COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING CDK9 ACTIVITY

Inhibitors of CDK9 that are pyrazolo[1,5-a]pyrimidine derivatives and salts thereof, corresponding to formula (I): 2. The compound or salt thereof of claim 1 , wherein{'sup': '1', 'sub': '2', 'claim-text': {'sup': 1', '8, 'Ris NHCOR;'}, 'Ris C1-C6 alkyl or C3-C6 cycloalkyl, optionally substituted at any position with NH, or'}{'sup': 2', '3', '4', '6, 'R, R, R, and Rare H;'}{'sup': 5', '8', '8, 'sub': '2', 'Ris cyclobutyl, cyclopentyl, or cyclohexyl, optionally substituted at any position with D, NH, OH, NHR, OR, or combinations thereof; and'}{'sup': '8', 'Ris C1-C4 alkyl.'}3. The compound or salt thereof of claim 1 , wherein{'sup': '1', 'sub': '3', 'Ris methyl, ethyl, isopropyl, sec-butyl, 3-pentyl, cyclopropyl, cyclopentyl, or NHCOCH;'}{'sup': 2', '3', '4', '6, 'R, R, R, and Rare H; and'}{'sup': '5', 'sub': '2', 'Ris cyclobutyl, cyclopentyl, or cyclohexyl, optionally substituted at any position with NH.'}5. The compound or salt of any one of to claim 1 , wherein the compound or salt is a racemic or non-racemic mixture of optically active stereoisomers.6. The compound or salt of any one of to claim 1 , wherein the compound or salt is a substantially pure single enantiomer or diastereomer.7. The compound or salt of any one of to as a dichloride salt.8. A composition comprising a compound or salt of any one of to and a pharmaceutically acceptable carrier.9. A method of treating a CDK9-mediated disease claim 1 , comprising administering to a subject in need thereof a compound according to any of to or a composition according to .10. The method of claim 9 , wherein the disease is a cancer caused by aberrant expression of MYC- or MCL-1 claim 9 , a hematologic malignancy claim 9 , or a solid tumor.11. The method of claim 9 , wherein the disease is acute myelogenous leukemia claim 9 , primary peritoneal carcinoma claim 9 , chronic lymphocytic leukemia claim 9 , relapsed multiple myeloma claim 9 , non-Hodgkin's lymphoma claim 9 , acute lymphoblastic leukemia claim 9 , acute ...

SUMO INHIBITOR COMPOUNDS AND USES THEREOF

The present invention relates to compounds and compositions capable of acting as inhibitors of small ubiquitin-like modifier (SUMO) family of proteins. The compounds and compositions may be used in the treatment of cancer. There are disclosed, inter alia, methods of inhibiting an E1 enzyme, and compounds useful for inhibiting an E1 enzyme. 2. The compound of wherein ring A is selected from dihydropyran claim 1 , dihydrothienyl claim 1 , dihydrofuryl claim 1 , oxo-dihydrofuryl claim 1 , pyrrolinyl claim 1 , dihydrothiazolyl claim 1 , dihydro-oxazolyl claim 1 , dihydro-isothiazolyl claim 1 , dihydro-isoxazolyl claim 1 , midazolinyl and pyrazolinyl claim 1 , wherein ring A is optionally substituted with one or more substituent groups.3. The compound of wherein ring A is selected from thienyl claim 1 , furanyl claim 1 , pyrrolyl claim 1 , thiazolyl claim 1 , oxazolyl claim 1 , midazolyl claim 1 , pyrazolyl claim 1 , isoxazolyl claim 1 , triazolyl and isothiazolyl claim 1 , wherein ring A is optionally substituted with one or more substituent groups.6. The compound of wherein ring A is selected from phenyl claim 1 , pyridyl claim 1 , pyrazinyl claim 1 , pyrimidinyl claim 1 , pyridazinyl claim 1 , and triazinyl claim 1 , wherein ring A is optionally substituted with one or more substituent groups.8. The compound of wherein ring A is selected from phenyl or thienyl claim 1 , wherein ring A is optionally substituted with one or more substituent groups.9. The compound of any one of - wherein Ris selected from substituted or unsubstituted phenyl claim 1 , substituted or unsubstituted cycloalkyl and substituted or unsubstituted 5- or 6-membered heteroaryl.10. The compound of any one of - wherein Ris selected from substituted or unsubstituted phenyl claim 1 , substituted or unsubstituted cyclopentyl claim 1 , substituted or unsubstituted cyclohexyl and substituted or unsubstituted pyridyl.11. The compound of any one of - wherein E is selected from —C(═O)CH═CH claim 1 , —C(═O)- ...

Compounds, Compositions, and Methods for Modulating CDK9 Activity

Inhibitors of CDK9 that are pyrazolo[1,5-a]pyrimidine derivatives and salts thereof, corresponding to formula (I):

Inhibitors of protein isoprenyl transferases

Compounds having formula (I) or a pharmaceutically acceptable salt thereof wherein R1 is (a) hydrogen, (b) lower alkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl -L2-, and (i) heterocyclic -L2-; R2 is selected from (a) formula (1), (b) -C(O)NH-CH(R14)-C(O)OR15, (c) formula (2), (d) -C(O)NH-CH(R14)-C(O)NHSO2R16, (e) -C(O)NH-CH(R14)-tetrazolyl, (f) -C(O)NH-heterocyclic, and (g) -C(O)NH-CH(R14)-C(O)NR17R18; R3 is substituted or unsubstituted heterocyclic or aryl, substituted or unsubstituted cycloalkyl or cycloalkenyl, formula (3), and -P(W)R?R3RR3'; R¿4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylalkyl, heterocyclic, or (heterocyclic)alkyl; L1 is absent or is selected from (a) -L4-N(R5)-L5-, (b) -L4-O-L5-, (c) -L4-S(O)n-L5-, (d) -L4-L6-C(W)-N(R5)-L5-, (e) -L4-L6-S(O)m-N(R5)-L5-, (f) -L4-N(R5)-C(W)-L7-L5-, (g) -L4-N(R5)-S(O)p-L7-L5-, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, (j) optionally substituted alkynylene, (k) a covalent bond, (1) formula (4), and (m) formula (5) are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

Substituted pyrazolo[1,5-a]pyrimidines for modulating CDK9 activity

Inhibitors of CDK9 that are pyrazolo[1,5-a]pyrimidine derivatives and salts thereof, corresponding to formula (I):

Benzoyl amino acid derivatives useful as inhibitors of protein isoprenyl tranferases

Compounds having formula (I) or a pharmaceutically acceptable salt thereof wherein R1 is (a) hydrogen, (b) lower alkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl -L2-, and (i) heterocyclic -L2-; R2 is selected from (a) formula (1), (b) -C(O)NH-CH(R14)-C(O)OR15, (c) formula (2), (d) -C(O)NH-CH(R14)-C(O)NHSO2R16, (e) -C(O)NH-CH(R14)-tetrazolyl, (f) -C(O)NH-heterocyclic, and (g) -C(O)NH-CH(R14)-C(O)NR17R18; R3 is substituted or unsubstituted heterocyclic or aryl, substituted or unsubstituted cycloalkyl or cycloalkenyl, formula (3), and -P(W)RR3RR3'; R4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylalkyl, heterocyclic, or (heterocyclic)alkyl; L1 is absent or is selected from (a) -L4-N(R5)-L5-, (b) -L4-O-L5-, (c) -L4-S(O)n-L5-, (d) -L4-L6-C(W)-N(R5)-L5-, (e) -L4-L6-S(O)m-N(R5)-L5-, (f) -L4-N(R5)-C(W)-L7-L5-, (g) -L4-N(R5)-S(O)p-L7-L5-, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, (j) optionally substituted alkynylene, (k) a covalent bond, (1) formula (4), and (m) formula (5) are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

Angiotensin ii receptor antagonists

ABSTRACT OF THE DISCLOSURE Novel pyrimidine, pyridine, pyridazine, pyrazine and triazine compounds are provided of the formula (I). (I)

Pyrrolidine carboxylic acid derivatives as endothelin antagonists

Endothelin antagonists

Novel benzo-1,3-dioxolyl- and benzofuranyl substituted pyrrolidine derivatives as endothelin antagonists

A compound of formula (I), or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

Endothelin antagonists

Pyrrolidine carboxylic acid derivatives as endothelin antagonists

A compound of formula (I), or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

Endothelin antagonists

A compound of formula (I) or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

Novel benzo-1,3-dioxolyl-and benzofuranyl substituted pyrrolidine derivatives as endothelin antagonists

A compound of formula (1), or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for intermediates in the preparation thereof, and a method of antagonizing endothelin.

ENDOTHELINE ANTAGONISTS.

SE DESCRIBE UN COMPUESTO DE FORMULA (I), O UNA SAL FARMACEUTICAMENTE ACEPTABLE DEL MISMO, ASI COMO PROCEDIMIENTOS E INTERMEDIARIOS PARA LA PREPARACION DEL MISMO, Y UN METODO DE ANTAGONIZACION DE ENDOTELINA. A COMPOSITE OF FORMULA (I), OR A PHARMACEUTICALLY ACCEPTABLE SALT OF THE SAME IS DESCRIBED, AS WELL AS PROCEDURES AND INTERMEDIARIES FOR THE PREPARATION OF THE SAME, AND AN ENDOTHELINE ANTAGONIZATION METHOD.

Endothelin antagonists

A compound of formula (I) or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

4-(benzo-1,3-dioxolyl)-pyrrolidine-3-carboxylic acid derivatives as endothelin antagonists

Inhibitors of protein isoprenyl transferases

Endothelin antagonists

Endothelin antagonists.

Bir formül (I) bilesigi veya farmasötik olarak kabul edilebilir bir tuzu açiklanmaktadir; ayrica bunlari hazirlamak için islemler ve bunlari hazirlamak için kullanilan ara maddelerin yani sira endotelini antagonize etmek için bir yöntem açiklanmaktadir. A compound of formula (I) or a pharmaceutically acceptable salt is disclosed; Also described is a process for antagonizing the endothelium as well as the processes for preparing them and the intermediates used to prepare them.

Angiotensin II receptor antagonists

Thiazole compounds as protein kinase b (pkb) inhibitors

The invention relates to thiazole compounds of Formula (I) and Formula (II) and compositions thereof useful for treating diseases mediated by protein kinase B (PKB) where the variables have the definitions provided herein. The invention also relates to the therapeutic use of such thiazole compounds and compositions thereof in treating disease states associated with abnormal cell growth, cancer, inflammation, and metabolic disorders.

4-(benzo-1,3-dioxolyl)-pyrrolidine-3-carboxylic acid derivatives as endothelin antagonists

A compound of formula (I) or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

Nitrile sumo inhibitors and uses thereof

The present invention relates to cyano-containing compounds and compositions capable of acting as inhibitors of small ubiquitin-like modifier (SUMO) family of proteins. The compounds and compositions may be used in the treatment of cancer. There are disclosed, inter alia, methods of inhibiting an E1 enzyme, and compounds useful for inhibiting an E1 enzyme.

Inhibitors of phosphoinositide 3-kinase (pi3k) and uses thereof

Disclosed herein are compounds of Formulae 1A, 1B, 1C and 1D, (1A), (1B), (1C) and (1D) and methods of making and methods of using the same.

Novel benzo-1,3-dioxolyl- and benzofuranyl substituted pyrrolidine derivatives as endothelin antagonists

A compound of formula (I), or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

Thiazole compounds as protein kinase B inhibitors (PKB)

Un compuesto de Fórmula 1:**Fórmula**en la que:A esy es _N(Rs)ReX es N(R\R' es RS, -CHR"-N(H)-RS, -CHR"-O-RS, alquinilo C2-Ce, hidroxialquinilo C2-Ce o -C::N;R2 es arilo o heteroarilo;R3 es -H o alquilo C,-Ce;A4 es -(CR9RlO)¡(arilo) o -(CR9R'O)¡(heteroarilo);RS es -H o alquilo C,-CS;Re y R7 se seleccionan independientemente de -H o alquilo C,-CS;RS es -H, alquilo C,-Ce, -(alquil C,-Ce)arilo, arilo o heteroarilo; yR9, R'O y R" se seleccionan independientemente de -H, alquilo C,-Ce o arilo;en la que m es 1; n es 1; Y t es 1;en la que cada uno de los restos alquilo, arilo y heteroarilo anteriores está opcional e independientemente sustituidocon 1-3 sustituyentes seleccionados deamino,alquilo C,-Ce, haloalquilo C,-Ce, hidroxialquilo C,-Ce, alcoxi C,-Ce, alquil C,-Ce-amino, alquenilo C2-Ce o alquiniloC2-Ce, pudiendo estar cada uno de los mismos interrumpidos con uno o varios heteroátomos,ciano,halo,hidroxilo,nitro, o-O-arilo;o una sal farmacéuticamente aceptable, hidrato o estereoisómero del mismo.

Inhibitoren der protein-isoprenyl-transferase

Isoprentransferase proteine inhibitoren

Substituted pyrazolo[1,5-a]pyrimidines for modulating CDK9 activity

Inhibitors of CDK9 that are pyrazolo[1,5-a]pyrimidine derivatives and salts thereof, corresponding to formula (I):

Neue benzo-1,3-dioxolyl-und benzofuranyl substituierte pyrrolidinederivate als endothelin antagonisten

Endotelin-antagonista hatású 4-(benzo-1,3-dioxolil)-pirrolidin-3-karbonsav-származékok és az ezeket tartalmazó gyógyszerkészítmények

A találmány endőtelin-antagőnista hatású, (I) általánős képletűvegyületekre, az ezeket tartalmazó gyógyszerkészítményekre (I)vőnatkőzik. A találmány szerinti (I) általánős képletű vegyületekben Rjelentése -(CH2)m-W általánős képletű csőpőrt, amelyben m értéke 0-6,és W jelentése karbőxil-, vagy védett karbőxilcsőpőrt, vagy főszfőrsav(származék), cianőcsőpőrt, adőtt esetben szűbsztitűált aminőcsőpőrt,hidrőxi-, alkőxicsőpőrt, szűlfőnamidcsőpőrt, R1 és R2 jelentéseegymástól függetlenül hidrőgénatőm, rövidszénláncú, alkilcsőpőrt,hidrőxi-, vagy halőgén-alkil-csőpőrt, alkőxicső- pőrt,ciklőalkilcsőpőrt, adőtt esetben szűbsztitűált aminőcsőpőrt vagyaralkilcsőpőrt, különböző heterciklűsős csőpőrtők, heterő- ciklűsttaralmazó alkilcsőpőrt, R3 jelentése R4-C(O)-R5- általánős képletűcsőpőrt, amelyben -R4 jelentése főként (j) általánős képletű csőpőrt,ahől R11 és R12 jelentése alkil-, alkőxi-, cianőcsőpőrt halőgénatőm,vagy fenilcsőpőrt, R13 jelentése hidrőgénatőm- vagy halőgénatőm-karbőxil-, nitrő- vgy cianőcsőpőrt, és R5 jelentése főkéntalkiléncsőpőrt. A találmány szerinti vegyületek főkéntkardiővaszkűláris megbetegedések, így pangásős szívelégtelenség,egyéni vagy szívizőm-iszkémia, trőmbózis. aterősklerózis kezelésérealkalmazhatók. ŕ

4-(benzo-1,3-dioxolyl)-pyrrolidin-3-carbonsaure derivate als endothelin-antagonisten

Compounds, compositions, and methods for modulating cdk9 activity

Inhibitors of CDK9 that are pyrazolo[1,5-a]pyrimidine derivatives and salts thereof, corresponding to formula (I):

Endothelin antagonists

Nitrile sumo inhibitors and uses thereof

The present invention relates to cyano-containing compounds and compositions capable of acting as inhibitors of small ubiquitin-like modifier (SUMO) family of proteins. The compounds and compositions may be used in the treatment of cancer. There are disclosed, inter alia, methods of inhibiting an E1 enzyme, and compounds useful for inhibiting an E1 enzyme.

Endothelin antagoniste