JP4828829B2 - ケモカイン受容体のモジュレーターとしての3−アミノピロリジン誘導体 - Google Patents
ケモカイン受容体のモジュレーターとしての3−アミノピロリジン誘導体 Download PDFInfo
- Publication number
- JP4828829B2 JP4828829B2 JP2004570963A JP2004570963A JP4828829B2 JP 4828829 B2 JP4828829 B2 JP 4828829B2 JP 2004570963 A JP2004570963 A JP 2004570963A JP 2004570963 A JP2004570963 A JP 2004570963A JP 4828829 B2 JP4828829 B2 JP 4828829B2
- Authority
- JP
- Japan
- Prior art keywords
- amino
- trifluoromethyl
- pyrrolidin
- benzamide
- oxoethyl
- 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.)
- Expired - Lifetime
Links
- 102000009410 Chemokine receptor Human genes 0.000 title abstract description 18
- 108050000299 Chemokine receptor Proteins 0.000 title abstract description 18
- NGXSWUFDCSEIOO-UHFFFAOYSA-N pyrrolidin-3-amine Chemical class NC1CCNC1 NGXSWUFDCSEIOO-UHFFFAOYSA-N 0.000 title abstract description 15
- -1 e.g. Proteins 0.000 claims abstract description 435
- 150000001875 compounds Chemical class 0.000 claims abstract description 274
- 239000000203 mixture Substances 0.000 claims abstract description 159
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 76
- 125000003118 aryl group Chemical group 0.000 claims description 57
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 125000003545 alkoxy group Chemical group 0.000 claims description 40
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000004385 trihaloalkyl group Chemical group 0.000 claims description 33
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical class 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
- 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 26
- 125000004952 trihaloalkoxy group Chemical group 0.000 claims description 26
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 150000003857 carboxamides Chemical class 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 125000004001 thioalkyl group Chemical group 0.000 claims description 20
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 17
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 15
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 14
- 125000004103 aminoalkyl group Chemical class 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000002619 bicyclic group Chemical group 0.000 claims description 11
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 claims description 10
- 229940124530 sulfonamide Drugs 0.000 claims description 10
- 150000003456 sulfonamides Chemical class 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 8
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 239000004202 carbamide Chemical class 0.000 claims description 8
- 239000013078 crystal Substances 0.000 claims description 8
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 8
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 8
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- PAMCRRDMORMCSM-UHFFFAOYSA-N n-(trifluoromethyl)benzamide Chemical compound FC(F)(F)NC(=O)C1=CC=CC=C1 PAMCRRDMORMCSM-UHFFFAOYSA-N 0.000 claims description 7
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 6
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 6
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 239000005977 Ethylene Substances 0.000 claims description 5
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
- 150000004657 carbamic acid derivatives Chemical class 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
- 125000004982 dihaloalkyl group Chemical group 0.000 claims description 5
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 4
- 125000005015 aryl alkynyl group Chemical group 0.000 claims description 4
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 4
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 4
- 125000005312 heteroarylalkynyl group Chemical group 0.000 claims description 4
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 4
- 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims description 4
- 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- 125000003003 spiro group Chemical group 0.000 claims description 4
- DEVTYEWCSUXPPX-KDARRYODSA-N n-[2-[[(3r)-1-(4-hydroxy-4-pyridin-2-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 DEVTYEWCSUXPPX-KDARRYODSA-N 0.000 claims description 3
- SAOZWMYDEMCMDX-MVBMGLOESA-N n-[2-[[(3r)-1-(4-hydroxy-4-pyrimidin-2-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC=CN=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 SAOZWMYDEMCMDX-MVBMGLOESA-N 0.000 claims description 3
- YAFRFZRHFCETGN-MVBMGLOESA-N n-[2-[[(3r)-1-(4-hydroxy-4-pyrimidin-4-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CN=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 YAFRFZRHFCETGN-MVBMGLOESA-N 0.000 claims description 3
- MAOMEWPFIBYKLH-PLKPZTHQSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(4-pyrimidin-5-ylphenyl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CC(=CC=1)C=1C=NC=NC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 MAOMEWPFIBYKLH-PLKPZTHQSA-N 0.000 claims description 3
- NXZNYBUBXWWKCP-JMOWIOHXSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(6-methoxypyridin-3-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 NXZNYBUBXWWKCP-JMOWIOHXSA-N 0.000 claims description 3
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- WDIQRIWLNMOHQT-MDPMHESRSA-N 2-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-n-methyl-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)NC)=CN=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 WDIQRIWLNMOHQT-MDPMHESRSA-N 0.000 claims description 2
- OVWDKALMNVPMII-DUHUICASSA-N n-[2-[[(3r)-1-(2-hydroxy-2-pyridin-3-yl-5-bicyclo[2.2.2]octanyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CC2CCC1CC2(O)C=1C=NC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 OVWDKALMNVPMII-DUHUICASSA-N 0.000 claims description 2
- JRQYGNBKTFKPQJ-HHHXNRCGSA-N n-[2-[[(3r)-1-(4,4-diphenylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(CC2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 JRQYGNBKTFKPQJ-HHHXNRCGSA-N 0.000 claims description 2
- PWYLFYWUKYSYEE-UZGSZPBKSA-N n-[2-[[(3r)-1-(4-fluoro-4-pyridin-3-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(F)(CC2)C=2C=NC=CC=2)=C1 PWYLFYWUKYSYEE-UZGSZPBKSA-N 0.000 claims description 2
- VVCJMAZMIRREGR-MVBMGLOESA-N n-[2-[[(3r)-1-(4-hydroxy-4-pyrazin-2-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC=NC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 VVCJMAZMIRREGR-MVBMGLOESA-N 0.000 claims description 2
- GAKKMSMTYSFQMD-RZFJCUDFSA-N n-[2-[[(3r)-1-(4-hydroxy-4-pyrimidin-5-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC=NC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GAKKMSMTYSFQMD-RZFJCUDFSA-N 0.000 claims description 2
- AXDCXMOZTWUHQV-JMOWIOHXSA-N n-[2-[[(3r)-1-[4-(5-cyanopyridin-2-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC(=CC=1)C#N)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 AXDCXMOZTWUHQV-JMOWIOHXSA-N 0.000 claims description 2
- FCSHUTWMCDMEGA-JNDNBTNTSA-N n-[2-[[(3r)-1-[4-(5-ethyl-1,3-thiazol-2-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound S1C(CC)=CN=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 FCSHUTWMCDMEGA-JNDNBTNTSA-N 0.000 claims description 2
- YWCYAZZTMVIAHR-PQXIJOGNSA-N n-[2-[[(3r)-1-[4-(6-cyanopyridin-3-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(=CC=1)C#N)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 YWCYAZZTMVIAHR-PQXIJOGNSA-N 0.000 claims description 2
- FFVOCIHNNQEMHX-JMOWIOHXSA-N n-[2-[[(3r)-1-[4-[2-(2-fluoroethoxy)pyrimidin-5-yl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(OCCF)=NC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 FFVOCIHNNQEMHX-JMOWIOHXSA-N 0.000 claims description 2
- NMNSNBYHMUBGTJ-FMGHMSBISA-N n-[2-[[(3r)-1-[4-[4-(dimethylcarbamoyl)phenyl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C1CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 NMNSNBYHMUBGTJ-FMGHMSBISA-N 0.000 claims description 2
- MHCKPQQAIJUGBK-WXFIPNSDSA-N n-[2-[[(3r)-1-[4-[5-[(dimethylamino)methyl]pyridin-2-yl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N1=CC(CN(C)C)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 MHCKPQQAIJUGBK-WXFIPNSDSA-N 0.000 claims description 2
- ZCIAGEMLCOBLHP-PDDLGQBUSA-N n-[2-[[(3r)-1-[4-fluoro-4-(1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(F)(CC2)C=2SC=CN=2)=C1 ZCIAGEMLCOBLHP-PDDLGQBUSA-N 0.000 claims description 2
- QEPLAAIBUWSCKZ-JMOWIOHXSA-N n-[2-[[(3r)-1-[4-fluoro-4-(6-methoxypyridin-3-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1C1(F)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 QEPLAAIBUWSCKZ-JMOWIOHXSA-N 0.000 claims description 2
- MVJLLZMAJRFREX-PDDLGQBUSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1SC=CN=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 MVJLLZMAJRFREX-PDDLGQBUSA-N 0.000 claims description 2
- MZEXAFCJVVIRSP-KDARRYODSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(2-methoxypyrimidin-5-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=NC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 MZEXAFCJVVIRSP-KDARRYODSA-N 0.000 claims description 2
- SBWSIJJXKGWBGI-USEFPYCQSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(2-propan-2-yl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound S1C(C(C)C)=NC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 SBWSIJJXKGWBGI-USEFPYCQSA-N 0.000 claims description 2
- FYRWJIZNXHBLFT-PQXIJOGNSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(4-iodophenyl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CC(I)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 FYRWJIZNXHBLFT-PQXIJOGNSA-N 0.000 claims description 2
- XNYRGJBLCSJWRJ-VEODAXLASA-N n-[2-[[(3r)-1-[4-hydroxy-4-(5-pyridin-3-yl-1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1SC(=CN=1)C=1C=NC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 XNYRGJBLCSJWRJ-VEODAXLASA-N 0.000 claims description 2
- HNTRFLLOZLDKQV-ZHYGNVHVSA-N n-[2-[[(3r,5s)-1-(4-hydroxy-4-phenylcyclohexyl)-5-methylpyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C[C@@H]1C)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)N1C(CC1)CCC1(O)C1=CC=CC=C1 HNTRFLLOZLDKQV-ZHYGNVHVSA-N 0.000 claims description 2
- MWYZERNYUXQMHI-IOXNAGQWSA-N n-[2-[[(3s,4s)-1-[4-(4-cyanophenyl)-4-hydroxycyclohexyl]-4-ethoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1C=CC(=CC=1)C#N)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 MWYZERNYUXQMHI-IOXNAGQWSA-N 0.000 claims description 2
- KLHQJQIPLYZOOT-ZCOIRKDISA-N n-[2-[[(3s,4s)-4-ethoxy-1-(4-hydroxy-4-phenylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KLHQJQIPLYZOOT-ZCOIRKDISA-N 0.000 claims description 2
- OUQTVCJXCWFIJC-YSYGYCFTSA-N n-[2-[[(9s)-7-(4-hydroxy-4-phenylcyclohexyl)-1-oxa-7-azaspiro[4.4]nonan-9-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(CC11OCCC1)C1CCC(CC1)(O)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 OUQTVCJXCWFIJC-YSYGYCFTSA-N 0.000 claims description 2
- UWQSSWJGMTYGDT-UHFFFAOYSA-N n-[2-[[3-(fluoromethyl)-1-(4-hydroxy-4-phenylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1CC(O)(C=2C=CC=CC=2)CCC1N(C1)CCC1(CF)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 UWQSSWJGMTYGDT-UHFFFAOYSA-N 0.000 claims description 2
- JNQUECFEWPYNIM-LNCJBJJNSA-N 2-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)N)=CN=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 JNQUECFEWPYNIM-LNCJBJJNSA-N 0.000 claims 1
- MYSFYUNLGKULPA-VLNJMECTSA-N 2-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-n,n-dimethyl-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)N(C)C)=CN=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 MYSFYUNLGKULPA-VLNJMECTSA-N 0.000 claims 1
- HQNHRRJCSPUIGI-MSUMSUTISA-N 2-fluoro-4-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-n,n-dimethylbenzamide Chemical compound C1=C(F)C(C(=O)N(C)C)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 HQNHRRJCSPUIGI-MSUMSUTISA-N 0.000 claims 1
- INXIZQQEZMHDRQ-NHKQPKSZSA-N 2-fluoro-4-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-n-methylbenzamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 INXIZQQEZMHDRQ-NHKQPKSZSA-N 0.000 claims 1
- PPULXIYWPSNVNY-MSUMSUTISA-N 3-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-4-methoxy-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(OC)C(C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 PPULXIYWPSNVNY-MSUMSUTISA-N 0.000 claims 1
- MFKRLNKKPKMKFT-QXIWCURZSA-N 3-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC(C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 MFKRLNKKPKMKFT-QXIWCURZSA-N 0.000 claims 1
- NRMZSYGTSQRQOJ-WXFIPNSDSA-N 3-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 NRMZSYGTSQRQOJ-WXFIPNSDSA-N 0.000 claims 1
- WOTPYPZQBQWHSC-ASNZNYLFSA-N 4-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-n,2-dimethylbenzamide Chemical compound C1=C(C)C(C(=O)NC)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 WOTPYPZQBQWHSC-ASNZNYLFSA-N 0.000 claims 1
- YAZIHWNMSUPPJG-ASNZNYLFSA-N 4-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-n,3-dimethylbenzamide Chemical compound CC1=CC(C(=O)NC)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 YAZIHWNMSUPPJG-ASNZNYLFSA-N 0.000 claims 1
- QIGXOWCTACMDGB-JPKAMZIXSA-N 4-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-n,n,2-trimethylbenzamide Chemical compound C1=C(C)C(C(=O)N(C)C)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 QIGXOWCTACMDGB-JPKAMZIXSA-N 0.000 claims 1
- OWRXUWHWTPVSEE-JPKAMZIXSA-N 4-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-n,n,3-trimethylbenzamide Chemical compound CC1=CC(C(=O)N(C)C)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 OWRXUWHWTPVSEE-JPKAMZIXSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- LDYSIQBWKUBFFP-PQXIJOGNSA-N n-[2-[[(3r)-1-(4-hydroxy-4-phenylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 LDYSIQBWKUBFFP-PQXIJOGNSA-N 0.000 claims 1
- HBTZTMSFUWNTTQ-RZFJCUDFSA-N n-[2-[[(3r)-1-(4-hydroxy-4-pyridazin-4-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NN=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 HBTZTMSFUWNTTQ-RZFJCUDFSA-N 0.000 claims 1
- KUWNDUYYSZHFCP-UZGSZPBKSA-N n-[2-[[(3r)-1-(4-hydroxy-4-pyridin-3-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KUWNDUYYSZHFCP-UZGSZPBKSA-N 0.000 claims 1
- HCWVPYIWVWLGPP-UZGSZPBKSA-N n-[2-[[(3r)-1-(4-hydroxy-4-pyridin-4-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CN=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 HCWVPYIWVWLGPP-UZGSZPBKSA-N 0.000 claims 1
- QCBZGANAMALUIF-GEUIHZRBSA-N n-[2-[[(3r)-1-[4-(1,3-benzothiazol-2-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1SC2=CC=CC=C2N=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 QCBZGANAMALUIF-GEUIHZRBSA-N 0.000 claims 1
- RRZBQGMHUDBETI-JNDNBTNTSA-N n-[2-[[(3r)-1-[4-(2-ethoxy-1,3-thiazol-5-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound S1C(OCC)=NC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 RRZBQGMHUDBETI-JNDNBTNTSA-N 0.000 claims 1
- JOOIRINNXLRETK-JNDNBTNTSA-N n-[2-[[(3r)-1-[4-(2-ethyl-1,3-thiazol-5-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound S1C(CC)=NC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 JOOIRINNXLRETK-JNDNBTNTSA-N 0.000 claims 1
