WO2018215801A1 - Benzimidazolone derived inhibitors of bcl6 - Google Patents

Benzimidazolone derived inhibitors of bcl6 Download PDF

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Publication number
WO2018215801A1
WO2018215801A1 PCT/GB2018/051447 GB2018051447W WO2018215801A1 WO 2018215801 A1 WO2018215801 A1 WO 2018215801A1 GB 2018051447 W GB2018051447 W GB 2018051447W WO 2018215801 A1 WO2018215801 A1 WO 2018215801A1
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Prior art keywords
methyl
chloro
amino
hydroxy
alkyl
Prior art date
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Ceased
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PCT/GB2018/051447
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English (en)
French (fr)
Inventor
Benjamin Richard BELLENIE
Michael Keith CARTER
Kwai Ming Jack CHEUNG
Owen Alexander DAVIS
Swen Hoelder
Matthew Garth LLOYD
Ana VARELA RODRÍGUEZ
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Cancer Research Technology Ltd
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Cancer Research Technology Ltd
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Priority claimed from GBGB1708502.8A external-priority patent/GB201708502D0/en
Priority claimed from GBGB1806130.9A external-priority patent/GB201806130D0/en
Priority to EA201992628A priority Critical patent/EA201992628A1/ru
Priority to EP24150697.1A priority patent/EP4374858A3/en
Priority to CN201880047061.XA priority patent/CN111163839B/zh
Priority to IL270869A priority patent/IL270869B2/en
Priority to IL302300A priority patent/IL302300A/en
Priority to BR112019024830-7A priority patent/BR112019024830B1/pt
Priority to ES18730042T priority patent/ES2975690T3/es
Priority to CA3065005A priority patent/CA3065005A1/en
Priority to AU2018274723A priority patent/AU2018274723B2/en
Priority to EP18730042.1A priority patent/EP3630291B9/en
Priority to KR1020247002176A priority patent/KR102828518B1/ko
Application filed by Cancer Research Technology Ltd filed Critical Cancer Research Technology Ltd
Priority to US16/616,901 priority patent/US12110286B2/en
Priority to JP2019565443A priority patent/JP7202315B2/ja
Priority to CN202410618580.4A priority patent/CN118561812A/zh
Priority to KR1020197038091A priority patent/KR102628675B1/ko
Publication of WO2018215801A1 publication Critical patent/WO2018215801A1/en
Anticipated expiration legal-status Critical
Priority to JP2022207230A priority patent/JP7534379B2/ja
Priority to AU2024202525A priority patent/AU2024202525B2/en
Priority to US18/798,355 priority patent/US20240417388A1/en
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed 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
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    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
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    • 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
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    • 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
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    • C07D487/04—Ortho-condensed systems

Definitions

  • the present invention relates to certain compounds that function as inhibitors of BCL6 (B-cell lymphoma 6) activity.
  • the present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.
  • BCL6 is a zinc finger transcription repressor that plays a key role in the formation and development of germinal centres, in which B cells undergo somatic hypermutation and recombination of the immunoglobulin genes, in order to generate diversity in antibodies against a variety of foreign antigens (Dent et al., Science, 1997, 276, 589-592). BCL6 allows the proliferation of antibody producing B cells by repressing genes involved in DNA damage response, cell cycle arrest and apoptosis.
  • BCL6 mediates this repression by recruiting the corepressor proteins SMRT, NCoR and BCoR to an extended groove motif that forms along the dimer interface of the BCL6 BTB (BR-C, Ttk and Bab) domain (Ahmad et al., Mol Cell, 2003, 12, 1551-1564; Ghetu et al., Mol Cell, 2008, 29, 384-391).
  • BR-C, Ttk and Bab BCL6 BTB domain
  • a pharmaceutical composition comprising a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in admixture with a pharmaceutically acceptable diluent or carrier.
  • a method of inhibiting BCL6 activity comprising contacting a cell with an effective amount of a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein.
  • a method of inhibiting cell proliferation comprising contacting a cell with an effective amount of a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein.
  • a method of treating a disease or disorder in which BCL6 activity is implicated in a patient in need of such treatment comprising administering to said patient a therapeutically effective amount of a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein.
  • a method of treating a proliferative disorder in a patient in need of such treatment comprising administering to said patient a therapeutically effective amount of a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein.
  • a method of treating cancer in a patient in need of such treatment comprising administering to said patient a therapeutically effective amount of a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein.
  • a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in therapy is provided.
  • a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in the treatment of cancer is human cancer.
  • a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein for use in the inhibition of BCL6 activity is provided.
  • a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein for use in the treatment of a disease or disorder in which BCL6 activity is implicated is provided.
  • the proliferative disorder is cancer, suitably a human cancer (for example haematological cancers such as lymphomas (including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt lymphoma (BL) and angioimmunoblastic T-cell lymphoma (AITL)), leukaemias (including acute lymphoblastic leukaemia (ALL) and chronic myeloid leukaemia (CML)) and multiple myeloma, and solid tumours (including glioma, breast cancer, non-small cell lung cancer (NSCLC) and squamous cell carcinomas (SCC) (including SCC of the head and neck, oesophagus, lung and ovary))).
  • haematological cancers such as lymphomas (including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt lymphoma (BL) and angioimmunoblastic T
  • a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof obtainable by, or obtained by, or directly obtained by a process of preparing a compound as defined herein.
  • references to "treating” or “treatment” include prophylaxis as well as the alleviation of established symptoms of a condition.
  • Treating” or “treatment” of a state, disorder or condition therefore includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a human that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition, (2) inhibiting the state, disorder or condition, i.e., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or subclinical symptom thereof, or (3) relieving or attenuating the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms.
  • a “therapeutically effective amount” means the amount of a compound that, when administered to a mammal for treating a disease, is sufficient to effect such treatment for the disease.
  • the “therapeutically effective amount” will vary depending on the compound, the disease and its severity and the age, weight, etc., of the mammal to be treated.
  • alkyl includes both straight and branched chain alkyl groups. References to individual alkyl groups such as “propyl” are specific for the straight chain version only and references to individual branched chain alkyl groups such as “isopropyl” are specific for the branched chain version only.
  • (1-6C)alkyl includes (1- 4C)alkyl, (1-3C)alkyl, propyl, isopropyl and f-butyl.
  • (m-nC) or "(m-nC) group” used alone or as a prefix, refers to any group having m to n carbon atoms.
  • alkylene is an alkyl group that is positioned between and serves to connect two other chemical groups.
  • (1-6C)alkylene means a linear saturated divalent hydrocarbon radical of one to six carbon atoms or a branched saturated divalent hydrocarbon radical of three to six carbon atoms, for example, methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), 2-methylpropylene (-CH 2 CH(CH3)CH2-), pentylene (- CH2CH2CH2CH2CH2-), and the like.
  • (3-10C)cycloalkyl means a hydrocarbon ring containing from 3 to 10 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and bicyclo[2.2.1]heptyl.
  • (3-10C)cycloalkenyl means a hydrocarbon ring containing from 3 to 10 carbon atoms and at least one double bond, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl or cycloheptenyl, such as 3-cyclohexen-1-yl, or cyclooctenyl.
  • halo or halogeno refers to fluoro, chloro, bromo and iodo, suitably fluoro, chloro and bromo, more suitably, fluoro and chloro.
  • heterocyclyl means a non-aromatic saturated or partially saturated monocyclic, fused, bridged, or spiro bicyclic heterocyclic ring system(s).
  • Monocyclic heterocyclic rings contain from about 3 to 12 (suitably from 3 to 7) ring atoms, with from 1 to 5 (suitably 1 , 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur in the ring.
  • Bicyclic heterocycles contain from 7 to 17 member atoms, suitably 7 to 12 member atoms, in the ring.
  • Bicyclic heterocyclic(s) rings may be fused, spiro, or bridged ring systems.
  • heterocyclic groups include cyclic ethers such as oxiranyl, oxetanyl, tetrahydrofuranyl, dioxanyl, and substituted cyclic ethers.
  • Heterocycles containing nitrogen include, for example, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrotriazinyl, tetrahydropyrazolyl, and the like.
  • Typical sulfur containing heterocycles include tetrahydrothienyl, dihydro-1 ,3-dithiol, tetrahydro-2/-/-thiopyran, and hexahydrothiepine.
  • heterocycles include dihydro-oxathiolyl, tetrahydro-oxazolyl, tetrahydro-oxadiazolyl, tetrahydrodioxazolyl, tetrahydro-oxathiazolyl, hexahydrotriazinyl, tetrahydro-oxazinyl, morpholinyl, thiomorpholinyl, tetrahydropyrimidinyl, dioxolinyl, octahydrobenzofuranyl, octahydrobenzimidazolyl, and octahydrobenzothiazolyl.
  • the oxidized sulfur heterocycles containing SO or SO2 groups are also included.
  • examples include the sulfoxide and sulfone forms of tetrahydrothienyl and thiomorpholinyl such as tetrahydrothiene 1 , 1 -dioxide and thiomorpholinyl 1 , 1 -dioxide.
  • heterocyclyl groups are saturated monocyclic 3 to 7 membered heterocyclyls containing 1 , 2 or 3 heteroatoms selected from nitrogen, oxygen or sulfur, for example azetidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, tetrahydrothienyl, tetrahydrothienyl 1 , 1 -dioxide, thiomorpholinyl, thiomorpholinyl 1 , 1 -dioxide, piperidinyl, homopiperidinyl, piperazinyl or homopiperazinyl.
  • any heterocycle may be linked to another group via any suitable atom, such as via a carbon or nitrogen atom.
  • reference herein to piperidino or morpholino refers to a piperidin-1- yl or morpholin-4-yl ring that is linked via the ring nitrogen.
  • bridged ring systems is meant ring systems in which two rings share more than two atoms, see for example Advanced Organic Chemistry, by Jerry March, 4 th Edition, Wiley Interscience, pages 131-133, 1992.
  • bridged heterocyclyl ring systems include, aza-bicyclo[2.2.1]heptane, 2-oxa-5-azabicyclo[2.2.1]heptane, aza-bicyclo[2.2.2]octane, aza- bicyclo[3.2.1]octane and quinuclidine.
  • spiro bi-cyclic ring systems we mean that the two ring systems share one common spiro carbon atom, i.e. the heterocyclic ring is linked to a further carbocyclic or heterocyclic ring through a single common spiro carbon atom.
  • spiro ring systems examples include 6- azaspiro[3.4]octane, 2-oxa-6-azaspiro[3.4]octane, 2-azaspiro[3.3]heptanes, 2-oxa-6- azaspiro[3.3]heptanes, 7-oxa-2-azaspiro[3.5]nonane, 6-oxa-2-azaspiro[3.4]octane, 2-oxa-7- azaspiro[3.5]nonane and 2-oxa-6-azaspiro[3.5]nonane.
  • heteroaryl or “heteroaromatic” means an aromatic mono-, bi-, or polycyclic ring incorporating one or more (for example 1-4, particularly 1 , 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur.
  • heteroaryl includes both monovalent species and divalent species. Examples of heteroaryl groups are monocyclic and bicyclic groups containing from five to twelve ring members, and more usually from five to ten ring members.
  • the heteroaryl group can be, for example, a 5- or 6-membered monocyclic ring or a 9- or 10- membered bicyclic ring, for example a bicyclic structure formed from fused five and six membered rings or two fused six membered rings.
  • Each ring may contain up to about four heteroatoms typically selected from nitrogen, sulfur and oxygen.
  • the heteroaryl ring will contain up to 3 heteroatoms, more usually up to 2, for example a single heteroatom.
  • the heteroaryl ring contains at least one ring nitrogen atom.
  • the nitrogen atoms in the heteroaryl rings can be basic, as in the case of an imidazole or pyridine, or essentially non-basic as in the case of an indole or pyrrole nitrogen. In general the number of basic nitrogen atoms present in the heteroaryl group, including any amino group substituents of the ring, will be less than five.
  • heteroaryl examples include furyl, pyrrolyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1 ,3,5-triazenyl, benzofuranyl, indolyl, isoindolyl, benzothienyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzothiazolyl, indazolyl, purinyl, benzofurazanyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, cinnolinyl, pteridinyl, naphthy
  • Heteroaryl also covers partially aromatic bi- or polycyclic ring systems wherein at least one ring is an aromatic ring and one or more of the other ring(s) is a non-aromatic, saturated or partially saturated ring, provided at least one ring contains one or more heteroatoms selected from nitrogen, oxygen or sulfur.
  • partially aromatic heteroaryl groups include for example, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 2-oxo- 1 ,2,3,4-tetrahydroquinolinyl, dihydrobenzthienyl, dihydrobenzfuranyl, 2,3-dihydro- benzo[1 ,4]dioxinyl, benzo[1 ,3]dioxolyl, 2,2-dioxo-1 ,3-dihydro-2-benzothienyl, 4,5,6,7- tetrahydrobenzofuranyl, indolinyl, 1 ,2,3,4-tetrahydro-1 ,8-naphthyridinyl,
  • heteroaryl groups examples include but are not limited to pyrrolyl, furanyl, thienyl, imidazolyl, furazanyl, oxazolyl, oxadiazolyl, oxatriazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl and tetrazolyl groups.
  • heteroaryl groups include but are not limited to pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl and triazinyl.
  • a bicyclic heteroaryl group may be, for example, a group selected from:
  • thiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms
  • bicyclic heteroaryl groups containing a six membered ring fused to a five membered ring include but are not limited to benzfuranyl, benzthiophenyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, benzisothiazolyl, isobenzofuranyl, indolyl, isoindolyl, indolizinyl, indolinyl, isoindolinyl, purinyl (e.g., adeninyl, guaninyl), indazolyl, benzodioxolyl and pyrazolopyridinyl groups.
  • bicyclic heteroaryl groups containing two fused six membered rings include but are not limited to quinolinyl, isoquinolinyl, chromanyl, thiochromanyl, chromenyl, isochromenyl, chromanyl, isochromanyl, benzodioxanyl, quinolizinyl, benzoxazinyl, benzodiazinyl, pyridopyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, naphthyridinyl and pteridinyl groups.
  • aryl means a cyclic or polycyclic aromatic ring having from 5 to 12 carbon atoms.
  • aryl includes both monovalent species and divalent species. Examples of aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl and the like. In a particular embodiment, an aryl is phenyl.
  • optionally substituted refers to either groups, structures, or molecules that are substituted and those that are not substituted.
  • the term "wherein a/any CH, CH2, CH3 group or heteroatom (i.e. NH) within a R 1 group is optionally substituted” suitably means that (any) one of the hydrogen radicals of the R 1 group is substituted by a relevant stipulated group.
  • the present invention relates to compounds, or pharmaceutically acceptable salts, hydrates or ral formula (I), shown below:
  • Xi is selected from N or CR a wherein R a is selected from hydrogen, (1-2C)alkyl, halogen, hydroxy, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy, (2- 4C)alkenyl, (2-4C)alkynyl, nitro, cyano or NR b R c , wherein R b and R c are independently selected from hydrogen or (1-2C)alkyl;
  • X2 is selected from N or CR d , wherein R d is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, (1-2C)alkoxy, (1-2C)haloalkyl or (1- 2C)haloalkoxy;
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-5C)alkylene optionally substituted by one or more substituents selected from (1-2C)alkyl or oxo;
  • Y is absent or O, S, SO, S0 2 , N(R e ), C(O), C(0)0, OC(O), C(0)N(R e ), N(R e )C(0), N(R e )C(0)N(R f ), N(R e )C(0)0, OC(0)N(R e ), S(0) 2 N(R e ), or N(R e )SC>2, wherein R e and R f are each independently selected from hydrogen or (1-4C)alkyl; and
  • Z is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3- 10C)cycloalkyl, (3-10C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, (1-4C)aminoalkyl, cyano, hydroxy, carboxy, carbamoyl, sulphamoyl, mercapto, ureido, NR 9 R h , OR 9 , C(0)R 9 , C(0)OR 9 , OC(0)R 9 , C(0)N(R 9 )R h , N(R 9 )C(0)R h , S(0) y R 9 (where y is 0, 1 or 2), S0 2 N(R 9 )R h , N(
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, (1- 2C)alkoxy, (1-2C)alkylamino, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)R', SO2R 1 , C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R 1 and R m are independently selected from hydrogen or (1-4C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1- 2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R n ), N(R n )C(0), S(0) 2 N(R n ), or N(R n )S02, wherein R n is selected from hydrogen or (1- 2C)alkyl; l_2 is absent or (1 -2C)alkylene; and
  • Z 2 is hydrogen, (1 -6C)alkyl, (2-4C)alkenyl, (2- 4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6-membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1 -4C)alkyl, halo, (1 -4C)haloalkyl, (1 - 4C)haloalkoxy, (1 -4C)alkoxy, (1 -4C)alkylamino, amino, cyano, nitro, hydroxy, C(0)R°, C(0)OR°, OC(0)R°, C(0)N(R°)RP, N R°C(0)R P , wherein R° and RP are independently selected from hydrogen or (1 -4C)alkyl; and
  • R 8 is selected from (1 -2C)alkyl, -C(0)OR Q , OR Q , -C(0)N R Q , N R Q R R , phenyl or a 5-membered heteroaryl, wherein R Q and R R are independently selected from hydrogen or (1 -2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1 -2C)alkyl, halo, (1 -2C)haloalkyl, (1 -2C)haloalkoxy, (1 - 2C)alkoxy, (1 -2C)alkylamino, amino, cyano or hydroxyl; or
  • ring A is a 4 to 6 membered cydoalkyi or heterocyclyl ring, optionally substituted with one or more substituent groups selected from (1- 2C)alkyl, halo, hydroxy, cyano or (1-2C)alkoxy;
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl, (1-4C)haloalkyl, (1-4C)hydroxyalkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1-4C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, cyclopropyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5- membered heteroaryl, wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl; and
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, (1- 2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF2H or
  • R 9 is selected from hydrogen, fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF2H or CFs;
  • R 10 is selected from hydrogen, halo, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 3 is absent or O, N(R S )(CR S R 1 (where qi is 0, 1 or 2), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R s ), N(R s )C(0), N(R s )C(0)N(R l ), N(R s )C(0)0, OC(0)N(R s ), S(0) 2 N(R s ), N(R s )S0 2 , wherein R s and R ⁇ are each independently selected from hydrogen or (1-4C)alkyl; and Z 3 is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (2- 4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkenyl, heteroaryl or 4 to 11-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from oxo, (1
  • l_z is absent or a (1-5C)alkylene optionally substituted by one or more substituents selected from (1-2C)alkyl or oxo;
  • Wz is aryl, heteroaryl, 4- to 7-membered heterocyclyl, 3- to 6-membered carbocycyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, hydroxy, (1-4C)alkoxy, C ⁇ R" 3 , COOR xa , C(0)NR xa R xb or NR ⁇ R ⁇ , wherein R* 3 and R* are each independently selected from hydrogen or (1-4C)alkyl; and wherein each aryl, heteroaryl, 4- to 7-membered heterocyclyl or 3- to 6-membered carbocycyl is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, amino, cyano or hydroxy;
  • Xc. Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCH 3 ;
  • R 11 is selected from hydrogen, halo, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, OC(O), C(0)N(R w ), N(R w )C(0), NiR ⁇ CiOJNiR 3 "), N(R w )C(0)0, OC(0)N(R w ), S(0) 2 N(R w ), N(R w )S0 2 , wherein R w and R x are each independently selected from hydrogen or (1- 4C)alkyl; and
  • Z 5 is hydrogen, (1-6C)alkyl, aryl, (3-8C)cycloalkyl, (3- 8C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1- 4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, (1- 4C)hydroxyalkyl, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl;
  • R 12 is selected from fluoro, chloro, bromo, (1-2C)alkyl, (1- 2C)alkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl, CH 2 F, CF 2 H or CF 3 ;
  • Xf and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, (1-2C)alkyl, (1- 2C)haloalkyl or (1-2C)haloalkoxy;
  • Xh, X and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • the present invention relates to compounds, or pharmaceutically acceptable salts, hydrates or ral formula (I), shown below:
  • Xi is selected from N or CR a wherein R a is selected from hydrogen, (1-2C)alkyl, halogen, hydroxy, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy, (2- 4C)alkenyl, (2-4C)alkynyl, nitro, cyano or NR b R c , wherein R b and R c are independently selected from hydrogen or (1-2C)alkyl;
  • X2 is selected from N or CR d , wherein R d is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, (1-2C)alkoxy, (1-2C)haloalkyl or (1- 2C)haloalkoxy;
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-5C)alkylene optionally substituted by one or more substituents selected from (1-2C)alkyl or oxo;
  • Y is absent or O, S, SO, S0 2 , N(R e ), C(O), C(0)0, OC(O), C(0)N(R e ), N(R e )C(0), N(R e )C(0)N(R f ), N(R e )C(0)0, OC(0)N(R e ), S(0) 2 N(R e ), or N(R e )S02, wherein R e and R f are each independently selected from hydrogen or (1-4C)alkyl; and
  • Z is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3- 10C)cycloalkyl, (3-10C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, (1-4C)aminoalkyl, cyano, hydroxy, carboxy, carbamoyl, sulphamoyl, mercapto, ureido, NR 9 R h , OR 9 , C(0)R 9 , C(0)OR 9 , OC(0)R 9 , C(0)N(R 9 )R h , N(R 9 )C(0)R h , S(0) y R 9 (where y is 0, 1 or 2), S0 2 N(R 9 )R h , N(
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, (1- 2C)alkoxy, (1-2C)alkylamino, amino, cyano or hydroxy;
  • W 2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)R', S0 2 R', C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-4C)alkyl, and wherein: R 6 is selected from hydrogen, (1 -2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1 -2C)alkoxy, (1 -2C)haloalkyl or (1 -2C)haloalkoxy;
  • R 7 is selected from hydrogen, (1 -2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1 -2C)alkoxy, (1 -2C)haloalkyl, (1 - 2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R N ), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R N ), N(R N )C(0), S(0) 2 N(R N ), or N(R N )SC>2, wherein R N is selected from hydrogen or (1 - 2C)alkyl;
  • L2 is absent or (1 -2C)alkylene
  • Z 2 is hydrogen, (1 -6C)alkyl, (2-4C)alkenyl, (2- 4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6-membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1 -4C)alkyl, halo, (1 -4C)haloalkyl, (1 - 4C)haloalkoxy, (1 -4C)alkoxy, (1 -4C)alkylamino, amino, cyano, nitro, hydroxy, C(0)R°, C(0)OR°, OC(0)R°, C(0)N(R°)R P , NR°C(0)R P , wherein R° and R P are independently selected from hydrogen or (1 -4C)alkyl; and
  • R 8 is selected from (1 -2C)alkyl, -C(0)OR Q , OR Q , -C(0)NR Q , NR Q R R , phenyl or a 5-membered heteroaryl, wherein R Q and R R are independently selected from hydrogen or (1 -2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1 -2C)alkyl, halo, (1 -2C)haloalkyl, (1 -2C)haloalkoxy, (1 - 2C)alkoxy, (1 -2C)alkylamino, amino, cyano or hydroxyl; or
  • ring A is a 4 to 6 membered cydoalkyi or heterocyclyl ring, optionally substituted with one or more substituent groups selected from (1- 2C)alkyl, halo, hydroxy, cyano or (1-2C)alkoxy;
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl, (1-4C)haloalkyl, (1-4C)hydroxyalkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, cyclopropyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5- membered heteroaryl, wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl; and
  • R 3 is selected from:
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, (1- 2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF2H or
  • R 9 is selected from hydrogen, fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF2H or CFs;
  • R 10 is selected from hydrogen, halo, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 3 is absent or O, N(R S )(CR S R 1 (where qi is 0, 1 or 2), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R s ), N(R s )C(0), N(R s )C(0)N(R l ), N(R s )C(0)0, OC(0)N(R s ), S(0) 2 N(R s ), N(R s )S0 2 , wherein R s and R ⁇ are each independently selected from hydrogen or (1-4C)alkyl; and
  • Z 3 is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (2- 4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkenyl, heteroaryl or 4 to 11-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from oxo, (1- 4C)alkyl, (3-6C)cycloalkyl, halo, (1-4C)haloalkyl, (1- 4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, C(0)NR u R v , NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl; or Z 3 is optionally further substituted by a group of the formula:
  • l_z is a (1-5C)alkylene optionally substituted by one or more substituents selected from (1- 2C)alkyl or oxo;
  • Wz is halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, hydroxy, (1-4C)alkoxy, C ⁇ R" 3 , COOR xa , C(0)NR xa R xb or NR ⁇ R ⁇ , wherein R* 3 and R* are each independently selected from hydrogen or (1-4C)alkyl;
  • Xc. Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCH 3 ;
  • R 11 is selected from hydrogen, halo, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, OC(O), C(0)N(R w ), N(R w )C(0), NCR ⁇ C ⁇ NCR ⁇ , N(R w )C(0)0, OC(0)N(R w ), S(0) 2 N(R w ), N(R w )S0 2 , wherein R w and R x are each independently selected from hydrogen or (1- 4C)alkyl; and
  • Z 5 is hydrogen, (1-6C)alkyl, aryl, (3-8C)cycloalkyl, (3- 8C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1- 4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen, (1- 4C)alkyl or (3-6C)cycloalkyl;
  • R 12 is selected from fluoro, chloro, bromo, (1 -2C)alkyl, (1 - 2C)alkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl, CH 2 F, CF 2 H or CF 3 ;
  • X f and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, (1-2C)alkyl, (1 - 2C)haloalkyl or (1 -2C)haloalkoxy;
  • X h , X and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1 -2C)alkyl, (1 -2C)alkoxy, (1 -2C)haloalkyl or (1 -2C)haloalkoxy;
  • the present invention relates to compounds, or pharmaceutically acceptable salts, hydrates or solvates thereof, having the structural formula (I), shown below:
  • Xi is selected from N or CR a wherein R a is selected from hydrogen, (1-2C)alkyl, halogen, hydroxy, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy, (2- 4C)alkenyl, (2-4C)alkynyl, nitro, cyano or NR b R c , wherein R b and R c are independently selected from hydrogen or (1-2C)alkyl;
  • X2 is selected from N or CR d , wherein R d is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, (1-2C)alkoxy, (1-2C)haloalkyl or (1- 2C)haloalkoxy;
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-5C)alkylene optionally substituted by one or more substituents selected from (1-2C)alkyl or oxo;
  • Y is absent or O, S, SO, S0 2 , N(R e ), C(O), C(0)0, OC(O), C(0)N(R e ), N(R e )C(0), N(R e )C(0)N(R f ), N(R e )C(0)0, OC(0)N(R e ), S(0) 2 N(R e ), or N(R e )S02, wherein R e and R f are each independently selected from hydrogen or (1-4C)alkyl; and
  • Z is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3- 10C)cycloalkyl, (3-10C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, (1-4C)aminoalkyl, cyano, hydroxy, carboxy, carbamoyl, sulphamoyl, mercapto, ureido, NR 9 R h , OR 9 , C(0)R 9 , C(0)OR 9 , OC(0)R 9 , C(0)N(R 9 )R h , N(R 9 )C(0)R h , S(0) y R 9 (where y is 0, 1 or 2), S0 2 N(R 9 )R h , N(
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, (1- 2C)alkoxy, (1-2C)alkylamino, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 7 is selected from hydrogen, (1 -2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1 -2C)alkoxy, (1 -2C)haloalkyl, (1 - 2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R N ), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R N ), N(R N )C(0), S(0) 2 N(R N ), or N(R N )SC>2, wherein R N is selected from hydrogen or (1 - 2C)alkyl;
  • l_2 is absent or (1 -2C)alkylene
  • Z 2 is hydrogen, (1 -6C)alkyl, (2-4C)alkenyl, (2- 4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6-membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1 -4C)alkyl, halo, (1 -4C)haloalkyl, (1 - 4C)haloalkoxy, (1 -4C)alkoxy, (1 -4C)alkylamino, amino, cyano, nitro, hydroxy, C(0)R°, C(0)OR°, OC(0)R°, C(0)N(R°)R P , NR°C(0)R P , wherein R° and R P are independently selected from hydrogen or (1 -4C)alkyl; and
  • R 8 is selected from (1 -2C)alkyl, -C(0)OR Q , OR Q , -C(0)NR Q , NR Q R R , phenyl or a 5-membered heteroaryl, wherein R Q and R R are independently selected from hydrogen or (1 -2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1 -2C)alkyl, halo, (1 -2C)haloalkyl, (1 -2C)haloalkoxy, (1 - 2C)alkoxy, (1 -2C)alkylamino, amino, cyano or hydroxyl; or
  • ring A is a 4 to 6 membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1- 2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1- 2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5-membered heteroaryl, wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl; and
  • R 3 is selected from:
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, (1- 2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF2H or CF 3 ;
  • R 9 is selected from hydrogen, fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF2H or CF 3 ;
  • R 10 is selected from hydrogen, halo, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 3 is absent or C(O), C(0)0, OC(O), C(0)N(R s ), N(R s )C(0), N(R s )C(0)N(R l ), N(R s )C(0)0, OC(0)N(R s ), S(0) 2 N(R s ), N(R s )S0 2 , wherein R s and R ⁇ are each independently selected from hydrogen or (1-4C)alkyl; and
  • Z 3 is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (2- 4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkenyl, 5- or 6- membered heteroaryl or 5- or 6-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from (1- 4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen, (1- 4C)alkyl or (3-6C)cycloalkyl;
  • Xc. Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCH 3 ;
  • R 11 is selected from hydrogen, halo, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, OC(O), C(0)N(R w ), N(R w )C(0), NKR ⁇ CCC NKR ⁇ , N(R w )C(0)0, OC(0)N(R w ), S(0) 2 N(R w ), N(R w )S0 2 , wherein R w and R x are each independently selected from hydrogen or (1- 4C)alkyl; and
  • Z 5 is hydrogen, (1-6C)alkyl, aryl, (3-8C)cycloalkyl, (3- 8C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1- 4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen, (1- 4C)alkyl or (3-6C)cycloalkyl;
  • R 12 is selected from fluoro, chloro, bromo, (1-2C)alkyl, (1- 2C)alkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl, CH 2 F, CF 2 H or CF 3 ;
  • Xf and X g are independently selected from N or CR 13 , wherein
  • R 13 is selected from hydrogen, fluoro, chloro, (1-2C)alkyl, (1- 2C)haloalkyl or (1-2C)haloalkoxy;
  • Xh, X and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 3 is a group of Formula C
  • no more than two of Xf, X g , Xh, X and Xj are nitrogen.
  • R 3 is a group of Formula C
  • no more than one of Xf, X g , Xh, X and Xj is nitrogen.
  • R 1 is hydrogen
  • R 2 is not hydrogen
  • Particular compounds of the invention include, for example, compounds of the Formula I, or pharmaceutically acceptable salts, hydrates and/or solvates thereof, wherein, unless otherwise stated, each of Xi , X2, R ⁇ R 2 , R 3 and any associated substituent groups has any of the meanings defined hereinbefore or in any of paragraphs (1) to (89) hereinafter: -
  • Xi is selected from N or CR a , wherein R a is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, (1-2C)alkoxy, CH2F, CHF2, CF3, OCF3, acetylenyl, nitro, cyano or NR b R c , wherein R b and R c are independently selected from hydrogen or (1- 2C)alkyl;
  • Xi is selected from N or CR a , wherein R a is selected from hydrogen, methyl, fluoro, chloro, hydroxy, OCH 3 , CH 2 F, CHF 2 , CF 3 , OCF 3 , acetylenyl, cyano or NH 2 ;
  • Xi is selected from N or CR a , wherein R a is selected from hydrogen, methyl, fluoro, chloro, hydroxy, OCH3, CH2F, CHF2, acetylenyl, cyano or NH2;
  • Xi is selected from N or CR a , wherein R a is selected from hydrogen, methyl, fluoro, chloro, hydroxy, OCH3, acetylenyl or cyano; (5) Xi is selected from N or CR a , wherein R a is selected from hydrogen, methyl, fluoro, chloro, hydroxy, OCH3 or cyano;
  • Xi is selected from N or CR a , wherein R a is selected from hydrogen, methyl, fluoro or chloro;
  • Xi is selected from N or CH;
  • X 2 is selected from N, CH, CF or C-CH 3 ;
  • X2 is selected from N or CH;
  • X 2 is selected from CH, CF or C-CH 3 ;
  • X 2 is CH
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-5C)alkylene optionally substituted by one or more substituents selected from (1-2C)alkyl or oxo;
  • Y is absent or O, S, SO, S0 2 , N(R e ), C(O), C(0)0, OC(O), C(0)N(R e ), N(R e )C(0), S(0) 2 N(R e ), or N(R e )S0 2 , wherein R e is selected from hydrogen or (1-4C)alkyl; and
  • Z is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3- 10C)cycloalkyl, (3-10C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, (1-4C)aminoalkyl, cyano, hydroxy, carboxy, carbamoyl, sulphamoyl, mercapto, ureido, NR 9 R h , OR 9 , C(0)R 9 , C(0)OR 9 , OC(0)R 9 , C(0)N(R 9 )R h , N(R 9 )C(0)R h , S(0) y R 9 (where y is 0, 1 or 2), S0 2 N(R 9 )R h , N(
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-5C)alkylene optionally substituted by one or more substituents selected from (1-2C)alkyl;
  • Y is absent or O, S, SO, S0 2 , N(R e ), C(O), C(0)0, OC(O), C(0)N(R e ), N(R e )C(0), S(0) 2 N(R e ), or N(R e )S0 2 , wherein R e is selected from hydrogen or (1-4C)alkyl; and
  • Z is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3- 10C)cycloalkyl, (3-10C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, (1-4C)aminoalkyl, cyano, hydroxy, carboxy, carbamoyl, sulphamoyl, mercapto, ureido, NR 9 R h , OR 9 , C(0)R 9 , C(0)OR 9 , OC(0)R 9 , C(0)N(R 9 )R h , N(R 9 )C(0)R h , S(0) y R 9 (where y is 0, 1 or 2), S0 2 N(R 9 )R h , N(
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-5C)alkylene
  • Y is absent or O, S0 2 , N(R e ), C(O), C(0)0, OC(O), C(0)N(R e ), N(R e )C(0), S(0) 2 N(R e ), or N(R e )S0 2 , wherein R e is selected from hydrogen or (1-4C)alkyl; and
  • Z is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3- 10C)cycloalkyl, (3-10C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, (1-4C)aminoalkyl, cyano, hydroxy, carboxy, carbamoyl, sulphamoyl, mercapto, ureido, NR 9 R h , OR 9 , C(0)R 9 , C(0)OR 9 , OC(0)R 9 , C(0)N(R 9 )R h , N(R 9 )C(0)R h , S(0) y R 9 (where y is 0, 1 or 2), S0 2 N(R 9 )R h , N(
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-5C)alkylene
  • Y is absent or O, S0 2 , C(O), C(0)0, C(0)N(R e ) or S(0) 2 N(R e ), wherein R e is selected from hydrogen or (1-4C)alkyl;
  • Z is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3- 10C)cycloalkyl, (3-10C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, amino, (1-2C)aminoalkyl, cyano, hydroxy, carboxy, carbamoyl, sulphamoyl, mercapto, ureido, NR 9 R h , OR 9 , C(0)R 9 , C(0)OR 9 , OC(0)R 9 , C(0)N(R 9 )R h , N(R 9 )C(0)R h , S(0) y R 9 (where y is 0, 1 or 2), S0 2 N(R 9 )R h , N(
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-5C)alkylene
  • Y is absent or O, S0 2 , C(O), C(0)0, C(0)N(R e ) or S(0) 2 N(R e ), wherein R e is selected from hydrogen or (1-4C)alkyl;
  • Z is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3- 10C)cycloalkyl, (3-10C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, amino, (1-2C)aminoalkyl, cyano, hydroxy, carboxy, carbamoyl, sulphamoyl, mercapto, ureido, NR 9 R h or OR 9 ; wherein R 9, R h and R' are each independently selected from hydrogen or (1- 4C)alkyl;
