CA2432908A1 - Diamines as modulators of chemokine receptor activity - Google Patents
Diamines as modulators of chemokine receptor activity Download PDFInfo
- Publication number
- CA2432908A1 CA2432908A1 CA002432908A CA2432908A CA2432908A1 CA 2432908 A1 CA2432908 A1 CA 2432908A1 CA 002432908 A CA002432908 A CA 002432908A CA 2432908 A CA2432908 A CA 2432908A CA 2432908 A1 CA2432908 A1 CA 2432908A1
- Authority
- CA
- Canada
- Prior art keywords
- amino
- methyl
- substituted
- crr
- trifluoromethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000000694 effects Effects 0.000 title claims description 14
- 102000009410 Chemokine receptor Human genes 0.000 title claims description 11
- 108050000299 Chemokine receptor Proteins 0.000 title claims description 11
- 150000004985 diamines Chemical class 0.000 title description 11
- 101710155857 C-C motif chemokine 2 Proteins 0.000 claims abstract description 56
- 102100021943 C-C motif chemokine 2 Human genes 0.000 claims abstract description 56
- 150000003839 salts Chemical group 0.000 claims abstract description 21
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 15
- 208000006673 asthma Diseases 0.000 claims abstract description 14
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 14
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 7
- -1 cyclic acetal Chemical class 0.000 claims description 434
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 308
- 125000000217 alkyl group Chemical group 0.000 claims description 281
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 276
- 238000000034 method Methods 0.000 claims description 218
- 125000002837 carbocyclic group Chemical group 0.000 claims description 209
- 150000001875 compounds Chemical class 0.000 claims description 188
- 125000005842 heteroatom Chemical group 0.000 claims description 180
- 229910052717 sulfur Inorganic materials 0.000 claims description 159
- 229910052760 oxygen Inorganic materials 0.000 claims description 158
- 125000003342 alkenyl group Chemical group 0.000 claims description 148
- 125000000304 alkynyl group Chemical group 0.000 claims description 147
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 134
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 117
- 125000000623 heterocyclic group Chemical group 0.000 claims description 102
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 96
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 86
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 75
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 74
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 73
- 229910052731 fluorine Inorganic materials 0.000 claims description 70
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 69
- 229910052794 bromium Inorganic materials 0.000 claims description 69
- 229910052740 iodine Inorganic materials 0.000 claims description 64
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 61
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 53
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 53
- 229910052801 chlorine Inorganic materials 0.000 claims description 52
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 50
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 43
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 41
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 39
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 37
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 36
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
- 125000002981 3-(trifluoromethyl)benzoyl group Chemical group FC(C=1C=C(C(=O)*)C=CC1)(F)F 0.000 claims description 33
- 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 33
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 32
- 125000004076 pyridyl group Chemical group 0.000 claims description 31
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 29
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 28
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 28
- 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 27
- 125000001041 indolyl group Chemical group 0.000 claims description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 23
- 125000001544 thienyl group Chemical group 0.000 claims description 23
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 22
- 125000004429 atom Chemical group 0.000 claims description 22
- 150000003951 lactams Chemical group 0.000 claims description 22
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 22
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 21
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 21
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 21
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 21
- 125000002541 furyl group Chemical group 0.000 claims description 21
- 125000002883 imidazolyl group Chemical group 0.000 claims description 21
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 21
- 125000002971 oxazolyl group Chemical group 0.000 claims description 21
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 21
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 21
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 21