- SBOSOBRMGSJSDR-SVRAFRINSA-N n-[2-[[(3r)-1-[4-(3-cyanophenyl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=C(C=CC=1)C#N)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 SBOSOBRMGSJSDR-SVRAFRINSA-N 0.000 claims 1
- HPSIJFYOFLSSGV-PQXIJOGNSA-N n-[2-[[(3r)-1-[4-(3-fluorophenyl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=C(F)C=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 HPSIJFYOFLSSGV-PQXIJOGNSA-N 0.000 claims 1
- UNZDFKYTSNRJMU-PQXIJOGNSA-N n-[2-[[(3r)-1-[4-(4-bromophenyl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CC(Br)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 UNZDFKYTSNRJMU-PQXIJOGNSA-N 0.000 claims 1
- CFIMBXSJBVDUEK-SVRAFRINSA-N n-[2-[[(3r)-1-[4-(4-cyanophenyl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CC(=CC=1)C#N)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 CFIMBXSJBVDUEK-SVRAFRINSA-N 0.000 claims 1
- PHCBNASWBBFZMV-PQXIJOGNSA-N n-[2-[[(3r)-1-[4-(4-fluorophenyl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CC(F)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 PHCBNASWBBFZMV-PQXIJOGNSA-N 0.000 claims 1
- ZEGPYANSCZFTDP-KDARRYODSA-N n-[2-[[(3r)-1-[4-(5-bromopyridin-2-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC(Br)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZEGPYANSCZFTDP-KDARRYODSA-N 0.000 claims 1
- GYNZOMSRISFPJH-KDARRYODSA-N n-[2-[[(3r)-1-[4-(6-bromopyridin-3-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(Br)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GYNZOMSRISFPJH-KDARRYODSA-N 0.000 claims 1
- GBHFJHHZNPQVSF-AGHUKTAOSA-N n-[2-[[(3r)-1-[4-(6-ethoxypyridin-3-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OCC)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 GBHFJHHZNPQVSF-AGHUKTAOSA-N 0.000 claims 1
- MSZTUQIDVIKVMT-PDRFFQIWSA-N n-[2-[[(3r)-1-[4-(6-methoxypyridin-3-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1C1CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 MSZTUQIDVIKVMT-PDRFFQIWSA-N 0.000 claims 1
- ZUTKGMWAIOUQAM-QXIWCURZSA-N n-[2-[[(3r)-1-[4-[4-[(dimethylamino)methyl]-3-fluorophenyl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(F)C(CN(C)C)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 ZUTKGMWAIOUQAM-QXIWCURZSA-N 0.000 claims 1
- CTSQWOMAUBANMB-YAAXVGMDSA-N n-[2-[[(3r)-1-[4-[4-[(dimethylamino)methyl]phenyl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(CN(C)C)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 CTSQWOMAUBANMB-YAAXVGMDSA-N 0.000 claims 1
- FXSVUSGYIRWVPS-DCWSAZFOSA-N n-[2-[[(3r)-1-[4-[5-(4-fluorophenyl)pyridin-2-yl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC(=CC=1)C=1C=CC(F)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 FXSVUSGYIRWVPS-DCWSAZFOSA-N 0.000 claims 1
- XQSVMPYHBRJHCB-SDPJGKNGSA-N n-[2-[[(3r)-1-[4-[5-[(dimethylamino)methyl]pyridin-2-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N1=CC(CN(C)C)=CC=C1C1CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 XQSVMPYHBRJHCB-SDPJGKNGSA-N 0.000 claims 1
- DIYZTCHYQUDYKS-SOSILRMKSA-N n-[2-[[(3r)-1-[4-[5-[2-[(dimethylamino)methyl]phenyl]pyridin-2-yl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CN(C)CC1=CC=CC=C1C1=CC=C(C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)N=C1 DIYZTCHYQUDYKS-SOSILRMKSA-N 0.000 claims 1
- JQKJTACJDXVKRD-BGPPBHKUSA-N n-[2-[[(3r)-1-[4-[6-(2,2-difluoroethoxy)pyridin-3-yl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(OCC(F)F)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 JQKJTACJDXVKRD-BGPPBHKUSA-N 0.000 claims 1
- MKUKWTGAMYNNAC-AGHUKTAOSA-N n-[2-[[(3r)-1-[4-[6-(2-fluoroethoxy)pyridin-3-yl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(OCCF)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 MKUKWTGAMYNNAC-AGHUKTAOSA-N 0.000 claims 1
- JZCKGGKZEXPDFX-WXFIPNSDSA-N n-[2-[[(3r)-1-[4-[6-(cyclopropylamino)pyridin-3-yl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(NC2CC2)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 JZCKGGKZEXPDFX-WXFIPNSDSA-N 0.000 claims 1
- UKXLYRLVJUIOEA-AGHUKTAOSA-N n-[2-[[(3r)-1-[4-[6-(dimethylamino)pyridin-3-yl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(N(C)C)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 UKXLYRLVJUIOEA-AGHUKTAOSA-N 0.000 claims 1
- XTMUALZZEORQKQ-AGHUKTAOSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(1h-indazol-5-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=C2C=NNC2=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 XTMUALZZEORQKQ-AGHUKTAOSA-N 0.000 claims 1
- FJKABBHTEABIJD-MVBMGLOESA-N n-[2-[[(3r)-1-[4-hydroxy-4-(2-methyl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound S1C(C)=NC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 FJKABBHTEABIJD-MVBMGLOESA-N 0.000 claims 1
- IQYTZDPZFOAORZ-NHKQPKSZSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(2-pyridin-2-yl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1SC(=NC=1)C=1N=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 IQYTZDPZFOAORZ-NHKQPKSZSA-N 0.000 claims 1
- KQBZIQGRGZGAMB-VEODAXLASA-N n-[2-[[(3r)-1-[4-hydroxy-4-(2-pyridin-3-yl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1SC(=NC=1)C=1C=NC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 KQBZIQGRGZGAMB-VEODAXLASA-N 0.000 claims 1
- SFXGMIKADNKNJK-MVBMGLOESA-N n-[2-[[(3r)-1-[4-hydroxy-4-(4-methyl-1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CSC(C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=N1 SFXGMIKADNKNJK-MVBMGLOESA-N 0.000 claims 1
- YKSPNNYIWLFVCY-SVRAFRINSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(4-methylphenyl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(C)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 YKSPNNYIWLFVCY-SVRAFRINSA-N 0.000 claims 1
- HLAVOYXHFGNRJF-FVEFLQRYSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(4-pyridin-3-ylphenyl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CC(=CC=1)C=1C=NC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 HLAVOYXHFGNRJF-FVEFLQRYSA-N 0.000 claims 1
- CXHZYVNAZPGLQE-MVBMGLOESA-N n-[2-[[(3r)-1-[4-hydroxy-4-(5-methyl-1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound S1C(C)=CN=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 CXHZYVNAZPGLQE-MVBMGLOESA-N 0.000 claims 1
- OSVAVCIMNDJGDX-JMOWIOHXSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(5-methylpyridin-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N1=CC(C)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 OSVAVCIMNDJGDX-JMOWIOHXSA-N 0.000 claims 1
- UWIZRACVSVVZDG-ASNZNYLFSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(5-phenyl-1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1SC(=CN=1)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 UWIZRACVSVVZDG-ASNZNYLFSA-N 0.000 claims 1
- WTDGGNXGJDFBJI-USEFPYCQSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(5-propyl-1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound S1C(CCC)=CN=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 WTDGGNXGJDFBJI-USEFPYCQSA-N 0.000 claims 1
- NTSGLCOWEAWPMA-NHKQPKSZSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(5-pyridin-2-yl-1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1SC(=CN=1)C=1N=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 NTSGLCOWEAWPMA-NHKQPKSZSA-N 0.000 claims 1
- RTKCKMGLSJBINS-ASNZNYLFSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(5-pyrimidin-2-ylpyridin-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC(=CC=1)C=1N=CC=CN=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 RTKCKMGLSJBINS-ASNZNYLFSA-N 0.000 claims 1
- GPFQGPRBUCHYKV-QXIWCURZSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(5-pyrimidin-5-ylpyridin-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC(=CC=1)C=1C=NC=NC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GPFQGPRBUCHYKV-QXIWCURZSA-N 0.000 claims 1
- UVEBSTGEJQICGK-USEFPYCQSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(6-methoxypyridin-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound COC1=CC=CC(C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=N1 UVEBSTGEJQICGK-USEFPYCQSA-N 0.000 claims 1
- IDOWXFKHSJBRPE-JMOWIOHXSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(6-methylpyridin-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CC1=CC=CC(C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=N1 IDOWXFKHSJBRPE-JMOWIOHXSA-N 0.000 claims 1
- VRAVLBVQFTVJPP-DCWSAZFOSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(6-phenylpyridin-3-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(=CC=1)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 VRAVLBVQFTVJPP-DCWSAZFOSA-N 0.000 claims 1
- SBWPRUZWQKMGCN-JNDNBTNTSA-N n-[2-[[(3r)-1-[4-hydroxy-4-[2-(methoxymethyl)-1,3-thiazol-5-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound S1C(COC)=NC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 SBWPRUZWQKMGCN-JNDNBTNTSA-N 0.000 claims 1
- PDIBNIHPPUYIKN-QXIWCURZSA-N n-[2-[[(3r)-1-[4-hydroxy-4-[4-(1,3-thiazol-2-yl)phenyl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CC(=CC=1)C=1SC=CN=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 PDIBNIHPPUYIKN-QXIWCURZSA-N 0.000 claims 1
- FNUTXWQFNSMLSG-YAAXVGMDSA-N n-[2-[[(3r)-1-[4-hydroxy-4-[4-(1h-pyrazol-4-yl)phenyl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CC(=CC=1)C1=CNN=C1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 FNUTXWQFNSMLSG-YAAXVGMDSA-N 0.000 claims 1
- KZTGVVAZIZGGMK-MNEVETPYSA-N n-[2-[[(3r)-1-[4-hydroxy-4-[4-(methoxymethyl)phenyl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(COC)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 KZTGVVAZIZGGMK-MNEVETPYSA-N 0.000 claims 1
- ROZPNFLZEKLKKH-VEODAXLASA-N n-[2-[[(3r)-1-[4-hydroxy-4-[5-(1,3-oxazol-2-yl)pyridin-2-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC(=CC=1)C=1OC=CN=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ROZPNFLZEKLKKH-VEODAXLASA-N 0.000 claims 1
- XZYZOVOAHIMREO-VEODAXLASA-N n-[2-[[(3r)-1-[4-hydroxy-4-[5-(1,3-thiazol-2-yl)pyridin-2-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC(=CC=1)C=1SC=CN=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 XZYZOVOAHIMREO-VEODAXLASA-N 0.000 claims 1
- WBAMCCHLVRNYDI-WXFIPNSDSA-N n-[2-[[(3r)-1-[4-hydroxy-4-[5-(1h-pyrazol-4-yl)pyridin-2-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC(=CC=1)C1=CNN=C1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 WBAMCCHLVRNYDI-WXFIPNSDSA-N 0.000 claims 1
- UNVHCLFXCZTUCW-ANTXIRGESA-N n-[2-[[(3r)-1-[4-hydroxy-4-[5-(3-methoxyphenyl)pyridin-2-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound COC1=CC=CC(C=2C=NC(=CC=2)C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 UNVHCLFXCZTUCW-ANTXIRGESA-N 0.000 claims 1
- PIHORZGMLFKCGG-ANTXIRGESA-N n-[2-[[(3r)-1-[4-hydroxy-4-[5-(4-methoxyphenyl)pyridin-2-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(OC)=CC=C1C1=CC=C(C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)N=C1 PIHORZGMLFKCGG-ANTXIRGESA-N 0.000 claims 1
- VFBFHJIJABPGMT-ANTXIRGESA-N n-[2-[[(3r)-1-[4-hydroxy-4-[5-[2-(hydroxymethyl)phenyl]pyridin-2-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound OCC1=CC=CC=C1C1=CC=C(C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)N=C1 VFBFHJIJABPGMT-ANTXIRGESA-N 0.000 claims 1
- SPINUELFJQLLLQ-DCWSAZFOSA-N n-[2-[[(3r)-1-[4-hydroxy-4-[5-[4-(trifluoromethyl)phenyl]pyridin-2-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC(=CC=1)C=1C=CC(=CC=1)C(F)(F)F)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 SPINUELFJQLLLQ-DCWSAZFOSA-N 0.000 claims 1
- YIYKLPPJNGZYFH-VEODAXLASA-N n-[2-[[(3r)-1-[4-hydroxy-4-[6-(1,3-oxazol-2-yl)pyridin-3-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(=CC=1)C=1OC=CN=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 YIYKLPPJNGZYFH-VEODAXLASA-N 0.000 claims 1
- JENXGAAEWOFAKP-VEODAXLASA-N n-[2-[[(3r)-1-[4-hydroxy-4-[6-(1,3-thiazol-2-yl)pyridin-3-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(=CC=1)C=1SC=CN=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 JENXGAAEWOFAKP-VEODAXLASA-N 0.000 claims 1
- ZENSIIADVLWRKG-JMOWIOHXSA-N n-[2-[[(3r)-1-[4-hydroxy-4-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(OCC(F)(F)F)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZENSIIADVLWRKG-JMOWIOHXSA-N 0.000 claims 1
- RYYGPYJSKUQZGE-BZIPVCSVSA-N n-[2-[[(3r,5s)-1-(4-hydroxy-4-pyridin-2-ylcyclohexyl)-5-methylpyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C[C@@H]1C)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)N1C(CC1)CCC1(O)C1=CC=CC=N1 RYYGPYJSKUQZGE-BZIPVCSVSA-N 0.000 claims 1
- CFWHTAPFHZDCCS-DDKHHDTNSA-N n-[2-[[(3r,5s)-1-(4-hydroxy-4-pyridin-3-ylcyclohexyl)-5-methylpyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C[C@@H]1C)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)N1C(CC1)CCC1(O)C1=CC=CN=C1 CFWHTAPFHZDCCS-DDKHHDTNSA-N 0.000 claims 1
- PBNFXMCZRJHVBL-DDKHHDTNSA-N n-[2-[[(3r,5s)-1-(4-hydroxy-4-pyridin-4-ylcyclohexyl)-5-methylpyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C[C@@H]1C)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)N1C(CC1)CCC1(O)C1=CC=NC=C1 PBNFXMCZRJHVBL-DDKHHDTNSA-N 0.000 claims 1
- FMPJOKHKDFTXPN-YXXMQHFLSA-N n-[2-[[(3r,5s)-1-[4-hydroxy-4-(4-methylphenyl)cyclohexyl]-5-methylpyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C[C@@H]1C)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)N1C(CC1)CCC1(O)C1=CC=C(C)C=C1 FMPJOKHKDFTXPN-YXXMQHFLSA-N 0.000 claims 1
- ARUQTHKMANHWRG-CWXVSUMLSA-N n-[2-[[(3r,5s)-1-[4-hydroxy-4-(5-methylpyridin-2-yl)cyclohexyl]-5-methylpyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C[C@@H]1C)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)N1C(CC1)CCC1(O)C1=CC=C(C)C=N1 ARUQTHKMANHWRG-CWXVSUMLSA-N 0.000 claims 1
- LUYQWYYTAOXEEG-ZCPMFJNGSA-N n-[2-[[(3r,5s)-1-[4-hydroxy-4-(6-methoxypyridin-3-yl)cyclohexyl]-5-methylpyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1C1(O)CCC(N2[C@H](C[C@H](C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)C)CC1 LUYQWYYTAOXEEG-ZCPMFJNGSA-N 0.000 claims 1
- DSWUOWQLLSQGNU-IOXNAGQWSA-N n-[2-[[(3s,4s)-1-(4-hydroxy-4-phenylcyclohexyl)-4-propoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCCC)C1CCC(O)(CC1)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 DSWUOWQLLSQGNU-IOXNAGQWSA-N 0.000 claims 1
- RCUMNFOFNDIQIF-XOTWMYLBSA-N n-[2-[[(3s,4s)-1-[4-hydroxy-4-(4-methoxyphenyl)cyclohexyl]-4-propoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCCC)C1CCC(O)(CC1)C=1C=CC(OC)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 RCUMNFOFNDIQIF-XOTWMYLBSA-N 0.000 claims 1
- ZZTHSVRCXTVHFO-BAWWGMJKSA-N n-[2-[[(3s,4s)-1-[4-hydroxy-4-(4-methylpyridin-2-yl)cyclohexyl]-4-propoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCCC)C1CCC(O)(CC1)C=1N=CC=C(C)C=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZZTHSVRCXTVHFO-BAWWGMJKSA-N 0.000 claims 1
- IBCIWAJWDTXVQF-BYQSVQIVSA-N n-[2-[[(3s,4s)-1-[4-hydroxy-4-(6-methoxypyridin-2-yl)cyclohexyl]-4-propoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCCC)C1CCC(O)(CC1)C=1N=C(OC)C=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 IBCIWAJWDTXVQF-BYQSVQIVSA-N 0.000 claims 1
