitors |
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US6204261B1 (en) * | 1995-12-20 | 2001-03-20 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1β Converting enzyme inhibitors |
US6420522B1 (en) * | 1995-06-05 | 2002-07-16 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1β converting enzyme |
US6200969B1 (en) | 1996-09-12 | 2001-03-13 | Idun Pharmaceuticals, Inc. | Inhibition of apoptosis using interleukin-1β-converting enzyme (ICE)/CED-3 family inhibitors |
US6610683B2 (en) | 1996-09-12 | 2003-08-26 | Idun Pharmaceuticals, Inc. | Treatment of infectious disease using interleukin-1β-converting enzyme (ICE)/CED-3 family inhibitors |
US6531467B2 (en) | 1996-09-12 | 2003-03-11 | Idun Pharmaceuticals, Inc. | Inhibition of inflammation using interleukin-1β-converting enzyme (ICE)/CED-3 family inhibitors |
IL129026A0 (en) | 1996-10-11 | 2000-02-17 | Warner Lambert Co | Sulfonamide interleukin-1beta converting enzyme inhibitors |
JP2001502330A (ja) * | 1996-10-11 | 2001-02-20 | ワーナー―ランバート・コンパニー | スルホンアミド置換アスパラギン酸インターロイキン―1β変換酵素阻害剤 |
US5919790A (en) * | 1996-10-11 | 1999-07-06 | Warner-Lambert Company | Hydroxamate inhibitors of interleukin-1β converting enzyme |
CA2274250A1 (en) | 1996-12-06 | 1998-06-11 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1.beta. converting enzyme |
EP1466921A1 (en) * | 1996-12-06 | 2004-10-13 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1 beta converting enzyme |
FR2766188B1 (fr) * | 1997-07-15 | 2000-02-11 | Hoechst Marion Roussel Inc | Nouveau procede de preparation de derives amines d'alkyloxy furanone, composes issus de ce procede et utilisation de ces composes |
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- 1998-06-19 MX MX9805016A patent/MX9805016A/es unknown
- 1998-07-13 BG BG102624A patent/BG64465B1/bg unknown
- 1998-07-13 BG BG108927A patent/BG108927A/en unknown
-
1999
- 1999-09-21 US US09/400,639 patent/US6258948B1/en not_active Expired - Fee Related
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2001
- 2001-01-31 US US09/773,477 patent/US6423840B1/en not_active Expired - Fee Related
-
2002
- 2002-01-28 US US10/058,522 patent/US20030225269A1/en not_active Abandoned
- 2002-10-21 JP JP2002306094A patent/JP2003137896A/ja not_active Withdrawn
-
2004
- 2004-11-29 US US10/999,865 patent/US20050143436A1/en not_active Abandoned
-
2007
- 2007-01-18 US US11/655,938 patent/US7790713B2/en not_active Expired - Fee Related
-
2008
- 2008-06-18 JP JP2008159803A patent/JP2008285493A/ja not_active Withdrawn
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2010
- 2010-05-24 US US12/786,221 patent/US8119631B2/en not_active Expired - Fee Related
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PSEA | Patent sealed | ||
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RENW | Renewal (renewal fees accepted) | ||
EXPY | Patent expired |