- 125000000335 thiazolyl group Chemical group 0.000 claims description 21
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 19
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 18
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 18
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 17
- 102000019034 Chemokines Human genes 0.000 claims description 15
- 108010012236 Chemokines Proteins 0.000 claims description 15
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 14
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 14
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 14
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 14
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 14
- 125000003386 piperidinyl group Chemical group 0.000 claims description 14
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 12
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 12
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 12
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 11
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 claims description 10
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 claims description 10
- 102100032366 C-C motif chemokine 7 Human genes 0.000 claims description 10
- 101710155834 C-C motif chemokine 7 Proteins 0.000 claims description 10
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 9
- 102100023702 C-C motif chemokine 13 Human genes 0.000 claims description 9
- 101710112613 C-C motif chemokine 13 Proteins 0.000 claims description 9
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 9
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- 206010001889 Alveolitis Diseases 0.000 claims description 8
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 8
- 125000005512 benztetrazolyl group Chemical group 0.000 claims description 8
- 206010009887 colitis Diseases 0.000 claims description 8
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 claims description 8
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 claims description 8
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 8
- 101710155833 C-C motif chemokine 8 Proteins 0.000 claims description 7
- 102100034871 C-C motif chemokine 8 Human genes 0.000 claims description 7
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 7
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 claims description 7
- VKEIRGOCEUAYTA-FQEVSTJZSA-N n-[2-[[(2s)-3-[(3-amino-4-methylphenyl)methylamino]-1-(tert-butylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(N)C(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 VKEIRGOCEUAYTA-FQEVSTJZSA-N 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 230000003589 nefrotoxic effect Effects 0.000 claims description 7
- 201000008383 nephritis Diseases 0.000 claims description 7
- 231100000381 nephrotoxic Toxicity 0.000 claims description 7
- 210000002966 serum Anatomy 0.000 claims description 7
- 101000978374 Mus musculus C-C motif chemokine 12 Proteins 0.000 claims description 6
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 6
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
- 239000005977 Ethylene Chemical group 0.000 claims description 5
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 101100054666 Streptomyces halstedii sch3 gene Chemical group 0.000 claims description 5
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 5
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 5
- IUGZYYHEZQQRHP-SFHVURJKSA-N (2s)-3-[(2,4-dimethylphenyl)methylamino]-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoic acid Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(O)=O)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 IUGZYYHEZQQRHP-SFHVURJKSA-N 0.000 claims description 4
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- USMGPXSMSPNEMF-DQEYMECFSA-N 2-(tert-butylamino)-n-[2-[[(2s,3s)-1-[(2,4-dimethylphenyl)methylamino]-3-hydroxyhexan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C([C@@H]([C@@H](O)CCC)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)NC(C)(C)C)NCC1=CC=C(C)C=C1C USMGPXSMSPNEMF-DQEYMECFSA-N 0.000 claims description 4
- PPUSECQFZJYKGS-SFHVURJKSA-N 2-amino-n-[2-[[(2s)-1-amino-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(N)=O)NC(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1N PPUSECQFZJYKGS-SFHVURJKSA-N 0.000 claims description 4
- REYPFIVSWQHOLV-FCHUYYIVSA-N 2-amino-n-[2-[[(2s,3r)-1-[(2,4-dimethylphenyl)methylamino]-3-hydroxyhexan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C([C@@H]([C@H](O)CCC)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)N)NCC1=CC=C(C)C=C1C REYPFIVSWQHOLV-FCHUYYIVSA-N 0.000 claims description 4
- ARWNEEWQGNYGBR-VXKWHMMOSA-N 2-amino-n-[2-[[(2s,3s)-1-[(4-ethylphenyl)methylamino]-3-hydroxyhexan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C([C@@H]([C@@H](O)CCC)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)N)NCC1=CC=C(CC)C=C1 ARWNEEWQGNYGBR-VXKWHMMOSA-N 0.000 claims description 4
- USZUJOVBEITWKE-GOTSBHOMSA-N 2-amino-n-[2-[[(2s,3s)-1-[[4-(dimethylamino)-2-methylphenyl]methylamino]-3-hydroxyhexan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C([C@@H]([C@@H](O)CCC)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)N)NCC1=CC=C(N(C)C)C=C1C USZUJOVBEITWKE-GOTSBHOMSA-N 0.000 claims description 4