- OBJMHLSHLUXFKU-BAWWGMJKSA-N n-[2-[[(3s,4s)-1-[4-hydroxy-4-(6-methoxypyridin-3-yl)cyclohexyl]-4-propoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCCC)C1CCC(O)(CC1)C=1C=NC(OC)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 OBJMHLSHLUXFKU-BAWWGMJKSA-N 0.000 claims 1
- FIWGLURXQQWFMV-BAWWGMJKSA-N n-[2-[[(3s,4s)-1-[4-hydroxy-4-(6-methylpyridin-2-yl)cyclohexyl]-4-propoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCCC)C1CCC(O)(CC1)C=1N=C(C)C=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 FIWGLURXQQWFMV-BAWWGMJKSA-N 0.000 claims 1
- NDZQBPKMKRMDQZ-DVZTWYNPSA-N n-[2-[[(3s,4s)-4-ethoxy-1-(4-pyridin-2-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(CC1)C=1N=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 NDZQBPKMKRMDQZ-DVZTWYNPSA-N 0.000 claims 1
- ZUVYVAATEZDRLD-FLLKZOGESA-N n-[2-[[(3s,4s)-4-ethoxy-1-(4-pyridin-3-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(CC1)C=1C=NC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZUVYVAATEZDRLD-FLLKZOGESA-N 0.000 claims 1
- XZOMZWVLAHXPKB-FLLKZOGESA-N n-[2-[[(3s,4s)-4-ethoxy-1-(4-pyridin-4-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(CC1)C=1C=CN=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 XZOMZWVLAHXPKB-FLLKZOGESA-N 0.000 claims 1
- LQLMQWXIQQJGGS-ZCOIRKDISA-N n-[2-[[(3s,4s)-4-ethoxy-1-[4-(3-fluorophenyl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1C=C(F)C=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 LQLMQWXIQQJGGS-ZCOIRKDISA-N 0.000 claims 1
- PHOLEOTXENIUDW-ZCOIRKDISA-N n-[2-[[(3s,4s)-4-ethoxy-1-[4-(4-fluorophenyl)-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1C=CC(F)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 PHOLEOTXENIUDW-ZCOIRKDISA-N 0.000 claims 1
- OVFQGCZXLQCEHS-FLLKZOGESA-N n-[2-[[(3s,4s)-4-ethoxy-1-[4-(6-methoxypyridin-3-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(CC1)C=1C=NC(OC)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 OVFQGCZXLQCEHS-FLLKZOGESA-N 0.000 claims 1
- UVIJCDZUVXDUOK-MDZVREACSA-N n-[2-[[(3s,4s)-4-ethoxy-1-[4-hydroxy-4-(3-methoxyphenyl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1C=C(OC)C=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 UVIJCDZUVXDUOK-MDZVREACSA-N 0.000 claims 1
- RNNAMHZABORLIG-MDZVREACSA-N n-[2-[[(3s,4s)-4-ethoxy-1-[4-hydroxy-4-(4-methoxyphenyl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1C=CC(OC)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 RNNAMHZABORLIG-MDZVREACSA-N 0.000 claims 1
- JQPQRYDIQFLFAA-IOXNAGQWSA-N n-[2-[[(3s,4s)-4-ethoxy-1-[4-hydroxy-4-(4-methylphenyl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1C=CC(C)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 JQPQRYDIQFLFAA-IOXNAGQWSA-N 0.000 claims 1
- GUZJEYVPUMKKLK-YKUCYRFJSA-N n-[2-[[(3s,4s)-4-ethoxy-1-[4-hydroxy-4-(4-methylpyridin-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1N=CC=C(C)C=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 GUZJEYVPUMKKLK-YKUCYRFJSA-N 0.000 claims 1
- DDGUFECXDQKCFJ-YKUCYRFJSA-N n-[2-[[(3s,4s)-4-ethoxy-1-[4-hydroxy-4-(5-methylpyridin-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1N=CC(C)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 DDGUFECXDQKCFJ-YKUCYRFJSA-N 0.000 claims 1
- DLSVFJLWICMECP-YKUCYRFJSA-N n-[2-[[(3s,4s)-4-ethoxy-1-[4-hydroxy-4-(6-methoxypyridin-3-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1C=NC(OC)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 DLSVFJLWICMECP-YKUCYRFJSA-N 0.000 claims 1
- PSFQENFUGCSXKE-YKUCYRFJSA-N n-[2-[[(3s,4s)-4-ethoxy-1-[4-hydroxy-4-(6-methylpyridin-2-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCC)C1CCC(O)(CC1)C=1N=C(C)C=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 PSFQENFUGCSXKE-YKUCYRFJSA-N 0.000 claims 1
- AAOYFRVMYXIGFD-TWMPVWRBSA-N n-[2-oxo-2-[[(3r)-1-(4-pyridin-2-ylcyclohexyl)pyrrolidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(CC2)C=2N=CC=CC=2)=C1 AAOYFRVMYXIGFD-TWMPVWRBSA-N 0.000 claims 1
- PYWSAWVTQQXEJA-PDRFFQIWSA-N n-[2-oxo-2-[[(3r)-1-(4-pyridin-3-ylcyclohexyl)pyrrolidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(CC2)C=2C=NC=CC=2)=C1 PYWSAWVTQQXEJA-PDRFFQIWSA-N 0.000 claims 1
- DJYNOSREKOEFMN-PDRFFQIWSA-N n-[2-oxo-2-[[(3r)-1-(4-pyridin-4-ylcyclohexyl)pyrrolidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(CC2)C=2C=CN=CC=2)=C1 DJYNOSREKOEFMN-PDRFFQIWSA-N 0.000 claims 1
- YLNKWAOODGCNHT-WTUOKKPGSA-N n-[2-oxo-2-[[(3s,4s)-4-propoxy-1-(4-pyridin-3-ylcyclohexyl)pyrrolidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCCC)C1CCC(CC1)C=1C=NC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 YLNKWAOODGCNHT-WTUOKKPGSA-N 0.000 claims 1
- FEFXPONLJKQWEC-WTUOKKPGSA-N n-[2-oxo-2-[[(3s,4s)-4-propoxy-1-(4-pyridin-4-ylcyclohexyl)pyrrolidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1OCCC)C1CCC(CC1)C=1C=CN=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 FEFXPONLJKQWEC-WTUOKKPGSA-N 0.000 claims 1
- MIXVCDZGACMOGR-NYLDSWQDSA-N n-[4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]pyridine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(CC2)NC(=O)C=2N=CC=CC=2)=C1 MIXVCDZGACMOGR-NYLDSWQDSA-N 0.000 claims 1
- DXWSOQGJQGDZPJ-ATKRNPRHSA-N n-[4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]pyridine-3-carboxamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(CC2)NC(=O)C=2C=NC=CC=2)=C1 DXWSOQGJQGDZPJ-ATKRNPRHSA-N 0.000 claims 1
- CCWIRBJJFODGHO-ATKRNPRHSA-N n-[4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]pyridine-4-carboxamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(CC2)NC(=O)C=2C=CN=CC=2)=C1 CCWIRBJJFODGHO-ATKRNPRHSA-N 0.000 claims 1
- AIFAXMFFYULXLO-OOMBGRCJSA-N n-[4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]quinoline-4-carboxamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(CC2)NC(=O)C=2C3=CC=CC=C3N=CC=2)=C1 AIFAXMFFYULXLO-OOMBGRCJSA-N 0.000 claims 1
- BIUFSSRQRZICKR-VLNJMECTSA-N n-ethyl-2-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)NCC)=CN=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 BIUFSSRQRZICKR-VLNJMECTSA-N 0.000 claims 1
- JVEQSFCDEUBODG-VLNJMECTSA-N n-ethyl-5-[1-hydroxy-4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]-1,3-thiazole-2-carboxamide Chemical compound S1C(C(=O)NCC)=NC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 JVEQSFCDEUBODG-VLNJMECTSA-N 0.000 claims 1
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 21
- 201000010099 disease Diseases 0.000 abstract description 19
- 102000019034 Chemokines Human genes 0.000 abstract description 16
- 108010012236 Chemokines Proteins 0.000 abstract description 16
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 12
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 abstract description 9
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 abstract description 9
- 102000004497 CCR2 Receptors Human genes 0.000 abstract description 9
- 108010017312 CCR2 Receptors Proteins 0.000 abstract description 9
- 201000001320 Atherosclerosis Diseases 0.000 abstract description 8
- 206010025135 lupus erythematosus Diseases 0.000 abstract description 8
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 abstract description 7
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 7
- 102000004274 CCR5 Receptors Human genes 0.000 abstract description 5
- 108010017088 CCR5 Receptors Proteins 0.000 abstract description 5
- 206010052779 Transplant rejections Diseases 0.000 abstract description 5
- 208000037803 restenosis Diseases 0.000 abstract description 5
- 210000000056 organ Anatomy 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 517
- 238000000034 method Methods 0.000 description 327
- 239000000243 solution Substances 0.000 description 295
- 230000008569 process Effects 0.000 description 243
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 237
- 235000019439 ethyl acetate Nutrition 0.000 description 237
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 234
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 189
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 90
- 239000011541 reaction mixture Substances 0.000 description 88
- 238000003756 stirring Methods 0.000 description 88
- 230000002829 reductive effect Effects 0.000 description 81
- 239000000741 silica gel Substances 0.000 description 78
- 229910002027 silica gel Inorganic materials 0.000 description 78
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 77
- 238000006243 chemical reaction Methods 0.000 description 71
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
- 239000012267 brine Substances 0.000 description 66
- 150000002576 ketones Chemical class 0.000 description 66
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 66
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 65
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- 239000000543 intermediate Substances 0.000 description 62
- 239000000460 chlorine Substances 0.000 description 61
- 239000012044 organic layer Substances 0.000 description 59
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 56
- 239000000284 extract Substances 0.000 description 51
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 51
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 51
- 239000007787 solid Substances 0.000 description 51
- 239000010410 layer Substances 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
- 239000000047 product Substances 0.000 description 47
- 239000011734 sodium Substances 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- 239000012074 organic phase Substances 0.000 description 35
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 238000004587 chromatography analysis Methods 0.000 description 32
- 229920006395 saturated elastomer Polymers 0.000 description 32
- 238000003818 flash chromatography Methods 0.000 description 31
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 29
- VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 239000003921 oil Substances 0.000 description 27
- 235000019198 oils Nutrition 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 26
- 150000001412 amines Chemical class 0.000 description 23
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 22
- 238000005984 hydrogenation reaction Methods 0.000 description 22
- 239000002253 acid Substances 0.000 description 20
- 239000003054 catalyst Substances 0.000 description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 20
- 238000000746 purification Methods 0.000 description 20
- 238000006268 reductive amination reaction Methods 0.000 description 20
- 239000000706 filtrate Substances 0.000 description 19
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- 125000001931 aliphatic group Chemical group 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 210000001616 monocyte Anatomy 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexyloxide Natural products O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 210000000265 leukocyte Anatomy 0.000 description 12
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 11
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 10
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 230000008878 coupling Effects 0.000 description 10
- 238000010168 coupling process Methods 0.000 description 10
- 238000005859 coupling reaction Methods 0.000 description 10
- 210000004698 lymphocyte Anatomy 0.000 description 10
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 239000003638 chemical reducing agent Substances 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 230000008485 antagonism Effects 0.000 description 8
- 208000006673 asthma Diseases 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 8
- HPILSJVIWVODDZ-LLVKDONJSA-N n-[2-oxo-2-[[(3r)-pyrrolidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CNCC2)=C1 HPILSJVIWVODDZ-LLVKDONJSA-N 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 239000000651 prodrug Substances 0.000 description 8
- 229940002612 prodrug Drugs 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 238000010791 quenching Methods 0.000 description 8
- 230000000171 quenching effect Effects 0.000 description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000010511 deprotection reaction Methods 0.000 description 7
- 230000002757 inflammatory effect Effects 0.000 description 7
- ZDGGJQMSELMHLK-UHFFFAOYSA-N m-Trifluoromethylhippuric acid Chemical compound OC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZDGGJQMSELMHLK-UHFFFAOYSA-N 0.000 description 7
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical group FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 7
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 201000004681 Psoriasis Diseases 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 description 6
- 125000005336 allyloxy group Chemical group 0.000 description 6
- 239000000908 ammonium hydroxide Substances 0.000 description 6
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 201000006417 multiple sclerosis Diseases 0.000 description 6
- XMYCKOVAGBTIPW-WXFUMESZSA-N n-[2-oxo-2-[[(3r)-1-[(1r,2r)-2-phenylmethoxycyclohexyl]pyrrolidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)[C@H]2[C@@H](CCCC2)OCC=2C=CC=CC=2)=C1 XMYCKOVAGBTIPW-WXFUMESZSA-N 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 6
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 5
- QKQTYROGIBUKKD-UHFFFAOYSA-N 8-(4-iodophenyl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2C=CC(I)=CC=2)CCC21OCCO2 QKQTYROGIBUKKD-UHFFFAOYSA-N 0.000 description 5
- 108700012434 CCL3 Proteins 0.000 description 5
- 102000000013 Chemokine CCL3 Human genes 0.000 description 5
- 101150003085 Pdcl gene Proteins 0.000 description 5
- 238000006859 Swern oxidation reaction Methods 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 5
- 238000010306 acid treatment Methods 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 150000001336 alkenes Chemical class 0.000 description 5
- 150000001350 alkyl halides Chemical class 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 238000009739 binding Methods 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 150000001768 cations Chemical class 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 229960002449 glycine Drugs 0.000 description 5
- 208000027866 inflammatory disease Diseases 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 description 5
- 230000007115 recruitment Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 239000012265 solid product Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 108091006027 G proteins Proteins 0.000 description 4
- 102000030782 GTP binding Human genes 0.000 description 4
- 108091000058 GTP-Binding Proteins 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 208000011200 Kawasaki disease Diseases 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 4
- 102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 210000003651 basophil Anatomy 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 230000000975 bioactive effect Effects 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- ICEQLCZWZXUUIJ-UHFFFAOYSA-N decan-3-ol Chemical compound CCCCCCCC(O)CC ICEQLCZWZXUUIJ-UHFFFAOYSA-N 0.000 description 4
- 150000002009 diols Chemical class 0.000 description 4
