US 2026/0250262 A1 · NEW COMPOUND AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

Abstract

The present invention relates to a new urea compound, an optical isomer thereof, a pharmaceutically acceptable salt of them, or a hydrate or solvate of them, and a new compound exhibits NAMPT inhibitory activity and may effectively prevent or treat cancer.

Claims20

Dependent claims

1-26. (canceled)

A urea compound represented by formula I below, an optical isomer thereof, a pharmaceutically acceptable salt of the compound or the optical isomer, or a hydrate or solvate of the compound, the optical isomer, or the pharmaceutically acceptable salt:

R1 is 6- to 12-membered aryl;
or 5- to 12-membered heteroaryl comprising at least one heteroatom selected from the group consisting of N, O and S, in which —H of the aryl or heteroaryl of R1 is each independently unsubstituted or at least one —H is each independently substituted with —NH2, —(C1-5 alkyl)NH2, —NH—(C1-5 alkyl), —N(C1-5 alkyl)2, —OH, —NO2, C1-5 alkyl, —F, —Cl, —Br, or —I;
R2 is
wherein the Rx1 is C1-5 alkyl;
C2-5 alkenyl;
6- to 12-membered aryl;
3- to 10-membered cycloalkyl;
3- to 10-membered heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, O and S;
or 5- to 12-membered heteroaryl comprising at least one heteroatom selected from the group consisting of N, O and S, and a is 0, 1, 2, 3, or 4;
—NRx2Rx3, wherein Rx2 or Rx3 is each independently H or C1-6 alkyl;
6- to 12-membered aryl;
5- to 12-membered heteroaryl comprising at least one heteroatom selected from the group consisting of N, O and S;
—ORx4 (Rx4 is 3- to 7-membered aryl);
3- to 10-membered heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, O and S;
3- to 10-membered cycloalkyl;
wherein Za is a single bond, —NH— or —CH2—, and Rx5 is 5- to 12-membered heteroaryl comprising at least one heteroatom selected from the group consisting of N, O and S, 6- to 12-membered aryl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, O and S, or —NYaYb, wherein Ya or Yb is each independently H or C1-6 alkyl;
wherein Zb is a single bond, —NH—, —NHCH2—, —NH(CH2)2—, —CH2—, —(CH2)2—, —(CH2)3—, or —CH2NH—, Rx6 is 5- to 12-membered heteroaryl comprising at least one heteroatom selected from the group consisting of N, O and S, 6- to 12-membered aryl, 3- to 10-membered heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, O and S, —NYcYd, wherein Yc or Yd is each independently —H, C1-6 alkyl or C3.6 cycloalkyl, or 3- to 10-membered cycloalkyl, and b is an integer of 0 to 4;
in which —H of each group of the R2 is each independently unsubstituted or at least one —H is each independently substituted with one selected from the group consisting of C1-5 alkyl, wherein —H of the C1-5 alkyl is unsubstituted or at least one —H is each independently substituted with one selected from the group consisting of phenyl, pyridinyl, morpholinyl, piperazinyl and piperidinyl;
—(C1-5 alkyl)NH2;
—NH2;
—NH(C1-5 alkyl);
—N(C1-5 alkyl)2;
—NHCH3;
—N(CH3)2;
—NHCH2CH3;
—OH;
—NO2;
—F;
—Cl;
—Br;
—I;
—CHF2;
—CF3;
C1-5alkoxy;
—C(═O)N(CH3)2;
—C(═O)NHCH3;
—C(═O)NH2;
—NHC(═O)CH3;
—C(═O)CH2CH3;
