Robert M Hesse

US Patent:

47724331, Sep 20, 1988

Filed:

Feb 10, 1986

Appl. No.:

6/827553

Inventors:

Robert Hesse - Cambridge MA

Assignee:

Research Institute for Medicine and Chemistry Inc. - Cambridge MA

International Classification:

C07J 900

US Classification:

2603972

Abstract:

Compounds of the general formula ##STR1## wherein R represents a hydrogen atom or a hydroxyl protecting group, Y represents a hydrogen atom or an optionally protected hydroxyl group, X represents the residue of a dienophile and either R. sup. 1 represents a halogen atom a hydrocarbylsulphonyloxy group or a group of the formula --Z--R. sup. 3 (in which Z represents --O--, --S--, --SO--, --NR. sup. 4 -- or --CR. sup. 4 R. sup. 5 -- and R. sup. 3, R. sup. 4 and R. sup. 5, which may be the same or different, each represent a hydrogen atom or a straight or branched aliphatic group having 1-12 carbon atoms and which may optionally carry one or more substituents) and R. sup. 2 represents a hydrogen atom or R. sup. 1 and R. sup. 2 together represent an oxo group or an optionally substituted alkylidene group, except that R. sup. 1 and R. sup. 2 together with the group --CH(CH. sub.

US Patent:

40641481, Dec 20, 1977

Filed:

May 21, 1976

Appl. No.:

5/688714

Inventors:

Derek H. R. Barton - London, EN
Robert H. Hesse - Cambridge MA

Assignee:

Research Institute for Medicine and Chemistry Inc. - Cambridge MA

International Classification:

C07J 500
C07J 300

US Classification:

26039745

Abstract:

The Specification describes a synthetic route for the preparation of a 9,11-dehydro-3-oxygenated 17. alpha. -hydroxy-20-ketopregnane which comprises the steps (i) electrophilically fluorinating a saturated 9,11-unsubstituted 3-oxygenated-17. alpha. -(esterified hydroxy)-20-ketopregnane, (ii) dehydrofluorinating the resulting 9. alpha. -fluorosteroid, if desired after transformations elsewhere in the molecule have been effected, and (iii) cleaving the ester group at the 17. alpha. -position to generate a 17. alpha. -hydroxy group.

US Patent:

54729572, Dec 5, 1995

Filed:

Aug 10, 1993

Appl. No.:

8/104496

Inventors:

Robert H. Hesse - Cambridge MA
Ezio Rizzardo - Wheelers Hill, AU
Derek H. R. Barton - College Station TX

Assignee:

Research Institute for Medicine and Chemistry - Cambridge MA

International Classification:

A61K 3159

US Classification:

514167

Abstract:

The invention provides novel compositions for use in pharmaceutical and veterinary medicine which contain 1. alpha. -hydroxy vitamin D compounds. Particular compositions are described which contain steroids which induce or assist in combatting osteoporosis together with 1. alpha. -hydroxy vitamin D. sub. 3 or 1. alpha. ,25-dihydroxy vitamin D. sub. 3. Methods of treatment of diseases are also provided including many which are resistant to vitamin D. sub. 3, in particular bone diseases.

US Patent:

39549801, May 4, 1976

Filed:

Jul 6, 1973

Appl. No.:

5/376961

Inventors:

Derek Harold Richard Barton - London, S.W.7, EN
Robert H. Hesse - Cambridge MA

International Classification:

C07J 7100

US Classification:

424241

Abstract:

A method of contraception which comprises orally administering steroidal 11, 19-hemiacetals of 11-hydroxy-19-oxo compounds to human beings.

