Quinazoline derivatives as GIPR antagonists

Abstract

The present specification relates to compounds of formula (I-X), (I) or their pharmaceutically acceptable salts, pharmaceutical compositions comprising them and their use as medicaments.

Description

[0001]201369 NOVEL COMPOUNDS The present specification claims benefit of priority to UK patent application number 2410225.3, filed 12 July 2024, and UK patent application number 2416572.2,filed 11 November 2024, the entire 5 contents of which are hereby incorporated by reference in their entirety for all purposes. Technical Field The specification relates to compounds of formula (I-X), (I) or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them and their use as medicaments.10 Background of the Specification Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone secreted from intestinal K cells in response to food intake. GIP was formerly called gastric inhibitory polypeptide. GIP and glucagon-like polypeptide-1 (GLP-1) are insulinotropic factors, known as incretins. The insulinotropic 15 effect of GIP is lost in type 2 diabetic patients (Nauck et al., J. Clin. Invest.1993;91(1):301-307). Gastric inhibitory polypeptide receptor (GIPR) is the receptor for GIP, and is highly expressed in a number of tissues, including the pancreas, gut, adipose tissue, heart, pituitary, adrenal cortex, and brain (Usdin et al., Endocrinology.1993, 133:2861-2870). Human GIPR comprises 466 amino acids and is encoded by a gene located on chromosome 19q13.3 (Gremlich et al., Diabetes.1995; 44: 1202-8; Volz et 20 al., FEBS Lett., 1995; 373: 23-29) GIPR is also expressed in adipocytes, which respond to increased GIP levels with increased glucose uptake, fatty acid synthesis, and fatty acid incorporation into lipids within the adipocytes (Getty-Kaushik et al., Obesity 2006;14(7):1124–1131). GIPR knockout mice (Gipr- / -) are resistant to high fat diet-induced weight gain and insulin resistance (Miyawaki et al., Nature Med. 2002;8:738-742). SKL-14959 is a small molecule antagonist of GIPR. Studies in mice found that SKL- 25 14959 suppressed weight gain and lipid deposit in the liver and the muscle (Nakamura et al., Obesity Science & Practice 2018;4(2):194-203). The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030 (Wild et al., Diabetes Care 2004:27(3):1047-1053). Furthermore, approximately 13% of the world’s adult population (11% of men and 15% of women) were obese in 2016, and the worldwide30 prevalence of obesity nearly tripled between 1975 and 2016 (source: World Health Organization). AMG133, which is a bispecific antibody-peptide GIPR antagonist / GLP-1 agonist, has entered clinical trials (see e.g. NCT05056246, NCT06352892, NCT05669599 and NCT04478708). WO2024 / 214038 discloses compounds which are said to have GIPR antagonist activity. However, to date no antagonists of GIPR, let alone any small molecule antagonists of GIPR, have been approved for 35 therapeutic use. Therefore, there remains a need to develop antagonists of GIPR which may be useful in the treatment of disorders such as obesity and related co-morbidities. 1 201369 Summary of the Specification In afirst aspect, the specification provides a compound of formula (I-X): , wherein: 5 R1is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by: 1) one or more groups independently selected from OH, NR1bR1c, C(O)OR1a, C(O)NR1bR1c, NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; 10 R1ais H, C1-6alkyl or C1-6haloalkyl; R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl; R1dis H, C1-6alkyl or C1-6haloalkyl; 15 R1eis C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein when present in R1, each C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl may be independently optionally substituted by 20 one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2; R2is C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl or phenyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by one 25 C3-6cycloalkyl or phenyl; wherein when present in R2, each C3-6cycloalkyl and phenyl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X1is N or CR10, and R10is H, halo, CN, C1-6alkyl or C1-6haloalkyl; 30 X2is N or CR11, and R11is H, halo, CN, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, phenyl or 5-6 membered heteroaryl; wherein said C3-6cycloalkyl, phenyl or 5-6 membered heteroaryl may each be independently 2 201369 optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X3is N or CR12, and R12is H, halo, CN, C1-6alkyl or C1-6haloalkyl; wherein 0 or 1 of X1, X2and X3is N; 5 R20is H, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl or C2-6alkenyl; wherein said C1-6alkyl or C1-6haloalkyl may each be optionally substituted by one OH or COOH; and wherein said C3-6cycloalkyl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R21is H, C1-6alkyl or C1-6haloalkyl; or 10 R20and R21together with the atom to which they are attached form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl or 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; Z1is CR23R24, O, NR22, S or S(O)2; 15 R22is H, C1-6alkyl, C1-6haloalkyl, CH2C≡CH or C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R23and R24are each independently H or C1-6alkyl; B is group (B1), (B2), (B3), (B4), (B5), (B6) or (B7):20 wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40; m, n, o, p and q are each independently 0, 1 or 2; R30, R31, R32, R33and R34are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, 25 C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O2)NMe2and C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; Y1is N, CH or CR31; 30 Y2is N; 3 201369 Y3is N; Y4is N, CH or CR32; Y5is N; Y6is N; 5 W1and W2are each independently N or CH, provided that when one of W1and W2is N, the other is CH; W3is S or O; R35is H or C1-6alkyl; R40is -A1NR41R42; A1is CH2or C(O); 10 R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which may be optionally substituted by: 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1- 6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl, 3-10 membered heterocycloalkyl and O(C3-15 6cycloalkyl); wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1- 20 6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently 25 selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 306cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH; or a pharmaceutically acceptable salt thereof. In a further aspect, the specification provides a compound of formula (I): 4 201369 , wherein: R1is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by: 5 1) one or more groups independently selected from OH, NR1bR1c, C(O)OR1a, C(O)NR1bR1c, NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or 10 R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl; R1dis H, C1-6alkyl or C1-6haloalkyl; R1eis C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-156cycloalkyl or 3-10 membered heterocycloalkyl; wherein when present in R1, each C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, 20 NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2; R2is C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl or phenyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by one C3-6cycloalkyl or phenyl; wherein when present in R2, each C3-6cycloalkyl and phenyl may be independently25 optionally substituted by one or more groups independently selected from halo, C1- 6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X1is N or CR10, and R10is H, halo, CN, C1-6alkyl or C1-6haloalkyl; X2is N or CR11, and R11is halo, CN, C1-6haloalkyl, C1-6alkoxy, phenyl or 5-6 membered heteroaryl; wherein said phenyl or 5-6 membered heteroaryl may each be independently optionally substituted by one or 30 more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X3is N or CR12, and R12is H, halo, CN, C1-6alkyl or C1-6haloalkyl; wherein 0 or 1 of X1, X2and X3is N; 5 201369 R20is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; wherein said C1-6alkyl or C1-6haloalkyl may each be optionally substituted by one OH or COOH; and wherein said C3-6cycloalkyl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 5 R21is H, C1-6alkyl or C1-6haloalkyl; or R20and R21together with the atom to which they are attached form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl or 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 10 Z1is O, NR22, S or S(O)2; R22is H, C1-6alkyl, C1-6haloalkyl, CH2C≡CH or C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1- 6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; B is group (B1), (B2), (B3), (B4) or (B5):15 w eren eno es the point of attachment to Z1, and denotes the point of attachment to R40; m, n, o, p and q are each independently 0, 1 or 2; R30, R31, R32, R33and R34are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, 20 C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O2)NMe2 and C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; Y1is N, CH or CR31; 25 Y2is N; Y3is N; Y4is N, CH or CR32; Y5is N; Y6is N; 6 201369 R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3- 10 membered heterocycloalkyl which may be optionally substituted by: 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, 5S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl and 3-10 membered heterocycloalkyl;wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-106haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently 15 selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 20 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa; or a pharmaceutically acceptable salt thereof. The specification also provides a compound of formula (I-X) or a pharmaceutically acceptable 25 salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), for use as a medicament. The specification also provides a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), for use in the prophylaxis or treatment of a disorder in which antagonism of GIPR provides a prophylactic or30 therapeutic effect. The specification also provides the use of a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), in the manufacture of a medicament for the prophylaxis or treatment of a disorder in which antagonism of GIPR provides a prophylactic or therapeutic effect. 35 The specification also provides a method of preventing or treating a disorder in which antagonism of GIPR provides a prophylactic or therapeutic effect, comprising administering a compound 7 201369 of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof). The specification also provides a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a 5 pharmaceutically acceptable salt thereof), and at least one pharmaceutically acceptable excipient. The specification also provides a combination comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and a second active agent. The specification also provides a kit comprising a compound of formula (I-X) or a10 pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and instructions for their use in prophylaxis or treatment, such as in the prophylaxis or treatment of the disorders described herein. The specification also provides processes for preparing compounds of formula (I-X) and their pharmaceutically acceptable salts (such as compounds of formula (I) and their pharmaceutically 15 acceptable salts), and intermediates and salts thereof used in their preparation. Detailed Description of the Specification Terms not specifically defined herein should be understood to have the meanings that would be given to them by one of skill in the art in light of the disclosure and the context. As used in the 20 specification, however, unless specified to the contrary, the following terms have the meaning indicated and the following conventions are adhered to. The term “alkyl” as used herein includes straight and branched chain saturated groups containing the specified number of carbon atoms. For example, C1-3alkyl encompasses methyl, ethyl, n- propyl and iso-propyl. 25 The term “haloalkyl” as used herein includes straight chain and branched chain alkyl groups containing the specified number of carbon atoms substituted by one or more halo atoms, such as one or morefluoro atoms. Examples of haloalkyl groups includefluoromethyl, difluoromethyl and trifluoromethyl. The term “alkoxy” as used herein includes straight and branched chain alkoxy groups containing 30 the specified number of carbon atoms. Examples of alkoxy groups include methoxy, ethoxy and propoxy (including n-propoxy and iso-propoxy). The term also extends to alkoxy groups in which the oxygen atom is located within the alkyl chain, for example CH2CH2OCH3or CH2OCH3. The term “haloalkoxy” as used herein includes straight and branched chain alkoxy groups containing the specified number of carbon atoms substituted by one or more halo atoms e.g. one or 35 morefluoro atoms. Examples of haloalkoxy groups include methoxy and ethoxy groups substituted with one to three halo atoms, such as one to threefluoro atoms. 8 201369 The term “halo” as used herein refers to afluorine (fluoro), chlorine (chloro), bromine (bromo), or iodine (iodo). The term “alkenyl” as used herein includes straight and branched chain groups containing the specified number of carbon atoms, and at least one double bond. Examples of alkenyl groups include 5 ethenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and its isomers, 2-hexenyl and its isomers and 2,4- pentadienyl. The term “cycloalkyl” as used herein refers to a fully saturated monocyclic, bicyclic, polycyclic, fused or bridged hydrocarbon ring containing the specified number of carbon atoms. Examples of cycloalkyl groups include the C3-6cycloalkyl groups cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. 10 The term “heteroaryl” as used herein refers to means an aromatic monocyclic ring system containing carbon atoms and at least one heteroatom (such as one to four nitrogen atoms) in the ring structure, and having the specified total number of atoms in the ring structure. For example, 5-6 membered heteroaryl groups include pyrazole, triazole, tetrazole, pyridine, pyrimidine, pyridazine and pyrazine. 15 The term “heterocycloalkyl” as used herein refers to a monocyclic, bicyclic, polycyclic, fused or bridged fully saturated ring containing carbon atoms and at least one heteroatom (for example one O, N, P or S; or for example one N and one O; or for example two N) in the ring structure, and having the specified total number of atoms in the ring structure. For example, 3-10 membered heterocycloalkyl includes groups such as aziridine, azetidine, oxetane, pyrrolidine, tetrahydrofuran, piperidine, 20 morpholine, diazinane, piperazine, azepane, oxepane, 1,4-oxazepane, 2-oxa-5-azabicyclo[4.1.0]heptane, 2-azabicyclo[2.2.1]heptane and 3-oxa-8-azabicyclo[3.2.1]octane. In embodiments where it is stated that “two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl”, it will be understood that such embodiments refer to spirocyclic and spiroheterocyclic ring systems respectively. 25 Examples of such spiro(hetero)cyclic ring systems include: , , , , , where Q represents a heteroatom, such as nitrogen or oxygen. Further examples of such spiro(hetero)cyclic ring systems include: 9 201369 where Q represents a heteroatom, such as nitrogen or oxygen. 5 In embodiments, a compound of formula (I-X) (such as a compound of formula (I)) is provided. In embodiments, a pharmaceutically acceptable salt of a compound of formula (I-X)) (such as a pharmaceutically acceptable salt of a compound of formula (I)) is provided. In embodiments, R1is H. In embodiments, R1is C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R1is C1-6haloalkyl, such as C1-3haloalkyl, such as CHF2or CF3. In embodiments, 10 the C1-6alkyl or C1-6haloalkyl are each independently unsubstituted. In embodiments, the C1-6alkyl or C1-6haloalkyl are each independently substituted by: one or more groups independently selected from OH, NR1bR1c, C(O)OR1a, C(O)NR1bR1c, NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; 15 R1ais H, C1-6alkyl or C1-6haloalkyl; R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3- 10 membered heterocycloalkyl; R1dis H, C1-6alkyl or C1-6haloalkyl; 20 R1eis C1-6alkyl or C1-6haloalkyl; wherein said C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl may each be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, 25 NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, the C1-6alkyl or C1-6haloalkyl are each independently substituted when: 10 201369 two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently 5 selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, the C1-6alkyl or C1-6haloalkyl are each independently substituted by: 1) one or more groups independently selected from OH, NR1bR1c, C(O)OR1a, C(O)NR1bR1c, 10 NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3- 15 10 membered heterocycloalkyl; R1dis H, C1-6alkyl or C1-6haloalkyl; R1eis C1-6alkyl or C1-6haloalkyl; wherein said C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl may each be independently optionally 20 substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2; and 2) two groups on the same atom, together with the atom to which they are attached, 25 form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, 30 NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, the C1-6alkyl or C1-6haloalkyl are each independently substituted by one group selected from OH, NR1bR1c, C(O)OR1a, C(O)NR1bR1c, NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl. In embodiments, the C1-6alkyl or C1-6haloalkyl are each independently substituted by two groups independently selected from OH, NR1bR1c, C(O)OR1a, 35 C(O)NR1bR1c, NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl. 11 201369 In embodiments, at least one group is OH. In embodiments, at least one group is NR1bR1c. In embodiments, R1bis H. In embodiments, R1bis C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R1bis C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2or CF3. In embodiments, R1cis H. In embodiments, R1cis C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R1cis 5 C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2 or CF3. In embodiments, R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl. In embodiments, the 3-10 membered heterocycloalkyl is unsubstituted. In embodiments, the 3-10 membered heterocycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, 10 COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, at least one group is C(O)OR1a. In embodiments, R1ais H. In embodiments, R1ais C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R1ais C1-6haloalkyl, such as C1- 3haloalkyl, for example CHF2 or CF3. In embodiments, C(O)OR1ais C(O)OH. In embodiments, at least one group is C(O)NR1bR1c. In embodiments, R1bis H. In embodiments, 15 R1bis C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R1bis C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2or CF3. In embodiments, R1cis H. In embodiments, R1cis C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R1cis C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2or CF3. In embodiments, R1bis H and R1cis methyl. In embodiments, R1band R1care both methyl. 20 In embodiments, R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl, such as a 5-membered heterocycloalkyl, such as a 6-membered heterocycloalkyl. In embodiments, the 3-10 membered heterocycloalkyl is pyrrolidinyl or morpholinyl. In embodiments, the 3-10 membered heterocycloalkyl is unsubstituted. In embodiments, the 3-10 membered heterocycloalkyl is substituted by one or more (such as one or two, e.g. one) groups 25 independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, at least one group is NR1dC(O)R1e. In embodiments, R1dis H. In embodiments, R1dis C1-6alkyl, such as C1-3alkyl, such as methyl or ethyl. In embodiments, R1dis C1-6haloalkyl, such as C1- 303haloalkyl, such as CHF2or CF3. In embodiments, R1eis C1-6alkyl, such as C1-3alkyl, such as methyl or ethyl. In embodiments, R1eis C1-6haloalkyl, such as C1-3haloalkyl, such as CHF2or CF3. In embodiments, at least one group is C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two, e.g. one) groups 35 independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, 12 201369 NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, at least one group is 3-10 membered heterocycloalkyl. In embodiments, the 3- 10 membered heterocycloalkyl is unsubstituted. In embodiments, the 3-10 membered heterocycloalkyl 5 is substituted by one or more (such as one or two, e.g. one) group independently selected from halo, C1- 6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, at least one group is phenyl. In embodiments, the phenyl is unsubstituted. In embodiments, the phenyl is substituted by one or more (such as one or two, e.g. one) groups 10 independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, at least one group is 5-6 membered heteroaryl, such as a 5-membered heteroaryl. In embodiments, the 5-6 membered heteroaryl is tetrazolyl or triazolyl, such as tetrazolyl. In 15 embodiments, the 5-6 membered heteroaryl is unsubstituted. In embodiments, the 5-6 membered heteroaryl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, the 5-6 membered heteroaryl is substituted by one C1-6alkyl, such as one methyl. 20 In embodiments, two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, 25 C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, two groups on the same atom, together with the atom to which they are attached, form a form a 3-10 membered heterocycloalkyl. In embodiments, the 3-10 membered heterocycloalkyl is unsubstituted. In embodiments, the 3-10 membered heterocycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1- 306haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. In embodiments, R1is C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1- 35 6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2. 13 201369 In embodiments, R1is selected from H, methyl, ethyl, cyclopropyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl. 5 In embodiments, R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl. In embodiments, R1is selected from H, methyl, ethyl, cyclopropyl, and C1-6alkyl substituted by 10 one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl. In embodiments, R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl. 15 In embodiments, R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one group selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl. In embodiments, R1is C1-6alkyl substituted by one C(O)OR1a(such as C(O)OH) and two groups on 20 the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl (such as cyclopropyl). In embodiments, R1is selected from:25 14 201369 wherein denotes the point of attachment to the (aza)quinazolinone moiety. In embodiments, R1is selected from: 5 wherein denotes the point of attachment to the (aza)quinazolinone moiety. In embodiments, R1is selected from:10 wherein denotes the point of attachment to the (aza)quinazolinone moiety. In embodiments, R2is C1-6alkyl, such as C1-3alkyl, for example as methyl, ethyl or iso-propyl e.g. 15 methyl. In embodiments, R2is C1-6alkoxy, such as OMe or OEt, for example OMe. In embodiments, R2is 15 201369 C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2 or CF3. In embodiments, R2is C1-6haloalkoxy, such as C1-3haloalkoxy, for example OCHF2or OCF3. In embodiments, the C1-6alkyl or C1-6haloalkyl are each independently unsubstituted. In embodiments, the C1-6alkyl or C1-6haloalkyl are each independently substituted by one C3-6cycloalkyl 5 (such as cyclopropyl, cyclobutyl or cyclopentyl e.g. cyclopropyl) or phenyl. In embodiments, the C1-6alkyl or C1-6haloalkyl are each independently substituted by one C3- 6cycloalkyl (such as cyclopropyl, cyclobutyl or cyclopentyl e.g. cyclopropyl). In embodiments, the C3- 6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-106haloalkoxy. In embodiments, the C1-6alkyl or C1-6haloalkyl are each independently substituted by one phenyl. In embodiments, the phenyl is unsubstituted. In embodiments, the phenyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. 15 In embodiments, R2is C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. In embodiments, R2is phenyl. In embodiments, the phenyl is unsubstituted. In embodiments, 20 the phenyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. In embodiments, R2is C1-6alkyl, C1-6alkoxy or C3-6cycloalkyl. In embodiments, R2is C1-6alkyl or C3- 6cycloalkyl. In embodiments, R2is methyl, ethyl, iso-propyl, OMe or cyclopropyl. In embodiments, R2is methyl, ethyl or cyclopropyl. In embodiments, R2is methyl. 25 In embodiments, X1is N. In embodiments, X1is CR10. In embodiments, R10is H. In embodiments, R10is halo, such as F, Cl or Br. In embodiments, R10is F. In embodiments, R10is CN. In embodiments, R10is C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R10is C1-6haloalkyl, such as C1- 3haloalkyl, for example CHF2 or CF3. In embodiments, X2is N. In embodiments, X2is CR11. In embodiments, R11is H. In embodiments,30 R11is halo, such as F, Cl or Br. In embodiments, R11is Cl. In embodiments, R11is CN. In embodiments, R11is C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2or CF3, e.g. CF3. In embodiments, R11is C1-6alkoxy, such as C1-3alkoxy, for example OMe or OEt. In embodiments, R11is C3-6cycloalkyl, such as cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two, e.g. one) group(s) independently selected from halo, C1-6alkyl, C1- 35 6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. In embodiments, R11is phenyl. In embodiments, the phenyl is unsubstituted. In embodiments, the phenyl is substituted by one or more (such as one or two, e.g. one) 16 201369 group(s) independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. In embodiments, the phenyl is substituted by one halo, such as one F. In embodiments, R11is 5-6 membered heteroaryl. In embodiments, the 5-6 membered heteroaryl is unsubstituted. In embodiments, the 5-6 membered heteroaryl is substituted by one or 5 more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1- 6alkoxy and C1-6haloalkoxy. In embodiments, the 5-6 membered heteroaryl is pyridyl. In embodiments, X2is CR11and R11is selected from halo (such as Cl), C1-6haloalkyl (such as CF3), cyclopropyl, phenyl substituted by one halo (such as one F) and pyridyl. In embodiments, X2is CR11and R11is selected from halo (such as Cl), C1-6haloalkyl (such as CF3) and phenyl substituted by one halo (such 10 as one F). In embodiments, X2is CR11and R11is selected from halo (such as Cl) and C1-6haloalkyl (such as CF3). In embodiments, X3is N. In embodiments, X3is CR12. In embodiments, R12is H. In embodiments, R12is halo, such as F, Cl or Br. In embodiments, R12is F. In embodiments, R12is CN. In embodiments, R12is C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R12is C1-6haloalkyl, such as C1- 15 3haloalkyl, for example CHF2 or CF3. In embodiments, X1is CR10, X2is CR11and X3is CR12. In embodiments, X1is N, X2is CR11and X3is CR12. In embodiments, X1is CR10, X2is N and X3is CR12. In embodiments, X1is CR10, X2is CR11and X3is N. In embodiments, X1 is CH, X2 is C-CF3 and X3 is CH. In embodiments, X1 is CH, X2 is C-Cl and X3 isCH. In embodiments, X1is CH, X2is C-Cl and X3is N. In embodiments, X1is C-F, X2is C-CF3 and X3is CH. In 20 embodiments, X1is CH, X2is CR11, R11is phenyl substituted by one halo (such as one F) and X3is CH. In embodiments, X1is CH, X2is C-CF3 and X3is C-F. In embodiments, X1is N, X2is C-CF3 and X3is CH. In embodiments, X1is N, X2is C-CF3 and X3is C-Me. In embodiments, X1is CH, X2is C-CF3 and X3is N. In embodiments, X1is CH, X2is C-Br and X3is CH. In embodiments, X1is CH, X2is CR11, R11is pyridyl and X3is CH. In embodiments, X1is CH, X2is C-Cl and X3is N. In embodiments, X1is C-F, X2is C-Cl and X3is CH. In 25 embodiments, X1is C-Me, X2is C-CF3and X3is CH. In embodiments, X1is C-CN, X2is CF3and X3is CH. In embodiments, X1is CH, X2is C-cyclopropyl and X3is CH. In embodiments, X1is CH, X2is C-F and X3is CH. In embodiments, X1is CH, X2is C-Cl and X3is C-Me. In embodiments, R20is H. In embodiments, R20is C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R20is C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2 or CF3. In 30 embodiments, the C1-6alkyl or C1-6haloalkyl are each independently unsubstituted. In embodiments, the C1-6alkyl or C1-6haloalkyl are each independently substituted by one OH or COOH. In embodiments, R20is CH2CH2OH. In embodiments, R20is CH2COOH. In embodiments, R20is C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is35 substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1- 6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. 17 201369 In embodiments, R20is C2-6alkenyl, such as ethenyl. In embodiments, R20is selected from C1-6alkyl optionally substituted by one OH or COOH, C1-6haloalkyl, C2-6alkenyl and C3-6cycloalkyl, such as C1-6alkyl optionally substituted by one OH, C1-6haloalkyl and C3-6cycloalkyl. In embodiments, R20is selected from methyl, ethyl, ethenyl, CF3, CH2CH2OH, CH2COOH 5 and cyclopropyl, such as methyl, ethyl, CF3, CH2CH2OH and cyclopropyl. In embodiments, R21is H. In embodiments, R21is C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R20is C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2 or CF3. In embodiments, R20and R21together with the atom to which they are attached form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl. 10 In embodiments, R20and R21together with the atom to which they are attached form a C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1- 6haloalkoxy. 15 In embodiments, R20and R21together with the atom to which they are attached form a 3-10 membered heterocycloalkyl. In embodiments, the 3-10 membered heterocycloalkyl is unsubstituted. In embodiments, the 3-10 membered heterocycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. In embodiments, R20is methyl and R21is H. In embodiments, R20is ethyl and R21is H. In 20 embodiments, R20is CH2CH2OH and R21is H. In embodiments, R20is CH2COOH and R21is H. In embodiments, R20is CF3 and R21is H. In embodiments. R20is cyclopropyl and R21is H. In embodiments, R20is H and R21is H. in embodiments, R20is ethenyl and R21is H. In embodiments, R20and R21have the following stereochemistry: , 25 wherein denotes the point of attachment to the (aza)quinazolinone moiety, and denotes the point of attachment to Z1. In embodiments, R20and R21have the following stereochemistry: , 18 201369 wherein denotes the point of attachment to the (aza)quinazolinone moiety, and denotes the point of attachment to Z1. In embodiments, Z1is CR23R24. In embodiments, R23is H. In embodiments, R23is C1-6alkyl, such as ethyl or methyl. In embodiments, R24is H. In embodiments, R24is C1-6alkyl, such as methyl or ethyl. In 5 embodiments, Z1is CH2. In embodiments, Z1is O. In embodiments, Z1is NR22. In embodiments, R22is H. In embodiments, R22is C1-6alkyl, such as C1- 3alkyl, such as methyl or ethyl e.g. methyl. In embodiments, R22is C1-6haloalkyl, such as C1-3haloalkyl, such as CHF2or CF3. In embodiments, R22is CH2C≡CH. In embodiments, R22is C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is 10 unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. In embodiments, R22is selected from H and C1-6alkyl, such as C1-3alkyl, such as methyl or ethyl e.g. methyl. In embodiments, Z1is S. In embodiments, Z1is S(O)2. 