US 2016/0102087 A1Published application

Compounds and methods for the treatment of isocitrate dehydrogenase related diseases

AssigneesThe Broad Institute, Inc., President and Fellows of Harvard College

InventorsMahmud Hussain, Daisuke Ito, Jason Law, Matthias Leiendecker, Ke Liu, Benito Munoz, Stuart Schreiber, Alykhan Shamji, Andrew Stern

Life of this patent

Estimating the term…

Abstract

The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof:

Claims47

Dependent claims

A compound of Formula IA, IB, IC or ID, or a pharmaceutically acceptable salt, ester or prodrug thereof:

wherein each n and m is independently 0, 1, 2 or 3;
each p and q is independently 0, 1, 2, 3, 4, 5, 6 or 7;
X1 is —C(O)N(RA)— or —C(S)N(RA)—;
wherein RA is independently hydrogen, aliphatic, substituted aliphatic, heteroaryl, substituted heteroaryl, aryl or substituted aryl;
X2 is —S——O—, —S(O)2— —C(R20)(R21)— or —N(RB)—;
wherein RB is independently hydrogen, aliphatic, substituted aliphatic, heteroaryl, substituted heteroaryl, aryl or substituted aryl;
each R1 and R2 is independently hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
R3 is hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
each R10, and R28 is independently absent, hydrogen, halogen, —OR20, —SR20, —NR20R21, —CF3, —CN, —NO2, —N3, —C(O)OR20, —C(O)R20, —C(O)NR20R21, acyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl, aliphatic, substituted aliphatic, aryl or substituted aryl;
alternatively two of R10 groups together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
wherein each R20 and R21 is independently hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
each R11 is independently absent, hydrogen, halogen, —OR20, —SR20, —NR20R21, —CF3, —CN, —NO2, —N3, —C(O)R20, —C(O)OR20, —C(O)NR20R21, acyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl, aliphatic, substituted aliphatic, aryl or substituted aryl;
alternatively two of R11 groups together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
each G1 and G2 is independently, absent, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl;
each R27 and R29 is independently hydrogen, alkyl, substituted alkyl, aryl or substituted aryl;
wherein R3a is selected from alkyl, aryl, alkyl substituted with aryl, straight chain or branched C1-C10 alkyl, C1-C10 alkenyl, C1-C10 alkynyl, C1-C10 alkoxy, alkoxyC1-C10alkoxy, C1-C10alkylamino, alkoxyC1-C10alkylamino, C1-C10alkylcarbonylamino, C1-C10 alkylaminocarbonyl, aryloxyC1-C10 alkoxy, aryloxyC1-C10alkylamino, aryloxyC1-C10 alkylamino carbonyl, C1-C10-alkylaminoalkylaminocarbonyl, C1-C10alkyl(N-alkyl)aminoalkyl-aminocarbonyl, alkylaminoalkylamino, alkylcarbonylaminoalkylamino, alkyl(N-alkyl)aminoalkylamino, (N-alkyl)alkylcarbonylaminoalkylamino, alkylaminoalkyl, alkylaminoalkylaminoalkyl, alkylpiperazinoalkyl, piperazinoalkyl, alkylpiperazino, alkenylaryloxyC1-C10 alkoxy, alkenylarylaminoC1-C10 alkoxy, alkenylaryllalkylamino C1-C10 alkoxy, alkenylaryloxyC1-C10 alkylamino, alkenylaryloxyC1-C10alkylaminocarbonyl, piperazinoalkylaryl, heteroarylC1-C10 alkyl, heteroarylC1-C10alkenyl, heteroarylC1-C10 alkynyl, heteroarylC1-C10 alkylamino, heteroarylC1-C10alkoxy, heteroaryloxyC1-C10alkyl, heteroaryloxyC1-C10 alkenyl, heteroaryloxyC2-C10 alkynyl, heteroaryloxyC1-C10alkylamino, and heteroaryloxyC1-C10 alkoxy;
Cy1 is an optionally substituted aryl or optionally substituted heteroaryl;
and,
R40 is selected from:
wherein, R41 is hydrogen, halogen, aliphatic, substituted aliphatic, aryl, substituted aryl, —OR20, —SR20, —NR20R21, —CF3, —CN, —NO2, —N3, —C(O)R20, —C(O)OR20, —C(O)NR20R21, acyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl.