6- to 12-membered aryl, wherein —H of the 6- to 12-membered aryl is unsubstituted or at least one —H is substituted with one selected from the group consisting of C1-3 alkyl and —CF3;
5- to 12-membered heteroaryl comprising at least one heteroatom selected from the group consisting of N, O and S, wherein —H of the 5- to 12-membered heteroaryl is unsubstituted or at least one —H is substituted with one selected from the group consisting of C1-3 alkyl and —CF3;
3- to 10-membered cycloalkyl;
3- to 10-membered heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, O and S, wherein —H of the 3- to 10-membered heterocycloalkyl is unsubstituted or at least one —H is substituted with one selected from the group consisting of C1-3 alkyl and —CF3;
3- to 10-membered cycloalkoxy;
—S(═O)2NHCH3;
—S(═O)2, —S(═O)2—CH3, —C(═O)NH2;
wherein the Ra1 and Ra2 are each independently —H, —F, —Cl, —Br, —I or C1-5 alkyl, and Y1 is selected from —CH2, —NH— and —O—;
wherein the Ra3 is —H, C1-5 alkyl or —CF3;
R3 is 6- to 12-membered aryl;
5- to 12-membered heteroaryl comprising at least one heteroatom selected from the group consisting of N, O and S;
3- to 10-membered heterocycloalkyl comprising at least one heteroatom selected from the group consisting of N, O and S;
or 3- to 10-membered cycloalkyl,
in which —H of each group of R3 is each independently unsubstituted or at least one —H is each independently substituted with one selected from the group consisting of 1) to 18) below:
1) C1-5 alkyl;
2) —F, —Cl, —Br, or —I
3)
in which Rx7 is C1-3 alkyl or —CF3;
4)
in which c is 0, 1, 2 or 3, Rx8 is C1-5 alkyl, —NH2, —NHCH3, —N(CH3)2, piperidinyl, piperazinyl, morpholinyl,
wherein the Rb1 is —NH2 or —CH2OH,
wherein the Rb2 is —CH2—, —NH— or —O—, and Rb3 and Rb4 are each independently —H, —F, —Cl, —Br, or —I, pyridinyl, pyrimidinyl or pyrrolyl, and Rx9 is —H or C1-5 alkyl;
5) —COOH;
6) —NRx10Rx11, in which Rx10 or Rx11 are each independently —H or —CH3;
7) —CF3;
8) —CN;
9) Morpholinyl or morpholinyl in which at least one —H is each independently substituted with C1-5 alkyl, —F, —Cl, —Br, —I, —C(═O)NHCH3, —C(═O)CH3 or —C(═O)CH═CH2;
10) Piperidinyl or piperidinyl in which at least one —H is each independently substituted with C1-5 alkyl, —F, —Cl, —Br, —I, —C(═O)NHCH3, —C(═O)CH3 or —C(═O)CH═CH2;
11) Piperazinyl or piperazinyl in which at least one —H is each independently substituted with C1-5 alkyl, —F, —Cl, —Br, —I, —C(═O)NHCH3, —C(═O)CH3 or —C(═O)CH═CH2;
12) —ORx12, in which Rx12 is —CF3 or C1-3 alkyl;
13) —OH;
14)
in which d is 0, 1, 2 or 3, and Rx13 is —NH2, —NH(CH3), —N(CH3)2, methylpyrazolyl, pyrazolyl, piperazinyl, piperidinyl, or morpholinyl;
15)
in which Rx14 is —CH2—, —NH— or —O—, and Rx15 is —H, C1-5 alkyl, —NH2, —F, —Cl, —Br, or —I;
16)
in which Rx16 is C1-5 alkyl or —CH2CH2N(CH3)2,
17)
and
18) —(C1-3 alkyl)-NH2,
Ak is —(CH2)n— or
in which —H of the —(CH2)n— or
each independently unsubstituted or at least one —H is each independently substituted with —NH2, —OH, —NO2, C1-5 alkyl, —CH2NH2, —CF3, —OCF3, —CN, —F, —Cl, —Br, or —I, and n is 1, 2 or 3, and
X1 to X3 are each independently —CH— or —N—.