15 In embodiments, B is group (B1): wherein denotes the point of attachment to Z1, denotes the point of attachment to R40. In embodiments, m is 0. In embodiments, m is 1. In embodiments, m is 2. In embodiments, R30is halo, such as Cl or F. In embodiments, R30is CN. In embodiments, R30is C1- 20 6alkyl, such as C1-3alkyl, for example methyl or ethyl e.g. methyl. In embodiments, R30is C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2 or CF3 e.g. CF3. In embodiments, R30is C1-6alkoxy, such as C1- 3alkoxy, for example OMe or OEt e.g. OMe. In embodiments, R30is C1-6haloalkoxy, such as C1-3haloalkoxy, for example OCHF2or OCF3e.g. OCF3. In embodiments, R30is NH2. In embodiments, R30is NHMe. In embodiments, R30is NMe2. In embodiments, R30is NHC(O)Me. In embodiments, R30is COOH. In 25 embodiments, R30is C(O)NH2. In embodiments, R30is C(O)NHMe. In embodiments, R30is C(O)NMe2. In embodiments, R30is NHS(O)2Me. In embodiments, R30is NHS(O)2CF3. In embodiments, R30is S(O)2NH2. In embodiments, R30is S(O)2NHMe. In embodiments, R30is S(O2)NMe2. In embodiments, R30is C3- 6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as30 one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. 19 201369 In embodiments, m is 1 or 2 and each R30is independently selected from halo (such as F or Cl), CN, C1-6alkyl (such as methyl), C1-6haloalkyl (such as CF3), C1-6alkoxy (such as OMe), C1-6haloalkoxy (such as OCF3) and C3-6cycloalkyl (such as cyclopropyl). In embodiments, m is 1 or 2 and each R30is independently selected from halo (such as F or Cl), CN, C1-6alkyl (such as methyl), C1-6alkoxy (such as 5 OMe), and C3-6cycloalkyl (such as cyclopropyl). In embodiments, m is 1 and R30is selected from halo (such as F or Cl), CN, C1-6alkyl (such as methyl), C1-6haloalkyl (such as CF3), C1-6alkoxy (such as OMe), C1-6haloalkoxy (such as OCF3), and C3- 6cycloalkyl (such as cyclopropyl). In embodiments, m is 1 and R30is selected from halo (such as F or Cl), CN, C1-6alkyl (such as methyl), C1-6alkoxy (such as OMe), and C3-6cycloalkyl. 10 In embodiments, m is 2, one R30is halo (such as F) and the other R30is C1-6alkoxy (such as OMe). In embodiment, m is 2 and each R30is halo (such as F or Cl). In embodiments, group (B1) is group (B1a), (B1b), (B1c) or (B1d): In embodiments, group (B1) is group (B1a), (B1b) or (B1c):15 wherein R30is as defined herein. In embodiments, group (B1) is group (B1a). In embodiments, group (B1) is group (B1b). In embodiments, group (B1) is group (B1c). In embodiments, group (B1) is group (B1d). In embodiments, group (B1) is selected from: 20 20 201369 In embodiments, group (B1) is selected from: , 5 wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40. In embodiments, Y1is N. In embodiments, Y1is CH. In embodiments, Y1is CR31. In embodiments, n is 0. In embodiments, n is 1. In embodiments, n is 2. 10 For the avoidance of doubt, the value of n is independent of Y1being N, CH or CR31. As an illustrative example, n may be 2 and Y1may be CR31. As a further illustrative example, n may be 0 and Y1may be CR31. In embodiments, R31is halo, such as Cl or F. In embodiments, R31is CN. In embodiments, R31is C1- 6alkyl, such as C1-3alkyl, for example methyl or ethyl e.g. methyl. In embodiments, R31is C1-6haloalkyl,15 such as C1-3haloalkyl, for example CHF2 or CF3 e.g. CF3. In embodiments, R31is C1-6alkoxy, such as C1- 3alkoxy, for example OMe or OEt e.g. OMe. In embodiments, R31is C1-6haloalkoxy, such as C1-3haloalkoxy, for example OCHF2or OCF3e.g. OCF3. In embodiments, R31is NH2. In embodiments, R31is NHMe. In embodiments, R31is NMe2. In embodiments, R31is NHC(O)Me. In embodiments, R31is COOH. In embodiments, R31is C(O)NH2. In embodiments, R31is C(O)NHMe. In embodiments, R31is C(O)NMe2. In 20 embodiments, R31is NHS(O)2Me. In embodiments, R31is NHS(O)2CF3. In embodiments, R31is S(O)2NH2. In embodiments, R31 is S(O)2NHMe. In embodiments, R31 is S(O2)NMe2. In embodiments, R31 is C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as 21 201369 one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1- 6haloalkoxy. In embodiments, n is 1 and R31is selected from halo (e.g. F), CN and C1-6alkoxy (e.g. OMe). In embodiments, n is 0, Y1is CR31and R31is selected from halo (e.g. F), CN and C1-6alkoxy (e.g. OMe). In 5 embodiments, Y1is CH and n is 0. In embodiments, Y1is N and n is 0. In embodiments, Y1is C-F and n is 0. In embodiments, group (B2) is group (B2a), (B2b) or (B2c): wherein R31is as defined herein. 10 In embodiments, group (B2) is group (B2a). In embodiments, group (B2) is group (B2b). In embodiments, group (B2) is group (B2c). In embodiments, group (B2) is selected from: 15 wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40. In embodiments, Y4is N. In embodiments, Y4is CH. In embodiments, Y4is CR32. 20 In embodiments, o is 0. In embodiments, o is 1. In embodiments, o is 2. In embodiments, Y4is CH and o is 1. For the avoidance of doubt, the value of o is independent of Y4being N, CH or CR32. As an illustrative example, o may be 2 and Y4may be CR32. As a further illustrative example, o may be 0 and Y4may be CR32. 22 201369 In embodiments, R32is halo, such as Cl or F. In embodiments, R32is CN. In embodiments, R32is C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl e.g. methyl. In embodiments, R32is C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2or CF3e.g. CF3. In embodiments, R32is C1-6alkoxy, such as C1-3alkoxy, for example OMe or OEt e.g. OMe. In embodiments, R32is C1-6haloalkoxy, such as C1-3haloalkoxy, 5 for example OCHF2 or OCF3 e.g. OCF3. In embodiments, R32is NH2. In embodiments, R32is NHMe. In embodiments, R32is NMe2. In embodiments, R32is NHC(O)Me. In embodiments, R32is COOH. In embodiments, R32is C(O)NH2. In embodiments, R32is C(O)NHMe. In embodiments, R32is C(O)NMe2. In embodiments, R32is NHS(O)2Me. In embodiments, R32is NHS(O)2CF3. In embodiments, R32is S(O)2NH2. In embodiments, R32is S(O)2NHMe. In embodiments, R32is S(O2)NMe2. In embodiments, R32is C3-106cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1- 6haloalkoxy. In embodiments, o is 1 and R32is selected from halo (such as F), C1-6alkyl (such as methyl) and C3-15 6cycloalkyl (such as cyclopropyl). In embodiments, o is 1 and R32is selected from halo (such as F) and C3- 6cycloalkyl. In embodiments, group (B3) is group (B3a), group (B3b) or group (B3c): wherein R32is as defined herein. 20 In embodiments, group (B3) is group (B3a). In embodiments, group (B3) is group (B3b). In embodiments, group (B3) is group (B3c). In embodiments, group (B3) is selected from: 25 In embodiments, group (B3) is selected from: 23 201369 5 wherein denotes the point of attachment to Z1, denotes the point of attachment to R40. In embodiments, p is 0. In embodiments, p is 1. In embodiments, p is 2. In embodiments, R33is halo, such as Cl or F. In embodiments, R33is CN. In embodiments, R33is C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl e.g. methyl. In embodiments, R33is C1-6haloalkyl,10 such as C1-3haloalkyl, for example CHF2or CF3e.g. CF3. In embodiments, R33is C1-6alkoxy, such as C1-3alkoxy, for example OMe or OEt e.g. OMe. In embodiments, R33is C1-6haloalkoxy, such as C1-3haloalkoxy, for example OCHF2 or OCF3 e.g. OCF3. In embodiments, R33is NH2. In embodiments, R33is NHMe. In embodiments, R33is NMe2. In embodiments, R33is NHC(O)Me. In embodiments, R33is COOH. In embodiments, R33is C(O)NH2. In embodiments, R33is C(O)NHMe. In embodiments, R33is C(O)NMe2. In 15 embodiments, R33is NHS(O)2Me. In embodiments, R33is NHS(O)2CF3. In embodiments, R33is S(O)2NH2. In embodiments, R33is S(O)2NHMe. In embodiments, R33is S(O2)NMe2. In embodiments, R33is C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1- 20 6haloalkoxy. In embodiments, group (B4) is: . In embodiments, B is group (B5): 24 201369 , wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40. In embodiments, q is 0. In embodiments, q is 1 or 2, such as q is 1. In embodiments, R34is halo, such as Cl or F. In embodiments, R34is CN. In embodiments, R34is C1- 56alkyl, such as C1-3alkyl, for example methyl or ethyl e.g. methyl. In embodiments, R34is C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2or CF3e.g. CF3. In embodiments, R34is C1-6alkoxy, such as C1-3alkoxy, for example OMe or OEt e.g. OMe. In embodiments, R34is C1-6haloalkoxy, such as C1-3haloalkoxy, for example OCHF2 or OCF3 e.g. OCF3. In embodiments, R34is NH2. In embodiments, R34is NHMe. In embodiments, R34is NMe2. In embodiments, R34is NHC(O)Me. In embodiments, R34is COOH. In 10 embodiments, R34is C(O)NH2. In embodiments, R34is C(O)NHMe. In embodiments, R34is C(O)NMe2. In embodiments, R34is NHS(O)2Me. In embodiments, R34is NHS(O)2CF3. In embodiments, R34is S(O)2NH2. In embodiments, R34is S(O)2NHMe. In embodiments, R34is S(O2)NMe2. In embodiments, R34is C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as15 one or two, e.g. one) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1- 6haloalkoxy. In embodiments, B is group (B6): In embodiments, W1is N and W2is CH. In embodiments, W1is CH and W2is N. In embodiments, 20 W1is CH and W2is CH. In embodiments, W3is S. In embodiments, W3is O. In embodiments, group (B6) is selected from: . 25 In embodiments, B is group (B7): 25 201369 In embodiments, R35is H. In embodiments, R35is C1-6alkyl, such as methyl. In embodiments, group (B7) is: . 5 In embodiments, B is group (B1), (B2) or (B3): ,wherein R30, m, Y1, Y2, R31, n, Y3, Y4, o and R32are as defined herein. In embodiments, R40is -A1NR41R42. In embodiments, A1is CH2. In embodiments, A1is C(O). In embodiments, R40is -CH2NR41R42, and R41and R42together with the nitrogen atom to which10 they are attached form a 3-10 membered heterocycloalkyl. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl. In embodiments, the 3-10 membered heterocycloalkyl is a 5- or 6-membered heterocycloalkyl, for example a 6-membered heterocycloalkyl. In embodiments, the 3-10 membered heterocycloalkyl is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, hexahydro-1H-furo[3,4-15 c]pyrrolyl, 2-oxa-5-azabicyclo[4.1.0]heptanyl, 2-azabicyclo[2.2.1]heptanyl, 3-oxa-8- zabicyclo[3.2.1]octanyl, 1,4-oxazapenyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 6-oxa-3- azabicyclo[3.1.1]heptanyl or (1R,5S)-8-oxa-3-azabicyclo[3.2.1]octanyl, such as azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, hexahydro-1H-furo[3,4-c]pyrrolyl, 2-oxa-5- azabicyclo[4.1.0]heptanyl, 2-azabicyclo[2.2.1]heptanyl, 3-oxa-8-zabicyclo[3.2.1]octanyl or 1,4- 20 oxazapenyl, such as piperidinyl, piperazinyl or morpholinyl. In embodiments, the 3-10 membered heterocycloalkyl is morpholinyl. In embodiments, the 3-10 membered heterocycloalkyl is unsubstituted. In embodiments, the 3-10 membered heterocycloalkyl is substituted by: one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-256haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl, 3-10 memberedheterocycloalkyl and O(C3-6cycloalkyl); wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered 26 201369 heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; 5 R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41acis H, C1-6alkyl or C1-6haloalkyl; 10 R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl. In embodiments, the 3-10 membered heterocycloalkyl is substituted by: one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1- 6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me,15 NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl and 3-10 memberedheterocycloalkyl; wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or20 more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1- 6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may 25 each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl. 30 In embodiments, the 3-10 membered heterocycloalkyl is substituted when two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH. In embodiments, the 3-10 membered heterocycloalkyl is substituted when two groups on the 27 201369 same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa. In embodiments, the 3-10 membered heterocycloalkyl is substituted by: 5 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1- 6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl, 3-10 memberedheterocycloalkyl and O(C3-6cycloalkyl); wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally 10 substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1- 6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; 15 R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41acis H, C1-6alkyl or C1-6haloalkyl; 20 R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected 25 from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH. In embodiments, the 3-10 membered heterocycloalkyl is substituted by: 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1- 6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl and 3-10 membered30 heterocycloalkyl; wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1- 35 6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; 28 201369 R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 5 R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally 10 substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa. In embodiments, the 3-10 membered heterocycloalkyl is substituted by one group selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl, 3-10 membered15 heterocycloalkyl and O(C3-6cycloalkyl); and / or two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH. In embodiments, the 3-10 membered heterocycloalkyl is substituted by one group selected from 20 halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl and 3-10 memberedheterocycloalkyl; and / or two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl 25 and C(O)R41aa. In embodiments, the 3-10 membered heterocycloalkyl is substituted by two groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl,3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); and / or two groups on the same atom, together 30 with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH. In embodiments, the 3-10 membered heterocycloalkyl is substituted by two groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa,35 NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyland 3-10 membered heterocycloalkyl; and / or two groups on the same atom, together with the atom to 29 201369 which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa. In embodiments, the 3-10 membered heterocycloalkyl is substituted by three groups 5 independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl,3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); and / or two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected 10 from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH. In embodiments, the 3-10 membered heterocycloalkyl is substituted by three groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyland 3-10 membered heterocycloalkyl; and / or two groups on the same atom, together with the atom to 15 which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa. In embodiments, at least one group is halo, such as Cl or F, for example F. In embodiments, at least one group is CN. In embodiments, at least one group is OH. In embodiments, at least one group is 20 =O. In embodiments, at least one group is C1-6alkyl, such as C1-3alkyl, for example iso-propyl, methyl or ethyl, for example methyl or ethyl. In embodiments, the C1-6alkyl is unsubstituted. In embodiments, the C1-6alkyl is substituted by one OH, such as the substituted C1-6alkyl group is CH2CH2OH, CH2OH or C(Me)2OH, for example CH2OH or C(Me)2OH. In embodiments, at least one group is C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2or CF3. In embodiments, the C1-6haloalkyl is unsubstituted. In 25 embodiments, at least one group is C1-6alkoxy, such as CH2OMe, OEt or OMe, such as OEt or OMe, for example OMe. In embodiments, at least one group is C1-6haloalkoxy, such as OCHF2 or OCF3, for example OCF3. In embodiments, at least one group is C(O)R41aa. In embodiments, R41aais OH. In embodiments, R41aais C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl e.g. methyl. In embodiments, R41aais C1- 306alkoxy, such as C1-4alkoxy, for example OMe, OEt, OiPr or OtBu. In embodiments, R41aais C1-6haloalkoxy, such as C1-3haloalkoxy, for example OCHF2or OCF3. In embodiments, R41aais NR41aeR41af. In embodiments, R41aeis H. In embodiments, R41aeis C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R41aeis C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2 or CF3. In embodiments, R41afis H. In embodiments, R41afis C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, 35 R41afis C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2 or CF3. In embodiments, at least one group is C(O)Me. In embodiments, at least one group is CO2H. In embodiments, at least one group is C(O)Ot-Bu. 30 201369 In embodiments, at least one group is NR41abR41ac. In embodiments, R41abis H. In embodiments, R41abis C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R41abis C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2or CF3. In embodiments, R41abis C(O)R41ad. In embodiments, R41adis C1-6alkyl, such as C1-3alkyl, for 5 example methyl or ethyl. In embodiments, R41adis C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2 or CF3. In embodiments, R41adis C1-6alkoxy, such as C1-4alkoxy, for example OMe, OEt, OiPr or OtBu. In embodiments, R41adis C1-6haloalkoxy, such as C1-3haloalkoxy, for example OCHF2 or OCF3. In embodiments, R41abis C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-106cycloalkyl is substituted by one or more (such as one or two e.g. one) groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. In embodiments, R41abis 3-10 membered heterocycloalkyl, such as 3-7 membered heterocycloalkyl, for example oxetanyl. In embodiments, the 3-10 membered heterocycloalkyl is unsubstituted. In embodiments, the 3-10 membered heterocycloalkyl is substituted by one or more15 (such as one or two e.g. one) groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1- 6alkoxy and C1-6haloalkoxy. In embodiments, R41acis H. In embodiments, R41acis C1-6alkyl, such as C1-3alkyl, for example methyl or ethyl. In embodiments, R41acis C1-6haloalkyl, such as C1-3haloalkyl, for example CHF2or CF3. In embodiments, at least one group is NH(oxetanyl). In embodiments, at least one group is 20 NHC(O)Me. In embodiments, at least one group is NHC(O)Ot-Bu. In embodiments, at least one group is NMeC(O)Ot-Bu. In embodiments, at least one group is S(O)2Me. In embodiments, at least one group is S(O)2CF3. In embodiments, at least one group is NHS(O)2Me. In embodiments, at least one group is NHS(O)2CF3. In embodiments, at least one group is S(O)2NH2. In embodiments, at least one group is S(O)2NHMe. 25 In embodiments, at least one group is S(O)2NMe2. In embodiments, at least one group is C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two e.g. one) groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. In 30 embodiments, the C3-6cycloalkyl is substituted by one OH. In embodiments, at least one group is 3-10 membered heterocycloalkyl, such as 3-7 membered heterocycloalkyl, for example oxetanyl. In embodiments, the 3-10 membered heterocycloalkyl is unsubstituted. In embodiments, the 3-10 membered heterocycloalkyl is substituted by one or more (such as one or two e.g. one) groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1- 35 6alkoxy and C1-6haloalkoxy. 31 201369 In embodiments, at least one group is O(C3-6cycloalkyl), such as O(cyclopropyl). In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one or two e.g. one) groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy. 5 In embodiments, two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl. In embodiments, the C3-6cycloalkyl is unsubstituted. In embodiments, the C3-6cycloalkyl is substituted by one or more (such as one, two or three e.g. one or two) groups independently selected from halo, C1- 6alkyl, C1-6haloalkyl and C(O)R41aa. In embodiments, two groups on the same atom, together with the 10 atom to which they are attached, form a C3-6cycloalkyl (such as cyclopropyl or cyclobutyl) which is substituted by two F groups. In embodiments, two groups on the same atom, together with the atom to which they are attached, form a 3-10 membered heterocycloalkyl, such as a 3-7 membered heterocycloalkyl, for example azetidinyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl, for example oxetanyl or 15 tetrahydrofuranyl. In embodiments, the 3-10 membered heterocycloalkyl is unsubstituted. In embodiments, the 3-10 membered heterocycloalkyl is substituted by one or more (such as one, two or three e.g. one or two) groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH, such as halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which 20 they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such as one, two, three or four, e.g. one or two) groups independently selected from CN, halo, OH, =O, C1- 6alkyl optionally substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3- 6cycloalkyl optionally substituted by one OH, 3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl 25 or 3-10 membered heterocycloalkyl, each of which may be optionally substituted by one or two groups independently selected from F, CF3, OH and C(O)Me. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such as one, two, three or four, e.g. one or two) groups independently selected from halo, OH, C1-6alkyl 30 optionally substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C(O)R41aa, C3-6cycloalkyl optionally substituted by one OH, and 3-10 membered heterocycloalkyl; or 2) two groups on the same atom, together with the atom to which they are attached, form a 3-10 membered heterocycloalkyl. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such 35 as one, two, three or four e.g. one or two) groups independently selected from CN, F, =O, OH, methyl, iso-propyl, CH2OH, CH2CH2OH, C(Me)2OH, CF3, OMe, CH2OMe, OCF3, C(O)Me, cyclopropyl substituted by 32 201369 one OH, oxetanyl, CO2H, C(O)Ot-Bu, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu and O(cyclopropyl); or 2) two groups on the same atom, together with the atom to which they are attached, form a cyclopropyl, cyclobutyl, azetidinyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl, each of which may be optionally substituted by one or two groups selected from F, CF3, OH and C(O)Me. 5 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such as one, two, three or four e.g. one or two) groups independently selected from F, OH, methyl, CH2OH, C(Me)2OH, CF3, OMe, C(O)Me, cyclopropyl substituted by one OH, and oxetanyl; or 2) two groups on the same atom, together with the atom to which they are attached, form an oxetanyl. 10 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such as one, two, three or four, e.g. one or two) groups independently selected from CN, halo, OH, =O, C1- 6alkyl optionally substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3- 6cycloalkyl optionally substituted by one OH, 3-10 membered heterocycloalkyl and O(C3-6cycloalkyl);15 and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be optionally substituted by one or two groups independently selected from F, CF3, OH and C(O)Me. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such 20 as one, two, three or four e.g. one or two) groups independently selected from CN, F, =O, OH, methyl, iso-propyl, CH2OH, CH2CH2OH, C(Me)2OH, CF3, OMe, CH2OMe, OCF3, C(O)Me, cyclopropyl substituted by one OH, oxetanyl, CO2H, C(O)Ot-Bu, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu and O(cyclopropyl); and / or 2) two groups on the same atom, together with the atom to which they are attached, form a cyclopropyl, cyclobutyl, azetidinyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl, 25 each of which may be optionally substituted by one or two groups selected from F, CF3, OH and C(O)Me. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: wherein: 30 r is 0, 1 or 2; each R43is independently halo, C1-3alkyl optionally substituted by one OH, C1-3haloalkyl, C1-3alkoxy, CO2H or NHC(O)Ot-Bu; or two R43together with the carbon atom to which they are both attached form a C3- 33 201369 6cycloalkyl or 3-7 membered heterocycloalkyl, each of which may be optionally substituted by one or two groups independently selected from F, CF3, OH and C(O)Me; each s is independently 0, 1, 2, 3 or 4; each R44is independently selected from CN, OH, =O, halo, C1-3alkyl optionally substituted by one OH, C1-5 3alkoxy, C1-3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, 3-7 membered heterocycloalkyl, CO2H, C(O)Me, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu, CO2H and O(C3-6cycloalkyl); or two R44together with the carbon atom to which they are both attached form a C3-6cycloalkyl or 3-7 membered heterocycloalkyl, each of which may be optionally substituted by one or two halo; J is S(O)2, NR45or O; and 10 R45is H, C(O)C1-3alkyl, C(O)C1-6alkoxy, C1-3alkyl optionally substituted by one OH or oxetanyl. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: wherein: 15 r is 0, 1 or 2; each R43is independently C1-3alkyl optionally substituted by one OH, C1-3haloalkyl or C1-3alkoxy; or two R43together with the carbon atom to which they are both attached form a 3-7 membered heterocycloalkyl; each s is independently 0, 1, 2 or 3; 20 each R44is independently selected from OH, halo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, and 3-7 membered heterocycloalkyl; or two R44together with the carbon atom to which they are both attached form a C3-6cycloalkyl or 3-7 membered heterocycloalkyl; J is NR45or O; R45is H or C(O)C1-3alkyl. 25 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: wherein: r is 0, 1 or 2; 34 201369 each R43is independently C1-3alkyl optionally substituted by one OH, C1-3haloalkyl or C1-3alkoxy; or two R43together with the carbon atom to which they are both attached form a 3-7 membered heterocycloalkyl; each s is independently 0, 1, 2 or 3; 5 each R44is independently selected from OH, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, and 3-7 membered heterocycloalkyl; or two R44together with the carbon atom to which they are both attached form a C3-6cycloalkyl or 3-7 membered heterocycloalkyl; J is NR45or O; R45is H or C(O)C1-3alkyl. 10 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: , wherein r and R43are as defined herein. In embodiments, r is 0. In embodiments, r is 1. In embodiments, R43is C1-3haloalkyl, such as CF3. 15 In embodiments, two R43together with the carbon atom to which they are both attached form a cyclobutyl, oxetanyl or azetidinyl, each of which are substituted by one or two groups selected from F, CF3, OH and C(O)Me. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: 20 , wherein r and R43are as defined herein. In embodiments, r is 0. In embodiments, r is 1. In embodiments, r is 2. In embodiments, each R43is halo, such as F. In embodiments, each R43is C1-3alkyl, such as iso-propyl. In embodiments, R43is C1-3alkyl substituted by one OHR43is C1-3alkyl substituted by one OH. In embodiments, R43is C(Me)2OH or 25 CH2OH. In embodiments, R43is C1-3alkoxy, such as CH2OMe or OMe, such as OMe. In embodiments, R43is CO2H. In embodiments, R43is NHC(O)Ot-Bu. In embodiments, two R43together with the carbon atom to which they are both attached form a 3-7 membered heterocycloalkyl, such as oxetanyl or tetrahydrofuranyl, such as tetrahydrofuranyl. In embodiments, two R43together with the carbon atom to which they are both attached form a C3-6cycloalkyl, such as cyclopropyl. In embodiments, the cyclopropyl 30 is substituted by two F. 35 201369 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: , wherein s and R44are as defined herein. 5 In embodiments, s is 1. In embodiments, s is 2. In embodiments, s is 3. In embodiments, s is 4. In embodiments, each R44is independently selected from CN, OH, =O, halo, C1-3alkyl optionally substituted by one OH, C1-3alkoxy, C1-3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, 3-7 membered heterocycloalkyl, CO2H, C(O)Me, C(O)Ot-Bu, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu, and O(C3-6cycloalkyl). In embodiments, each R44is independently selected from OH, halo, C1-3alkyl, C1- 10 3alkoxy, C1-3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, and 3-7 membered heterocycloalkyl. In embodiments, each R44is independently selected from OH, C1-3alkyl, C1-3alkoxy, C1- 3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, and 3-7 membered heterocycloalkyl. In embodiments, each R44is independently selected from OH, =O, F, methyl, CH2OH, C(Me2)OH, OMe, CF3, cyclopropyl substituted by one OH, oxetanyl, CO2H, C(O)Me, C(O)Ot-Bu,NH(oxetanyl), NHC(O)Me, 15 NHC(O)Ot-Bu, NMeC(O)Ot-Bu, and O(cyclopropyl). In embodiments, each R44is independently selected from OH, F, methyl, OMe, CF3, cyclopropyl substituted by one OH, and oxetanyl. In embodiments, each R44is independently selected from OH, methyl, OMe, CF3, cyclopropyl substituted by one OH and oxetanyl. In embodiments, two R43together with the carbon atom to which they are both attached form a C3-6cycloalkyl, such as cyclopropyl. In embodiments, the C3-6cycloalkyl is optionally substituted by one 20 or two F. In embodiments, two R43together with the carbon atom to which they are both attached form a 3-7 membered heterocycloalkyl, such as tetrahydropyranyl or oxetanyl, such as oxetanyl. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: , 25 wherein J, s and R44are as defined herein. In embodiments, s is 0. In embodiments, s is 1. In embodiments, s is 2. In embodiments, each R44is independently selected from =O, C1-3alkyl optionally substituted by one OH, C1-3haloalkyl and 3-7 membered heterocycloalkyl. In embodiments, each R44is independently selected from C1-3alkyl and C1- 3haloalkyl. In embodiments, each R44is independently selected from =O, methyl, CH2OH, CF3and 30 oxetanyl, such as methyl and CF3. In embodiments, two R44together with the carbon atom to which they 36 201369 are both attached form a C3-6cycloalkyl, such as cyclobutyl or cyclopropyl, such as cyclopropyl. In embodiments, two R44together with the carbon atom to which they are both attached form a 3-7 membered heterocycloalkyl, such as oxetanyl. In embodiments, J is S(O)2. In embodiments, J is NR45. In embodiments, R45is selected from H, 5 C(O)methyl, methyl, CH2CH2OH, C(O)O-tBu and oxetanyl, such as H and C(O)methyl. In embodiments, J is O. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: . 10 In embodiments, s is 0. In embodiments, s is 1. In embodiments, s is 2. In embodiments, each R44is independently selected from C1-3alkyl and C1-3haloalkyl. In embodiments, each R44is methyl. In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is selected from: 15 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: . In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: 37 2013695 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: 38 201369 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from:5 39 2013695 40 201369 5 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: 41 201369 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which 5 they are attached form a 3-10 membered heterocycloalkyl selected from: 10 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: 42 201369 5 . In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: 43 201369 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is selected from: 510 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is selected from: 44 201369 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: 5 In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which 10 they are attached form a 3-10 membered heterocycloalkyl which is selected from: In embodiments, R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: 15 In embodiments: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or C3-6cycloalkyl; and X1is CR10, X2is CR11and X3is CR12. 45 201369 In embodiments: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or C3-6cycloalkyl; X1is CR10, X2is CR11and X3is CR12; R20is H, C1-6alkyl or C3-6cycloalkyl; and R21is H or C1-5 6alkyl. In embodiments: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or C3-6cycloalkyl; X1is CR10, X2is CR11and X3is CR12; R20is H, C1-6alkyl or C3-6cycloalkyl;R21is H or C1-6alkyl; and 10 Z1is O or NH. In embodiments: R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NH; B is group (B1), (B2), (B3) or (B4); and R30, R31, R32and R33are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1- 6haloalkoxy and C3-6cycloalkyl.15 In embodiments: R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NH; B is group (B1), (B2), (B3) or (B4); R30, R31, R32and R33are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl; and R40 is C(O)NR41R42, and R41 and R42 together with the nitrogen atom towhich they are attached form a 3-10 membered heterocycloalkyl which may be optionally substituted by20 one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1- 6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe,S(O)2NMe2, C3-6cycloalkyl and 3-10 membered heterocycloalkyl. In embodiments: R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NH; B is group (B1), (B2), (B3) or (B4); R30,25 R31, R32and R33are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl; and R40 is C(O)NR41R42, and R41 and R42 together with the nitrogen atom towhich they are attached form a piperazinyl or morpholinyl which may be optionally substituted by one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1- 6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe,30 S(O)2NMe2, C3-6cycloalkyl and 3-10 membered heterocycloalkyl. In embodiments: R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NH; B is group (B1), (B2) or (B3); R30, R31and R32are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl; and R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they 35 are attached form a piperazinyl which may be optionally substituted by one or two groups independently 46 201369 selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3- 6cycloalkyl and 3-10 membered heterocycloalkyl. In embodiments: R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NH; B is group (B1), (B2) or (B3); R30, R315 and R32are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl; and R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a morpholinyl which may be optionally substituted by one or two groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3-6cycloalkyl and 3-10 membered heterocycloalkyl. 10 In embodiments: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or C3-6cycloalkyl; X1is CH, X2is C-CF3 and X3is CH; andR40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a piperazinyl which may be optionally substituted by one15 or two groups independently selected from halo, OH, C1-6alkyl optionally substituted by one OH, C1- 6haloalkyl, C1-6alkoxy, C(O)R41aa, C3-6cycloalkyl optionally substituted by one OH, and 3-10 membered heterocycloalkyl. In embodiments: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently 20 selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or C3-6cycloalkyl; X1is CH, X2is C-CF3 and X3is CH; and R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a morpholinyl which may be optionally substituted by one or two groups independently selected from halo, OH, C1-6alkyl optionally substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C(O)R41aa, C3-6cycloalkyl optionally substituted by one OH and 3-10 membered 25 heterocycloalkyl. In embodiments: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or C3-6cycloalkyl; X1is CH, X2is C-CF3 and X3is CH; and R40is C(O)NR41R42, and R41and R42together with the 30 nitrogen atom to which they are attached form a morpholinyl which may be optionally substituted by one or two groups independently selected from C1-6alkyl, C1-6haloalkyl and C1-6alkoxy. In embodiments: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or 35 C3-6cycloalkyl; and X1is N, X2is CR11and X3is CR12. In embodiments: 47 201369 R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or C3-6cycloalkyl; and X1is CR10, X2is CR11and X3is N. In embodiments: 5 R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or C3-6cycloalkyl; X1is N, X2is C-CF3 and X3is CH; and R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a morpholinyl which may be optionally substituted by one or two groups independently selected from C1-6alkyl, C1-6haloalkyl and C1-6alkoxy. 10 In embodiments: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or C3-6cycloalkyl; X1is CH, X2is C-CF3 and X3is N; and R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a morpholinyl which may be optionally substituted by 15 one or two groups independently selected from C1-6alkyl, C1-6haloalkyl and C1-6alkoxy. In embodiments: R1is selected from H, methyl, ethyl, cyclopropyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl, C1-6alkoxy or C3-6cycloalkyl; R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NH;20 B is group (B1), (B2) or (B3); R30, R31and R32are each independently selected from halo, CN, C1-6alkyl, C1- 6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl; and R40 is C(O)NR41R42, and R41 and R42 togetherwith the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such as one, two, three or four e.g. one or two) groups independently selected from CN, F, =O, OH, methyl, iso-propyl, CH2OH, CH2CH2OH, C(Me)2OH, CF3, OMe, CH2OMe, OCF3, 25 C(O)Me, cyclopropyl substituted by one OH, oxetanyl, CO2H, C(O)Ot-Bu, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu and O(cyclopropyl); and / or 2) two groups on the same atom, together with the atom to which they are attached, form a cyclopropyl, cyclobutyl, azetidinyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl, each of which may be optionally substituted by one or two groups selected from F, CF3, OH and C(O)Me. 30 It will be understood that throughout this specification, references and embodiments relating to compounds of formula (I-X), (I) and pharmaceutically acceptable salts thereof apply equally to other compounds and pharmaceutically acceptable salts described herein, such as compounds of formulae (IA), (IA-I), (IB), (IB-I), (IC), (IC-I), (ID), (ID-I), (IE), (IE-I), (IF), (IF-I), (IG), (IG-I), (IH), (IH-I), (IJ), (IJ-I), (IK), (IK- 35 I), (IL), (IL-I), (IM), (IM-I), (IN) (IN-I), (IO), (IO-I), (IP), (IP-I), (IQ), (IQ-I), (IR), (IR-I), (IS), (IS-I), (IT), (IT-I), (IU), (IU-I), (I-XA), (I-XA-I), and pharmaceutically acceptable salts of any one thereof. Such references are also 48 201369 applicable to the intermediate compounds and salts thereof, such as pharmaceutically acceptable salts thereof described herein, such as compounds of formulae (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (XI) and salts, such as pharmaceutically acceptable salts of any one thereof. 5 In embodiments, the compound of formula (I-X) or (I) is a compound of formula (IA): , wherein: R1is H, C1-6alkyl or C3-6cycloalkyl; wherein said C1-6alkyl may be optionally substituted by: 10 1) one or more groups independently selected from OH, NR1bR1c, C(O)OR1a, C(O)NR1bR1c, NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or 15 R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl; R1dis H, C1-6alkyl or C1-6haloalkyl; R1eis C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 20 6cycloalkyl or 3-10 membered heterocycloalkyl; wherein when present in R1, each C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, 25 NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2; R2is C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by one C3-6cycloalkyl or phenyl; X1is N or CR10, and R10is H, halo, CN, C1-6alkyl or C1-6haloalkyl; 30 X2is N or CR11, and R11is halo, CN, C1-6haloalkyl, C1-6alkoxy, phenyl or 5-6 membered heteroaryl; X3is N or CR12, and R12is H, halo, CN, C1-6alkyl or C1-6haloalkyl; wherein 0 or 1 of X1, X2and X3is N; 49 201369 R20is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; R21is H, C1-6alkyl or C1-6haloalkyl; or R20and R21together with the atom to which they are attached form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; 5 Z1is O or NR22; R22is H, C1-6alkyl, C1-6haloalkyl, CH2C≡CH or C3-6cycloalkyl; B is group (B1), (B2), (B3) or (B4): wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40; 10 m, n, o and p are each independently 0, 1 or 2; R30, R31, R32and R33are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1- 6haloalkoxy and C3-6cycloalkyl; Y1is N, CH or CR31; Y2is N; 15 Y3is N; Y4is N, CH or CR32; Y5is N; Y6is N; R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3- 20 10 membered heterocycloalkyl which may be optionally substituted by: 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3-6cycloalkyl and 3-10 membered heterocycloalkyl; wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may 25 each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may 30 each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; 50 201369 R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and 5 C(O)R41aa; or a pharmaceutically acceptable salt thereof. In embodiments, the compound of formula (IA) is a compound of formula (IA-A): , or a pharmaceutically acceptable salt thereof. 10 In embodiments, the compound of formula (I-X) or (I) is a compound of formula (IB): wherein: R1is H or C1-6alkyl; wherein said C1-6alkyl may be optionally substituted by:15 1) one or more groups independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 20 membered heterocycloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl; wherein when present in R1, each C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl may be independently optionally substituted by 25 one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R2is C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; X1is N or CR10, and R10is H; 51 201369 X2is N or CR11, and R11is halo, CN, C1-6haloalkyl, C1-6alkoxy, phenyl or 5-6 membered heteroaryl; X3is N or CR12, and R12is H, halo, CN, C1-6alkyl or C1-6haloalkyl; wherein 0 or 1 of X1, X2and X3is N; R20is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; 5 R21is H or C1-6alkyl; or R20and R21together with the atom to which they are attached form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; Z1is O or NR22; R22is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; 10 B is group (B1), (B2), (B3) or (B4): wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40; m, n, o and p are each independently 0, 1 or 2; R30, R31, R32and R33are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-156haloalkoxy and C3-6cycloalkyl; Y1is N, CH or CR31; Y2is N; Y3is N; Y4is N, CH or CR32; 20 Y5is N; Y6is N; R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3- 10 membered heterocycloalkyl which may be optionally substituted by: 1) one or more groups independently selected from OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1- 25 6haloalkoxy, C(O)R41aa, C3-6cycloalkyl and 3-10 membered heterocycloalkyl; wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 30 R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally 52 201369 substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa; or a pharmaceutically acceptable salt thereof. In embodiments, the compound of formula (IB) is a compound of formula (IB-A): 5 or a pharmaceutically acceptable salt thereof. In embodiments, the compound of formula (I-X) or (I) is a compound of formula (IC): wherein: 10 R1is H or C1-6alkyl; wherein said C1-6alkyl may be optionally substituted by: 1) one or two groups independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and5-6 membered heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; 15 R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl; 20 R2is C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; X1is N or CR10, and R10is H; X2is CR11, and R11is halo, CN, C1-6haloalkyl, C1-6alkoxy, phenyl or 5-6 membered heteroaryl; X3is N or CR12, and R12is H; wherein 0 or 1 of X1and X3is N; 25 R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NR22; R22is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; 53 201369 B is group (B1), (B2) or (B3): wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40; m, n and o are each independently 0, 1 or 2; 5 R30, R31and R32are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1- 6haloalkoxy and C3-6cycloalkyl; Y1is N, CH or CR31; Y2is N; Y3is N; 10 Y4is N, CH or CR32; Y5is N; Y6is N; R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3- 10 membered heterocycloalkyl which may be optionally substituted by: 15 1) one or two groups independently selected from OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, C3-6cycloalkyl and 3-10 membered heterocycloalkyl; wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or two groups independently 20 selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or two groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and 25 C(O)R41aa. In embodiments, the compound of formula (IC) is a compound of formula (IC-A): , or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (ID): 54 201369 , or a pharmaceutically acceptable salt thereof, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; 5 and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31and R40are as defined herein. In embodiments, the compound of formula (ID) is a compound of formula (ID-I): or a pharmaceutically acceptable salt thereof. 10 In embodiments, the specification provides a compound of formula (IE): or a pharmaceutically acceptable salt thereof, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; 15 and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2 is C1-6alkyl or C3-6cycloalkyl; Z1 is O or NH; and Y1, Y2, n, R20, R21, R31, s, and R44 are as defined herein.In embodiments, the compound of formula (IE) is a compound of formula (IE-I): 55 201369 or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IF): , 5 or a pharmaceutically acceptable salt thereof, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and J, Y1, Y2, n, R20, R21, R31, s and R44are as defined herein. 10 In embodiments, the compound of formula (IF) is a compound of formula (IF-I): or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IG): 15 or a pharmaceutically acceptable salt thereof, wherein: R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31, s and R44are as defined herein. In embodiments, the compound of formula (IG) is a compound of formula (IG-I): 56 201369 or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IH): 5 or a pharmaceutically acceptable salt thereof, wherein: R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31, s, R44and R45are as defined herein. In embodiments, the compound of formula (IH) is a compound of formula (IH-I): or a pharmaceutically acceptable salt thereof. 10 In embodiments, the specification provides a compound of formula (IJ): , or a pharmaceutically acceptable salt thereof, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; 15 and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and J, Y1, Y2, n, R20, R21, R31, s and R44are as defined herein. In embodiments, the compound of formula (IJ) is a compound of formula (IJ-I): 57 201369 or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IK): 5 or a pharmaceutically acceptable salt thereof, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and J, Y1, Y2, n, R20, R21, R31, s and R44are as defined herein. 10 In embodiments, the compound of formula (IK) is a compound of formula (IK-I): or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IL): 15 or a pharmaceutically acceptable salt thereof, wherein: R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31, s and R44are as defined herein. In embodiments, the compound of formula (IL) is a compound of formula (IL-I): 58 201369 or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IM): 5 or a pharmaceutically acceptable salt thereof, wherein: R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31, s and R44are as defined herein. In embodiments, the compound of formula (IM) is a compound of formula (IM-I): or a pharmaceutically acceptable salt thereof. 10 In embodiments, the specification provides a compound of formula (IN): or a pharmaceutically acceptable salt thereof, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; 15 and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31and R40are as defined herein. In embodiments, the compound of formula (IN) is a compound of formula (IN-I): 59 201369 or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IO): 5 or a pharmaceutically acceptable salt thereof, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31and R40are as defined herein. 10 In embodiments, the compound of formula (IO) is a compound of formula (IO-I): , or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IP): 15 or a pharmaceutically acceptable salt thereof, wherein: 60 201369 R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31and R40are as defined herein. 5 In embodiments, the compound of formula (IP) is a compound of formula (IP-I): or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IQ): , 10 or a pharmaceutically acceptable salt thereof, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and J, Y1, Y2, n, R20, R21, R31, s and R44are as defined herein. 15 In embodiments, the compound of formula (IQ) is a compound of formula (IQ-I): or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IR): 61 201369 or a pharmaceutically acceptable salt thereof, wherein: R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31, s and R44are as defined herein. In embodiments, the compound of formula (IR) is a compound of formula (IR-I): 5 or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IS): , or a pharmaceutically acceptable salt thereof, wherein: 10 R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31and R40are as defined herein. In embodiments, the compound of formula (IS) is a compound of formula (IS-I): 15 or a pharmaceutically acceptable salt thereof. 62 201369 In embodiments, the specification provides a compound of formula (IT): or a pharmaceutically acceptable salt thereof, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each 5 independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups together with the atom to which they are attached form a C3-6cycloalkyl; R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and J, Y1, Y2, n, R20, R21, R31, s and R44are as defined herein. In embodiments, the compound of formula (IT) is a compound of formula (IT-I): 10 or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound of formula (IU): or a pharmaceutically acceptable salt thereof, wherein: R2is C1-6alkyl or C3-6cycloalkyl; Z1is O or NH; and Y1, Y2, n, R20, R21, R31, s and R44are as defined herein. 15 In embodiments, the compound of formula (IU) is a compound of formula (IU-I): 63 201369 or a pharmaceutically acceptable salt thereof. In embodiments, the compound of formula (I-X) is a compound of formula (I-XA): 5 wherein: R1is H, C1-6alkyl or C3-6cycloalkyl; wherein said C1-6alkyl may be optionally substituted by: 1) one or more groups independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl, and 5-6 membered heteroaryl; 10 R1ais H, C1-6alkyl or C1-6haloalkyl; R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-156cycloalkyl; wherein when present in R1, each C3-6cycloalkyl, 3-10 membered heterocycloalkyl and 5- 6 membered heteroaryl may be independently optionally substituted by one or more groups independently selected from C1-6alkyl and C1-6haloalkyl; R2is C1-6alkyl, C1-6alkoxy or C3-6cycloalkyl; 20 X1is N or CR10, and R10is H, halo, CN, C1-6alkyl or C1-6haloalkyl; X2is N or CR11, and R11is halo, CN, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, phenyl or 5-6 membered heteroaryl; X3is N or CR12, and R12is H, halo, CN, C1-6alkyl or C1-6haloalkyl; wherein 0 or 1 of X1, X2and X3is N; 25 R20is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; R21is H, C1-6alkyl or C1-6haloalkyl; or 64 201369 Z1is CH2, S, O or NR22; R22is H or C1-6alkyl; B is group (B1), (B2), (B3), (B4), (B6) or (B7): 5 wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40; m, n, o and p are each independently 0, 1 or 2; R30, R31, R32and R33are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl; 10 Y1is N, CH or CR31; Y2is N; Y3is N; Y4is N, CH or CR32; Y5is N; 15 Y6is N; W1and W2are each independently N or CH, provided that when one of W1and W2is N, the other is CH; W3is S or O; R35is H or C1-6alkyl; R40is -A1NR41R42; 20 A1is CH2or C(O); R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which may be optionally substituted by: 1) one or more groups independently selected from CN, halo, OH, =O, C1-6alkyl optionally substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3-25 6cycloalkyl optionally substituted by one OH, 3-10 membered heterocycloalkyl and O(C3- 6cycloalkyl); R41aais OH, C1-6alkyl or C1-6alkoxy; R41abis H, C1-6alkyl, C(O)R41ador 3-10 membered heterocycloalkyl; R41acis H or C1-6alkyl; 30 R41adis C1-6alkyl or C1-6alkoxy; and / or 65 201369 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be optionally substituted by one or two groups independently selected from F, CF3, OH and C(O)Me; or a pharmaceutically acceptable salt thereof. 5 In embodiments, the compound of formula (I-XA) is a compound of formula (I-XA-I): , or a pharmaceutically acceptable salt thereof. In embodiments, the specification provides a compound or pharmaceutically acceptable salt 10 thereof which is selected from: 6-(1-((2-(2,6-Dimethylmorpholine-4-carbonyl)benzo[d]thiazol-6-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((2-(2,6-Dimethyl-1,1-dioxidothiomorpholine-4-carbonyl)benzo[d]thiazol-6-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 15 6-(1-((2-(2,6-Dimethylmorpholine-4-carbonyl)benzo[d]thiazol-6-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((2-(2,6-Dimethylmorpholine-4-carbonyl)thiazolo[5,4-b]pyridin-5-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((2-(2,6-Dimethylmorpholine-4-carbonyl)benzo[d]oxazol-6-yl)amino)ethyl)-2-methyl-7- 20 (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((2-(2,6-Dimethylmorpholine-4-carbonyl)thiazolo[4,5-c]pyridin-6-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((2-(2,6-Dimethylmorpholine-4-carbonyl)thiazolo[4,5-c]pyridin-6-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 25 6-(1-((2-(2,6-Dimethylmorpholine-4-carbonyl)thiazolo[5,4-b]pyridin-5-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((5-(4-Cyclopropoxypiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 2-Methyl-6-(1-((5-(4-(trifluoromethoxy)piperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-7- 30 (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((5-(4-Methoxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 66 201369 6-(1-((5-(4-Fluoro-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((3-Fluoro-5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 5 6-(1-((3-Fluoro-5-(4-fluoro-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((3-Fluoro-5-(4-(trifluoromethyl)piperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)-2,2,2-trifluoroethyl)-2-methyl-7- 10 (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 2-Methyl-6-(2,2,2-trifluoro-1-((5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 7-Chloro-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methylpyrido[3,2- d]pyrimidin-4(3H)-one; 15 7-Chloro-6-(1-((5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2- methylpyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)propan-2-yl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)propan-2-yl)-2-methyl-7- 20 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)thio)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3- d]pyrimidin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)thio)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3- d]pyrimidin-4(3H)-one; 25 2-Methyl-7-(trifluoromethyl)-6-(1-((4-(4-(trifluoromethyl)piperidine-1- carbonyl)phenyl)sulfonyl)ethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((2-(Azetidine-1-carbonyl)benzo[d]thiazol-6-yl)amino)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3- d]pyrimidin-4(3H)-one; 6-(1-((2-(2,6-Dimethylmorpholine-4-carbonyl)benzo[d]thiazol-6-yl)amino)ethyl)-2-methyl-7- 30 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-Methyl-6-(1-((2-(pyrrolidine-1-carbonyl)benzo[d]thiazol-6-yl)amino)ethyl)-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 3-Cyclopropyl-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 35 3-Cyclopropyl-6-(1-(4-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 67 201369 3-Cyclopropyl-6-(1-(4-(2,6-dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((4-(3,3-Difluoropiperidine-1-carbonyl)phenyl)amino)propyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 5 6-(1-((5-(4-Cyclopropoxy-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3-(2-Hydroxypropan-2-yl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3-Hydroxy-3-methylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- 10 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3-Hydroxy-3-methylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(2-Oxa-6-azaspiro[3.5]nonane-6-carbonyl)phenoxy)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3- d]pyrimidin-4(3H)-one; 15 6-(1-(4-(3-(2-Hydroxypropan-2-yl)piperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(2-Oxa-8-azaspiro[5.5]undecane-8-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(6-Hydroxy-2-azaspiro[3.3]heptane-2-carbonyl)phenoxy)ethyl)-2-methyl-7- 20 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3-(1-Hydroxycyclopropyl)piperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(5-Oxa-8-azaspiro[3.5]nonane-8-carbonyl)phenoxy)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3- d]pyrimidin-4(3H)-one; 25 6-(1-(4-(4-Hydroxy-3-(2-hydroxypropan-2-yl)piperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3-Fluoro-5-methoxypiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3-(Hydroxymethyl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- 30 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3-(Hydroxymethyl)piperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3- d]pyrimidin-4(3H)-one; 6-(1-(4-(3-Methoxypyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3- d]pyrimidin-4(3H)-one; 35 3,5-Dimethyl-1-(4-(1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-d]pyrimidin-6- yl)ethoxy)benzoyl)piperidine-4-carbonitrile; 68 201369 6-(1-(4-(4-Methoxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3-(2-Hydroxypropan-2-yl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 5 6-(1-((2-Fluoro-4-(3-methoxypyrrolidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((2-Fluoro-4-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((2-Fluoro-4-(3-(2-hydroxypropan-2-yl)pyrrolidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 10 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((2-Fluoro-4-(1-oxa-6-azaspiro[3.5]nonane-6-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((2-Fluoro-4-(1-oxa-7-azaspiro[3.5]nonane-7-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 15 6-(1-((2-Fluoro-4-(8-methyl-2-oxa-6-azaspiro[3.5]nonane-6-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 1-(3-Fluoro-4-((1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-d]pyrimidin-6- yl)ethyl)amino)benzoyl)-3,5-dimethylpiperidine-4-carbonitrile; 6-(1-((4-(8-Oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)-2-fluorophenyl)amino)ethyl)-2-methyl-7- 20 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((1-(4-(3-Fluoro-4-methoxypyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-Methyl-6-(1-(4-(6-methyl-5-oxa-8-azaspiro[3.5]nonane-8-carbonyl)phenoxy)ethyl)-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 25 6-(1-(4-(3-Fluoro-3-(hydroxymethyl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3-Fluoro-3-(methoxymethyl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3-Fluoro-4-methoxypyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- 30 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(6,6-Difluoro-2-azaspiro[3.3]heptane-2-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(3,3-Bis(hydroxymethyl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 35 2-Methyl-6-(2,2,2-trifluoro-1-((5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 69 201369 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)-2,2,2-trifluoroethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((5-(4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)-3-methoxypyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 5 2-Cyclopropyl-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2,3-Dimethyl-7-(trifluoromethyl)-6-(1-((5-(4-(trifluoromethyl)piperidine-1-carbonyl)pyrimidin-2- yl)amino)ethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 10 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((5-(4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((6-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 15 6-(1-((4-(4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((3-Fluoro-5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2,3-dimethyl- 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(2-Fluoro-4-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2,3-dimethyl-7- 20 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-(1-(2,3-Dimethyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-d]pyrimidin-6-yl)ethoxy)-5-(2,6- dimethylmorpholine-4-carbonyl)nicotinonitrile; 2-((1-(2,3-Dimethyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-d]pyrimidin-6-yl)ethyl)amino)-5- (2,6-dimethylmorpholine-4-carbonyl)benzonitrile; 25 6-(1-((2-Fluoro-4-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-((1-(2,3-Dimethyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-d]pyrimidin-6-yl)ethyl)amino)-5- (2,6-dimethylmorpholine-4-carbonyl)nicotinonitrile; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-8-fluoro-2-methyl-7- 30 (trifluoromethyl)quinazolin-4(3H)-one; 8-Fluoro-6-(1-((5-(3-(2-hydroxypropan-2-yl)pyrrolidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(4-Acetylpiperazine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-8-fluoro-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 8-Fluoro-6-(1-((5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 70 201369 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-8-fluoro-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 8-Fluoro-6-(1-((5-(4-fluoro-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyrazin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((1-((2-(2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-5-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((3-(2,6-Dimethylmorpholine-4-carbonyl)-1-methyl-1H-pyrazol-5-yl)amino)ethyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 3-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)-3-(2-methyl-4-oxo-7- (trifluoromethyl)-3,4-dihydroquinazolin-6-yl)propanoic acid; 7-Chloro-2-methyl-6-(((4-(morpholine-4-carbonyl)phenyl)amino)methyl)quinazolin-4(3H)-one; 7-Bromo-2-methyl-6-(((4-(morpholine-4-carbonyl)phenyl)amino)methyl)quinazolin-4(3H)-one; 15 6-(-Cyclopropyl((4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)methyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-methoxypyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-2-(trifluoromethoxy)phenyl)amino)ethyl)-2-methyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((2-Chloro-4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-2-fluoro-6-methoxyphenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluorophenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-2-(trifluoromethyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5-(2,6-Dimethylmorpholine-4-carbonyl)-2-((1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin- 