US Patent:

42845580, Aug 18, 1981

Filed:

Mar 9, 1977

Appl. No.:

5/775879

Inventors:

Derek H. R. Barton - London, GB2
Robert H. Hesse - Cambridge MA

Assignee:

Research Institute for Medicine and Chemistry, Inc. - Cambridge MA

International Classification:

C07J 100

US Classification:

26023955R

Abstract:

Saturated organic compounds containing a hydrogen atom bound to a tertiary carbon atom may be electrophilically fluorinated by reaction with an electrophilic fluorinating agent such as molecular fluorine or trifluoromethyl hypofluorite under conditions whereby the formation of free fluorine radicals is suppressed, e. g. by the presence of a free radical inhibitor such as oxygen or nitrobenzene, the reactants being substantially homogeneously dispersed in a liquid medium, e. g. a solvent medium such as fluorotrichloromethane or chloroform/fluorotrichloromethane, so that the said hydrogen atom is electrophilically replaced by a fluorine atom. The fluorination is highly selective and, in the case of complex substrates such as saturated steroids which contain a number of tertiary C--H bonds, may be substantially completely confined to replacement of the hydrogen atom at the tertiary carbon atom which has the highest electron density about the C--H bond. The electron density and thus the direction of the fluorination may be controlled by appropriate selection of substituent groupings in the substrate molecule. Novel 14. alpha.

US Patent:

46701907, Jun 2, 1987

Filed:

Oct 3, 1984

Appl. No.:

6/657270

Inventors:

Robert H. Hesse - Cambridge MA
Ezzio Rizzardo - Garran, ACT 2605, AU
Derek H. R. Barton - London S.W. 7, GB2

International Classification:

C07J 900

US Classification:

2603972

Abstract:

The invention provides novel 1. alpha. -hydroxy vitamin D compounds and a method for their preparation from 1. alpha. -hydroxy-25-hydrogen cholesta-5,7-dienes by irradiation and isomerization techniques. The invention also includes the said 1. alpha. -hydroxy-25-hydrogen-cholesta-5,7-dienes and the corresponding cholest-5-enes. The new compounds may be obtained in a crystalline form substantially free from isomeric or other impurities arising from manufacture.

US Patent:

40368645, Jul 19, 1977

Filed:

May 27, 1975

Appl. No.:

5/581283

Inventors:

Derek Harold Richard Barton - London, EN
Robert Henry Hesse - Cambridge MA

Assignee:

Research Institute for Medicine and Chemistry Inc. - Cambridge MA

International Classification:

C07J 100

US Classification:

2603973

Abstract:

Saturated organic compounds containing a hydrogen atom bound to a tertiary carbon atom may be electrophilically fluorinated by reaction with an electrophilic fluorinating agent such as molecular fluorine or trifluoromethyl hypofluorite under conditions whereby the formation of free fluorine radicals is suppressed, e. g. by the presence of a free radical inhibitor such as oxygen or nitrobenzene, the reactants being substantially homogeneously dispersed in a liquid medium, e. g. a solvent medium such as fluorotrichloromethane or chloroform/fluorotrichloromethane, so that the said hydrogen atom is electrophilically replaced by a fluorine atom. The fluoroination is highly selective and, in the case of complex substrates such as saturated steroids which contain a number of tertiary C--H bonds, may be substantially completely confined to replacement of the hydrogen atom at the tertiary carbon atom which has the highest electron density about the C--H bond. The electron density and thus the direction of the fluorination may be controlled by appropriate selection of substituent groupings in the substrate molecule. Novel 14. alpha.

US Patent:

39911039, Nov 9, 1976

Filed:

Oct 21, 1974

Appl. No.:

5/516735

Inventors:

Derek Harold Richard Barton - London, EN
Robert Henry Hesse - Cambridge MA

Assignee:

Research Institute for Medicine and Chemistry Inc. - Cambridge MA

International Classification:

C07C 8700
C07C 8729

US Classification:

2605011

Abstract:

11-Halo derivatives of amitriptyline and its analogues, i. e. 5-(1'-halo-3'-aminoprop-1'-yl-idene)-5H-dibenzo[a,d]-10,11-dihydrocyclohep tenes and corresponding 11-oxa analogues as well as the acid addition salts thereof, have notable anti-depressant and tranquillising activity. They are prepared by reacting a 5-(3'-aminoprop-1'-ylidene)-5H-dibenz[a,d]-10,11-dihydrocycloheptene or an 11-oxa analogue thereof, or an acid addition salt thereof, with an electrophilic halogenating agent.