- NAXALRVAGKOJOY-FCHUYYIVSA-N 3-amino-n-[2-[[(2s,3r)-1-[(2,4-dimethylphenyl)methylamino]-3-hydroxyhexan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C([C@@H]([C@H](O)CCC)NC(=O)CNC(=O)C=1C=C(C=C(N)C=1)C(F)(F)F)NCC1=CC=C(C)C=C1C NAXALRVAGKOJOY-FCHUYYIVSA-N 0.000 claims description 4
- NAXALRVAGKOJOY-VXKWHMMOSA-N 3-amino-n-[2-[[(2s,3s)-1-[(2,4-dimethylphenyl)methylamino]-3-hydroxyhexan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C([C@@H]([C@@H](O)CCC)NC(=O)CNC(=O)C=1C=C(C=C(N)C=1)C(F)(F)F)NCC1=CC=C(C)C=C1C NAXALRVAGKOJOY-VXKWHMMOSA-N 0.000 claims description 4
- 102000004497 CCR2 Receptors Human genes 0.000 claims description 4
- 108010017312 CCR2 Receptors Proteins 0.000 claims description 4
- OBTXHENLXXGGFV-IBGZPJMESA-N methyl (2s)-2-[[2-[[2-amino-5-(trifluoromethyl)benzoyl]amino]acetyl]amino]-3-[(2,4-dimethylphenyl)methylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)N)NCC1=CC=C(C)C=C1C OBTXHENLXXGGFV-IBGZPJMESA-N 0.000 claims description 4
- UVNPCXNRDPHVII-IBGZPJMESA-N methyl (2s)-3-(1h-indol-3-ylmethylamino)-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound N([C@@H](CNCC=1C2=CC=CC=C2NC=1)C(=O)OC)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 UVNPCXNRDPHVII-IBGZPJMESA-N 0.000 claims description 4
- OXJASFHPELQTQM-QFIPXVFZSA-N methyl (2s)-3-[(2,4-dimethylphenyl)methylamino]-2-[[2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)NC(=O)OC(C)(C)C)NCC1=CC=C(C)C=C1C OXJASFHPELQTQM-QFIPXVFZSA-N 0.000 claims description 4
- OIGPUPVQQUOVAP-KRWDZBQOSA-N methyl (2s)-3-[(4-bromophenyl)methylamino]-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(Br)C=C1 OIGPUPVQQUOVAP-KRWDZBQOSA-N 0.000 claims description 4
- BJWBULQNXBITAU-KRWDZBQOSA-N methyl (2s)-3-[(4-chlorophenyl)methylamino]-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(Cl)C=C1 BJWBULQNXBITAU-KRWDZBQOSA-N 0.000 claims description 4
- ZBIJSTZDZCPBBF-AHWVRZQESA-N n-[2-[[(1s,2s)-3-[(2,4-dimethylphenyl)methylamino]-1-hydroxy-1-phenylpropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H]([C@@H](O)C=1C=CC=CC=1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZBIJSTZDZCPBBF-AHWVRZQESA-N 0.000 claims description 4
- IPMQGPCHTHBTNQ-RUZDIDTESA-N n-[2-[[(2r)-1-[(2,4-dimethylphenyl)methylamino]-3-phenylpropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@H](NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)CC1=CC=CC=C1 IPMQGPCHTHBTNQ-RUZDIDTESA-N 0.000 claims description 4
- KEUFKEFYFXTLDW-GOSISDBHSA-N n-[2-[[(2r)-1-amino-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@H](C(N)=O)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KEUFKEFYFXTLDW-GOSISDBHSA-N 0.000 claims description 4
- WBXYZOVCGSOHBB-VWLOTQADSA-N n-[2-[[(2s)-1-(benzylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NCC=1C=CC=CC=1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 WBXYZOVCGSOHBB-VWLOTQADSA-N 0.000 claims description 4
- UAHNSQXDPXCBOR-FQEVSTJZSA-N n-[2-[[(2s)-1-(dimethylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)N(C)C)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C UAHNSQXDPXCBOR-FQEVSTJZSA-N 0.000 claims description 4
- KNRXZXWLFHXTFX-IBGZPJMESA-N n-[2-[[(2s)-1-[(2,4-dimethylphenyl)methylamino]-3-hydroxypropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](CO)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KNRXZXWLFHXTFX-IBGZPJMESA-N 0.000 claims description 4
- STJUEHWSZYBOFD-SFHVURJKSA-N n-[2-[[(2s)-1-amino-3-(1h-indol-3-ylmethylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H](CNCC=1C2=CC=CC=C2NC=1)C(=O)N)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 STJUEHWSZYBOFD-SFHVURJKSA-N 0.000 claims description 4
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- HZJNYHOLJLBWIK-GOTSBHOMSA-N 2-amino-n-[2-[[(2s,3s)-1-[(2,4-dimethylphenyl)methylamino]-3-hydroxy-5-methylhexan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C([C@@H]([C@@H](O)CC(C)C)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)N)NCC1=CC=C(C)C=C1C HZJNYHOLJLBWIK-GOTSBHOMSA-N 0.000 claims description 2
- KLPGONLPFCFALU-GOTSBHOMSA-N 2-amino-n-[2-[[(2s,3s)-1-[(2,4-dimethylphenyl)methylamino]-3-methoxyhexan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C([C@@H]([C@@H](OC)CCC)NC(=O)CNC(=O)C=1C(=CC=C(C=1)C(F)(F)F)N)NCC1=CC=C(C)C=C1C KLPGONLPFCFALU-GOTSBHOMSA-N 0.000 claims description 2
- SZOLNJSZQCIUGQ-UHFFFAOYSA-N 2-amino-n-[2-[[1-[[(2,4-dimethylphenyl)methylamino]methyl]cyclopropyl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNCC1(NC(=O)CNC(=O)C=2C(=CC=C(C=2)C(F)(F)F)N)CC1 SZOLNJSZQCIUGQ-UHFFFAOYSA-N 0.000 claims description 2
- UAJQFDSDEGNECB-VWLOTQADSA-N 3-(butylamino)-n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(NCCCC)=CC(C(=O)NCC(=O)N[C@@H](CNCC=2C(=CC(C)=CC=2)C)C(=O)NC(C)(C)C)=C1 UAJQFDSDEGNECB-VWLOTQADSA-N 0.000 claims description 2
- ZEYAHFUIXMLOML-NRFANRHFSA-N 3-amino-n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(N)=CC(C(F)(F)F)=C1 ZEYAHFUIXMLOML-NRFANRHFSA-N 0.000 claims description 2
- WGVMZSAOQQDEFJ-QFIPXVFZSA-N 3-amino-n-[2-[[(2s)-1-(tert-butylamino)-4-[(2,4-dimethylphenyl)methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNCC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(N)=CC(C(F)(F)F)=C1 WGVMZSAOQQDEFJ-QFIPXVFZSA-N 0.000 claims description 2
- LWEYMQQVLUOWLP-QFIPXVFZSA-N 3-amino-n-[2-[[(2s)-1-(tert-butylamino)-4-[(4-ethylphenyl)methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound C1=CC(CC)=CC=C1CNCC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(N)=CC(C(F)(F)F)=C1 LWEYMQQVLUOWLP-QFIPXVFZSA-N 0.000 claims description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 208000031886 HIV Infections Diseases 0.000 claims description 2
- 208000037357 HIV infectious disease Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 206010037660 Pyrexia Diseases 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- ZXYFWDUOJFDXFE-QHCPKHFHSA-N ethyl n-[3-[[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]-5-(trifluoromethyl)phenyl]carbamate Chemical compound FC(F)(F)C1=CC(NC(=O)OCC)=CC(C(=O)NCC(=O)N[C@@H](CNCC=2C(=CC(C)=CC=2)C)C(=O)NC(C)(C)C)=C1 ZXYFWDUOJFDXFE-QHCPKHFHSA-N 0.000 claims description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 2
- SQFGQHITJDKNEK-LJQANCHMSA-N methyl (2r)-2-[(2,4-dimethylphenyl)methylamino]-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound C([C@H](C(=O)OC)NCC=1C(=CC(C)=CC=1)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 SQFGQHITJDKNEK-LJQANCHMSA-N 0.000 claims description 2
- VFBXQEUUDUQOBO-LJQANCHMSA-N methyl (2r)-3-[(2,4-dimethylphenyl)methylamino]-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound C([C@H](C(=O)OC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C VFBXQEUUDUQOBO-LJQANCHMSA-N 0.000 claims description 2
- ZJPSEVOKBYZNIC-INIZCTEOSA-N methyl (2s)-3-(1,3-benzodioxol-5-ylmethylamino)-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound N([C@@H](CNCC=1C=C2OCOC2=CC=1)C(=O)OC)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZJPSEVOKBYZNIC-INIZCTEOSA-N 0.000 claims description 2
- VFBXQEUUDUQOBO-IBGZPJMESA-N methyl (2s)-3-[(2,4-dimethylphenyl)methylamino]-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C VFBXQEUUDUQOBO-IBGZPJMESA-N 0.000 claims description 2
- LWOYRAWIPWSLMT-FQEVSTJZSA-N methyl (2s)-4-[(2,4-dimethylphenyl)methylamino]-2-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]butanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)CNCC1=CC=C(C)C=C1C LWOYRAWIPWSLMT-FQEVSTJZSA-N 0.000 claims description 2
- ZBIJSTZDZCPBBF-AZGAKELHSA-N n-[2-[[(1r,2s)-3-[(2,4-dimethylphenyl)methylamino]-1-hydroxy-1-phenylpropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H]([C@H](O)C=1C=CC=CC=1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZBIJSTZDZCPBBF-AZGAKELHSA-N 0.000 claims description 2
- LHLMXUIIDZMSKK-OAQYLSRUSA-N n-[2-[[(2r)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 LHLMXUIIDZMSKK-OAQYLSRUSA-N 0.000 claims description 2
- KNRXZXWLFHXTFX-LJQANCHMSA-N n-[2-[[(2r)-1-[(2,4-dimethylphenyl)methylamino]-3-hydroxypropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@H](CO)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KNRXZXWLFHXTFX-LJQANCHMSA-N 0.000 claims description 2
- GSINUEDWKBKBBC-HXUWFJFHSA-N n-[2-[[(2r)-2-[(2,4-dimethylphenyl)methylamino]-3-(ethylamino)-3-oxopropyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@H](C(=O)NCC)NCC=1C(=CC(C)=CC=1)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GSINUEDWKBKBBC-HXUWFJFHSA-N 0.000 claims description 2
- JQTQSHYGYDYRLA-HXUWFJFHSA-N n-[2-[[(2r)-3-[(2,4-dimethylphenyl)methylamino]-1-(ethylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@H](C(=O)NCC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C JQTQSHYGYDYRLA-HXUWFJFHSA-N 0.000 claims description 2
- KNCWDGUPSSDGDF-OAQYLSRUSA-N n-[2-[[(2r)-3-[(2,4-dimethylphenyl)methylamino]-1-[(1-hydroxy-2-methylpropan-2-yl)amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@H](C(=O)NC(C)(C)CO)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KNCWDGUPSSDGDF-OAQYLSRUSA-N 0.000 claims description 2
- SOOBKLCQZMCQOI-YSYXNDDBSA-N n-[2-[[(2s)-1-(butan-2-ylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NC(C)CC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C SOOBKLCQZMCQOI-YSYXNDDBSA-N 0.000 claims description 2
- QAPFGTQCICZVMD-DEOSSOPVSA-N n-[2-[[(2s)-1-(cyclohexylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC1CCCCC1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 QAPFGTQCICZVMD-DEOSSOPVSA-N 0.000 claims description 2
- GKHDPJJGUXXRIQ-QHCPKHFHSA-N n-[2-[[(2s)-1-(cyclopentylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC1CCCC1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GKHDPJJGUXXRIQ-QHCPKHFHSA-N 0.000 claims description 2
- KLSWMLOBDUZIGN-NRFANRHFSA-N n-[2-[[(2s)-1-(cyclopropylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC1CC1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KLSWMLOBDUZIGN-NRFANRHFSA-N 0.000 claims description 2
- GZJMMFZYCCQPPI-QFIPXVFZSA-N n-[2-[[(2s)-1-(cyclopropylmethylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NCC1CC1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GZJMMFZYCCQPPI-QFIPXVFZSA-N 0.000 claims description 2