30 6-yl)ethyl)amino)benzonitrile; 7-Chloro-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2-methylquinazolin- 4(3H)-one; 7-Chloro-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-2-methylquinazolin- 4(3H)-one; 35 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-2-methoxyphenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 71 201369 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-3-methoxyphenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-(6-(((4-(3-Fluoropyrrolidine-1-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 5 2-(6-(((4-(3,3-Difluoropyrrolidine-1-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(2-Methyl-6-((methyl(4-(1-(trifluoromethyl)-2-oxa-6-azaspiro[3.3]heptane-6- carbonyl)phenyl)amino)methyl)-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(1,1-Difluoro-5-azaspiro[2.4]heptane-5-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-10 oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(1-Oxa-7-azaspiro[3.5]nonane-7-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(6-Acetyl-2,6-diazaspiro[3.3]heptane-2-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4- oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 15 2-(2-Methyl-6-((methyl(4-(4-(oxetan-3-yl)piperazine-1-carbonyl)phenyl)amino)methyl)-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(4-((tert-Butoxycarbonyl)amino)-3-methoxypiperidine-1- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 20 2-(6-(((4-(4-((tert-Butoxycarbonyl)(methyl)amino)-3-fluoropiperidine-1- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(4-((tert-Butoxycarbonyl)(methyl)amino)-3-fluoropiperidine-1- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic 25 acid; 2-(6-(((4-(4-((tert-Butoxycarbonyl)amino)-3-fluoropiperidine-1-carbonyl)phenyl)(methyl)amino)methyl)- 2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(5-(tert-Butoxycarbonyl)-2-oxa-5,8-diazaspiro[3.5]nonane-8- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic 30 acid; 2-(6-(((4-(3-((tert-Butoxycarbonyl)amino)-4-methoxypyrrolidine-1- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(3-((tert-Butoxycarbonyl)amino)-4,4-difluoropiperidine-1- 35 carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 72 201369 2-(6-(((4-(3-((tert-Butoxycarbonyl)amino)-4-fluoropiperidine-1-carbonyl)phenyl)(methyl)amino)methyl)- 2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(3-((tert-Butoxycarbonyl)amino)-4-fluoropiperidine-1-carbonyl)phenyl)(methyl)amino)methyl)- 2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 5 2-(6-(((4-(3-Acetamidopiperidine-1-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(2-Methyl-6-((methyl(4-(4-(oxetan-3-ylamino)piperidine-1-carbonyl)phenyl)amino)methyl)-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-((2-methyl-2H-tetrazol-5- 10 yl)methyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-((1-methyl-1H-tetrazol-5- yl)methyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-(2-(1-methyl-1H-tetrazol- 5-yl)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 15 3-((1H-1,2,3-Triazol-4-yl)methyl)-6-(1-((4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 2-(6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)propanoic acid; 2-Cyclopropyl-2-(6-(1-((4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-4-oxo-7-20 (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 1-((2-Methyl-4-oxo-7-(trifluoromethyl)-6-(1-((4-(4-(trifluoromethyl)piperidine-1- carbonyl)phenyl)amino)ethyl)quinazolin-3(4H)-yl)methyl)cyclopropane-1-carboxylic acid; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)allyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 2-Methyl-7-(trifluoromethyl)-6-(1-((4-(2-(trifluoromethyl)morpholine-4- carbonyl)phenyl)amino)ethyl)quinazolin-4(3H)-one; 2-Methyl-7-(trifluoromethyl)-6-(1-((4-(3-(trifluoromethyl)morpholine-4- carbonyl)phenyl)amino)ethyl)quinazolin-4(3H)-one; 2-Methyl-6-(1-((4-(morpholine-4-carbonyl)phenyl)amino)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one;30 2-Methyl-6-(1-((4-(3-methylmorpholine-4-carbonyl)phenyl)amino)ethyl)-7-(trifluoromethyl)quinazolin- 4(3H)-one; 6-(1-((4-(4-(2-Hydroxyethyl)piperazine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2-Oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 35 (trifluoromethyl)quinazolin-4(3H)-one; 73 201369 6-(1-((4-(6-Oxa-3-azabicyclo[3.1.1]heptane-3-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-6-(1-((4-(3-methyl-5-oxopiperazine-1-carbonyl)phenyl)amino)ethyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 6-(1-((4-(2-Oxa-8-azaspiro[5.5]undecane-8-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(3-(Hydroxymethyl)piperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(3-(2-Hydroxypropan-2-yl)piperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2-Oxa-6-azaspiro[3.4]octane-6-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 4-Isopropyl-1-(4-((1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6- yl)ethyl)amino)benzoyl)pyrrolidine-3-carboxylic acid; 15 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethyl-1,1-dioxidothiomorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(3-(Hydroxymethyl)piperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 1-(4-((1-(2-Methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6-yl)ethyl)amino)benzoyl)pyrrolidine- 3-carboxylic acid; 25 1-(4-((1-(2-Methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6-yl)ethyl)amino)benzoyl)piperidine- 3-carboxylic acid; 1-(4-((1-(2-Methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6-yl)ethyl)amino)benzoyl)pyrrolidine- 3-carboxylic acid; 7-Chloro-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)oxy)ethyl)-2- 30 methylquinazolin-4(3H)-one; 7-Chloro-6-(1-((6-(2,6-dimethylmorpholine-4-carbonyl)pyridin-3-yl)oxy)ethyl)-2-methylquinazolin-4(3H)- one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,5-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 6-(1-(4-(4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2,5-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 74 201369 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2,5-dimethyl-7-(trifluoromethyl)quinazolin- 4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-5-fluoro-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 5-Fluoro-6-(1-(4-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2,3-Dimethyl-6-(1-((4-(morpholine-4-carbonyl)phenyl)amino)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)- one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2,3-dimethyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-methoxypyridin-2-yl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyrazin-2-yl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)propyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-(6-(1-((4-(1,1-Difluoro-6-azaspiro[2.5]octane-6-carbonyl)phenyl)(methyl)amino)ethyl)-2-methyl-4-oxo- 7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-Methyl-6-(1-(methyl(4-(morpholine-4-carbonyl)phenyl)amino)ethyl)-7-(trifluoromethyl)quinazolin- 20 4(3H)-one; 2-(6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)(methyl)amino)ethyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 6-(1-((6-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-4-oxo-7- 30 (trifluoromethyl)-3,4-dihydroquinazoline-8-carbonitrile; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,8-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 7-Chloro-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-8-fluoro-2- methylquinazolin-4(3H)-one; 35 7-Chloro-6-(1-((4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)propyl)-2-methylquinazolin-4(3H)- one; 75 201369 7-Chloro-6-(1-((3-fluoro-5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2- methylquinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-7-(2-fluorophenyl)-2- methylquinazolin-4(3H)-one; 5 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(pyridin-2-yl)quinazolin- 4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-7-(3-fluorophenyl)-2- methylquinazolin-4(3H)-one; 6-(1-((4-(3,4-Dimethyl-5-oxopiperazine-1-carbonyl)phenyl)amino)propyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-6-(1-((4-(2-methyl-5-(trifluoromethyl)piperazine-1-carbonyl)phenyl)amino)propyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-6-(1-((4-(3-methylpiperazine-1-carbonyl)phenyl)amino)propyl)-7-(trifluoromethyl)quinazolin- 4(3H)-one; 15 2-Methyl-7-(trifluoromethyl)-6-(1-((4-(3,4,5-trimethylpiperazine-1- carbonyl)phenyl)amino)propyl)quinazolin-4(3H)-one; 6-(1-((2-Fluoro-4-(2-methylmorpholine-4-carbonyl)phenyl)amino)propyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((2-Fluoro-4-(2-methylmorpholine-4-carbonyl)phenyl)amino)propyl)-2-methyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)propyl)-2-isopropyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)methyl)-2-methoxy-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 6-(1-(2-Chloro-4-(2,6-dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((6-(2,6-Dimethylmorpholine-4-carbonyl)-2-methylpyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-Cyclopropyl-6-(2,6-dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2-methyl-7- 30 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((6-(2,6-Dimethylmorpholine-4-carbonyl)-4-methylpyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((2-Chloro-4-(2,6-dimethylmorpholine-4-carbonyl)-6-fluorophenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 6-(1-((6-(2,6-Dimethylmorpholine-4-carbonyl)-2-fluoropyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 76 201369 6-(1-(4-(3,5-Dimethylpiperazine-1-carbonyl)phenoxy)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin- 4(3H)-one; 6-(1-(4-(4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 6-(1-((3-Fluoro-5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-((2,6-Dimethylmorpholino)methyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-((2,6-Dimethylmorpholino)methyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-((2,6-Dimethylmorpholino)methyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 7-Chloro-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-2,5- dimethylquinazolin-4(3H)-one; 15 7-Chloro-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,5- dimethylquinazolin-4(3H)-one; 7-Cyclopropyl-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2- methylquinazolin-4(3H)-one; 6-(1-((3-Fluoro-5-(2-(hydroxymethyl)-6-methylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2- 20 methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((3-Fluoro-5-(2-(hydroxymethyl)-6-methylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 8-Fluoro-6-(1-((5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2,3- dimethyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 25 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methylquinazolin- 4(3H)-one; 7-Chloro-8-fluoro-6-(1-((5-(4-fluoro-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2- methylquinazolin-4(3H)-one; 7-Chloro-8-fluoro-6-(1-((5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2- 30 methylquinazolin-4(3H)-one; 7-Chloro-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-5-fluoro-2- methylquinazolin-4(3H)-one; 7-Chloro-6-(1-((5-(4-fluoro-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2- methylquinazolin-4(3H)-one; 35 6-(1-(4-(8-Oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 77 201369 6-(1-((5-(4-Fluoro-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(2,6-Dimethyl-1,1-dioxidothiomorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 5 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2,5-dimethyl-7-(trifluoromethyl)pyrido[2,3- d]pyrimidin-4(3H)-one; 6-(1-((5-(4-Fluoro-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2,5-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-2,5-dimethyl-7- 10 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,5-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-7-fluoro-2- methylquinazolin-4(3H)-one; and 15 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)(methyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one, or a pharmaceutically acceptable salt of any one thereof, such as selected from: 6-((S)-1-((2-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)benzo[d]thiazol-6-yl)amino)ethyl)-2-methyl-7- 20 (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((1S)-1-((2-(2,6-Dimethyl-1,1-dioxidothiomorpholine-4-carbonyl)benzo[d]thiazol-6-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((2-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)benzo[d]thiazol-6-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 25 6-((S)-1-((2-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)thiazolo[5,4-b]pyridin-5-yl)oxy)ethyl)-2-methyl- 7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((2-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)benzo[d]oxazol-6-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((2-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)thiazolo[4,5-c]pyridin-6-yl)oxy)ethyl)-2-methyl- 30 7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((2-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)thiazolo[4,5-c]pyridin-6-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((2-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)thiazolo[5,4-b]pyridin-5-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 35 (S)-6-(1-((5-(4-Cyclopropoxypiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 78 201369 (S)-2-Methyl-6-(1-((5-(4-(trifluoromethoxy)piperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((3S,4S,5R)-4-Methoxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 5 6-((S)-1-((5-((3S,4S,5R)-4-Fluoro-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((3-Fluoro-5-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)- 2-methyl-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((3-Fluoro-5-((3S,4R,5R)-4-fluoro-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2- 10 methyl-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((3-Fluoro-5-((3S,4S,5R)-4-fluoro-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; (S)-6-(1-((3-Fluoro-5-(4-(trifluoromethyl)piperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 15 6-((R)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)-2,2,2-trifluoroethyl)-2-methyl- 7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 2-Methyl-6-((R)-2,2,2-trifluoro-1-((5-((3S,4R,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2- yl)oxy)ethyl)-7-(trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 7-Chloro-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2- 20 methylpyrido[3,2-d]pyrimidin-4(3H)-one; 7-Chloro-6-((S)-1-((5-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2- methylpyrido[3,2-d]pyrimidin-4(3H)-one; 7-Chloro-6-((S)-1-(4-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2- methylpyrido[3,2-d]pyrimidin-4(3H)-one; 25 6-((R)-1-(4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)propan-2-yl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-(4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)propan-2-yl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)thio)ethyl)-2-methyl-7- 30 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((R)-1-((4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)thio)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; (S)-2-Methyl-7-(trifluoromethyl)-6-(1-((4-(4-(trifluoromethyl)piperidine-1- carbonyl)phenyl)sulfonyl)ethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 35 (S)-6-(1-((2-(Azetidine-1-carbonyl)benzo[d]thiazol-6-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 79 201369 6-((S)-1-((2-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)benzo[d]thiazol-6-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; (S)-2-Methyl-6-(1-((2-(pyrrolidine-1-carbonyl)benzo[d]thiazol-6-yl)amino)ethyl)-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 5 3-Cyclopropyl-6-((R)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2- yl)amino)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 3-Cyclopropyl-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2- yl)amino)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 3-Cyclopropyl-6-((S)-1-(4-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2- 10 methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 3-Cyclopropyl-6-((S)-1-(4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; (S)-6-(1-((4-(3,3-Difluoropiperidine-1-carbonyl)phenyl)amino)propyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 15 6-((S)-1-((5-((3S,4S,5R)-4-Cyclopropoxy-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((R)-1-((5-((3S,4R,5R)-4-Cyclopropoxy-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)- 2-methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-(4-((S)-3-(2-Hydroxypropan-2-yl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- 20 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-(4-((S)-3-Hydroxy-3-methylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-(4-((R)-3-Hydroxy-3-methylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 25 (S)-6-(1-(4-(2-Oxa-6-azaspiro[3.5]nonane-6-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((1S)-1-(4-(3-(2-Hydroxypropan-2-yl)piperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((1S)-1-(4-(2-Oxa-8-azaspiro[5.5]undecane-8-carbonyl)phenoxy)ethyl)-2-methyl-7- 30 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; (S)-6-(1-(4-(6-Hydroxy-2-azaspiro[3.3]heptane-2-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((1S)-1-(4-(3-(1-Hydroxycyclopropyl)piperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 35 (S)-6-(1-(4-(5-Oxa-8-azaspiro[3.5]nonane-8-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 80 201369 6-((S)-1-(4-((3RS,4RS)-4-Hydroxy-3-(2-hydroxypropan-2-yl)piperidine-1-carbonyl)phenoxy)ethyl)-2- methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-(4-((3R,5R)-3-Fluoro-5-methoxypiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 5 6-((S)-1-(4-((R)-3-(Hydroxymethyl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-(4-((S)-3-(Hydroxymethyl)piperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-(4-((S)-3-Methoxypyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3- 10 d]pyrimidin-4(3H)-one; (3S,4R,5R)-3,5-Dimethyl-1-(4-((S)-1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3- d]pyrimidin-6-yl)ethoxy)benzoyl)piperidine-4-carbonitrile; 6-((S)-1-(4-((3R,4S,5S)-4-Methoxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 15 6-((S)-1-(4-((R)-3-(2-Hydroxypropan-2-yl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((2-Fluoro-4-((R)-3-methoxypyrrolidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((2-Fluoro-4-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2- 20 methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((2-Fluoro-4-((R)-3-(2-hydroxypropan-2-yl)pyrrolidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((1S)-1-((2-Fluoro-4-(1-oxa-6-azaspiro[3.5]nonane-6-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 25 (S)-6-(1-((2-Fluoro-4-(1-oxa-7-azaspiro[3.5]nonane-7-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((1S)-1-((2-Fluoro-4-(8-methyl-2-oxa-6-azaspiro[3.5]nonane-6-carbonyl)phenyl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; (3S,4R,5R)-1-(3-Fluoro-4-(((S)-1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-d]pyrimidin- 30 6-yl)ethyl)amino)benzoyl)-3,5-dimethylpiperidine-4-carbonitrile; 6-((S)-1-((4-((1R,5S)-8-Oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)-2-fluorophenyl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; rel-6-((R)-1-(4-((3S,4S)-3-Fluoro-4-methoxypyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 35 2-Methyl-6-(1-(4-(6-methyl-5-oxa-8-azaspiro[3.5]nonane-8-carbonyl)phenoxy)ethyl)-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 81 201369 rel-6-((R)-1-(4-((R)-3-Fluoro-3-(hydroxymethyl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; rel-6-((R)-1-(4-((R)-3-Fluoro-3-(methoxymethyl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 5 6-((R)-1-(4-((3R,4S)-3-Fluoro-4-methoxypyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-(4-((3R,4S)-3-Fluoro-4-methoxypyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; (R)-6-(1-(4-(6,6-Difluoro-2-azaspiro[3.3]heptane-2-carbonyl)phenoxy)ethyl)-2-methyl-7- 10 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; (S)-6-(1-(4-(6,6-Difluoro-2-azaspiro[3.3]heptane-2-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; (R)-6-(1-(4-(3,3-Bis(hydroxymethyl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 15 (S)-6-(1-(4-(3,3-Bis(hydroxymethyl)pyrrolidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-Methyl-6-((R)-2,2,2-trifluoro-1-((5-((3S,4R,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2- yl)oxy)ethyl)-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((R)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)-2,2,2-trifluoroethyl)-2-methyl- 20 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((3S,4S,5R)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)-3-methoxypyridin-2-yl)oxy)ethyl)- 2-methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-Cyclopropyl-6-((S)-1-((5-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2- yl)amino)ethyl)-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 25 (S)-2,3-Dimethyl-7-(trifluoromethyl)-6-(1-((5-(4-(trifluoromethyl)piperidine-1-carbonyl)pyrimidin-2- yl)amino)ethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((3S,4S,5R)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- 30 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((6-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((4-((3R,4S,5S)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2,3-dimethyl- 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 35 6-((S)-1-((3-Fluoro-5-((3R,4S,5S)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)- 2,3-dimethyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 82 201369 6-((S)-1-(2-Fluoro-4-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2,3- dimethyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-((S)-1-(2,3-Dimethyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-d]pyrimidin-6-yl)ethoxy)-5- ((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)nicotinonitrile; 5 2-(((S)-1-(2,3-Dimethyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-d]pyrimidin-6-yl)ethyl)amino)-5- ((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)benzonitrile; 6-((S)-1-((2-Fluoro-4-((3R,4S,5S)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2,3- dimethyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-(((S)-1-(2,3-Dimethyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-d]pyrimidin-6-yl)ethyl)amino)-5-10 ((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)nicotinonitrile; 6-((R)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-8-fluoro-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 8-Fluoro-6-((S)-1-((5-((R)-3-(2-hydroxypropan-2-yl)pyrrolidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 15 (S)-6-(1-((5-(4-Acetylpiperazine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-8-fluoro-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 8-Fluoro-6-((S)-1-((5-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2- yl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-8-fluoro-2-methyl- 20 7-(trifluoromethyl)quinazolin-4(3H)-one; 8-Fluoro-6-((S)-1-((5-((3S,4S,5R)-4-fluoro-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)- 2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyrazin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 6-((1-((2-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-5-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((3-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-1-methyl-1H-pyrazol-5-yl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 3-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)-3-(2-methyl-4-oxo-7- 30 (trifluoromethyl)-3,4-dihydroquinazolin-6-yl)propanoic acid; 7-Chloro-2-methyl-6-(((4-(morpholine-4-carbonyl)phenyl)amino)methyl)quinazolin-4(3H)-one; 7-Bromo-2-methyl-6-(((4-(morpholine-4-carbonyl)phenyl)amino)methyl)quinazolin-4(3H)-one; 6-(-Cyclopropyl((4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)methyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-methoxypyridin-2-yl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 83 201369 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-(trifluoromethoxy)phenyl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((2-Chloro-4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluoro-6-methoxyphenyl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluorophenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-(trifluoromethyl)phenyl)amino)ethyl)-2-methyl- 10 7-(trifluoromethyl)quinazolin-4(3H)-one; 5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-((1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4- dihydroquinazolin-6-yl)ethyl)amino)benzonitrile; 7-Chloro-6-((S)-1-((5-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2- methylquinazolin-4(3H)-one; 15 7-Chloro-6-((S)-1-((5-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-2- methylquinazolin-4(3H)-one; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-methoxyphenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-methoxyphenyl)amino)ethyl)-2-methyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; (S)-2-(6-(((4-(3-Fluoropyrrolidine-1-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(3,3-Difluoropyrrolidine-1-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 25 2-(2-Methyl-6-((methyl(4-(1-(trifluoromethyl)-2-oxa-6-azaspiro[3.3]heptane-6- carbonyl)phenyl)amino)methyl)-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(1,1-Difluoro-5-azaspiro[2.4]heptane-5-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4- oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(1-Oxa-7-azaspiro[3.5]nonane-7-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-30 (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(6-Acetyl-2,6-diazaspiro[3.3]heptane-2-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4- oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(2-Methyl-6-((methyl(4-(4-(oxetan-3-yl)piperazine-1-carbonyl)phenyl)amino)methyl)-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 84 201369 2-(6-(((4-((3R,4R)-4-((tert-Butoxycarbonyl)amino)-3-methoxypiperidine-1- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-((3S,4S)-4-((tert-Butoxycarbonyl)(methyl)amino)-3-fluoropiperidine-1- 5 carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-((3S,4R)-4-((tert-Butoxycarbonyl)(methyl)amino)-3-fluoropiperidine-1- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 10 2-(6-(((4-((3S,4R)-4-((tert-Butoxycarbonyl)amino)-3-fluoropiperidine-1- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-(5-(tert-Butoxycarbonyl)-2-oxa-5,8-diazaspiro[3.5]nonane-8- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic 15 acid; 2-(6-(((4-((3S,4R)-3-((tert-Butoxycarbonyl)amino)-4-methoxypyrrolidine-1- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; (S)-2-(6-(((4-(3-((tert-Butoxycarbonyl)amino)-4,4-difluoropiperidine-1- 20 carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 2-(6-(((4-((3S,4S)-3-((tert-Butoxycarbonyl)amino)-4-fluoropiperidine-1- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 25 2-(6-(((4-((3S,4R)-3-((tert-Butoxycarbonyl)amino)-4-fluoropiperidine-1- carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; (S)-2-(6-(((4-(3-Acetamidopiperidine-1-carbonyl)phenyl)(methyl)amino)methyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 30 2-(2-Methyl-6-((methyl(4-(4-(oxetan-3-ylamino)piperidine-1-carbonyl)phenyl)amino)methyl)-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-((2-methyl-2H- tetrazol-5-yl)methyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-((1-methyl-1H- 35 tetrazol-5-yl)methyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 85 201369 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-(2-(1-methyl- 1H-tetrazol-5-yl)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 3-((1H-1,2,3-Triazol-4-yl)methyl)-6-((S)-1-((4-((2S,6R)-2,6-dimethylmorpholine-4- carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 5 (R)-2-(6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)propanoic acid; (S)-2-(6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)propanoic acid; (R)-2-Cyclopropyl-2-(6-((S)-1-((4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-10 methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; (S)-2-Cyclopropyl-2-(6-((S)-1-((4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2- methyl-4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; (S)-1-((2-Methyl-4-oxo-7-(trifluoromethyl)-6-(1-((4-(4-(trifluoromethyl)piperidine-1- carbonyl)phenyl)amino)ethyl)quinazolin-3(4H)-yl)methyl)cyclopropane-1-carboxylic acid; 15 6-(1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)allyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-7-(trifluoromethyl)-6-((1S)-1-((4-(2-(trifluoromethyl)morpholine-4- carbonyl)phenyl)amino)ethyl)quinazolin-4(3H)-one; 2-Methyl-7-(trifluoromethyl)-6-((1S)-1-((4-(3-(trifluoromethyl)morpholine-4- 20 carbonyl)phenyl)amino)ethyl)quinazolin-4(3H)-one; (S)-2-Methyl-6-(1-((4-(morpholine-4-carbonyl)phenyl)amino)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)- one; 2-Methyl-6-((S)-1-((4-((R)-3-methylmorpholine-4-carbonyl)phenyl)amino)ethyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 (S)-6-(1-((4-(4-(2-Hydroxyethyl)piperazine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((1S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((1S)-1-((4-(6-Oxa-3-azabicyclo[3.1.1]heptane-3-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 30 (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-6-((S)-1-((4-((S)-3-methyl-5-oxopiperazine-1-carbonyl)phenyl)amino)ethyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((1S)-1-((4-(2-Oxa-8-azaspiro[5.5]undecane-8-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 6-((S)-1-((4-((S)-3-(Hydroxymethyl)piperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 86 201369 6-((1S)-1-((4-(3-(2-Hydroxypropan-2-yl)piperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; (S)-6-(1-((4-(2-Oxa-6-azaspiro[3.4]octane-6-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 (3R,4R)-4-Isopropyl-1-(4-(((S)-1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6- yl)ethyl)amino)benzoyl)pyrrolidine-3-carboxylic acid; 6-((S)-1-((4-((2S,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((1S)-1-((4-(2,6-Dimethyl-1,1-dioxidothiomorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((2R,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((R)-3-(Hydroxymethyl)piperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 (R)-1-(4-(((S)-1-(2-Methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6- yl)ethyl)amino)benzoyl)pyrrolidine-3-carboxylic acid; (S)-1-(4-(((S)-1-(2-Methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6- yl)ethyl)amino)benzoyl)piperidine-3-carboxylic acid; (S)-1-(4-(((S)-1-(2-Methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydroquinazolin-6- 20 yl)ethyl)amino)benzoyl)pyrrolidine-3-carboxylic acid; 7-Chloro-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)oxy)ethyl)-2- methylquinazolin-4(3H)-one; 7-Chloro-6-((S)-1-((6-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyridin-3-yl)oxy)ethyl)-2- methylquinazolin-4(3H)-one; 25 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,5-dimethyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-(4-((3S,4S,5R)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2,5-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-(4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2,5-dimethyl-7- 