NZ765656B2 - Substituted bicyclic heterocyclic compounds as prmt5 inhibitors - Google Patents

Substituted bicyclic heterocyclic compounds as prmt5 inhibitors

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Publication number
NZ765656B2
NZ765656B2 NZ765656A NZ76565618A NZ765656B2 NZ 765656 B2 NZ765656 B2 NZ 765656B2 NZ 765656 A NZ765656 A NZ 765656A NZ 76565618 A NZ76565618 A NZ 76565618A NZ 765656 B2 NZ765656 B2 NZ 765656B2
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NZ
New Zealand
Prior art keywords
pyrrolo
diol
pyrimidinyl
amino
ethyl
Prior art date
Application number
NZ765656A
Other versions
NZ765656A (en
Inventor
Balasaheb Arjun Gore
Ganesh Bhausaheb Gudade
Anil Kashiram Hajare
Rajender Kumar Kamboj
Chaitanya Prabhakar Kulkarni
Sanjeev Anant Kulkarni
Dipak Raychand Lagad
Prathap Sreedharan Nair
Venkata P Palle
Chetan Sanjay Pawar
Original Assignee
Lupin Limited
Filing date
Publication date
Application filed by Lupin Limited filed Critical Lupin Limited
Priority claimed from PCT/IB2018/060015 external-priority patent/WO2019116302A1/en
Publication of NZ765656A publication Critical patent/NZ765656A/en
Publication of NZ765656B2 publication Critical patent/NZ765656B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The invention relates to substituted bicyclic heterocyclic compounds of formula (I), pharmaceutically acceptable salts thereof and pharmaceutical compositions for treating diseases, disorders or conditions associated with the overexpression of PRMT5 5 enzyme. The invention also relates to methods of treating diseases, disorders or conditions associated with the overexpression of PRMT5 enzyme.

Claims (20)