- UBFRIZPGWMKHSQ-IBGZPJMESA-N n-[2-[[(2s)-1-(tert-butylamino)-1-oxo-3-[[4-(trifluoromethoxy)phenyl]methylamino]propan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(OC(F)(F)F)C=C1 UBFRIZPGWMKHSQ-IBGZPJMESA-N 0.000 claims description 2
- PVLOUXXXZOSIQQ-QFIPXVFZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methyl-methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H](CN(C)CC=1C(=CC(C)=CC=1)C)C(=O)NC(C)(C)C)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 PVLOUXXXZOSIQQ-QFIPXVFZSA-N 0.000 claims description 2
- JHAFSIDCLSAERO-VWLOTQADSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(2-methylpropylamino)-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(NCC(C)C)=CC(C(=O)NCC(=O)N[C@@H](CNCC=2C(=CC(C)=CC=2)C)C(=O)NC(C)(C)C)=C1 JHAFSIDCLSAERO-VWLOTQADSA-N 0.000 claims description 2
- UGCKLKBKXFXRGZ-QFIPXVFZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(methylamino)-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(NC)=CC(C(=O)NCC(=O)N[C@@H](CNCC=2C(=CC(C)=CC=2)C)C(=O)NC(C)(C)C)=C1 UGCKLKBKXFXRGZ-QFIPXVFZSA-N 0.000 claims description 2
- YZACLYAPEALTDY-DEOSSOPVSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(propylamino)-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(NCCC)=CC(C(=O)NCC(=O)N[C@@H](CNCC=2C(=CC(C)=CC=2)C)C(=O)NC(C)(C)C)=C1 YZACLYAPEALTDY-DEOSSOPVSA-N 0.000 claims description 2
- CIRPPSNKYVUJNF-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethoxy)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(OC(F)(F)F)=C1 CIRPPSNKYVUJNF-NRFANRHFSA-N 0.000 claims description 2
- XWZSYNVMIJQPAE-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2-ethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CCC1=CC=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 XWZSYNVMIJQPAE-NRFANRHFSA-N 0.000 claims description 2
- SBZAYKSXVNAATR-FQEVSTJZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2-methylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 SBZAYKSXVNAATR-FQEVSTJZSA-N 0.000 claims description 2
- GYWKVWRKXAGCMG-QFIPXVFZSA-N n-[2-[[(2s)-1-(tert-butylamino)-4-[(2,4-dimethylphenyl)methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNCC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GYWKVWRKXAGCMG-QFIPXVFZSA-N 0.000 claims description 2
- KCLTXFAVDKVUKK-QFIPXVFZSA-N n-[2-[[(2s)-1-(tert-butylamino)-4-[(4-ethylphenyl)methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(CC)=CC=C1CNCC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KCLTXFAVDKVUKK-QFIPXVFZSA-N 0.000 claims description 2
- PPJQDLFXARGOSQ-IBGZPJMESA-N n-[2-[[(2s)-1-amino-4-[(2,4-dimethylphenyl)methylamino]-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNCC[C@@H](C(N)=O)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 PPJQDLFXARGOSQ-IBGZPJMESA-N 0.000 claims description 2
- MIDCFBUVBVHNTM-QFIPXVFZSA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-(2-methylbutan-2-ylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NC(C)(C)CC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C MIDCFBUVBVHNTM-QFIPXVFZSA-N 0.000 claims description 2
- SVGYEBVMEHPHCS-QFIPXVFZSA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-(2-methylpropylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NCC(C)C)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C SVGYEBVMEHPHCS-QFIPXVFZSA-N 0.000 claims description 2
- JQTQSHYGYDYRLA-FQEVSTJZSA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-(ethylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NCC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C JQTQSHYGYDYRLA-FQEVSTJZSA-N 0.000 claims description 2
- KNCWDGUPSSDGDF-NRFANRHFSA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-[(1-hydroxy-2-methylpropan-2-yl)amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)CO)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KNCWDGUPSSDGDF-NRFANRHFSA-N 0.000 claims description 2
- BBDNWXOVFUSDDU-NRFANRHFSA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-[(1-methylcyclopropyl)amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC1(C)CC1)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 BBDNWXOVFUSDDU-NRFANRHFSA-N 0.000 claims description 2
- BRRZJXMTXJQZFT-NRFANRHFSA-N n-[2-[[(2s)-3-[(2,4-dimethylphenyl)methylamino]-1-oxo-1-(propan-2-ylamino)propan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NC(C)C)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)NCC1=CC=C(C)C=C1C BRRZJXMTXJQZFT-NRFANRHFSA-N 0.000 claims description 2
- HHCXTVSNSLXIJU-QFIPXVFZSA-N n-[2-[[(2s)-4-[(2,4-dimethylphenyl)methyl-methylamino]-1-(ethylamino)-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NCC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)CN(C)CC1=CC=C(C)C=C1C HHCXTVSNSLXIJU-QFIPXVFZSA-N 0.000 claims description 2
- IZWURKUUGCCQGO-NRFANRHFSA-N n-[2-[[(2s)-4-[(2,4-dimethylphenyl)methylamino]-1-(ethylamino)-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NCC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)CNCC1=CC=C(C)C=C1C IZWURKUUGCCQGO-NRFANRHFSA-N 0.000 claims description 2
- BGJXTHUPBFNGMD-QFIPXVFZSA-N n-[2-[[(2s)-5-[(2,4-dimethylphenyl)methylamino]-1-(ethylamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C(=O)NCC)NC(=O)CNC(=O)C=1C=C(C=CC=1)C(F)(F)F)CCNCC1=CC=C(C)C=C1C BGJXTHUPBFNGMD-QFIPXVFZSA-N 0.000 claims description 2