30 (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-5-fluoro-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5-Fluoro-6-((S)-1-(4-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 (S)-2,3-Dimethyl-6-(1-((4-(morpholine-4-carbonyl)phenyl)amino)ethyl)-7-(trifluoromethyl)quinazolin- 4(3H)-one; 87 201369 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-methoxypyridin-2-yl)amino)ethyl)-2,3- dimethyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 5 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyrazin-2-yl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)propyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; (S)-2-(6-(1-((4-(1,1-Difluoro-6-azaspiro[2.5]octane-6-carbonyl)phenyl)(methyl)amino)ethyl)-2-methyl-4-10 oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; (S)-2-Methyl-6-(1-(methyl(4-(morpholine-4-carbonyl)phenyl)amino)ethyl)-7-(trifluoromethyl)quinazolin- 4(3H)-one; 2-(6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)(methyl)amino)ethyl)-2-methyl-4- oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 15 6-((S)-1-(4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((6-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2,3-dimethyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-4- oxo-7-(trifluoromethyl)-3,4-dihydroquinazoline-8-carbonitrile; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,8-dimethyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 25 7-Chloro-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-8- fluoro-2-methylquinazolin-4(3H)-one; 7-Chloro-6-((S)-1-((4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)propyl)-2- methylquinazolin-4(3H)-one; 7-Chloro-6-((S)-1-((3-fluoro-5-((3R,4S,5S)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2- 30 yl)amino)ethyl)-2-methylquinazolin-4(3H)-one; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-7-(2-fluorophenyl)-2- methylquinazolin-4(3H)-one; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(pyridin-2- yl)quinazolin-4(3H)-one; 35 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-7-(3-fluorophenyl)-2- methylquinazolin-4(3H)-one; 88 201369 6-((S)-1-((4-((S)-3,4-Dimethyl-5-oxopiperazine-1-carbonyl)phenyl)amino)propyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-6-((S)-1-((4-((2R,5R)-2-methyl-5-(trifluoromethyl)piperazine-1-carbonyl)phenyl)amino)propyl)- 7-(trifluoromethyl)quinazolin-4(3H)-one; 5 2-Methyl-6-((S)-1-((4-((2S,5S)-2-methyl-5-(trifluoromethyl)piperazine-1-carbonyl)phenyl)amino)propyl)- 7-(trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-6-((S)-1-((4-((R)-3-methylpiperazine-1-carbonyl)phenyl)amino)propyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-7-(trifluoromethyl)-6-((S)-1-((4-((3S,5R)-3,4,5-trimethylpiperazine-1- 10 carbonyl)phenyl)amino)propyl)quinazolin-4(3H)-one; 6-((S)-1-((2-Fluoro-4-((S)-2-methylmorpholine-4-carbonyl)phenyl)amino)propyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((2-Fluoro-4-((R)-2-methylmorpholine-4-carbonyl)phenyl)amino)propyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)propyl)-2-isopropyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)methyl)-2-methoxy-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-(2-Chloro-4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((6-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-methylpyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-Cyclopropyl-6-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 25 6-((S)-1-((6-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-4-methylpyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((2-Chloro-4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-6-fluorophenyl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((6-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluoropyridin-3-yl)amino)ethyl)-2-methyl-7- 30 (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-(4-((3S,5R)-3,5-Dimethylpiperazine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-(4-((3R,4R,5S)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 6-((S)-1-((3-Fluoro-5-((3R,4S,5S)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)- 2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 89 201369 6-((S)-1-((5-(((2S,6R)-2,6-Dimethylmorpholino)methyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((R)-1-((5-(((2S,6R)-2,6-Dimethylmorpholino)methyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 6-((S)-1-((5-(((2S,6R)-2,6-Dimethylmorpholino)methyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 7-Chloro-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-2,5- dimethylquinazolin-4(3H)-one; 7-Chloro-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,5- 10 dimethylquinazolin-4(3H)-one; 7-Cyclopropyl-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2- yl)amino)ethyl)-2-methylquinazolin-4(3H)-one; 6-((S)-1-((3-Fluoro-5-((2RS,6RS)-2-(hydroxymethyl)-6-methylmorpholine-4-carbonyl)pyridin-2- yl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 15 6-((S)-1-((3-Fluoro-5-((2R,6R)-2-(hydroxymethyl)-6-methylmorpholine-4-carbonyl)pyridin-2- yl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 8-Fluoro-6-((S)-1-((5-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2- yl)amino)ethyl)-2,3-dimethyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2- 20 methylquinazolin-4(3H)-one; 7-Chloro-8-fluoro-6-((S)-1-((5-((3S,4S,5R)-4-fluoro-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2- yl)amino)ethyl)-2-methylquinazolin-4(3H)-one; 7-Chloro-8-fluoro-6-((S)-1-((5-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2- yl)amino)ethyl)-2-methylquinazolin-4(3H)-one; 25 7-Chloro-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-5-fluoro- 2-methylquinazolin-4(3H)-one; 7-Chloro-6-((S)-1-((5-((3S,4S,5R)-4-fluoro-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)- 2-methylquinazolin-4(3H)-one; 6-((S)-1-(4-((1R,5S)-8-Oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)phenoxy)ethyl)-2-methyl-7- 30 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((3R,4S,5S)-4-Fluoro-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((1S)-1-(4-(2,6-Dimethyl-1,1-dioxidothiomorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 35 6-((S)-1-(4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2,5-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 90 201369 6-((S)-1-((5-((3S,4S,5R)-4-Fluoro-3,5-dimethylpiperidine-1-carbonyl)pyrimidin-2-yl)amino)ethyl)-2,5- dimethyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-2,5-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 5 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,5-dimethyl- 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-7-fluoro-2- methylquinazolin-4(3H)-one; and 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)(methyl)amino)ethyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one, or a pharmaceutically acceptable salt of any one thereof. In embodiments, the specification provides a compound or pharmaceutically acceptable salt thereof which is selected from: 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,3-dimethyl-7- 15 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 20 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3- d]pyrimidin-4(3H)-one; 5-(2,6-Dimethylmorpholine-4-carbonyl)-2-((1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3-25 d]pyrimidin-6-yl)ethyl)amino)nicotinonitrile; 6-(1-(4-(4-Fluoro-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((2-Fluoro-4-(4-methoxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 30 3-(Cyclopropylmethyl)-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- 35 (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 91 201369 6-(1-((5-(4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 7-Chloro-6-(1-(4-(2,6-dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methylpyrido[3,2-d]pyrimidin- 4(3H)-one; 5 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-(4-(4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-5-fluoro-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 6-(Cyclopropyl((5-(2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)methyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-6-(2,2,2-trifluoro-1-((5-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 7-Chloro-6-(1-(4-(2,6-dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)ethyl)-2-methylquinazolin- 4(3H)-one; 7-Chloro-6-(1-(4-(4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methylquinazolin- 4(3H)-one; 7-Chloro-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methylquinazolin-4(3H)- 20 one; 6-(1-((6-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-3-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 3-((1H-Tetrazol-5-yl)methyl)-6-(1-((4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 25 6-(1-(4-(4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-7-(3-fluorophenyl)-2- methylquinazolin-4(3H)-one; 6-(1-(4-(4-Hydroxy-3,4,5-trimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- 30 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-(2-(2-methyl-2H-tetrazol- 5-yl)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; and 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-8-fluoro-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one, 35 or a pharmaceutically acceptable salt of any one thereof. 92 201369 In embodiments, the specification provides a compound selected from: 6-((1S)-1-((4-((1RS,4RS, 5S)-5-Hydroxy-2-azabicyclo[2.2.1]heptane-2-carbonyl)phenyl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,3-dimethyl- 5 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((R)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,3- dimethyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((R)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 10 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((R)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)oxy)ethyl)-2-methyl-7- 15 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 20 6-((R)-1-(4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-(4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-(((S)-1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-25 dihydropyrido[2,3-d]pyrimidin-6-yl)ethyl)amino)nicotinonitrile; 5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-(((R)-1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4- dihydropyrido[2,3-d]pyrimidin-6-yl)ethyl)amino)nicotinonitrile; 6-((S)-1-(4-((3S,4S,5R)-4-Fluoro-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 30 6-((S)-1-((2-Fluoro-4-((3S,4S,5R)-4-methoxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2- methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 3-(Cyclopropylmethyl)-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyridin-2- yl)amino)ethyl)-2-methyl-7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- 35 (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 93 201369 6-((R)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 5 6-((R)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((3S,4S,5R)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((R)-1-((5-((3S,4R,5R)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- 10 (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 7-Chloro-6-((R)-1-(4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methylpyrido[3,2- d]pyrimidin-4(3H)-one; 7-Chloro-6-((S)-1-(4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methylpyrido[3,2- d]pyrimidin-4(3H)-one; 15 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((R)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-(4-((3S,4S,5R)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- 20 (trifluoromethyl)pyrido[3,2-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-5-fluoro-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((R)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-5-fluoro-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 25 6-((R)-Cyclopropyl((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)methyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-Cyclopropyl((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)methyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-6-((R)-2,2,2-trifluoro-1-((5-((3S,4R,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2- 30 yl)oxy)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-6-((S)-2,2,2-trifluoro-1-((5-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2- yl)oxy)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 7-Chloro-6-((S)-1-(4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)ethyl)-2- methylquinazolin-4(3H)-one; 35 7-Chloro-6-((R)-1-(4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)ethyl)-2- methylquinazolin-4(3H)-one; 94 201369 7-Chloro-6-((S)-1-(4-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2- methylquinazolin-4(3H)-one; 7-Chloro-6-((R)-1-(4-((3S,4R,5R)-4-hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2- methylquinazolin-4(3H)-one; 5 7-Chloro-6-((R)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2- methylquinazolin-4(3H)-one; 7-Chloro-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2- methylquinazolin-4(3H)-one; 6-((S)-1-((6-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-3-yl)oxy)ethyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 3-((1H-Tetrazol-5-yl)methyl)-6-((S)-1-((4-((2S,6R)-2,6-dimethylmorpholine-4- carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-(4-((3S,4S,5R)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 6-((S)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-7-(3-fluorophenyl)-2- methylquinazolin-4(3H)-one; 6-((S)-1-(4-((3R,4R,5S)-4-Hydroxy-3,4,5-trimethylpiperidine-1-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-(2-(2-methyl- 20 2H-tetrazol-5-yl)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; and 6-((S)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-8-fluoro-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one, or a pharmaceutically acceptable salt of any one thereof. 25 In embodiments, the specification provides a compound selected from: 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((2-Cyclopropyl-4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 30 6-(1-((2-Cyclopropyl-6-(2,6-dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-(2-Methyl-6-(1-(methyl(4-(3-(trifluoromethyl)azetidine-1-carbonyl)phenyl)amino)ethyl)-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2-methyl-7- 35 (trifluoromethyl)quinazolin-4(3H)-one; 95 201369 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 3-(Cyclopropylmethyl)-6-(1-((4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-(6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)-N,N-dimethylacetamide; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-3-(2-hydroxy-2-methylpropyl)-2- 10 methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((3-Fluoro-5-(3-(2-hydroxypropan-2-yl)pyrrolidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 6-(1-((3-Fluoro-5-(3-(hydroxymethyl)pyrrolidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(-1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 7-Chloro-6-(1-((5-(2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2- 20 methylquinazolin-4(3H)-one; 2-Methyl-7-(trifluoromethyl)-6-(1-((4-(3-(trifluoromethyl)piperazine-1- carbonyl)phenyl)amino)ethyl)quinazolin-4(3H)-one; 6-(1-((4-(3-(Hydroxymethyl)pyrrolidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 6-(1-((4-(2,7-Dimethyl-1,4-oxazepane-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-6-(1-((4-(4-methylpiperidine-1-carbonyl)phenyl)amino)ethyl)-7-(trifluoromethyl)quinazolin- 4(3H)-one; 6-(1-((4-(4-Acetylpiperazine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin- 30 4(3H)-one; 6-(1-((4-(1,4-Oxazepane-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)- one; 6-(1-((4-(4-Methoxypiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin- 4(3H)-one; 35 6-(1-((4-(2-Oxa-7-azaspiro[3.5]nonane-7-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 96 201369 6-(1-((4-(6-Azaspiro[2.5]octane-6-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin- 4(3H)-one; 6-(1-((4-(3-Methoxypyrrolidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin- 4(3H)-one; 5 6-(1-((4-(3-Hydroxypiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin- 4(3H)-one; 6-(1-((4-(4-Acetyl-3,5-dimethylpiperazine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(3-methoxypiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin- 10 4(3H)-one; 6-(1-((4-(4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2-Oxa-6-azaspiro[3.5]nonane-6-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 7-Chloro-6-(1-((4-(2,6-dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2-methylquinazolin- 4(3H)-one; 6-(1-((4-(3,5-Dimethylpiperazine-1-carbonyl)-2-fluorophenyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,3-dimethyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((3-Fluoro-5-(4-(trifluoromethyl)piperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 25 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((6-(3-(2-Hydroxypropan-2-yl)pyrrolidine-1-carbonyl)pyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((6-(2,6-Dimethylmorpholine-4-carbonyl)-4-fluoropyridin-3-yl)amino)ethyl)-2-methyl-7- 30 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((6-(2,6-Dimethylmorpholine-4-carbonyl)-4-fluoropyridin-3-yl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-Cyclopropyl-6-(1-((4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)propyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 7-Chloro-6-(1-(4-(2,6-dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methylquinazolin-4(3H)-one 97 201369 5-(2,6-Dimethylmorpholine-4-carbonyl)-2-(1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3- d]pyrimidin-6-yl)ethoxy)nicotinonitrile; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 6-(1-((5-(4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(4-Methoxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin- 10 4(3H)-one; 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)-2,2,2-trifluoroethyl)-2-methyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-2-methylphenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(Hexahydro-1H-furo[3,4-c]pyrrole-5-carbonyl)phenyl)(methyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 2-Methyl-6-(1-((4-(3-methylpiperidine-1-carbonyl)phenyl)amino)ethyl)-7-(trifluoromethyl)quinazolin- 4(3H)-one; 6-(1-((4-(3-Oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2-Oxa-5-azabicyclo[4.1.0]heptane-5-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 30 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(3-(1-Hydroxycyclopropyl)piperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 2-Methyl-7-(trifluoromethyl)-6-(1-((4-(4-(trifluoromethyl)piperidine-1- carbonyl)phenyl)amino)ethyl)quinazolin-4(3H)-one; 35 2-Methyl-6-(1-((4-(4-(oxetan-3-yl)piperidine-1-carbonyl)phenyl)amino)ethyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 98 201369 6-(1-((4-(5-Hydroxy-2-azabicyclo[2.2.1]heptane-2-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-2-methoxyphenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 5 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-2-fluoro-3-methoxyphenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5-(2,6-Dimethylmorpholine-4-carbonyl)-2-((1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4-dihydropyrido[2,3- d]pyrimidin-6-yl)ethyl)amino)benzonitrile; 6-(1-((6-(2,6-Dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-methoxypyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)propyl)-2-ethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 6-(1-((4-(2-Oxa-7-azaspiro[4.4]nonane-7-carbonyl)phenyl)(methyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 7-Chloro-6-(1-((4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methylquinazolin-4(3H)- one; 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)propyl)-2,3-dimethyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-(6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)-N-methylacetamide; 25 1-((6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)methyl)cyclopropane-1-carboxylic acid; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-(2-morpholino-2- oxoethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-3-ethyl-2-methyl-7- 30 (trifluoromethyl)quinazolin-4(3H)-one; 3-(2-(1H-Tetrazol-5-yl)ethyl)-6-(1-((4-(2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 6-(1-((4-(2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-(2-oxo-2-(pyrrolidin-1- yl)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 35 2-(2-Methyl-4-oxo-7-(trifluoromethyl)-6-(1-((4-(4-(trifluoromethyl)piperidine-1- carbonyl)phenyl)amino)ethyl)quinazolin-3(4H)-yl)propanoic acid; 99 201369 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)phenoxy)propyl)-2-methyl-7-(trifluoromethyl)quinazolin- 4(3H)-one; 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)propyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 6-(1-(4-(2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2,3-dimethyl-7-(trifluoromethyl)pyrido[2,3- d]pyrimidin-4(3H)-one; 2-Methyl-7-(trifluoromethyl)-6-(1-(4-(3-(trifluoromethyl)piperazine-1- carbonyl)phenoxy)ethyl)quinazolin-4(3H)-one; 6-(Cyclopropyl((5-(2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)methyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; and 6-(1-((5-(2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)-3-hydroxypropyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one, or a pharmaceutically acceptable salt of any one thereof. 15 In embodiments, there is provided a compound selected from: 6-((R)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 20 6-((S)-1-((2-Cyclopropyl-4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((2-Cyclopropyl-6-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; (S)-2-(2-Methyl-6-(1-(methyl(4-(3-(trifluoromethyl)azetidine-1-carbonyl)phenyl)amino)ethyl)-4-oxo-7-25 (trifluoromethyl)quinazolin-3(4H)-yl)acetic acid; 6-((R)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 30 6-((R)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 35 (trifluoromethyl)quinazolin-4(3H)-one; 100 201369 3-(Cyclopropylmethyl)-6-((S)-1-((4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 2-(6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)-N,N-dimethylacetamide; 5 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-3-(2-hydroxy-2- methylpropyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((3-Fluoro-5-((R)-3-(2-hydroxypropan-2-yl)pyrrolidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((3-Fluoro-5-((S)-3-(2-hydroxypropan-2-yl)pyrrolidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2- 10 methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((3-Fluoro-5-((R)-3-(hydroxymethyl)pyrrolidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 7-Chloro-6-((S)-1-((5-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2- methylquinazolin-4(3H)-one; 2-Methyl-7-(trifluoromethyl)-6-((S)-1-((4-((R)-3-(trifluoromethyl)piperazine-1- 20 carbonyl)phenyl)amino)ethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((R)-3-(Hydroxymethyl)pyrrolidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((2R,7S)-2,7-Dimethyl-1,4-oxazepane-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 6-((S)-1-((4-((2S,7R)-2,7-Dimethyl-1,4-oxazepane-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; (S)-2-Methyl-6-(1-((4-(4-methylpiperidine-1-carbonyl)phenyl)amino)ethyl)-7-(trifluoromethyl)quinazolin- 4(3H)-one; (S)-6-(1-((4-(4-Acetylpiperazine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin- 30 4(3H)-one; (S)-6-(1-((4-(1,4-Oxazepane-4-carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin- 4(3H)-one; (S)-6-(1-((4-(4-Methoxypiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 (S)-6-(1-((4-(2-Oxa-7-azaspiro[3.5]nonane-7-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 101 201369 (S)-6-(1-((4-(6-Azaspiro[2.5]octane-6-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((S)-3-Methoxypyrrolidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 6-((S)-1-((4-((S)-3-Hydroxypiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((3S,5R)-4-Acetyl-3,5-dimethylpiperazine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((S)-3-Methoxypiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((3R,4R,5S)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((3S,4S,5R)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 (S)-6-(1-((4-(2-Oxa-6-azaspiro[3.5]nonane-6-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 7-Chloro-6-((S)-1-((4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2- methylquinazolin-4(3H)-one; 6-((S)-1-((4-((3S,5R)-3,5-Dimethylpiperazine-1-carbonyl)-2-fluorophenyl)amino)ethyl)-2,3-dimethyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2,3-dimethyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 25 6-((R)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; (S)-6-(1-((3-Fluoro-5-(4-(trifluoromethyl)piperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; (R)-6-(1-((3-Fluoro-5-(4-(trifluoromethyl)piperidine-1-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- 30 (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((1S)-1-((6-(3-(2-Hydroxypropan-2-yl)pyrrolidine-1-carbonyl)pyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 35 6-((S)-1-((6-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-4-fluoropyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 102 201369 6-((S)-1-((6-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-4-fluoropyridin-3-yl)amino)ethyl)-2,3-dimethyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 2-Cyclopropyl-6-((S)-1-((4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)propyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 7-Chloro-6-((S)-1-(4-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methylquinazolin- 4(3H)-one; 5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-2-((S)-1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4- dihydropyrido[2,3-d]pyrimidin-6-yl)ethoxy)nicotinonitrile; 5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-2-((R)-1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4- 10 dihydropyrido[2,3-d]pyrimidin-6-yl)ethoxy)nicotinonitrile; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((3S,4S,5R)-4-Hydroxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 6-((S)-1-((5-((3S,4S,5R)-4-Methoxy-3,5-dimethylpiperidine-1-carbonyl)pyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-(4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-(4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)ethyl)-2-methyl-7- 20 (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-(4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((R)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 6-((S)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((R)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)oxy)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)oxy)ethyl)-2-methyl-7- 30 (trifluoromethyl)quinazolin-4(3H)-one; 6-((R)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)-2,2,2-trifluoroethyl)-2-methyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-2-yl)oxy)-2,2,2-trifluoroethyl)-2-methyl- 7-(trifluoromethyl)quinazolin-4(3H)-one; 35 6-((R)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-methylphenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 103 201369 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-methylphenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((3aR,6aS)-Hexahydro-1H-furo[3,4-c]pyrrole-5-carbonyl)phenyl)(methyl)amino)ethyl)-2,3- dimethyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 5 2-Methyl-6-((1S)-1-((4-(3-methylpiperidine-1-carbonyl)phenyl)amino)ethyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((1R,5S)-3-Oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((1RS,6SR)-2-Oxa-5-azabicyclo[4.1.0]heptane-5-carbonyl)phenyl)amino)ethyl)-2-methyl-7- 10 (trifluoromethyl)quinazolin-4(3H)-one; 6-((1S)-1-((4-(3-(1-Hydroxycyclopropyl)piperidine-1-carbonyl)phenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; (S)-2-Methyl-6-(1-((4-(4-(oxetan-3-yl)piperidine-1-carbonyl)phenyl)amino)ethyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 15 (S)-2-Methyl-7-(trifluoromethyl)-6-(1-((4-(4-(trifluoromethyl)piperidine-1- carbonyl)phenyl)amino)ethyl)quinazolin-4(3H)-one; (S)-2-Methyl-6-(1-((4-(4-(oxetan-3-yl)piperidine-1-carbonyl)phenyl)amino)ethyl)-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((1S)-1-((4-((1RS,4RS)-5-Hydroxy-2-azabicyclo[2.2.1]heptane-2-carbonyl)phenyl)amino)ethyl)-2-methyl- 20 7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-methoxyphenyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((R)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluoro-3-methoxyphenyl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 25 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluoro-3-methoxyphenyl)amino)ethyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-(((S)-1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4- dihydropyrido[2,3-d]pyrimidin-6-yl)ethyl)amino)benzonitrile; 5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-2-(((R)-1-(2-methyl-4-oxo-7-(trifluoromethyl)-3,4- 30 dihydropyrido[2,3-d]pyrimidin-6-yl)ethyl)amino)benzonitrile; 6-((R)-1-((6-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((6-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)pyridin-3-yl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 6-((R)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-methoxypyridin-2-yl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 104 201369 6-((S)-1-((5-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)-3-methoxypyridin-2-yl)amino)ethyl)-2-methyl- 7-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 6-((S)-1-((4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)propyl)-2-ethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 5 6-((1S)-1-((4-(2-Oxa-7-azaspiro[4.4]nonane-7-carbonyl)phenyl)(methyl)amino)ethyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 7-Chloro-6-((R)-1-((4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2- methylquinazolin-4(3H)-one; 7-Chloro-6-((S)-1-((4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2- 10 methylquinazolin-4(3H)-one; 6-((S)-1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)pyrimidin-2-yl)amino)propyl)-2,3-dimethyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 15 6-((R)-1-((4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenyl)amino)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-(6-((S)-1-((4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-4-oxo-7- (trifluoromethyl)quinazolin-3(4H)-yl)-N-methylacetamide; 1-((6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-4-oxo-7- 20 (trifluoromethyl)quinazolin-3(4H)-yl)methyl)cyclopropane-1-carboxylic acid; 6-((S)-1-((4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-(2- morpholino-2-oxoethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((2S,6R)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-3-ethyl-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 25 3-(2-(1H-Tetrazol-5-yl)ethyl)-6-((S)-1-((4-((2R,6S)-2,6-dimethylmorpholine-4- carbonyl)phenyl)amino)ethyl)-2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-1-((4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenyl)amino)ethyl)-2-methyl-3-(2-oxo-2- (pyrrolidin-1-yl)ethyl)-7-(trifluoromethyl)quinazolin-4(3H)-one; (R)-2-(2-Methyl-4-oxo-7-(trifluoromethyl)-6-((S)-1-((4-(4-(trifluoromethyl)piperidine-1- 30 carbonyl)phenyl)amino)ethyl)quinazolin-3(4H)-yl)propanoic acid; (S)-2-(2-Methyl-4-oxo-7-(trifluoromethyl)-6-((S)-1-((4-(4-(trifluoromethyl)piperidine-1- carbonyl)phenyl)amino)ethyl)quinazolin-3(4H)-yl)propanoic acid; 6-((S)-1-(4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenoxy)propyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 35 6-((S)-1-(4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-2-fluorophenoxy)propyl)-2-methyl-7- (trifluoromethyl)quinazolin-4(3H)-one; 105 201369 6-((S)-1-(4-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)phenoxy)ethyl)-2,3-dimethyl-7- (trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-one; 2-Methyl-7-(trifluoromethyl)-6-((S)-1-(4-((S)-3-(trifluoromethyl)piperazine-1- carbonyl)phenoxy)ethyl)quinazolin-4(3H)-one; 5 6-((R)-Cyclopropyl((5-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)methyl)- 2-methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; 6-((S)-Cyclopropyl((5-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)methyl)-2- methyl-7-(trifluoromethyl)quinazolin-4(3H)-one; and 6-(1-((5-((2R,6S)-2,6-Dimethylmorpholine-4-carbonyl)-3-fluoropyridin-2-yl)amino)-3-hydroxypropyl)-2- 10 methyl-7-(trifluoromethyl)quinazolin-4(3H)-one, or a pharmaceutically acceptable salt of any one thereof. The present specification is intended to include all isotopes of atoms occurring in the present compounds. Isotopes will be understood to include those atoms having the same atomic number but 15 different mass numbers. For example, isotopes of hydrogen include tritium and deuterium. Isotopes of carbon include13C and14C. Isotopically labelled compounds of formula (I-X) or (I) can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying Examples using appropriate isotopically labelled reagents in place of the non-labelled reagents previously employed. 