Pyrazolo[1,5-A][1,3,5]triazine and pyrazolo[1,5-A]pyrimidine derivatives as CDK inhibitors

1. A compound of formula (I):

or a pharmaceutically acceptable salt or a stereoisomer thereof;

wherein,

X is CH or N;

Ring A is 1,3-phenylene, pyridyl or pyridine-N-oxide;

Ring B is cycloalkyl, heterocycloalkyl or heteroaryl;

R 1 is hydrogen, alkyl or cycloalkyl;

R 2 is an optionally substituted alkyl, cycloalkyl or heterocycloalkyl; wherein the optional substituents are amino, halo, hydroxy, alkyl, alkoxy, alkoxyalkoxy, alkylamino, or haloalkyl;

R 3 at each occurrence independently is halo, alkyl, hydroxy, or haloalkyl;

R 4 at each occurrence independently is —(NH) q —S(O) 2 —CH═CH 2 , —(NH) q —CH 2 —CH═CH—

C(O)—NR a R b , wherein R 5 and R 5 ″ at each occurrence independently are hydrogen or alkyl; R 5 ′ is hydrogen, halo, alkyl, alkoxyalkyl or —CH 2 —NR a R b ;

R 6 is hydrogen or alkyl;

R a and R b are independently hydrogen or alkyl; or R a and R b along with the nitrogen atom to which they are attached form an optionally substituted heterocyclic ring having 0-2 additional heteroatoms selected from O, S and N; wherein the optional substituent is one or more alkyl or halo;

L 1 is —O—, or —NH—;

L 2 is absent or optionally substituted C 1 -C 6 alkylene, wherein one or more methylene units of the alkylene is optionally and independently replaced with —C(O)—, —O—, —N(R 7 )—or cycloalkylene; wherein R 7 is hydrogen or alkyl;

m is 0 to 1;

n is 0, 1 or 2;

p is 1; and

q is 0 to 1.

2. The compound of claim 1 , wherein the compound of formula (I) is a compound of formula (IB):

or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

3. The compound of claim 1 , wherein the compound of formula (I) is a compound of formula (IC):

or a pharmaceutically acceptable salt thereof or a stereoisomer thereof;

wherein,

R 2 is optionally substituted cycloalkyl or optionally substituted heterocycloalkyl.

4. The compound of claim 1 , wherein the compound of formula (I) is a compound of formula (IE):

or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

5. The compound of claim 1 , wherein ring A is 1,3-phenylene or pyridyl.

6. The compound of claim 1 , wherein R 2 is cyclohexyl or other optionally substituted cycloalkyl, or R 2 is N-methyl-4-piperidinyl, tetrahydro-4-pyranyl or other optionally substituted heterocycloalkyl.

7. The compound of claim 1 , wherein R 1 is hydrogen, isopropyl or other alkyl.

8. The compound of claim 1 , wherein R 4 is

9. The compound of claim 8 , wherein R 5 ′ is —CH 2 —NR a R b ; wherein R a and R b are independently hydrogen or alkyl.

10. The compound of claim 1 , wherein the compound is selected from:

Compound

No:

IUPAC name

 1.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)piperidine-3-carboxamide;

 2.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)azetidine-2-carboxamide;

 3.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)pyrrolidine-2-carboxamide;

 4.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

 7.

(1,4-cis)-4-acrylamido-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

 8.

1-acryloyl-N-(3-(((8-isopropyl-2-((1-methylpiperidin-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)piperidine-3-carboxamide;

 9.

(1,4-cis)-4-acrylamido-N-(3-(((2-(((1r,4r)-4-hydroxycyclohexyl)amino)-8-

isopropylpyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

 10.

Isomer-1: 4-acrylamido-N-(3-(((2-((3-hydroxycyclohexyl)amino)-8-

isopropyl pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

 12.

Isomer-1: 1-acryloyl-N-(3-(((2-((3-hydroxycyclohexyl)amino)-8-isopropyl

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)pyrrolidine-3-

carboxamide;

 14.

1-acryloyl-N-(3-(((2-(((3S,4S)-3-fluoropiperidin-4-yl)amino)-8-isopropyl

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)pyrrolidine-3-

carboxamide;

 15.

1-acryloyl-N-(3-(((2-((3-aminocyclohexyl)amino)-8-isopropylpyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

 16.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-3-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)piperidine-2-carboxamide;

 17.

N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)-1-(3-methylbut-2-

enoyl)azetidine-2-carboxamide;

 18.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)azetidine-3-carboxamide;

 19.

(R)-1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)azetidine-2-

carboxamide;

 20.

(S)-1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)azetidine-2-

carboxamide;

 21.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)piperidine-2-carboxamide;

 22.

3-acrylamido-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

 23.

