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US 8,895,535 B2Granted
Pyrrolidinones as MetAP-2 inhibitors
AssigneeMerck Patent GmbH
InventorsTimo Heinrich, Frank Zenke, Michel Calderini, Djordje Musil
Life of this patent
Estimating the term…
Abstract
Compounds of the formula I in which R1, R2, R3 and R4 have the meanings indicated in Claim 1, are inhibitors of methionine aminopeptidase and can be employed for the treatment of tumors.
Claims15
A compound of formula I
- in which
- R1 denotes [C(R4)2]nAr1, (CH2)nHet, (CH2)nCyc,
- or A,
- R2 denotes [C(R4)2]nAr2, CH[B(OH)2]CH2Het,
- (CH2)nHet, (CH2)nCyc, CH(C≡CH)phenyl or A,
- R3 denotes OH, Hal, NH2, CN, CF3, CHF2 or N3,
- R4 denotes H or alkyl having 1, 2, 3 or 4 C atoms, or
- R2 and R4 together denote alkylene having 2, 3, 4 or 5 C atoms, where one CH2 group is optionally replaced by NH, NA, N—COA, N—(CH2)nAr3, N—(CH2)nHet2, CH-A, CH—O—(CH2)nAr3, N—SO2A or O and/or is optionally substituted by A,
- Ar1 denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, OH, OA, NH2, NHA, NA2, NO2, CN, COOH, COOA, CONH2, CONHA, CONA2, NHCOA, NHSO2A, COA, CHO, Het1, SO2NH2 and/or SO2A,
- Ar2 denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, OH, OA, NH2, NHA, NA2, NO2, CN, COOH, COOA, CONH2, CONHA, CONA2, NHCOA, NHSO2A, COA, CHO, Het1, SO2NH2 and/or SO2A,
- Ar3 denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal, OH, OA and/or A,
- Het denotes a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, and/or O and/or S atoms which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH, OA, NH2, NHA, NA2, NO2, CN, COOH, COOA, (CH2)nCONH2, (CH2)nCONHA, (CH2)nCONA2, NHCOA, NHSO2A, COA, CHO, Het1, SO2NH2, SO2A and/or ═O,
- Het1 denotes a monocyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, and/or O and/or S atoms which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH, OA, NH2, NHA, NA2, NO2, CN, COOH and/or COOA,
- Het2 denotes pyridyl, pyrimidinyl, furyl, thienyl, imidazolyl, pyrrolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl or thiadiazole,
- A denotes unbranched or branched alkyl having 1-10 C atoms, in which 1-7 H atoms are optionally replaced by F, Cl, Br, OH, CHO, COA, COOA, CN, CONA2, CONHA and/or CONH2, and/or in which one or two non-adjacent CH and/or CH2 groups are optionally replaced by O, N and/or NR4, or Cyc,
- Cyc denotes cyclic alkyl having 3-7 C atoms,
- Hal denotes F, Cl, Br or I,
- n denotes 0, 1, 2, 3 or 4,
- or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.
16 more elements
A compound, which is one of the following compounds
- Compound
- No.