20 A suitable pharmaceutically acceptable salt of a compound of the formula (I-X) or (I) may be, for example, an acid addition salt or a base addition salt. A suitable pharmaceutically acceptable salt of a compound of the formula (I-X) or (I) may be, for example, an acid-addition salt of a compound of the formula (I-X) or (I), for example an acid-addition salt with an inorganic or organic acid. The compounds of the specification may be provided as the free compound, i.e. in the non-salified state. Certain of the 25 compounds of formula (I-X) or (I) may form acid or base addition salts with one or more equivalents of the acid or base. The present specification is intended to include all possible stoichiometric and non- stoichiometric forms of acid- and base-addition salts. An example list of pharmaceutically acceptable salts can be found in the Handbook of Pharmaceutical Salts: Properties, Selection and Use, P. H. Stahl and C. G.Wermuth, editors, Weinheim / Zürich:Wiley-VCH / VHCA, 2002. 30 A further suitable pharmaceutically acceptable salt of a compound of formula (I-X) or (I) may be, for example, a salt formed within the human or animal body after administration of a compound of formula (I-X) or (I) to said human or animal body. The compounds of formula (I-X) or (I) or pharmaceutically acceptable salts thereof may be solvated. The present specification is intended to include all stoichiometric and non-stoichiometric 35 solvates. It will be understood that the present specification encompasses pharmaceutically acceptable prodrugs of compounds of formula (I-X) or (I) and their pharmaceutically acceptable salts i.e. 106 201369 pharmaceutically acceptable derivatives which, upon administration to a subject, are capable of directly or indirectly providing a compound of formula (I-X), (I) or a pharmaceutically acceptable salt thereof. Further information on pharmaceutically acceptable prodrugs can be found, for example, in Rautio, J., Meanwell, N., Di, L. et al., Nat Rev Drug Discov 17, 559–587 (2018).5 It will be understood that the present specification encompasses all isomers of compounds of formula (I-X), (I) and their pharmaceutically acceptable salts, including all geometric, tautomeric and optical forms, and mixtures thereof (e.g. racemic mixtures). Where additional chiral centres are present in compounds of formula (I-X), (I) and their pharmaceutically acceptable salts, the present specification includes within its scope all possible diastereoisomers, including mixtures thereof. The different isomeric 10 forms may be separated or resolved one from the other by conventional methods, or any given isomer may be obtained by conventional synthetic methods or by stereospecific or asymmetric syntheses. Therapeutic Uses The compounds and pharmaceutically acceptable salts of the specification are antagonists of 15 GIPR. Therefore, the compounds and pharmaceutically acceptable salts of the specification are expected to be useful in the prophylaxis or treatment of disorders in which antagonism of GIPR provides a prophylactic or therapeutic effect. The term “antagonists of GIPR” as used herein, refers to a compound or pharmaceutically acceptable salt thereof as defined herein which is capable of binding to the GIPR and preventing its20 activation by the endogenous receptor ligand GIP. As used herein, “prophylaxis” is intended to have its normal meaning and includes primary prophylaxis to prevent the development of the disease or condition and secondary prophylaxis whereby the disease or condition has already developed and the subject is temporarily or permanently protected against exacerbation or worsening of the disease or condition, or the development of new symptoms 25 associated with the disease or condition. The terms “prophylactic”, “preventing” and “prevention” are used synonymously with “prophylaxis”. As used herein, “treatment” is intended to have its normal meaning of dealing with a disease or condition in order to entirely or partially relieve one, some or all of its symptoms in a subject, or to correct or compensate for the underlying pathology. The terms “treatment” and “treating” are used 30 synonymously with “therapy”. The phrase "effective amount", as used herein, means an amount of a compound of formula (I) or pharmaceutically acceptable salt thereof, or pharmaceutical composition which is sufficient enough to significantly and positively modify the symptoms and / or conditions to be treated (e.g., provide a positive clinical response). The effective amount of an active ingredient for use in a pharmaceutical composition 35 will vary with the particular condition being treated, the severity of the condition, the duration of the treatment, the nature of concurrent therapy, the particular active ingredient(s) being employed, the 107 201369 particular pharmaceutically acceptable excipient(s) / carrier(s) utilized, and like factors within the knowledge and expertise of the attending physician. In embodiments, the specification provides a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt 5 thereof), for use as a medicament. In embodiments, the specification provides a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), for use in the prophylaxis or treatment of a disorder in which antagonism of GIPR provides a prophylactic or therapeutic effect. In embodiments, the specification provides a compound of formula (I- 10 X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), for use in the prophylaxis of a disorder in which antagonism of GIPR provides a prophylactic effect. In embodiments, the specification provides a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), for use in the treatment of a disorder in which antagonism of 15 GIPR provides a therapeutic effect. In embodiments, the specification provides the use of a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), in the manufacture of a medicament for the prophylaxis or treatment of a disorder in which antagonism of GIPR provides a prophylactic or therapeutic effect. In embodiments, the 20 specification provides the use of a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), in the manufacture of a medicament for the prophylaxis of a disorder in which antagonism of GIPR provides a prophylactic effect. In embodiments, the specification provides the use of a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically 25 acceptable salt thereof), in the manufacture of a medicament for the treatment of a disorder in which antagonism of GIPR provides a therapeutic effect. In embodiments, the specification provides a method of preventing or treating a disorder in which antagonism of GIPR provides a prophylactic or therapeutic effect, comprising administering a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of 30 formula (I) or a pharmaceutically acceptable salt thereof). In embodiments, the specification provides a method of preventing a disorder in which antagonism of GIPR provides a prophylactic effect, comprising administering a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof). In embodiments, the specification provides a method of treating a disorder in which antagonism of GIPR provides a 35 therapeutic effect, comprising administering a compound of formula (I-X) or a pharmaceutically 108 201369 acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof). In embodiments, the disorder is diabetes, type 1 diabetes, type 2 diabetes, hyperinsulinemia (such as congenital hyperinsulinism), Cushing’s syndrome, gestational diabetes, pre-diabetes, insulin 5 resistance syndrome, impaired glucose tolerance (IGl), disease states associated with elevated blood glucose levels, metabolic disease including metabolic syndrome, or hyperglycemia (such as abnormal postprandial hyperglycemia). In embodiments, the disorder is an eating disorder, hepatic steatosis ("fatty liver"), kidney failure, arteriosclerosis (such as atherosclerosis), cardiovascular disease, macrovascular disease, 10 microvascular disease, diabetic heart (including diabetic cardiomyopathy and heart failure as a diabetic complication), coronary heart disease, peripheral artery disease or stroke, cancer, dumping syndrome, hypertension e.g. pulmonary hypertension, or dyslipidemia (such as atherogenic dyslipidemia, cholescystitis, or short bowel syndrome). In embodiments, the disorder is type 2 diabetes, obesity and related comorbidities (such as sleep apnoea, metabolic associated steatohepatitis or osteoarthritis), 15 cardiovascular disease, heart failure or chronic kidney disease. In embodiments, the disorder is obesity. In embodiments, the disorder is cardiovascular disease. In embodiments, the compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as the compound of formula (I) or a pharmaceutically acceptable salt thereof) is administered to a human subject. In embodiments, the human subject is obese. 20 In embodiments, administration of a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) results in a reduction in appetite, reduces food intake, reduces weight gain, promotes weight loss and / or reduces excess body weight e.g. in an obese subject. In embodiments, the disorder is diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes 25 mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal30 tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., 35 caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), excessive sugar craving, dyslipidemia [including hyperlipidemia, 109 201369 hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH),fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), 5 peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post-prandial lipemia, metabolic acidosis, ketosis, arthritis, 10 osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease, macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot 15 ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), or addiction (e.g., addition to alcohol, nicotine, and / or drug). 20 Pharmaceutical Compositions The term "pharmaceutical composition", as used herein, refers to a preparation which is in such form as to permit the biological activity of the active ingredient to be expressed, and which contains no additional components which are unacceptably toxic to a subject to which the composition would be administered. Such compositions can be sterile. 25 For use in prophylaxis or therapy, a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) will typically be administered in the form of a pharmaceutical composition. Therefore, in embodiments the specification provides a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of 30 formula (I) or a pharmaceutically acceptable salt thereof) and at least one pharmaceutically acceptable excipient. In embodiments, the specification provides a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and at least one pharmaceutically acceptable 35 excipient, for use as a medicament. 110 201369 In embodiments, the specification provides a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and at least one pharmaceutically acceptable excipient, for use in the prophylaxis or treatment of a disorder in which antagonism of GIPR provides a 5 prophylactic or therapeutic effect, such as the disorders disclosed herein. In embodiments, the specification provides a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and at least one pharmaceutically acceptable excipient, for use in the prophylaxis of a disorder in which antagonism of GIPR provides a prophylactic effect, such as the 10 disorders disclosed herein. In embodiments, the specification provides a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and at least one pharmaceutically acceptable excipient, for use in the treatment of a disorder in which antagonism of GIPR provides a therapeutic effect, such as the disorders disclosed herein. 15 In embodiments, the specification provides the use of a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and at least one pharmaceutically acceptable excipient, in the manufacture of a medicament for the prophylaxis or treatment of a disorder in which antagonism of GIPR provides a prophylactic or therapeutic effect, such as the disorders disclosed herein. 20 In embodiments, the specification provides the use of a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and at least one pharmaceutically acceptable excipient, in the manufacture of a medicament for the prophylaxis of a disorder in which antagonism of GIPR provides a prophylactic effect, such as the disorders disclosed herein. In embodiments, the 25 specification provides the use of a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and at least one pharmaceutically acceptable excipient, in the manufacture of a medicament for the treatment of a disorder in which antagonism of GIPR provides a therapeutic effect, such as the disorders disclosed herein. 30 In embodiments, the specification provides a method of preventing or treating a disorder in which antagonism of GIPR provides a prophylactic or therapeutic effect, such as the disorders disclosed herein, comprising administering a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), and at least one pharmaceutically acceptable excipient. In embodiments, the 35 specification provides a method of preventing a disorder in which antagonism of GIPR provides a prophylactic effect, such as the disorders disclosed herein, comprising administering a pharmaceutical 111 201369 composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), and at least one pharmaceutically acceptable excipient. In embodiments, the specification provides a method of treating a disorder in which antagonism of GIPR provides a therapeutic effect, such as the disorders disclosed 5 herein, comprising administering a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), and at least one pharmaceutically acceptable excipient. Pharmaceutical compositions according to the present specification will typically be administered in a pharmaceutically acceptable dosage form via the oral, parenteral, intravenous, 10 intramuscular, subcutaneous or in other injectable ways, buccal, rectal, vaginal, transdermal and / or nasal route and / or via inhalation. Depending upon the disorder and patient to be treated and the route of administration, the compositions may be administered at varying doses. In embodiments, a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), or a pharmaceutical composition comprising a 15 compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and at least one pharmaceutically acceptable excipient are administered orally. Dosage forms suitable for oral use form one aspect of the specification. In embodiments, the specification provides a solid oral dosage form comprising compound of formula (I-X) or a 20 pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and at least one pharmaceutically acceptable excipient are administered orally. In embodiments, the solid oral dosage form is a tablet. 25 The compositions of the specification may be obtained by conventional procedures using conventional pharmaceutical excipients, well known in the art. Thus, compositions intended for oral use may contain, for example, one or more colouring, sweetening,flavouring and / or preservative agents. Suitable pharmaceutically acceptable excipients for a tablet formulation include, for example, inert diluents; granulating and disintegrating agents; binding agents; and lubricating agents. Tablet 30 formulations may be uncoated or coated using conventional coating agents and procedures well known in the art. Further information regarding formulations is described in, for example, Chapter 25.2 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press 1990. The amount of active ingredient that is combined with one or more excipients to produce a single dosage form will necessarily vary depending upon the host treated and the particular35 route of administration. Further information regarding routes of administration and dosage regimes are112 201369 described in, for example, Chapter 25.3 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press 1990. Combinations 5 A compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) may be administered in conjunction with a second active agent for the prophylaxis or treatment of the disorders described herein. Therefore, in embodiments there is provided a combination comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically 10 acceptable salt thereof) and a second active agent. Administration of the compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and the second active agent may be concurrent, sequential or simultaneous. Combinations described herein may also be administered with a further active agent or agents. 15 Kits In embodiments, the specification provides a kit comprising a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I) or a pharmaceutically acceptable salt thereof) and instructions for their use in prophylaxis or treatment, such as in the 20 prophylaxis or treatment of the disorders described herein. Processes Compounds of formula (I-X) or a pharmaceutically acceptable salt thereof (such as compounds of formula (I) and their pharmaceutically acceptable salts thereof) may be prepared according to 25 conventional methods known to the skilled person. In embodiments, the specification provides a compound of formula (I-X) or a pharmaceutically acceptable salt thereof (such as a compound of formula (I), or a pharmaceutically acceptable salt thereof), which is obtainable by the methods disclosed in the “Examples” section. Therefore, in embodiments there is provided a process for preparing the compounds of the 30 formula (I-X) or a pharmaceutically acceptable salt thereof, which comprises any one of methods a1 to a5 described herein. Where necessary converting the resultant compound of formula (I-X) into a pharmaceutically acceptable salt thereof, and where desired separating the resultant compound of formula (I-X) into its individual optical isomers. Method a1: The compounds of formula (I-X) in which R1, R2, R20, R21, R40, Z1, X1, X2, X3and B are 35 defined as in formula (I-X) may be formed by reacting a compound of formula (II) in which R1, R2, R20, 113 201369 R21, Z1, X1, X2, X3and B are defined as in formula (I-X), with a compound of formula (III) in which R41, R42are defined as in formula (I-X). The reaction may be carried out in an inert organic solvent such as DCM, DMF, DMSO or MeCN or 5 mixtures thereof, in the presence of a suitable coupling reagent (typically 1.2 – 4 eq) such as EDC, EDCxHCl, HATU or T3P and a suitable base (typically 1.1 – 10 eq) such as DIPEA or TEA; or in the presence of TCFH (typically 2 ^ 4 eq.) in combination with NMI (typically 3 ^ 10 eq). The reaction may be carried out at temperatures ranging typically from 20oC to 75oC for a prolonged time (typically 0.5 – 72 h) using standard equipment under an inert atmosphere. Formula (III) is normally used in a slight excess 10 (typically 1.1 – 3 eq) to formula (II) but can also be used in equimolar amount to formula (II). Method a2: The compounds of formula (I-X) in which R1, R2, R20, R21, R40, Z1, X1, X2, X3and B are defined as in formula (I-X) and Z1is NR22or O or S may be formed by reacting a compound of formula (IV) in which R1, R2, R20, R21, X1, X2and X3are defined as in formula (I-X), with a compound of formula (V) in which R40and B are defined as in formula (I-X) and W is OH or SH, or formula (VI) in which R40and B 15 are defined as in formula (I-X). LG1is a suitable leaving group such as halogen (typically Br or Cl) or mesylate (OMs) or triflate (OTf). (IV) (V) (VI) The reaction may be carried out in an inert organic solvent such as 1,4-dioxane, DMA or MeCN 20 in the presence of a suitable base (typically 1 ^ 3 eq) such as Ag2CO3, Cs2CO3, DIPEA or K2CO3. The reaction may be carried out at temperatures ranging typically from 20^C to 100oC for a prolonged reaction time (10 min – 72 h) using standard equipment. Formula (V) or (VI) is normally used in a slight excess (typically 1.1 – 3 eq) to formula (IV). Alternatively, the reaction may be catalyzed with a suitable palladium catalyst or pre-catalyst such as for example Xantphos Pd G4 in the presence of a base 25 (typically 2 – 4 eq) such as Cs2CO3, in an inert organic solvent such as 1,4-dioxane. The reaction may be carried out at temperatures ranging from 60oC to 120oC and preferentially under an inert atmosphere (e.g. an N2atmosphere) for a prolonged reaction time (typically 2 – 16 h). Method a3: The compounds of formula (I-X) in which R1, R2, R20, R21, R40, X1, X2, X3and B are defined as in formula (I-X) and Z1is NR22or O may be formed by reacting a compound of formula (VII) or 30 (VIII) in which R1, R2, R20, R21, R22, X1, X2and X3are defined as in formula (I-X), with a compound of 114 201369 formula (IX) in which R40and B are defined as in formula (I-X). LG3is a suitable leaving group such as halogen (F, Cl, Br or I) or mesylate (OMs) or triflate (OTf). 5 The reaction may be catalyzed with a suitable palladium catalyst or pre-catalyst such as BrettPhos Pd G3 , Pd-PEPPSI-IPentClor Pd-PEPPSI-IPentCl-o-picoline (typically 0.1 – 0.3 eq) in combination when needed with a suitable phosphine ligand, e.g. XPhos or XantPhos, in the presence of a base (typically 2 – 4 eq) such as Cs2CO3or NaOtBu in an inert organic solvent such as for example 1,4-dioxane or 2-MeTHF. The reaction may be carried out at temperatures ranging from 30oC to 100oC and 10 preferentially under an inert atmosphere (e.g. an N2 atmosphere) for a prolonged reaction time (typically 2 – 16 h). Alternatively, the reaction may also be performed without using a metal catalyst in an inert organic solvent such as DMF, DMSO, MeCN, 2-MeTHF, NMP or THF or mixtures thereof, in the presence of KF (typically 1 – 3 eq) or a suitable base such as Cs2CO3, K2CO3, DIPEA, NaOtBu or NaH (typically ranging from 1.5 to 3 eq) at temperatures typically ranging from 0^C to 150^C using 15 conventional or microwaved heating systems for a prolonged reaction time (typically 2 h – 6 days). Formula (IX) can also be used in a slight excess (typically 1.2 – 3 eq) to formula (VII) or formula (VIII) but can also be used in equimolar amount to formula (VII) or formula (VIII). Method a4: The compounds of formula (I-X) in which R1is not H and R2, R20, R21, R40, Z1, X1, X2, X3and B are defined as in formula (I-X) may be formed by reacting a compound of formula (X) in which R2, 20 R20, R21, R40, Z1, X1, X2, X3and B are defined as in formula (I-X), with a compound of formula (XI) in which R1is defined as in formula (I-X). LG3is a suitable leaving group such as halogen (Cl, Br, I) or mesylate (OMs) or triflate (OTf). 25 The reaction may be carried out in an organic solvent such as DMF, MeCN, MeOH, NMP or THF in the presence of a suitable base such as Cs2CO3, K2CO3, NaH or NaOH used in excess (1.2 – 6 eq). The reaction may be carried out at temperatures ranging typically from 20^C to 75oC for a prolonged reaction time (typically 1 – 60 h) using standard equipment. Formula (XI) can also be used in a slight excess (typically 1.1 – 1.5 eq) to formula (X). 30 Method a5: The compounds of formula (I-X) in which R1, R2, R20, R21, R40, Z1, X1, X2, X3and B are defined as in formula (I-X) may be formed through a Suzuki or Stille palladium catalyzed coupling by reacting a compound of 115 201369 formula (XII) in which R1, R2, R20, R21, R40, Z1, X1, X3and B are defined as in formula (I-X) and X2is CBr, with a compound of formula (XIII) in which R11is defined as in formula (I-X). LG4is a boron derivative such as boronic acid, boronic ester (e.g. B(OAlkyl)2) or trifluoroborate salt, or tin derivatives (e.g. SnBu3). 5 (XII) (XIII) The reaction may be catalyzed with a suitable palladium catalyst or pre-catalyst such as for example PdCl2(dtbpf) (typically 0.05 – 0.3 eq) in the presence of a base (typically 2 – 4 eq) such as Cs2CO3 or K2CO3in an inert organic solvent such as 1,4-dioxane, DMF, H2O, 2-MeTHF or THF or mixtures thereof, at elevated temperatures typically ranging from 60^C to 100^C for a prolonged reaction time (typically 3 10 h – 16 h) under an inert atmosphere (e.g. N2 atmosphere). The compounds of Formula (II) to (XIII) above may be commercially available, known in the art ormay be prepared by methods analogous to those described in the intermediates and examples or in a conventional manner known by a person skilled in the art. Where necessary converting the resultant compound of formula (I-X) into a pharmaceutically15 acceptable salt thereof, and where desired separating the resultant compound of formula (I-X) into its individual diastereoisomers or enantiomers using chiral resolving agents described in the literature and known to person skilled in the art, or using chiral chromatography methods described in the literature and known to person skilled in the art, or as described further in the Examples. It is understood that the processes for preparation described above also can be performed 20 starting from any enantiomer, or a racemic mixture, of compounds of Formula (II) to (XIII) above to give compounds of formula (I-X) or any stereoisomer of formula (I-X). It will also be appreciated that in some of the reactions mentioned herein it may be necessary / desirable to protect any sensitive or reactive groups, that otherwise could interfere in the reaction, in the compounds. The instances where protection is necessary or desirable, suitable methods 25 for protection are known to those skilled in the art. Conventional protecting groups may be used in accordance with standard practice (for illustration see “Protective groups in Organic Chemistry”, edited by J W F McOmie, 1Plenum Press (1973), and “Protective Groups in Organic Synthesis”, 4thedition, T.W. Greene & P.G.M Wutz, Wiley-Interscience (2007)). Thus, if reactants include groups such as amino, thiol, carboxy or hydroxy it may be desirable to protect the group in some of the reactions mentioned herein. 