80 more elements

A urea compound represented by formula I-1 or I-2 below, an optical isomer thereof, a pharmaceutically acceptable salt of the compound or the optical isomer, or a hydrate or solvate of the compound, the optical isomer, or the pharmaceutically acceptable salt:

R1 is pyridinyl;
pyrimidinyl;
pyrazolyl;
imidazolyl;
pyrrolyl;
furanyl;
phenyl;
phenolic;
in which —H of each of the R1 is unsubstituted or at least one —H is each independently substituted with —NH2, —(C1-3 alkyl)-NH2, —NH—(C1-3 alkyl), —N(C1-3 alkyl)2, —OH, —NO2, C1-5 alkyl, —F, —Cl, —Br, or —I,
R2 is pyridinyl;
pyrimidinyl;
phenyl;
piperidinyl;
piperazinyl;
morpholinyl;
pyrazolyl, imidazolyl;
phenolic;
—CH2C(═O)NH2;
—C(═O)NH2;
—C(═O)NHCH2CH3;
—CH2NHC(═O)CH2CH3;
—NH2;
—NHCH3;
—NHCH2CH2CH3;
in which —H of each of the R2 is each independently unsubstituted or at least one —H is each independently substituted with —NH2, —NH(C1-5 alkyl), —N(C1-5 alkyl)2, —NHCH3, —N(CH3)2, —NHCH2CH3, —OH, —NO2, —S(═O)2CH3, C1-5 alkyl, wherein —H of the C1-5 alkyl may be unsubstituted or at least one —H is each independently substituted with one selected from the group consisting of phenyl, pyridinyl, morpholinyl, piperazinyl and piperidinyl, morpholinyl, piperidinyl, piperazinyl, phenyl, pyridinyl, pyrimidinyl, wherein —H of the morpholinyl, piperidinyl, piperazinyl, phenyl, pyridinyl and pyrimidinyl is unsubstituted or at least one —H is each independently substituted with one selected from the group consisting of C1-3 alkyl and —CF3, cyclohexyl, cyclobutoxy, cyclopropoxy, cyclopentoxy, —F, —Cl, —Br, —I, —CHF2, —CF3, C1-3 alkoxy, —NHC(═O)CH3, —C(═O)CH2CH3, —C(═O)N(CH3)2, —C(═O)NH(CH3), —C(═O)NH2, —S(═O)2NHCH3;
—S(═O)2, —S(═O)2CH3, trifluoromethylphenyl,
wherein the Ra1 and Ra2 are each independently —H, —F, —Cl, —Br, —I or C1-5 alkyl, and Y1 is one selected from —CH2, —NH— and —O—,
wherein the Ra3 is —H, C1-5 alkyl or —CF3,
R3 is phenyl, in which —H of the phenyl is unsubstituted or at least one —H is each independently substituted with one group selected from the group consisting of 1) to 18) below:
1) C1-5 alkyl;
2) —F, —Cl, —Br, or —I
3)
in which Rx7 may be —CF3;
4)
in which if c is 0, Rx8 is C1-5 alkyl or piperidinyl, and Rx9 is —H or C1-5 alkyl;
if c is 1, Rx8 is
wherein the Rb1 is —NH2 or —CH2OH, and Rx9 is —H or C1-5 alkyl;
if c is 2, Rx8 is C1-5 alkyl, —NH2, —NHCH3, —N(CH3)2, piperidinyl, difluoropiperidinyl, piperazinyl, morpholinyl,
wherein the Rb1 is —NH2 or —CH2OH, pyridinyl, or pyrrolyl, and Rx9 is —H or C1-5 alkyl;
5) —COOH;
6) —NRx10Rx11, in which Rx10 and Rx11 are each independently —H or —CH3;
7) —CF3;
8) —CN;
9) Morpholinyl or morpholinyl in which at least one —H is each independently substituted with C1-5 alkyl, —F, —Cl, —Br, —I, —C(═O)NHCH3, —C(═O)CH3 or —C(═O)CH═CH2;
10) Piperidinyl or piperidinyl in which at least one —H is each independently substituted with C1-5 alkyl, —F, —Cl, —Br, —I, —C(═O)NHCH3, —C(═O)CH3 or —C(═O)CH═CH2;
11) Piperazinyl or piperazinyl in which at least one —H is each independently substituted with C1-5 alkyl, —F, —Cl, —Br, I, —C(═O)NHCH3, —C(═O)CH3 or —C(═O)CH═CH2;
12) —ORx12, in which Rx12 is —CF3;
C1-3 alkyl;
13) —OH;
14)
in which d is 1, 2 or 3, and Rx13 is —NH2, —NH(CH3), —N(CH3)2, methylpyrazolyl, pyrazolyl, piperazinyl, piperidinyl, or morpholinyl;
15)
in which Rx14 is —CH2—, —NH— or —O—, and Rx15 is —H, C1-5 alkyl, —NH2, —F, —Cl, —Br, or —I;