1. A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, 5 wherein, a b a L is selected from -CR R -, -NR -, S, and O; Z is selected from CH and N; R and R are independently selected at each occurrence from hydrogen, substituted or unsubstituted alkyl, and cycloalkyl; 10 ring A is selected from, R and R are selected from substituted or unsubstituted alkyl or together with the carbon atoms to which they are attached form a C -C cycloalkyl ring; R is selected from –NR R , hydrogen, halogen, substituted or unsubstituted alkyl, 15 alkoxy, substituted or unsubstituted heteroaryl and cycloalkyl; R and R together with the carbon atoms to which they are attached form a bond in order to form a –C=C-; or R and R together with the carbon atoms to which they are attached form a cyclopropane ring; 2’ 2a R and R which may be same or different and are independently selected from 20 hydrogen and substituted or unsubstituted alkyl; R is independently selected at each occurrence from halogen, cyano, nitro, 6 7 8 substituted or unsubstituted alkyl, -OR , -NR R , cycloalkyl, -C(O)OH, -C(O)O- 9 7 8 7 9 alkyl, -C(O)R , -C(O)NR R , –NR C(O)R substituted or unsubstituted aryl, wherein when substituted the substituent is halogen, substituted or unsubstituted 5 heteroaryl, and substituted or unsubstituted heterocyclyl; R and R are independently selected from hydrogen, substituted or unsubstituted alkyl, and cycloalkyl; R is selected from hydrogen, substituted or unsubstituted alkyl, and cycloalkyl; R and R are independently selected from hydrogen, substituted or unsubstituted 10 alkyl, and cycloalkyl; R is selected from substituted or unsubstituted alkyl and cycloalkyl; R is selected from hydrogen, halogen, and substituted or unsubstituted alkyl; ‘n’ is an integer ranging from 0 to 4, both inclusive; when an alkyl group is substituted, it is substituted with 1 to 4 substituents 15 independently selected from oxo (=O), halogen, cyano, cycloalkyl, aryl, 7a 8a 8b heteroaryl, heterocyclyl, -OR , -C(=O)OH, -C(=O)O(alkyl), -NR R , - 8a 9a 8a 8b NR C(=O)R , and –C(=O)NR R ; when the heteroaryl group is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, nitro, cyano, alkyl, haloalkyl, perhaloalkyl, 7a 8a 8b 7a 9a 20 cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR , -NR R , -NR C(=O)R , – 9a 8a 8b C(=O)R , –C(=O)NR R , -SO -alkyl, -C(=O)OH, and -C(=O)O-alkyl; when the heterocycle group is substituted, it is substituted either on a ring carbon atom or on a ring hetero atom, and when it is substituted on a ring carbon atom, it is substituted with 1 to 4 substituents independently selected from oxo (=O), 7a 8a 8b 25 halogen, cyano, alkyl, cycloalkyl, perhaloalkyl, -OR , –C(=O)NR R , - C(=O)OH, -C(=O)O-alkyl, -N(H)C(=O)(alkyl), -N(H)R , and -N(alkyl) ; and when the heterocycle group is substituted on a ring nitrogen, it is substituted with substituents independently selected from alkyl, cycloalkyl, aryl, heteroaryl, - SO (alkyl), –C(=O)R , and -C(=O)O(alkyl); when the heterocycle group is substituted on a ring sulfur, it is substituted with 1 or 2 oxo (=O) group(s); R is selected from hydrogen, alkyl, perhaloalkyl, and cycloalkyl; 8a 8b 5 R and R are each independently selected from hydrogen, alkyl, and cycloalkyl; R is selected from alkyl and cycloalkyl.
2. The compound of claim 1 having the structure of Formula (II), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein, a b 2’ 2a 3 10 Ring A, Z, L , R , R , R , R, R , R , R and ‘n’ are as defined herein above.
3. The compound of claim 1 having the structure of Formula (III), a stereoisomer 15 thereof, or a pharmaceutically acceptable salt thereof, wherein, a b 2’ 2a 3 10 Ring A, Z, L , R , R , R , R, R , R , R and ‘n’ are as defined herein above.
4. The compound of claim 1 having the structure of Formula (IV), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, 5 wherein, X is Br or Cl; a b 1 2’ 2 2a 10 L , R , R , R ,R , R , R, R and R are as defined herein above.
5. The compound of claim 1 to 4, wherein L is selected from –CH -, –CH(CH )-, - 1 2 3 NH-, -N(CH )-, S, and O. 10
6. The compound of claim 1 to 3, wherein R is selected from F, Cl, Br, CN, -NH , - NH(CH ), -NHCH(CH ) , -CH , cyclopropyl, -CH(CH ) , -CF CH , -OCH , CF , 3 3 2 3 3 2 2 3 3 3 , , , , and
7. The compound of claim 1 to 4, wherein R is selected from hydrogen, –NH , Cl, - 15 CH(CH ) methyl, ethyl, cyclopropyl and .