4-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)morpholine-2-carboxamide;

 24.

4-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)morpholine-3-carboxamide;

 25.

N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)-4-propioloylmorpholine-3-

carboxamide;

 26.

4-acryloyl-N-(4-ethyl-3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)morpholine-3-

carboxamide;

 27.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)-4-

methylphenyl)azetidine-2-carboxamide;

 28.

1-acryloyl-N-(5-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)-2-

methylphenyl)azetidine-2-carboxamide;

 29.

1-acryloyl-N-(4-fluoro-3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)azetidine-2-carboxamide;

 30.

1-acryloyl-N-(2-fluoro-3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)azetidine-2-carboxamide;

 31.

1-acryloyl-N-(3-fluoro-5-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)azetidine-2-carboxamide;

 32.

1-acryloyl-N-(4-fluoro-3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

 33.

1-acryloyl-N-(3-fluoro-5-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

 34.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)-4-

methylphenyl)piperidine-2-carboxamide;

 35.

1-acryloyl-N-(2-fluoro-3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)piperidine-2-carboxamide;

 36.

1-acryloyl-N-(3-fluoro-5-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)piperidine-2-carboxamide;

 37.

1-acryloyl-N-(4-fluoro-3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)piperidine-2-carboxamide;

 38.

(1,4-cis)-4-acrylamido-N-(2-fluoro-3-(((8-isopropyl-2-((tetrahydro-2H-

pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

 39.

(1,4-cis)-4-acrylamido-N-(4-fluoro-3-(((8-isopropyl-2-((tetrahydro-2H-

pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

 40.

4-acryloyl-N-(5-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)pyridin-3-

yl)morpholine-3-carboxamide;

 40D.

1-acryloyl-N-(3-(((8-isopropyl-2-(((S)-tetrahydro-2H-pyran-3-yl)amino)

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)piperidine-2-

carboxamide;

 40E.

1-acryloyl-N-(3-(((8-isopropyl-2-(((R)-tetrahydro-2H-pyran-3-yl)amino)

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)piperidine-2-

carboxamide;

 41.

(S)-N-(1-acryloylpiperidin-3-yl)-3-(((8-isopropyl-2-((tetrahydro-2H-pyran-

4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)benzamide;

 42.

1-acryloyl-N-(4-fluoro-3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)azetidine-2-carboxamide;

 43.

1-acryloyl-N-(2-fluoro-5-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)but-2-enamide;

 44.

1-acryloyl-N-(2-fluoro-5-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)piperidine-2-

carboxamide;

 45.

1-acryloyl-N-(3-(1-((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)ethyl)phenyl)piperidine-3-

carboxamide;

 46.

3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl 4-acryloylpiperazine-1-carboxylate;

 64.

(E)-1-(4-(dimethylamino)but-2-enoyl)-N-(2-fluoro-5-(((8-isopropyl-2-

((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

 65.

(E)-1-(but-2-enoyl)-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)azetidine-2-carboxamide;

 66.

N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-

a][1,3,5] triazin-4-yl)amino)methyl)phenyl)-1-propioloylazetidine-2-

carboxamide;

 67.

N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]

[1,3,5]triazin-4-yl)amino)methyl)phenyl)-1-methacryloylazetidine-2-

carboxamide;

 68.

(E)-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-

a] [1,3,5]triazin-4-yl)amino)methyl)phenyl)-1-(4-methoxybut-2-

enoyl)pyrrolidine-3-carboxamide;

 69.

(E)-1-(4-(dimethylamino)but-2-enoyl)-N-(3-(((8-isopropyl-2-((tetrahydro-

2H-pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

 70.

(E)-1-(4-(dimethylamino)but-2-enoyl)-N-(4-fluoro-3-(((8-isopropyl-2-

((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)

methyl)phenyl)pyrrolidine-3-carboxamide;

 71.

(E)-1-(4-(dimethylamino)but-2-enoyl)-N-(3-fluoro-5-(((8-isopropyl-2-

((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)

methyl)phenyl)pyrrolidine-3-carboxamide;

 72.

(E)-1-(4-(dimethylamino)but-2-enoyl)-N-(3-(1-((8-isopropyl-2-((tetrahydro-

2H-pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)ethyl)phenyl)piperidine-3-carboxamide;

 73.

(E)-4-(4-(dimethylamino)but-2-enoyl)-N-(3-(((8-isopropyl-2-((tetrahydro-

2H-pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)morpholine-3-carboxamide;

 74.

(E)-1-(4-(dimethylamino)but-2-enoyl)-N-(3-(((8-isopropyl-2-((tetrahydro-

2H-pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl) piperidine-2-carboxamide;

 75.

3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]

triazin-4-yl)amino)methyl)phenyl(E)-4-(4-(dimethylamino)but-2-enoyl)

piperazine-1-carboxylate;

 76.

(E)-1-(4-(dimethylamino)-4-oxobut-2-en-1-yl)-N-(3-(((8-isopropyl-2-

((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl) phenyl)azetidine-2-carboxamide;

 77.

(E)-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)-1-(4-(pyrrolidin-1-yl)but-2-

enoyl)piperidine-2-carboxamide;

 78.

N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)-1-(vinylsulfonyl)piperidine-2-

carboxamide;

 83.

1-acrylamido-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo [1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclopropane-1-carboxamide;

 84.

N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]

[1,3,5]triazin-4-yl)amino)methyl)phenyl)-1-(N-

methylacrylamido)cyclopropane-1-carboxamide;

 85.

4-acrylamido-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo [1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)-1-

methyl-1H-pyrazole-3-carboxamide;

 86.

1-acryloyl-N-(3-((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)phenyl)azetidine-2-

carboxamide;

 87.

(1,4-cis)-4-acrylamido-N-(3-((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)phenyl)cyclohexane-1-

carboxamide;

 88.

1-acryloyl-N-(3-(((8-ethyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-

a][1,3,5] triazin-4-yl)amino)methyl)phenyl)piperidine-4-carboxamide;

 89.

1-acryloyl-N-(3-(((2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)piperidine-3-carboxamide;

 90.

(1,4-cis)-4-acrylamido-N-(3-(((8-ethyl-2-((1-methylpiperidin-4-

yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)

cyclohexane-1-carboxamide;

 91.

(1,4-trans)-4-acrylamido-N-(3-(((8-isoproprayl-2-((1-methylpiperidin-4-

yl)oxy) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

 92.

4-acrylamido-N-(3-(((2-((3-fluoro-1-methylpiperidin-4-

yl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

 94.

1-acryloyl-N-(3-(((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)azetidine-2-carboxamide;

 95.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)pyrrolidine-

3-carboxamide;

 96.

1-acryloyl-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)piperidine-

3-carboxamide;

 97.

(1,4-cis)-4-acrylamido-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)oxy) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

 98.

4-acrylamido-N-(3-(((2-((3-fluorotetrahydro-2H-pyran-4-yl)oxy)-

8-isopropylpyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

100.

(1,4-cis)-4-acrylamido-N-(3-(((8-isopropyl-2-((tetrahydrofuran-3-

yl)oxy)pyrazolo [1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

101.

(1,4-cis)-4-acrylamido-N-(3-(((8-isopropyl-2-((1-methylpyrrolidin-3-yl)oxy)

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)cyclohexane-1-

carboxamide;

102.

1-acryloyl-N-(3-(((2-isobutoxy-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

103.

1-acryloyl-N-(3-(((8-isopropyl-2-(2-methoxyethoxy)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

104.

1-acryloyl-N-(3-(((8-isopropyl-2-(2-(2-

methoxyethoxy)ethoxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

105.

(1,4-cis)-4-acrylamido-N-(3-(((8-cyclopropyl-2-((1-methylpiperidin-4-

yl)oxy) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

106.

(1,4-cis)-4-acrylamido-N-(3-(((8-isopropyl-2-((tetrahydro-2H-pyran-4-

yl)amino) pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

107.

1-acryloyl-N-(3-(((2-(4-aminobutoxy)-8-isopropylpyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)piperidine-4-carboxamide;

108.

1-acryloyl-N-(3-(((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)pyrrolidine-3-carboxamide;

111.

1-acryloyl-N-(3-(((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)piperidine-4-carboxamide;

112.

4-acryloyl-N-(3-(((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)morpholine-2-carboxamide;

113.

4-acryloyl-N-(3-(((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)morpholine-3-carboxamide;

114.

3-acrylamido-N-(3-(((8-isopropyl-2-((1-methylpiperidin-4-

yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

115.

(1,4-cis)-4-acrylamido-N-(3-(((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)cyclohexane-1-

carboxamide;

116.

1-acryloyl-N-(3-(((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl)piperidine-3-carboxamide;

117.

1-acryloyl-N-(2-fluoro-5-(((8-isopropyl-2-((1-methylpiperidin-4-

yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)piperidine-

3-carboxamide;

118.

(1,4-cis)-4-acrylamido-N-(2-fluoro-5-(((8-isopropyl-2-((1-methylpiperidin-

4-yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

119.

1-acryloyl-N-(3-(1-((8-isopropyl-2-((1-methylpiperidin-4-

yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)ethyl)phenyl)piperidine-3-

carboxamide;

120.

2-(1-acryloylpiperidine-3-carboxamido)-5-(((8-isopropyl-2-((1-

methylpiperidin-4-yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)pyridine 1-oxide;

121.

3-(((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)methyl)phenyl 4-acryloylpiperazine-1-

carboxylate;

122.

(E)-1-(4-(dimethylamino)but-2-enoyl)-N-(3-(((8-isopropyl-2-((1-

methylpiperidin-4-yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)piperidine-3-carboxamide;

123.

(E)-1-(4-(dimethylamino)but-2-enoyl)-N-(2-fluoro-5-(((8-isopropyl-2-((1-

methylpiperidin-4-yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)

phenyl)piperidine-3-carboxamide;

124.

(1,4-cis)-4-((E)-4-(dimethylamino)but-2-enamido)-N-(2-fluoro-5-(((8-

isopropyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl) phenyl)cyclohexane-1-carboxamide;

126.

(1,4-cis)-4-acrylamido-N-(3-((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)phenyl)cyclohexane-1-

carboxamide;

127.

1-acryloyl-N-(3-((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-

a][1,3,5]triazin-4-yl)amino)phenyl)piperidine-4-carboxamide;

128.

N-(1-acryloylpiperidin-4-yl)-3-((8-isopropyl-2-((1-methylpiperidin-4-

yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)benzamide;

129.

N-(1-acryloylpiperidin-3-yl)-3-((8-isopropyl-2-((1-methylpiperidin-4-yl)oxy)

pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)benzamide;

131.

(1,4-cis)-4-((E)-4-(dimethylamino)but-2-enamido)-N-(3-((8-isopropyl-2-

((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)phenyl) cyclohexane-1-carboxamide;

132.

(1,4-Trans)-4-((E)-4-(dimethylamino)but-2-enamido)-N-(3-((8-isopropyl-2-

((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)phenyl) cyclohexane-1-carboxamide;

133.

(E)-N-(1-(4-(dimethylamino)but-2-enoyl)piperidin-3-yl)-3-((8-isopropyl-2-

((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)benzamide;

134.

(E)-N-(1-(4-(dimethylamino)but-2-enoyl)piperidin-4-yl)-3-((8-isopropyl-2-

((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)benzamide;

135.

(1,4-cis)-4-(((E)-4-(dimethylamino)-4-oxobut-2-en-1-yl)amino)-N-(3-(((8-

isopropyl-2-((1-methylpiperidin-4-yl)oxy)pyrazolo[1,5-a][1,3,5]triazin-4-

yl)amino)methyl)phenyl)cyclohexane-1-carboxamide;

136.

1-acryloyl-N-(3-(((8-isopropyl-2-methoxypyrazolo[1,5-a][1,3,5]triazin-4-yl)

amino)methyl)phenyl)piperidine-4-carboxamide; or

139.

1-acryloyl-N-(3-(((3-isopropyl-5-((tetrahydro-2H-pyran-4-

yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)phenyl)azetidine-2-

carboxamide,

or a pharmaceutically acceptable salt or a stereoisomer thereof.

11. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof and at least one pharmaceutically acceptable carrier or excipient.

12. A method of treating a subject suffering from a hematopoietic cancer with aberrant activity of selective transcriptional CDKs comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 11 .

13. A method of treating a hematopoietic cancer mediated by selective transcriptional CDKs in a subject comprising administering a therapeutically effective amount of the compound of claim 1 .

14. A method of inhibiting selective transcriptional CDKs in a subject, comprising administering to the subject a compound of claim 1 .

15. The method of claim 13 , wherein the hematopoietic cancer is leukemia, acute lymphoblastic leukemia, acute lymphocytic leukemia, Hodgkins lymphoma, non-Hodgkins lymphoma, B-cell lymphoma, T-cell lymphoma, hairy cell lymphoma, myeloma, mantle cell lymphoma, Burkett's lymphoma, chronic myelogenous leukemia, or promyelocytic leukemia.

16. The method of claim 13 , wherein the hematopoietic cancer is acute myeloid leukemia.

17. The method of claim 13 , further comprising a step of administering to the subject in need thereof one or more chemotherapeutic agents independently selected from anti-proliferative agents, anti-cancer agents, immunosuppressant agents and pain-relieving agents.

18. The method of claim 13 , wherein the selective transcriptional CDKs are CDK7, CDK9, CDK12, CDK13 or CDK 18.

19. The compound of claim 10 , wherein compound 119 has the structure:

or a pharmaceutically acceptable salt or a stereoisomer thereof.

20. The compound of claim 10 , wherein compound 94 has the structure:

or a pharmaceutically acceptable salt or a stereoisomer thereof.

21. The compound of claim 10 , wherein compound 46 has the structure:

or a pharmaceutically acceptable salt or a stereoisomer thereof.

22. The compound of claim 10 , wherein compound 115 has the structure:

or a pharmaceutically acceptable salt or a stereoisomer thereof.