- 210000003979 eosinophil Anatomy 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- 230000002519 immonomodulatory effect Effects 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 238000006138 lithiation reaction Methods 0.000 description 4
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 4
- 201000008383 nephritis Diseases 0.000 description 4
- 208000005069 pulmonary fibrosis Diseases 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
- HKQTYQDNCKMNHZ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)CCC21OCCO2 HKQTYQDNCKMNHZ-UHFFFAOYSA-N 0.000 description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 3
- OQISMXPUYQRVLR-UHFFFAOYSA-N 2-[2-(2-hydroxyethyl)-1,3-dioxolan-2-yl]ethanol Chemical compound OCCC1(CCO)OCCO1 OQISMXPUYQRVLR-UHFFFAOYSA-N 0.000 description 3
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 3
- PAIJMBCCHZKCPD-UHFFFAOYSA-N 3-[3-(trifluoromethyl)phenyl]-4,5-dihydro-1,2-oxazole-5-carboxylic acid Chemical compound O1C(C(=O)O)CC(C=2C=C(C=CC=2)C(F)(F)F)=N1 PAIJMBCCHZKCPD-UHFFFAOYSA-N 0.000 description 3
- YRPHHTBMHQUQAC-UHFFFAOYSA-N 4-(1-hydroxy-4-oxocyclohexyl)benzonitrile Chemical compound C=1C=C(C#N)C=CC=1C1(O)CCC(=O)CC1 YRPHHTBMHQUQAC-UHFFFAOYSA-N 0.000 description 3
- RLJRYHFQMFVWRK-UHFFFAOYSA-N 4-hydroxy-4-(4-iodophenyl)cyclohexan-1-one Chemical compound C=1C=C(I)C=CC=1C1(O)CCC(=O)CC1 RLJRYHFQMFVWRK-UHFFFAOYSA-N 0.000 description 3
- FAQXRYQUQBSKEC-UHFFFAOYSA-N 4-hydroxy-4-phenylcyclohexan-1-one Chemical compound C=1C=CC=CC=1C1(O)CCC(=O)CC1 FAQXRYQUQBSKEC-UHFFFAOYSA-N 0.000 description 3
- UUXDKGQUPSOSAU-UHFFFAOYSA-N 8-(1,3-thiazol-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2SC=CN=2)CCC21OCCO2 UUXDKGQUPSOSAU-UHFFFAOYSA-N 0.000 description 3
- LMXWFQPXVACYFQ-UHFFFAOYSA-N 8-(5-bromopyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2N=CC(Br)=CC=2)CCC21OCCO2 LMXWFQPXVACYFQ-UHFFFAOYSA-N 0.000 description 3
- FPJPGSBHJRUASU-UHFFFAOYSA-N 8-pyrimidin-5-yl-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2C=NC=NC=2)CCC21OCCO2 FPJPGSBHJRUASU-UHFFFAOYSA-N 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 description 3
- 229940122444 Chemokine receptor antagonist Drugs 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 206010009900 Colitis ulcerative Diseases 0.000 description 3
- 201000009273 Endometriosis Diseases 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102000004890 Interleukin-8 Human genes 0.000 description 3
- 108090001007 Interleukin-8 Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- 238000006069 Suzuki reaction reaction Methods 0.000 description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 125000005127 aryl alkoxy alkyl group Chemical group 0.000 description 3
- MJSHDCCLFGOEIK-UHFFFAOYSA-N benzyl (2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCC1=CC=CC=C1 MJSHDCCLFGOEIK-UHFFFAOYSA-N 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 230000012292 cell migration Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000002975 chemoattractant Substances 0.000 description 3
- 239000002559 chemokine receptor antagonist Substances 0.000 description 3
- 230000003399 chemotactic effect Effects 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 239000012039 electrophile Substances 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- WQBHMWMSIUYBSQ-UHFFFAOYSA-N ethyl 1-benzyl-3-(fluoromethyl)pyrrolidine-3-carboxylate Chemical compound C1C(C(=O)OCC)(CF)CCN1CC1=CC=CC=C1 WQBHMWMSIUYBSQ-UHFFFAOYSA-N 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 208000006454 hepatitis Diseases 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 230000004968 inflammatory condition Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 3
- 229940096397 interleukin-8 Drugs 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 125000002346 iodo group Chemical group I* 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 208000017169 kidney disease Diseases 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- LVAUHOGCZGDDIX-UHFFFAOYSA-N methyl 2-[2-(2-methoxy-2-oxoethyl)-1,3-dioxolan-2-yl]acetate Chemical compound COC(=O)CC1(CC(=O)OC)OCCO1 LVAUHOGCZGDDIX-UHFFFAOYSA-N 0.000 description 3
- XWJPBZBZBCBAQB-UHFFFAOYSA-N methyl 3-[3-(trifluoromethyl)phenyl]-4,5-dihydro-1,2-oxazole-5-carboxylate Chemical compound O1C(C(=O)OC)CC(C=2C=C(C=CC=2)C(F)(F)F)=N1 XWJPBZBZBCBAQB-UHFFFAOYSA-N 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- SMJNINIPTPWZSE-UHFFFAOYSA-N n,n-dimethyl-4-(4-oxocyclohexyl)benzamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C1CCC(=O)CC1 SMJNINIPTPWZSE-UHFFFAOYSA-N 0.000 description 3
- GIONPAPDKZQLTK-UHFFFAOYSA-N n-[[3-(trifluoromethyl)phenyl]methylidene]hydroxylamine Chemical compound ON=CC1=CC=CC(C(F)(F)F)=C1 GIONPAPDKZQLTK-UHFFFAOYSA-N 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000007142 ring opening reaction Methods 0.000 description 3
- 201000000306 sarcoidosis Diseases 0.000 description 3
- NAXSVVOZXIPRIP-UHFFFAOYSA-N spiro[1,3-dioxolane-2,5'-2,3,3a,4,6,6a-hexahydro-1h-pentalene]-2'-ol Chemical compound C1C2CC(O)CC2CC21OCCO2 NAXSVVOZXIPRIP-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229960002317 succinimide Drugs 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 3
- XXXOMKRMYVHLQB-UHFFFAOYSA-N tert-butyl 3-(fluoromethyl)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC1(CF)NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 XXXOMKRMYVHLQB-UHFFFAOYSA-N 0.000 description 3
- VCUPYPHVRNFASM-UHFFFAOYSA-N tert-butyl 3-amino-3-(fluoromethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)(CF)C1 VCUPYPHVRNFASM-UHFFFAOYSA-N 0.000 description 3
- DQQJBEAXSOOCPG-SSDOTTSWSA-N tert-butyl n-[(3r)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCNC1 DQQJBEAXSOOCPG-SSDOTTSWSA-N 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- IOWGHQGLUMEZKG-UHFFFAOYSA-N (2-bromophenyl)methanol Chemical class OCC1=CC=CC=C1Br IOWGHQGLUMEZKG-UHFFFAOYSA-N 0.000 description 2
- ZHXUWDPHUQHFOV-UHFFFAOYSA-N 2,5-dibromopyridine Chemical compound BrC1=CC=C(Br)N=C1 ZHXUWDPHUQHFOV-UHFFFAOYSA-N 0.000 description 2
- GIMWGWNJYAWERO-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)-1,3-thiazole Chemical compound O1CCOC11CCC(C=2SC=CN=2)CC1 GIMWGWNJYAWERO-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 2
- ZPVFWPFBNIEHGJ-UHFFFAOYSA-N 2-octanone Chemical compound CCCCCCC(C)=O ZPVFWPFBNIEHGJ-UHFFFAOYSA-N 0.000 description 2
- BZFIPFGRXRRZSP-UHFFFAOYSA-N 2-propan-2-yl-1,3-thiazole Chemical compound CC(C)C1=NC=CS1 BZFIPFGRXRRZSP-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- DWRBUHFHONCAED-UHFFFAOYSA-N 3-(fluoromethyl)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(CF)(C(O)=O)C1 DWRBUHFHONCAED-UHFFFAOYSA-N 0.000 description 2
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 2
- QJPHZZUBQAASNR-UHFFFAOYSA-N 4,4-diphenylcyclohexan-1-one Chemical compound C1CC(=O)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 QJPHZZUBQAASNR-UHFFFAOYSA-N 0.000 description 2
- TXGXYODPONPBDR-UHFFFAOYSA-N 4-(1,3-thiazol-2-yl)cyclohexan-1-one Chemical compound C1CC(=O)CCC1C1=NC=CS1 TXGXYODPONPBDR-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- APJQOFZMUGLMPD-UHFFFAOYSA-N 4-hydroxy-4-(1,3-thiazol-2-yl)cyclohexan-1-one Chemical compound N=1C=CSC=1C1(O)CCC(=O)CC1 APJQOFZMUGLMPD-UHFFFAOYSA-N 0.000 description 2
- BNQDPWPXXIFZNN-UHFFFAOYSA-N 4-hydroxy-4-(2-propan-2-yl-1,3-thiazol-5-yl)cyclohexan-1-one Chemical compound S1C(C(C)C)=NC=C1C1(O)CCC(=O)CC1 BNQDPWPXXIFZNN-UHFFFAOYSA-N 0.000 description 2
- OJCQFJMNSSELCN-UHFFFAOYSA-N 4-hydroxy-4-[5-(methoxymethyl)pyridin-2-yl]cyclohexan-1-one Chemical compound N1=CC(COC)=CC=C1C1(O)CCC(=O)CC1 OJCQFJMNSSELCN-UHFFFAOYSA-N 0.000 description 2
- FOZKLMLVBIHOAO-UHFFFAOYSA-N 4-hydroxy-4-pyrimidin-2-ylcyclohexan-1-one Chemical compound N=1C=CC=NC=1C1(O)CCC(=O)CC1 FOZKLMLVBIHOAO-UHFFFAOYSA-N 0.000 description 2
- MOFXSVPGVNPBAU-UHFFFAOYSA-N 4-hydroxy-4-pyrimidin-5-ylcyclohexan-1-one Chemical compound C=1N=CN=CC=1C1(O)CCC(=O)CC1 MOFXSVPGVNPBAU-UHFFFAOYSA-N 0.000 description 2
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 2
- DZZLGMLLNNTZKL-UHFFFAOYSA-N 4-phenoxycyclohexan-1-one Chemical compound C1CC(=O)CCC1OC1=CC=CC=C1 DZZLGMLLNNTZKL-UHFFFAOYSA-N 0.000 description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 2
- XADICJHFELMBGX-UHFFFAOYSA-N 5-bromo-2-methoxypyridine Chemical compound COC1=CC=C(Br)C=N1 XADICJHFELMBGX-UHFFFAOYSA-N 0.000 description 2
- PVUKGNBRJFTFNJ-UHFFFAOYSA-N 6-bromopyridine-3-carbaldehyde Chemical compound BrC1=CC=C(C=O)C=N1 PVUKGNBRJFTFNJ-UHFFFAOYSA-N 0.000 description 2
- WCTNZRJYZYTAOB-UHFFFAOYSA-N 8-(5-pyrazin-2-ylpyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2N=CC(=CC=2)C=2N=CC=NC=2)CCC21OCCO2 WCTNZRJYZYTAOB-UHFFFAOYSA-N 0.000 description 2
- GTHRCIGLVKMIOM-UHFFFAOYSA-N 8-phenoxy-1,4-dioxaspiro[4.5]decane Chemical compound O1CCOC11CCC(OC=2C=CC=CC=2)CC1 GTHRCIGLVKMIOM-UHFFFAOYSA-N 0.000 description 2
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 2
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 2
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 2
- 102000001902 CC Chemokines Human genes 0.000 description 2
- 108010040471 CC Chemokines Proteins 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 102000011652 Formyl peptide receptors Human genes 0.000 description 2
- 108010076288 Formyl peptide receptors Proteins 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 206010027260 Meningitis viral Diseases 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 208000009525 Myocarditis Diseases 0.000 description 2
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 206010033645 Pancreatitis Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 230000008484 agonism Effects 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 238000005576 amination reaction Methods 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 150000001503 aryl iodides Chemical class 0.000 description 2
- 150000004792 aryl magnesium halides Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- XSKKIFJNZPNVGO-UHFFFAOYSA-N benzyl 2,5-dihydropyrrole-1-carboxylate Chemical compound C1C=CCN1C(=O)OCC1=CC=CC=C1 XSKKIFJNZPNVGO-UHFFFAOYSA-N 0.000 description 2
- FZDACFZWWMAUBO-UHFFFAOYSA-N benzyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1C2OC2CN1C(=O)OCC1=CC=CC=C1 FZDACFZWWMAUBO-UHFFFAOYSA-N 0.000 description 2
- MKOSBHNWXFSHSW-UHFFFAOYSA-N bicyclo[2.2.1]hept-2-en-5-ol Chemical compound C1C2C(O)CC1C=C2 MKOSBHNWXFSHSW-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 2
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- DCZFGQYXRKMVFG-UHFFFAOYSA-N cyclohexane-1,4-dione Chemical compound O=C1CCC(=O)CC1 DCZFGQYXRKMVFG-UHFFFAOYSA-N 0.000 description 2
- 125000002243 cyclohexanonyl group Chemical class *C1(*)C(=O)C(*)(*)C(*)(*)C(*)(*)C1(*)* 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- UTUTVSDZKFYNBW-IXDOHACOSA-N diazonio-[(1s,2r)-2-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]azanide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)[C@H]2[C@H](CCCC2)N=[N+]=[N-])=C1 UTUTVSDZKFYNBW-IXDOHACOSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000006735 epoxidation reaction Methods 0.000 description 2
- AGJSHQLIDFFEQY-UHFFFAOYSA-N ethyl 3-(fluoromethyl)pyrrolidine-3-carboxylate Chemical compound CCOC(=O)C1(CF)CCNC1 AGJSHQLIDFFEQY-UHFFFAOYSA-N 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 108091008053 gene clusters Proteins 0.000 description 2
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000007813 immunodeficiency Effects 0.000 description 2
- 230000004957 immunoregulator effect Effects 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- BNHFWQQYLUPDOG-UHFFFAOYSA-N lithium;1,2,2,3-tetramethylpiperidine Chemical compound [Li].CC1CCCN(C)C1(C)C BNHFWQQYLUPDOG-UHFFFAOYSA-N 0.000 description 2
- DQEUYIQDSMINEY-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C=C DQEUYIQDSMINEY-UHFFFAOYSA-M 0.000 description 2
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000000968 medical method and process Methods 0.000 description 2
- 238000003328 mesylation reaction Methods 0.000 description 2
- 125000006682 monohaloalkyl group Chemical group 0.000 description 2
- QYGUIBXTDARAMJ-USEFPYCQSA-N n-[(3r)-1-[4-hydroxy-4-[5-(methoxymethyl)-1,3-thiazol-2-yl]cyclohexyl]pyrrolidin-3-yl]-4-oxo-4-[3-(trifluoromethyl)phenyl]butanamide Chemical compound S1C(COC)=CN=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CCC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 QYGUIBXTDARAMJ-USEFPYCQSA-N 0.000 description 2
- OOVGLJCFBGAHRS-IXDOHACOSA-N n-[2-[[(3r)-1-[(1r,2s)-2-aminocyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N[C@H]1CCCC[C@H]1N1C[C@H](NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 OOVGLJCFBGAHRS-IXDOHACOSA-N 0.000 description 2
- PRUYLKNBFOFGBI-UHFFFAOYSA-N n-[2-[[3-(fluoromethyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C=1C=CC(C(F)(F)F)=CC=1C(=O)NCC(=O)NC1(CF)CCNC1 PRUYLKNBFOFGBI-UHFFFAOYSA-N 0.000 description 2
- SOPGRSZTMMCLLZ-RFVHGSKJSA-N n-[2-oxo-2-[[(3r)-pyrrolidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CNCC2)=C1 SOPGRSZTMMCLLZ-RFVHGSKJSA-N 0.000 description 2
- VFBILHPIHUPBPZ-UHFFFAOYSA-N n-[[2-[4-(difluoromethoxy)-3-propan-2-yloxyphenyl]-1,3-oxazol-4-yl]methyl]-2-ethoxybenzamide Chemical compound CCOC1=CC=CC=C1C(=O)NCC1=COC(C=2C=C(OC(C)C)C(OC(F)F)=CC=2)=N1 VFBILHPIHUPBPZ-UHFFFAOYSA-N 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 125000005593 norbornanyl group Chemical group 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- YLKIYLSIHWAMIC-UHFFFAOYSA-N pyrimidin-2-ylstannane Chemical class [SnH3]C1=NC=CC=N1 YLKIYLSIHWAMIC-UHFFFAOYSA-N 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
- DQARDWKWPIRJEH-UHFFFAOYSA-N tert-butyl n-(4-hydroxycyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(O)CC1 DQARDWKWPIRJEH-UHFFFAOYSA-N 0.000 description 2
- UJDYFIDKXPKQHW-JHJVBQTASA-N tert-butyl n-[(3r)-1-[(1r,2r)-2-hydroxycyclohexyl]pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCN1[C@H]1[C@H](O)CCCC1 UJDYFIDKXPKQHW-JHJVBQTASA-N 0.000 description 2
- IFCNZVDQUYRYDB-FRRDWIJNSA-N tert-butyl n-[(3r)-1-[(1r,2s)-2-azidocyclohexyl]pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCN1[C@H]1[C@@H](N=[N+]=[N-])CCCC1 IFCNZVDQUYRYDB-FRRDWIJNSA-N 0.000 description 2
- 150000003509 tertiary alcohols Chemical class 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 150000003536 tetrazoles Chemical class 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 201000010044 viral meningitis Diseases 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 1
- SDJMPRGSSWSXBK-XFLKPENQSA-N (3as,6ar)-5-hydroxy-5-(6-methoxypyridin-3-yl)-1,3,3a,4,6,6a-hexahydropentalen-2-one Chemical compound C1=NC(OC)=CC=C1C1(O)C[C@H]2CC(=O)C[C@H]2C1 SDJMPRGSSWSXBK-XFLKPENQSA-N 0.000 description 1
- JLUGOUFVUXRUIO-BRWVUGGUSA-N (3r)-1-[(1r,2r)-2-phenylmethoxycyclohexyl]pyrrolidin-3-amine Chemical compound C1[C@H](N)CCN1[C@H]1[C@H](OCC=2C=CC=CC=2)CCCC1 JLUGOUFVUXRUIO-BRWVUGGUSA-N 0.000 description 1
- HBVNLKQGRZPGRP-LLVKDONJSA-N (3r)-1-benzylpyrrolidin-3-amine Chemical compound C1[C@H](N)CCN1CC1=CC=CC=C1 HBVNLKQGRZPGRP-LLVKDONJSA-N 0.000 description 1