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-5C)alkylene
  • Y is absent or O, S0 2 , C(O), C(0)0, C(0)N(R e ) or S(0) 2 N(R e ), wherein R e is selected from hydrogen or (1-4C)alkyl;
  • Z is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3- 10C)cycloalkyl, (3-10C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, amino, (1-2C)aminoalkyl, cyano, hydroxy, NR 9 R h or OR 9 ; wherein R 9, R h and R' are each independently selected from hydrogen or (1-4C)alkyl;
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-3C)alkylene
  • Y is absent or O, C(O), C(0)0 or C(0)N(R e ), wherein R e is selected from hydrogen or (1-4C)alkyl;
  • Z is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, aryl, (3- 6C)cycloalkyl, (3-6C)cycloalkenyl, a 5 or 6 membered heteroaryl or a 4- to 7-membered heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1- 2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, amino, (1- 2C)aminoalkyl, cyano, hydroxy, NR 9 R h or OR 9 ; wherein R 9 ' R h and R' are each independently selected from hydrogen or (1-4C)alkyl;
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-3C)alkylene
  • Y is absent or O, C(O), C(0)0 or C(0)N(R e ), wherein R e is selected from hydrogen or (1-4C)alkyl;
  • Z is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, aryl, (3- 6C)cycloalkyl, (3-6C)cycloalkenyl, 5 or 6 membered heteroaryl or 5 or 6 membered heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1- 2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, amino, (1- 2C)aminoalkyl, cyano, hydroxy, NR 9 R h or OR 9 ; wherein R 9, R h and R' are each independently selected from hydrogen or (1-4C)alkyl;
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-3C)alkylene
  • Y is absent or O, C(O), 0(0)0 or C(0)N(R e ), wherein R e is selected from hydrogen or (1-4C)alkyl;
  • Z is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (3-6C)cycloalkenyl, 5 or 6 membered heteroaryl or 4- to 7-membered heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1- 2C)haloalkoxy, amino, (1-2C)aminoalkyl, cyano, hydroxy or Nhb;
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-3C)alkylene
  • Y is absent or O, 0(0), 0(0)0 or C(0)N(R e ), wherein R e is selected from hydrogen or (1-4C)alkyl;
  • Z is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (3-6C)cycloalkenyl, 5 or 6 membered heteroaryl or 5 or 6 membered heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1- 2C)haloalkoxy, amino, (1-2C)aminoalkyl, cyano, hydroxy or Nhb;
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-3C)alkylene
  • Z is (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (3-6C)cycloalkenyl, 5 or 6 membered heteroaryl or 4 to 7 membered heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from oxo, (1-2C)alkyl, halo, (1-2C)haloalkyl, (1- 2C)haloalkoxy, amino, (1-2C)aminoalkyl, cyano, hydroxy, NR 9 R h or OR 9 ; wherein R 9 and R h are each independently selected from hydrogen or (1-2C)alkyl;
  • R 1 is selected from hydrogen or a group of the formula:
  • L is absent or (1-2C)alkylene
  • Z is (1-6C)alkyl, (3-6C)cycloalkyl or 4 to 7 membered heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from oxo, (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, amino, (1-2C)aminoalkyl, cyano, hydroxy, NR 9 R h or OR 9 ; wherein R 9 and R h are each independently selected from hydrogen or (1-2C)alkyl;
  • R 1 is selected from hydrogen, (1-6C)alkyl or a group of the formula:
  • L is (1-2C)alkylene
  • Z is (3-6C)cycloalkyl or 4 to 7 membered heterocyclyl; wherein Z is optionally further substituted by one or more substituent groups independently selected from oxo, (1-2C)alkyl, halo, (1-2C)haloalkyl, (1- 2C)haloalkoxy, amino, (1-2C)aminoalkyl, cyano, hydroxy, NR 9 R h or OR 9 ; wherein R 9 and R h are each independently selected from hydrogen or methyl;
  • R 1 is selected from hydrogen, (1-6C)alkyl or (3-6C)cycloalkyl; wherein each (1- 6C)alkyl or (3-6C)cycloalkyl is optionally further substituted by one or more substituent groups independently selected from oxo, (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, amino, (1-2C)aminoalkyl, cyano, hydroxy or NH2;
  • R 1 is selected from hydrogen, (1-6C)alkyl or (3-6C)cycloalkyl;
  • R 1 is selected from hydrogen or (1-4C)alkyl (e.g. methyl);
  • R 1 is (1-4C)alkyl (e.g. methyl);
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, (1- 2C)alkoxy, (1-2C)alkylamino, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)R', SO2R 1 , C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R 1 and R m are independently selected from hydrogen or (1-4C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1- 2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R n ) or N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • l_2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2- 4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6-membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1- 4C)haloalkoxy, (1-4C)alkoxy, (1-4C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , -C(0)NR q , NR q R r , phenyl or a 5-membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH 2 F, CF 2 H or CF 3 , (1-2C)alkoxy, amino, cyano or hydroxy; or
  • ring A is a 4 to 6 membered cydoalkyi or heterocyclyl ring, optionally substituted with one or more substituent groups selected from (1- 2C)alkyl, halo, hydroxy, cyano or (1-2C)alkoxy;
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl, (1-2C)haloalkyl, (1-2C)hydroxyalkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1-4C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, cyclopropyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5- membered heteroaryl, wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, (1- 2C)alkoxy, (1-2C)alkylamino, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)R', SO2R 1 , C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R 1 and R m are independently selected from hydrogen or (1-4C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1- 2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R n ) or N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2- 4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6-membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1- 4C)haloalkoxy, (1-4C)alkoxy, (1-4C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , -C(0)NR q , NR q R r , phenyl or a 5-membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl; or R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH 2 F, CF 2 H or CF 3 , (1-2C)alkoxy, amino, cyano or hydroxy; or
  • ring A is a 4 to 6 membered cydoalkyi or heterocyclyl ring, optionally substituted with one or more substituent groups selected from (1- 2C)alkyl, halo, hydroxy, cyano or (1-2C)alkoxy;
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl, (1-2C)haloalkyl, (1-2C)hydroxyalkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, cyclopropyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5- membered heteroaryl, wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, (1- 2C)alkoxy, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)R', SO2R 1 , C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R 1 and R m are independently selected from hydrogen or (1-4C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1- 2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), C(O), C(0)0, OC(O), C(0)N(R n ) or N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2- 4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6-membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1- 4C)haloalkoxy, (1-4C)alkoxy, (1-4C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , -C(0)NR q , NR q R r , phenyl or a 5-membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH 2 F, CF 2 H or CF 3 , (1-2C)alkoxy, amino, cyano or hydroxy; or
  • ring A is a 4 to 6 membered cydoalkyi or heterocyclyl ring, optionally substituted with one or more substituent groups selected from (1- 2C)alkyl, halo, hydroxy, cyano or (1-2C)alkoxy;
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl, (1-2C)haloalkyl, (1-2C)hydroxyalkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, cyclopropyl, fluoro, chloro, bromo, hydroxy, amino, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5-membered heteroaryl, wherein R ac and R ad are independently selected from hydrogen or methyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)alkoxy, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)R', SO2R 1 , C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R 1 and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, CH2F, CF2H or CFs;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1- 2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), C(O), C(0)0, OC(O), C(0)N(R n ) or N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl; l_2 is absent or (1-2C)alkylene; and
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2- 4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6-membered heterocyclyl; wherein Z 2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1- 2C)haloalkoxy, (1-2C)alkoxy, (1-2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , -C(0)NR q , NR q R r , phenyl or a 5-membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring; or
  • ring A is a 4 to 6 membered cydoalkyi or heterocyclyl ring, optionally substituted with one or more substituent groups selected from (1- 2C)alkyl or halo;
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl, (1-2C)haloalkyl, (1-2C)hydroxyalkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 and R 102 are each independently selected from (1-2C)alkyl, fluoro, chloro, hydroxy, (1- 2C)alkoxy, CH 2 F, CF 2 H, CF 3 , -C(0)OR ac or-NR ac R ad , wherein R ac and R ad are independently selected from hydrogen or methyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, SO2R 1 , C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R 1 and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, (1-2C)alkoxy, CH2F, CF2H or CFs;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1- 2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), C(O), C(0)0, OC(O), C(0)N(R n ) or N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • l_2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, phenyl, (3- 6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)alkoxy, amino, cyano or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , -C(0)NR q , NR q R r , phenyl or a 5-membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring; or a group of the formula:
  • ring A is a 4 to 6 membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl, (1-2C)haloalkyl, (1-2C)hydroxyalkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 and R 102 are each independently selected from (1-2C)alkyl, fluoro, chloro, hydroxy, (1- 2C)alkoxy, CH 2 F, CF 2 H, CF 3 , -C(0)OR ac or-NR ac R ad , wherein R ac and R ad are independently selected from hydrogen or methyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, (1- 2C)alkoxy, (1-2C)alkylamino, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1- 2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R n ), N(R n )C(0), S(0) 2 N(R n ), or N(R n )S02, wherein R n is selected from hydrogen or (1- 2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2- 4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6-membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1 -4C)alkyl, halo, (1 -4C)haloalkyl, (1 - 4C)haloalkoxy, (1 -4C)alkoxy, (1 -4C)alkylamino, amino, cyano, nitro, hydroxy, C(0)R°, C(0)OR°, OC(0)R°, C(0)N(R°)RP, N R°C(0)R P , wherein R° and RP are independently selected from hydrogen or (1 -4C)alkyl; and
  • R 8 is selected from (1 -2C)alkyl, -C(0)OR q , OR q , -C(0)NR q , NR q R r , phenyl or a 5-membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1 -2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1 -2C)alkyl, halo, (1 -2C)haloalkyl, (1 -2C)haloalkoxy, (1 - 2C)alkoxy, (1 -2C)alkylamino, amino, cyano or hydroxyl; or a group of the formula:
  • ring A is a 4 to 6 membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1 -2C)alkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1 - 2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1 -2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1 - 2C)alkoxy, (1 -2C)haloalkyl, (1 -2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5-membered heteroaryl, wherein R ac and R ad are independently selected from hydrogen or (1 -2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkoxy, (1-2C)alkylamino, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl or (1- 2C)haloalkoxy;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R n ), N(R n )C(0), S(0) 2 N(R n ), or N(R n )S02, wherein R n is selected from hydrogen or (1-2C)alkyl; l_2 is absent or (1-2C)alkylene; and
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-4C)alkyl, halo, (1- 4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)alkoxy, (1- 4C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5-membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 4-6-membered carbocyclic ring or a 4-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH2F, CF2H or CF3, (1-2C)alkoxy, amino, cyano or hydroxy; or
  • ring A is a 4 to 6 membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1- 2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5- membered heteroaryl, and wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH2F, CF2H, CF3, (1-2C)alkoxy, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl or (1- 2C)haloalkoxy;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R n ), N(R n )C(0), S(0) 2 N(R n ), or N(R n )S02, wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene; and Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkoxy, (1- 2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5-membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 4-6-membered carbocydic ring or a 4-6-membered heterocyclic ring; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl, -C(0)-CH 3 or -C(0)OR ab wherein R ab is (1- 2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5- membered heteroaryl, and wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1- 2C)alkyl; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH2F, CF2H, CF3, (1-2C)alkoxy, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, amino, cyano, nitro, (1-2C)alkoxy, CH2F, CF2H or CFs;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, bromo, hydroxy, cyano, nitro, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), C(O), C(0)0, OC(O), C(0)N(R n ), N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkoxy, (1- 2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5-membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 4-6-membered carbocydic ring or a 4-6-membered heterocyclic ring; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, (1-2C)alkoxy, CH 2 F, CF 2 H, CF 3 , -C(0)OR ac or-NR ac R ad , and wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, (1-2C)alkoxy, CH2F, CF2H, CF3 or amino; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH2F, CF2H, CF3, (1-2C)alkoxy, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, amino, cyano, (1-2C)alkoxy, CH2F or CF2H;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), C(O), C(0)0, OC(O), C(0)N(R n ), N(R n )C(0), wherein R n is selected from hydrogen or (1- 2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3- 6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6-membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1- 2C)haloalkoxy, (1-2C)alkoxy, (1-2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5- membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl; or R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 4-6-membered carbocyclic ring or a 4-6- membered heterocyclic ring; or
  • R 100 is selected from hydrogen, (1-2C)alkyl, -C(0)-CH 3 or -C(0)OR : wherein R ab is (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, (1-2C)alkoxy, CH2F, CF2H, CF3 or amino; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH2F, CF2H, CF3, (1-2C)alkoxy, amino, cyano or hydroxy; W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R 1 and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, amino, cyano, (1-2C)alkoxy, CH2F or CF2H;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), C(O), C(0)0, OC(O), C(0)N(R n ), N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkoxy, (1- 2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5- membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 4-6-membered carbocyclic ring or a 4-6-membered heterocyclic ring; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring
  • R 101 and R 102 are each independently selected from hydrogen, (1- 2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5-membered heteroaryl, wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, (1-2C)alkoxy, CH2F, CF2H, CF3 or amino; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH2F, CF2H, CF3, (1-2C)alkoxy, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, amino, cyano, (1-2C)alkoxy, CH2F or CF2H;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), C(O), C(0)0, OC(O), C(0)N(R n ), N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • l_2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkoxy, (1- 2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5- membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl;
  • R 6 and R 7 can be linked such that, together with the carbon atom to which they are attached, they form a 4-6-membered carbocydic ring or a 4-6-membered heterocyclic ring; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring
  • R 101 is selected from hydrogen or methyl; and R 102 is selected from (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1- 2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy, -C(0)OR ac , -NR ac R ad , phenyl or a 5-membered heteroaryl, wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, (1-2C)alkoxy, CH2F, CF2H or amino; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered carbocyclic ring or a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from methyl, fluoro, chloro, OCH3, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, amino, cyano or (1-2C)alkoxy;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, C(O), C(0)0, OC(O), C(0)N(R n ) or N(R n )C(0, wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkoxy, (1- 2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5- membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, (1-2C)alkoxy, CH 2 F, CF 2 H, CF 3 , -C(0)OR ac or-NR ac R ad , and wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CR 4 R 5 or C(O), wherein R 4 and R 5 are independently selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, (1-2C)alkoxy, CH2F, CF2H or amino; or
  • R 4 and R 5 can be linked such that, together with the carbon atom to which they are attached, they form a 3-6-membered heterocyclic ring, which is optionally substituted by one or more substituents selected from methyl, fluoro, chloro, OCH3, amino, cyano or hydroxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, amino, cyano or (1-2C)alkoxy;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, C(O), C(0)0, OC(O), C(0)N(R n ) or N(R n )C(0, wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1 -2C)haloalkoxy, (1 -2C)alkoxy, (1 - 2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1 -2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5- membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1 -2C)alkyl; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1 -2C)alkyl or -C(0)OR ab wherein R ab is (1 -2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1 -2C)alkyl, fluoro, chloro, hydroxy, (1 -2C)alkoxy, CH 2 F, CF 2 H, CF 3 , -C(0)OR ac or-NR ac R ad , and wherein R ac and R ad are independently selected from hydrogen or (1 -2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CHR 4 or C(O), wherein R 4 is selected from hydrogen, (1 -2C)alkyl, fluoro, hydroxy, cyano, nitro, (1 -2C)alkoxy, (1 - 2C)haloalkyl, (1-2C)haloalkoxy or NR j R k , wherein R j and R k are independently selected from hydrogen or (1-2C)alkyl;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, amino, cyano, (1-2C)alkoxy, CH2F, CF2H or CFs;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), S0 2 , C(O), C(0)0, OC(O), C(0)N(R n ), N(R n )C(0), S(0) 2 N(R n ), or N(R n )S0 2 , wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkoxy, (1- 2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5- membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl; or
  • R 6 and R 7 can be linked such that, together with the carbon atoms to which they are attached, they form a 4-6 membered carbocyclic ring or a 4-6 membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH2F, CF2H or CF3, (1-2C)alkoxy, amino, cyano or hydroxy; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, (1-2C)alkoxy, CH 2 F, CF 2 H, CF 3 , -C(0)OR ac or-NR ac R ad , and wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CHR 4 or C(O), wherein R 4 is selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, (1-2C)alkoxy, CH2F, CF2H, CFs or amino;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, amino, cyano, (1-2C)alkoxy, CH2F, CF2H or CF 3 ;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, N(R n ), S0 2 , C(O), C(0)0, OC(O), C(0)N(R n ) or N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkoxy, (1- 2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5- membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl; or
  • R 6 and R 7 can be linked such that, together with the carbon atoms to which they are attached, they form a 4-6 membered carbocyclic ring or a 4-6 membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro, CH2F, CF2H or CF3, (1-2C)alkoxy, amino, cyano or hydroxy; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring;
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, (1-2C)alkoxy, CH 2 F, CF 2 H, CF 3 , -C(0)OR ac or-NR ac R ad , and wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CHR 4 or C(O), wherein R 4 is selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, (1-2C)alkoxy, CH2F, CF2H, CFs or amino;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, amino, cyano, (1-2C)alkoxy, CH2F, CF2H or CF 3 ;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, C(0)0, C(0)N(R n ) or N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene; and Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkoxy, (1- 2C)alkylamino, amino, cyano, nitro or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5- membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl; or
  • R 6 and R 7 can be linked such that, together with the carbon atoms to which they are attached, they form a 4-6 membered carbocyclic ring or a 4-6 membered heterocyclic ring, which is optionally substituted by one or more substituents selected from (1-2C)alkyl, fluoro, chloro or hydroxy; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 and R 102 are each independently selected from hydrogen, (1-2C)alkyl, hydroxy, (1-2C)alkoxy or -C(0)OR ac , and wherein R ac is selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CHR 4 or C(O), wherein R 4 is selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano, (1-2C)alkoxy, CH2F, CF2H or amino;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein:
  • R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, amino, cyano, (1-2C)alkoxy, CH2F or CF2H;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, C(0)0, C(0)N(R n ) or N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3-6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6- membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkoxy, (1- 2C)alkylamino, amino, cyano or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or a 5- membered heteroaryl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl; or R 6 and R 7 can be linked such that, together with the carbon atoms to which they are attached, they form a 4-6 membered carbocyclic ring or a 4-6 membered heterocyclic ring; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 is selected from hydrogen or methyl and R 102 is selected from (1-2C)alkyl, hydroxy, (1-2C)alkoxy, C(0)OR ac or -NR ac R ad , and wherein R ac and R ad are independently selected from hydrogen or (1-2C)alkyl;
  • R 2 is selected from:
  • Wi is selected from CHR 4 or C(O), wherein R 4 is selected from hydrogen, (1-2C)alkyl, fluoro, hydroxy, cyano or (1-2C)alkoxy;
  • W2 is selected from cyano, a 5- or 6-membered heteroaryl, phenyl, C(0)OCH 3 , C(0)N(H)CH 3 , CR 6 R 7 R 8 or NR'R m , wherein R' and R m are independently selected from hydrogen or (1-2C)alkyl, and wherein: R 6 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, amino, cyano or (1-2C)alkoxy;
  • R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy or a group of the formula:
  • Y 2 is absent or selected from O, C(0)0, C(0)N(R n ) or N(R n )C(0), wherein R n is selected from hydrogen or (1-2C)alkyl;
  • L2 is absent or (1-2C)alkylene
  • Z 2 is hydrogen, (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, phenyl, (3- 6C)cycloalkyl, 5-6 membered heteroaryl or a 4-6-membered heterocyclyl; wherein Z2 is optionally substituted by one or more substituents selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1- 2C)haloalkoxy, (1-2C)alkoxy, (1-2C)alkylamino, amino, cyano or hydroxy; and
  • R 8 is selected from (1-2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or pyrazolyl, wherein R q and R r are independently selected from hydrogen or (1-2C)alkyl; or
  • ring A is a 5-membered cycloalkyl or heterocyclyl ring
  • W 3 is selected from NR 100 or CR 101 R 102 , wherein R 100 is selected from hydrogen, (1-2C)alkyl or -C(0)OR ab wherein R ab is (1-2C)alkyl, R 101 is selected from hydrogen or methyl and R 102 is selected from (1-2C)alkyl, hydroxy or C(0)OR ac wherein R ac is selected from hydrogen or (1 - 2C)alkyl;
  • R 2 is selected from a group of the formula:
  • Wi is selected from CHR 4 , wherein R 4 is selected from hydrogen, (1 -2C)alkyl, fluoro, hydroxy, cyano or (1 -2C)alkoxy;
  • W 2 is CR 6 R 7 R 8 , wherein:
  • R 6 is selected from hydrogen, (1 -2C)alkyl, fluoro, chloro, hydroxy, amino, cyano or (1 -2C)alkoxy;
  • R 7 is selected from hydrogen, (1 -2C)alkyl, fluoro, chloro, hydroxy, cyano, (1 -2C)alkoxy, (1 -2C)haloalkyl, (1 -2C)haloalkoxy; and
  • R 8 is selected from (1 -2C)alkyl, -C(0)OR q , OR q , NR q R r , phenyl or pyrazolyl, wherein R q and R r are independently selected from hydrogen or (1 -2C)alkyl;
  • R 2 is selected from a group of the formula:
  • W 2 is CR 6 R 7 R 8 , wherein:
  • R 6 is selected from (1 -2C)alkyl, fluoro, chloro, hydroxy, amino, cyano or (1 -2C)alkoxy; and R 7 is selected from hydrogen, (1-2C)alkyl, fluoro, chloro, hydroxy, cyano, (1-2C)alkoxy, (1-2C)haloalkyl, (1-2C)haloalkoxy;
  • R 2 is a group of the formula:
  • R 3 is selected from:
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH 2 F, CF 2 H or CF 3 ;
  • R 9 is selected from hydrogen, fluoro, chloro, bromo, (1- 2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF 2 H or CF 3 ;
  • R 10 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula: -Y 3 -Z 3
  • Y 3 is absent or O, N(R S )(CR S R 1 (where qi is 0, 1 or 2), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R s ), N(R s )C(0), S(0) 2 N(R s ) or N(R s )S0 2 , wherein R s is selected from hydrogen or (1- 4C)alkyl; and
  • Z 3 is hydrogen, (1-6C)alkyl, aryl, (3- 6C)cycloalkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3- 6C)cycloalkenyl, heteroaryl or 4 to 11- membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from oxo, (1- 4C)alkyl, (3-6C)cycloalkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)hydroxyalkyl, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, C(0)NR u R v , NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen, (1-4C)alkyl or (3- 6C)cycloalkyl; and/or Z 3 is optionally further substituted by
  • l_z is absent or a (1 -5C)alkylene optionally substituted by one or more (1-2C)alkyl groups;
  • Wz is aryl, 5- or 6-membered heteroaryl, 4- to 7-membered heterocyclyl, halo, (1- 4C)haloalkyl, (1-4C)haloalkoxy, cyano, hydroxy, (1-4C)alkoxy, C(0)R xa , COOR" 3 , C(0)NR xa R xb or NR xa R xb , wherein R* 3 and R xb are each independently selected from hydrogen or (1-4C)alkyl; and wherein each aryl, 5- or 6-membered heteroaryl or 4- to 7- membered heterocyclyl is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1- 2C)haloalkyl, amino, cyano or hydroxy; a group of Formula B shown below:
  • Xc.Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCH 3 ;
  • R 11 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, OC(O), C(0)N(R w ), N(R w )C(0), S(0) 2 N(R w ) or N(R W )SC>2, wherein R w is selected from hydrogen or (1-4C)alkyl; and
  • Z5 is hydrogen, (1-6C)alkyl, aryl, (3- 8C)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, (1- 4C)hydroxyalkyl, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen, (1- 4C)alkyl or (3-6C)cycloalkyl;
  • R 12 is selected from fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, (2-4C)alkynyl, CH 2 F, CF 2 H or
  • Xf and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, (1- 2C)alkyl, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • Xh, X and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 3 is selected from: i) a group of Formula A shown below:
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH 2 F, CF 2 H or CF 3 ;
  • R 9 is selected from hydrogen, fluoro, chloro, bromo, (1- 2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF 2 H or CF 3 ;
  • R 10 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 3 is absent or O, N(R S )(CR S R (where qi is 0, 1 or 2), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R s ), N(R s )C(0), S(0) 2 N(R s ) or N(R s )S0 2 , wherein R s is selected from hydrogen or (1- 4C)alkyl; and
  • Z3 is hydrogen, (1-6C)alkyl, aryl, (3- 6C)cycloalkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3- 6C)cycloalkenyl, heteroaryl or 4 to 11- membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from oxo, (1- 4C)alkyl, (3-6C)cycloalkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)hydroxyalkyl, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, C(0)NR u R v , NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen, (1-4C)alkyl or (3- 6C)cycloalkyl; and/or Z 3 is optionally further substituted by
  • l_z is absent or a (1 -3C)alkylene optionally substituted by one or more (1-2C)alkyl groups;
  • Wz is aryl, 5- or 6-membered heteroaryl, 4- to 7-membered heterocyclyl, halo, (1- 4C)haloalkyl, (1-4C)haloalkoxy, cyano, hydroxy, (1-4C)alkoxy, C(0)R xa , COOR" 3 , C(0)NR xa R xb or NR xa R xb , wherein R* 3 and R xb are each independently selected from hydrogen or (1-4C)alkyl;
  • Xc.Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCH 3 ;
  • R 11 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, OC(O), C(0)N(R w ), N(R w )C(0), S(0) 2 N(R w ) or N(R W )SC>2, wherein R w is selected from hydrogen or (1 -4C)alkyl;
  • Z5 is hydrogen, (1 -6C)alkyl, aryl, (3- 8C)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1 -4C)alkyl, halo, (1 -4C)haloalkyl, (1 -4C)haloalkoxy, (1 - 4C)hydroxyalkyl, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen, (1 - 4C)alkyl or (3-6C)cycloalkyl;
  • R 12 is selected from fluoro, chloro, bromo, (1 -2C)alkyl, (1 -2C)alkoxy, cyano, nitro, (2-4C)alkynyl, CH 2 F, CF 2 H or CF 3 ;
  • X f and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, (1 - 2C)alkyl, (1 -2C)haloalkyl or (1 -2C)haloalkoxy;
  • Xh, X and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 3 is selected from: i) a group of Formula A shown below:
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH 2 F, CF 2 H or CF 3 ;
  • R 9 is selected from hydrogen, fluoro, chloro, bromo, (1- 2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF 2 H or CF 3 ;
  • R 10 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 3 is absent or O, N(R S )(CR S R 1 (where qi is 0, 1 or 2), S, SO, S0 2 , C(O), C(0)0, OC(O), C(0)N(R s ), N(R s )C(0), S(0) 2 N(R s ) or N(R s )S0 2 , wherein R s is selected from hydrogen or (1- 4C)alkyl; and Z3 is hydrogen, (1 -6C)alkyl, aryl, (3- 6C)cycloalkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3- 6C)cycloalkenyl, heteroaryl or 4 to 1 1 - membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from oxo, (1 - 4C)alkyl, (3-6C)cycloalkyl, halo, (1 -4C)haloalkyl, (1
  • l_z is a (1 -5C)alkylene optionally substituted by one or more substituents selected from (1 -2C)alkyl or oxo;
  • Wz is halo, (1 -4C)haloalkyl, (1 - 4C)haloalkoxy, cyano, hydroxy, (1 - 4C)alkoxy, 0(0) ⁇ , COOR xa , C(0)NR xa R xb or NR xa R xb , wherein R" 3 and R* are each independently selected from hydrogen or (1 -4C)alkyl;
  • Xc.Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCH 3 ;
  • R 11 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, OC(O), C(0)N(R w ), N(R w )C(0), S(0) 2 N(R w ) or N(R W )S02, wherein R w is selected from hydrogen or (1-4C)alkyl;
  • Z5 is hydrogen, (1-6C)alkyl, aryl, (3- 8C)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl;
  • R 12 is selected from fluoro, chloro, bromo, (1-2C)alkyl,
  • Xf and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, (1- 2C)alkyl, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • Xh, X and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 3 is selected from: i) a group of Formula A shown below:
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH 2 F, CF 2 H or CF 3 ;
  • R 9 is selected from hydrogen, fluoro, chloro, bromo, (1- 2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH 2 F, CF 2 H or CF 3 ;
  • R 10 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 3 is absent or N(R S )(CR S R (where qi is 0, 1 or 2), S, C(O), C(0)0, C(0)N(R s ), N(R s )C(0), S(0) 2 N(R s ) or N(R s )S0 2 , wherein R s is selected from hydrogen or (1-4C)alkyl; and
  • Z3 is hydrogen, (1-6C)alkyl, aryl, (3- 6C)cycloalkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3- 6C)cycloalkenyl, 5- or 6-membered heteroaryl or 4 to 1 1-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from oxo, (1-4C)alkyl, (3-6C)cycloalkyl, halo, (1- 4C)haloalkyl, (1-4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, C(0)NR u R v , NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen, (1-4C)alkyl or (3- 6C)cycloalkyl; and/or Z 3 is optionally further substituted by a group
  • l_z is absent or a (1-3C)alkylene
  • Wz is phenyl, 5- or 6-membered heteroaryl, 6-membered heterocyclyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, hydroxy, (1-4C)alkoxy, C(0)R xa , COOR" 3 , C(0)NR xa R xb or NR xa R xb , wherein R* 3 and R xb are each independently selected from hydrogen or (1-4C)alkyl; ii) a group of Formula B shown below:
  • Xc.Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCH 3 ;
  • R 11 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, C(0)N(R w ) or S(0) 2 N(R w ), wherein R w is selected from hydrogen or (1-4C)alkyl;
  • Z5 is hydrogen, (1-6C)alkyl, aryl, (3- 8C)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, (1- 4C)hydroxyalkyl, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen, (1- 4C)alkyl or (3-6C)cycloalkyl;
  • R 12 is selected from fluoro, chloro, bromo, (1-2C)alkyl, (1- 2C)alkoxy, cyano, nitro, (2-4C)alkynyl, CH 2 F, CF 2 H or CF 3 ;
  • X f and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, methyl, CH2F,
  • X h , Xi and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 3 is selected from:
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH 2 F, CF 2 H or CF 3 ; R 9 is selected from hydrogen, fluoro, chloro, bromo, (1 - 2C)alkyl, (1 -2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF 2 H or CF 3 ;
  • R 10 is selected from hydrogen, halo, (1-4C)alkyl, (1 - 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 3 is absent or N(R S )(CR S R (where qi is 0, 1 or 2), S, C(O), C(0)0, C(0)N(R s ), N(R s )C(0), S(0) 2 N(R s ) or N(R s )S0 2 , wherein R s is selected from hydrogen or (1-4C)alkyl; and
  • Z3 is hydrogen, (1-6C)alkyl, aryl, (3- 6C)cycloalkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3- 6C)cycloalkenyl, 5- or 6-membered heteroaryl or 4 to 1 1-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from oxo, (1-4C)alkyl, (3-6C)cycloalkyl, halo, (1 - 4C)haloalkyl, (1-4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, C(0)NR u R v , NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen, (1-4C)alkyl or (3- 6C)cycloalkyl; or Z 3 is optionally further substituted by a group of
  • l_z is a (1-3C)alkylene
  • Wz is halo, (1-4C)haloalkyl, (1 - 4C)haloalkoxy, cyano, hydroxy, (1 - 4C)alkoxy, 0(0) ⁇ , COOR xa , C(0)NR xa R xb or NR xa R xb , wherein R" 3 and are each independently selected from hydrogen or (1-4C)alkyl;
  • Xc.Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCH 3 ;
  • R 11 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, C(0)N(R w ) or S(0) 2 N(R w ), wherein R w is selected from hydrogen or (1-4C)alkyl;
  • Z5 is hydrogen, (1-6C)alkyl, aryl, (3- 8C)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl;
  • R 12 is selected from fluoro, chloro, bromo, (1-2C)alkyl, (1- 2C)alkoxy, cyano, nitro, (2-4C)alkynyl, CH 2 F, CF 2 H or CF 3 ;
  • X f and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, methyl, CH2F,
  • X h , Xi and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 3 is selected from
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH 2 F, CF 2 H or CF 3 ; R 9 is selected from hydrogen, fluoro, chloro, bromo, (1- 2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF 2 H or CF 3 ;
  • R 10 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 3 is absent or C(O), C(0)0, OC(O), C(0)N(R s ), N(R s )C(0), N(R s )C(0)N(R l ), N(R s )C(0)0, OC(0)N(R s ), S(0) 2 N(R s ), N(R s )S0 2 , wherein R s and R' are each independently selected from hydrogen or (1-4C)alkyl; and
  • Z3 is hydrogen, (1-6C)alkyl, aryl, (3- 6C)cycloalkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3- 6C)cycloalkenyl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1- 4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen, (1- 4C)alkyl or (3-6C)cycloalkyl;
  • Xc.Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCH 3 ;
  • R 11 is selected from hydrogen, halo, (1-4C)alkyl, (1- 4C)alkoxy, (1-4C)haloalkyl, (1-4C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, OC(O), C(0)N(R w ), N(R w )C(0), NiR ⁇ CiOJNiR 3 "), N(R w )C(0)0, OC(0)N(R w ), S(0) 2 N(R w ), N(R w )S0 2 , wherein R w and R x are each independently selected from hydrogen or (1- 4C)alkyl; and
  • Z5 is hydrogen, (1-6C)alkyl, aryl, (3- 8C)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl;
  • R 12 is selected from fluoro, chloro, bromo, (1-2C)alkyl, (1- 2C)alkoxy, cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl, CH 2 F, CF 2 H or CF 3 ;
  • Xf and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, (1-2C)alkyl, (1- 2C)haloalkyl or (1-2C)haloalkoxy;
  • Xh, X and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • R 3 is selected from:
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, (1-2C)alkyl, (1- 2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF2H or CF3;
  • R 9 is selected from fluoro, chloro, bromo, (1-2C)alkyl, (1-2C)alkoxy, cyano, nitro, acetylenyl, CH2F, CF2H or CF3;
  • R 10 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2- 4C)alkynyl or a group of the formula:
  • Y 3 is absent or C(O), C(0)0, OC(O), C(0)N(R s ), N(R s )C(0), S(0)2N(R S ), N(R S )S02, wherein R s is selected from hydrogen or (1-4C)alkyl;
  • Z 3 is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (2- 4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkenyl, 5- or 6- membered heteroaryl or 5- or 6-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyi, mercapto, NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl;
  • Xc.Xd and X e are independently selected from N, CH, CF, CCI, C-CN or
  • R 11 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2- 4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, OC(O), C(0)N(R w ), N(R w )C(0), S(0) 2 N(R w ), N(R w )S0 2 , wherein R w is selected from hydrogen or (1-4C)alkyl;
  • Z 5 is hydrogen, (1-6C)alkyl, aryl, (3-8C)cycloalkyl, (3- 8C)cycloalkenyl, heteroaryl or heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1 -4C)alkyl, halo, (1 -4C)haloalkyl, (1 -4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, carbamoyl, sulphamoyl, mercapto, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen, (1 -4C)alkyl or (3-6C)cycloalkyl; and
  • R 12 is selected from fluoro, chloro, bromo, (1 -2C)alkyl, (1 -2C)alkoxy, cyano, nitro, (2-4C)alkynyl, CH 2 F, CF 2 H or CF 3 ;
  • X f and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, (1 -2C)alkyl, (1 -2C)haloalkyl or (1 -2C)haloalkoxy;
  • X h , Xi and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1 -2C)alkyl, (1 -2C)alkoxy, (1 - 2C)haloalkyl or (1 -2C)haloalkoxy;
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, methyl, OCH3, cyano, nitro, acetylenyl, CH2F, CF2H or CF3;
  • R 9 is selected from fluoro, chloro, bromo, methyl, OCH3, cyano, nitro, acetylenyl, CH 2 F or CF 2 H;
  • R 10 is selected from hydrogen, halo, (1 -2C)alkyl, (1 -2C)alkoxy, (1 - 2C)haloalkyl, (1 -2C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2- 4C)alkynyl or a group of the formula:
  • Y 3 is absent or C(O), C(0)0, OC(O), C(0)N(R s ), N(R s )C(0), S(0)2N(R S ), N(R S )SC>2, wherein R s is selected from hydrogen or (1 -4C)alkyl; and
  • Z 3 is hydrogen, (1 -6C)alkyl, aryl, (3-6C)cycloalkyl, (2- 4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkenyl, 5- or 6- membered heteroaryl or 5- or 6-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from (1 -4C)alkyl, halo, (1 -4C)haloalkyl, (1 -4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen or (1 -4C)alkyl;
  • Xc. Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCHs;
  • R 11 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2- 4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, OC(O), C(0)N(R w ), N(R w )C(0), S(0) 2 N(R w ), N(R w )S0 2 , wherein R w is selected from hydrogen or (1-4C)alkyl;
  • Z 5 is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (3- 6C)cycloalkenyl, 5 or 6 memebered heteroaryl or 5 or 6 membered heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1- 4C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen or (1-4C)alkyl; and
  • R 12 is selected from fluoro, chloro, bromo, methyl, OCH3, cyano, nitro, acetylenyl, CH 2 F, CF 2 H or CF 3 ;
  • Xf and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, (1-2C)alkyl, (1-2C)haloalkyl or (1-2C)haloalkoxy;
  • Xh, X and Xj are independently selected from N or CR 14 , wherein R 14 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1- 2C)haloalkyl or (1-2C)haloalkoxy;
  • R 3 is selected from:
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, methyl, OCH3, cyano, acetylenyl, CH 2 F, CF 2 H or CF 3 ;
  • R 9 is selected from fluoro, chloro, bromo, methyl, OCH3, cyano, nitro or acetylenyl;
  • R 10 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2- 4C)alkynyl or a group of the formula:
  • Y 3 is absent or C(O), C(0)0, C(0)N(R s ) or S(0) 2 N(R s ), wherein R s is selected from hydrogen or (1-4C)alkyl;
  • Z 3 is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (2- 4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkenyl, 5- or 6- membered heteroaryl or 5- or 6-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen or (1-2C)alkyl;
  • Xc. Xd and X e are independently selected from N, CH, CF, CCI, C-CN or CCHs;
  • R 11 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2- 4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, C(0)N(R w ) or S(0) 2 N(R w ), wherein R w is selected from hydrogen or (1- 4C)alkyl;
  • Z 5 is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (3- 6C)cycloalkenyl, 5 or 6 memebered heteroaryl or 5 or 6 membered heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1- 2C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen or (1-2C)alkyl; and
  • R 9 is selected from fluoro, chloro, bromo, methyl, OCH3, cyano, acetylenyl, CH 2 F, CF 2 H or CF 3 ;
  • Xf and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro, methyl, CH2F, CF2H or CFs;
  • R 14 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1- 2C)haloalkyl or (1-2C)haloalkoxy;
  • R 3 is selected from:
  • X a and Xb are independently selected from N or CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, methyl, OCH3, cyano, acetylenyl, CH 2 F, CF 2 H or CF 3 ;
  • R 9 is selected from fluoro, chloro, bromo, methyl, OCH3, cyano, nitro or acetylenyl;
  • R 10 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2- 4C)alkynyl or a group of the formula:
  • Y 3 is absent or C(O), C(0)0, C(0)N(R s ) or S(0) 2 N(R s ), wherein R s is selected from hydrogen or (1-4C)alkyl;
  • Z 3 is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (2- 4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkenyl, 5- or 6- membered heteroaryl or 5- or 6-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1-2C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen or (1-2C)alkyl;
  • Xc. Xd and X e are independently selected from N, CH, CF, CCI, C-CN or
  • R 11 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, cyano, nitro, (2-4C)alkenyl, (2- 4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, C(0)N(R w ) or
  • Z 5 is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (3- 6C)cycloalkenyl, 5 or 6 memebered heteroaryl or 5 or 6 membered heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1- 2C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen or (1-2C)alkyl; and
  • R 12 is selected from fluoro, chloro, bromo, methyl, OCH3, cyano, acetylenyl, CH 2 F, CF 2 H or CF 3 ;
  • Xf and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro or methyl;
  • R 14 is selected from hydrogen, halo, methyl, OCH 3 , CH 2 F, CF 2 H or CF 3 ;
  • R 3 is selected from:
  • X a and Xb are both CR x1 , wherein R x1 is selected from hydrogen, fluoro, chloro, bromo, methyl, OCH3, cyano or acetylenyl;
  • R 9 is selected from fluoro, chloro, bromo, methyl, OCH3, cyano or acetylenyl;
  • R 10 is selected from hydrogen, halo, (1 -2C)alkyl, (1 -2C)alkoxy, (1 - 2C)haloalkyl, (1 -2C)haloalkoxy, cyano, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 3 is absent or C(O), C(0)0, C(0)N(R s ) or S(0) 2 N(R s ), wherein R s is selected from hydrogen or (1 -4C)alkyl;
  • Z 3 is hydrogen, (1 -6C)alkyl, aryl, (3-6C)cycloalkyl, (2- 4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkenyl, 5- or 6- membered heteroaryl or 5- or 6-membered heterocyclyl; wherein Z3 is optionally further substituted by one or more substituent groups independently selected from (1 -2C)alkyl, halo, (1 -2C)haloalkyl, (1 -2C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, NR U R V or OR u , wherein R u and R v are each independently selected from hydrogen or (1 -2C)alkyl;
  • X c and Xd are independently selected from N, CH, CF, CCI, C-CN or CCHs;
  • R 11 is selected from hydrogen, halo, (1-2C)alkyl, (1-2C)alkoxy, (1- 2C)haloalkyl, (1-2C)haloalkoxy, cyano, (2-4C)alkenyl, (2-4C)alkynyl or a group of the formula:
  • Y 5 is absent or O, N(R W ), C(O), C(0)0, C(0)N(R w ) or S(0) 2 N(R w ), wherein R w is selected from hydrogen or (1- 4C)alkyl;
  • Z 5 is hydrogen, (1-6C)alkyl, aryl, (3-6C)cycloalkyl, (3- 6C)cycloalkenyl, 5 or 6 memebered heteroaryl or 5 or 6 membered heterocyclyl; wherein Z5 is optionally further substituted by one or more substituent groups independently selected from (1-2C)alkyl, halo, (1-2C)haloalkyl, (1- 2C)haloalkoxy, amino, cyano, hydroxy, amido, carboxy, NR y R z , OR y , wherein R y and R z are each independently selected from hydrogen or (1-2C)alkyl; and
  • R 12 is selected from fluoro, chloro, bromo, methyl, OCH 3 , cyano or acetylenyl;
  • X f and X g are independently selected from N or CR 13 , wherein R 13 is selected from hydrogen, fluoro, chloro or methyl;

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PCT/GB2018/051447 2017-05-26 2018-05-25 Benzimidazolone derived inhibitors of bcl6 Ceased WO2018215801A1 (en)

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CN202410618580.4A CN118561812A (zh) 2017-05-26 2018-05-25 苯并咪唑酮衍生的bcl6抑制剂
KR1020197038091A KR102628675B1 (ko) 2017-05-26 2018-05-25 벤즈이미다졸론 유래된 bcl6의 저해제
KR1020247002176A KR102828518B1 (ko) 2017-05-26 2018-05-25 벤즈이미다졸론 유래된 bcl6의 저해제
CN201880047061.XA CN111163839B (zh) 2017-05-26 2018-05-25 苯并咪唑酮衍生的bcl6抑制剂
IL270869A IL270869B2 (en) 2017-05-26 2018-05-25 Benzimidazolone derivative inhibitors of bcl6
IL302300A IL302300A (en) 2017-05-26 2018-05-25 Benzimidazolone derivative inhibitors of BCL6
BR112019024830-7A BR112019024830B1 (pt) 2017-05-26 2018-05-25 Inibidores de bcl6 derivados de benzimidazolona, seus usos e composição farmacêutica
ES18730042T ES2975690T3 (es) 2017-05-26 2018-05-25 Inhibidores de BCL6 derivados de benzimidazolona
CA3065005A CA3065005A1 (en) 2017-05-26 2018-05-25 Benzimidazolone derived inhibitors of bcl6
AU2018274723A AU2018274723B2 (en) 2017-05-26 2018-05-25 Benzimidazolone derived inhibitors of BCL6
US16/616,901 US12110286B2 (en) 2017-05-26 2018-05-25 Benzimidazolone derived inhibitors of BCL6
EA201992628A EA201992628A1 (ru) 2018-04-13 2018-05-25 Ингибиторы bcl6, полученные из бензимидазолона
EP24150697.1A EP4374858A3 (en) 2017-05-26 2018-05-25 Benzimidazolone derived inhibitors of bcl6
EP18730042.1A EP3630291B9 (en) 2017-05-26 2018-05-25 Benzimidazolone derived inhibitors of bcl6
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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020104820A1 (en) * 2018-11-23 2020-05-28 Cancer Research Technology Limited Substituted benzimidazolones as anti-cancer agents
KR20200144109A (ko) * 2018-04-13 2020-12-28 캔써 리서치 테크놀로지 리미티드 Bcl6 저해제
WO2021001567A1 (en) 2019-07-03 2021-01-07 Cancer Research Technology Limited Modulation of t cell cytotoxicity and related therapy
EP3765516A2 (en) * 2018-03-14 2021-01-20 Elstar Therapeutics, Inc. Multifunctional molecules and uses thereof
WO2021077010A1 (en) * 2019-10-17 2021-04-22 Arvinas Operations, Inc. Bifunctional molecules containing an e3 ubiquitine ligase binding moiety linked to a bcl6 targeting moiety
CN114364667A (zh) * 2019-04-09 2022-04-15 紐力克斯治疗公司 用于Cbl-b抑制的3-取代哌啶类化合物以及Cbl-b抑制剂与癌症疫苗和/或溶瘤病毒联合的用途
CN116669725A (zh) * 2020-09-24 2023-08-29 奥克兰联合服务有限公司 新型氨基吡啶及其在治疗癌症中的用途
WO2023240038A1 (en) 2022-06-06 2023-12-14 Treeline Biosciences, Inc. Tricyclic quinolone bcl6 bifunctional degraders
WO2023244918A1 (en) 2022-06-13 2023-12-21 Treeline Biosciences, Inc. Quinolone bcl6 bifunctional degraders
WO2023244917A1 (en) 2022-06-13 2023-12-21 Treeline Biosciences, Inc. 1,8-naphthyridin-2-one heterobifunctional bcl6 degraders
US11986532B2 (en) 2021-04-16 2024-05-21 Arvinas Operations, Inc. Modulators of BCL6 proteolysis and associated methods of use
WO2024118887A1 (en) 2022-11-30 2024-06-06 Blueprint Medicines Corporation N-phenyl-pyrazolo[1,5-a]pyridine-3-carboxamide derivatives as wild type c-kit kinase inhibitors for the treatment of urticaria
US12016860B2 (en) 2021-04-08 2024-06-25 Nurix Therapeutics, Inc. Combination therapies with Cbl-b inhibitor compounds
US12528826B2 (en) 2019-10-14 2026-01-20 Cancer Research Technology Limited [1,4]oxazepino[2,3-c]quinolinone derivatives as BCL6 inhibitors

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7202315B2 (ja) * 2017-05-26 2023-01-11 キャンサー・リサーチ・テクノロジー・リミテッド ベンズイミダゾロン由来のｂｃｌ６阻害剤
IL315310A (en) 2017-12-26 2024-10-01 Kymera Therapeutics Inc Irak degraders and uses thereof
WO2019140380A1 (en) 2018-01-12 2019-07-18 Kymera Therapeutics, Inc. Protein degraders and uses thereof
WO2020010227A1 (en) 2018-07-06 2020-01-09 Kymera Therapeutics, Inc. Protein degraders and uses thereof
CA3119773A1 (en) 2018-11-30 2020-06-04 Kymera Therapeutics, Inc. Irak degraders and uses thereof
PH12022500002A1 (en) 2019-06-28 2023-04-03 Kymera Therapeutics Inc Irak degraders and uses thereof
WO2021011868A1 (en) 2019-07-17 2021-01-21 Kymera Therapeutics, Inc. Irak degraders and uses thereof
WO2021119159A1 (en) 2019-12-10 2021-06-17 Kymera Therapeutics, Inc. Irak degraders and uses thereof
KR20220145325A (ko) 2019-12-17 2022-10-28 카이메라 쎄라퓨틱스 인코포레이티드 Irak 분해제 및 이의 용도
CN116867758A (zh) 2020-12-30 2023-10-10 凯麦拉医疗公司 Irak降解剂和其用途
US12171768B2 (en) 2021-02-15 2024-12-24 Kymera Therapeutics, Inc. IRAK4 degraders and uses thereof
CA3236265A1 (en) 2021-10-29 2023-05-04 William Leong Irak4 degraders and synthesis thereof
US20230277519A1 (en) * 2022-01-14 2023-09-07 Kymera Therapeutics, Inc. Irak4 degraders and uses thereof
CA3243560A1 (en) 2022-01-31 2023-08-03 Kymera Therapeutics, Inc. Iraqi Degradation Agents and Their Uses
EP4604946A1 (en) * 2022-10-17 2025-08-27 Dana-Farber Cancer Institute, Inc. Alkylamine-containing small molecule degraders of bcl6
WO2024191788A1 (en) * 2023-03-10 2024-09-19 Kymera Therapeutics, Inc. Irak4 degraders and uses thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0259572A (ja) * 1988-08-23 1990-02-28 Mitsubishi Kasei Corp ベンズイミダゾロン誘導体又はその塩類
WO2008066887A2 (en) * 2006-11-30 2008-06-05 Albert Einstein College Of Medicine Of Yeshiva University Small molecule inhibitors of bcl6
WO2016033416A1 (en) * 2014-08-29 2016-03-03 Board Of Regents, University Of Texas System Bromodomain inhibitors for treating disease

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9624482D0 (en) 1995-12-18 1997-01-15 Zeneca Phaema S A Chemical compounds
DE69720965T2 (de) 1996-02-13 2004-02-05 Astrazeneca Ab Chinazolinderivate und deren verwendung als vegf hemmer
NZ331191A (en) 1996-03-05 2000-03-27 Zeneca Ltd 4-anilinoquinazoline derivatives and pharmaceutical compositions thereof
GB9718972D0 (en) 1996-09-25 1997-11-12 Zeneca Ltd Chemical compounds
GB9714249D0 (en) 1997-07-08 1997-09-10 Angiogene Pharm Ltd Vascular damaging agents
GB9900334D0 (en) 1999-01-07 1999-02-24 Angiogene Pharm Ltd Tricylic vascular damaging agents
GB9900752D0 (en) 1999-01-15 1999-03-03 Angiogene Pharm Ltd Benzimidazole vascular damaging agents
PT1154774E (pt) 1999-02-10 2005-10-31 Astrazeneca Ab Derivados de quinazolina como inibidores de angiogenese
AU2001258628A1 (en) 2000-05-31 2001-12-11 Astrazeneca Ab Indole derivatives with vascular damaging activity
UA73993C2 (uk) 2000-06-06 2005-10-17 Астразенека Аб Хіназолінові похідні для лікування пухлин та фармацевтична композиція
MXPA02012903A (es) 2000-07-07 2004-07-30 Angiogene Pharm Ltd Derivados de colquinol como inhibidores de angiogenesis.
MXPA02012905A (es) 2000-07-07 2004-07-30 Angiogene Pharm Ltd Derivados de colquinol como agentes de dano vascular..
WO2003095448A1 (en) 2002-05-06 2003-11-20 Bayer Pharmaceuticals Corporation Pyridinyl amino pyrimidine derivatives useful for treating hyper-proliferative disorders
US20050256157A1 (en) 2002-08-23 2005-11-17 Chiron Corporation Combination therapy with CHK1 inhibitors
WO2009063240A1 (en) * 2007-11-16 2009-05-22 Arrow Therapeutics Limited 2,4-diaminopyrimidine derivatives useful as inhibitors of aurora kinase
SG187502A1 (en) 2008-02-01 2013-02-28 Takeda Pharmaceutical Oxim derivatives as hsp90 inhibitors
BRPI1006942A2 (pt) * 2009-01-23 2016-04-12 Rigel Pharmaceuticals Inc composto, composição farmacêutica, kit, métodos para inibir uma atividade de uma jak quinase, para tratar uma doença, para tratar a rejeição de transplante de aloenxerto em um receptor de transplante, para tratar uma reação de hipersensibilidade, e para inibir uma cascata de transdução de sinal, e, uso do composto
KR20120114355A (ko) * 2010-01-13 2012-10-16 글락소스미스클라인 엘엘씨 화합물 및 방법
CA2840883C (en) * 2011-07-07 2019-07-16 Merck Patent Gmbh Substituted azaheterocycles
CN102503896A (zh) * 2011-10-25 2012-06-20 西北农林科技大学 甲基丙烯酰基苯并咪唑（硫）酮衍生物及其作为抗菌药物的用途
CN104922116B (zh) * 2014-03-23 2020-08-11 上海诗丹德生物技术有限公司 甲基丙烯酰基苯并咪唑酮衍生物的用途
CN105017159B (zh) * 2014-04-28 2019-05-17 四川大学 5-氟-2,4-二取代氨基嘧啶衍生物及其制备方法和用途
US10266549B2 (en) * 2014-08-25 2019-04-23 Salk Institute For Biological Studies ULK1 inhibitors and methods using same
WO2017007658A1 (en) 2015-07-07 2017-01-12 Rigel Pharmaceuticals, Inc. A combination for immune mediated cancer treatment
US11001570B2 (en) 2016-12-13 2021-05-11 Boehringer Ingelheim International Gmbh 6-amino-quinolinone compounds and derivatives as BCL6 inhibitors
US11161839B2 (en) 2017-05-26 2021-11-02 The Institute Of Cancer Research: Royal Cancer Hospital 2-quinolone derived inhibitors of BCL6
JP7202315B2 (ja) 2017-05-26 2023-01-11 キャンサー・リサーチ・テクノロジー・リミテッド ベンズイミダゾロン由来のｂｃｌ６阻害剤

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0259572A (ja) * 1988-08-23 1990-02-28 Mitsubishi Kasei Corp ベンズイミダゾロン誘導体又はその塩類
WO2008066887A2 (en) * 2006-11-30 2008-06-05 Albert Einstein College Of Medicine Of Yeshiva University Small molecule inhibitors of bcl6
WO2016033416A1 (en) * 2014-08-29 2016-03-03 Board Of Regents, University Of Texas System Bromodomain inhibitors for treating disease

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3765516A2 (en) * 2018-03-14 2021-01-20 Elstar Therapeutics, Inc. Multifunctional molecules and uses thereof
KR20200144109A (ko) * 2018-04-13 2020-12-28 캔써 리서치 테크놀로지 리미티드 Bcl6 저해제
US11512095B2 (en) 2018-04-13 2022-11-29 The Institute Of Cancer Research: Royal Cancer Hospital BCL6 inhibitors
US12486285B2 (en) 2018-04-13 2025-12-02 Cancer Research Technology Limited BCL6 inhibitors
KR102830237B1 (ko) 2018-04-13 2025-07-07 캔써 리서치 테크놀로지 리미티드 Bcl6 저해제
WO2020104820A1 (en) * 2018-11-23 2020-05-28 Cancer Research Technology Limited Substituted benzimidazolones as anti-cancer agents
CN114364667A (zh) * 2019-04-09 2022-04-15 紐力克斯治疗公司 用于Cbl-b抑制的3-取代哌啶类化合物以及Cbl-b抑制剂与癌症疫苗和/或溶瘤病毒联合的用途
US12485144B2 (en) 2019-04-09 2025-12-02 Nurix Therapeutics, Inc. 3-substituted piperidine compounds for Cbl-b inhibition, and use thereof
WO2021001567A1 (en) 2019-07-03 2021-01-07 Cancer Research Technology Limited Modulation of t cell cytotoxicity and related therapy
US12528826B2 (en) 2019-10-14 2026-01-20 Cancer Research Technology Limited [1,4]oxazepino[2,3-c]quinolinone derivatives as BCL6 inhibitors
CN115397821B (zh) * 2019-10-17 2024-09-03 阿尔维纳斯运营股份有限公司 含有与bcl6靶向部分连接的e3泛素连接酶结合部分的双官能分子
US12310975B2 (en) 2019-10-17 2025-05-27 Arvinas Operations, Inc. Modulators of BCL6 proteolysis and associated methods of use
WO2021077010A1 (en) * 2019-10-17 2021-04-22 Arvinas Operations, Inc. Bifunctional molecules containing an e3 ubiquitine ligase binding moiety linked to a bcl6 targeting moiety
AU2020368542B2 (en) * 2019-10-17 2024-02-29 Arvinas Operations, Inc. Bifunctional molecules containing an E3 ubiquitine ligase binding moiety linked to a BCL6 targeting moiety
JP2024052757A (ja) * 2019-10-17 2024-04-12 アルヴィナス・オペレーションズ・インコーポレイテッド Ｂｃｌ６標的化部分に連結されたｅ３ユビキチンリガーゼ結合部分を含有する二官能性分子
CN115397821A (zh) * 2019-10-17 2022-11-25 阿尔维纳斯运营股份有限公司 含有与bcl6靶向部分连接的e3泛素连接酶结合部分的双官能分子
JP2022552006A (ja) * 2019-10-17 2022-12-14 アルヴィナス・オペレーションズ・インコーポレイテッド Ｂｃｌ６標的化部分に連結されたｅ３ユビキチンリガーゼ結合部分を含有する二官能性分子
EP4217357A4 (en) * 2020-09-24 2024-11-06 Auckland Uniservices Limited NEW AMINOPYRIDINES AND THEIR USE IN THE TREATMENT OF CANCER
CN116669725A (zh) * 2020-09-24 2023-08-29 奥克兰联合服务有限公司 新型氨基吡啶及其在治疗癌症中的用途
US12016860B2 (en) 2021-04-08 2024-06-25 Nurix Therapeutics, Inc. Combination therapies with Cbl-b inhibitor compounds
US11986532B2 (en) 2021-04-16 2024-05-21 Arvinas Operations, Inc. Modulators of BCL6 proteolysis and associated methods of use
WO2023240038A1 (en) 2022-06-06 2023-12-14 Treeline Biosciences, Inc. Tricyclic quinolone bcl6 bifunctional degraders
WO2023244918A1 (en) 2022-06-13 2023-12-21 Treeline Biosciences, Inc. Quinolone bcl6 bifunctional degraders
WO2023244917A1 (en) 2022-06-13 2023-12-21 Treeline Biosciences, Inc. 1,8-naphthyridin-2-one heterobifunctional bcl6 degraders
WO2024118887A1 (en) 2022-11-30 2024-06-06 Blueprint Medicines Corporation N-phenyl-pyrazolo[1,5-a]pyridine-3-carboxamide derivatives as wild type c-kit kinase inhibitors for the treatment of urticaria

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