17 more elements

A compound selected from Table 1A or a pharmaceutically acceptable salt, ester or prodrug thereof:

TABLE 1A
1
(4R,5R)-8-(cyclopent-1-en-1-yl)-2-((S)-1-hydroxypropan-2-yl)-4-methyl-5-
((methyl(pyridin-3-ylmethyl)amino)methyl)-2,3,4,5-
tetrahydrobenzo[b][1,4,5]oxathiazocine 1,1-dioxide
2
1-(4-fluorophenyl)-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-
((methyl(pyridin-4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
4
N-(((4R,5R)-8-(cyclohexylethynyl)-2-((S)-1-hydroxypropan-2-yl)-4-methyl-1,1-
dioxido-2,3,4,5-tetrahydrobenzo[b][1,4,5]oxathiazocin-5-yl)methyl)-N-methyl-2-
(pyridin-4-yl)acetamide
6
N-(((4R,5R)-2-((R)-1-hydroxypropan-2-yl)-4-methyl-8-(4-methylpent-1-yn-1-yl)-1,1-
dioxido-2,3,4,5-tetrahydrobenzo[b][1,4,5]oxathiazocin-5-yl)methyl)-N-methyl-2-
(pyridin-3-yl)acetamide
7
N-((2S,3S)-5-((R)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-3,4,5,6-tetrahydro-2H-benzo[b][1,5]oxazocin-10-
yl)benzo[d]thiazole-2-carboxamide
8
(4R,5R)-8-(cyclopropylethynyl)-2-((R)-1-hydroxypropan-2-yl)-4-methyl-5-
((methyl(pyridin-3-ylmethyl)amino)methyl)-2,3,4,5-
tetrahydrobenzo[b][1,4,5]oxathiazocine 1,1-dioxide
9
(4R,5S)-2-((R)-1-hydroxypropan-2-yl)-4-methyl-5-((methyl(pyridin-4-
ylmethyl)amino)methyl)-8-(p-tolyl)-2,3,4,5-tetrahydrobenzo[b][1,4,5]oxathiazocine 1,1-
dioxide
10
(4S,5R)-2-((S)-1-hydroxypropan-2-yl)-4-methyl-5-((methyl(pyridin-3-
ylmethyl)amino)methyl)-8-(pent-1-yn-1-yl)-2,3,4,5-
tetrahydrobenzo[b][1,4,5]oxathiazocine 1,1-dioxide
11
N-(((4R,5S)-2-((R)-1-hydroxypropan-2-yl)-4-methyl-8-(4-methylpent-1-yn-1-yl)-1,1-
dioxido-2,3,4,5-tetrahydrobenzo[b][1,4,5]oxathiazocin-5-yl)methyl)-N-methyl-2-
(pyridin-3-yl)acetamide
12
(4R,5S)-8-(cyclohex-1-en-1-yl)-2-((S)-1-hydroxypropan-2-yl)-4-methyl-5-
((methyl(pyridin-3-ylmethyl)amino)methyl)-2,3,4,5-
tetrahydrobenzo[b][1,4,5]oxathiazocine 1,1-dioxide
13
(4S,5S)-8-(cyclopent-1-en-1-yl)-2-((R)-1-hydroxypropan-2-yl)-4-methyl-5-
((methyl(pyridin-4-ylmethyl)amino)methyl)-2,3,4,5-
tetrahydrobenzo[b][1,4,5]oxathiazocine 1,1-dioxide
14
N-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-
yl)cyclohexanecarboxamide
16
(4S,5S)-2-((S)-1-hydroxypropan-2-yl)-4-methyl-5-((methyl(pyridin-4-
ylmethyl)amino)methyl)-8-(o-tolyl)-2,3,4,5-tetrahydrobenzo[b][1,4,5]oxathiazocine 1,1-
dioxide
17
(2S,3S)-5-((R)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyrimidin-5-
ylmethyl)amino)methyl)-8-((E)-styryl)-4,5-dihydro-2H-pyrido[2,3-b][1,5]oxazocin-
6(3H)-one
18
4-(((((4R,5R)-8-(3-cyclopentylprop-1-yn-1-yl)-2-((R)-1-hydroxypropan-2-yl)-4-methyl-
1,1-dioxido-2,3,4,5-tetrahydrobenzo[b][1,4,5]oxathiazocin-5-
yl)methyl)(methyl)amino)methyl)benzoic acid
19
N-(((4R,5R)-2-((S)-1-hydroxypropan-2-yl)-4-methyl-8-(3-methylbut-1-yn-1-yl)-1,1-
dioxido-2,3,4,5-tetrahydrobenzo[b][1,4,5]oxathiazocin-5-yl)methyl)-N-
methylnicotinamide
20
N-(((4R,5R)-8-(cyclohex-1-en-1-yl)-2-((S)-1-hydroxypropan-2-yl)-4-methyl-1,1-
dioxido-2,3,4,5-tetrahydrobenzo[b][1,4,5]oxathiazocin-5-yl)methyl)-N-methyl-2-
(pyridin-3-yl)acetamide
21
N-(((4S,5S)-2-((S)-1-hydroxypropan-2-yl)-4-methyl-8-(4-methylpent-1-yn-1-yl)-1,1-
dioxido-2,3,4,5-tetrahydrobenzo[b][1,4,5]oxathiazocin-5-yl)methyl)-N-methyl-2-
(pyridin-3-yl)acetamide
23
1-(4-bromophenyl)-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-
((methyl(pyridin-4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
24
1-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-yl)-3-(4-
methoxyphenyl)urea
25
1-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-yl)-3-
(pyridin-3-yl)urea
26
1-cyclopentyl-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
27
1-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-yl)-3-(2-
morpholinopyridin-4-yl)urea
28
1-ethyl-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
29
1-(4-chlorophenyl)-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-
((methyl(pyridin-4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
30
1-(cyclohexylmethyl)-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-
((methyl(pyridin-4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
32
1-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-yl)-3-
(naphthalen-1-yl)urea
34
1-(benzo[d][1,3]dioxo1-5-yl)-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-
((methyl(pyridin-4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
37
N-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-
yl)isonicotinamide
38
1-(2-fluorophenyl)-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-
((methyl(pyridin-4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
39
1-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-yl)-3-
(1,2,3,4-tetrahydronaphthalen-1-yl)urea
40
1-(4-cyanophenyl)-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-
((methyl(pyridin-4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
41
1-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-yl)-3-(3-
(pyrimidin-2-yl)phenyl)urea
42
1-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-yl)-3-(2-
(piperidin-1-yl)phenyl)urea
43
1-(benzofuran-5-yl)-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-
((methyl(pyridin-4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
44
1-cyclohexyl-3-((2R,3R)-2-((((3-fluoropyridin-4-yl)methyl)(methyl)amino)methyl)-5-
((S)-1-hydroxypropan-2-yl)-3-methyl-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
45
1-((2R,3R)-2-((((3-chloropyridin-4-yl)methyl)(methyl)amino)methyl)-5-((S)-1-
hydroxypropan-2-yl)-3-methyl-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-
yl)-3-cyclohexylurea
46
1-cyclohexyl-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(pyrimidin-
4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-
yl)urea
47
1-cyclohexyl-3-((2R,3R)-5-((S)-1-hydroxypropan-2-yl)-3-methyl-2-((methyl(quinolin-
4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-
yl)urea
48
1-((2R,3R)-2-((((1H-imidazol-2-yl)methyl)(methyl)amino)methyl)-5-((S)-1-
hydroxypropan-2-yl)-3-methyl-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-
yl)-3-cyclohexylurea
49
1-cyclohexyl-3-((2R,3R)-3-methyl-2-((methyl(pyridin-4-ylmethyl)amino)methyl)-6-
oxo-5-((S)-1-(2-(pyrrolidin-1-yl)ethoxy)propan-2-yl)-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
50
1-cyclohexyl-3-((2R,3R)-5-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-3-methyl-2-
((methyl(pyridin-4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
51
1-cyclohexyl-3-((2R,3R)-5-((S)-1-(4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)propan-
2-yl)-3-methyl-2-((methyl(pyridin-4-ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
52
1-cyclohexyl-3-((2R,3R)-5-isopropyl-3-methyl-2-((methyl(pyridin-4-
ylmethyl)amino)methyl)-6-oxo-2,3,4,5,6,7-hexahydrobenzo[h][1,5]oxazonin-9-yl)urea
53
1-cyclohexyl-3-((2R,3R)-5-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-3-methyl-2-
((methyl((3-methylpyridin-4-yl)methyl)amino)methyl)-6-oxo-2,3,4,5,6,7-
hexahydrobenzo[h][1,5]oxazonin-9-yl)urea.