- GWKOSRIHVSBBIA-UWTATZPHSA-N (3r)-3-aminooxolane-2,5-dione Chemical compound N[C@@H]1CC(=O)OC1=O GWKOSRIHVSBBIA-UWTATZPHSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- HAFQHNGZPQYKFF-UHFFFAOYSA-N 1,3,3a,4,6,6a-hexahydropentalene-2,5-dione Chemical compound C1C(=O)CC2CC(=O)CC21 HAFQHNGZPQYKFF-UHFFFAOYSA-N 0.000 description 1
- LFMWZTSOMGDDJU-UHFFFAOYSA-N 1,4-diiodobenzene Chemical compound IC1=CC=C(I)C=C1 LFMWZTSOMGDDJU-UHFFFAOYSA-N 0.000 description 1
- 125000000196 1,4-pentadienyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])=C([H])[H] 0.000 description 1
- XGLOOOXUPLGJIB-UHFFFAOYSA-N 1-(6-bromopyridin-3-yl)-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=C(Br)N=C1 XGLOOOXUPLGJIB-UHFFFAOYSA-N 0.000 description 1
- LNNXOEHOXSYWLD-UHFFFAOYSA-N 1-bromobut-2-yne Chemical compound CC#CCBr LNNXOEHOXSYWLD-UHFFFAOYSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- FRHIQRUGEWKYKJ-MDPMHESRSA-N 2-(1,3-benzothiazol-2-ylamino)-n-[(3r)-1-(4-hydroxy-4-pyridin-2-ylcyclohexyl)pyrrolidin-3-yl]acetamide Chemical compound C1CC(N2C[C@@H](CC2)NC(=O)CNC=2SC3=CC=CC=C3N=2)CCC1(O)C1=CC=CC=N1 FRHIQRUGEWKYKJ-MDPMHESRSA-N 0.000 description 1
- RAKJIUKKWFLCPU-UHFFFAOYSA-N 2-(1-hydroxy-4-oxocyclohexyl)-n-methyl-1,3-thiazole-4-carboxamide Chemical compound CNC(=O)C1=CSC(C2(O)CCC(=O)CC2)=N1 RAKJIUKKWFLCPU-UHFFFAOYSA-N 0.000 description 1
- RVCUMWNXZSCWFD-UHFFFAOYSA-N 2-[2-(2-methylsulfonyloxyethyl)-1,3-dioxolan-2-yl]ethyl methanesulfonate Chemical compound CS(=O)(=O)OCCC1(CCOS(C)(=O)=O)OCCO1 RVCUMWNXZSCWFD-UHFFFAOYSA-N 0.000 description 1
- VYADQLKEISKNDT-UHFFFAOYSA-N 2-bromo-5-(methoxymethyl)pyridine Chemical compound COCC1=CC=C(Br)N=C1 VYADQLKEISKNDT-UHFFFAOYSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- BSQLQMLFTHJVKS-UHFFFAOYSA-N 2-chloro-1,3-benzothiazole Chemical compound C1=CC=C2SC(Cl)=NC2=C1 BSQLQMLFTHJVKS-UHFFFAOYSA-N 0.000 description 1
- GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 description 1
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
- LIOLIMKSCNQPLV-UHFFFAOYSA-N 2-fluoro-n-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide Chemical class C1=C(F)C(C(=O)NC)=CC=C1C1=NN2C(CC=3C=C4C=CC=NC4=CC=3)=CN=C2N=C1 LIOLIMKSCNQPLV-UHFFFAOYSA-N 0.000 description 1
- TZZFIUBLIIFZRY-UHFFFAOYSA-N 2-hydroxy-2-phenylbicyclo[2.2.1]heptan-5-one Chemical compound C1C(C(C2)=O)CC2C1(O)C1=CC=CC=C1 TZZFIUBLIIFZRY-UHFFFAOYSA-N 0.000 description 1
- GWYYNQJOHHZUTA-UHFFFAOYSA-N 2-hydroxy-2-pyridin-3-ylbicyclo[2.2.2]octan-5-one Chemical compound C1C(C(C2)=O)CCC2C1(O)C1=CC=CN=C1 GWYYNQJOHHZUTA-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- JUIPGCXELPIYJO-UHFFFAOYSA-N 2-phenylbicyclo[2.2.1]heptane-2,5-diol Chemical compound OC1CC2CC1CC2(O)C1=CC=CC=C1 JUIPGCXELPIYJO-UHFFFAOYSA-N 0.000 description 1
- UDPXHYZDXKTGLD-UHFFFAOYSA-N 2-prop-1-en-2-yl-1,3-thiazole Chemical compound CC(=C)C1=NC=CS1 UDPXHYZDXKTGLD-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- UYWWLYCGNNCLKE-UHFFFAOYSA-N 2-pyridin-4-yl-1h-benzimidazole Chemical compound N=1C2=CC=CC=C2NC=1C1=CC=NC=C1 UYWWLYCGNNCLKE-UHFFFAOYSA-N 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- BYUJNDAVDCNDHG-UHFFFAOYSA-N 3'-pyridin-2-ylspiro[1,3-dioxolane-2,8'-bicyclo[3.2.1]octane]-3'-ol Chemical compound C1C(O)(C=2N=CC=CC=2)CC2CCC1C21OCCO1 BYUJNDAVDCNDHG-UHFFFAOYSA-N 0.000 description 1
- MRCGMTLLNDKWCM-UHFFFAOYSA-N 3-(1-hydroxy-4-oxocyclohexyl)benzonitrile Chemical compound C=1C=CC(C#N)=CC=1C1(O)CCC(=O)CC1 MRCGMTLLNDKWCM-UHFFFAOYSA-N 0.000 description 1
- ONCAZCNPWWQQMW-UHFFFAOYSA-N 3-(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)(F)C1=CC=CC(S(Cl)(=O)=O)=C1 ONCAZCNPWWQQMW-UHFFFAOYSA-N 0.000 description 1
- RUJYJCANMOTJMO-UHFFFAOYSA-N 3-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC(C(Cl)=O)=C1 RUJYJCANMOTJMO-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- UMFPUUCXHDTIEG-UHFFFAOYSA-N 3-hydroxy-3-pyridin-2-ylbicyclo[3.2.1]octan-8-one Chemical compound C1C(C2=O)CCC2CC1(O)C1=CC=CC=N1 UMFPUUCXHDTIEG-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- WOTIUKDGJBXFLG-UHFFFAOYSA-N 3-methyl-1,2-thiazole Chemical compound CC=1C=CSN=1 WOTIUKDGJBXFLG-UHFFFAOYSA-N 0.000 description 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
- RNJOKCPFLQMDEC-UHFFFAOYSA-N 4(R),8-dimethyl-trans-2-nonenoyl-CoA Chemical compound COC(=O)CC(=O)CC(=O)OC RNJOKCPFLQMDEC-UHFFFAOYSA-N 0.000 description 1
- UCFSYHMCKWNKAH-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OBOC1(C)C UCFSYHMCKWNKAH-UHFFFAOYSA-N 0.000 description 1
- LUFGFXHHSGISSL-UHFFFAOYSA-N 4,4-diphenylcyclohex-2-en-1-one Chemical compound C1=CC(=O)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 LUFGFXHHSGISSL-UHFFFAOYSA-N 0.000 description 1
- PRSGSJMIVYYPSW-UHFFFAOYSA-N 4-(1-hydroxy-4-oxocyclohexyl)-n-methylbenzamide Chemical compound C1=CC(C(=O)NC)=CC=C1C1(O)CCC(=O)CC1 PRSGSJMIVYYPSW-UHFFFAOYSA-N 0.000 description 1
- ICEZAAWAFMCYIW-UHFFFAOYSA-N 4-(2-ethoxypyrimidin-5-yl)-4-hydroxycyclohexan-1-one Chemical compound C1=NC(OCC)=NC=C1C1(O)CCC(=O)CC1 ICEZAAWAFMCYIW-UHFFFAOYSA-N 0.000 description 1
- QJUAGKBDTHHPJH-UHFFFAOYSA-N 4-(5-ethyl-1,3-thiazol-2-yl)-4-hydroxycyclohexan-1-one Chemical compound S1C(CC)=CN=C1C1(O)CCC(=O)CC1 QJUAGKBDTHHPJH-UHFFFAOYSA-N 0.000 description 1
- VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
- WHKZKHRRIQZNBU-VEAWUBTESA-N 4-[(3r)-3-aminopyrrolidin-1-yl]-1-(2-propan-2-yl-1,3-thiazol-5-yl)cyclohexan-1-ol Chemical compound S1C(C(C)C)=NC=C1C1(O)CCC(N2C[C@H](N)CC2)CC1 WHKZKHRRIQZNBU-VEAWUBTESA-N 0.000 description 1
- AXXGEBJYVDYPEM-SBBDCZDESA-N 4-[(3r)-3-aminopyrrolidin-1-yl]-1-[2-(methoxymethyl)-1,3-thiazol-4-yl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.S1C(COC)=NC(C2(O)CCC(CC2)N2C[C@H](N)CC2)=C1 AXXGEBJYVDYPEM-SBBDCZDESA-N 0.000 description 1
- YKESULBXCAJTSY-DNOWBOINSA-N 4-[(3r)-3-aminopyrrolidin-1-yl]-1-pyridin-2-ylcyclohexan-1-ol Chemical compound C1[C@H](N)CCN1C1CCC(O)(C=2N=CC=CC=2)CC1 YKESULBXCAJTSY-DNOWBOINSA-N 0.000 description 1
- OTJDHLSHHISAKA-UHFFFAOYSA-N 4-[3-(trifluoromethyl)pyrazol-1-yl]cyclohexan-1-ol Chemical compound C1CC(O)CCC1N1N=C(C(F)(F)F)C=C1 OTJDHLSHHISAKA-UHFFFAOYSA-N 0.000 description 1
- NSFUAXUYLKWYBA-UHFFFAOYSA-N 4-[3-(trifluoromethyl)pyrazol-1-yl]cyclohexan-1-one Chemical compound N1=C(C(F)(F)F)C=CN1C1CCC(=O)CC1 NSFUAXUYLKWYBA-UHFFFAOYSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- IXVVAEXOBSZYRA-UHFFFAOYSA-N 4-[5-(pyrrolidine-1-carbonyl)-1,3-thiazol-2-yl]cyclohexan-1-one Chemical compound C=1N=C(C2CCC(=O)CC2)SC=1C(=O)N1CCCC1 IXVVAEXOBSZYRA-UHFFFAOYSA-N 0.000 description 1
- ZCUBDPUDYGZZTC-UHFFFAOYSA-N 4-[6-(azetidin-1-yl)pyridin-3-yl]-4-hydroxycyclohexan-1-one Chemical compound C=1C=C(N2CCC2)N=CC=1C1(O)CCC(=O)CC1 ZCUBDPUDYGZZTC-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 description 1
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical class BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- FFXLPJMZWJSNBR-UHFFFAOYSA-N 4-hydroxy-4-(4-imidazol-1-ylphenyl)cyclohexan-1-one Chemical compound C=1C=C(N2C=NC=C2)C=CC=1C1(O)CCC(=O)CC1 FFXLPJMZWJSNBR-UHFFFAOYSA-N 0.000 description 1
- SQGONYYHYNKSOQ-UHFFFAOYSA-N 4-hydroxy-4-(4-morpholin-4-ylphenyl)cyclohexan-1-one Chemical compound C=1C=C(N2CCOCC2)C=CC=1C1(O)CCC(=O)CC1 SQGONYYHYNKSOQ-UHFFFAOYSA-N 0.000 description 1
- XWIXNYGAJYDIJJ-UHFFFAOYSA-N 4-hydroxy-4-(5-pyrimidin-5-ylpyridin-2-yl)cyclohexan-1-one Chemical compound C=1C=C(C=2C=NC=NC=2)C=NC=1C1(O)CCC(=O)CC1 XWIXNYGAJYDIJJ-UHFFFAOYSA-N 0.000 description 1
- VQZVMRZEBPGSFQ-UHFFFAOYSA-N 4-hydroxy-4-(6-methoxypyridin-3-yl)cyclohexan-1-one Chemical compound C1=NC(OC)=CC=C1C1(O)CCC(=O)CC1 VQZVMRZEBPGSFQ-UHFFFAOYSA-N 0.000 description 1
- CFBQESWMKLPLTH-UHFFFAOYSA-N 4-hydroxy-4-[4-(1,3-oxazol-2-yl)phenyl]cyclohexan-1-one Chemical compound C=1C=C(C=2OC=CN=2)C=CC=1C1(O)CCC(=O)CC1 CFBQESWMKLPLTH-UHFFFAOYSA-N 0.000 description 1
- ZWLFHRIPUNXJMV-UHFFFAOYSA-N 4-hydroxy-4-pyridazin-3-ylcyclohexan-1-one Chemical compound C=1C=CN=NC=1C1(O)CCC(=O)CC1 ZWLFHRIPUNXJMV-UHFFFAOYSA-N 0.000 description 1
- AHPJOXSVJPJNPD-UHFFFAOYSA-N 4-hydroxy-4-pyridin-2-ylcyclohexan-1-one Chemical compound C=1C=CC=NC=1C1(O)CCC(=O)CC1 AHPJOXSVJPJNPD-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- GKXOABVSZWCJJK-UHFFFAOYSA-N 4-oxo-1-phenylcyclohexane-1-carbonitrile Chemical compound C1CC(=O)CCC1(C#N)C1=CC=CC=C1 GKXOABVSZWCJJK-UHFFFAOYSA-N 0.000 description 1
- GLNOAEGCWGDNDG-UHFFFAOYSA-N 4-oxo-4-[3-(trifluoromethyl)phenyl]butanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=CC(C(F)(F)F)=C1 GLNOAEGCWGDNDG-UHFFFAOYSA-N 0.000 description 1
- FFGVIYUANJAFJS-UHFFFAOYSA-N 4-phenylmethoxycyclohexan-1-one Chemical compound C1CC(=O)CCC1OCC1=CC=CC=C1 FFGVIYUANJAFJS-UHFFFAOYSA-N 0.000 description 1
- NFQXGFVVBYVBGR-UHFFFAOYSA-N 4-pyridin-3-ylcyclohexan-1-one Chemical compound C1CC(=O)CCC1C1=CC=CN=C1 NFQXGFVVBYVBGR-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- MJWQBNFUENPMST-UHFFFAOYSA-N 5'-pyridin-3-ylspiro[1,3-dioxolane-2,2'-bicyclo[2.2.2]octane]-5'-ol Chemical compound C=1C=CN=CC=1C1(O)CC2CCC1CC21OCCO1 MJWQBNFUENPMST-UHFFFAOYSA-N 0.000 description 1
- KVJLDBAMMNBFIL-UHFFFAOYSA-N 5-(1-hydroxy-4-oxocyclohexyl)pyridine-2-carbonitrile Chemical compound C=1C=C(C#N)N=CC=1C1(O)CCC(=O)CC1 KVJLDBAMMNBFIL-UHFFFAOYSA-N 0.000 description 1
- HATLLUIOEIXWGD-UHFFFAOYSA-N 5-bromo-1-methylimidazole Chemical compound CN1C=NC=C1Br HATLLUIOEIXWGD-UHFFFAOYSA-N 0.000 description 1
- XPGIBDJXEVAVTO-UHFFFAOYSA-N 5-bromo-2-chloropyrimidine Chemical compound ClC1=NC=C(Br)C=N1 XPGIBDJXEVAVTO-UHFFFAOYSA-N 0.000 description 1
- WQXZKMUZWPUZGL-UHFFFAOYSA-N 5-bromo-2-ethoxypyridine Chemical compound CCOC1=CC=C(Br)C=N1 WQXZKMUZWPUZGL-UHFFFAOYSA-N 0.000 description 1
- MYUQKYGWKHTRPG-UHFFFAOYSA-N 5-bromo-2-fluoropyridine Chemical compound FC1=CC=C(Br)C=N1 MYUQKYGWKHTRPG-UHFFFAOYSA-N 0.000 description 1
- GYCPLYCTMDTEPU-UHFFFAOYSA-N 5-bromopyrimidine Chemical compound BrC1=CN=CN=C1 GYCPLYCTMDTEPU-UHFFFAOYSA-N 0.000 description 1
- FKVIKTMLTIPULX-UHFFFAOYSA-N 5-phenylbicyclo[2.2.1]hept-2-en-5-ol Chemical compound C1C(C=C2)CC2C1(O)C1=CC=CC=C1 FKVIKTMLTIPULX-UHFFFAOYSA-N 0.000 description 1
- ROQMMVIHFADGGP-UHFFFAOYSA-N 6-(1-hydroxy-4-oxocyclohexyl)pyridine-3-carbonitrile Chemical compound C=1C=C(C#N)C=NC=1C1(O)CCC(=O)CC1 ROQMMVIHFADGGP-UHFFFAOYSA-N 0.000 description 1
- XHYGUDGTUJPSNX-UHFFFAOYSA-N 6-bromopyridine-3-carbonitrile Chemical compound BrC1=CC=C(C#N)C=N1 XHYGUDGTUJPSNX-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- ZTZXZMXLDWHDOZ-UHFFFAOYSA-N 8-(1,3-thiazol-5-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2SC=NC=2)CCC21OCCO2 ZTZXZMXLDWHDOZ-UHFFFAOYSA-N 0.000 description 1
- CWVHSZJBFSEREI-UHFFFAOYSA-N 8-(1-oxidopyridin-1-ium-4-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2C=C[N+]([O-])=CC=2)CCC21OCCO2 CWVHSZJBFSEREI-UHFFFAOYSA-N 0.000 description 1
- QZVAKNFXYBFRQH-UHFFFAOYSA-N 8-(2-ethoxypyrimidin-5-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1=NC(OCC)=NC=C1C1(O)CCC2(OCCO2)CC1 QZVAKNFXYBFRQH-UHFFFAOYSA-N 0.000 description 1
- KJFQSKDOFMENMI-UHFFFAOYSA-N 8-(2-propan-2-yl-1,3-thiazol-5-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound S1C(C(C)C)=NC=C1C1(O)CCC2(OCCO2)CC1 KJFQSKDOFMENMI-UHFFFAOYSA-N 0.000 description 1
- XPIAZELHBIXTGD-UHFFFAOYSA-N 8-(3-methyl-1,2-thiazol-5-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound S1N=C(C)C=C1C1(O)CCC2(OCCO2)CC1 XPIAZELHBIXTGD-UHFFFAOYSA-N 0.000 description 1
- PZFNLQSLQXNSIN-UHFFFAOYSA-N 8-(4-fluorophenyl)-1,4-dioxaspiro[4.5]decane Chemical compound C1=CC(F)=CC=C1C1CCC2(OCCO2)CC1 PZFNLQSLQXNSIN-UHFFFAOYSA-N 0.000 description 1
- JDZDQJLILODJLH-UHFFFAOYSA-N 8-(5-ethyl-1,3-thiazol-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound S1C(CC)=CN=C1C1(O)CCC2(OCCO2)CC1 JDZDQJLILODJLH-UHFFFAOYSA-N 0.000 description 1
- KYKQTANCFOBYMV-UHFFFAOYSA-N 8-(5-pyridin-3-yl-1,3-thiazol-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2SC(=CN=2)C=2C=NC=CC=2)CCC21OCCO2 KYKQTANCFOBYMV-UHFFFAOYSA-N 0.000 description 1
- UIJNXKRSXIWWJP-UHFFFAOYSA-N 8-(6-fluoropyridin-3-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2C=NC(F)=CC=2)CCC21OCCO2 UIJNXKRSXIWWJP-UHFFFAOYSA-N 0.000 description 1
- ROGWOKOMFSPRMV-UHFFFAOYSA-N 8-(6-methoxypyridin-3-yl)-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1=NC(OC)=CC=C1C1(O)CCC2(OCCO2)CC1 ROGWOKOMFSPRMV-UHFFFAOYSA-N 0.000 description 1
- ZLOYNHJYVCJDOJ-UHFFFAOYSA-N 8-[2-(hydroxymethyl)phenyl]-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound OCC1=CC=CC=C1C1(O)CCC2(OCCO2)CC1 ZLOYNHJYVCJDOJ-UHFFFAOYSA-N 0.000 description 1
- ICHYMBALGOTLHD-UHFFFAOYSA-N 8-[5-(2-hydroxypropan-2-yl)pyridin-2-yl]-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound N1=CC(C(C)(O)C)=CC=C1C1(O)CCC2(OCCO2)CC1 ICHYMBALGOTLHD-UHFFFAOYSA-N 0.000 description 1
- ODHJKDCIQWMCOS-UHFFFAOYSA-N 8-phenylmethoxy-1,4-dioxaspiro[4.5]decane Chemical compound C=1C=CC=CC=1COC(CC1)CCC21OCCO2 ODHJKDCIQWMCOS-UHFFFAOYSA-N 0.000 description 1
- LBMSYBZZPYVINE-UHFFFAOYSA-N 8-pyridazin-3-yl-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2N=NC=CC=2)CCC21OCCO2 LBMSYBZZPYVINE-UHFFFAOYSA-N 0.000 description 1
- KMZIXLXSFSDBGN-UHFFFAOYSA-N 8-pyridin-2-yl-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2N=CC=CC=2)CCC21OCCO2 KMZIXLXSFSDBGN-UHFFFAOYSA-N 0.000 description 1
- JYNRHCKBNIPZAG-UHFFFAOYSA-N 8-pyridin-4-yl-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2C=CN=CC=2)CCC21OCCO2 JYNRHCKBNIPZAG-UHFFFAOYSA-N 0.000 description 1
- FSNXNZJAOSSXMY-UHFFFAOYSA-N 8-pyrimidin-2-yl-1,4-dioxaspiro[4.5]decan-8-ol Chemical compound C1CC(O)(C=2N=CC=CN=2)CCC21OCCO2 FSNXNZJAOSSXMY-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- BMFMQGXDDJALKQ-BYPYZUCNSA-N Argininic acid Chemical compound NC(N)=NCCC[C@H](O)C(O)=O BMFMQGXDDJALKQ-BYPYZUCNSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- PSINATRMLYVQIZ-UHFFFAOYSA-N BrC1=NC=C(C#N)C=C1.C(C1=CN=CC=C1)#N Chemical compound BrC1=NC=C(C#N)C=C1.C(C1=CN=CC=C1)#N PSINATRMLYVQIZ-UHFFFAOYSA-N 0.000 description 1
- XWTVBCGGSPGOIK-UHFFFAOYSA-N BrC1=NC=C(C=C1)Br.BrC1=NC=C(C=C1)C(C)(C)O Chemical compound BrC1=NC=C(C=C1)Br.BrC1=NC=C(C=C1)C(C)(C)O XWTVBCGGSPGOIK-UHFFFAOYSA-N 0.000 description 1
- PLYJACJCNREMHY-UHFFFAOYSA-N BrC1=NC=C(C=C1)C.BrC1=NC=C(C=C1)CBr Chemical compound BrC1=NC=C(C=C1)C.BrC1=NC=C(C=C1)CBr PLYJACJCNREMHY-UHFFFAOYSA-N 0.000 description 1
- FZNYXGDOFVFLPR-UHFFFAOYSA-N BrC=1C=CC(=NC1)F.FC1=CC=C(C=N1)C1(CCC2(OCCO2)CC1)O Chemical compound BrC=1C=CC(=NC1)F.FC1=CC=C(C=N1)C1(CCC2(OCCO2)CC1)O FZNYXGDOFVFLPR-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 108050005711 C Chemokine Proteins 0.000 description 1
- 102000017483 C chemokine Human genes 0.000 description 1
- MZMYYHLYYBLUFS-KZYPOYLOSA-N C(C)N(CC)CC.N(=[N+]=[N-])[C@@H]1C[C@@H](N(C1)C(=O)OC(C)(C)C)C Chemical compound C(C)N(CC)CC.N(=[N+]=[N-])[C@@H]1C[C@@H](N(C1)C(=O)OC(C)(C)C)C MZMYYHLYYBLUFS-KZYPOYLOSA-N 0.000 description 1
- KRIAUKREGMCFJN-IODNYQNNSA-N C(C)O.C(C1=CC=CC=C1)N[C@H]1CN(C[C@@H]1O)C(=O)OC(C)(C)C Chemical compound C(C)O.C(C1=CC=CC=C1)N[C@H]1CN(C[C@@H]1O)C(=O)OC(C)(C)C KRIAUKREGMCFJN-IODNYQNNSA-N 0.000 description 1