- Structure/name
- “A1”
- “A2”
- “A3”
- “A4”
- “A5”
- “A6”
- “A7”
- “A8”
- “A9”
- “A10”
- “A11”
- “A12”
- “A13”
- “A14”
- “A15”
- “A16”
- “A17”
- “A18”
- “A19”
- “A20”
- “A21”
- “A22”
- “A23”
- “A24”
- “A25”
- “A26”
- “A27”
- “A28”
- “A29”
- “A30”
- “A31”
- “A32”
- “A33”
- “A34”
- “A35”
- “A36”
- “A37”
- “A38”
- “A39”
- “A40”
- “A41”
- “A42”
- “A43”
- “A44”
- “A45”
- “A46”
- “A47”
- “A48”
- “A49”
- “A50”
- “A51”
- “A52”
- “A53”
- “A54”
- “A55”
- “A56”
- “A57”
- “A58”
- “A59”
- “A60”
- “A61”
- “A62”
- “A63”
- “A64”
- “A65”
- “A66”
- “A67”
- “A68”
- “A69”
- “A70”
- “A71”
- “A72”
- “A73”
- “A74”
- “A75”
- “A76”
- “A77”
- “A78”
- “A79”
- “A80”
- “A81”
- “A82”
- “A83”
- “A84”
- “A85”
- “A86”
- “A87”
- “A88”
- “A89”
- “A90”
- “A91”
- “A91a”
- (S)-3-Amino-2-oxo-1-phenylpyrrolidine-3-
- carboxylic acid (3-chloro-5-fluorobenzyl) amide
- “A92”
- “A93”
- “A94”
- “A95”
- “A96”
- “A97”
- “A98”
- “A99”
- “A100”
- “A101”
- “A102”
- “A103”
- “A104”
- “A105”
- “A106”
- “A107”
- “A108”
- “A109”
- “A110”
- “A111”
- “A112”
- “A113”
- “A114”
- “A115”
- “A116”
- “A117”
- “A118”
- “A119”
- “A120”
- “A150”
- 3-Azido-2-oxo-1-phenylpyrrolidine-3-
- carboxylic acid (3-chloro-5-fluorobenzyl) amide
- “A151”
- 3-Amino-2-oxo-1-phenylpyrrolidine-3-
- carboxylic acid (3-chloro-5-fluorobenzyl) amide
- “A162”
- “A163”
- “A164”
- “A165”
- “A166”
- “A167”
- “A168”
- “A169”
- “A170”
- “A171”
- “A172”
- “A173”
- “A174”
- “A175”
- “A176”
- “A177”
- “A178”
- “A179”
- “A180”
- “A181”
- “A182”
- “A183”
- “A184”
- “A185”
- “A186”
- “A187”
- “A188”
- “A189”
- “A190”
- “A191”
- “A192”
- “A193”
- “A194”
- “A195”
- “A196”
- “A197”
- “A198”
- “A199”
- “A200”
- “A201”
- “A202”
- “A203”
- “A204”
- “A205”
- “A206”
- “A207”
- “A208”
- “A209”
- “A210”
- “A211”
- “A212”
- “A213”
- “A214”
- “A215”
- “A216”
- “A217”
- “A218”
- “A219”
- “A220”
- “A221”
- “A222”
- “A223”
- “A224”
- “A225”
- “A226”
- “A227”
- “A228”
- “A229”
- “A230”
- “A231”
- “A232”
- “A233”
- “A234”
- “A235”
- “A236”
- “A237”
- “A238”
- “A239”
- “A240”
- “A241”
- “A242”
- “A243”
- “A244”
- “A245”
- “A246”
- “A247”
- “A248”
- “A249”
- “A250”
- “A251”
- “A252”
- “A253”
- “A254”
- “A255”
- “A256”
- “A257”
- “A258”
- “A259”
- “A260”
- “A261”
- “A262”
- “A263”
- “A264”
- “A265”
- “A266”
- “A267”
- “A268”
- “A269”
- “A270”
- “A271”
- “A272”
- “A273”
- “A274”
- “A275”
- “A276”
- “A277”
- “A278”
- “A279”
- “A280”
- “A281”
- “A282”
- “A283”
- “A284”
- “A285”
- “A286”
- “A287”
- “A288”
- “A289”
- “A290”
- “A291”
- “A292”
- “A293”
- “A294”
- “A295”
- “A296”
- “A297”
- “A298”
- “A299”
- “A300”
- “A301”
- “A302”
- “A303”
- “A304”
- “A305”
- “A306”
- “A307”
- “A308”
- “A309”
- “A310”
- “A311”
- “A312”
- “A313”
- “A314”
- “A315”
- “A316”
- “A317”
- “A318”
- “A319”
- “A320”
- “A321”
- “A322”
- “A323”
- “A324”
- “A325”
- “A326”
- “A327”
- “A328”
- “A329”
- “A330”
- “A331”
- “A332”
- “A333”
- “A334”
- “A335”
- “A336”
- “A337”
- “A338”
- “A339”
- “A340”
- “A341”
- “A342”
- “A343”
- “A344”
- “A345”
- or
- “A346”
- or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.
316 more elements
Dependencies are inferred from the claim text.