175 more elements

A method of treating a disease related to a defect in isocitrate dehydrogenase comprising the step of administering a compound of Formula I to a patient in need thereof:

each n and m is independently 0, 1, 2 or 3;
each p and q is independently 0, 1, 2, 3, 4, 5, 6 or 7;
X1 is —C(O)N(RA)—, —C(S)N(RA)—, or —S(O)2N(RA)—;
wherein RA is hydrogen, aliphatic, substituted aliphatic, heteroaryl, substituted heteroaryl, aryl or substituted aryl;
X2 is —S——O—, —S(O)2—, —C(R20)(R21)— or —N(RB)—;
wherein RB is hydrogen, aliphatic, substituted aliphatic, heteroaryl, substituted heteroaryl, aryl or substituted aryl;
each R1 and R2 is independently hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
each R10 is independently absent, hydrogen, halogen, —OR20, —SR20, —NR20R21, —CF3, —CN, —NO2, —N3, —C(O)OR20, —C(O)R20, —C(O)NR20R21, acyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl, aliphatic, substituted aliphatic, aryl or substituted aryl;
alternatively two of R10 groups together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
wherein each R20 and R21 is independently hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
each R11 is independently absent, hydrogen, halogen, —OR20, —SR20, —NR20R21, —CF3, —CN, —NO2, —N3, —C(O)OR20, —C(O)R20, —C(O)NR20R21, acyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl, aliphatic, substituted aliphatic, aryl or substituted aryl;
alternatively two of R11 groups together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
and,
Cy1 is an optionally substituted aryl or optionally substituted heteroaryl.

11 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/818,009Filed 4 Aug 2015
Priority: 29 Mar 2011
Published: 14 Apr 2016
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 419/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 35/00
Antineoplastic agents
C07D 413/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 413/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms:…

Family

Application61/469,054Us provisional application · filed 29 Mar 2011
Application14/037,761Continuation · filed 26 Sep 2013
Application14/818,009Continuation
US 2014/0100223 A1Published application
US 9,120,810 B2Related patent
US 9,944,633 B2Related patent
US 2016/0102087 A1This patent

From the US filing history. Foreign family members aren’t listed.