- GZOIWMMNAOLBOI-UHFFFAOYSA-N C(C1=CC=CC=C1)#N.BrC1=CC=C(C#N)C=C1 Chemical compound C(C1=CC=CC=C1)#N.BrC1=CC=C(C#N)C=C1 GZOIWMMNAOLBOI-UHFFFAOYSA-N 0.000 description 1
- 102100023702 C-C motif chemokine 13 Human genes 0.000 description 1
- 101710112613 C-C motif chemokine 13 Proteins 0.000 description 1
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 1
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 1
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
- 102100034871 C-C motif chemokine 8 Human genes 0.000 description 1
- 101710155833 C-C motif chemokine 8 Proteins 0.000 description 1
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 1
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 1
- 108091008927 CC chemokine receptors Proteins 0.000 description 1
- 102000005674 CCR Receptors Human genes 0.000 description 1
- 108050006947 CXC Chemokine Proteins 0.000 description 1
- 102000019388 CXC chemokine Human genes 0.000 description 1
- 108091008928 CXC chemokine receptors Proteins 0.000 description 1
- 102000054900 CXCR Receptors Human genes 0.000 description 1
- 101100043261 Caenorhabditis elegans spop-1 gene Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000001326 Chemokine CCL4 Human genes 0.000 description 1
- 108010055165 Chemokine CCL4 Proteins 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 108010078239 Chemokine CX3CL1 Proteins 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- DCXYFEDJOCDNAF-UWTATZPHSA-N D-Asparagine Chemical compound OC(=O)[C@H](N)CC(N)=O DCXYFEDJOCDNAF-UWTATZPHSA-N 0.000 description 1
- 229930182846 D-asparagine Natural products 0.000 description 1
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102100023688 Eotaxin Human genes 0.000 description 1
- 101710139422 Eotaxin Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000013818 Fractalkine Human genes 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 101000777599 Homo sapiens C-C chemokine receptor type 2 Proteins 0.000 description 1
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 1
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 101000978374 Mus musculus C-C motif chemokine 12 Proteins 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- XEDKKOYOEPKZCX-UHFFFAOYSA-N O1CCOC11CCC2(C3=CC=CC=C3C=C2)CC1 Chemical compound O1CCOC11CCC2(C3=CC=CC=C3C=C2)CC1 XEDKKOYOEPKZCX-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 244000250129 Trigonella foenum graecum Species 0.000 description 1
- 206010047112 Vasculitides Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- ZDGVDTRMQHGUEW-KXUCPTDWSA-N [(1s,2r)-2-[(3r)-3-aminopyrrolidin-1-yl]cyclohexyl]-diazonioazanide Chemical compound C1[C@H](N)CCN1[C@H]1[C@@H](N=[N+]=[N-])CCCC1 ZDGVDTRMQHGUEW-KXUCPTDWSA-N 0.000 description 1
- SAHIZENKTPRYSN-UHFFFAOYSA-N [2-[3-(phenoxymethyl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound O(C1=CC=CC=C1)CC=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 SAHIZENKTPRYSN-UHFFFAOYSA-N 0.000 description 1
- MIOMSJAJALNCIT-UHFFFAOYSA-N [4-[tert-butyl(dimethyl)silyl]oxycyclohexyl] methanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OC1CCC(OS(C)(=O)=O)CC1 MIOMSJAJALNCIT-UHFFFAOYSA-N 0.000 description 1
- SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 description 1
- DZJXKISLUDYJSV-UHFFFAOYSA-N [N].C1CCNC1 Chemical compound [N].C1CCNC1 DZJXKISLUDYJSV-UHFFFAOYSA-N 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000005236 alkanoylamino group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 235000015241 bacon Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- IXPLJRREJIUKLG-GHMZBOCLSA-N benzyl (3r,4r)-3-amino-4-hydroxypyrrolidine-1-carboxylate Chemical compound C1[C@@H](O)[C@H](N)CN1C(=O)OCC1=CC=CC=C1 IXPLJRREJIUKLG-GHMZBOCLSA-N 0.000 description 1
- IXPLJRREJIUKLG-QWRGUYRKSA-N benzyl (3s,4s)-3-amino-4-hydroxypyrrolidine-1-carboxylate Chemical compound C1[C@H](O)[C@@H](N)CN1C(=O)OCC1=CC=CC=C1 IXPLJRREJIUKLG-QWRGUYRKSA-N 0.000 description 1
- CMXBVXJSFDXHTE-KBPBESRZSA-N benzyl (3s,4s)-3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidine-1-carboxylate Chemical compound C1[C@H](O)[C@@H](NC(=O)OC(C)(C)C)CN1C(=O)OCC1=CC=CC=C1 CMXBVXJSFDXHTE-KBPBESRZSA-N 0.000 description 1
- CMXBVXJSFDXHTE-UHFFFAOYSA-N benzyl 3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidine-1-carboxylate Chemical compound C1C(O)C(NC(=O)OC(C)(C)C)CN1C(=O)OCC1=CC=CC=C1 CMXBVXJSFDXHTE-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- HUQXEIFQYCVOPD-UHFFFAOYSA-N bicyclo[2.2.1]hept-2-en-5-one Chemical compound C1C2C(=O)CC1C=C2 HUQXEIFQYCVOPD-UHFFFAOYSA-N 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- XRGPFNGLRSIPSA-UHFFFAOYSA-N butyn-2-one Chemical compound CC(=O)C#C XRGPFNGLRSIPSA-UHFFFAOYSA-N 0.000 description 1
- VNWKTOKETHGBQD-YPZZEJLDSA-N carbane Chemical compound [10CH4] VNWKTOKETHGBQD-YPZZEJLDSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000006041 cell recruitment Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000012085 chronic inflammatory response Effects 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- VKONPUDBRVKQLM-UHFFFAOYSA-N cyclohexane-1,4-diol Chemical compound OC1CCC(O)CC1 VKONPUDBRVKQLM-UHFFFAOYSA-N 0.000 description 1
- ZWAJLVLEBYIOTI-UHFFFAOYSA-N cyclohexene oxide Chemical compound C1CCCC2OC21 ZWAJLVLEBYIOTI-UHFFFAOYSA-N 0.000 description 1
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohexene oxide Natural products O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 125000006009 dihaloalkoxy group Chemical group 0.000 description 1
- BYHXBBOSJKPUJL-SCSAIBSYSA-N dimethyl (2r)-2-aminobutanedioate Chemical compound COC(=O)C[C@@H](N)C(=O)OC BYHXBBOSJKPUJL-SCSAIBSYSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 230000007646 directional migration Effects 0.000 description 1
- TXKMVPPZCYKFAC-UHFFFAOYSA-N disulfur monoxide Inorganic materials O=S=S TXKMVPPZCYKFAC-UHFFFAOYSA-N 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- UMJWVRIJGCYYTH-UHFFFAOYSA-N ethyl 2-(fluoromethyl)prop-2-enoate Chemical compound CCOC(=O)C(=C)CF UMJWVRIJGCYYTH-UHFFFAOYSA-N 0.000 description 1
- SYGAXBISYRORDR-UHFFFAOYSA-N ethyl 2-(hydroxymethyl)prop-2-enoate Chemical compound CCOC(=O)C(=C)CO SYGAXBISYRORDR-UHFFFAOYSA-N 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 230000033687 granuloma formation Effects 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000004820 halides Chemical group 0.000 description 1
- 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 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 102000043994 human CCR2 Human genes 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 150000002469 indenes Chemical class 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000004501 isothiazol-5-yl group Chemical group S1N=CC=C1* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 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 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- NAFBIYLNNXZOFN-UHFFFAOYSA-N methyl n-(1,3-thiazol-2-yl)carbamate Chemical compound COC(=O)NC1=NC=CS1 NAFBIYLNNXZOFN-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 108010065176 monocyte chemoattractant protein 1 (9-76) Proteins 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- NMUXPVMDAYGGGN-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)-2-(4-chlorophenoxy)-2-methylpropanamide Chemical group N=1C2=CC=CC=C2SC=1NC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 NMUXPVMDAYGGGN-UHFFFAOYSA-N 0.000 description 1
- RPZAAFUKDPKTKP-UHFFFAOYSA-N n-(methoxymethyl)-1-phenyl-n-(trimethylsilylmethyl)methanamine Chemical compound COCN(C[Si](C)(C)C)CC1=CC=CC=C1 RPZAAFUKDPKTKP-UHFFFAOYSA-N 0.000 description 1
- PFYGLJDZACOOGI-ZGGTZUKQSA-N n-[(3r)-1-(4-hydroxy-4-pyridin-2-ylcyclohexyl)pyrrolidin-3-yl]-2-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]acetamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1N=CC=CC=1)C(=O)CNC1=NC=C(C(F)(F)F)C=N1 PFYGLJDZACOOGI-ZGGTZUKQSA-N 0.000 description 1
- DODIQVYFIPAFNG-BGPPBHKUSA-N n-[(3r)-1-[4-hydroxy-4-(2-propan-2-yl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl]-4-oxo-4-[3-(trifluoromethyl)phenyl]butanamide Chemical compound S1C(C(C)C)=NC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CCC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 DODIQVYFIPAFNG-BGPPBHKUSA-N 0.000 description 1
- YJNIOQCPYIOBNA-CMZFYYCHSA-N n-[(3r)-1-[4-hydroxy-4-[2-(methoxymethyl)-1,3-thiazol-5-yl]cyclohexyl]pyrrolidin-3-yl]-3-[3-(trifluoromethyl)phenyl]-4,5-dihydro-1,2-oxazole-5-carboxamide Chemical compound S1C(COC)=NC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)C2ON=C(C2)C=2C=C(C=CC=2)C(F)(F)F)CC1 YJNIOQCPYIOBNA-CMZFYYCHSA-N 0.000 description 1
- SLBGEOHOQYOJDQ-GBFLJEJBSA-N n-[(3r)-1-[4-hydroxy-4-[5-(methoxymethyl)-1,3-thiazol-2-yl]cyclohexyl]pyrrolidin-3-yl]-2-[[3-(trifluoromethyl)phenyl]sulfonylamino]acetamide Chemical compound S1C(COC)=CN=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNS(=O)(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 SLBGEOHOQYOJDQ-GBFLJEJBSA-N 0.000 description 1
- XGBQQIOZTRKZBT-TZRRMPRUSA-N n-[2-[[(3r)-1-[(1r,2s)-2-(benzylamino)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)[C@H]2[C@H](CCCC2)NCC=2C=CC=CC=2)=C1 XGBQQIOZTRKZBT-TZRRMPRUSA-N 0.000 description 1
- ZSIFWDIDYHWREH-XPWALMASSA-N n-[2-[[(3r)-1-[(1r,2s)-2-benzamidocyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)[C@H]2[C@H](CCCC2)NC(=O)C=2C=CC=CC=2)=C1 ZSIFWDIDYHWREH-XPWALMASSA-N 0.000 description 1
- CJBYIXYFDKYORO-WXFIPNSDSA-N n-[2-[[(3r)-1-[4-[6-(azetidin-1-yl)pyridin-3-yl]-4-hydroxycyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=NC(=CC=1)N1CCC1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 CJBYIXYFDKYORO-WXFIPNSDSA-N 0.000 description 1
- AILFACXPIFCOQB-PXLQRDNWSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(4-morpholin-4-ylphenyl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@@H]1CCN(C1)C1CCC(CC1)(O)C=1C=CC(=CC=1)N1CCOCC1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 AILFACXPIFCOQB-PXLQRDNWSA-N 0.000 description 1
- BNVBPNFTCXVZFU-ANTXIRGESA-N n-[2-[[(3r)-1-[4-hydroxy-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(C2(O)CCC(CC2)N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)C=C1 BNVBPNFTCXVZFU-ANTXIRGESA-N 0.000 description 1
- FAAVOKBSFIJHRY-GOSISDBHSA-N n-[2-[[(3r)-1-benzylpyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC=3C=CC=CC=3)CC2)=C1 FAAVOKBSFIJHRY-GOSISDBHSA-N 0.000 description 1
- PMDFLMLMKGRVMO-JOYOIKCWSA-N n-[2-[[(3r,5s)-5-methylpyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1N[C@@H](C)C[C@H]1NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 PMDFLMLMKGRVMO-JOYOIKCWSA-N 0.000 description 1
- MOGZKELVHMJQEA-ZQFKLAOWSA-N n-[2-[[(3s,4s)-1-(4-cyano-4-phenylcyclohexyl)-4-hydroxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1O)C1CCC(CC1)(C#N)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 MOGZKELVHMJQEA-ZQFKLAOWSA-N 0.000 description 1
- BRUXGNAPXGHDCI-XRYVGEESSA-N n-[2-[[(3s,4s)-1-[4-(4-fluorophenyl)cyclohexyl]-4-hydroxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1O)C1CCC(CC1)C=1C=CC(F)=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 BRUXGNAPXGHDCI-XRYVGEESSA-N 0.000 description 1
- BUPXXNZCSAFGJW-GOTSBHOMSA-N n-[2-[[(3s,4s)-1-cyclohexyl-4-(pyridin-2-ylmethoxy)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@@H]2[C@H](CN(C2)C2CCCCC2)OCC=2N=CC=CC=2)=C1 BUPXXNZCSAFGJW-GOTSBHOMSA-N 0.000 description 1
- RQHCXVKNDMXMHM-GOTSBHOMSA-N n-[2-[[(3s,4s)-1-cyclohexyl-4-(pyridin-3-ylmethoxy)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@@H]2[C@H](CN(C2)C2CCCCC2)OCC=2C=NC=CC=2)=C1 RQHCXVKNDMXMHM-GOTSBHOMSA-N 0.000 description 1
- YDYMBWBMCHCIGW-IRXDYDNUSA-N n-[2-[[(3s,4s)-1-cyclohexyl-4-hydroxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1O)C1CCCCC1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 YDYMBWBMCHCIGW-IRXDYDNUSA-N 0.000 description 1
- VGTKGBXYMBWRLP-ZEQRLZLVSA-N n-[2-[[(3s,4s)-1-cyclohexyl-4-phenylmethoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@@H]2[C@H](CN(C2)C2CCCCC2)OCC=2C=CC=CC=2)=C1 VGTKGBXYMBWRLP-ZEQRLZLVSA-N 0.000 description 1
- VWTUFSFJTJNEGZ-STQMWFEESA-N n-[2-[[(3s,4s)-4-ethoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound CCO[C@H]1CNC[C@@H]1NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 VWTUFSFJTJNEGZ-STQMWFEESA-N 0.000 description 1
- MZIHXQCZYGZXOH-NFJKTXFASA-N n-[2-[[(3s,4s)-4-hydroxy-1-(4-hydroxy-4-phenylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1O)C1CCC(O)(CC1)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 MZIHXQCZYGZXOH-NFJKTXFASA-N 0.000 description 1
- FIFCGZJWFIFLMF-ZNJKDYDLSA-N n-[2-[[(3s,4s)-4-hydroxy-1-(4-pyridin-2-ylcyclohexyl)pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound N([C@H]1CN(C[C@@H]1O)C1CCC(CC1)C=1N=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 FIFCGZJWFIFLMF-ZNJKDYDLSA-N 0.000 description 1
- WLTSTGUAEABPSL-QWRGUYRKSA-N n-[2-[[(3s,4s)-4-hydroxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound O[C@H]1CNC[C@@H]1NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 WLTSTGUAEABPSL-QWRGUYRKSA-N 0.000 description 1
- OQIWLKCCJDGVMN-KNVGNIICSA-N n-[2-[[(9s)-1-oxa-7-azaspiro[4.4]nonan-9-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@@H]2C3(OCCC3)CNC2)=C1 OQIWLKCCJDGVMN-KNVGNIICSA-N 0.000 description 1
- WZNKSIIQOAVQIF-UHFFFAOYSA-N n-[2-oxo-2-[(4-propoxypyrrolidin-3-yl)amino]ethyl]-3-(trifluoromethyl)benzamide;hydrochloride Chemical compound Cl.CCCOC1CNCC1NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 WZNKSIIQOAVQIF-UHFFFAOYSA-N 0.000 description 1
- AILUUVYEEYSXLA-HVIUMASTSA-N n-[2-oxo-2-[[(3r)-1-(4-phenoxycyclohexyl)pyrrolidin-3-yl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)N[C@H]2CN(CC2)C2CCC(CC2)OC=2C=CC=CC=2)=C1 AILUUVYEEYSXLA-HVIUMASTSA-N 0.000 description 1
- FSZSDNUJVRRJGL-GFCCVEGCSA-N n-[2-oxo-2-[[2-oxo-2-[[(3r)-pyrrolidin-3-yl]amino]ethyl]amino]ethyl]-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC(C(=O)NCC(=O)NCC(=O)N[C@H]2CNCC2)=C1 FSZSDNUJVRRJGL-GFCCVEGCSA-N 0.000 description 1
- IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-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
- DOWVMJFBDGWVML-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-(1-oxidopyridin-1-ium-3-yl)imidazole-1-carboxamide Chemical compound C1=NC(C=2C=[N+]([O-])C=CC=2)=CN1C(=O)N(C)C1CCCCC1 DOWVMJFBDGWVML-UHFFFAOYSA-N 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- BMGNSKKZFQMGDH-FDGPNNRMSA-L nickel(2+);(z)-4-oxopent-2-en-2-olate Chemical compound [Ni+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O BMGNSKKZFQMGDH-FDGPNNRMSA-L 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- HZFPPBMKGYINDF-UHFFFAOYSA-N pyrimidin-5-ylboronic acid Chemical compound OB(O)C1=CN=CN=C1 HZFPPBMKGYINDF-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- NJPNCMOUEXEGBL-UHFFFAOYSA-N pyrrolidin-1-ium-3-ylazanium;dichloride Chemical class Cl.Cl.NC1CCNC1 NJPNCMOUEXEGBL-UHFFFAOYSA-N 0.000 description 1
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 229940075993 receptor modulator Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000005316 response function Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000003567 signal transduction assay Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- KRLYHLGATLMEHM-UHFFFAOYSA-N sodium;sulfane;dihydrate Chemical compound O.O.[Na].S KRLYHLGATLMEHM-UHFFFAOYSA-N 0.000 description 1