8. The compound of claim 1 to 4, wherein R and R are independently selected from hydrogen, methyl, and cyclopropyl. 2’ 2a
9. The compound of claim 1 to 4, wherein R and R are independently selected from hydrogen and methyl.
10. The compound of claim 1 to 4, wherein R is selected from hydrogen, -F, and methyl. 5
11. The compound of claim 1, wherein ring A is selected from- L1 is selected from –CH2-, –CH(CH3)-, -NH-, -N(CH3)-, S, and O; R is selected from F, Cl, Br, CN, -NH , -NH(CH ), -NHCH(CH ) , -CH , cyclopropyl, - 2 3 3 2 3 CH(CH ) , -CF CH , -OCH , CF , 3 2 2 3 3 3 10 , , , , and ; R is selected from hydrogen, –NH , Cl, -CH(CH ) methyl, ethyl, 2 3 2, cyclopropyl and ; R and R are independently selected from hydrogen, 2’ 2a methyl, and cyclopropyl; R and R are independently selected from hydrogen and methyl; R is selected from hydrogen, -F, and methyl. 15
12. The compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, as claimed in any one of preceding claims, wherein the compound is selected from: (1S,2R,5R)(2-(2-Aminobromoquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; 20 (1S,2R,5R)(((2-aminochloroquinolinyl)thio)methyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(1-(2-Aminobromoquinolinyl)propanyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(((2-aminochlorofluoroquinolinyl)oxy)methyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)methylcyclopentene-1,2-diol (Compound-9); (1S,2R,5R)(1-(2-Aminochlorofluoroquinolinyl)propanyl)(4- 5 methyl-7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-methyl-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(1-((2-aminochlorofluoroquinolinyl)oxy)ethyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; 10 (1S,2R,5R)(2-(2-aminochloroquinolinyl)ethyl)(4-methyl-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (2-(2-Aminofluoroquinolinyl)ethyl)(4-amino-7H-pyrrolo[2,3- d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-amino-7H- 15 pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; 20 (1S,2R,5R)(2-(2-amino-3,5-dichloroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(((2-aminochlorofluoroquinolinyl)oxy)methyl)(4-amino- 7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-isopropyl- 25 7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-(1-methyl- 1H-pyrazolyl)-7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(1-(2-aminochlorofluoroquinolinyl)propanyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(1-(2-aminochloroquinolinyl)propanyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)methylcyclopentene-1,2-diol; 5 (1S,2R,5R)(1-(2-aminochlorofluoroquinolinyl)propanyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)methylcyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)ethylcyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-ethyl-7H- 10 pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4- cyclopropyl-7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-Aminobromofluoroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; 15 (1S,2R,5R)(2-(2-Aminobromofluoroquinolinyl)ethyl)(4-methyl- 7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(1-(2-Aminobromofluoro quinolinyl)propanyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-Aminochlorofluoro quinolinyl)ethyl)(4-methyl- 20 1H-pyrrolo[3,2-c]pyridinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-Aminofluoroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminofluoroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; 25 (1R,2R,3S,4R,5S)(2-(2-Aminomethylquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl) bicyclo[3.1.0]hexane-2,3-diol; (1R,2R,3S,4R,5S)(2-(2-Aminochloroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)bicyclo[3.1.0]hexane-2,3-diol; (1R,2R,3S,4R,5S)(2-(2-Aminochlorofluoroquinolinyl)ethyl)(4- 30 amino-7H-pyrrolo[2,3-d]pyrimidinyl) bicyclo[3.1.0]hexane-2,3-diol; (1R,2R,3S,4R,5S)(2-(2-Aminochlorofluoroquinolinyl)ethyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl) bicyclo[3.1.0]hexane-2,3-diol; (1R,2R,3S,4R,5S)(2-(2-aminobromofluoroquinolinyl)ethyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)bicyclo[3.1.0]hexane-2,3-diol; 5 (1R,2R,3S,4R,5S)(2-(2-Aminobromofluoroquinolinyl)ethyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)bicyclo[3.1.0]hexane-2,3-diol; and (1R,2R,3S,4R,5S)(2-(2-Aminobromoquinolinyl)ethyl)(4-amino-7H- pyrrolo [2,3-d]pyrimidinyl)bicyclo [3.1.0]hexane-2,3-diol.