16)
in which Rx16 is C1-5 alkyl or —CH2CH2N(CH3)2;
17)
and
18) Ethylamine,
Ak is —CH2—, —(CH2)2—, —(CH2)3— or
wherein —H of —CH2—, —(CH2)2—, —(CH2)3— or
is each independently unsubstituted or at least one —H is each independently substituted with —NH2, —OH, —NO2, C1-5 alkyl, —CH2NH2, —CF3, —OCF3, —CN, —F, —Cl, —Br, or —I;
or in Formula I-1,
the R1 is a functional group of Table 1, wherein —H of each of the functional group is unsubstituted or at least one H is each independently substituted with —NH2, —OH, —NO2, —CH2NH2, —CF3, —OCF3, —CN, C1-5 alkyl, —F, —Cl, —Br, or —I,
R2 is a functional group of Table 2, wherein —H of each of the functional group is unsubstituted or at least one H is each independently substituted with —NH2, —OH, NO2, C1-5 alkyl, —CH2NH2, —CF3, —OCF3, —CN, —F, —Cl, —Br, or —I, R3 is a functional group of Table 3, wherein —H of each of the functional group is unsubstituted or at least one H is each independently substituted with —NH2, —NHCH3, —OH, —NO2, —CH2NH2, —CF3, —OCF3, —CN, —F, —Cl, —Br, C1-5alkyl, or —I,
TABLE 1
TABLE 2
TABLE 3
Ak is —CH2—, —(CH2)2—, —(CH2)3— or
wherein —H of —CH2—, —(CH2)2—, —(CH2)3— or
is each independently unsubstituted or at least one —H is each independently substituted with —NH2, —OH, —NO2, C1-5 alkyl, —CH2NH2, —CF3, —OCF3, —CN, —F, —Cl, —Br, or —I;
wherein
R1 is pyridinyl;
pyrimidinyl;
pyrazolyl;
imidazolyl;
pyrrolyl;
furanyl;
phenyl;
phenolic;
in which —H of each of the R1 is unsubstituted or at least one —H is each independently substituted with —NH2, —(C1-3 alkyl)NH2, —NH—(C1-3 alkyl), —N(C1-3 alkyl)2, —OH, —NO2, C1-5 alkyl, —F, —Cl, —Br, or —I,
R2 is pyridinyl;
pyrimidinyl;
phenyl;
piperidinyl;
piperazinyl;
morpholinyl;
pyrazolyl;
imidazolyl;
phenolic;
—CH2C(═O)NH2;
—C(═O)NH2;
—C(═O)NHCH2CH3;
—CH2NHC(═O)CH2CH3;
—NH2;
—NHCH3;
—NHCH2CH2CH3;
in which —H of each of the R2 is each independently unsubstituted or at least one —H is each independently substituted with —NH2, —NH(C1-5 alkyl), —N(C1-5 alkyl)2, —NHCH3, —N(CH3)2, —NHCH2CH3, —OH, —NO2, —S(═O)2CH3, C1-5 alkyl, wherein —H of the C1-5 alkyl may be unsubstituted or at least one —H is each independently substituted with one selected from the group consisting of phenyl, pyridinyl, morpholinyl, piperazinyl and piperidinyl, morpholinyl, piperidinyl, piperazinyl, phenyl, pyridinyl, pyrimidinyl, wherein —H of the morpholinyl, piperidinyl, piperazinyl, phenyl, pyridinyl and pyrimidinyl is unsubstituted or at least one —H is each independently substituted with one selected from the group consisting of C1-3 alkyl and —CF3, cyclohexyl, cyclobutoxy, cyclopropoxy, cyclopentoxy, —F, —Cl, —Br, —I, —CHF2, —CF3, C1-3 alkoxy, —NHC(═O)CH3, —C(═O)CH2CH3, —C(═O)N(CH3)2, —C(═O)NH(CH3), —C(═O)NH2, —S(═O)2NHCH3;
—S(═O)2, —S(═O)2CH3, trifluoromethylphenyl,
wherein the Ra1 and Ra2 are each independently —H, —F, —Cl, —Br, —I or C1-5 alkyl, and Y1 is one selected from —CH2—, —NH— and —O—,
wherein the Ra3 is —H, C1-5 alkyl or —CF3,
Ak is —CH2—, —(CH2)2—, —(CH2)3— or
wherein —H of —CH2—, —(CH2)2—, —(CH2)3— or
is each independently unsubstituted or at least one —H is each independently substituted with —NH2, —OH, —NO2, C1-5 alkyl, —CH2NH2, —CF3, OCF3, —CN, —F, —Cl, —Br, or —I;
and
Za and Zb are each independently —H or one selected from the group consisting of 1) to 18) below:
1) C1-5 alkyl;
2) —F, —Cl, —Br, or —I
3)
in which Rx7 is C1-5 alkyl or —CF3;
4)
in which c is 0, 1, 2 or 3, Rx8 is C1-5 alkyl, —NH2, —NHCH3, —N(CH3)2, piperidinyl, piperazinyl, morpholinyl,
wherein the Rb1 is —NH2 or —CH2OH,
wherein the Rb2 is —CH2—, —NH— or —O—, and Rb3 and Rb4 are each independently —H, —F, —Cl, —Br, or —I, pyrimidinyl or pyrrolyl, and Rx9 is —H or C1-5 alkyl;
5) —COOH;
6) —NRx10Rx11, in which Rx10 or Rx11 are each independently —H or —CH3;
7) —CF3;
8) —CN;
9) Morpholinyl or morpholinyl in which at least one —H is each independently substituted with C1-5 alkyl, —F, —Cl, —Br, —I, —C(═O)NHCH3, —C(═O)CH3 or —C(═O)CH═CH2;
10) Piperidinyl or piperidinyl in which at least one —H is each independently substituted with C1-5 alkyl, —F, —Cl, —Br, —I, —C(═O)NHCH3, —C(═O)CH3 or —C(═O)CH═CH2;
11) Piperazinyl or piperazinyl in which at least one —H is each independently substituted with C1-5 alkyl, —F, —Cl, —Br, —I, —C(═O)NHCH3, —C(═O)CH3 or —C(═O)CH═CH2;
12) —ORx12, in which Rx12 is —CF3;
C1-3 alkyl;
13) —OH;
14)
in which d is 0, 1, 2 or 3, and Rx13 is —NH2, —NH(CH3), —N(CH3)2, methylpyrazolyl, pyrazolyl, piperazinyl, piperidinyl, or morpholinyl;
15)
in which Rx14 is —CH2—, —NH— or —O—, and Rx15 is —H, linear or branched C1-5 alkyl, —NH2, —F, —Cl, —Br, or —I;
16)
in which Rx16 is C1-5 alkyl or —CH2CH2N(CH3)2,
17)
and
18) —(C1-3 alkyl)-NH2;
or in Formula I-2,
R1 is pyridinyl;
pyrimidinyl;
imidazolyl;
pyrazolyl;
phenyl;
in which —H of each group of R1 is each independently unsubstituted or at least one —H is each independently substituted with morpholinyl, piperidinyl, piperazinyl, —NH2, —(C1-3 alkyl)NH2, —NH—(C1-3 alkyl), —N(C1-3 alkyl)2, —OH, —NO2, C1-5alkyl, —F, —Cl, —Br, or —I,
R2 is pyridinyl;
pyrimidinyl;
phenyl;
piperazinyl;
piperidinyl;
and the p1, p2, p3 or p4 are each independently an integer of 0 to 3, in which —H of each group of R2 is each independently unsubstituted or at least one —H is each independently substituted with morpholinyl, piperidinyl, piperazinyl, —NH2, —(C1-3 alkyl)NH2, —NH—(C1-3 alkyl), —N(C1-3alkyl)2, —OH, —NO2, C1-5 alkyl, —F, —Cl, —Br, or —I,
Za or Zb is each independently —H, morpholinyl, piperidinyl, piperazinyl, —NHC(═O)(C1-3 alkyl), —NH2, —(C1-3 alkyl)NH2, —NH(C1-3 alkyl), —N(C1-3 alkyl)2, —OH, —NO2, C1-5alkyl, —F, —Cl, —Br, —I,
and the q1 or q2 is each independently an integer of 0 to 3, in which —H of each group of the Za or Zb is each independently unsubstituted or at least one —H is each independently substituted with C1-5alkyl, —NH2, —(C1-3 alkyl)NH2, —NH—(C1-3alkyl), or —N(C1-3alkyl)2, and
the Ak is —(CH2)n—, in which the n is 1, 2 or 3.

145 more elements

Dependencies are inferred from the claim text.

Facts

Application

19/154,726Filed 8 Feb 2024

Priority

KR 10-2023-001833310 Feb 2023

Published

27 Aug 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification27 codes

A61P 35/00
Antineoplastic agents
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61K 31/437
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring…
A61K 31/438
Having six-membered rings with one nitrogen as the only ring hetero atom: the ring being spiro-condensed with carbocyclic or heterocyclic ring systems

New compound and pharmaceutical composition comprising same

Life of this patent

Abstract

Claims20

New compound and pharmaceutical composition comprising same

Life of this patent

Abstract

Claims20