- PAEHPXBPMYLKFT-UHFFFAOYSA-N spiro[1,3-dioxolane-2,2'-bicyclo[2.2.2]octane]-5'-one Chemical compound O=C1CC2CCC1CC21OCCO1 PAEHPXBPMYLKFT-UHFFFAOYSA-N 0.000 description 1
- GXXDQCQJQADFEF-UHFFFAOYSA-N spiro[1,3-dioxolane-2,8'-bicyclo[3.2.1]octane]-3'-one Chemical compound C1C(=O)CC2CCC1C21OCCO1 GXXDQCQJQADFEF-UHFFFAOYSA-N 0.000 description 1
- WYCAULLRAUQXQI-UHFFFAOYSA-N spiro[1h-2-benzofuran-3,4'-cyclohexane]-1'-one Chemical compound C1CC(=O)CCC21C1=CC=CC=C1CO2 WYCAULLRAUQXQI-UHFFFAOYSA-N 0.000 description 1
- VJXXFAOBEQXONX-UHFFFAOYSA-N spiro[cyclohexane-4,1'-indene]-1-one Chemical compound C1CC(=O)CCC21C1=CC=CC=C1C=C2 VJXXFAOBEQXONX-UHFFFAOYSA-N 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical compound S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- LHXOHIGFGUYCQA-SWLSCSKDSA-N tert-butyl (2s,4r)-2-methyl-4-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@@H](C)C[C@H]1NC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 LHXOHIGFGUYCQA-SWLSCSKDSA-N 0.000 description 1
- RDMVVTNPIKHJHP-JGVFFNPUSA-N tert-butyl (2s,4r)-4-amino-2-methylpyrrolidine-1-carboxylate Chemical compound C[C@H]1C[C@@H](N)CN1C(=O)OC(C)(C)C RDMVVTNPIKHJHP-JGVFFNPUSA-N 0.000 description 1
- BXZADLGAYWRZCR-JGVFFNPUSA-N tert-butyl (2s,4r)-4-hydroxy-2-methylpyrrolidine-1-carboxylate Chemical compound C[C@H]1C[C@@H](O)CN1C(=O)OC(C)(C)C BXZADLGAYWRZCR-JGVFFNPUSA-N 0.000 description 1
- XHRFATITHHJMOL-JSGCOSHPSA-N tert-butyl (2s,4s)-4-benzoyloxy-2-methylpyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@@H](C)C[C@@H]1OC(=O)C1=CC=CC=C1 XHRFATITHHJMOL-JSGCOSHPSA-N 0.000 description 1
- BXZADLGAYWRZCR-YUMQZZPRSA-N tert-butyl (2s,4s)-4-hydroxy-2-methylpyrrolidine-1-carboxylate Chemical compound C[C@H]1C[C@H](O)CN1C(=O)OC(C)(C)C BXZADLGAYWRZCR-YUMQZZPRSA-N 0.000 description 1
- MOZOQDNRVPHFOO-RNFRBKRXSA-N tert-butyl (3r,4r)-3-amino-4-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@@H](N)[C@H](O)C1 MOZOQDNRVPHFOO-RNFRBKRXSA-N 0.000 description 1
- CSWBTQKOSPXYIE-RNFRBKRXSA-N tert-butyl (3r,4r)-3-azido-4-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@@H](O)[C@H](N=[N+]=[N-])C1 CSWBTQKOSPXYIE-RNFRBKRXSA-N 0.000 description 1
- AQAYKZPAVJQYHP-GOTSBHOMSA-N tert-butyl (3s,4s)-3-[benzyl(phenylmethoxycarbonyl)amino]-4-ethoxypyrrolidine-1-carboxylate Chemical compound CCO[C@H]1CN(C(=O)OC(C)(C)C)C[C@@H]1N(C(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 AQAYKZPAVJQYHP-GOTSBHOMSA-N 0.000 description 1
- SBNLGJLMZOOKSR-SFTDATJTSA-N tert-butyl (3s,4s)-3-[benzyl(phenylmethoxycarbonyl)amino]-4-hydroxypyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)C[C@H](O)[C@H]1N(C(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 SBNLGJLMZOOKSR-SFTDATJTSA-N 0.000 description 1
- FHDMKFDRCCQJTA-IUCAKERBSA-N tert-butyl (3s,4s)-3-amino-4-ethoxypyrrolidine-1-carboxylate Chemical compound CCO[C@H]1CN(C(=O)OC(C)(C)C)C[C@@H]1N FHDMKFDRCCQJTA-IUCAKERBSA-N 0.000 description 1
- MOZOQDNRVPHFOO-BQBZGAKWSA-N tert-butyl (3s,4s)-3-amino-4-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@H](N)[C@@H](O)C1 MOZOQDNRVPHFOO-BQBZGAKWSA-N 0.000 description 1
- QBBSDMSNGMRKCQ-KBPBESRZSA-N tert-butyl (3s,4s)-3-hydroxy-4-(phenylmethoxycarbonylamino)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)C[C@H](O)[C@H]1NC(=O)OCC1=CC=CC=C1 QBBSDMSNGMRKCQ-KBPBESRZSA-N 0.000 description 1
- SAEXPDXDLNMAHL-DJZRFWRSSA-N tert-butyl (4s)-3-hydroxy-3-(3-hydroxypropyl)-4-(phenylmethoxycarbonylamino)pyrrolidine-1-carboxylate Chemical compound OCCCC1(O)CN(C(=O)OC(C)(C)C)C[C@@H]1NC(=O)OCC1=CC=CC=C1 SAEXPDXDLNMAHL-DJZRFWRSSA-N 0.000 description 1
- RYZYWTOZMAUABX-ZDUSSCGKSA-N tert-butyl (4s)-3-oxo-4-(phenylmethoxycarbonylamino)pyrrolidine-1-carboxylate Chemical compound O=C1CN(C(=O)OC(C)(C)C)C[C@@H]1NC(=O)OCC1=CC=CC=C1 RYZYWTOZMAUABX-ZDUSSCGKSA-N 0.000 description 1
- MDTWVDPWLATSSK-DJZRFWRSSA-N tert-butyl (9s)-9-(phenylmethoxycarbonylamino)-1-oxa-7-azaspiro[4.4]nonane-7-carboxylate Chemical compound N([C@H]1CN(CC11OCCC1)C(=O)OC(C)(C)C)C(=O)OCC1=CC=CC=C1 MDTWVDPWLATSSK-DJZRFWRSSA-N 0.000 description 1
- PYMXLJHFKQVGHD-BJQOMGFOSA-N tert-butyl (9s)-9-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]-1-oxa-7-azaspiro[4.4]nonane-7-carboxylate Chemical compound N([C@H]1CN(CC11OCCC1)C(=O)OC(C)(C)C)C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 PYMXLJHFKQVGHD-BJQOMGFOSA-N 0.000 description 1
- HNYUXHMUVZLBQY-QHGLUPRGSA-N tert-butyl (9s)-9-amino-1-oxa-7-azaspiro[4.4]nonane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)C[C@H](N)C11OCCC1 HNYUXHMUVZLBQY-QHGLUPRGSA-N 0.000 description 1
- UEXPMSITLUGIPA-UHFFFAOYSA-N tert-butyl 2,5-dihydro-1h-pyrrole-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1NCC=C1 UEXPMSITLUGIPA-UHFFFAOYSA-N 0.000 description 1
- YEBDZDMYLQHGGZ-UHFFFAOYSA-N tert-butyl 2,5-dihydropyrrole-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC=CC1 YEBDZDMYLQHGGZ-UHFFFAOYSA-N 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- NXZIGGBPLGAPTI-UHFFFAOYSA-N tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2OC21 NXZIGGBPLGAPTI-UHFFFAOYSA-N 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- VSUVTEPINAOAJR-LSWWBPAMSA-N tert-butyl n-[(3r)-1-(4-hydroxy-4-pyridin-2-ylcyclohexyl)pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCN1C1CCC(O)(C=2N=CC=CC=2)CC1 VSUVTEPINAOAJR-LSWWBPAMSA-N 0.000 description 1
- KIMBFGIZSUREMC-DNPZQZLWSA-N tert-butyl n-[(3r)-1-(8-hydroxy-8-phenyl-3-bicyclo[3.2.1]octanyl)pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCN1C1CC(C2(O)C=3C=CC=CC=3)CCC2C1 KIMBFGIZSUREMC-DNPZQZLWSA-N 0.000 description 1
- SVMKNWMGKZSVSZ-WCFLAILDSA-N tert-butyl n-[(3r)-1-(8-oxo-3-bicyclo[3.2.1]octanyl)pyrrolidin-3-yl]carbamate Chemical class C1[C@H](NC(=O)OC(C)(C)C)CCN1C1CC(C2=O)CCC2C1 SVMKNWMGKZSVSZ-WCFLAILDSA-N 0.000 description 1
- IWVSLZYKDPTYLO-VAMGGRTRSA-N tert-butyl n-[(3r)-1-[(1r,2r)-2-phenylmethoxycyclohexyl]pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCN1[C@H]1[C@H](OCC=2C=CC=CC=2)CCCC1 IWVSLZYKDPTYLO-VAMGGRTRSA-N 0.000 description 1
- GYFSNPWKIQHPNM-IZINQKCZSA-N tert-butyl n-[(3r)-1-[4-hydroxy-4-(2-propan-2-yl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl]carbamate Chemical compound S1C(C(C)C)=NC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)OC(C)(C)C)CC1 GYFSNPWKIQHPNM-IZINQKCZSA-N 0.000 description 1
- XKUFMQCHDANOOL-IOJLRTSASA-N tert-butyl n-[4-[(3r)-3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]pyrrolidin-1-yl]cyclohexyl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCC1N1C[C@H](NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 XKUFMQCHDANOOL-IOJLRTSASA-N 0.000 description 1
- DQQJBEAXSOOCPG-UHFFFAOYSA-N tert-butyl n-pyrrolidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNC1 DQQJBEAXSOOCPG-UHFFFAOYSA-N 0.000 description 1
- CDHGDNKFIYSGLO-UHFFFAOYSA-N tert-butyl-dimethyl-[4-[3-(trifluoromethyl)pyrazol-1-yl]cyclohexyl]oxysilane Chemical compound C1CC(O[Si](C)(C)C(C)(C)C)CCC1N1N=C(C(F)(F)F)C=C1 CDHGDNKFIYSGLO-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/08—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Ophthalmology & Optometry (AREA)
- Otolaryngology (AREA)
- Transplantation (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42960502P | 2002-11-27 | 2002-11-27 | |
| US60/429,605 | 2002-11-27 | ||
| US46397603P | 2003-04-18 | 2003-04-18 | |
| US60/463,976 | 2003-04-18 | ||
| PCT/US2003/037946 WO2004050024A2 (en) | 2002-11-27 | 2003-11-26 | 3-aminopyrrolidine derivatives as modulators of chemokine receptors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011160080A Division JP2011251987A (ja) | 2002-11-27 | 2011-07-21 | ケモカイン受容体のモジュレーターとしての3−アミノピロリジン誘導体 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2006516145A JP2006516145A (ja) | 2006-06-22 |
| JP2006516145A5 JP2006516145A5 (enExample) | 2007-01-18 |
| JP4828829B2 true JP4828829B2 (ja) | 2011-11-30 |
Family
ID=32474514
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004570963A Expired - Lifetime JP4828829B2 (ja) | 2002-11-27 | 2003-11-26 | ケモカイン受容体のモジュレーターとしての3−アミノピロリジン誘導体 |
| JP2011160080A Pending JP2011251987A (ja) | 2002-11-27 | 2011-07-21 | ケモカイン受容体のモジュレーターとしての3−アミノピロリジン誘導体 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011160080A Pending JP2011251987A (ja) | 2002-11-27 | 2011-07-21 | ケモカイン受容体のモジュレーターとしての3−アミノピロリジン誘導体 |
Country Status (26)
| Country | Link |
|---|---|
| US (4) | US7834021B2 (enExample) |
| EP (2) | EP1565436B1 (enExample) |
| JP (2) | JP4828829B2 (enExample) |
| KR (1) | KR100895968B1 (enExample) |
| CN (1) | CN102153539B (enExample) |
| AT (1) | ATE555087T1 (enExample) |
| AU (1) | AU2003293129B2 (enExample) |
| BR (1) | BRPI0316732B8 (enExample) |
| CA (1) | CA2507501C (enExample) |
| CO (1) | CO5690550A2 (enExample) |
| CR (2) | CR7846A (enExample) |
| EA (1) | EA010027B1 (enExample) |
| EC (1) | ECSP055856A (enExample) |
| ES (1) | ES2383296T3 (enExample) |
| GE (1) | GEP20115290B (enExample) |
| HU (1) | HU230612B1 (enExample) |
| IL (1) | IL168742A (enExample) |
| IS (1) | IS2892B (enExample) |
| MX (1) | MXPA05005660A (enExample) |
| NO (1) | NO330860B1 (enExample) |
| NZ (1) | NZ540290A (enExample) |
| PL (1) | PL376925A1 (enExample) |
| RU (1) | RU2355679C2 (enExample) |
| SE (1) | SE529361C2 (enExample) |
| SG (1) | SG173922A1 (enExample) |
| WO (1) | WO2004050024A2 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011251987A (ja) * | 2002-11-27 | 2011-12-15 | Incyte Corp | ケモカイン受容体のモジュレーターとしての3−アミノピロリジン誘導体 |
| US8635940B2 (en) | 2008-01-07 | 2014-01-28 | Vanderbilt University | Solenoid valve assembly |
Families Citing this family (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0202133D0 (sv) * | 2002-07-08 | 2002-07-08 | Astrazeneca Ab | Novel compounds |
| US7378409B2 (en) | 2003-08-21 | 2008-05-27 | Bristol-Myers Squibb Company | Substituted cycloalkylamine derivatives as modulators of chemokine receptor activity |
| SE0302755D0 (sv) * | 2003-10-17 | 2003-10-17 | Astrazeneca Ab | Novel compounds |
| US20070021498A1 (en) * | 2004-10-14 | 2007-01-25 | Nafizal Hossain | Novel tricyclic spiroderivatives as modulators of chemokine receptor activity |
| SE0303090D0 (sv) * | 2003-11-20 | 2003-11-20 | Astrazeneca Ab | Novel compounds |
| CN102344398B (zh) * | 2003-12-18 | 2015-02-25 | 因赛特公司 | 作为趋化因子受体调控剂的3-环烷基氨基吡咯烷衍生物 |
| SE0303541D0 (sv) | 2003-12-22 | 2003-12-22 | Astrazeneca Ab | New compounds |
| CA2562235C (en) | 2004-04-13 | 2013-09-24 | Incyte Corporation | Piperazinylpiperidine derivatives as chemokine receptor antagonists |
| CN1950085A (zh) | 2004-05-11 | 2007-04-18 | 因赛特公司 | 作为趋化因子受体调节剂的3-(4-杂芳基环己基氨基)环戊烷羧酰胺 |
| CN1329374C (zh) * | 2004-06-09 | 2007-08-01 | 上海靶点药物有限公司 | 作为ccr5拮抗剂的化合物 |
| AU2005260013A1 (en) | 2004-06-28 | 2006-01-12 | Incyte Corporation | 3-aminocyclopentanecarboxamides as modulators of chemokine receptors |
| CN102382088A (zh) | 2004-06-28 | 2012-03-21 | 因赛特公司 | 作为趋化因子受体调节剂的3-氨基环戊烷甲酰胺类 |
| GB0417801D0 (en) * | 2004-08-10 | 2004-09-15 | Novartis Ag | Organic compounds |
| UY29219A1 (es) * | 2004-11-22 | 2006-04-28 | Incyte Corp | Sales de la n-(2- (((3r)-1-(trans-4-hidroxi-4-(6-metoxipiridin-3-il)-cilohexil) pirrolidin-3-il)amino)-2-oxoetil)-3- (trifluorometil) benzamida |
| KR20070091677A (ko) | 2004-12-24 | 2007-09-11 | 아스트라제네카 아베 | Ccr2b 길항제로서의 헤테로시클릭 화합물 |
| US8067457B2 (en) | 2005-11-01 | 2011-11-29 | Millennium Pharmaceuticals, Inc. | Compounds useful as antagonists of CCR2 |
| WO2007053499A2 (en) | 2005-11-01 | 2007-05-10 | Millennium Pharmaceuticals, Inc. | Compounds useful as antagonists of ccr2 |
| GB0525957D0 (en) | 2005-12-21 | 2006-02-01 | Astrazeneca Ab | Methods |
| CN101553493B (zh) * | 2006-07-19 | 2012-07-04 | 阿斯利康(瑞典)有限公司 | 三环螺哌啶化合物、它们的合成和它们作为趋化因子受体活性调节剂的用途 |
| WO2008045564A2 (en) * | 2006-10-12 | 2008-04-17 | Epix Delaware, Inc. | Carboxamide compounds and their use as antagonists of the chemokine ccr2 receptor |
| WO2008060621A2 (en) | 2006-11-17 | 2008-05-22 | Abbott Laboratories | Aminopyrrolidines as chemokine receptor antagonists |
| WO2008063714A1 (en) * | 2006-11-20 | 2008-05-29 | N.V. Organon | Metabolically-stabilized inhibitors of fatty acid amide hydrolase |
| US7496166B1 (en) * | 2008-04-29 | 2009-02-24 | International Business Machines Corporation | Dual clock spread for low clock emissions with recovery |
| ES2567786T3 (es) * | 2008-07-17 | 2016-04-26 | Bayer Cropscience Ag | Compuestos heterocíclicos como pesticidas |
| US20110230428A1 (en) * | 2008-07-22 | 2011-09-22 | John Wityak | Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
| CA2745969C (en) | 2008-12-10 | 2017-04-25 | Janssen Pharmaceutica Nv | 4-azetidinyl-1-heteroaryl-cyclohexanol antagonists of ccr2 |
| KR101084551B1 (ko) * | 2008-12-26 | 2011-11-17 | 양지화학 주식회사 | Ccr2 길항제로서의 3-아미노피롤리딘 유도체 |
| KR20120061060A (ko) | 2009-04-16 | 2012-06-12 | 얀센 파마슈티카 엔.브이. | Ccr2의 4-아제티디닐-1-헤테로아릴-사이클로헥산 길항제 |
| MX2011010963A (es) * | 2009-04-17 | 2011-11-02 | Janssen Pharmaceutica Nv | Antagonistas del receptor 2 de citocina quimiotrayente de ciclohexano unido al 4-azetidinil-1-heteroatomo. |
| CN102459227B (zh) * | 2009-04-17 | 2014-08-20 | 詹森药业有限公司 | Ccr2的4-氮杂环丁烷基-1-苯基-环己烷拮抗剂 |
| KR101151415B1 (ko) | 2009-07-10 | 2012-06-01 | 양지화학 주식회사 | Ccr2 길항제로서의 피페라지닐에틸 3-아미노피롤리딘 유도체 |
| TW201211027A (en) * | 2010-06-09 | 2012-03-16 | Janssen Pharmaceutica Nv | Cyclohexyl-azetidinyl antagonists of CCR2 |
| AU2011268375B2 (en) | 2010-06-17 | 2015-02-05 | Janssen Pharmaceutica Nv | Cyclohexyl-azetidinyl antagonists of CCR2 |
| KR101318656B1 (ko) | 2010-10-08 | 2013-10-16 | 양지화학 주식회사 | 항천식 활성을 가진 3-아미노피롤리딘 유도체를 포함하는 약학 조성물 |
| US20140005165A1 (en) * | 2011-03-17 | 2014-01-02 | Anilkumar G. Nair | Substituted 3-azabicyclo[3.1.0]hexane derivatives useful as ccr2 antagonists |
| US9428464B2 (en) | 2011-08-30 | 2016-08-30 | Chdi Foundation, Inc. | Kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
| MY166890A (en) | 2011-08-30 | 2018-07-24 | Chdi Foundation Inc | Kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
| JP5878178B2 (ja) | 2011-09-30 | 2016-03-08 | 大鵬薬品工業株式会社 | 1,2,4−トリアジン−6−カルボキサミド誘導体 |
| US9187451B2 (en) | 2011-11-18 | 2015-11-17 | Heptares Therapeutics Limited | Muscarinic M1 receptor agonists |
| WO2013149376A1 (en) | 2012-04-02 | 2013-10-10 | Abbott Laboratories | Chemokine receptor antagonists |
| GB201404922D0 (en) | 2014-03-19 | 2014-04-30 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| JP2017520610A (ja) | 2014-07-17 | 2017-07-27 | シーエイチディーアイ ファウンデーション,インコーポレーテッド | Hiv関連障害を治療するための方法及び組成物 |
| GB201513743D0 (en) | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonists |
| RU2606230C1 (ru) * | 2015-10-20 | 2017-01-10 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Пермский государственный национальный исследовательский университет" | (Z)-Этил 2-(4-(4-хлорфенил)-2,4-диоксо-3-(3-оксо-3,4-дигидрохиноксалин-2(1Н)-илиден)бутанамидо)-4-метил-5-фенилтиофен-3-карбоксилат, обладающий противодиабетической активностью, и способ его получения |