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- ADDSRJLIAIYEIZ-VWLOTQADSA-N tert-butyl n-[2-[[2-[[(1s)-2-[(2,4-dimethylphenyl)methylamino]-1-(1-hydroxycyclopentyl)ethyl]amino]-2-oxoethyl]carbamoyl]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C1(O)CCCC1)NC(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1NC(=O)OC(C)(C)C ADDSRJLIAIYEIZ-VWLOTQADSA-N 0.000 claims description 2
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- XQZGMUFOLNFTJY-QHCPKHFHSA-N tert-butyl n-[2-[[2-[[(2s)-1-[(2,4-dimethylphenyl)methylamino]-3-hydroxy-3-methylbutan-2-yl]amino]-2-oxoethyl]carbamoyl]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(C)(C)O)NC(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1NC(=O)OC(C)(C)C XQZGMUFOLNFTJY-QHCPKHFHSA-N 0.000 claims description 2
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- 125000000686 lactone group Chemical group 0.000 claims 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 8
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 5
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 2
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- WNDBBJRVNVBRDI-NDEPHWFRSA-N 3-(benzylamino)-n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(NCC=2C=CC=CC=2)=CC(C(F)(F)F)=C1 WNDBBJRVNVBRDI-NDEPHWFRSA-N 0.000 claims 1
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- JMLLAWDCFALEEX-MHZLTWQESA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-2-(cyclohexylamino)-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(C(F)(F)F)=CC=C1NC1CCCCC1 JMLLAWDCFALEEX-MHZLTWQESA-N 0.000 claims 1
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- WECKWZIUSZAMKC-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethylsulfanyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(SC(F)(F)F)=C1 WECKWZIUSZAMKC-NRFANRHFSA-N 0.000 claims 1
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- CCCRXCYCHFZAEL-QFIPXVFZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-ethenyl-2-methylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(C=C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 CCCRXCYCHFZAEL-QFIPXVFZSA-N 0.000 claims 1
- QRPKNKZUXDIPJG-QFIPXVFZSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-ethyl-2-methylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC(CC)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 QRPKNKZUXDIPJG-QFIPXVFZSA-N 0.000 claims 1
- RBTPLFXLAYIKKD-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-ethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(CC)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 RBTPLFXLAYIKKD-NRFANRHFSA-N 0.000 claims 1
- TZUMZWROSICREM-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(4-methoxy-2,3-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=C(C)C(OC)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 TZUMZWROSICREM-NRFANRHFSA-N 0.000 claims 1
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- QGEFGPVWRJCFQP-UHFFFAOYSA-M magnesium;methanidylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1=CC=CC=C1 QGEFGPVWRJCFQP-UHFFFAOYSA-M 0.000 description 1
- QBNOPZJAURRQCE-UHFFFAOYSA-M magnesium;prop-1-yne;bromide Chemical compound [Mg+2].[Br-].CC#[C-] QBNOPZJAURRQCE-UHFFFAOYSA-M 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
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- 230000004048 modification Effects 0.000 description 1
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- 239000002808 molecular sieve Substances 0.000 description 1
- 108010065176 monocyte chemoattractant protein 1 (9-76) Proteins 0.000 description 1
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- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- QOMRENHPVPBXEW-NRFANRHFSA-N n-[2-[[(2s)-1-(tert-butylamino)-3-[(2,4-dimethylphenyl)methylamino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-3-[(2,2,2-trifluoroacetyl)amino]-5-(trifluoromethyl)benzamide Chemical compound CC1=CC(C)=CC=C1CNC[C@@H](C(=O)NC(C)(C)C)NC(=O)CNC(=O)C1=CC(NC(=O)C(F)(F)F)=CC(C(F)(F)F)=C1 QOMRENHPVPBXEW-NRFANRHFSA-N 0.000 description 1
- VSHPKTCPENWJED-UHFFFAOYSA-N n-[2-[[1-amino-2-[[(2,4-dimethylphenyl)methylamino]methyl]-1-oxobutan-2-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C=1C=CC(C(F)(F)F)=CC=1C(=O)NCC(=O)NC(C(N)=O)(CC)CNCC1=CC=C(C)C=C1C VSHPKTCPENWJED-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
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- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 208000012318 pareses Diseases 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical group C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
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- 229920002647 polyamide Polymers 0.000 description 1
- 125000003367 polycyclic group Polymers 0.000 description 1
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- 238000002360 preparation method Methods 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
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Classifications
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- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- 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
- C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Physical Education & Sports Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
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- Neurology (AREA)
- Diabetes (AREA)
- Crystallography & Structural Chemistry (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US25685500P | 2000-12-20 | 2000-12-20 | |
| US60/256,855 | 2000-12-20 | ||
| PCT/US2001/050619 WO2002050019A2 (en) | 2000-12-20 | 2001-12-20 | Diamines as modulators of chemokine receptor activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2432908A1 true CA2432908A1 (en) | 2002-06-27 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CA002432908A Abandoned CA2432908A1 (en) | 2000-12-20 | 2001-12-20 | Diamines as modulators of chemokine receptor activity |
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| Country | Link |
|---|---|
| US (2) | US6974836B2 (OSRAM) |
| EP (1) | EP1351924A2 (OSRAM) |
| JP (1) | JP2005506949A (OSRAM) |
| AR (1) | AR035720A1 (OSRAM) |
| AU (1) | AU2002241724A1 (OSRAM) |
| CA (1) | CA2432908A1 (OSRAM) |
| HU (1) | HUP0303540A2 (OSRAM) |
| WO (1) | WO2002050019A2 (OSRAM) |
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| AU2002241724A1 (en) | 2000-12-20 | 2002-07-01 | Bristol-Myers Squibb Company | Diamines as modulators of chemokine receptor activity |
| WO2002060859A2 (en) * | 2000-12-20 | 2002-08-08 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| WO2003075853A2 (en) | 2002-03-08 | 2003-09-18 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| TW200508224A (en) | 2003-02-12 | 2005-03-01 | Bristol Myers Squibb Co | Cyclic derivatives as modulators of chemokine receptor activity |
| WO2004071449A2 (en) * | 2003-02-12 | 2004-08-26 | Bristol-Myers Squibb Company | Lactams as modulators of chemokine receptor activity |
| JP2006521382A (ja) | 2003-03-28 | 2006-09-21 | イーライ リリー アンド カンパニー | Akt(プロテインキナーゼb)阻害剤 |
| US7291615B2 (en) | 2003-05-01 | 2007-11-06 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| US7230133B2 (en) * | 2003-05-01 | 2007-06-12 | Bristol-Myers Squibb Company | Malonamides and malonamide derivatives as modulators of chemokine receptor activity |
| US7317019B2 (en) * | 2003-08-21 | 2008-01-08 | Bristol Myers Squibb Co. | N-alkylated diaminopropane derivatives as modulators of chemokine receptor activity |
| US7863317B2 (en) * | 2003-08-21 | 2011-01-04 | Bristol-Myers Squibb Company | Lactams of alkylated acyclic diamine derivatives as modulators of chemokine receptor activity |
| US20050043392A1 (en) * | 2003-08-21 | 2005-02-24 | Carter Percy H. | Lactams of alkylated acyclic diamine derivatives as modulators of chemokine receptor activity |
| US7378409B2 (en) | 2003-08-21 | 2008-05-27 | Bristol-Myers Squibb Company | Substituted cycloalkylamine derivatives as modulators of chemokine receptor activity |
| US7163937B2 (en) * | 2003-08-21 | 2007-01-16 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| US20070073064A1 (en) * | 2003-10-08 | 2007-03-29 | Teijin Pharma Limited | Method for producing aminopyrrolidine derivatives and intermediate compounds |
| EP1689719A1 (en) | 2003-11-25 | 2006-08-16 | Eli Lilly And Company | 7-phenyl-isoquinoline-5-sulfonylamino derivatives as inhibitors of akt (proteinkinase b) |
| US7479496B2 (en) | 2004-02-19 | 2009-01-20 | Bristol-Myers Squibb Company | Substituted spiro azabicyclics as modulators of chemokine receptor activity |
| US7381738B2 (en) | 2004-02-19 | 2008-06-03 | Bristol-Myers Squibb Company | Substituted bicycloalkylamine derivatives as modulators of chemokine receptor activity |
| US7288563B2 (en) | 2004-02-19 | 2007-10-30 | Bristol-Myers Squibb Company | Substituted bicycloalkylamine derivatives as modulators of chemokine receptor activity |
| US7230022B2 (en) | 2004-02-19 | 2007-06-12 | Bristol-Myers Squibb Company | Substituted fused bicyclic amines as modulators of chemokine receptor activity |
| SI1771463T1 (sl) * | 2004-07-16 | 2008-06-30 | Lonza Ag | Postopek za sintezo peptidov |
| BRPI0517701A8 (pt) | 2004-11-10 | 2018-01-23 | Genzyme Corp | métodos de tratamento de diabetes mellitus |
| JP2008526861A (ja) * | 2005-01-06 | 2008-07-24 | メルク エンド カムパニー インコーポレーテッド | 炎症性障害を治療するための薬剤併用療法および医薬組成物 |
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| US7629351B2 (en) * | 2006-07-28 | 2009-12-08 | Bristol-Myers Squibb Company | N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino) pyrrolidin-1-yl)cyclohexyl)acetamide and other modulators of chemokine receptor activity, crystalline forms and process |
| US7671062B2 (en) * | 2006-07-28 | 2010-03-02 | Bristol-Myers Squibb Company | Modulators of chemokine receptor activity, crystalline forms and process |
| US7687508B2 (en) * | 2006-07-28 | 2010-03-30 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| US20080076120A1 (en) * | 2006-09-14 | 2008-03-27 | Millennium Pharmaceuticals, Inc. | Methods for the identification, evaluation and treatment of patients having CC-Chemokine receptor 2 (CCR-2) mediated disorders |
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| CA2701649C (en) | 2007-10-05 | 2016-05-24 | Genzyme Corporation | Method of treating polycystic kidney diseases with ceramide derivatives |