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A compound of Formula IA, IB, IC or ID, or a pharmaceutically acceptable salt, ester or prodrug thereof:

wherein each n and m is independently 0, 1, 2 or 3;
each p and q is independently 0, 1, 2, 3, 4, 5, 6 or 7;
X1 is —C(O)N(RA)— or —C(S)N(RA)—;
wherein RA is independently hydrogen, aliphatic, substituted aliphatic, heteroaryl, substituted heteroaryl, aryl or substituted aryl;
X2 is —S——O—, —S(O)2— —C(R20)(R21)— or —N(RB)—;
wherein RB is independently hydrogen, aliphatic, substituted aliphatic, heteroaryl, substituted heteroaryl, aryl or substituted aryl;
each R1 and R2 is independently hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
R3 is hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
each R10, and R28 is independently absent, hydrogen, halogen, —OR20, —SR20, —NR20R21, —CF3, —CN, —NO2, —N3, —C(O)OR20, —C(O)R20, —C(O)NR20R21, acyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl, aliphatic, substituted aliphatic, aryl or substituted aryl;
alternatively two of R10 groups together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
wherein each R20 and R21 is independently hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
each R11 is independently absent, hydrogen, halogen, —OR20, —SR20, —NR20R21, —CF3, —CN, —NO2, —N3, —C(O)R20, —C(O)OR20, —C(O)NR20R21, acyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl, aliphatic, substituted aliphatic, aryl or substituted aryl;
alternatively two of R11 groups together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
each G1 and G2 is independently, absent, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl;
each R27 and R29 is independently hydrogen, alkyl, substituted alkyl, aryl or substituted aryl;
wherein R3a is selected from alkyl, aryl, alkyl substituted with aryl, straight chain or branched C1-C10 alkyl, C1-C10 alkenyl, C1-C10 alkynyl, C1-C10 alkoxy, alkoxyC1-C10alkoxy, C1-C10alkylamino, alkoxyC1-C10alkylamino, C1-C10alkylcarbonylamino, C1-C10 alkylaminocarbonyl, aryloxyC1-C10 alkoxy, aryloxyC1-C10alkylamino, aryloxyC1-C10 alkylamino carbonyl, C1-C10-alkylaminoalkylaminocarbonyl, C1-C10alkyl(N-alkyl)aminoalkyl-aminocarbonyl, alkylaminoalkylamino, alkylcarbonylaminoalkylamino, alkyl(N-alkyl)aminoalkylamino, (N-alkyl)alkylcarbonylaminoalkylamino, alkylaminoalkyl, alkylaminoalkylaminoalkyl, alkylpiperazinoalkyl, piperazinoalkyl, alkylpiperazino, alkenylaryloxyC1-C10 alkoxy, alkenylarylaminoC1-C10 alkoxy, alkenylaryllalkylamino C1-C10 alkoxy, alkenylaryloxyC1-C10 alkylamino, alkenylaryloxyC1-C10alkylaminocarbonyl, piperazinoalkylaryl, heteroarylC1-C10 alkyl, heteroarylC1-C10alkenyl, heteroarylC1-C10 alkynyl, heteroarylC1-C10 alkylamino, heteroarylC1-C10alkoxy, heteroaryloxyC1-C10alkyl, heteroaryloxyC1-C10 alkenyl, heteroaryloxyC2-C10 alkynyl, heteroaryloxyC1-C10alkylamino, and heteroaryloxyC1-C10 alkoxy;
Cy1 is an optionally substituted aryl or optionally substituted heteroaryl;
and,
R40 is selected from:
wherein, R41 is hydrogen, halogen, aliphatic, substituted aliphatic, aryl, substituted aryl, —OR20, —SR20, —NR20R21, —CF3, —CN, —NO2, —N3, —C(O)R20, —C(O)OR20, —C(O)NR20R21, acyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl.

17 more elements

Facts

Application

14/818,009Filed 4 Aug 2015

Priority

29 Mar 2011

Published

14 Apr 2016

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 419/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 35/00
Antineoplastic agents
C07D 413/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 413/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms:…

Family

Application61/469,054Us provisional application · filed 29 Mar 2011

Application14/037,761Continuation · filed 26 Sep 2013

Application14/818,009Continuation

US 2014/0100223 A1Published application

US 9,120,810 B2Related patent

US 9,944,633 B2Related patent

US 2016/0102087 A1This patent

From the US filing history. Foreign family members aren’t listed.