30 Examples of suitable protecting groups for hydroxy include trialkyl silyl or diarylalkylsilyl groups (e.g. tert-butyldimethylsilyl, tert-butyldiphenylsilyl or trimethylsilyl ethers). Suitable protecting groups for carboxylic acids include (C1-C6)alkyl or benzyl esters. Examples of suitable protecting groups for amino include tert-butyloxycarbonyl, benzyloxycarbonyl, and 9-fluorenylmethoxycrbonyl and trialkyl silyl 116 201369 groups (e.g. tert-butyldimethylsilyl and trimethylsilyl groups). Examples of suitable protecting groups for thiols include acetyl and 4-methoxy benzyl groups. The protecting groups may be removed and / or introduced at any convenient stage in the synthesis using conventional techniques well known in the chemical art. It will be appreciated by those skilled in the art how a compound comprising such a group 5 can be deprotected (see “Protective groups in Organic Chemistry”, edited by J W F McOmie, Plenum Press (1973), and “Protective Groups in Organic Synthesis”, 4rdedition, T.W. Greene & P.G.M Wutz, Wiley-Interscience (2007)). Persons skilled in the art will appreciate that certain compounds of formula (II) to (XIII) described above may also be referred to as being “protected derivatives“. Persons skilled inthe art will appreciate that in order to obtain compounds of the specification in an alternative, and on 10 some occasions, more convenient, manner, the individual process steps mentioned hereinbefore may be performed in different order, and / or the individual reactions may be performed at a different stage in the overall route (i.e. substituents may be added to and / or chemical transformations performed upon, different intermediates to those mentioned hereinbefore in conjunction with a particular reaction). This may negate, or render necessary, the need for protecting groups. Persons skilled in the 15 art will appreciate that chiral isomers of compounds herein can be resolved at any stage in the synthetic process using chiral resolving agents described in the literature and known to person skilled in the art, or using chiral chromatography methods described in the literature and known to person skilled in the art, or as described further in the Examples. Persons skilled in the art will appreciate that a -C=O, -CHO or C- OH group can be transferred into a -CF2, -CF2H or C-F respectively using a deoxofluorinating agent such20 as for example DAST (N,N-diethyl-1,1,1-trifluoro-l4-sulfanamine), deoxo-fluor reagent (e.g.1,1,1- trifluoro-N,N-bis(2-methoxyethyl)-l4-sulfanamine), XtalFluor-E or XtalFluor-M (See J. Org. Chem.2010, 75, 3401). Persons skilled in the art will appreciate that starting materials for any of the above processes can in some cases be commercially available. Persons skilled in the art will appreciate that processes could for some starting materials above be found in the general common knowledge. It will also be 25 understood that some of the compounds described in the processes above may exhibit the phenomenon of tautomerism and the processes described above include any tautomeric form. Intermediates In a further aspect the specification provides intermediates used in the preparation of 30 compounds of formula (I-X) and their pharmaceutically acceptable salts (such as compounds of formula (I) and their pharmaceutically acceptable salts), such as those disclosed in the “Examples” section. In embodiments, the specification provides an intermediate as disclosed in the “Examples” section, or a salt thereof, such as a pharmaceutically acceptable salt thereof. In embodiments, there is provided a compound of formula (II): 117 201369 , or a salt thereof, such as a pharmaceutically acceptable salt thereof, wherein R1, R2, X1, X2, X3, R20, R21, Z1and B are as defined herein. In embodiments, there is provided a compound of formula (III): 5 (III), or a salt thereof, such as a pharmaceutically acceptable salt thereof, wherein R41and R42are as defined herein. In embodiments, there is provided a compound of formula (IV): , 10 or a salt thereof, such as a pharmaceutically acceptable salt thereof, wherein LG1is a leaving group, such as halogen (for example Br or Cl), triflate (OTf) or mesylate (OMs), and R1, R2, X1, X2, X3, R20and R21are as defined herein. In embodiments, there is provided a compound of formula (V): , 15 or a salt thereof, such as a pharmaceutically acceptable salt thereof, wherein W is O or SH, and B and R40are as defined herein. In embodiments, there is provided a compound of formula (VI): , or a salt thereof, such as a pharmaceutically acceptable salt thereof, wherein R22, B and R40are as 20 defined herein. In embodiments, there is provided a compound of formula (VII): , 118 201369 or a salt thereof, such as a pharmaceutically acceptable salt thereof, wherein R1, R2, X1, X2, X3, R20, R21and R22are as defined herein. In embodiments, there is provided a compound of formula (VIII): 5 or a salt thereof, such as a pharmaceutically acceptable salt thereof, wherein R1, R2, X1, X2, X3, R20and R21are as defined herein. In embodiments, there is provided a compound of formula (IX): or a salt thereof, such as a pharmaceutically acceptable salt thereof, wherein LG3is a leaving group such 10 as halogen (for example F, Cl, Br or I), triflate (OTf) or mesylate (OMs), and B and R40are as defined herein. In embodiments, there is provided a compound of formula (XII): (XII), or a salt thereof, such as a pharmaceutically acceptable salt thereof, wherein R1R2, X1, X3, R20, R21, Z1, B 15 and R40are as defined herein. Clauses The specification may be further defined by the following clauses: Clause 1. A compound of formula (I-X): 20 , wherein: R1is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by: 119 201369 1) one or more groups independently selected from OH, NR1bR1c, C(O)OR1a, C(O)NR1bR1c, NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; 5 R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl; R1dis H, C1-6alkyl or C1-6haloalkyl; R1eis C1-6alkyl or C1-6haloalkyl; and / or 10 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein when present in R1, each C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, 15 C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2; R2is C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl or phenyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by one C3-6cycloalkyl or phenyl; 20 wherein when present in R2, each C3-6cycloalkyl and phenyl may be independently optionally substituted by one or more groups independently selected from halo, C1- 6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X1is N or CR10, and R10is H, halo, CN, C1-6alkyl or C1-6haloalkyl; X2is N or CR11, and R11is H, halo, CN, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, phenyl or 5-6 membered 25 heteroaryl; wherein said C3-6cycloalkyl, phenyl or 5-6 membered heteroaryl may each be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X3is N or CR12, and R12is H, halo, CN, C1-6alkyl or C1-6haloalkyl; wherein 0 or 1 of X1, X2and X3is N; 30 R20is H, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl or C2-6alkenyl; wherein said C1-6alkyl or C1-6haloalkyl may each be optionally substituted by one OH or COOH; and wherein said C3-6cycloalkyl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R21is H, C1-6alkyl or C1-6haloalkyl; or 35 R20and R21together with the atom to which they are attached form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl or 3-10 membered heterocycloalkyl may each be 120 201369 independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; Z1is CR23R24, O, NR22, S or S(O)2; R22is H, C1-6alkyl, C1-6haloalkyl, CH2C≡CH or C3-6cycloalkyl; wherein said C3-6cycloalkyl may be 5 optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1- 6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R23and R24are each independently H or C1-6alkyl; B is group (B1), (B2), (B3), (B4), (B5), (B6) or (B7): 10 wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40; m, n, o, p and q are each independently 0, 1 or 2; R30, R31, R32, R33and R34are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, 15 NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O2)NMe2 and C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; Y1is N, CH or CR31; Y2is N; 20 Y3is N; Y4is N, CH or CR32; Y5is N; Y6is N; W1and W2are each independently N or CH, provided that when one of W1and W2is N, the other is CH; 25 W3is S or O; R35is H or C1-6alkyl; R40is -A1NR41R42; A1is CH2or C(O); R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered 30 heterocycloalkyl which may be optionally substituted by: 121 201369 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1- 6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl, 3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); 5 wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1- 6haloalkoxy; 10 R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 15 R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally 20 substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH; or a pharmaceutically acceptable salt thereof. Clause 2. The compound or pharmaceutically acceptable salt thereof according to clause 1, which is a compound of formula (I): 25 wherein: R1is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by: 1) one or more groups independently selected from OH, NR1bR1c, C(O)OR1a, C(O)NR1bR1c, 30 NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; 122 201369 R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl; R1dis H, C1-6alkyl or C1-6haloalkyl; 5 R1eis C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl; wherein when present in R1, each C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl may be independently optionally substituted by 10 one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2; R2is C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl or phenyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by one 15 C3-6cycloalkyl or phenyl; wherein when present in R2, each C3-6cycloalkyl and phenyl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X1is N or CR10, and R10is H, halo, CN, C1-6alkyl or C1-6haloalkyl; 20 X2is N or CR11, and R11is halo, CN, C1-6haloalkyl, C1-6alkoxy, phenyl or 5-6 membered heteroaryl; wherein said phenyl or 5-6 membered heteroaryl may each be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X3is N or CR12, and R12is H, halo, CN, C1-6alkyl or C1-6haloalkyl; wherein 0 or 1 of X1, X2and X3is N; 25 R20is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; wherein said C1-6alkyl or C1-6haloalkyl may each be optionally substituted by one OH or COOH; and wherein said C3-6cycloalkyl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R21is H, C1-6alkyl or C1-6haloalkyl; or 30 R20and R21together with the atom to which they are attached form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl or 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; Z1is O, NR22, S or S(O)2; 123 201369 R22is H, C1-6alkyl, C1-6haloalkyl, CH2C≡CH or C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; B is group (B1), (B2), (B3), (B4) or (B5): 5 w eren eno es the point of attachment to Z1, and denotes the point of attachment to R40; m, n, o, p and q are each independently 0, 1 or 2; R30, R31, R32, R33and R34are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, 10 C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O2)NMe2and C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; Y1is N, CH or CR31; 15 Y2is N; Y3is N; Y4is N, CH or CR32; Y5is N; Y6is N; 20 R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3- 10 membered heterocycloalkyl which may be optionally substituted by: 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl and 3-10 membered heterocycloalkyl;25 wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1- 6haloalkoxy; 30 R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; 124 201369 R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 5 R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally 10 substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa; or a pharmaceutically acceptable salt thereof. Clause 3. The compound or pharmaceutically acceptable salt thereof according to clause 1 or 2, wherein R1is selected from H, methyl, ethyl, cyclopropyl, and C1-6alkyl substituted by 1) one or two 15 groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, such as R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups on the same atom, 20 together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl. Clause 4. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 3, wherein R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by 1) one group selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and 2) two groups 25 on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl. Clause 5. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 4, wherein R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered 30 heteroaryl. Clause 6. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 5, wherein R1ais H. Clause 7. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 6, wherein R1bis H. 35 Clause 8. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 6, wherein R1bis methyl . 125 201369 Clause 9. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 8, wherein R1cis H. Clause 10. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 8, wherein R1cis methyl. 5 Clause 11. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 6, wherein R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl, such as a 5-membered heterocycloalkyl, such as a 6-membered heterocycloalkyl. Clause 12. The compound or pharmaceutically acceptable salt thereof according to clause 10 11, wherein the 3-10 membered heterocycloalkyl is pyrrolidinyl or morpholinyl. Clause 13. The compound or pharmaceutically acceptable salt thereof according to clause 11 or 12, wherein the 3-10 membered heterocycloalkyl is unsubstituted. Clause 14. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 12, wherein R1is selected from: 15 20 such as R1is selected from: 126 201369 5 Clause 15. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 14, wherein R1is H. 10 Clause 16. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 15, wherein R2is C1-6alkyl, C1-6alkoxy or C3-6cycloalkyl, such as C1-6alkyl or C3-6cycloalkyl. Clause 17. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 16, wherein R2is methyl, ethyl, iso-propyl, OMe or cyclopropyl, such as methyl, ethyl or cyclopropyl. 15 Clause 18. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 17, wherein R2is methyl. Clause 19. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 18, wherein X1is CR10. Clause 20. The compound or pharmaceutically acceptable salt thereof according to any one 20 of clauses 1 to 19, wherein R10is H. Clause 21. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 20, wherein X1is N. 127 201369 Clause 22. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 21, wherein X2is CR11. Clause 23. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 20 or 22, wherein R11is selected from halo (such as Cl), C1-6haloalkyl (such as CF3), 5 cyclopropyl, phenyl substituted by one halo (such as one F) and pyridyl, such as R11is selected from halo (such as Cl), C1-6haloalkyl (such as CF3) and phenyl substituted by one halo (such as one F), such as R11is selected from halo (such as Cl) and C1-6haloalkyl (such as CF3). Clause 24. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 20, 22 or 23, wherein R11is CF3. 10 Clause 25. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 24, wherein X3is CR12. Clause 26. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 25, wherein R12is H. Clause 27. The compound or pharmaceutically acceptable salt thereof according to any one 15 of clauses 1 to 20 or 22 to 26, wherein X1is CR10, X2is CR11and X3is CR12. Clause 28. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 20 or 22 to 27, wherein X1is CH, X2is C-CF3and X3is CH. Clause 29. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 26 wherein X1 is CH, X2 is C-Cl and X3 is CH; or X1 is C-F, X2 is C-Cl and X3 is CH.20 Clause 30. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 18 or 21 to 26, wherein X1is N, X2is CR11and X3is CR12. Clause 31. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 18, 21 to 26 or 30, wherein X1is N, X2is C-CF3and X3is CH. Clause 32. The compound or pharmaceutically acceptable salt thereof according to any one 25 of clauses 1 to 20, 23 or 24, wherein X1is CR10, X2is CR11is X3is N. Clause 33. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 20, 23 or 24, wherein X1is CH, X2is C-CF3 and X3is N; or X1is C-F, X2is C-CF3 and X3is CH. Clause 34. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 33, wherein R20is selected from C1-6alkyl optionally substituted by one OH or COOH, C1- 306haloalkyl, C2-6alkenyl and C3-6cycloalkyl, such as C1-6alkyl optionally substituted by one OH, C1-6haloalkyl and C3-6cycloalkyl, such as C1-6alkyl optionally substituted by one OH, and C3-6cycloalkyl. Clause 35. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 34, wherein R20is selected from methyl, ethyl, ethenyl, CF3, CH2CH2OH, CH2COOH and cyclopropyl, such as methyl, ethyl, CF3, CH2CH2OH and cyclopropyl, such as methyl, ethyl, CH2CH2OH and 35 cyclopropyl. 128 201369 Clause 36. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 34, wherein R21is H. Clause 37. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 35, wherein R20is methyl and R21is H. 5 Clause 38. The compound or pharmaceutically acceptable salt according to any one of clauses 1 to 37, wherein R20and R21have the following stereochemistry: , wherein denotes the point of attachment to the (aza)quinazolinone moiety, and denotes the point of attachment to Z1. 10 Clause 39. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 38, wherein Z1is NR22. Clause 40. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 39, wherein R22is selected from H and C1-6alkyl (such as C1-3alkyl, such as methyl or ethyl e.g. methyl), such as R22is H. 15 Clause 41. The compound or pharmaceutically acceptable salt according to any one of clauses 1 to 38, wherein Z1is O. Clause 42. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 39, wherein B is group (B1): 20 wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40. Clause 43. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 42, wherein m is 1 or 2 and each R30is independently selected from halo (such as F or Cl), CN, C1-6alkyl (such as methyl), C1-6haloalkyl (such as CF3), C1-6alkoxy (such as OMe), C1-6haloalkoxy (such as OCF3) and C3-6cycloalkyl (such as cyclopropyl), such as m is 1 or 2 and each R30is independently25 selected from halo (such as F or Cl), CN, C1-6alkyl (such as methyl), C1-6alkoxy (such as OMe), and C3- 6cycloalkyl (such as cyclopropyl). Clause 44. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 43, wherein m is 1 and R30is selected from halo (such as F or Cl), CN, C1-6alkyl (such as methyl), C1-6haloalkyl (such as CF3), C1-6alkoxy (such as OMe), C1-6haloalkoxy (such as OCF3), and C3-129 201369 6cycloalkyl (such as cyclopropyl), such as m is 1 and R30is selected from halo (such as F or Cl), CN, C1- 6alkyl (such as methyl), C1-6alkoxy (such as OMe), and C3-6cycloalkyl (such as cyclopropyl). Clause 45. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 43, wherein m is 2, one R30is halo (such as F) and the other R30is C1-6alkoxy (such as 5 OMe); or wherein m is 2 and each R30is halo (such as F or Cl). Clause 46. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 42, wherein m is 0. Clause 47. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 46, wherein group (B1) is group (B1a), (B1b), (B1c) or (B1d):10 such as group (B1) is group (B1a), (B1b) or (B1c): wherein R30is as defined in any previous clause. Clause 48. The compound or pharmaceutically acceptable salt thereof according to any one 15 of clauses 1 to 47, wherein group (B1) is selected from: such as group (B1) is selected from: 130 201369 such as group ( 5 Clause 49. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41, wherein B is group (B2): , wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40. Clause 50. The compound or pharmaceutically acceptable salt thereof according to any one 10 of clauses 1 to 41 or 49, wherein Y1is N. Clause 51. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41 or 49, wherein Y1is CR31. Clause 52. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41 or 49 to 51, wherein n is 1 and R31is selected from halo (e.g. F), CN and C1-6alkoxy (e.g. 15 OMe). Clause 53. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 51, wherein n is 0. Clause 54. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 51, wherein n is 0, Y1is CR31and R31is selected from halo (e.g. F), CN and C1-6alkoxy (e.g. 20 OMe). Clause 55. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41 or 49 to 53, wherein Y1is C-F and n is 0. Clause 56. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41 or 49 to 55, wherein group (B2) is group (B2a), (B2b) or (B2c): 131 201369 wherein R31is as defined in any previous clause. Clause 57. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41 or 49 to 56, wherein group (B2) is selected from: 5 such as group ( such as group such as group ( Clause 58. The compound or pharmaceutically acceptable salt thereof according to any one 10 of clauses 1 to 41, wherein B is group (B3): , wherein denotes the point of attachment to Z1, denotes the point of attachment to R40. Clause 59. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41 or 58, wherein o is 1 and R32is selected from halo (such as F), C1-6alkyl (such as methyl)15 and C3-6cycloalkyl (such as cyclopropyl), such as o is 1 and R32is selected from halo (such as F) and C3-6cycloalkyl (such as cyclopropyl). Clause 60. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41, 58 or 59, wherein group (B3) is group (B3a), group (B3b) or group (B3c): 20 wherein R32is as defined in any previous clause. 132 201369 Clause 61. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41 or 58 to 60, wherein group (B3) is selected from: 5 such as group (B3) is selected from: 10 Clause 62. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41, wherein B is group (B4): wherein denotes the point of attachment to Z1, denotes the point of attachment to R40. Clause 63. The compound or pharmaceutically acceptable salt thereof according to any one 15 of clauses 1 to 41, wherein group (B4) is: 133 201369 . Clause 64. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41, wherein B is group (B5): , 5 wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40. Clause 65. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 41, wherein B is group (B1), (B2) or (B3). Clause 66. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 65, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which 10 they are attached form a 3-10 membered heterocycloalkyl which is substituted by one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl,3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one 15 OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered 20 heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; 25 R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; such as substituted by one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1- 6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl and 3-10 membered heterocycloalkyl;wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one 30 OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be 134 201369 independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered 5 heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; 10 R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl. Clause 67. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 65, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted when two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered 15 heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH, such as substituted when two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa. 20 Clause 68. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 65, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by: 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me,25 NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl, 3-10 memberedheterocycloalkyl and O(C3-6cycloalkyl); wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or30 more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may 35 each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 135 201369 R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and 2) two groups on the same atom, together with the atom to which they are attached, 5 form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH; such as substituted by: 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-106haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl and 3-10 memberedheterocycloalkyl; wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered 15 heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered 20 heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; 25 R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa. 30 Clause 69. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 65, wherein the 3-10 membered heterocycloalkyl is substituted by one group selected fromhalo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl, 3-10 memberedheterocycloalkyl and O(C3-6cycloalkyl); and / or two groups on the same atom, together with the atom to 35 which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, 136 201369 C1-6haloalkyl, C(O)R41aaand OH, such as substituted by one group selected from halo, CN, OH, =O, C1- 6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl and 3-10 membered heterocycloalkyl;and / or two groups on the same atom, together with the atom to which they are attached, form a C3-5 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa. Clause 70. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 65, wherein the 3-10 membered heterocycloalkyl is substituted by two groups 10 independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl,3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); and / or two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected 15 from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH, such as substituted by two groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl and 3-10membered heterocycloalkyl; and / or two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be 20 independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa. Clause 71. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 65, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such25 as one, two, three or four, e.g. one or two) groups independently selected from CN, halo, OH, =O, C1-6alkyl optionally substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3- 6cycloalkyl optionally substituted by one OH, 3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be optionally substituted by one or two groups 30 independently selected from F, CF3, OH and C(O)Me, such as substituted by 1) one or more (such as one, two, three or four, e.g. one or two) groups independently selected from halo, OH, C1-6alkyl optionally substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C(O)R41aa, C3-6cycloalkyl optionally substituted by one OH, and 3-10 membered heterocycloalkyl; or 2) two groups on the same atom, together with the atom to which they are attached, form a 3-10 membered heterocycloalkyl. 35 Clause 72. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 71, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which 137 201369 they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such as one, two, three or four e.g. one or two) groups independently selected from CN, F, =O, OH, methyl, iso-propyl, CH2OH, CH2CH2OH, C(Me)2OH, CF3, OMe, CH2OMe, OCF3, C(O)Me, cyclopropyl substituted by one OH, oxetanyl, CO2H, C(O)Ot-Bu, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu and 5 O(cyclopropyl); or 2) two groups on the same atom, together with the atom to which they are attached, form a cyclopropyl, cyclobutyl, azetidinyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl, each of which may be optionally substituted by one or two groups selected from F, CF3, OH and C(O)Me, such as substituted by 1) one or more (such as one, two, three or four e.g. one or two) groups independently selected from F, OH, methyl, CH2OH, C(Me)2OH, CF3, OMe, C(O)Me, cyclopropyl substituted by one OH, 10 and oxetanyl; or 2) two groups on the same atom, together with the atom to which they are attached, form an oxetanyl. Clause 73. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 68, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such15 as one, two, three or four, e.g. one or two) groups independently selected from CN, halo, OH, =O, C1- 6alkyl optionally substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3-6cycloalkyl optionally substituted by one OH, 3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be optionally substituted by one or 20 two groups independently selected from F, CF3, OH and C(O)Me; such as substituted by 1) one or more (such as one, two, three or four e.g. one or two) groups independently selected from CN, F, =O, OH, methyl, iso-propyl, CH2OH, CH2CH2OH, C(Me)2OH, CF3, OMe, CH2OMe, OCF3, C(O)Me, cyclopropyl substituted by one OH, oxetanyl, CO2H, C(O)Ot-Bu, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu and O(cyclopropyl); and / or 2) two groups on the same atom, 25 together with the atom to which they are attached, form a cyclopropyl, cyclobutyl, azetidinyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl, each of which may be optionally substituted by one or two groups selected from F, CF3, OH and C(O)Me. Clause 74. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 73, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which 30 they are attached form a 5- or 6-membered heterocycloalkyl, for example a 6-membered heterocycloalkyl. Clause 75. The compound or pharmaceutically acceptable salt thereof according to clause 73, wherein the 3-10 membered heterocycloalkyl is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, hexahydro-1H-furo[3,4-c]pyrrolyl, 2-oxa-5-azabicyclo[4.1.0]heptanyl, 2-35 azabicyclo[2.2.1]heptanyl, 3-oxa-8-zabicyclo[3.2.1]octanyl, 1,4-oxazapenyl, 2-oxa-5- azabicyclo[2.2.1]heptanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl or (1R,5S)-8-oxa-3-azabicyclo[3.2.1]octanyl, 138 201369 such as azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, hexahydro-1H-furo[3,4-c]pyrrolyl, 2- oxa-5-azabicyclo[4.1.0]heptanyl, 2-azabicyclo[2.2.1]heptanyl, 3-oxa-8-zabicyclo[3.2.1]octanyl or 1,4- oxazapenyl, such as piperidinyl, piperazinyl or morpholinyl, for example morpholinyl. Clause 76. The compound or pharmaceutically acceptable salt thereof according to any one 5 of clauses 1 to 75, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: wherein: r is 0, 1 or 2; 10 each R43is independently halo, C1-3alkyl optionally substituted by one OH, C1-3haloalkyl, C1-3alkoxy, CO2H or NHC(O)Ot-Bu; or two R43together with the carbon atom to which they are both attached form a C3- 6cycloalkyl or 3-7 membered heterocycloalkyl, each of which may be optionally substituted by one or two groups independently selected from F, CF3, OH and C(O)Me; each s is independently 0, 1, 2, 3 or 4; 15 each R44is independently selected from CN, OH, =O, halo, C1-3alkyl optionally substituted by one OH, C1- 3alkoxy, C1-3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, 3-7 membered heterocycloalkyl, CO2H, C(O)Me, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu, CO2H and O(C3-6cycloalkyl); or two R44together with the carbon atom to which they are both attached form a C3-6cycloalkyl or 3-7 membered heterocycloalkyl, each of which may be optionally substituted by one or two halo; 20 J is S(O)2, NR45or O; and R45is H, C(O)C1-3alkyl, C(O)C1-6alkoxy, C1-3alkyl optionally substituted by one OH or oxetanyl. Clause 77. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 76, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from:25 wherein: r is 0, 1 or 2; each R43is independently C1-3alkyl optionally substituted by one OH, C1-3haloalkyl or C1-3alkoxy; or two R43together with the carbon atom to which they are both attached form a 3-7 membered 30 heterocycloalkyl; 139 201369 each s is independently 0, 1, 2 or 3; each R44is independently selected from OH, halo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, and 3-7 membered heterocycloalkyl; or two R44together with the carbon atom to which they are both attached form a C3-6cycloalkyl or 3-7 membered heterocycloalkyl; 5 J is NR45or O; R45is H or C(O)C1-3alkyl. Clause 78. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 77, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from:10 wherein r is 0, 1 or 2; each R43is independently C1-3alkyl optionally substituted by one OH, C1-3haloalkyl or C1-3alkoxy; or two R43together with the carbon atom to which they are both attached form a 3-7 membered 15 heterocycloalkyl; each s is independently 0, 1, 2 or 3; each R44is independently selected from OH, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, and 3-7 membered heterocycloalkyl; or two R44together with the carbon atom to which they are both attached form a C3-6cycloalkyl or 3-7 membered heterocycloalkyl; 20 J is NR45or O; R45is H or C(O)C1-3alkyl. Clause 79. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 76 to 78, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: 25 , wherein s, J and R44are as defined in any one of clauses 76 or 78. Clause 80. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 76 to 78, wherein J is O. Clause 81. The compound or pharmaceutically acceptable salt thereof according to any one 30 of clauses 76 to 80, wherein s is 2. 140 201369 Clause 82. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 76 to 81, wherein each R44is independently selected from =O, C1-3alkyl optionally substituted by one OH, C1-3haloalkyl and 3-7 membered heterocycloalkyl, such as =O, methyl, CH2OH, CF3and oxetanyl; or selected from C1-3alkyl and C1-3haloalkyl, such as selected from methyl and CF3. 5 Clause 83. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 76 to 79, 81 or 82, wherein J is NR45. Clause 84. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 76 to 79 or 81 to 83, wherein R45is selected from H and C(O)methyl. Clause 85. The compound or pharmaceutically acceptable salt thereof according to any one of 10 clauses 1 to 77, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: 15 141 2013695 142 201369 5 143 201369 5 144 201369 5 or selected from: Clause 86. The compound or pharmaceutically acceptable salt thereof according to any one 10 of clauses 1 to 85, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: such as is: 145 201369 Clause 87. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 86, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently 5 selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or C3-6cycloalkyl; and X1is CR10, X2is CR11and X3is CR12. Clause 88. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 86, wherein: R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl;Z1is O or NH; B is group (B1), (B2), (B3) or (B4); and10 R30, R31, R32and R33are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl.Clause 89. The compound or pharmaceutically acceptable salt thereof according to any one of clauses 1 to 86, wherein: R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NH; B is group (B1), (B2) or (B3); R30, R3115 and R32are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl; a...