| CA2731685A1 (en) | 2008-07-28 | 2010-02-04 | Genzyme Corporation | Glucosylceramide synthase inhibition for the treatment of collapsing glomerulopathy and other glomerular disease |
| CN102271678B (zh) | 2008-10-03 | 2017-06-30 | 简詹姆公司 | 2‑酰胺基丙醇型葡糖神经酰胺合成酶抑制剂 |
| US8383812B2 (en) | 2009-10-13 | 2013-02-26 | Bristol-Myers Squibb Company | N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-A][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide, a dual modulator of chemokine receptor activity, crystalline forms and processes |
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| JP2867450B2 (ja) | 1989-08-17 | 1999-03-08 | 吉富製薬株式会社 | アルキレンビスアミド化合物 |
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| US6306840B1 (en) | 1995-01-23 | 2001-10-23 | Biogen, Inc. | Cell adhesion inhibitors |
| EP0731107A1 (en) | 1995-02-13 | 1996-09-11 | Takeda Chemical Industries, Ltd. | Production of aldehyde derivatives |
| EP0824543A1 (en) | 1995-05-10 | 1998-02-25 | Chiroscience Limited | Peptide compounds which inhibit metalloproteinase and tnf liberation, and their therapeutic use |
| US5710171A (en) | 1995-05-24 | 1998-01-20 | Merck & Co., Inc. | Bisphenyl inhibitors of farnesyl-protein transferase |
| TW438591B (en) | 1995-06-07 | 2001-06-07 | Arris Pharm Corp | Reversible cysteine protease inhibitors |
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| CZ287948B6 (cs) | 1995-06-22 | 2001-03-14 | Novo Nordisk A/S | Peptidový derivát uvolňující růstový hormon, farmaceutický prostředek s jeho obsahem a jejich použití |
| US6100423A (en) | 1995-08-30 | 2000-08-08 | G. D. Searle & Co. | Amino benzenepropanoic acid compounds and derivatives thereof |
| RO118290B1 (ro) | 1995-08-30 | 2003-04-30 | Gdsearle & Co | Derivati de fenilcarboniluree si compozitie farmaceutica |
| US5843904A (en) | 1995-12-20 | 1998-12-01 | Vertex Pharmaceuticals, Inc. | Inhibitors of interleukin-1βconverting enzyme |
| US6011052A (en) | 1996-04-30 | 2000-01-04 | Warner-Lambert Company | Pyrazolone derivatives as MCP-1 antagonists |
| CA2256492C (en) | 1996-05-20 | 2006-04-04 | Teijin Limited | Diarylalkyl cyclic diamine derivatives as chemokine receptor antagonists |
| JP2000516611A (ja) | 1996-08-14 | 2000-12-12 | ワーナー―ランバート・コンパニー | Mcp―1アンタゴニストとしての2―フェニルベンズイミダゾール誘導体 |
| GB9716656D0 (en) * | 1997-08-07 | 1997-10-15 | Zeneca Ltd | Chemical compounds |
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| US6150378A (en) | 1997-10-07 | 2000-11-21 | Cephalon, Inc. | Peptidyl-containing α-ketoamide cysteine and serine protease inhibitors |
| IL135488A0 (en) | 1997-11-18 | 2001-05-20 | Teijin Ltd | Cyclic amine derivatives |
| US6048861A (en) | 1997-12-17 | 2000-04-11 | Merck & Co., Inc. | Integrin receptor antagonists |
| US6028087A (en) | 1998-01-21 | 2000-02-22 | Smithkline Beecham Corporation | Platelet aggregation inhibiting compounds |
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| US6541208B1 (en) | 1998-03-17 | 2003-04-01 | University Of Maryland Biotechnology Institute | Diagnostic method for distinguishing HIV-associated dementia from other forms of dementia |
| EP2386565A3 (en) | 1999-01-12 | 2013-11-20 | Cambridge Enterprise Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
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| WO2000069815A1 (en) | 1999-05-13 | 2000-11-23 | Teijin Limited | Ureido-substituted cyclic amine derivatives and their use as drug |
| CA2373607A1 (en) | 1999-05-14 | 2000-11-23 | Bristol-Myers Squibb Pharma Research Labs, Inc. | Cyclic amine derivatives and their uses |
| WO2002060859A2 (en) | 2000-12-20 | 2002-08-08 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| AU2002241724A1 (en) | 2000-12-20 | 2002-07-01 | Bristol-Myers Squibb Company | Diamines as modulators of chemokine receptor activity |
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| WO2004071449A2 (en) | 2003-02-12 | 2004-08-26 | Bristol-Myers Squibb Company | Lactams as modulators of chemokine receptor activity |
| TW200508224A (en) | 2003-02-12 | 2005-03-01 | Bristol Myers Squibb Co | Cyclic derivatives as modulators of chemokine receptor activity |
| JP3655616B2 (ja) | 2003-03-19 | 2005-06-02 | ファナック株式会社 | 射出成形機 |
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| US20050043392A1 (en) | 2003-08-21 | 2005-02-24 | Carter Percy H. | Lactams of alkylated acyclic diamine derivatives as modulators of chemokine receptor activity |
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| US7317019B2 (en) | 2003-08-21 | 2008-01-08 | Bristol Myers Squibb Co. | N-alkylated diaminopropane derivatives as modulators of chemokine receptor activity |
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2005
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| WO2002050019A2 (en) | 2002-06-27 |
| EP1351924A2 (en) | 2003-10-15 |
| US20030060459A1 (en) | 2003-03-27 |
| HUP0303540A2 (hu) | 2004-01-28 |
| JP2005506949A (ja) | 2005-03-10 |
| AR035720A1 (es) | 2004-07-07 |
| AU2002241724A1 (en) | 2002-07-01 |
| US20050282882A1 (en) | 2005-12-22 |
| US6974836B2 (en) | 2005-12-13 |
| US7449493B2 (en) | 2008-11-11 |
| WO2002050019A3 (en) | 2003-03-13 |
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Discontinued |