13. The compound of formula (I), a stereoisomer thereof, or a pharmaceutically 10 acceptable salt thereof, as claimed in any one of preceding claims, wherein the compound is selected from: (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-methyl-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-amino-7H- 15 pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(1-(2-aminochlorofluoroquinolinyl)propanyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)methylcyclopentene-1,2-diol; 20 (1R,2R,3S,4R,5S)(2-(2-Aminochlorofluoroquinolinyl)ethyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl) bicyclo[3.1.0]hexane-2,3-diol; (1R,2R,3S,4R,5S)(2-(2-Aminochlorofluoroquinolinyl)ethyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl) bicyclo[3.1.0]hexane-2,3-diol; (1R,2R,3S,4R,5S)(2-(2-Aminobromoquinolinyl)ethyl)(4-amino-7H- 25 pyrrolo [2,3-d]pyrimidinyl)bicyclo [3.1.0]hexane-2,3-diol; (1S,2R,5R)(2-(2-Aminobromoquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(2-(2-aminochlorofluoroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(((2-aminochlorofluoroquinolinyl)oxy)methyl)(4-amino- 7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(1-(2-aminochloroquinolinyl)propanyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; 5 (1S,2R,5R)(1-(2-aminochlorofluoroquinolinyl)propanyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(1-(2-aminochlorofluoroquinolinyl)propanyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)methylcyclopentene-1,2-diol; (1R,2R,3S,4R,5S)(2-(2-Aminochloroquinolinyl)ethyl)(4-amino-7H- 10 pyrrolo[2,3-d]pyrimidinyl)bicyclo[3.1.0]hexane-2,3-diol; (1S,2R,5R)(2-(2-Aminobromofluoroquinolinyl)ethyl)(4-amino-7H- pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1S,2R,5R)(1-(2-Aminobromofluoro quinolinyl)propanyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; 15 (1S,2R,5R)(2-(2-Aminobromofluoroquinolinyl)ethyl)(4-methyl- 7H-pyrrolo[2,3-d]pyrimidinyl)cyclopentene-1,2-diol; (1R,2R,3S,4R,5S)(2-(2-Aminobromofluoroquinolinyl)ethyl)(4- amino-7H-pyrrolo[2,3-d]pyrimidinyl)bicyclo[3.1.0]hexane-2,3-diol; and (1R,2R,3S,4R,5S)(2-(2-aminobromofluoroquinolinyl)ethyl)(4- 20 amino-7H-pyrrolo[2,3-d]pyrimidinyl)bicyclo[3.1.0]hexane-2,3-diol.
14. A pharmaceutical composition comprising at least one compound of any one of the claims 1 to 13, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
15. Use of a compound, of any one of claim 1 to 13, in the preparation of medicament 25 for treating the diseases, disorders, syndromes or conditions associated by inhibition of PRMT5 in a subject in need thereof.
16. The use as claimed in claim 15, wherein the diseases, disorders, syndromes or conditions associated by inhibition of PRMT5 are selected from the group consisting of glioblastoma multiforme, prostate cancer, pancreatic cancer, mantle 30 cell lymphoma, non-Hodgkin’s lymphomas and diffuse large B-cell lymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, non- small cell lung cancer, small cell lung cancer, breast cancer, triple negative breast cancer, gastric cancer, colorectal cancer, ovarian cancer, bladder cancer, hepatocellular cancer, melanoma, sarcoma, oropharyngeal squamous cell 5 carcinoma, chronic myelogenous leukemia, epidermal squamous cell carcinoma, nasopharyngeal carcinoma, neuroblastoma, endometrial carcinoma, and cervical cancer.
17. The use as claimed in claim 15, wherein the diseases, disorders, syndromes or conditions associated by inhibition of PRMT5 is cancer. 10
18. The compound as claimed in any one of claims 1 to 13, substantially as herein described with reference to any example thereof.
19. The pharmaceutical composition as claimed in claim 14, substantially as herein described with reference to any example thereof.
20. The use as claimed in any one of claims 15 to 17, substantially as herein described 15 with reference to any example thereof.
NZ765656A 2018-12-13 Substituted bicyclic heterocyclic compounds as prmt5 inhibitors NZ765656B2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN201721044886 2017-12-13
IN201821024634 2018-07-02
IN201821040029 2018-10-23
PCT/IB2018/060015 WO2019116302A1 (en) 2017-12-13 2018-12-13 Substituted bicyclic heterocyclic compounds as prmt5 inhibitors

Publications (2)

Publication Number Publication Date
NZ765656A NZ765656A (en) 2025-02-28
NZ765656B2 true NZ765656B2 (en) 2025-06-04

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