Claims

1. 201369 Claims 1. A compound of formula (I-X): 5 wherein: R1is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by: 1) one or more groups independently selected from OH, NR1bR1c, C(O)OR1a, C(O)NR1bR1c, NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered 10 heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl; 15 R1dis H, C1-6alkyl or C1-6haloalkyl; R1eis C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl; wherein when present in R1, each C3-6cycloalkyl, 3-10 membered heterocycloalkyl, 20 phenyl and 5-6 membered heteroaryl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2; R2is C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl or phenyl; 25 wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by one C3-6cycloalkyl or phenyl; wherein when present in R2, each C3-6cycloalkyl and phenyl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 30 X1is N or CR10, and R10is H, halo, CN, C1-6alkyl or C1-6haloalkyl; X2is N or CR11, and R11is H, halo, CN, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, phenyl or 5-6 membered heteroaryl; wherein said C3-6cycloalkyl, phenyl or 5-6 membered heteroaryl may each be independently 644 201369 optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X3is N or CR12, and R12is H, halo, CN, C1-6alkyl or C1-6haloalkyl; wherein 0 or 1 of X1, X2and X3is N; 5 R20is H, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl or C2-6alkenyl; wherein said C1-6alkyl or C1-6haloalkyl may each be optionally substituted by one OH or COOH; and wherein said C3-6cycloalkyl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R21is H, C1-6alkyl or C1-6haloalkyl; or 10 R20and R21together with the atom to which they are attached form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl or 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; Z1is CR23R24, O, NR22, S or S(O)2; 15 R22is H, C1-6alkyl, C1-6haloalkyl, CH2C≡CH or C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R23and R24are each independently H or C1-6alkyl; B is group (B1), (B2), (B3), (B4), (B5), (B6) or (B7):20 wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40; m, n, o, p and q are each independently 0, 1 or 2; R30, R31, R32, R33and R34are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, 25 C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O2)NMe2 and C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; Y1is N, CH or CR31; 30 Y2is N; Y3is N; 645 201369 Y4is N, CH or CR32; Y5is N; Y6is N; W1and W2are each independently N or CH, provided that when one of W1and W2is N, the other is CH; 5 W3is S or O; R35is H or C1-6alkyl; R40is -A1NR41R42; A1is CH2 or C(O); R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered 10 heterocycloalkyl which may be optionally substituted by: 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl, 3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); 15 wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 20 R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 25 R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally 30 substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C(O)R41aaand OH; or a pharmaceutically acceptable salt thereof.

2. The compound or pharmaceutically acceptable salt thereof according to claim 1, which is a 35 compound of formula (I): 646 201369 , wherein: R1is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by: 5 1) one or more groups independently selected from OH, NR1bR1c, C(O)OR1a, C(O)NR1bR1c, NR1dC(O)R1e, C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or 10 R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl; R1dis H, C1-6alkyl or C1-6haloalkyl; R1eis C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-156cycloalkyl or 3-10 membered heterocycloalkyl; wherein when present in R1, each C3-6cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, 20 NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe and S(O)2NMe2; R2is C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl or phenyl; wherein said C1-6alkyl or C1-6haloalkyl may each be independently optionally substituted by one C3-6cycloalkyl or phenyl; wherein when present in R2, each C3-6cycloalkyl and phenyl may be independently25 optionally substituted by one or more groups independently selected from halo, C1- 6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X1is N or CR10, and R10is H, halo, CN, C1-6alkyl or C1-6haloalkyl; X2is N or CR11, and R11is halo, CN, C1-6haloalkyl, C1-6alkoxy, phenyl or 5-6 membered heteroaryl; wherein said phenyl or 5-6 membered heteroaryl may each be independently optionally substituted by one or 30 more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; X3is N or CR12, and R12is H, halo, CN, C1-6alkyl or C1-6haloalkyl; wherein 0 or 1 of X1, X2and X3is N; 647 201369 R20is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; wherein said C1-6alkyl or C1-6haloalkyl may each be optionally substituted by one OH or COOH; and wherein said C3-6cycloalkyl may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 5 R21is H, C1-6alkyl or C1-6haloalkyl; or R20and R21together with the atom to which they are attached form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl or 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; 10 Z1is O, NR22, S or S(O)2; R22is H, C1-6alkyl, C1-6haloalkyl, CH2C≡CH or C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1- 6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; B is group (B1), (B2), (B3), (B4) or (B5):15 w eren eno es the point of attachment to Z1, and denotes the point of attachment to R40; m, n, o, p and q are each independently 0, 1 or 2; R30, R31, R32, R33and R34are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, 20 C1-6haloalkoxy, NH2, NHMe, NMe2, NHC(O)Me, COOH, C(O)NH2, C(O)NHMe, C(O)NMe2, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe, S(O2)NMe2 and C3-6cycloalkyl; wherein said C3-6cycloalkyl may be optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; Y1is N, CH or CR31; 25 Y2is N; Y3is N; Y4is N, CH or CR32; Y5is N; Y6is N; 648 201369 R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3- 10 membered heterocycloalkyl which may be optionally substituted by: 1) one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, 5S(O)2NH2, S(O)2NHMe, S(O)2NMe2, C3-6cycloalkyl and 3-10 membered heterocycloalkyl;wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-106haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or NR41aeR41af; R41abis H, C1-6alkyl, C1-6haloalkyl, C(O)R41ad, C3-6cycloalkyl or 3-10 membered heterocycloalkyl; wherein said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may each be independently optionally substituted by one or more groups independently 15 selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41acis H, C1-6alkyl or C1-6haloalkyl; R41adis C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; R41aeand R41afare each independently H, C1-6alkyl or C1-6haloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 20 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or more groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa; or a pharmaceutically acceptable salt thereof. 25 3. The compound or pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein R1is selected from H, methyl, ethyl, cyclopropyl, and C1-6alkyl substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3- 6cycloalkyl or 3-10 membered heterocycloalkyl, such as R1is selected from H, methyl, ethyl, and C1-6alkyl30 substituted by 1) one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl.

4. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 35 wherein R1is selected from: 649 201369 5 10 such as selected from: 650 201369 wherein denotes the point of attachment to the (aza)quinazolinone moiety. 5 5. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, wherein R1is H.

6. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, 10 wherein R2is C1-6alkyl, C1-6alkoxy or C3-6cycloalkyl, such as methyl, ethyl, iso-propyl, OMe or cyclopropyl, such as methyl, ethyl or cyclopropyl, for example R2is methyl.

7. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, wherein X1is CR10, X2is CR11and X3is CR12. 15 8. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, wherein R10is H, R11is selected from halo (such as Cl) and C1-6haloalkyl (such as CF3), and R12is H.

9. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 7,20 wherein X1 is CH, X2 is C-Cl and X3 is CH; X1 is C-F, X2 is C-Cl and X3 is CH; C-F, X2 is C-Cl and X3 is CH.

10. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, wherein X1is N, X2is CR11and X3is CR12, such as X1is N, X2is C-CF3and X3is CH. 25 11. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, wherein X1is CR10, X2is CR11and X3is N.

12. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 11, wherein R20is selected from C1-6alkyl optionally substituted by one OH or COOH, C1-6haloalkyl, C2-651 201369 6alkenyl and C3-6cycloalkyl, such as C1-6alkyl optionally substituted by one OH, C1-6haloalkyl and C3- 6cycloalkyl, such as R20is selected from methyl, ethyl, ethenyl, CF3, CH2CH2OH, CH2COOH and cyclopropyl, such as methyl, ethyl, CF3, CH2CH2OH and cyclopropyl; and R21is H; or R20is selected from C1-6alkyl optionally substituted by one OH, and C3-6cycloalkyl, such as R20is selected from methyl, ethyl, 5 CH2CH2OH and cyclopropyl; and R21is H.

13. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 12, wherein R20is methyl and R21is H. 10 14. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 13, wherein R20and R21have the following stereochemistry: , wherein denotes the point of attachment to the (aza)quinazoline moiety, and denotes the point of attachment to Z1. 15 15. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 14, wherein Z1is NR22and R22is selected from H and C1-6alkyl (such as C1-3alkyl, such as methyl or ethyl e.g. methyl), such as R22is H. 20 16. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 14, wherein Z1is O.

17. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 16, wherein B is group (B1), (B2) or (B3):25 wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40.

18. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 17, wherein B is group (B2): 65220136919. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 18, wherein Y1is CR31. 5 20. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 18, wherein Y1is N.

21. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 10 20, wherein n is 1 and R31is selected from halo (e.g. F), CN and C1-6alkoxy (e.g. OMe).

22. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 20, wherein n is 0, Y1is CR31and R31is selected from halo (e.g. F), CN and C1-6alkoxy (e.g. OMe). 15 23. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 18, wherein group (B2) is selected from:

24. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 20 18, wherein group (B2) is:wherein group (B2) is:wherein group (B2) is:

25. 653201369 25. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 24, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such as one, 5 two, three or four, e.g. one or two) groups independently selected from CN, halo, OH, =O, C1-6alkyl optionally substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3- 6cycloalkyl optionally substituted by one OH, 3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be optionally substituted by one or two groups 10 independently selected from F, CF3, OH and C(O)Me, such as substituted by 1) one or more (such as one, two, three or four, e.g. one or two) groups independently selected from halo, OH, C1-6alkyl optionally substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C(O)R41aa, C3-6cycloalkyl optionally substituted by one OH, and 3-10 membered heterocycloalkyl; or 2) two groups on the same atom, together with the atom to which they are attached, form a 3-10 membered heterocycloalkyl. 15 26. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 25, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such as one, two, three or four e.g. one or two) groups independently selected from CN, F, =O, OH, methyl, iso-propyl, 20 CH2OH, CH2CH2OH, C(Me)2OH, CF3, OMe, CH2OMe, OCF3, C(O)Me, cyclopropyl substituted by one OH, oxetanyl, CO2H, C(O)Ot-Bu, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu and O(cyclopropyl); or 2) two groups on the same atom, together with the atom to which they are attached, form a cyclopropyl, cyclobutyl, azetidinyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl, each of which may be optionally substituted by one or two groups selected from F, CF3, OH and C(O)Me, such as substituted 25 by 1) one or more (such as one, two, three or four e.g. one or two) groups independently selected from F, OH, methyl, CH2OH, C(Me)2OH, CF3, OMe, C(O)Me, cyclopropyl substituted by one OH, and oxetanyl; or 2) two groups on the same atom, together with the atom to which they are attached, form an oxetanyl. 30 27. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 26, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl, for example a 6-membered heterocycloalkyl.

28. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 35 24, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl selected from: 654201369wherein: r is 0, 1 or 2; each R43is independently halo, C1-3alkyl optionally substituted by one OH, C1-3haloalkyl, C1-3alkoxy, CO2H 5 or NHC(O)Ot-Bu; or two R43together with the carbon atom to which they are both attached form a C3-6cycloalkyl or 3-7 membered heterocycloalkyl, each of which may be optionally substituted by one or two groups independently selected from F, CF3, OH and C(O)Me; each s is independently 0, 1, 2, 3 or 4; each R44is independently selected from CN, OH, =O, halo, C1-3alkyl optionally substituted by one OH, C1- 10 3alkoxy, C1-3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, 3-7 membered heterocycloalkyl, CO2H, C(O)Me, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu, CO2H and O(C3-6cycloalkyl); or two R44together with the carbon atom to which they are both attached form a C3-6cycloalkyl or 3-7 membered heterocycloalkyl, each of which may be optionally substituted by one or two halo; J is S(O)2, NR45or O; and 15 R45is H, C(O)C1-3alkyl, C(O)C1-6alkoxy, C1-3alkyl optionally substituted by one OH or oxetanyl; such as selected from:wherein: r is 0, 1 or 2; 20 each R43is independently C1-3alkyl optionally substituted by one OH, C1-3haloalkyl or C1-3alkoxy; or two R43together with the carbon atom to which they are both attached form a 3-7 membered heterocycloalkyl; each s is independently 0, 1, 2 or 3; each R44is independently selected from OH, halo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, C3-6cycloalkyl 25 optionally substituted by one OH, and 3-7 membered heterocycloalkyl; or two R44together with the carbon atom to which they are both attached form a C3-6cycloalkyl or 3-7 membered heterocycloalkyl; J is NR45or O; R45is H or C(O)C1-3alkyl; such as selected from: 655201369wherein r is 0, 1 or 2; each R43is independently C1-3alkyl optionally substituted by one OH, C1-3haloalkyl or C1-3alkoxy; or two 5 R43together with the carbon atom to which they are both attached form a 3-7 membered heterocycloalkyl; each s is independently 0, 1, 2 or 3; each R44is independently selected from OH, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, C3-6cycloalkyl optionally substituted by one OH, and 3-7 membered heterocycloalkyl; or two R44together with the carbon atom 10 to which they are both attached form a C3-6cycloalkyl or 3-7 membered heterocycloalkyl; J is NR45or O; R45is H or C(O)C1-3alkyl.

29. The compound or pharmaceutically acceptable salt thereof according to claim 28, wherein R40is 15 C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is: , wherein s, J and R44are as defined in claim 28. 20 30. The compound or pharmaceutically acceptable salt thereof according to claim 28 or 29, wherein J is O and s is 2.

31. The compound or pharmaceutically acceptable salt thereof according to any one of claims 28 to 30, wherein each R44is independently selected from =O, C1-3alkyl optionally substituted by one OH, C1-25 3haloalkyl and 3-7 membered heterocycloalkyl, such as =O, methyl, CH2OH, CF3 and oxetanyl; or selected from C1-3alkyl and C1-3haloalkyl, such as selected from methyl and CF3.

32. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 29, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are 30 attached form a 3-10 membered heterocycloalkyl which is selected from: 656201369 5657201369 33. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 29, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is selected from: 5 10658201369 34. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 28, wherein R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is selected from:5659201369 56602013695 35. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 34, wherein: R1is selected from H, methyl, ethyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl or 10 C3-6cycloalkyl; X1is CR10, X2is CR11and X3is CR12; R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; and Z1is O or NH.

36. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 34, wherein: 15 R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NH; B is group (B1), (B2), (B3) or (B4); R30, R31, R32, R33and R34are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl; and R40 is C(O)NR41R42, and R41 and R42 together with the nitrogen atom towhich they are attached form a 3-10 membered heterocycloalkyl which may be optionally substituted by one or more groups independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-20 6haloalkoxy, C(O)R41aa, NR41abR41ac, S(O)2Me, SO2CF3, NHS(O)2Me, NHS(O)2CF3, S(O)2NH2, S(O)2NHMe,S(O)2NMe2, C3-6cycloalkyl and 3-10 membered heterocycloalkyl.

37. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 34, wherein: 661201369 R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NH; B is group (B1), (B2) or (B3)’R30, R31, R32, R33and R34are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl; and R40 is C(O)NR41R42, and R41 and R42 together with the nitrogen atom towhich they are attached form a piperazinyl which may be optionally substituted by one or two groups 5 independently selected from halo, CN, OH, =O, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3-6cycloalkyl and 3-10 membered heterocycloalkyl.

38. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 34, wherein: 10 R1is selected from H, methyl, ethyl, cyclopropyl, and C1-6alkyl substituted by one or two groups each independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and 5-6 membered heteroaryl; R2is C1-6alkyl, C1-6alkoxy or C3-6cycloalkyl; R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NH; B is group (B1), (B2) or (B3); R30, R31and R32are each independently selected from halo, CN, C1-6alkyl, C1- 6haloalkyl, C1-6alkoxy, C1-6haloalkoxy and C3-6cycloalkyl; and R40 is C(O)NR41R42, and R41 and R42 together15 with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which is substituted by 1) one or more (such as one, two, three or four e.g. one or two) groups independently selected from CN, F, =O, OH, methyl, iso-propyl, CH2OH, CH2CH2OH, C(Me)2OH, CF3, OMe, CH2OMe, OCF3, C(O)Me, cyclopropyl substituted by one OH, oxetanyl, CO2H, C(O)Ot-Bu, NH(oxetanyl), NHC(O)Me, NHC(O)Ot-Bu, NMeC(O)Ot-Bu and O(cyclopropyl); and / or 2) two groups on the same atom, together 20 with the atom to which they are attached, form a cyclopropyl, cyclobutyl, azetidinyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl, each of which may be optionally substituted by one or two groups selected from F, CF3, OH and C(O)Me.

39. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 25 38, which a compound of formula (IC):wherein: R1is H or C1-6alkyl; wherein said C1-6alkyl may be optionally substituted by:30 1) one or two groups independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl and5-6 membered heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; 662201369 R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-5 6cycloalkyl; R2is C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; X1is N or CR10, and R10is H; X2is CR11, and R11is halo, CN, C1-6haloalkyl, C1-6alkoxy, phenyl or 5-6 membered heteroaryl; X3is N or CR12, and R12is H; 10 wherein 0 or 1 of X1and X3is N; R20is H, C1-6alkyl or C3-6cycloalkyl; R21is H or C1-6alkyl; Z1is O or NR22; R22is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; 15 B is group (B1), (B2) or (B3):wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40; m, n and o are each independently 0, 1 or 2; R30, R31and R32are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1- 20 6haloalkoxy and C3-6cycloalkyl; Y1is N, CH or CR31; Y2is N; Y3is N; Y4is N, CH or CR32; 25 Y5is N; Y6is N; R40is C(O)NR41R42, and R41and R42together with the nitrogen atom to which they are attached form a 3- 10 membered heterocycloalkyl which may be optionally substituted by: 1) one or two groups independently selected from OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-306haloalkoxy, C(O)R41aa, C3-6cycloalkyl and 3-10 membered heterocycloalkyl; wherein said C1-6alkyl and C1-6haloalkyl may each be independently optionally substituted by one OH, and said C3-6cycloalkyl and 3-10 membered heterocycloalkyl may 663201369 each be independently optionally substituted by one or two groups independently selected from halo, OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy and C1-6haloalkoxy; R41aais OH, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy or C1-6haloalkoxy; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-5 6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be independently optionally substituted by one or two groups independently selected from halo, C1-6alkyl, C1-6haloalkyl and C(O)R41aa.

40. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 10 38, which is a compound of formula (I-XA):, wherein: R1is H, C1-6alkyl or C3-6cycloalkyl; wherein said C1-6alkyl may be optionally substituted by: 15 1) one or more groups independently selected from OH, C(O)OR1a, C(O)NR1bR1c, C3-6cycloalkyl, and 5-6 membered heteroaryl; R1ais H, C1-6alkyl or C1-6haloalkyl; R1band R1care each independently H, C1-6alkyl or C1-6haloalkyl; or R1band R1ctogether with the nitrogen atom to which they are attached form a 3-10 20 membered heterocycloalkyl; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl; wherein when present in R1, each C3-6cycloalkyl, 3-10 membered heterocycloalkyl and 5- 6 membered heteroaryl may be independently optionally substituted by one or more 25 groups independently selected from C1-6alkyl and C1-6haloalkyl; R2is C1-6alkyl, C1-6alkoxy or C3-6cycloalkyl; X1is N or CR10, and R10is H, halo, CN, C1-6alkyl or C1-6haloalkyl; X2is N or CR11, and R11is halo, CN, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, phenyl or 5-6 membered heteroaryl; 30 X3is N or CR12, and R12is H, halo, CN, C1-6alkyl or C1-6haloalkyl; wherein 0 or 1 of X1, X2and X3is N; R20is H, C1-6alkyl, C1-6haloalkyl or C3-6cycloalkyl; 664201369 R21is H, C1-6alkyl or C1-6haloalkyl; or Z1is CH2, S, O or NR22; R22is H or C1-6alkyl; B is group (B1), (B2), (B3), (B4), (B6) or (B7): 5wherein denotes the point of attachment to Z1, and denotes the point of attachment to R40; m, n, o and p are each independently 0, 1 or 2; R30, R31, R32and R33are each independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1- 106haloalkoxy and C3-6cycloalkyl; Y1is N, CH or CR31; Y2is N; Y3is N; Y4is N, CH or CR32; 15 Y5is N; Y6is N; W1and W2are each independently N or CH, provided that when one of W1and W2is N, the other is CH; W3is S or O; R35is H or C1-6alkyl; 20 R40is -A1NR41R42; A1is CH2 or C(O); R41and R42together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl which may be optionally substituted by: 1) one or more groups independently selected from CN, halo, OH, =O, C1-6alkyl optionally25 substituted by one OH, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C(O)R41aa, NR41abR41ac, C3-6cycloalkyl optionally substituted by one OH, 3-10 membered heterocycloalkyl and O(C3-6cycloalkyl); R41aais OH, C1-6alkyl or C1-6alkoxy; R41abis H, C1-6alkyl, C(O)R41ador 3-10 membered heterocycloalkyl; 30 R41acis H or C1-6alkyl; 665201369 R41adis C1-6alkyl or C1-6alkoxy; and / or 2) two groups on the same atom, together with the atom to which they are attached, form a C3-6cycloalkyl or 3-10 membered heterocycloalkyl, each of which may be optionally substituted by one or two groups independently selected from F, CF3, OH and C(O)Me; 5 or a pharmaceutically acceptable salt thereof.

41. The compound according to any one of claims 1 to 40.

42. The pharmaceutically acceptable salt according to any one of claims 1 to 40. 10 43. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 42, and at least one pharmaceutically acceptable excipient.

44. The compound or pharmaceutically acceptable salt according to any one of claims 1 to 42, or the 15 pharmaceutical composition according to claim 43, for use as a medicament.

45. The compound for use, pharmaceutically acceptable salt for use or pharmaceutical composition for use according to claim 44, for use in the prophylaxis or treatment of a disorder in which antagonism of GIPR provides a prophylactic or therapeutic effect. 20 46. Use of the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 42, or the pharmaceutical composition according to claim 43, in the manufacture of a medicament for the prophylaxis or treatment of a disorder in which antagonism of GIPR provides a prophylactic or therapeutic effect. 25 47. A method of preventing or treating a disorder in which antagonism of GIPR provides a prophylactic or therapeutic effect, comprising administering a compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 42, or a pharmaceutical composition according to claim 43. 30 48. The compound for use, pharmaceutically acceptable salt for use, pharmaceutical composition for use, use or method according to any one of claims 44 to 47, wherein the disorder is diabetes, type 1 diabetes, type 2 diabetes, hyperinsulinemia (such as congenital hyperinsulinism), Cushing’s syndrome, gestational diabetes, pre-diabetes, insulin resistance syndrome, impaired glucose tolerance (IGl), disease 35 states associated with elevated blood glucose levels, metabolic disease including metabolic syndrome, or hyperglycemia (such as abnormal postprandial hyperglycemia); or 666201369 wherein the disorder is diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early- onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin 5 resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders 10 (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low 15 HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH),fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure 20 with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post-prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease, macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, 25 syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel 30 syndrome, polycystic ovary syndrome (PCOS), or addiction (e.g., addition to alcohol, nicotine, and / or drug).

49. The compound for use, pharmaceutically acceptable salt for use, pharmaceutical composition for use, use or method according to any one of claims 44 to 47, wherein the disorder is type 2 diabetes, 35 obesity and related comorbidities (such as sleep apnoea, metabolic associated steatohepatitis or osteoarthritis), cardiovascular disease, heart failure or chronic kidney disease. 667201369 50. The compound for use, pharmaceutically acceptable salt for use, pharmaceutical composition for use, use or method according to any one of claims 44 to 47 or 49, wherein the disorder is obesity. 668

Images