| GB201519352D0 (en) | 2015-11-02 | 2015-12-16 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| LT3490986T (lt) | 2016-07-28 | 2022-02-10 | Idorsia Pharmaceuticals Ltd | Piperidino cxcr7 receptoriaus moduliatoriai |
| GB201617454D0 (en) * | 2016-10-14 | 2016-11-30 | Heptares Therapeutics Limited | Pharmaceutical compounds |
| EP3551034A1 (en) | 2016-12-07 | 2019-10-16 | Progenity, Inc. | Gastrointestinal tract detection methods, devices and systems |
| CA3045310A1 (en) | 2016-12-14 | 2018-06-21 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a chemokine/chemokine receptor inhibitor |
| AU2018358160B2 (en) | 2017-11-02 | 2023-03-16 | Abbvie Inc. | Modulators of the integrated stress pathway |
| JP7076010B2 (ja) | 2018-01-26 | 2022-05-26 | イドーシア ファーマシューティカルズ リミテッド | (3s,4s)-1-シクロプロピルメチル-4-{[5-(2,4-ジフルオロ-フェニル)-イソオキサゾール-3-カルボニル]-アミノ}-ピペリジン-3-カルボン酸 (1-ピリミジン-2-イル-シクロプロピル)-アミドの結晶形 |
| GB201810239D0 (en) | 2018-06-22 | 2018-08-08 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| WO2020106704A2 (en) | 2018-11-19 | 2020-05-28 | Progenity, Inc. | Ingestible device for delivery of therapeutic agent to the gastrointestinal tract |
| GB201819961D0 (en) | 2018-12-07 | 2019-01-23 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201819960D0 (en) | 2018-12-07 | 2019-01-23 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| MX2021011606A (es) | 2019-04-02 | 2021-12-10 | Aligos Therapeutics Inc | Compuestos dirigidos a prmt5. |
| GB202020191D0 (en) | 2020-12-18 | 2021-02-03 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| CN121197633A (zh) | 2019-12-13 | 2025-12-26 | 比特比德科有限责任公司 | 用于将治疗剂递送至胃肠道的可摄取装置 |
| TWI822326B (zh) | 2021-09-14 | 2023-11-11 | 美商美國禮來大藥廠 | Sstr4促效劑鹽 |
| WO2023081665A1 (en) * | 2021-11-02 | 2023-05-11 | Aria Pharmaceuticals, Inc. | Compounds as crr2 modulators |
| WO2023081662A1 (en) * | 2021-11-02 | 2023-05-11 | Aria Pharmaceuticals, Inc. | Bicyclic derivatives as ccr2 modulators |
| WO2023081661A1 (en) * | 2021-11-02 | 2023-05-11 | Aria Pharmaceuticals, Inc. | Bicyclic derivatives as ccr2 modulators |
| TW202334135A (zh) * | 2021-11-02 | 2023-09-01 | 美商雅力雅製藥公司 | 化合物、組合物及方法 |
| CN119462429B (zh) * | 2024-11-19 | 2025-10-31 | 河北工业大学 | 一种由对甲苯胺合成氨基-甲基-苯氨基甲酸甲酯类化合物的方法 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995008533A1 (en) * | 1993-09-21 | 1995-03-30 | Yamanouchi Pharmaceutical Co., Ltd. | N-(3-pyrrolidinyl)benzamide derivative |
| JPH10298180A (ja) * | 1997-04-25 | 1998-11-10 | Shionogi & Co Ltd | ドーパミン受容体拮抗作用を有する化合物 |
| WO2000026186A1 (en) * | 1998-11-02 | 2000-05-11 | Welfide Corporation | Pyrrolidine compounds and medicinal utilization thereof |
| WO2001028987A1 (en) * | 1999-10-15 | 2001-04-26 | Du Pont Pharmaceuticals Company | Benzylcycloalkyl amines as modulators of chemokine receptor activity |
| JP2002505684A (ja) * | 1997-06-18 | 2002-02-19 | メルク エンド カンパニー インコーポレーテッド | α1aアドレナリン受容体拮抗薬 |
| JP2006505533A (ja) * | 2002-09-17 | 2006-02-16 | アクテリオン ファマシューティカルズ リミテッド | 1−ピリジン−4−イル−尿素誘導体 |
Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US26186A (en) * | 1859-11-22 | Cut-off arrangement for steam-valves | ||
| PH15259A (en) | 1972-04-03 | 1982-11-02 | Robins Co Inc A H | Method for controlling emesis with n-(1-substituted-3-pyrrolidinyl)benzamides and thiobenzamides |
| US4026836A (en) * | 1975-12-29 | 1977-05-31 | Texaco Development Corporation | Isocyanurate foam catalyst |
| HU175454B (hu) | 1977-07-25 | 1980-08-28 | Chinoin Gyogyszer Es Vegyeszet | Sposob poluchenija novykh predel'nykh i chastichno predel'nykh n-acil-pirrol-2,5-dionov |
| US4333734A (en) * | 1980-01-18 | 1982-06-08 | Sloan-Kettering Institute For Cancer Research | Diagnostic device for fecal occult blood and method of use |
| US4785119A (en) | 1985-10-11 | 1988-11-15 | Tokyo Kasei Kogyo Co., Ltd. | 3-aminopyrrolidine compound and process for preparation thereof |
| AU8131694A (en) * | 1993-11-02 | 1995-05-23 | Neurobiological Technologies, Inc. | Treatment for rheumatoid arthritis |
| US5770573A (en) * | 1993-12-06 | 1998-06-23 | Cytel Corporation | CS-1 peptidomimetics, compositions and methods of using the same |
| CA2256492C (en) | 1996-05-20 | 2006-04-04 | Teijin Limited | Diarylalkyl cyclic diamine derivatives as chemokine receptor antagonists |
| WO1998002151A2 (en) | 1996-07-12 | 1998-01-22 | Leukosite, Inc. | Chemokine receptor antagonists and methods of use therefor |
| IL135488A0 (en) | 1997-11-18 | 2001-05-20 | Teijin Ltd | Cyclic amine derivatives |
| US6312689B1 (en) | 1998-07-23 | 2001-11-06 | Millennium Pharmaceuticals, Inc. | Anti-CCR2 antibodies and methods of use therefor |
| US6197974B1 (en) | 1998-10-26 | 2001-03-06 | Abbott Laboratories | Enantioselective synthesis of 3-aminopyrrolidines |
| US7217714B1 (en) | 1998-12-23 | 2007-05-15 | Agouron Pharmaceuticals, Inc. | CCR5 modulators |
| US6248755B1 (en) | 1999-04-06 | 2001-06-19 | Merck & Co., Inc. | Pyrrolidine modulators of chemokine receptor activity |
| WO2000069815A1 (en) | 1999-05-13 | 2000-11-23 | Teijin Limited | Ureido-substituted cyclic amine derivatives and their use as drug |
| WO2000069432A1 (en) * | 1999-05-18 | 2000-11-23 | Teijin Limited | Remedies or preventives for diseases in association with chemokines |
| RU2144397C1 (ru) * | 1999-05-25 | 2000-01-20 | Институт ревматологии РАМН | Способ лечения ревматоидного артрита |
| US6313117B1 (en) * | 1999-07-30 | 2001-11-06 | Boehringer Ingelheim Pharmaceuticals, Inc. | Succinate derivative compounds useful as cysteine protease inhibitors |
| CN1192773C (zh) | 1999-08-04 | 2005-03-16 | 帝人株式会社 | 环胺ccr3拮抗剂 |
| JP2001131145A (ja) | 1999-08-20 | 2001-05-15 | Toray Ind Inc | 光学活性3−アミノピロリジン誘導体の製造法 |
| ES2199856T3 (es) | 1999-09-13 | 2004-03-01 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nuevos compuestos heterociclicos, utiles como inhibidores reversibles de cisteina proteasas. |
| GB2355263A (en) | 1999-09-30 | 2001-04-18 | Merck & Co Inc | Lactam and cyclic urea derivatives useful as alpha 1a adrenoceptor antagonists |
| US6544992B1 (en) | 1999-12-21 | 2003-04-08 | Smithkline Beecham Corporation | Urotensin-II receptor antagonists |
| US6410566B1 (en) | 2000-05-16 | 2002-06-25 | Teijin Limited | Cyclic amine derivatives and their use as drugs |
| GB0011838D0 (en) | 2000-05-17 | 2000-07-05 | Astrazeneca Ab | Chemical compounds |
| US7125887B2 (en) | 2000-10-11 | 2006-10-24 | Merck & Co., Inc. | Pyrrolidine modulators of CCR5 chemokine receptor activity |
| US20020094989A1 (en) | 2000-10-11 | 2002-07-18 | Hale Jeffrey J. | Pyrrolidine modulators of CCR5 chemokine receptor activity |
| US6670364B2 (en) * | 2001-01-31 | 2003-12-30 | Telik, Inc. | Antagonists of MCP-1 function and methods of use thereof |
| WO2002070523A1 (en) * | 2001-03-07 | 2002-09-12 | Pfizer Products Inc. | Modulators of chemokine receptor activity |
| CA2440389A1 (en) | 2001-03-09 | 2002-10-03 | Ortho-Mcneil Pharmaceutical, Inc. | Aminopyrrolidine sulfonamides as serine protease inhibitors |
| WO2003092586A2 (en) | 2002-04-29 | 2003-11-13 | Merck & Co., Inc. | Tetrahydropyranyl cyclopentyl tetrahydropyridopyridine modulators of chemokine receptor activity |
| ATE404538T1 (de) | 2002-04-29 | 2008-08-15 | Merck & Co Inc | Tetrahydropyranylcyclopentyltetrahydroisochino- linmodulatoren der chemokinrezeptoraktivität |
| TWI262077B (en) | 2002-04-29 | 2006-09-21 | Merck & Co Inc | Tetrahydropyranyl cyclopentyl tetrahydropyridopyridine modulators of chemokine receptor activity |
| WO2004020584A2 (en) | 2002-08-27 | 2004-03-11 | Bristol-Myers Squibb Company | Antagonists of chemokine receptors |
| JP2004083511A (ja) | 2002-08-28 | 2004-03-18 | Yamanouchi Pharmaceut Co Ltd | アクリルアミド誘導体 |
| WO2004041161A2 (en) | 2002-10-30 | 2004-05-21 | Merck & Co., Inc. | Tetrahydropyranyl cyclopentyl benzylamide modulators of chemokine receptor activity |
| JP2006511500A (ja) | 2002-10-30 | 2006-04-06 | メルク エンド カムパニー インコーポレーテッド | γ−アミノアミド系のケモカイン受容体活性調節剤 |
| US7491737B2 (en) | 2002-10-30 | 2009-02-17 | Merck & Co., Inc. | Heterarylpiperidine modulators of chemokine receptor activity |
| AU2003284188B2 (en) | 2002-10-30 | 2010-02-25 | Merck Sharp & Dohme Corp. | Piperidinyl cyclopentyl aryl benzylamide modulators of chemokine receptor activity |
| CA2503844A1 (en) | 2002-10-30 | 2004-05-21 | Merck & Co., Inc. | Piperidinyl-alpha-aminoamide modulators of chemokine receptor activity |
| AU2003293129B2 (en) * | 2002-11-27 | 2009-03-12 | Incyte Holdings Corporation | 3-aminopyrrolidine derivatives as modulators of chemokine receptors |
| UA81365C2 (en) | 2003-10-27 | 2007-12-25 | Merck & Co Inc | Ccr-2 antagonist salt, method for modulation of chemokine receptor activity, method for treating (variants) and pharmaceutical composition |
| AR045875A1 (es) | 2003-10-27 | 2005-11-16 | Merck & Co Inc | Procedimiento para la preparacion del antagonista ccr-2 |
| CN102344398B (zh) * | 2003-12-18 | 2015-02-25 | 因赛特公司 | 作为趋化因子受体调控剂的3-环烷基氨基吡咯烷衍生物 |
| AU2004313486A1 (en) | 2004-01-02 | 2005-07-28 | Merck & Co., Inc. | Alkylamino, arylamino, and sulfonamido cyclopentyl amide modulators of chemokine receptor activity |
| JP2007518799A (ja) | 2004-01-20 | 2007-07-12 | メルク エンド カムパニー インコーポレーテッド | ケモカイン受容体活性モジュレーターとしての2,6−二置換ピペリジン |
| US20070155731A1 (en) | 2004-01-28 | 2007-07-05 | Gabor Butora | Aminocyclopentyl pyridopyrazinone modulators of chemokine receptor activity |
| CA2562235C (en) | 2004-04-13 | 2013-09-24 | Incyte Corporation | Piperazinylpiperidine derivatives as chemokine receptor antagonists |
| CN1950085A (zh) | 2004-05-11 | 2007-04-18 | 因赛特公司 | 作为趋化因子受体调节剂的3-(4-杂芳基环己基氨基)环戊烷羧酰胺 |
| AU2005260013A1 (en) | 2004-06-28 | 2006-01-12 | Incyte Corporation | 3-aminocyclopentanecarboxamides as modulators of chemokine receptors |
| CN102382088A (zh) | 2004-06-28 | 2012-03-21 | 因赛特公司 | 作为趋化因子受体调节剂的3-氨基环戊烷甲酰胺类 |
| UY29219A1 (es) * | 2004-11-22 | 2006-04-28 | Incyte Corp | Sales de la n-(2- (((3r)-1-(trans-4-hidroxi-4-(6-metoxipiridin-3-il)-cilohexil) pirrolidin-3-il)amino)-2-oxoetil)-3- (trifluorometil) benzamida |
| TWI449692B (zh) | 2005-05-13 | 2014-08-21 | Otsuka Pharma Co Ltd | 吡咯烷化合物(三) |
| MEP1008A (xx) | 2005-12-21 | 2010-02-10 | Incyte Corp | 3-aminociklopentankarboksamidi kao modulatori receptora hemokina |
-
2003
- 2003-11-26 AU AU2003293129A patent/AU2003293129B2/en not_active Expired
- 2003-11-26 CA CA2507501A patent/CA2507501C/en not_active Expired - Lifetime
- 2003-11-26 PL PL376925A patent/PL376925A1/pl unknown
- 2003-11-26 RU RU2005120020/04A patent/RU2355679C2/ru active
- 2003-11-26 WO PCT/US2003/037946 patent/WO2004050024A2/en not_active Ceased
- 2003-11-26 JP JP2004570963A patent/JP4828829B2/ja not_active Expired - Lifetime
- 2003-11-26 ES ES03790120T patent/ES2383296T3/es not_active Expired - Lifetime
- 2003-11-26 EP EP03790120A patent/EP1565436B1/en not_active Expired - Lifetime
- 2003-11-26 SG SG2007037260A patent/SG173922A1/en unknown
- 2003-11-26 CN CN201110045106.XA patent/CN102153539B/zh not_active Expired - Lifetime
- 2003-11-26 MX MXPA05005660A patent/MXPA05005660A/es active IP Right Grant
- 2003-11-26 NZ NZ540290A patent/NZ540290A/en not_active IP Right Cessation
- 2003-11-26 KR KR1020057009692A patent/KR100895968B1/ko not_active Expired - Lifetime
- 2003-11-26 AT AT03790120T patent/ATE555087T1/de active
- 2003-11-26 EP EP11175373A patent/EP2431357A3/en not_active Withdrawn
- 2003-11-26 BR BRPI0316732A patent/BRPI0316732B8/pt not_active IP Right Cessation
- 2003-11-26 GE GEAP20038862A patent/GEP20115290B/en unknown
- 2003-11-26 HU HU0500848A patent/HU230612B1/hu unknown
- 2003-11-26 EA EA200500875A patent/EA010027B1/ru unknown
- 2003-11-26 US US10/535,795 patent/US7834021B2/en not_active Expired - Lifetime
-
2005
- 2005-05-23 CR CR7846A patent/CR7846A/es unknown
- 2005-05-23 IL IL168742A patent/IL168742A/en active IP Right Grant
- 2005-05-26 SE SE0501185A patent/SE529361C2/sv not_active IP Right Cessation
- 2005-05-26 NO NO20052543A patent/NO330860B1/no not_active IP Right Cessation
- 2005-06-01 CO CO05053243A patent/CO5690550A2/es active IP Right Grant
- 2005-06-15 EC EC2005005856A patent/ECSP055856A/es unknown
- 2005-06-22 IS IS7905A patent/IS2892B/is unknown
-
2009
- 2009-04-27 US US12/430,446 patent/US7985730B2/en not_active Expired - Lifetime
-
2011
- 2011-06-16 US US13/162,286 patent/US8362003B2/en not_active Expired - Fee Related
- 2011-07-21 JP JP2011160080A patent/JP2011251987A/ja active Pending
-
2012
- 2012-03-27 CR CR20120152A patent/CR20120152A/es unknown
- 2012-12-20 US US13/722,740 patent/US8729063B2/en not_active Expired - Lifetime
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995008533A1 (en) * | 1993-09-21 | 1995-03-30 | Yamanouchi Pharmaceutical Co., Ltd. | N-(3-pyrrolidinyl)benzamide derivative |
| JPH10298180A (ja) * | 1997-04-25 | 1998-11-10 | Shionogi & Co Ltd | ドーパミン受容体拮抗作用を有する化合物 |
| JP2002505684A (ja) * | 1997-06-18 | 2002-02-19 | メルク エンド カンパニー インコーポレーテッド | α1aアドレナリン受容体拮抗薬 |
| WO2000026186A1 (en) * | 1998-11-02 | 2000-05-11 | Welfide Corporation | Pyrrolidine compounds and medicinal utilization thereof |
| WO2001028987A1 (en) * | 1999-10-15 | 2001-04-26 | Du Pont Pharmaceuticals Company | Benzylcycloalkyl amines as modulators of chemokine receptor activity |
| JP2006505533A (ja) * | 2002-09-17 | 2006-02-16 | アクテリオン ファマシューティカルズ リミテッド | 1−ピリジン−4−イル−尿素誘導体 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011251987A (ja) * | 2002-11-27 | 2011-12-15 | Incyte Corp | ケモカイン受容体のモジュレーターとしての3−アミノピロリジン誘導体 |
| US8635940B2 (en) | 2008-01-07 | 2014-01-28 | Vanderbilt University | Solenoid valve assembly |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4828829B2 (ja) | ケモカイン受容体のモジュレーターとしての3−アミノピロリジン誘導体 | |
| JP4740151B2 (ja) | ケモカイン受容体のモジュレーターとしての3‐シクロアルキルアミノピロリジン誘導体 | |
| ZA200504322B (en) | 3-Aminopyrrolidine derivatives as modulators of chemokine receptors. | |
| WO2012114223A1 (en) | A method of treating liver fibrosis | |
| HK1079773B (en) | 3-aminopyrrolidine derivatives as modulators of chemokine receptors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20061122 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061122 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100427 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100722 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100729 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100827 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100903 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101027 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20101124 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110224 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20110322 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110721 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20110801 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20110823 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110915 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140922 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4828829 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |