IP Library › Granted Patent US 12673951

Granted Patent B2

US 12673951 · App. 17/626,029 · Granted Jul 7, 2026

Substituted pyrazoloquinazolinone compounds and application thereof

Inventors: Sui Xiong Cai (Shanghai, CN); Ye Edward Tian (Shanghai, CN); Xiaozhu Wang (Nanjing, CN)

Assignee: Impact Therapeutics (Shanghai) Inc

C07D487/04 A61K31/519 A61K45/06 A61P35/00

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 12673951
App. No.: 17/626,029
Granted: Jul 7, 2026
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

A compound of formula I, or a stereoisomer, tautomer, N-oxide, hydrate, isotope-substituted derivative, or solvate thereof, or a pharmacologically acceptable salt thereof, or a mixture thereof, of a prodrug thereof. The compound of formula I is a kinase inhibitor which can be used for treating clinical disorder caused by DDR deficiencies, such as cancers.

Claims (88)

1 . A compound having the Formula I:

or stereoisomers, tautomers, N-oxides, hydrates, isotope-substituted derivatives, solvates or pharmaceutically acceptable salts thereof, or mixtures thereof, wherein:

A 1 , A 2 and A 3 each are CR 4 , CR 5 and CR 6 , respectively;

B 1 is CH, B 2 is N, B 3 is CH and B 4 is CH; or

B 1 is CH, B 2 is CR 8 , B 3 is CH and B 4 is CH;

R 1 is C 1-4 alkyl or tetrahydropyranyl, optionally substituted by 1-4 C 1-6 alkyl groups;

R 2 is C 1-6 alkyl;

R 3 is C 1-6 alkoxy substituted by —NR 11 R 12 , wherein R 11 and R 12 each are independently H or C 1-6 alkyl, or R 11 and R 12 together with the N atom to which they are both bonded links to form an optionally substituted 4-8 membered heterocyclic group; or R 3 is piperidinyl substituted by —NR 11 R 12 , wherein R 11 and R 12 each are independently H or C 1-6 alkyl; and

R 4 , R 5 , and R 6 are H; and

R 8 is H, halogen, C 1-4 alkyl, or halo C 1-4 alkyl;

wherein the compound of Formula I is not 9-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-c]quinazolin-2(3H)-one.

2 . The compound of claim 1 , wherein

R 2 is C 1-4 alkyl.

3 . The compound of claim 1 , wherein the compound has Formula IIa or IIb:

or stereoisomers, tautomers, N-oxides, hydrates, isotope-substituted derivatives, solvates or pharmaceutically acceptable salts thereof, or mixtures thereof, wherein

R 7 , R 9 , and R 10 are H.

4 . The compound of claim 1 , wherein said compound is selected from the group consisting of:

9-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(4-(3-(dimethylamino)propoxy)-3-(trifluoromethyl)phenyl)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(4-(4-(dimethylamino)piperidin-1-yl)-3-fluorophenyl)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(3-chloro-4-(4-(dimethylamino)piperidin-1-yl)phenyl)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(4-(4-(dimethylamino)piperidin-1-yl)-3-(trifluoromethyl)phenyl)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(4-(4-(methylamino)piperidin-1-yl)-3-(trifluoromethyl)phenyl)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(4-(4-(ethylamino)piperidin-1-yl)-3-(trifluoromethyl)phenyl)-3-methyl-1-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-1-isopropyl-3-methylpyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-1-isopropyl-3-methylpyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(4-(4-(dimethylamino)piperidin-1-yl)-3-fluorophenyl)-1-isopropyl-3-methylpyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(3-chloro-4-(4-(dimethylamino)piperidin-1-yl)phenyl)-1-isopropyl-3-methylpyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(4-(4-(dimethylamino)piperidin-1-yl)-3-(trifluoromethyl)phenyl)-1-isopropyl-3-methylpyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(4-(3-(dimethylamino)propoxy)-3-fluorophenyl)-1-isopropyl-3-methylpyrazolo[1,5-c]quinazolin-2(3H)-one;

9-(4-(3-(dimethylamino)propoxy)-3-(trifluoromethyl)phenyl)-1-isopropyl-3-methylpyrazolo[1,5-c]quinazolin-2(3H)-one; and

9-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-3-ethyl-1-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-c]quinazolin-2(3H)-one;

or stereoisomers, tautomers, N-oxides, hydrates, isotope-substituted derivatives, solvates or pharmaceutically acceptable salts thereof, or mixtures thereof.

5 . A pharmaceutical composition comprising a compound of claim 1 , or a stereoisomer, a tautomer, a N-oxide, a hydrate, an isotope-substituted derivative, a solvate or a pharmaceutically acceptable salt thereof, or a mixture thereof, and a pharmaceutically acceptable carrier.

6 . The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition further comprises at least one known anticancer drug, or its pharmaceutically acceptable salts.

7 . The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition further comprises at least one of the following anticancer drugs: busulfan, melphalan, chlorambucil, cyclophosphamide, ifosfamide, temozolomide, bendamustine, cis-platin, mitomycin C, bleomycin, carboplatin, camptothecin, irinotecan, topotecan, doxorubicin, epirubicin, aclarubicin, mitoxantrone, methylhydroxy ellipticine, etoposide, 5-azacytidine, gemcitabine, 5-fluorouracil, methotrexate, 5-fluoro-2′-deoxy-uridine, fludarabine, nelarabine, ara-C, alanosine, pralatrexate, pemetrexed, hydroxyurea, thioguanine, colchicine, vinblastine, vincristine, vinorelbine, paclitaxel, ixabepilone, cabazitaxel, docetaxel, mAb, panitumumab, ofatumumab, avastin, trastuzumab, rituximab, imatinib, gefitinib, erlotinib, lapatinib, sorafinib, sunitinib, nilotinib, dasatinib, pazopanib, bortezomib, torisel, everolimus, vorinostat, romidepsin, tamoxifen, letrozole, fulvestrant, mitoguazone, octreotide, retinoic acid, arsenic trioxide, zoledronic acid, bortezomib, thalidomide, lenalidomide, venetoclax, aldesleukin (recombinant human interleukin-2), sipueucel-T (prostate cancer therapeutic vaccine), palbociclib, olaparib, niraparib, rucaparib, talazoparib or senaparib.

8 . The pharmaceutical composition of claim 5 , wherein the compound of Formula I has a structure of Formula IIa or IIb:

or stereoisomers, tautomers, N-oxides, hydrates, isotope-substituted derivatives, solvates or pharmaceutically acceptable salts thereof, or mixtures thereof, wherein R 7 , R 9 , and R 10 are H.

9 . The pharmaceutical composition of claim 5 , wherein the compound is selected from the group consisting of: