Aminopyrimidine derivatives as LRRK2 modulators

Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n. X, R1, R2, R3, R5, R6 and R7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

Amido spirocyclic amide and sulfonamide derivatives

Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

Sand spreading system for light rail vehicle

The invention discloses a sand spreading system for a light rail vehicle, which comprises a sand box for bearing sand grains and a sand spreading device for spreading the sand grains in the sand box to a preset position and also comprises a sand position indicating device for indicating a sand position in the sand box. The sand spreading system has the advantages that as the sand spreading system is provided with the sand position indicating device, an operator can obtain the sand quantity information in the sand box according to the sand position information reacted by the sand position indicating device; according to the sand quantity information, whether sand grains need to be supplemented into the sand box or not can be judged so as to achieve the purpose of timely supplementing the sand quantity; and compared with the background art, a sand spreading effect can be always kept, and the work efficiency is not influenced.

RAF inhibitor compounds and methods of use thereof

Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer. 2. The antibody-drug conjugate of wherein Y is heteroaryl; and Rand Rtogether form a cyclobutyl ring.11. The antibody-drug conjugate of claim 6 , wherein Y is heteroaryl claim 6 , aryl or alkenyl; and Ris C-Calkylene.30. The compound of claim 29 , wherein Ris C-Calkylene claim 29 , Sp is —Ar—R— claim 29 , wherein Ar is aryl Ris (C-Calkylene)O—.32. The antibody-drug conjugate according to claim 1 , wherein p is 2.33. The antibody conjugate of claim 1 , wherein the antibody binds to one or more of polypeptides selected from the group consisting of:CLL1;BMPR1B;E16;STEAP1;0772P;MPF;NaPi2b;Sema 5b;PSCA hlg;ETBR;MSG783;STEAP2;TrpM4;CRIPTO;CD21;CD79b;FcRH2;HER2;NCA;MDP;IL20Rα;Brevican;EphB2R;ASLG659;PSCA;GEDA;BAFF-R;CD22;CD79a;CXCR5;HLA-DOB;P2X5;CD72;LY64;FcRH1;IRTA2;TENB2;PMEL17;TMEFF1;GDNF-Ra1;Ly6E;TMEM46;Ly6G6D;LGR5;RET;LY6K;GPR19;GPR54;ASPHD1;Tyrosinase;TMEM118;GPR172A;MUC16 andCD33.34. The antibody-drug conjugate or non-peptide compound according to or claim 1 , wherein D is an anti-tumor agent or an antibiotic moiety.35. The antibody-drug conjugate or non-peptide compound according to or claim 1 , wherein D is selected from the group consisting of:methotrexate, adriamicin, vincristine, vinblastine, etoposide, doxorubicin, melphalan, mitomycin C, chlorambucil and daunorubicin.37. An antibody conjugate compound of which is prepared by covalently attaching an antibody with one to eight compounds of .38. A method of treating a disease in a human in need thereof claim 1 , comprising administering to said human an effective amount of an antibody-drug conjugate of .39. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.40. A compound of claim 1 , wherein the antibody binds to one or more of polypeptides selected from the ...

BICYCLIC LACTAMS AND METHODS OF USE THEREOF

The invention provides novel compounds having the general formula I: 4. A compound according to claim 3 , wherein each Ris selected from the group consisting of hydrogen claim 3 , C-Calkyl claim 3 , C-Chaloalkyl claim 3 , CHCHOCH claim 3 , C-Ccycloalkyl claim 3 , C-Ccycloalkyl substituted by 1 to 2 fluorine atoms claim 3 , CH—(C-Ccycloalkyl) claim 3 , CH—(C-Ccycloalkyl substituted by 1 to 2 fluorine atoms) claim 3 , and CH—(Cheterocyclyl).8. A compound according to claim 6 , wherein Y is O.9. A compound according to claim 6 , wherein Rand Rare each H.15. A compound according to claim 12 , wherein Ris H or methyl; the A ring is 6 membered aryl or 5 membered heteroaryl; Zis C or N; and X is CHor O.16. A compound according to claim 13 , wherein Ris H or methyl; the A ring is 6 membered aryl or 5 membered heteroaryl; Zis C or N; and X is CHor O.17. A compound according to claim 14 , wherein Ris H or methyl; the A ring is 6 membered aryl or 5 membered heteroaryl; Zis C or N; and X is CHor O.18. A compound according to claim 1 , wherein the compound is selected from the compounds of Table 1 claim 1 , Table 2 claim 1 , Table 3 claim 1 , Table 4 and Table 5.19. A compound according to claim 17 , wherein the compound is selected from the compounds of Table 1 claim 17 , Table 2 claim 17 , Table 3 claim 17 , Table 4 and Table 5 which have a Kin the RIP1 kinase inhibitory assay of less than or equal to 0.1 μM.20. A pharmaceutical composition comprising a compound in accordance with and a therapeutically inert carrier.21. A method for the treatment or prophylaxis of a disease or disorder in a patient by administering to the patient a compound of claim 1 , wherein the disease or disorder is selected from the group consisting of prophylaxis of irritable bowel disorders (IBD) claim 1 , irritable bowel syndrome (IBS) claim 1 , Crohn's disease claim 1 , ulcerative colitis claim 1 , myocardial infarction claim 1 , stroke claim 1 , traumatic brain injury claim 1 , atherosclerosis claim ...

PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer. 2. The antibody-drug conjugate of wherein Y is heteroaryl; and Rand Rtogether form a cyclobutyl ring.11. The antibody-drug conjugate compound of claim 4 , wherein Y is heteroaryl claim 4 , aryl or alkenyl; and Ris C-Calkylene.26. The compound of or claim 4 , where Ris —(CH);29. The antibody-drug conjugate according to wherein p is 2.30. The antibody-drug conjugate of claim 1 , wherein the antibody binds to one or more of polypeptides selected from the group consisting of:CLL1;BMPR1B;E16;STEAP1;0772P;MPF;NaPi2b;Sema 5b;PSCA hlg;ETBR;MSG783;STEAP2;TrpM4;CRIPTO;CD21;CD79b;FcRH2;HER2;NCA;MDP;IL20Rα;Brevican;EphB2R;ASLG659;PSCA;GEDA;BAFF-R;CD22;CD79a;CXCR5;HLA-DOB;P2X5;CD72;LY64;FcRH1;IRTA2;TENB2;PMEL17;TMEFF1;GDNF-Ra1;Ly6E;TMEM46;Ly6G6D;LGR5;RET;LY6K;GPR19;GPR54;ASPHD1;Tyrosinase;TMEM118;GPR172A;MUC16 andCD33.31. A method of treating a disease in a human in need thereof claim 1 , comprising administering to said human an effective amount of an antibody-drug conjugate of .32. A pharmaceutical composition comprising an antibody-drug conjugate of and a pharmaceutically acceptable excipient thereof.33. The antibody-drug conjugate of claim 30 , wherein the antibody binds to one or more of polypeptides selected from the group consisting of:CLL1;STEAP1;NaPi2b;STEAP2;TrpM4;CRIPTO;CD21;CD79b;FcRH2;HER2;CD22;CD79a;CD72;LY64;Ly6E;MUC16; andCD33.34. The antibody-drug conjugate of claim 1 , wherein the antibody binds to CD33; orthe antibody-drug conjugate comprises an HVR-L1 comprising the amino acid sequence of SEQ ID NO:11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:12, an HVR-L3 comprising the amino acid sequence of SEQ ID NO:13, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:15, and an ...

RAF INHIBITOR COMPOUNDS AND METHODS OF USE THEREOF

Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed. 2. The compound of claim 1 , wherein:{'sup': '12', 'X is N or CR;'}{'sup': '13', 'Y is N or CR;'}{'sup': '14', 'Z is N or CR, wherein no more than two of X, Y and Z can be N at the same time;'}{'sup': 1', '2, 'sub': 1', '3', '1', '3, 'Rand Rare independently selected from hydrogen, halogen, CN, C-Calkyl and C-Calkoxy;'}{'sup': '3', 'sub': 1', '3, 'Ris hydrogen, halogen or C-Calkyl;'}{'sup': 4', '6', '7', '15, 'sub': 3', '5', '1', '6', '2', '6', '2', '6', '3', '4', '1', '4, 'Ris C-Ccycloalkyl, C-Calkyl, C-Calkenyl, C-Calkynyl, phenyl, a 5-6 membered heteroaryl or NRR, wherein the cycloalkyl, alkyl, alkenyl, alkynyl, phenyl and heteroaryl are optionally substituted with OR, halogen, phenyl, C-Ccycloalkyl, or C-Calkyl optionally substituted with halogen;'}{'sup': 5', '8', '9, 'Ris hydrogen or NRR;'}{'sup': 6', '7, 'sub': 1', '6, 'Rand Rare each independently hydrogen or C-Calkyl optionally substituted by halogen; or'}{'sup': 6', '7, 'sub': 1', '3, 'Rand Rare independently taken together with the atom to which they are attached to form a 3-6 membered heterocyclyl optionally substituted by halogen, oxo or C-Calkyl;'}{'sup': '8', 'Ris hydrogen;'}{'sup': 9', '10', '11', '10', '10', '16', '16', '17, 'sub': 0', '3', '0', '3', '1', '3', '1', '6', '2', '6', '2', '6', '0', '3', '3', '6', '0', '3', '0', '3', '0', '3', '1', '3, 'Ris hydrogen, (C-Calkyl)NRR, (C-Calkyl)OR, (C-Calkyl)SR, C-Calkyl, C-Calkenyl, C-Calkynyl, (C-Calkyl)C-Ccycloalkyl, (C-Calkyl)phenyl, (C-Calkyl)3-6-membered heterocyclyl or (C-Calkyl)5-6-membered heteroaryl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, heteroaryl and phenyl are optionally ...

AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS

Compounds of the formula I: 126-. (canceled)28. The compound of claim 27 , wherein X is —NH—.29. The compound of claim 27 , wherein X is —O—.30. The compound of claim 27 , wherein Ris Calkyl.32. The compound of claim 28 , wherein Ris: methyl; ethyl; orcyclopropyl.33. The compound of claim 32 , wherein Ris trifluoromethyl.34. The compound of claim 27 , wherein Ris: halo; or Calkoxy;35. The compound of claim 27 , wherein Ris: halo; Calkyl; or Calkoxy.36. The compound of claim 33 , wherein Ris: methoxy; chloro; or fluoro.37. The compound of claim 34 , wherein Ris: fluoro; chloro; methyl; or methoxy.38. The compound of claim 36 , wherein m is 1.39. A composition comprising:(a) a pharmaceutically acceptable carrier; and{'claim-ref': {'@idref': 'CLM-00027', 'claim 27'}, '(b) a compound of .'}40. A method for treating Parkinson's disease claim 27 , said method comprising administering to a subject in need thereof an effective amount of a compound of . This invention pertains to compounds that modulate the function of LRRK2 and are useful for treatment of LRRK2-mediated diseases and conditions such as Parkinson's disease.Neurodegenerative diseases such as Parkinson's disease, Lewy body dementia and Huntington's disease affect millions of individuals. Parkinson's disease is a chronic, progressive motor system disorder that afflicts approximately one out of every 1000 people, with hereditary Parkinson's disease accounting for 5-10% of all of patients. Parkinson's disease is caused by progressive loss of mid-brain dopamine neurons, leaving patients with impaired ability to direct and control their movements. The primary Parkinson's disease symptoms are trembling, rigidity, slowness of movement, and impaired balance. Many Parkinson's disease patients also experience other symptoms such as emotional changes, memory loss, speech problems, and sleeping disorders.The gene encoding the leucine-rich repeat kinase 2 protein (LRRK2) has been identified in association with hereditary ...

Aminopyrimidine derivatives as lrrk2 modulators

Specific Compounds of formula I: or pharmaceutically acceptable salts thereof, wherein m, X, R 1 , R 2 , R 3 , R 5 , R 6 and R 7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

PYRAZOLOPYRIMIDONE AND PYRAZOLOPYRIDONE INHIBITORS OF TANKYRASE

There are provided compounds of the formula 3. The compound of wherein Y is NRand Q is N.4. The compound of wherein Y is NRand Q is CH.5. The compound of wherein Y is CRRand Q is N.6. The compound of wherein Y is CRRand Q is CH.7. The compound of any of claim 2 , claim 2 , or wherein Ris optionally substituted phenyl.11. The compound of any of claim 2 , claim 2 , or wherein Ris optionally substituted pyridinyl and R claim 2 , when present claim 2 , is hydrogen or Calkyl.12. The compound of any of claim 2 , claim 2 , or wherein Ris optionally substituted heteroaryl and R claim 2 , when present claim 2 , is hydrogen or Calkyl.13. The compound of wherein said optionally substituted heteroaryl is selected from the group consisting of (a) pyridinyl claim 12 , (b) pyrimidinyl claim 12 , (c) thiazolyl claim 12 , (d) isothiazolyl claim 12 , (e) oxazolyl claim 12 , (f) isoxazole claim 12 , (g) imidazolyl claim 12 , (h) pyrazolyl claim 12 , (i) 1 claim 12 ,2 claim 12 ,4-triazolyl claim 12 , (j) 3-(pyrazinyl)-1 claim 12 ,2 claim 12 ,4-oxadiazolyl and (k) 1 claim 12 ,2 claim 12 ,4-oxadiazolyl.15. The compound of wherein where each X is CH.16. The compound of wherein where one X is N and the other X is CH.17. The compound according to any of or wherein each Ris independently selected from the group consisting of Calkyl claim 15 , Chaloalkyl claim 15 , halo claim 15 , cyano claim 15 , Calkylsulfonyl claim 15 , and ORwherein Ris selected from the group consisting of (i) Calkyl (ii) Calkoxy-Calkyl claim 15 , (iii) Chydroxyalkyl and (iv) C-dihydroxyalkyl.18. The compound of selected from the compounds I-1 to I-144 in Table 1.19. A method of inhibiting tankyrase 1 and/or tankyrase 2 by contacting either or both with a compound of .20. A method for treating cancer by administering to a patient in need thereof a therapeutically active amount of a compound of .21. The method of wherein the cancer is colorectal cancer.22. The use of a compound according to for the preparation of a ...

AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES

Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds. 2. The compound of , wherein R is an 8- or 9-membered heteroaryl , unsubstituted or substituted as described for .4. The compound of , wherein , R is a five- or six-membered nitrogen-linked heterocycloalkyl ring fused to an unsubstituted or substituted phenyl or monocyclic heteroaryl , as defined in .6. The compound of claim 1 , wherein Ris H claim 1 , —C(O)R claim 1 , —COR claim 1 , —S(O)R claim 1 , or —SOR.7. (canceled)8. (canceled)9. The compound of claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , tert-butyl claim 1 , isobutyl claim 1 , isopentyl claim 1 , phenyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , thiophenyl claim 1 , imidazolyl claim 1 , pyrazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , thiazolyl claim 1 , triazoyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , pyridazinyl claim 1 , isoindolinyl claim 1 , azetidinyl claim 1 , oxetanyl claim 1 , pyrrolidinyl claim 1 , piperidinyl claim 1 , morpholinyl claim 1 , piperazinyl claim 1 , tetrahydrofuranyl claim 1 , tetrahydropyranyl claim 1 , or tetrahydrothiophenyl claim 1 , each unsubstituted or substituted.10. The compound of claim 1 , wherein Ris phenyl claim 1 , cycloalkyl claim 1 , heteroaryl claim 1 , or heterocycloalkyl claim 1 , each unsubstituted or substituted with one or more substituents selected from the group consisting of fluoro claim 1 , oxo claim 1 , methyl claim 1 , —CONH claim 1 , acetyl claim 1 , —SOmethyl claim 1 , —C(O)-isopropyl claim 1 , pyridazinyl claim 1 , triazolyl claim 1 , dimethylaminomethyl claim 1 , cyano claim 1 , methyl-triazolyl-methoxy claim 1 , trifluoromethoxy claim 1 , pyrrolidinylmethyl claim 1 , acetylamino claim 1 , tetrazolylmethyl claim 1 ...

THERAPEUTIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF

Compounds of Formula (I): 2. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CH.3. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CN.9. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris cyclopropylcarbonylamino.14. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': c', 'x, 'sub': 1', '6, 'Ris C-Calkyl that is substituted with R; and'}{'sup': x', 'm', 'm', 'n', 'm', 'm', 'm', 'n, 'sub': 1', '6', '1', '6, 'Ris selected from the group consisting of 3-10 membered carbocyclyl, 3-10 membered heterocycle, 6-10 membered aryl, and 5-10 membered heteroaryl, wherein any 3-10 membered carbocyclyl, 3-10 membered heterocycle, 6-10 membered aryl, and 5-10 membered heteroaryl is optionally substituted with 3-10 membered carbocyclyl, 3-10 membered heterocycle, 6-10 membered aryl, or 5-10 membered heteroaryl, wherein any 3-10 membered carbocyclyl, 3-10 membered heterocycle, 6-10 membered aryl, and 5-10 membered heteroaryl is optionally substituted with halo, hydroxy, cyano, oxo, —OR, —NRR, —C(O)R, —C(O)OR, —C(O)NRR, or C-Calkyl that is optionally substituted with halo, hydroxy, cyano, oxo or C-Calkoxy.'}21. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent or excipient.22. A method of preventing claim 1 , treating or lessening the severity of a disease or condition responsive to the inhibition of a Janus kinase activity in a patient claim 1 , comprising administering to the patient in need thereof a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.23. The method of claim 22 , wherein the disease or condition is asthma.24. The method of claim 22 , wherein the Janus kinase is JAK1. This application is a continuation of International Application No. PCT/EP2017/060349, filed May 2, ...

PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer. 125-. (canceled)2962-. (canceled)63. The compound of wherein Y is heteroaryl.65. The compound of wherein Rand Rare each independently selected from H and C-Calkyl.68. The compound of wherein T is (C-Calkenylene)-Y—(C-Calkenylene); and Yis aryl substituted with a bond to Sp. This application is a divisional of and claims priority to U.S. Ser. No. 15/182,429, filed 14 Jun. 2016, which is a continuation of and claims priority to PCT patent application no. PCT/US2014/070660, filed 16 Dec. 2014, and also claims priority to U.S. provisional application No. 61/916,661 filed on 16 Dec. 2013, and U.S. provisional application No. 61/916,691 filed on 16 Dec. 2013, all of which applications are hereby incorporated by reference in their entirety.The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jun. 13, 2016, is named P05760_US_2 Sequence_Listing.txt and is 35,111 bytes in size.This invention relates to novel peptidomimetic compounds which are useful as linkers of antibody-drug conjugates (ADC). This invention also relates to ADCs containing peptidomimetic linkers. This invention also relates to methods of treating diseases in humans.The use of monoclonal antibodies (mABs) to deliver anticancer drugs directly to tumor cells has attracted a great deal of focus in recent years. Two new antibody-drug conjugates have been approved by the FDA for the treatment of cancer. Adcetris® (brentuximab vedotin) is a CD30-directed antibody-drug conjugate (ADC) indicated for the treatment of relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL). Kadcyla® (ado-trastuzumab emtansine), is a new therapy approved for ...

BICYCLIC KETONE COMPOUNDS AND METHODS OF USE THEREOF

The invention provides novel compounds having the general formula I: 2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': 1', 'N', '1', '1, 'sub': 1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2, 'Ris selected from the group consisting of C-Calkyl, C-Ccycloalkyl, C-Calkoxy, C-Chaloalkyl, C-Chaloalkoxy, C-Calkyl-N(R), phenyl, benzyl, 4 to 6 membered heterocyclyl and 5 to 6 membered heteroaryl; wherein Ris bound to the adjacent carbonyl by a carbon atom, and wherein Ris optionally substituted by one or two substituents selected from the group consisting of F, Cl, methyl, ethyl, hydroxyl, hydroxymethyl, methoxymethyl, cyano, trifluoromethyl, difluoromethoxy and trifluoromethoxy.'}{'sup': N', 'N, 'sub': 1', '6', '3', '6', '1', '6', '1', '6, 'each Ris independently selected from the group consisting of H, C-Calkyl, C-Ccycloalkyl, C-Calkoxy, and C-Chaloalkyl; or two Rmay together with the adjacent N form a 4-6 membered ring;'}the A ring is a 5 membered heteroaryl having as the only heteroatoms, either (i) two or three nitrogen atoms, (ii) one nitrogen atom and one oxygen atom, or (iii) one nitrogen atom and one sulfur atom;wherein the A ring is bound to the adjacent carbonyl by a carbon atom; and [{'sub': 1', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '1', '6', '1', '6', '1', '6', '1', '6, 'sup': 'N', '(a) 1 to 2 substituents selected from the group consisting of halogen, C-Calkyl, C-Chaloalkyl, C-Ccycloalkyl, C-Calkoxy, C-Chaloalkoxy, C-Cthioalkyl, C-Calkyl-N(R), and cyano; wherein two C-Calkyl substituents may together for a bridged or spirocyclic ring; and wherein if a nitrogen atom in the B ring is substituted, the substituent is not halogen, cyano, or a C-Calkoxy, C-Chaloalkoxy or C-Cthioalkyl having an oxygen or sulfur atom directly bonded to the nitrogen atom;'}, {'sub': 1', '6', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '2', '3', '6', '2', '2', '3', '6', ' ...

BICYCLIC KETONE COMPOUNDS AND METHODS OF USE THEREOF

The invention provides novel compounds having the general formula I: 112.-. (canceled)131. A method for the treatment of a disease or disorder in a human , the method comprising administration to the human of an effective treatment amount of a compound of claim , or a pharmaceutically acceptable salt thereof , wherein the disease or disorder is selected from the group consisting of Parkinson's Disease , Lewy body dementia , multiple system atrophy , Parkinson-plus syndromes , taupathies , Alzheimer's Disease , frontotemporal dementia , amyotrophic lateral sclerosis , spinal muscular atrophy , primary lateral sclerosis , Huntington's disease , ischemia , stroke , intracranial hemorrhage , cerebral hemorrhage , muscular dystrophy , progressive muscular atrophy , pseudobulbar palsy , progressive bulbar palsy , spinal muscular atrophy , inherited muscular atrophy , peripheral neuropathies , progressive supranuclear palsy , corticobasal degeneration , and demyelinating diseases.141. A method for the treatment of a disease or disorder in a human , the method comprising administration to the human of an effective treatment amount of a compound of claim , or a pharmaceutically acceptable salt thereof , wherein the disease or disorder is selected from the group consisting of inflammatory bowel disease , Crohn's disease , ulcerative colitis , glaucoma , psoriasis , psoriatic arthritis , rheumatoid arthritis , spondyloarthritis , juvenile idiopathic arthritis , and osteoarthritis15. The method of claim 13 , wherein the disease or disorder is Alzheimer's disease.16. The method of claim 13 , wherein the disease or disorder is multiple sclerosis.17. The method of claim 13 , wherein the disease or disorder is Parkinson's disease.18. The method of claim 13 , wherein the disease or disorder is amyotrophic lateral sclerosis.19. The method of claim 13 , wherein the disease or disorder is Huntington's disease.20. The method of claim 13 , wherein the disease or disorder is spinal ...

AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES

Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds. 2. The compound of , wherein R is an 8- or 9-membered heteroaryl , unsubstituted or substituted as described for .4. The compound of , wherein R is a five- or six-membered nitrogen-linked heterocycloalkyl ring fused to an unsubstituted or substituted phenyl or monocyclic heteroaryl , as defined in .6. The compound of claim 1 , wherein Ris H.7. The compound of claim 1 , wherein Ris —C(O)R claim 1 , —COR claim 1 , —S(O)R claim 1 , or —SOR.8. The compound of claim 1 , wherein Ris alkyl claim 1 , unsubstituted or substituted as described for .9. The compound of claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , tert-butyl claim 1 , isobutyl claim 1 , isopentyl claim 1 , phenyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , thiophenyl claim 1 , imidazolyl claim 1 , pyrazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , thiazolyl claim 1 , triazoyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , pyridazinyl claim 1 , isoindolinyl claim 1 , azetidinyl claim 1 , oxetanyl claim 1 , pyrrolidinyl claim 1 , piperidinyl claim 1 , morpholinyl claim 1 , piperazinyl claim 1 , tetrahydrofuranyl claim 1 , tetrahydropyranyl claim 1 , or tetrahydrothiophenyl claim 1 , each unsubstituted or substituted.10. The compound of claim 1 , wherein R is phenyl claim 1 , cycloalkyl claim 1 , heteroaryl claim 1 , or heterocycloalkyl claim 1 , each unsubstituted or substituted with one or more substituents selected from the group consisting of fluoro claim 1 , oxo claim 1 , methyl claim 1 , —CONH claim 1 , acetyl claim 1 , —SOmethyl claim 1 , —C(O)-isopropyl claim 1 , pyridazinyl claim 1 , triazolyl claim 1 , dimethylaminomethyl claim 1 , cyano claim 1 , methyl-triazolyl-methoxy claim ...

THERAPEUTIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF

Compounds of Formula (I): 2. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CH.3. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CN.9. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris cyclopropylcarbonylamino.14. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': c', 'x, 'sub': 1', '6, 'Ris C-Calkyl that is substituted with R; and'}{'sup': x', 'm', 'm', 'n', 'm', 'm', 'm', 'n, 'sub': 1', '6', '1', '6, 'Ris selected from the group consisting of 3-10 membered carbocyclyl, 3-10 membered heterocycle, 6-10 membered aryl, and 5-10 membered heteroaryl, wherein any 3-10 membered carbocyclyl, 3-10 membered heterocycle, 6-10 membered aryl, and 5-10 membered heteroaryl is optionally substituted with 3-10 membered carbocyclyl, 3-10 membered heterocycle, 6-10 membered aryl, or 5-10 membered heteroaryl, wherein any 3-10 membered carbocyclyl, 3-10 membered heterocycle, 6-10 membered aryl, and 5-10 membered heteroaryl is optionally substituted with halo, hydroxy, cyano, oxo, —OR, —NRR, —C(O)R, —C(O)OR, —C(O)NRR, or C-Calkyl that is optionally substituted with halo, hydroxy, cyano, oxo or C-Calkoxy.'}21. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent or excipient.22. A method of preventing claim 1 , treating or lessening the severity of a disease or condition responsive to the inhibition of a Janus kinase activity in a patient claim 1 , comprising administering to the patient in need thereof a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.23. The method of claim 22 , wherein the disease or condition is asthma.24. The method of claim 22 , wherein the Janus kinase is JAK1. This application is a continuation of U.S. application Ser. No. 16/181,228 filed on Nov. 5, 2018, ...

BICYCLIC AMIDE COMPOUNDS AND METHODS OF USE THEREOF

The invention provides novel compounds having the general formula I: 2. A compound of Formula (I) of claim 1 , wherein Rand Rtogether with the adjacent amide N claim 1 , form a 4 to 6 membered unsaturated heterocyclic ring optionally substituted by one or two R claim 1 , containing zero or one additional heteroatom selected from the group consisting of O and S.4. A compound of claim 3 , wherein n is 1.5. A compound of claim 3 , wherein each Ris selected from the group consisting of methyl claim 3 , ethyl claim 3 , F and Cl.6. A compound of claim 5 , wherein each Ris methyl or F.11. A compound of claim 1 , wherein Ris selected from the group consisting of C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , and C-Chaloalkyl; and Ris selected from the group consisting of C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , C-Calkoxy claim 1 , phenyl claim 1 , and 4 to 5 membered heterocyclyl.12. A compound of claim 11 , wherein Ris selected from the group consisting of methyl claim 11 , cyclopropyl claim 11 , —CHCFH and —CHCF; and Ris selected from the group consisting of methyl claim 11 , cyclopropyl claim 11 , —CHCHOCH claim 11 , phenyl claim 11 , and oxetan-3-yl.17. A compound of claim 1 , wherein the compound is selected from Table 1 and Table 2.18. A pharmaceutical composition comprising a compound of and a therapeutically inert carrier.19. A method for the treatment or prophylaxis of a disease or disorder in a human claim 1 , the method comprising administration to the human of an effective amount of a compound of claim 1 , wherein the disease or disorder is selected from the group consisting of irritable bowel disorders (IBD) claim 1 , irritable bowel syndrome (IBS) claim 1 , Crohn's disease claim 1 , ulcerative colitis claim 1 , myocardial infarction claim 1 , stroke claim 1 , traumatic brain injury claim 1 , atherosclerosis claim 1 , ischemia-reperfusion injury of kidneys claim 1 , liver and lungs claim 1 , cisplatin-induced kidney injury claim 1 , sepsis claim 1 , systemic ...

Peptidomimetic compounds and antibody-drug conjugates thereof

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof pharmaceutical compositions containing them, and to their use in therapy for the prevention treatment of cancer.

AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES

Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds. 2. The compound of , wherein R is an 8- or 9-membered heteroaryl , unsubstituted or substituted as described for .4. The compound of , wherein , R is a five- or six-membered nitrogen-linked heterocycloalkyl ring fused to an unsubstituted or substituted phenyl or monocyclic heteroaryl , as defined in .6. The compound of claim 1 , wherein Ris H.7. The compound of claim 1 , wherein Ris —C(O)R claim 1 , —COR claim 1 , —S(O)R claim 1 , or —SOR.8. The compound of claim 1 , wherein Ris alkyl claim 1 , unsubstituted or substituted as described for .9. The compound of claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , tert-butyl claim 1 , isobutyl claim 1 , isopentyl claim 1 , phenyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , thiophenyl claim 1 , imidazolyl claim 1 , pyrazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , thiazolyl claim 1 , triazoyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , pyridazinyl claim 1 , isoindolinyl claim 1 , azetidinyl claim 1 , oxetanyl claim 1 , pyrrolidinyl claim 1 , piperidinyl claim 1 , morpholinyl claim 1 , piperazinyl claim 1 , tetrahydrofuranyl claim 1 , tetrahydropyranyl claim 1 , or tetrahydrothiophenyl claim 1 , each unsubstituted or substituted.10. The compound of claim 1 , wherein Ris phenyl claim 1 , cycloalkyl claim 1 , heteroaryl claim 1 , or heterocycloalkyl claim 1 , each unsubstituted or substituted with one or more substituents selected from the group consisting of fluoro claim 1 , oxo claim 1 , methyl claim 1 , —CONH claim 1 , acetyl claim 1 , —SOmethyl claim 1 , —C(O)-isopropyl claim 1 , pyridazinyl claim 1 , triazolyl claim 1 , dimethylaminomethyl claim 1 , cyano claim 1 , methyl-triazolyl-methoxy ...

Bicyclic ketone compounds and methods of use thereof

Some embodiments of the invention provide compounds having the general formula I:wherein R1, R2, R3a and R3b are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

BICYCLIC COMPOUNDS FOR USE AS RIP1 KINASE INHIBITORS

The invention provides novel compounds having the general formula I: 7. A compound of , or , or a pharmaceutically acceptable salt thereof , wherein Ris selected from the group consisting of H , F , Cl , CH , CHCH , OCH , CF , OCF , CFH , and OCFH.8. A compound of any one of to , or a pharmaceutically acceptable salt thereof , wherein{'sup': '1', 'sub': 2', '1', '6', '3', '6', '1', '6', '1', '6', '1', '5, 'Ris selected from the group consisting of hydrogen, fluoro, hydroxyl, cyano, CHCN, C-Calkyl, C-Ccycloalkyl, C-Calkoxy, C-Chaloalkyl, C-Chaloalkoxy, and 4 to 5 membered heterocyclyl;'}m is 0, 1, 2 or 3;{'sup': 2a', '2b, 'sub': 1', '3', '1', '3, 'Rand Rare each independently selected from the group consisting of hydrogen, deutero, fluoro, hydroxyl, C-Calkyl, C-Cfluoroalkyl; or'}{'sup': 1', '2a', '2b, 'sub': 1-3', '2', '1-3, 'Ris hydrogen, deutero, fluoro, methyl or cyano, and Rand R, together with the carbon atom to which they are both attached, form 1,1-cyclopropylene that is optionally substituted by one or two substituents selected from the group consisting of F, Calkyl, hydroxyl, hydroxymethyl, methoxymethyl, cyano, CO—Calkyl, trifluoromethyl, difluoromethoxy, and trifluoromethoxy.'}12. A compound of any of to , or a pharmaceutically acceptable salt thereof , selected from the group consisting of:cis-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]propan-1-ol;cis-2-(1,1-difluoropropyl)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole;cis-7-fluoro-2-(1-fluoropropyl)-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole;cis-2,2,2-trifluoro-1-(7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)ethanol;cis-2-[cyclopropyl(difluoro)methyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole;cis-7-fluoro-2-(1-fluoro-1-methyl-propyl)-5-phenyl-6,7-dihydro-5H-pyrrolo[,2-b][1,2,4]triazole;rac-(5S,7S)-7-fluoro-5-phenyl-2-[rac-(1R)-1-fluoropropyl]-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole;rac-(5S,7S)-7-fluoro-2 ...

PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, pharmaceutical compositions containing them, and to their use in therapy for the prevention treatment of cancer. 2. The antibody-drug conjugate of wherein Y is heteroaryl; and Rand Rtogether form a cyclobutyl ring.9. (canceled)10. (canceled)11. The antibody-drug conjugate compound of claim 4 , wherein Y is heteroaryl claim 4 , aryl or alkenyl; and Ris C-Calkylene.13. (canceled)14. (canceled)17. (canceled)2029-. (canceled)30. The antibody-drug conjugate of claim 1 , wherein the antibody binds to one or more of polypeptides selected from the group consisting of:BMPR1B;E16;STEAP1;0772P;MPF;Napi3b;Sema 5b;PSCA hlg;ETBR;MSG783;STEAP2;TrpM4;CRIPTO;CD21;CD79b;FcRH2;HER2;NCA;MDP;IL20Rα;Brevican;EphB2R;ASLG659;PSCA;GEDA;BAFF-R;CD22;CD79a;CXCR5;HLA-DOB;P2X5;CD72;LY64;FcRH1;IRTA2;TEN B2;PMEL17;TMEFF1;GDNF-Ra1;Ly6E;TMEM46;Ly6G6D;LGR5;RET;LY6K;GPR19;GPR54;ASPHD1;Tyrosinase;TMEM118;GPR172A;MUC16 andCD33.31. A method of treating a disease in a human in need thereof claim 1 , comprising administering to said human an effective amount of an antibody-drug conjugate of .32. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier thereof.3340-. (canceled) This invention relates to novel peptidomimetic compounds which are useful as linkers of antibody-drug conjugates (ADC). This invention also relates to ADCs containing peptidomimetic linkers and pyrrolobenzodiazepines (PBD). This invention also relates to methods of treating diseases in humans.The use of monoclonal antibodies (mABs) to deliver anticancer drugs directly to tumor cells has attracted a great deal of focus in recent years. Two new antibody-drug conjugates have been approved by the FDA for the treatment of cancer. Adcetris® (brentuximab vedotin) is a CD30-directed antibody-drug conjugate (ADC) indicated for the treatment of relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell ...

AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES

Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds. 126-. (canceled)28. The compound of claim 27 , wherein Ris —C(O)R.29. The compound of claim 28 , wherein Ris (1) alkyl.30. The compound of claim 29 , wherein Ris isobutyl.31. The compound of claim 28 , wherein Ris (2) heteroaryl or heterocycloalkyl claim 28 , each substituted with one or more alkyl.32. The compound of claim 31 , wherein Ris 2 claim 31 ,4-dimethyloxazolyl.33. The compound of claim 27 , wherein Ris —COR.34. The compound of claim 33 , wherein Ris (1) alkyl.35. The compound of claim 34 , wherein Ris tert-butyl.36. The compound of claim 34 , wherein Ris isopropyl.37. The compound of claim 33 , wherein Ris (2) heteroaryl or heterocycloalkyl claim 33 , each substituted with one or more alkyl.38. The compound of claim 37 , wherein Ris 3-methyloxetan-3-yl.39. The compound of claim 27 , wherein the compound is tert-butyl 2-[(1 claim 27 ,3-dihydropyrrolo[3 claim 27 ,4-c]pyridine-2-carbonylamino)methyl]-6-azaspiro[2.5]octane-6-carboxylate.40. The compound of claim 27 , wherein the compound is isopropyl 2-[(1 claim 27 ,3-dihydropyrrolo[3 claim 27 ,4-c]pyridine-2-carbonylamino)methyl]-6-azaspiro[2.5]octane-6-carboxylate.41. A pharmaceutical composition comprising a compound of claim 27 , or a pharmaceutically acceptable salt thereof claim 27 , and a pharmaceutically acceptable excipient.42. The pharmaceutical composition of claim 27 , comprising the compound of as a pharmaceutically acceptable salt. The present invention relates to certain amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treating cancer, including leukemias and solid tumors, inflammatory diseases, osteoporosis, atherosclerosis, irritable bowel syndrome, and other diseases and medical conditions, with such compounds and pharmaceutical compositions. The present ...

PYRAZOLOPYRIMIDINE COMPOUNDS AND METHODS OF USE THEREOF

Compounds of Formula (IA), or a pharmaceutically acceptable salt thereof, and methods of use as Janus kinase inhibitors are described herein. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A is substituted with 1-5 R claim 1 , wherein each Ris independently selected from the group consisting of: oxo; cyano; C-Calkyl; —(C-Calkyl)C(O)R claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , C-Calkyl claim 1 , or a 6-membered heterocyclic group claim 1 , optionally substituted with —(C-Calkyl)C(O)OR claim 1 , wherein Ris C-Calkyl; —(C-Calkyl)OR claim 1 , wherein Ris hydrogen or C-Calkyl; —(C-Calkyl)C(O)OR claim 1 , wherein Ris hydrogen or C-Calkyl; —(C-Calkyl)NRR claim 1 , wherein each Rand Ris independently hydrogen or C-Calkyl; and —(C-Calkyl)C(O)NRR claim 1 , wherein each Rand Ris independently hydrogen or C-Calkyl.2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A is the 6-membered aromatic group.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A is the 5-membered heterocyclic group.4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein the 5-membered heterocyclic group is a 5-membered heteroaryl group.5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein the 5-membered heteroaryl group is substituted with 1-5 R claim 4 , wherein R″ is selected from the group consisting of cyano; unsubstituted C-Calkyl; —(C-Calkyl)C(O)OR claim 4 , wherein Ris hydrogen or C-Calkyl; —(C-Calkyl)C(O)R claim 4 , wherein Ris selected from the group consisting of hydrogen claim 4 , C-Calkyl claim 4 , or a 6-membered heterocyclic group claim 4 , optionally substituted with —(C-Calkyl)C(O)OR claim 4 , wherein Ris C-Calkyl; and —(C-Calkyl)C(O)NRR claim 4 , wherein each Rand Ris independently hydrogen or C-Calkyl.6. The compound of claim 1 , or a pharmaceutically ...

Peptidomimetic compounds and antibody-drug conjugates thereof

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Peptidomimetic compounds and antibody-drug conjugates thereof

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Peptidomimetic compounds and antibody-drug conjugates thereof

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Peptidomimetic compounds and antibody-drug conjugates thereof

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, pharmaceutical compositions containing them, and to their use in therapy for the prevention treatment of cancer.

drug-antibody conjugate, drug-antibody conjugate, non-peptide compound, method of treating human disease and pharmaceutical composition

a presente invenção refere-se a ligantes peptidomiméticos e seus conjugados de droga e anticorpo, composições farmacêuticas que os compreendem e seu uso na terapia de prevenção ou tratamento de câncer. The present invention relates to peptidomimetic ligands and their drug and antibody conjugates, pharmaceutical compositions comprising them and their use in cancer prevention or treatment therapy.

Peptidomimetic compounds and antibody-drug conjugates thereof

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Aminopyrimidine derivatives as lrrk2 modulators

Peptidomimetic compounds and antibody-drug conjugates thereof

This invention relates to peptidomimetic linkers, cleavable by lysosomal enzymes and anti-body drug conjugates thereof, pharmaceutical compositions containing them, and to their use in therapy for the prevention and treatment of cancer. The drug of the anti-body drug conjugate being a Pyrrolobenzodiazepine dimer.

Aminopyrimidine derivatives as LRRK2 modulators

AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS Abstract Compounds of the formula I or pharmaceutically acceptable salts thereof, wherein m, n, X, R', R2, R', R , R' and R7 are as defined herein. Also disclosed are methods of making the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

Amido-benzyl sulfone and sulfoxide derivatives

The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

Bicyclic lactams and methods of use thereof

The invention relates to compounds having the general formula I: (see formula I) wherein R1, X, L, n, the A ring, the B ring, and the C ring are as described herein, pharmaceutical compositions including the compounds, and uses of the compounds relating to treatment or prophylaxis of irritable bowel disorders (IBD), irritable bowel syndrome (IBS), Crohn's disease, ulcerative colitis, myocardial infarction, stroke, traumatic brain injury, atherosclerosis, ischemia~reperfusion injury of kidneys, liver and lungs, cisplatin-induced kidney injury, sepsis, systemic inflammatory response syndrome (SIRS), pancreatits, psoriasis, retinitis pigmentosa, retinal degeneration, chronic kidney diseases, acute respiratory distress syndrome (ARDS) or chronic obstructive pulmonary disease (COPD).

Bicyclic lactams and methods of use thereof

Amido-benzyl sulfone and sulfonamide derivatives

Disclosed are certain amido-benzyl sulfone and sulfonamide compounds, pharmaceutical compositions comprising such compounds, land methods of treatment using such compounds.

Bicyclic lactams and methods of use thereof

The invention provides novel compounds having the general formula I: (I) wherein R

Amido spirocyclic amide and sulfonamide derivatives

Aminopyrimidine derivatives as lrrk2 modulators

PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR METHODS OF USE

Bicyclic ketone compounds and methods of use thereof

The invention provides novel compounds having the general formula (I): (I) wherein R1, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

Amido-benzyl sulfone and sulfoxide derivatives

The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

2-phenylaminopyrimidine derivatives as lrrk2 kinase modulators for the treatment of parkinson's disease

resumo patente de invenção: "derivados de 2-fenilaminopirimidina como moduladores de cinase lrrk2 para o tratamento de doença de parkinson". a presente invenção refere-se a compostos específicos de fórmula i: i ou sais farmaceuticamente aceitáveis do mesmo, em que m, x, r1, r2, r3, r5, r6 e r7 são como definidos aqui. são também descritos métodos de preparação dos compostos e uso dos compostos para o tratamento de doenças associadas com o receptor de lrrk2, tal como doença de parkinson. 21303466v1 Patent Summary: "2-phenylaminopyrimidine derivatives as lrrk2 kinase modulators for the treatment of parkinson's disease". The present invention relates to specific compounds of formula I: or pharmaceutically acceptable salts thereof, wherein m, x, r 1, r 2, r 3, r 5, r 6 and r 7 are as defined herein. Also disclosed are methods of preparing the compounds and using the compounds for the treatment of lrrk2 receptor associated diseases such as parkinson's disease. 21303466v1

Peptidomimetic compounds and antibody-drug conjugates thereof

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Amido spirocyclic amide and sulfonamide derivatives

Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

Bicyclic compounds for use as RIP 1 kinase inhibitors

The invention provides novel compounds having the general formula (I) or pharmaceutically acceptable salts thereof, wherein R

Bicyclic lactams and methods of use thereof

The invention relates to compounds having the general formula I: (see formula I) wherein R1, X, L, n, the A ring, the B ring, and the C ring are as described herein, pharmaceutical compositions including the compounds, and uses of the compounds relating to treatment or prophylaxis of irritable bowel disorders (IBD), irritable bowel syndrome (IBS), Crohn's disease, ulcerative colitis, myocardial infarction, stroke, traumatic brain injury, atherosclerosis, ischemia~reperfusion injury of kidneys, liver and lungs, cisplatin-induced kidney injury, sepsis, systemic inflammatory response syndrome (SIRS), pancreatits, psoriasis, retinitis pigmentosa, retinal degeneration, chronic kidney diseases, acute respiratory distress syndrome (ARDS) or chronic obstructive pulmonary disease (COPD).

Peptidomimetic compounds and antibody-drug conjugates thereof

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Amido-benzyl sulfone and sulfoxide derivatives

Aminopyrimidine derivatives as lrrk2 modulators

Bicyclic lactams and methods of use thereof

The invention relates to compounds having the general formula I: (see formula I) wherein R1, X, Z1, I, n, the A ring, the B ring, and the C ring are as described herein, pharmaceutical compositions including the compounds, and uses of the compounds relating to treatment or prophylaxis of irritable bowel disorders (IBD), irritable bowel syndrome (IBS), Crohn's disease, ulcerative colitis, myocardial infarction, stroke, traumatic brain injury, atherosclerosis, ischemia¨reperfusion injury of kidneys, liver and lungs, cisplatin-induced kidney injury, sepsis, systemic inflammatory response syndrome (SIRS), pancreatits, psoriasis, retinitis pigmentosa, retinal degeneration, chronic kidney diseases, acute respiratory distress syndrome (ARDS) or chronic obstructive pulmonary disease (COPD).

2-phenylaminopyrimidine derivatives as kinase lrrk2 modulators for the treatment of parkinson's disease

Specific Compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein m, X, R, R2, R3, R, R6 and R7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

2-phenylaminopyrimidine derivatives as kinase lrrk2 modulators for the treatment of parkinson's disease

Specific Compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein m, X, R, R2, R3, R, R6 and R7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

Bicyclic ketone compounds and methods of use thereof

The invention provides novel compounds having the general formula I: (see formula I) wherein R1 the A ring and the B ring are as described herein, and pharmaceutical compositions thereof, which relate to receptor-interacting protein-1 (RIP1) kinase inhibition, for treatment of a disease or disorder such as Parkinson's Disease, Lewy body dementia, multiple system atrophy, Parkinson-plus syndrome, taupathy, Alzheimer's Disease, frontotemporal dementia, amyotrophic lateral sclerosis, spinal muscular atrophy, primary lateral sclerosis, Huntington's disease, ischemia, stroke, intracranial hemorrhage, cerebral hemorrhage, muscular dystrophy, progressive muscular atrophy, pseudobulbar palsy, progressive bulbar palsy, spinal muscular atrophy, inherited muscular atrophy, peripheral neuropathy, progressive supranuclear palsy, corticobasal degeneration, demyelinating disease, inflammatory bowel disease, Crohn's disease, ulcerative colitis, glaucoma, psoriasis, psoriatic arthritis, rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, osteoarthritis, kidney damage, acute kidney injury (AKI), transplant rejection, ischemia reperfusion injury of solid organs, sepsis, or systemic inflammatory response syndrome (SIRS).

BICYCLIC COMPOUNDS INTENDED FOR USE AS KINASE RIP1 INHIBITORS

Bicyclic compounds for use as rip1 kinase inhibitors

The invention provides novel compounds having the general formula (I) or pharmaceutically acceptable salts thereof, wherein RA, RB1, RB2, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds as RIP1 kinase inhibitors.

pyrazolopyrimidone and pyrazolopyridone tanquirase inhibitors

BICYCLE BEDS AND METHODS OF USING THEM

SE REFIERE A COMPUESTOS DERIVADOS DE LACTAMAS BICICLICAS DE FORMULA (I) EN DONDE R1, X, Z1, L, n, EL ANILLO A, EL ANILLO B Y EL ANILLO C SON TAL COMO SE DESCRIBEN EN EL PRESENTE DOCUMENTO. SON COMPUESTOS PREFERIDOS: (S)-N-(4-METIL-5-OXO-5,6,7,8-TETRAHIDRO-4H-PIRAZOLO[1,5-a][1,3]DIAZEPIN-6-IL)-4-FENOXIPICOLINAMIDA; 1-BENCIL-N-(1-METIL-2-OXO-1,2,3,4,5,6-HEXAHIDROIMIDAZO[1,5-a][1,3]DIAZOCIN-3-IL)-1H-1,2,4-TRIAZOL-3-CARBOXAMIDA; ENTRE OTROS. TAMBIEN SE REFIERE A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS SON INHIBIDORES DE LA PROTEINA QUE INTERACTUA CON EL RECEPTOR 1 (RIP1) CINASA SIENDO UTILES EN EL TRATAMIENTO DE TRASTORNOS DEL INTESTINO IRRITABLE, ENFERMEDAD DE CROHN, COLITIS ULCEROSA REFERS TO COMPOUNDS DERIVED FROM BICYCLE LACTAMS OF FORMULA (I) WHERE R1, X, Z1, L, n, RING A, RING B AND RING C ARE AS DESCRIBED IN THIS DOCUMENT. PREFERRED COMPOUNDS ARE: (S) -N- (4-METHYL-5-OXO-5,6,7,8-TETRAHYDRO-4H-PIRAZOLO [1,5-a] [1,3] DIAZEPIN-6-IL) -4-PHENOXYPICOLINAMIDE; 1-BENZYL-N- (1-METHYL-2-OXO-1,2,3,4,5,6-HEXAHYDROIMIDAZO [1,5-a] [1,3] DIAZOCIN-3-IL) -1H-1 , 2,4-TRIAZOL-3-CARBOXAMIDE; AMONG OTHERS. IT ALSO REFERS TO A PHARMACEUTICAL COMPOSITION. SUCH COMPOUNDS ARE INHIBITORS OF THE PROTEIN THAT INTERACT WITH THE RECEPTOR 1 (RIP1) KINASE BEING USEFUL IN THE TREATMENT OF IRRITABLE BOWEL DISORDERS, CROHN'S DISEASE, ULCEROUS COLITIS

Bicyclic compounds for use as rip1 kinase inhibitors

La invención proporciona nuevos compuestos que presentan la fórmula general I o sales farmacéuticamente aceptable de los mismos, en los que: RA, RB1, RB2, el anillo A y el anillo B son tal como se indica en la presente memoria, composiciones farmacéuticas que incluyen los compuestos y métodos de utilización de los compuestos.

bicyclic compounds for use as rip1 kinase inhibitors

A invenção prove novos compostos apresentando a fórmula geral I; ou sais farmaceuticamente aceitáveis dos mesmos, em que; RA, RB1, RB2, o anel A e o anel B são conforme descritos no presente documento, composições farmacêuticas incluindo os compostos, os métodos de uso dos compostos como inibidores de RIP1 quinase. The invention provides new compounds showing the general formula I; or pharmaceutically acceptable salts thereof, wherein; RA, RB1, RB2, ring A and ring B are as described herein, pharmaceutical compositions including the compounds, methods of using the compounds as inhibitors of RIP1 kinase.

PEPTIDOMIMETIC COMPOUNDS AND THEIR ANTIBODY-DRUG CONJUGATES

Se refiere a conjugados de anticuerpo-farmaco (ADCs) de formula: Ab-(L-D)p, donde Ab es un anticuerpo anti CD33, anti NaPi2b y anti CD-22, de los cuales el Ab anti CD33 comprende: a) tres regiones hipervariables de cadena ligera HVR-L1 de SEQ ID NO: 11, HVR-L2 de SEQ ID NO:12 y HVR-L3 de SEQ ID NO: 13 y b) tres regiones hipervariables de cadena pesada HVR-H1 de SEQ ID NO: 14, HVR-H2 de SEQ ID NO: 15 y HVR-H3 de SEQ ID NO: 16; L es un ligador peptidomimetico de formula: -Str-(PM)-Sp-, donde; Str es una unidad extensora covalentemente unida a Ab; Sp es un enlace o unidad espaciadora covalentemente unida a D; PM es un resto quimico no peptidico, selccionado de -C(O)-W-C(R1)-C(O)-N-, entre otros; p es un numero entero de 1 a 8 y D es un resto farmacologico de formula (I) donde R11 y R22 son H, P(O)3H2, entre otros; T es un grupo de traba como alquileno C3-C12, entre otros; X1 es O, NH, entre otros. Tambien se refiere a un compuesto donde D es un agente antitumoral o un resto antibiotico tal como metotrexato, adriamicina, entre otros. Dichos ADCs son utiles en terapia para la prevencion y/o tratamiento de cancer Refers to antibody-drug conjugates (ADCs) of the formula: Ab- (LD) p, where Ab is an anti-CD33, anti-NaPi2b and anti-CD-22 antibody, of which the anti-CD33 Ab comprises: a) three regions hypervariable light chain HVR-L1 of SEQ ID NO: 11, HVR-L2 of SEQ ID NO: 12 and HVR-L3 of SEQ ID NO: 13 and b) three hypervariable regions of heavy chain HVR-H1 of SEQ ID NO: 14 , HVR-H2 of SEQ ID NO: 15 and HVR-H3 of SEQ ID NO: 16; L is a peptidomimetic linker of the formula: -Str- (PM) -Sp-, where; Str is an extender unit covalently attached to Ab; Sp is a bond or spacer unit covalently attached to D; PM is a non-peptide chemical moiety, selected from -C (O) -W-C (R1) -C (O) -N-, among others; p is an integer from 1 to 8 and D is a pharmacological residue of formula (I) where R11 and R22 are H, P (O) 3H2, among others; T is a locking group such as C3-C12 alkylene, among others; ...

PYRAZOLOPYRIMIDINE COMPOUNDS AND METHODS OF USE OF THEM

Referido a un compuesto de formula general (IA), o una sal farmaceuticamente aceptable, en donde: A es un anillo condensado seleccionado entre el grupo que consiste en un grupo aromatico de 6 miembros, un grupo heterociclico de 5 o 6 miembros, entre otros; R es H, halogeno, ciano, entre otros; R0 es H, halogeno, ciano, alquilo C1-C3, entre otros; R1 es H, alquenilo C2-C6, entre otros. Un compuesto preferido es N-[3-[3-(difluorometoxi)-2-naftil]-1H-pirazol-4-il]pirazolo[1,5-a]pirimidin-3-carboxamida. Estos compuestos son inhibidores de molecula pequena de una Janus cinasa, tal como JAK1. Tambien se refiere a metodos de preparacion de los mismos, sus compuestos intermedios y su uso en el tratamiento de una enfermedad inflamatoria como el asma.

Pyrazole derivatives, compositions and therapeutic use thereof

Compounds of Formula (I): and salts thereof, and methods of use as Janus kinase inhibitors are described herein.

Amido spirocyclic amide and sulfonamide derivatives

ll:\aar\Interwovn\NRPortbl\DCC\AAR843266_l.docx-l/ It2017 Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

Lactamas bicíclicas e métodos de uso das mesmas

LACTAMAS BICÍCLICAS E MÉTODOS DE USO DAS MESMAS. A invenção proporciona novos compostos que são dotados da fórmula geral I, em que R1, X, Z1, L, n, o anel A, o anel B, e o anel C são tais como se encontram descritos neste contexto, composições farmacêuticas que incluem os compostos e métodos de utilização dos compostos.

Bicyclic lactams and methods of use thereof

Bicyclic lactams as receptor-interacting protein-1 (rip1) kinase inhibitors for treating e.g. inflammatory diseases

Axl compounds

Compounds of Formula I that inhibit AXL, and compositions containing the compound(s) and methods for synthesizing the compounds, are described herein. Also described are the use of such compounds and compositions for the treatment of a diverse array of diseases, disorders, and conditions, including cancer- and immune-related disorders that are mediated, at least in part, by AXL.

Bisyklisiä ketoniyhdisteitä ja niiden käyttömenetelmiä

Bicyclic ketone compounds and methods of use thereof

Axl inhibitor compounds

Compounds of Formula I that inhibit AXL, and compositions containing the compound(s) and methods for synthesizing the compounds, are described herein. Also described are the use of such compounds and compositions for the treatment of a diverse array of diseases, disorders, and conditions, including cancer- and immune-related disorders that are mediated, at least in part, by AXL.

Neuroactive steroids and pharmaceutical composition containing the same

The invention of this disclosure is directed to a neuroactive steroid (NAS) of a novel structure. This invention is also directed to a pharmaceutical composition comprising the neuroactive steroid (NAS) and salts thereof. The pharmaceutical composition can be used for preventing and/or treating CNS conditions or diseases related to GABA-modulation, such as depression, bipolar disorder, dementia, Huntington's disease, Parkinson's disease, etc. This invention is further directed to a method for treating a CNS disorder in a subject in need thereof.

Bicyclic ketone compounds and methods of use thereof

The invention provides novel compounds having the general formula I: wherein R 1 , the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

Bicikliniai ketoniniai junginiai ir jų naudojimo būdai

Bicykliske ketonforbindelser og fremgangsmåder til anvendelse deraf

Bicyclic lactams and methods of use thereof

The invention provides novel compounds having the general formula I: (I) wherein R1, X, Z1, L, n, the A ring, the B ring, and the C ring are as described herein, pharmaceutical compositions including the compounds and methods of using the compounds.

Therapeutic compounds, compositions and methods of use thereof

Compounds of Formula (I): and salts thereof, and methods of use as Janus kinase inhibitors are described herein.

Esteroides neuroativos e composição farmacêutica que contém os mesmos

ESTEROIDES NEUROATIVOS E COMPOSIÇÃO FARMACÊUTICA QUE CONTÉM OS MESMOS. A invenção desta divulgação refere-se a um esteroide neuroativo (NAS) de uma estrutura. Esta invenção também se refere a uma composição farmacêutica que compreende o esteroide neuroativo (NAS) e sais do mesmo. A composição farmacêutica pode ser usada para prevenir e/ou tratar afecções ou doenças do SNC relacionadas à modulação de GABA, tais como depressão, transtorno bipolar, demência, doença de Huntington, mal de Parkinson, etc. Esta invenção se refere, adicionalmente, a um método para tratamento de um transtorno de SNC em um indivíduo que necessita do mesmo.

Bicyclic lactams as receptor-interacting protein-1 (rip1) kinase inhibitors for treating e.g. inflammatory diseases

Bicyclic lactams and methods of use thereof

The invention provides novel compounds having the general formula I: (I) wherein R?, X, Z?, L, n, the A ring, the B ring, and the C ring are as described herein, pharmaceutical compositions including the compounds and methods of using the compounds. (No suitable figure)

Neuroactive steroids and pharmaceutical composition containing the same

The invention of this disclosure is directed to a neuroactive steroid (NAS) of a novel structure. This invention is also directed to a pharmaceutical composition comprising the neuroactive steroid (NAS) and salts thereof. The pharmaceutical composition can be used for preventing and/or treating CNS conditions or diseases related to GABA-modulation, such as depression, bipolar disorder, dementia, Huntington's disease, Parkinson's disease, etc. This invention is further directed to a method for treating a CNS disorder in a subject in need thereof.

Neuroactive steroids and pharmaceutical composition containing the same

Composés cétoniques bicycliques et leurs procédés d'utilisation

L'invention concerne de nouveaux composés représentés par la formule générale i : (i) dans laquelle r1, le cycle a et le cycle b sont tels que décrits dans la description, ainsi que des compositions pharmaceutiques comprenant lesdits composés et des procédés d'utilisation de ces composés.

Compuestos de cetona bicíclica y procedimientos de uso de los mismos

La invención proporciona nuevos compuestos que tienen la fórmula general (I): (I) en la que R1, el anillo A y el anillo B son como se describen en el presente documento, composiciones farmacéuticas que incluyen los compuestos y métodos para usar los compuestos. (Traducción automática con Google Translate, sin valor legal)

Bicyclic pyrrolotriazolr ketone compounds and methods of use thereof

Some embodiments of the invention provide compounds having the general formula (I) wherein R1, R2, R3a and R3b are as described herein, pharmaceutical compositions including the compounds, and the compounds for use in methods of treating illnesses.

Axl inhibitor compounds

Compounds of Formula I that inhibit AXL, and compositions containing the compound(s) and methods for synthesizing the compounds, are described herein. Also described are the use of such compounds and compositions for the treatment of a diverse array of diseases, disorders, and conditions, including cancer- and immune-related disorders that are mediated, at least in part, by AXL.

Biciklički ketonski spojevi i postupci njihove primjene

Biciklična ketonska jedinjenja i postupci za njihovu upotrebu

Bicykliczne związki ketonowe i sposoby ich stosowania

Esteroides neuroactivos y composicion farmaceutica que contiene los mismos.

La invención de esta descripción está dirigida a un esteroide neuroactivo (NAS) de una estructura novedosa. Esta invención también se dirige a una composición farmacéutica que comprende el esteroide neuroactivo (NAS) y sales del mismo. La composición farmacéutica se puede usar para prevenir y/o tratar afecciones o enfermedades del SNC relacionadas con la modulación de GABA, como la depresión, trastorno bipolar, demencia, enfermedad de Huntington, enfermedad de Parkinson, etc. Esta invención también se refiere a un método para tratar un trastorno del SNC en un sujeto que lo necesite.

Axl compounds

Compounds of Formula I that inhibit AXL, and compositions containing the compound(s) and methods for synthesizing the compounds, are described herein. Also described are the use of such compounds and compositions for the treatment of a diverse array of diseases, disorders, and conditions, including cancer- and immune-related disorders that are mediated, at least in part, by AXL.

Biciklične ketonske spojine in načini njihove uporabe

Bicyclic ketone compounds and methods of use thereof

The invention provides novel compounds having the general formula I:wherein R', the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

Pharmceutical Compositions Containing Polydatin or Its Salts and Their Application

The invention discloses pharmaceutical compositions containing polydatin or its pharmaceutically acceptable salts with the effect of improving microcirculation, and their application in preparing drugs which can improve microcirculation. The compositions are an non-gastrointestinal injection preparation, the preparation can be an aqueous solution which have pH 7.0-10.0 comprising 5-50% propandiol. The dosage forms of the compositions may be lyophilizing powder injection, oral form, suppository of procto-administration and other forms of administrations comprising unguent, ointment, paste film coating and the like. The compositions may be used to treat and/or prevent diseases related to microcirculation blockage. The unit form may contain 1-1000 mg polydatin or its derivatives. The invention solves the problem of using polydatin to improve microcirculation. The composition of the invention can be used in treating shock, cardiac and cerebrovascular diseases, diseases of sense organs, diabetes complication, vaculitis related to blockage of blood vessel, hemorrhoid related to circulation obstruction, skin injury and burn.

Bicyclic ketone compounds and methods of use thereof

The invention provides novel compounds having the general formula I:wherein R', the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

Bicyclic ketone compounds and methods of use thereof

The invention provides novel compounds having the general formula I:wherein R1, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

Bicyclic lactams and methods of use thereof

The invention provides novel compounds having the general formula I: (I) wherein R1, X, Z1, L, n, the A ring, the B ring, and the C ring are as described herein, pharmaceutical compositions including the compounds and methods of using the compounds.

Bicyclic ketone compounds and methods of use thereof

The invention provides novel compounds which are RIP1 kinase inhibitors having the general formula (I): (I) wherein R1, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds in the treatment of diseases such as Parkinson’s disease, inflammatory bowel disorder and acute kidney injury.

Bicyclic lactams and methods of use thereof

The invention provides novel compounds having the general formula I: (I) wherein R1, X, Z1, L, n, the A ring, the B ring, and the C ring are as described herein, pharmaceutical compositions including the compounds and methods of using the compounds in particular to inhibitors of RIP1 kinase useful for treating diseases and disorders associated with inflammation, cell death and others.

Peptidomimetic compounds and antibody-drug conjugates thereof

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.