PT2766361T - Derivados de 8-carbamoíl-2-(pirid-6-il 2,3-dissubstituído)-1,2,3,4-tetra-hidroisoquinolina como agentes indutores da apoptose, para o tratamento de cancro e doenças imunes e autoimunes - Google Patents

Derivados de 8-carbamoíl-2-(pirid-6-il 2,3-dissubstituído)-1,2,3,4-tetra-hidroisoquinolina como agentes indutores da apoptose, para o tratamento de cancro e doenças imunes e autoimunes Download PDF

Info

Publication number
PT2766361T
PT2766361T PT127806057T PT12780605T PT2766361T PT 2766361 T PT2766361 T PT 2766361T PT 127806057 T PT127806057 T PT 127806057T PT 12780605 T PT12780605 T PT 12780605T PT 2766361 T PT2766361 T PT 2766361T
Authority
PT
Portugal
Prior art keywords
methyl
dec
benzothiazol
ylcarbamoyl
carboxylic acid
Prior art date
Application number
PT127806057T
Other languages
English (en)
Portuguese (pt)
Inventor
R Kunzer Aaron
Song Xiaohong
J Souers Andrew
Le Wang
Wang Xilu
M Hansen Todd
Doherty George
Tao Zhi-Fu
Brunko Milan
D Wendt Michael
Frey Robin
Judd Andrew
M Sullivan Gerard
Original Assignee
Abbvie Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=47116421&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=PT2766361(T) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Abbvie Inc filed Critical Abbvie Inc
Publication of PT2766361T publication Critical patent/PT2766361T/pt

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41881,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/472Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
PT127806057T 2011-10-14 2012-10-11 Derivados de 8-carbamoíl-2-(pirid-6-il 2,3-dissubstituído)-1,2,3,4-tetra-hidroisoquinolina como agentes indutores da apoptose, para o tratamento de cancro e doenças imunes e autoimunes PT2766361T (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161547162P 2011-10-14 2011-10-14
CN2012079012 2012-07-23

Publications (1)

Publication Number Publication Date
PT2766361T true PT2766361T (pt) 2016-10-27

Family

ID=47116421

Family Applications (1)

Application Number Title Priority Date Filing Date
PT127806057T PT2766361T (pt) 2011-10-14 2012-10-11 Derivados de 8-carbamoíl-2-(pirid-6-il 2,3-dissubstituído)-1,2,3,4-tetra-hidroisoquinolina como agentes indutores da apoptose, para o tratamento de cancro e doenças imunes e autoimunes

Country Status (36)

Country Link
EP (1) EP2766361B1 (https=)
JP (2) JP6155270B2 (https=)
KR (1) KR102019643B1 (https=)
AR (1) AR088327A1 (https=)
AU (2) AU2012322698A1 (https=)
BR (1) BR112014009053B1 (https=)
CA (1) CA2851364C (https=)
CL (1) CL2014000905A1 (https=)
CO (1) CO6950476A2 (https=)
CR (2) CR20200097A (https=)
CY (1) CY1118224T1 (https=)
DK (1) DK2766361T3 (https=)
DO (2) DOP2014000070A (https=)
EC (1) ECSP14000357A (https=)
ES (1) ES2598877T3 (https=)
GT (1) GT201400064A (https=)
HR (1) HRP20161319T1 (https=)
HU (1) HUE030589T2 (https=)
IL (1) IL231856A (https=)
LT (1) LT2766361T (https=)
ME (1) ME02514B (https=)
MX (1) MX356031B (https=)
MY (1) MY172723A (https=)
PE (1) PE20141282A1 (https=)
PH (2) PH12014500729A1 (https=)
PL (1) PL2766361T3 (https=)
PT (1) PT2766361T (https=)
RS (1) RS55342B1 (https=)
RU (1) RU2625315C2 (https=)
SG (1) SG11201401279XA (https=)
SI (1) SI2766361T1 (https=)
TW (1) TWI571466B (https=)
UA (1) UA115042C2 (https=)
UY (1) UY34382A (https=)
WO (1) WO2013055897A1 (https=)
ZA (1) ZA201402556B (https=)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI561521B (en) * 2011-10-14 2016-12-11 Abbvie Inc Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
CN103987711B (zh) 2011-10-14 2016-08-24 艾伯维公司 作为用于治疗癌症和免疫性和自身免疫性疾病的凋亡诱导剂的8-氨基甲酰基-2-(2,3-二取代吡啶-6-基)-1,2,3,4-四氢异喹啉衍生物
BR112017012342A2 (pt) * 2014-12-09 2018-02-27 Abbvie Inc compostos inibitórios de bcl-xl e conjugados de anticorpo-fármaco incluindo os mesmos
KR20170093943A (ko) * 2014-12-09 2017-08-16 애브비 인코포레이티드 낮은 세포 투과성을 갖는 bcl xl 억제 화합물 및 이를 포함하는 항체 약물 접합체
JP2018506509A (ja) * 2014-12-09 2018-03-08 アッヴィ・インコーポレイテッド 細胞透過性Bcl−xL阻害剤との抗体薬物コンジュゲート
CN104473923B (zh) * 2014-12-29 2016-08-17 巩春智 一种防治慢性心力衰竭的药物组合物及其应用
WO2016131100A1 (en) * 2015-02-18 2016-08-25 The Walter And Eliza Hall Institute Of Medical Research Methods of treating infectious diseases
US10195213B2 (en) 2015-03-13 2019-02-05 Unity Biotechnology, Inc. Chemical entities that kill senescent cells for use in treating age-related disease
CN109641874A (zh) 2016-05-10 2019-04-16 C4医药公司 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体
CN109563168A (zh) * 2016-06-08 2019-04-02 艾伯维公司 抗egfr抗体药物偶联物
CN116173232A (zh) * 2016-06-08 2023-05-30 艾伯维公司 抗cd98抗体及抗体药物偶联物
BR112018075630A2 (pt) * 2016-06-08 2019-03-19 Abbvie Inc. anticorpos anti-cd98 e conjugados de fármaco de anticorpo
BR112018075639A2 (pt) * 2016-06-08 2019-04-09 Abbvie Inc. conjugados de anticorpo fármaco anti-egfr
BR112018075644A2 (pt) * 2016-06-08 2019-04-09 Abbvie Inc. anticorpos anti-cd98 e conjugados de anticorpo e fármaco
EP3458479B1 (en) * 2016-06-08 2020-11-04 AbbVie Inc. Anti-b7-h3 antibodies and antibody drug conjugates
JP2019521975A (ja) * 2016-06-08 2019-08-08 アッヴィ・インコーポレイテッド 抗egfr抗体薬物コンジュゲート
WO2018092064A1 (en) * 2016-11-18 2018-05-24 Novartis Ag Combinations of mdm2 inhibitors and bcl-xl inhibitors
WO2019000236A1 (en) * 2017-06-27 2019-01-03 Merck Sharp & Dohme Corp. ALLOSTERIC MODULATORS OF 3- (1H-PYRAZOL-4-YL) PYRIDINE FROM THE M4 ACETYLCHOLINE MUSCARINIC RECEPTOR
WO2019178433A1 (en) 2018-03-15 2019-09-19 Abbvie Inc. Abbv-621 in combination with anti-cancer agents for the treatment of pancreatic cancer
AR119494A1 (es) * 2019-07-29 2021-12-22 Servier Lab DERIVADOS DE 6,7-DIHIDRO-5H-PIRIDO[2,3-c]PIRIDAZIN-8-ILO, COMPOSICIONES FARMACÉUTICAS QUE LOS CONTIENEN Y SUS USOS COMO AGENTES PROAPOPTÓTICOS
AU2021386367A1 (en) 2020-11-24 2023-06-22 Les Laboratoires Servier Bcl-xl inhibitor antibody-drug conjugates and methods of use thereof
UY39610A (es) 2021-01-20 2022-08-31 Abbvie Inc Conjugados anticuerpo-fármaco anti-egfr
CN117794929A (zh) 2021-02-02 2024-03-29 法国施维雅药厂 选择性bcl-xl protac化合物及使用方法
JP2025516359A (ja) * 2022-05-06 2025-05-27 ツリーライン バイオサイエンシズ インコーポレイテッド テトラヒドロイソキノリンヘテロ二官能性bcl-xl分解剤
PE20250007A1 (es) * 2022-05-06 2025-01-07 Treeline Biosciences Inc Degradadores bcl-xl-heterobifuncionales de tetrahidroisoquinolina
CN120787162A (zh) 2022-05-20 2025-10-14 诺华股份有限公司 抗肿瘤化合物的抗体-药物缀合物及其使用方法
US20250339547A1 (en) 2022-05-20 2025-11-06 Novartis Ag Met bcl-xl inhibitor antibody-drug conjugates and methods of use thereof
IL317102A (en) 2022-05-20 2025-01-01 Novartis Ag EPHA2 BCL-XL inhibitor antibody-drug conjugates and methods of using them
EP4538273A1 (en) * 2022-06-10 2025-04-16 Hitgen Inc. Compound and use thereof in preparation of bcl-xl inhibitor
TW202540186A (zh) 2023-11-22 2025-10-16 瑞士商諾華公司 抗cd7抗體藥物結合物及其使用方法
PY24103486A (es) 2023-11-22 2025-06-06 Servier Lab Conjugados de anticuerpo anti-cd74-fármaco y métodos de uso de los mismos

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY115155A (en) 1993-09-09 2003-04-30 Upjohn Co Substituted oxazine and thiazine oxazolidinone antimicrobials.
PT1019385E (pt) 1995-09-15 2004-06-30 Upjohn Co N-oxidos de aminoaril-oxazolidinona
US20030220234A1 (en) 1998-11-02 2003-11-27 Selvaraj Naicker Deuterated cyclosporine analogs and their use as immunodulating agents
GB9918037D0 (en) 1999-07-30 1999-09-29 Biochemie Gmbh Organic compounds
AU8181701A (en) * 2000-06-21 2002-01-02 Hoffmann La Roche Benzothiazole derivatives
WO2004058266A1 (en) 2002-12-20 2004-07-15 Merck & Co., Inc. 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
WO2005099353A2 (en) 2004-04-19 2005-10-27 Symed Labs Limited A novel process for the preparation of linezolid and related compounds
EP1768967B1 (en) 2004-07-20 2009-04-22 Symed Labs Limited Novel intermediates for linezolid and related compounds
WO2006039164A2 (en) 2004-09-29 2006-04-13 Amr Technology, Inc. Novel cyclosporin analogues and their pharmaceutical uses
TW200716636A (en) 2005-05-31 2007-05-01 Speedel Experimenta Ag Heterocyclic spiro-compounds
US7514068B2 (en) 2005-09-14 2009-04-07 Concert Pharmaceuticals Inc. Biphenyl-pyrazolecarboxamide compounds
US8796267B2 (en) 2006-10-23 2014-08-05 Concert Pharmaceuticals, Inc. Oxazolidinone derivatives and methods of use
CA2676944C (en) 2007-02-15 2016-01-19 F. Hoffmann-La Roche Ag 2-aminooxazolines as taar1 ligands
JP2010524972A (ja) 2007-04-19 2010-07-22 コンサート ファーマシューティカルズ インコーポレイテッド 重水素化したモルホリニル化合物
US7531685B2 (en) 2007-06-01 2009-05-12 Protia, Llc Deuterium-enriched oxybutynin
US20090131485A1 (en) 2007-09-10 2009-05-21 Concert Pharmaceuticals, Inc. Deuterated pirfenidone
US20090118238A1 (en) 2007-09-17 2009-05-07 Protia, Llc Deuterium-enriched alendronate
US20090088416A1 (en) 2007-09-26 2009-04-02 Protia, Llc Deuterium-enriched lapaquistat
US20090082471A1 (en) 2007-09-26 2009-03-26 Protia, Llc Deuterium-enriched fingolimod
EP2209774A1 (en) 2007-10-02 2010-07-28 Concert Pharmaceuticals Inc. Pyrimidinedione derivatives
US20090105338A1 (en) 2007-10-18 2009-04-23 Protia, Llc Deuterium-enriched gabexate mesylate
WO2009051782A1 (en) 2007-10-18 2009-04-23 Concert Pharmaceuticals Inc. Deuterated etravirine
AU2008317375B2 (en) 2007-10-26 2013-02-28 Concert Pharmaceuticals, Inc. Deuterated darunavir
RU2561109C2 (ru) * 2008-12-19 2015-08-20 Дженентек, Инк. Соединения и способы применения
US8232273B2 (en) * 2008-12-19 2012-07-31 Genentech, Inc. Heterocyclic compounds and methods of use
KR20110123657A (ko) * 2010-05-07 2011-11-15 에스케이케미칼주식회사 피콜린아마이드 및 피리미딘-4-카복사미드 화합물, 이의 제조방법 및 이를 함유하는 약제학적 조성물
TWI561521B (en) * 2011-10-14 2016-12-11 Abbvie Inc Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases

Also Published As

Publication number Publication date
DK2766361T3 (en) 2016-12-05
SI2766361T1 (sl) 2016-11-30
LT2766361T (lt) 2016-11-10
BR112014009053B1 (pt) 2022-03-29
RU2014119250A (ru) 2015-11-20
HK1200167A1 (zh) 2015-07-31
CR20200097A (es) 2020-03-31
EP2766361B1 (en) 2016-08-10
AR088327A1 (es) 2014-05-28
MX356031B (es) 2018-05-09
CA2851364A1 (en) 2013-04-18
CR20140205A (es) 2014-07-17
NZ623100A (en) 2016-04-29
HRP20161319T1 (hr) 2016-12-16
KR102019643B1 (ko) 2019-09-10
ME02514B (me) 2017-02-20
ECSP14000357A (es) 2015-11-30
AU2017206246B2 (en) 2018-07-26
WO2013055897A1 (en) 2013-04-18
IL231856A0 (en) 2014-05-28
JP2014530238A (ja) 2014-11-17
RS55342B1 (sr) 2017-03-31
PE20141282A1 (es) 2014-10-26
JP2017197530A (ja) 2017-11-02
CY1118224T1 (el) 2017-06-28
AU2012322698A1 (en) 2014-04-17
HUE030589T2 (en) 2017-05-29
EP2766361A1 (en) 2014-08-20
ES2598877T3 (es) 2017-01-30
JP6155270B2 (ja) 2017-06-28
IL231856A (en) 2017-07-31
PH12015501498A1 (en) 2015-12-14
MY172723A (en) 2019-12-11
TW201319064A (zh) 2013-05-16
SG11201401279XA (en) 2014-05-29
KR20140075793A (ko) 2014-06-19
PL2766361T3 (pl) 2017-03-31
ZA201402556B (en) 2017-09-27
CL2014000905A1 (es) 2014-09-22
AU2017206246A1 (en) 2017-08-10
TWI571466B (zh) 2017-02-21
UA115042C2 (uk) 2017-09-11
JP6395893B2 (ja) 2018-09-26
MX2014004556A (es) 2014-07-09
DOP2019000022A (es) 2019-02-15
BR112014009053A2 (pt) 2017-06-13
DOP2014000070A (es) 2014-07-31
UY34382A (es) 2013-05-31
PH12014500729A1 (en) 2014-05-12
CA2851364C (en) 2020-03-10
CO6950476A2 (es) 2014-05-20
GT201400064A (es) 2014-12-23
PH12015501498B1 (en) 2018-03-14
RU2625315C2 (ru) 2017-07-13

Similar Documents

Publication Publication Date Title
US11786519B2 (en) Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
AU2017206246B2 (en) 8 - carbamoyl - 2 - (2 , 3 - disubstituted pyrid - 6 - yl) -1 , 2 , 3 , 4 - tetrahydroisoquinoline derivatives as apoptosis - inducing agents for the treatment of cancer and immune and autoimmune diseases
TWI634118B (zh) 用於治療癌症及免疫與自體免疫疾病之細胞凋亡誘導劑
AU2017206149B2 (en) Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
US20150152097A1 (en) Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
HK1200167B (en) 8-carbamoyl-2-(2,3-disubstituted pyrid-6-yl)-1,2,3,4-tetrahydroisoquinoline derivatives as apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
NZ623100B2 (en) 8 - carbamoyl - 2 - (2,3- di substituted pyrid - 6 - yl) -1,2,3,4 -tetrahydroisoquinoline derivatives as apoptosis - inducing agents for the treatment of cancer and immune and autoimmune diseases